HYPERTENSION A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES
J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2003 by ICON Group International, Inc. Copyright 2003 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1
Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Hypertension: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-83657-4 1. Hypertension-Popular works. I. Title.
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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.
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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on hypertension. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.
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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.
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About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes & Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health
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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON HYPERTENSION ......................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Hypertension................................................................................. 9 E-Journals: PubMed Central ....................................................................................................... 73 The National Library of Medicine: PubMed ................................................................................ 83 CHAPTER 2. NUTRITION AND HYPERTENSION ............................................................................. 175 Overview.................................................................................................................................... 175 Finding Nutrition Studies on Hypertension ............................................................................. 175 Federal Resources on Nutrition ................................................................................................. 184 Additional Web Resources ......................................................................................................... 185 CHAPTER 3. ALTERNATIVE MEDICINE AND HYPERTENSION....................................................... 191 Overview.................................................................................................................................... 191 The Combined Health Information Database............................................................................. 191 National Center for Complementary and Alternative Medicine................................................ 192 Additional Web Resources ......................................................................................................... 204 General References ..................................................................................................................... 224 CHAPTER 4. DISSERTATIONS ON HYPERTENSION......................................................................... 225 Overview.................................................................................................................................... 225 Dissertations on Hypertension .................................................................................................. 225 Keeping Current ........................................................................................................................ 236 CHAPTER 5. CLINICAL TRIALS AND HYPERTENSION ................................................................... 237 Overview.................................................................................................................................... 237 Recent Trials on Hypertension .................................................................................................. 237 Keeping Current on Clinical Trials ........................................................................................... 258 CHAPTER 6. PATENTS ON HYPERTENSION ................................................................................... 261 Overview.................................................................................................................................... 261 Patents on Hypertension............................................................................................................ 261 Patent Applications on Hypertension........................................................................................ 298 Keeping Current ........................................................................................................................ 332 CHAPTER 7. BOOKS ON HYPERTENSION ....................................................................................... 333 Overview.................................................................................................................................... 333 Book Summaries: Federal Agencies............................................................................................ 333 Book Summaries: Online Booksellers......................................................................................... 335 The National Library of Medicine Book Index ........................................................................... 362 Chapters on Hypertension ......................................................................................................... 363 Directories.................................................................................................................................. 374 CHAPTER 8. MULTIMEDIA ON HYPERTENSION ............................................................................ 377 Overview.................................................................................................................................... 377 Video Recordings ....................................................................................................................... 377 Audio Recordings....................................................................................................................... 378 Bibliography: Multimedia on Hypertension .............................................................................. 378 CHAPTER 9. PERIODICALS AND NEWS ON HYPERTENSION ......................................................... 381 Overview.................................................................................................................................... 381 News Services and Press Releases.............................................................................................. 381 Newsletters on Hypertension..................................................................................................... 384 Newsletter Articles .................................................................................................................... 386 Academic Periodicals covering Hypertension............................................................................ 387 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................. 389 Overview.................................................................................................................................... 389
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U.S. Pharmacopeia..................................................................................................................... 389 Commercial Databases ............................................................................................................... 395 Researching Orphan Drugs ....................................................................................................... 396 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 401 Overview.................................................................................................................................... 401 NIH Guidelines.......................................................................................................................... 401 NIH Databases........................................................................................................................... 403 Other Commercial Databases..................................................................................................... 406 The Genome Project and Hypertension ..................................................................................... 406 APPENDIX B. PATIENT RESOURCES ............................................................................................... 411 Overview.................................................................................................................................... 411 Patient Guideline Sources.......................................................................................................... 411 Associations and Hypertension.................................................................................................. 421 Finding Associations.................................................................................................................. 427 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 429 Overview.................................................................................................................................... 429 Preparation................................................................................................................................. 429 Finding a Local Medical Library................................................................................................ 429 Medical Libraries in the U.S. and Canada ................................................................................. 429 ONLINE GLOSSARIES................................................................................................................ 435 Online Dictionary Directories ................................................................................................... 443 HYPERTENSION DICTIONARY............................................................................................... 445 INDEX .............................................................................................................................................. 573
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FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with hypertension is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about hypertension, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to hypertension, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on hypertension. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to hypertension, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on hypertension. The Editors
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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.
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CHAPTER 1. STUDIES ON HYPERTENSION Overview In this chapter, we will show you how to locate peer-reviewed references and studies on hypertension.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and hypertension, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “hypertension” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •
Bleeding Esophageal Varices: How to Treat This Dreaded Complication of Portal Hypertension Source: Postgraduate Medicine. 109(2): 75-76, 81-86, 89. February 2001. Contact: Available from McGraw-Hill, Inc. 1221 Avenue of the Americas, New York, NY 10020. (612) 832-7869. Summary: Bleeding esophageal varices, one of the most feared complications of portal hypertension (high blood pressure in the liver venous system), contribute to the estimated 32,000 deaths annually attributed to cirrhosis (liver scarring). This article describes the care of patients with this complication. The authors stress that successful control requires knowledge of the pertinent anatomy, underlying pathophysiology of portal hypertension, and natural history of gastroesophageal varices. The authors
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discuss the various prophylactic (preventive) and therapeutic approaches to management, including pharmacologic agents (drug therapy), endoscopic sclerotherapy, and transjugular intrahepatic portosystemic shunt (TIPS). Nonselective beta blockers are the treatment of choice for prevention of the first bleeding episode. Active bleeding is managed with octreotide and endoscopic sclerotherapy. Goals in the management of active bleeding are hemodynamic resuscitation, prevention and treatment of complications, and control of bleeding. Complications related to bleeding or its treatment can substantially increase the risk of death in each episode. TIPS and shunt surgery are reserved for those in whom octreotide and endoscopic surgery have failed. Endoscopic band ligation (tying off) should be used for prevention of recurrent bleeding. If endoscopic band ligation fails, patients can be offered TIPS or surgical therapy; they should be evaluated for liver transplantation. 4 figures. 4 tables. 11 references. •
Hypertension Management in Patients With Diabetes Source: Diabetes Care. 26(2): 355-359. February 2003. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: Clinical trials have demonstrated the importance of tight blood pressure control among patients with diabetes. However, little is known regarding the management of hypertension (high blood pressure) in patients with coexisting diabetes. This article reports on a study undertaken to determine whether hypertensive patients with coexisting diabetes are achieving lower levels of blood pressure than patients without diabetes; whether there are differences in the intensity of antihypertensive medication therapy provided to patients with and without diabetes; and whether diabetes management affects decisions to increase antihypertensive medication therapy. The authors abstracted medical records to collect detailed information on 2 years of care provided for 800 male veterans with hypertension. Of the 274 hypertensive patients with diabetes, 73 percent had a blood pressure greater than 140 over 90 mmHg, compared with 66 percent in the 526 patients without diabetes. Patients with diabetes also received significantly less intensive antihypertensive medication therapy than patients without diabetes. Less intensive blood pressure therapy in patients with diabetes could not be explained by clinicians being distracted by the treatment for diabetes. The authors conclude that there is an urgent need to improve hypertension care and blood pressure control in patients with diabetes. Additional information is required to understand why clinicians are not more aggressive in managing blood pressure when patients also have diabetes. 1 figure. 2 tables. 26 references.
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Treatment of Hypertension in Adult Patients with Diabetes Source: Diabetes Care. 25(1): 134-147. January 2002. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: Hypertension (high blood pressure) is an extremely common comorbidity of diabetes, affecting 20 to 60 percent of people with diabetes. Hypertension is also a major risk factor for cardiovascular events, such as myocardial infarction and stroke, as well as for microvascular complications, such as retinopathy (eye disease) and nephropathy (kidney disease). This review article focuses on the treatment of hypertension in adult patients with diabetes. Recent studies have demonstrated the effectiveness of blood pressure treatment versus placebo in reducing complications of diabetes, helped to
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define the optimal level of blood pressure control, and compared treatment strategies based on different drug classes. The results of these studies support an aggressive approach to the diagnosis and treatment of hypertension in patients with diabetes in order to substantially reduce the incidence of both macrovascular and microvascular complications. Treatment decisions should be individualized based on the clinical characteristics of the patient, including comorbidities as well as tolerability, personal preference, and cost, especially for patients who must pay out of pocket for medications. Fixed dose combinations of many drugs are available and may help with compliance and be less expensive for patients with a prescription copayment. 2 tables. 117 references. •
Emergency Treatment of Upper Gastrointestinal Bleeding Due to Portal Hypertension in Cirrhotic Patients: Report on a French Consensus Meeting Source: European Journal of Gastroenterology and Hepatology. 3(5): 413-418. May 1991. Summary: In October 1989, a French national consensus meeting dealing with the emergency treatment of upper gastrointestinal bleeding of portal hypertension in cirrhosis was conducted. This article reports on that meeting, addressing the following issues: the place and the limits of digestive tract endoscopy concerning the diagnosis of bleeding source; the selection of patients in whom emergency treatment should be started; the nature of the first treatment that should be used in case of active bleeding; what measures are specific to intensive care of bleeding cirrhotic patients; how to manage upper gastrointestinal bleeding unrelated to esophageal varices in cirrhotic patients; and what to do in case of an early recurrence. 12 references.
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Cost-Effectiveness of Intensive Glycemic Control, Intensified Hypertension Control, and Serum Cholesterol Level Reduction for Type 2 Diabetes Source: JAMA. Journal of the American Medical Association. 287(19): 2542-2551. May 15, 2002. Summary: Several treatment interventions can reduce the complications associated with type 2 diabetes, but their relative cost-effectiveness is not known. This article reports on a study undertaken to estimate the incremental cost-effectiveness of intensive glycemic control (relative to conventional control), intensified hypertension (high blood pressure) control, and reduction in serum cholesterol level for patients with type 2 diabetes. Results show that the incremental cost-effectiveness ratio for intensive glycemic control is $41,384 per quality adjusted life year (QALY); this ratio increased with age at diagnosis from $9614 per QALY for patients aged 25 to 34 years to $2.1 million for patients aged 85 to 94 years. For intensified hypertension control, the cost-effectiveness ratio is minus $1959 per QALY. The cost-effectiveness ratio for reduction in serum cholesterol level is $51,889 per QALY; this ratio varied by age at diagnosis and is lowest for patients diagnosed between the ages of 45 and 84 years. The authors conclude that intensified hypertension control reduces costs and improves health outcomes relative to moderate hypertension control. Intensive glycemic control and reduction in serum cholesterol level increase costs and improve health outcomes. The cost-effectiveness ratios for these latter 2 interventions are comparable with those of several other frequently adopted health care interventions. 3 figures. 5 tables. 46 references.
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Exercise Training and the Cardiovascular Consequences of Type 2 Diabetes and Hypertension: Plausible Mechanisms for Improving Cardiovascular Health Source: JAMA. Journal of the American Medical Association. 288(13): 1622-1631. October 2, 2002. Summary: The coexistence of type 2 diabetes and hypertension (high blood pressure) is especially damaging to cardiovascular health. Most trials of exercise training for these conditions have focused on glycemic control and blood pressure reduction. Less is known about the effects of exercise on the cardiovascular consequences of diabetes and hypertension. This article reviews the available evidence and plausible mechanisms by which exercise training may improve the cardiovascular health of persons with type 2 diabetes and hypertension and provides practical guidelines for exercise prescription. A MEDLINE search was performed for January 1985 to June 2002. Bibliographies from relevant articles, professional society clinical practice guidelines, and books were also reviewed. Because few large, randomized trials exist on these topics, metanalyses, professional society clinical practice guidelines, and books were also reviewed. Type 2 diabetes and hypertension result in abnormalities in central and peripheral parameters of cardiovascular structure and function. Evidence for an exercise training benefit is strongest for improvements in endothelial vasodilator function and left ventricular diastolic function. The data for exercise training's improvement of arterial stiffness and system inflammation and for reduction of left ventricular mass are less robust. However, this assertion is based more on a lack of randomized controlled trials rather than data to the contrary. Exercise training also reduces total and abdominal fat. These changes in body composition mediate improvements in insulin sensitivity and blood pressure and may improve endothelial vasodilator function. The current evidence, albeit not fully confirmed in randomized trials, suggests that the benefits of exercise training go beyond the recognized benefits of glycemic control and blood pressure reduction. 1 figure. 1 table. 113 references.
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Portal Hypertension Source: Current Opinion in Gastroenterology. 6(3): 370-375. June 1990. Summary: The mortality rate from the initial bleeding episodes of ruptured esophageal varices is 36-70 percent, depending on the patient's hepatic reserve. This, coupled with a 1-year survival rate of 30 percent, has encouraged the identification of patients with varices that have not bled, but who are at a high risk for a bleed. This article discusses the factors that predict the first bleed, the management of varices, congestive gastropathy, and pulmonary hypertension complicating portal hypertension. The author notes that patients who seem to be at high risk for bleeding may benefit from prophylactic treatment (sclerotherapy and/or beta blockers) to prevent an impending hemorrhage. 2 tables. 33 annotated references.
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Control of Cardiovascular Risk Factors in Patients with Diabetes and Hypertension at Urban Academic Medical Centers Source: Diabetes Care. 25(4): 718-723. April 2002. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: There are national mandates to reduce blood pressure (BP) to less than 130 over 85 mmHg, to reduce LDL cholesterol to less than 100 milligrams per deciliter, and to reduce HbA1c (glycosylated hemoglobin, a measure of blood glucose over time)
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levels to less than 7 percent, and to institute aspirin therapy in patients with diabetes. This article reports on a study undertaken to determine the proportion of patients in urban institutions with diabetes and hypertension (high blood pressure) who meet these treatment goals. Using American Diabetes Association (ADA) guidelines, the authors evaluated the control of cardiovascular disease (CVD) risk factors in 1,372 patients receiving medical care at two major urban medical centers in Brooklyn and Detroit. Information was extracted from charts of outpatient clinics. Of 1,372 active clinic patients with diabetes and hypertension, 1,247 (90.9 percent) had type 2 diabetes, and 26.7 percent met the target blood pressure. A total of 35.5 percent met the LDL cholesterol goal, 26.7 percent met the HbA1c goal, and 45.6 percent were on antiplatelet therapy (such as aspirin). Only 3.2 percent of patients met the combined ADA goal for blood pressure, cholesterol and glycosylated hemoglobin. The authors conclude that optimal control of CVD risk factors in adults with diabetes was achieved only in a minority of patients. Results reflect the inherent difficulties in achieving these complex guidelines in the present health care systems. 3 tables. 36 references. •
Hearing and Neurodevelopmental Outcome in Survivors of Persistent Pulmonary Hypertension of the Newborn Source: Pediatrics. 90(3): 392-396. September 1992. Summary: This article reports on a study that assessed neurodevelopmental outcome and hearing in infants who survived persistent pulmonary hypertension in the neonatal period, for which they were managed conservatively. A total of 27 of 34 infants with this diagnosis underwent neurological, intelligence, and audiologic testing between 10 months and 6 years of age. Children who were younger than 1 year of age at the initial hearing test were retested after they reached 2 years of age. The average IQ score was within the normal range (mean = 96.23). None of the children had sensorineural hearing loss. Severe neurologic abnormalities were seen in four children, three of whom had been severely asphyxiated at birth. Mild neurologic abnormalities were observed in five children. Two infants had bronchopulmonary dysplasia because they required supplemental oxygen for 29 and 66 days respectively, and had abnormal chest roentgenograms. The authors conclude that this study suggests that conservative management without induced alkalosis or respiratory paralysis is accompanied by no sensorineural hearing loss and a good neurologic outcome. 6 tables. 33 references. (AAM).
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Control of Hypertension in Diabetes. (editorial) Source: Diabetes Care. 26(2): 534-535. February 2003. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This editorial on the control of hypertension in diabetes serves as an introduction to an article that reports that patients with diabetes and hypertension are receiving less intensive antihypertensive therapy than patients without diabetes. In this editorial, the author discusses the reasons why this therapeutic gap in blood pressure control may exist, the difficulties of treating hypertension (high blood pressure) in patients with diabetes, the role of diabetic nephropathy (kidney disease associated with diabetes), and the role of guidelines for appropriate care of patients with diabetes and hypertension. 9 references.
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Prevention of Dementia in Randomised Double-Blind Placebo-Controlled Systolic Hypertension in Europe (Syst-Eur) Trial Source: Lancet. 352: 1347-1351. October 24, 1998. Summary: This jounral article describes the Systolic Hypertension in Europe (Syst-Eur) trial, a study exploring whether antihypertensive drug treatment could reduce the incidence of dementia. The participants in Syst-Eur had no dementia, were at least 60 years old, and had a systolic blood pressure of 160 to 219 mm Hg and diastolic below 95 mm Hg. They were treated with nitrendipine with the possible addition of enalapril, hydrochlorothiazide, or both. The data from this study showed that antihypertensive treatment was associated with a lower incidence of dementia in older people with isolated systolic hypertension. 27 references, 3 tables, 3 figures.
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Long-Term Predictors of Cognitive Outcome in a Cohort of Older People With Hypertension Source: British Journal of Psychiatry. 177: 66-71. July 2000. Summary: This journal article describes a study designed to identify early predictors of late-life cognitive outcome in a cohort of older people with mild hypertension. The study examined 387 survivors from 1,083 individuals recruited into the cognitive substudy of the Medical Research Council Treatment Trial of Hypertension in Older Adults. Researchers recorded cognitive function, premorbid IQ, and cardiovascular risk exposure on entry into the trial. This study followed up the cohort 9 to 12 years later to investigate cognitive function, update exposure status, and collect genomic material. Data analysis indicated that poorer cognitive outcome was independently related to a family history of dementia, increasing age, lower premorbid IQ, less decline in systolic blood pressure, and alcohol abstinence. The researchers concluded that reduction in systolic blood pressure among people with hypertension and moderate alcohol intake may protect against cognitive deterioration in later life. 3 tables, 30 references.
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Portal Hypertension and Variceal Bleeding Source: Current Opinion in Gastroenterology. 8: 388-397. June 1992. Summary: This review article summarizes recent advances in the area of portal hypertension and variceal bleeding. Topics include the pathophysiology of portal hypertension; Doppler ultrasound as an investigative tool in portal hypertension; the role of vasoactive drugs in treating acute variceal bleeding, including glypressin and vasopressin, somatostatin, and emergency sclerotherapy; the primary prophylaxis of variceal bleeding; prevention of rebleeding from varices; endoscopic features and portal hypertensive gastropathy; the hemodynamic effects of beta-blockers and other drugs; and noncirrhotic portal hypertension and Budd-Chiari syndrome. 76 annotated references.
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Cognitive Performance in Hypertensive and Normotensive Older Subjects Source: Hypertension. 36:1079-1082. December 2000. Summary: This study examines the association between blood pressure and cognitive function in older individuals. The study sample consisted of 107 untreated hypertensives and 116 normotensives without dementia or stroke, age 70 years or older, recruited from local general practices. Cognitive performance was measured with the Cognitive Drug Research Computerized Assessment Battery. The hypertensive group was significantly slower in all tests (simple reaction time, memory scanning, immediate
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and delayed word recognition, picture recognition, and spatial memory) except choice reaction time. In addition, accuracy was impaired in tests of number vigilence, delayed word recognition, and spatial memory. The results suggest that hypertension in older individuals may be associated with impaired cognitive function in the absence of target organ damage. 1 table, 49 references. (AA-M). •
Role of Transjugular Intrahepatic Portosystemic Shunt for Treatment of Portal Hypertension and Its Complications: A Conference Sponsored by the National Digestive Diseases Advisory Board Source: Hepatology. 22(5): 1591-1597. November 1995. Contact: Available from W.B. Saunders Company, Periodicals Department. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452 or (407) 345-3668. Summary: Transjugular intrahepatic portosystemic shunting (TIPS) is a recently developed radiological procedure that involves the creation of a parenchymal tract between the portal and hepatic veins followed by reinforcement of the tract with a metallic stent. In this article, the authors critically review the current data available on TIPS and make recommendations on the safety, efficacy, and indications for this procedure. Indications include acute variceal bleeding in which medical treatment, including sclerotherapy, has failed; recurrent variceal bleeding in patients who are refractory or intolerant to conventional medical management; treatment of refractory ascites; Budd-Chiari syndrome; and uses where TIPS is not indicated. Other topics include the contraindications to TIPS; the use of TIPS in pediatric patients; adverse effects and complications of TIPS; the efficacy and long-term patency of TIPS; research needs in this area; and recommended qualifications of physicians who perform TIPS. 78 references. (AA-M).
Federally Funded Research on Hypertension The U.S. Government supports a variety of research studies relating to hypertension. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to hypertension. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore hypertension. The following is typical of the type of information found when searching the CRISP database for hypertension:
2 Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
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Project Title: A HYPERTENSION
GENE-BASED
THERAPEUTIC
FOR
PULMONARY
Principal Investigator & Institution: Brigham, Kenneth L.; Professor; Generx+, Inc. 3200 West End Ave, Ste 500 Nashville, TN 372011322 Timing: Fiscal Year 2001; Project Start 30-SEP-1998; Project End 31-OCT-2002 Summary: (Adapted from the Investigator's abstract) Primary pulmonary hypertension is a uniformly fatal disease of young and middle aged people; there is little understanding of the pathogenesis and no specific therapy. The principal pharmacologic therapy in current use is chronic constant intravenous infusion of the vasodilator prostanoid, prostacyclin. This therapy is effective, but requires maintenance of an intravenous catheter and continuous intravenous infusion; the only alternative is lung transplantation. The investigators showed some time ago that it is possible to transfect the lungs with the arachidonate cyclooxygenase (COX) gene and achieve selective increases in prostacyclin and PGE2 prostanoids which are potentially therapeutic for pulmonary hypertension. Studies supported by this phase I grant have documented that aerosol delivery of the COX gene as a plasmid-cationic liposome complex can decrease pulmonary vascular reactivity significantly in an animal model which is anatomically and physiologically similar to humans with no adverse effects on lung function. The investigators hypothesize that aerosol delivery of the COX gene in an expression plasmid complexed with cationic liposomes will prevent development and/or progression of the physiologic and pathologic changes of chronic pulmonary hypertension. The investigators further speculate that this therapy will prove superior to any current therapy for the treatment of patients with primary pulmonary hypertension and may provide a new therapeutic modality for treatment of a much larger group of patients with secondary pulmonary hypertension. In this Phase II application, the PI will determine: 1) effects of repeated administration of the COX gene in a plasmid-cationic liposome complex by aerosol on lung function, 2) prostanoid generation and pulmonary vascular reactivity in unanesthetized sheep; 3) determine whether administration of the COX gene by aerosol in a plasmid-liposome complex will prevent development or progression of sustained pulmonary hypertension and pulmonary vascular remodeling in a well-characterized chronic air embolization model of sustained pulmonary hypertension in sheep; and 4) increase the efficiency of aerosol delivery of plasmid-cationic liposome complexes by using newer generation aerosol delivery devices and improved liposome-DNA formulations. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ABNORMAL PRESSURE NATRIURESIS IN HYPERTENSION Principal Investigator & Institution: Granger, Joey P.; Professor; Physiology and Biophysics; University of Mississippi Medical Center 2500 N State St Jackson, MS 39216 Timing: Fiscal Year 2001; Project Start 01-JUL-1990; Project End 31-DEC-2004 Summary: (Verbatim from the application): A major objective of the current proposal is to examine the role of and the mechanisms whereby endothelin B receptors modulate renal-pressure natriuresis and blood pressure regulation. Endothelin- 1 acts through two receptors, ETA and ETB receptors. Both of these receptors are located in the kidney with the highest concentration of ETB receptors existing within the medulla. Although the role of ETA receptors has been well characterized in the pathophysiology of hypertension and other disease states, the physiological importance of ETB receptors in modulating renal-pressure natriuresis and blood pressure regulation is unclear.
Studies 11
Preliminary data from our laboratory indicate that the renal production of endothelin is enhanced by chronic sodium loading. Moreover, data from our laboratory and others suggest that chronic ETB receptor blockade results in a salt-sensitive form of hypertension. The exact mechanisms involved in mediating the hypertension induced by chronic ETB receptor blockade, however, are unknown. Specific aims to be addressed are: 1) To test the hypothesis that the renal endothelin system is upregulated in response to increases in sodium intake. 2) To test the hypothesis that the hypertension induced by chronic ETB receptor blockade is associated with a chronic hypertensive shift in the pressure-natriuresis relationship. 3) To test the hypothesis that the renal medulla plays an important role in mediating the hypertension induced by chronic ETB receptor blockade. 4) To test the hypothesis that reduced nitric oxide synthesis mediates the reduction in renal function and elevation in arterial pressure during ETa receptor blockade-induced hypertension. 5) To test the hypothesis that angiotensin II mediates the reduction in pressure natriuresis and elevation in arterial pressure during chronic receptor blockade-induced hypertension. 6) To test the hypothesis that ETb blockade reduces pressure-induced natriuresis by blunting the transmission of renal perfusion pressure into the renal interstitium. To test these specific hypotheses, an integrated analysis of arterial pressure, renal microcirculatory, hormonal, and sodium excretory function will be determined in a conscious, chronically-instrumented rat model of hypertension induced by chronic ET1 receptor blockade. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: AC-SDKP IN TARGET ORGAN DAMAGE IN HYPERTENSION Principal Investigator & Institution: Carretero, Oscar A.; Division Head; Case Western Reserve Univ-Henry Ford Hsc Research Administraion Cfp-046 Detroit, MI 48202 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant) Hypertension is a cardiovascular risk factor that often leads to target organ damage. Angiotensin-converting enzyme inhibitors (ACEi) significantly reduce cardiovascular events, especially in high-risk patients. The effects of ACEi are mediated by inhibition of both the conversion of Ang I to Ang II and kinin degradation. We have evidence that in hypertension another peptide hydrolyzed by ACE, N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP), prevents and reverses cardiac fibrosis without altering blood pressure (BP) or cardiocyte hypertrophy. This is the first demonstration that administration of Ac-SDKP has an effect on cardiac fibrosis; however, we do not know whether Ac-SDKP has a physiological role, the mechanism by which it inhibits fibrosis or whether it contributes to the cardiovascular protective effects of ACEi. In this project we propose to test the general hypothesis that in hypertension cardiac fibrosis is the result of an alteration of the balance between pro-fibrotic and proinflammatory vs anti-fibrotic and anti-inflammatory systems. Ac-SDKP alters this balance in favor of the latter, reversing fibrosis (an important component of target organ damage) and improving cardiac function. The mechanisms by which Ac-SDKP antagonizes pro-fibrotic stimuli are: a) directly by inhibiting fibroblast proliferation and collagen synthesis and b) indirectly by acting as an anti-inflammatory cytokine, thus inhibiting production of TGF beta 1 and other cytokines and macrophage activation and infiltration. We also hypothesize that part of the anti-fibrotic effect of ACEi on target organ damage is mediated by Ac-SDKP interacting synergistically with kinins and NO. To test this hypothesis, we propose to conduct in vivo studies, using a combination of physiological, pharmacological and molecular approaches (gene deletion). In the first two aims we will determine the mechanisms by which Ac-SDKP prevents and reverses cardiac fibrosis. In Aim 1 we will study its effect on fibroblast proliferation and collagen
12 Hypertension
synthesis and degradation. In Aim 2 we will study whether Ac-SDKP inhibits cardiac fibrosis in part by acting as an anti-inflammatory cytokine, decreasing proinflammatory cytokines and macrophage activation and infiltration and reactive oxygen species production. In Aim 3, we will study whether in hypertension Ac- SDKP improves diastolic dysfunction by reversing cardiac fibrosis. In Aim 4 we will determine whether endogenous Ac-SDKP antagonizes the inflammatory and fibrotic effect of angiotensin II (Ang II), aldosterone, and myocardial infarction (MI). In addition, we will study whether part of the cardiovascular protective effect of ACEi is due to an increase in AcSDKP, which interacts with kinins and NO to decrease extracellular matrix deposition in the cardiovascular system. These studies are significant since they will demonstrate: 1) the mechanism by which Ac-SDKP decreases cardiac fibrosis; 2) whether it has a therapeutic effect, improving diastolic and systolic dysfunction by reversing cardiac fibrosis; 3) whether it has a physiological role by antagonizing pro-fibrotic stimuli in the cardiovascular system; and 4) whether it mediates the cardiovascular protective effect of ACEi. In the future, non-peptidic analogues of Ac-SDKP could be developed to treat fibrosis in hypertension, aging, heart failure (HF) post-MI, diabetes and other diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ADAPTATIONS TO HYPOXIA Principal Investigator & Institution: Mcmurtry, Ivan F.; Professor; Medicine; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, CO 800450508 Timing: Fiscal Year 2001; Project Start 01-APR-1977; Project End 31-MAR-2003 Summary: This is a resubmission seeking renewal of a 25-year program encompassing 4 sub-projects. The present application sharpens the focus of the laboratory on the pulmonary circulation, by a multi-faceted study of the mechanisms of hypoxic pulmonary circulation, by a multi-faceted study of the mechanisms of hypoxic pulmonary hypertension (PH). The work is collectively founded on the hypothesis that PH smooth muscle cell (SMC) function. Studies of functional contributions explore the influence of hypoxia on the ratio of pulmonary vasoconstrictors/dilators and of altered ion channel function . Work exploring structural aspects tests the idea that there exist specific subpopulations of hypoxia-responsive SMCs responsible for a preponderance of remodeling of lung vessels in hypoxia and that hypoxic proliferative response is dependent on specific isoforms of protein kinase C. The projects share experimental models of hypoxic pulmonary hypertension in rats and cows, as well as 3 core laboratories. This project will test 3 specific aims: 1) If hypoxic pulmonary hypertension is associated with increased endothelial NOS but not ET-1 protein, whereas the opposite is true in genetic pulmonary hypertension; 2) If the mechanisms of action of nitric oxide synthase (eNOS) and ET-1 gene expression are hypoxia and hemodynamic stress, respectively in these models. This project will investigate 4 specific aims: 1) What changes in PA SMC ion channels develops as a result of hypoxic pulmonary hypertension; 2) How does Ca2+ enter the hypertensive PA SMC; 3) How do NO and cGMP regulate ion channels in the hypertensive PA SMC; and 4) Are changes in ion channel expression and regulation a direct result of chronic hypoxia. This project will test 3 hypothesis: 1) Gi coupled receptors activate the MAPK signaling pathway in selected populations of PA SMCs; 2) Hypoxia selectively stimulates in hypoxiaresponsive PA SMCs through MAPK-dependent mechanisms; and 3) Connective Tissue Growth Factor (CTGF), is expressed selectively in subpopulations of PA SMCs during hypoxia and contributes to the fibroproliferative response. This project will test 2 specific aims: 1) Are PKC-alpha expression and activation critical determinants of PA
Studies 13
SMC proliferation to hypoxia in vivo, and 2) Are PKC-alpha expression and activation critical determinants of PA SMC proliferation to hypoxia in vitro. The 4 projects are highly interactive both conceptually, as well as in the performance and communication of experimental results. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ADRENERGIC RECEPTORS AND HYPERTENSION IN BLACKS Principal Investigator & Institution: Lockette, Warren E.; Professor; Internal Medicine; Wayne State University 656 W. Kirby Detroit, MI 48202 Timing: Fiscal Year 2001; Project Start 01-MAY-1995; Project End 31-MAY-2002 Summary: (Verbatim from the application): Abnormalities in sympathetic nervous system activity have been reported for many patients with salt-sensitive, essential hypertension. Autonomic responsiveness is mediated by alpha-2 adrenergic receptors (A2ARs). During the previous funding cycle, we performed an extensive populationbased association study. We reported that a common mutation of the A2AR was associated with severe hypertension in Detroit Blacks. This polymorphism was also associated with increased platelet aggregation, altered baroreceptor sensitivity, and diminished salt excretion in healthy, college-age students with no evidence of high blood pressure. We postulated that severe blood pressure elevations may be a "marker" of individuals at risk for stroke due to a common gene defect encoding increased vascular resistance and platelet sensitivity. In this continuation, we will measure the proportion of the total variance of A2AR-mediated platelet aggregation and central baroreceptor activity that may be attributable to additive genetic factors in humans. A2AR-mediated platelet aggregation will be measured with standard laboratory techniques. Autonomic responses to increases and decreases in baroreceptor activity will be assessed by loading, and unloading, of the central blood volume with immersion in thermal-neutral water and graded lower body negative pressure (LBNP), respectively. We postulate that abnormal A2AR-mediated transport of chloride is a necessary link between the autonomic nervous system and salt-sensitive hypertension. Before that hypothesis can be proven, we must first establish the mechanism(s) by which A2AR agonists affect chloride transport. We documented a role for A2ARs in mediating intracellular chloride transport. We will now use microfluorometry to test our hypothesis that A2AR-dependent agonists mediate increases in intracellular chloride concentrations ([Cl-]i) in platelets and vascular smooth muscle by enhancing the activity of the chloride/bicarbonate exchanger and the Na/Cl and the Na/K/2Cl-coupled cotransporters in these effector cells. We predict: (1) a significant heritable component exists for platelet aggregation, heart rate responses to LBNP, and immersion-induced salt excretion; (2) the squared difference of measurements for a particular phenotype between sibs negatively correlate with the number of alleles shared at the C10 A2AR locus; and (3) agonist-induced increases in platelet calcium and aggregation are enhanced by A2AR-dependent increases in {Cl-]i mediated by the chloride/bicarbonate exchanger. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ANGIOTENSIN, HYPERTENSION
SODIUM
AND
GENES
IN
PRIMATE
Principal Investigator & Institution: Shade, Robert E.; Southwest Foundation for Biomedical Res San Antonio, TX 782450549 Timing: Fiscal Year 2003; Project Start 01-APR-2002; Project End 31-MAR-2006
14 Hypertension
Summary: (provided by applicant): Sodium-dependent hypertension has long been associated with a defect in renal function. Experimental models as well as human studies have also suggested that an alteration in genetic expression may contribute to the hypertensive process. Sodium-lithium countertransport (SLC) activity is one mechanism that helps maintain intracellular sodium concentrations, and in some hypertensive patients, SLC activity is increased. These individuals also experience an inappropriate response to sodium challenges that appears to result from a lack of suppression of the renin-angiotensin-aldosterone system (RAAS). The association between SLC activity and hypertension is genetically determined since it occurs in families. It is uncertain whether this reflects an alteration in the gene for SLC, one of the genes that may increase RAAS function, or an interaction between genes for the two systems. The goal of the proposed studies is to examine the relationship between SLC activity and the RAAS in a non-human primate model in which the SLC phenotype is high or low. The hypothesis to be tested is that a high SLC activity is associated with inappropriately high RAAS function and a greater arterial pressure sensitivity to dietary sodium. In three aims, the contributions of peripheral and central RAAS components to sodium-dependent hypertension will be studied in baboons with the high and low SLC phenotypes. In the first aim, regulation of the RAAS will be examined in high and low SLC animals during a step-wise increase in sodium intake. These experiments will determine whether animals with high SLC activity have a reduced ability to suppress the RAAS and develop salt-sensitive hypertension. The second aim will investigate the role of angiotensin and aldosterone in the stimulation of hypertension by sodium and their ability to cause blood pressure to rise in high and low SLC animals. This aim will determine whether by raising plasma angiotensin or aldosterone the high SLC animals are more likely to become hypertensive. The third aim will focus on central nervous system mechanisms associated with an inappropriately high RAAS in high and low SLC animals. These studies will determine whether the high SLC activity results in more sensitive central mechanisms driving the sympathetic nervous system to raise arterial pressure. These studies will help provide data to determine whether an inappropriately high RAAS activity can cause hypertension. Importantly, this work will also reveal whether the genetically determined phenotype of high SLC is important in predisposing an animal to sodium-dependent hypertension. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ARTERIAL HYPERTENSION
BARORECEPTOR
UNLOADING
CAUSES
Principal Investigator & Institution: Thrasher, Terry N.; Surgery; University of Maryland Balt Prof School Baltimore, MD 21201 Timing: Fiscal Year 2002; Project Start 01-JAN-2002; Project End 31-DEC-2005 Summary: (provided by the applicant): This application is based on the hypothesis that unloading arterial baroreceptors can cause hypertension. We have developed a model with carotid baroreceptors on one side functional (all other carotid and aortic baroreceptors denervated) in conscious dogs. In this model, ligation of the common carotid artery proximal to the innervated carotid sinus produces a significant and sustained increase in systemic arterial pressure (SAP, 22 +/- 3 mmHg for at least seven days duration, n=6) and plasma renin activity (PRA). Carotid ligation unloads baroreceptors downstream and the reflex increase in SAP returns mean carotid sinus pressure (CSP) to control levels. The cause of the increase in SAP must be related to unloading carotid baroreceptors because removing the ligature on the innervated side after seven days results in a reduction in SAP to control levels. Furthermore, ligation of
Studies 15
the common carotid on the denervated side results in a fall in CSP distal to the ligature and does not cause an increase in SAP (n=4). The goal of this application is to elucidate the mechanisms, which drive the hypertension in this model. The aims are first, to extend the observations to include continuous measurements of SAP with the animals in their home cages using telemetry. The second aim is to test the hypothesis that the renal nerves are essential for the maintenance of the hypertension. Carotid baroreceptors will be unloaded as above in dogs with denervated kidneys. The third aim will test the hypothesis that the hypertension is primarily due to an increase in peripheral resistance by measuring cardiac output and pressure simultaneously. The fourth aim will test the hypothesis that increased sympathetic efferent activity is responsible for the hypertension. Control experiments will utilize ligation of the carotid proximal to a denervated carotid sinus. The health implications of this project are startling because current theories disregard participation of baroreceptors in the long-term control of blood pressure. These studies will provide a new framework for understanding the development and maintenance of hypertension. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ARTERIAL COMPRESSION OF THE VENTRO-LATERAL MEDULLA Principal Investigator & Institution: Patel, Sunil J.; Neurological Surgery; Medical University of South Carolina 171 Ashley Ave Charleston, SC 29425 Timing: Fiscal Year 2002; Project Start 05-APR-2002; Project End 31-MAR-2007 Summary: (provided by applicant) The Principal Investigator (PI) is a full time academic neurosurgeon who specializes in surgery of the posterior fossa for neurovascular compression syndromes. This research career award will afford him the time to acquire the skills needed to perform further patient-oriented research in neurogenic hypertension and obtain a Master of Science degree in Clinical Research. The research and training experience he will obtain during the period of the K23 Award will allow him to become an independent clinical investigator with a focus on mechanisms of neurogenic hypertension, and to be able to design and conduct studies on its therapy. The PI has the commitment and support of his sponsor, department and institution to permit the time and allocate the resources needed to attain his research career goals and complete his proposed research. Training will be facilitated through the institutions K30 Award and a NIH supported GCRC. The hypothesis to be tested is that neurogenically mediated hypertension is caused by arterial compression of areas along the retroolivary sulcus of the ventro-lateral medulla. Therefore the aims of the project are to: 1) electrically establish in humans the locations along the normal surface of the ventrolateral medulla that are sensitive to stimulation and produce pressor responses; and 2) show an association between arterial compression of these 'pressor-sensitive' areas along the medullary surface (established in Aim 1) and aberrations in sympathetic tone and cardiovascular functions in volunteering subjects with neurogenic hypertension. Hemodynamic and sympathetic response patterns to electrical stimulation of the medullary surface will be recorded to map the location of the pressor-regulating neuronal groups under the surface of the ventro-lateral medulla in patients undergoing surgery of the posterior fossa. This information on response patterns will then be used in a second study to investigate associations between arterial compression of these pressor-regulating areas and similar measured patterns in hypertensive individuals. Results from this research should help to better define the physiologic criteria to be used to relate arterial compression of the ventro-lateral medulla to neurogenic hypertension. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
16 Hypertension
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Project Title: AT2 RECEPTOR MECHANISMS IN ANG II DEPENDENT HYPERTENSION Principal Investigator & Institution: Carey, Robert M.; Professor and Dean; Medicine; University of Virginia Charlottesville Box 400195 Charlottesville, VA 22904 Timing: Fiscal Year 2001; Project Start 01-MAY-1998; Project End 31-MAR-2003 Summary: The overall objective is to test the hypothesis that the angiotensin II (ANG II) subtype-2 (AT2) receptor plays an important counter-regulatory role in the control of blood pressure in ANG II-dependent hypertension through the renal generation of vasodilator substances. The specific aims will test two hypotheses in ANG II-dependent hypertension: (1) that the AT2 receptor mediates enhanced renal production of bradykinin (BK) and/or nitric oxide (NO) and (2) that AT1 and AT2 receptors regulate renal prostaglandin E2 (PGE2), both leading to counter-regulatory renal vasodilation. The investigators have developed a rat model of renovascular hypertension, the 2kidney, 1-wrap (Grollman) hypertensive rat and have demonstrated that the hypertension is ANG II-dependent. In this model, the investigators have demonstrated that AT2 receptor blockade prevents the hypotensive response to AT1 receptor blockade, indicating that the AT2 receptor mediates counter-regulatory vasodilation. Using a novel renal interstitial fluid (RIF) microdialysis technique, the investigators have demonstrated in the normal rat that the AT2 receptor mediates ANG II induced renal NO production. The proposed experiments represent a systematic approach to the role of the AT2 receptor in the renal production of BK, NO and PGE2 and their roles in renal vasodilation in ANG II-dependent hypertension. RIF levels of these mediators will be determined in response to AT2 receptor blockade, and distal pathways will be dissected to determine the mechanisms by which AT2 receptors mediate counterregulatory changes. The proposed studies will provide for the first time in any form of hypertension an understanding of the relevance and mediators of AT2 receptors in the long term control of blood pressure and kidney function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BIOLOGY OF MONOCROTALINE INDUCED PULMONARY HYPERTENSION Principal Investigator & Institution: Segall, Henry J.; Vet Molecular Biosciences; University of California Davis Sponsored Programs, 118 Everson Hall Davis, CA 95616 Timing: Fiscal Year 2002; Project Start 01-JAN-1993; Project End 31-MAR-2006 Summary: Monocrotaline (MCT) induced pulmonary hypertension remains a principle model for the biology and development of intervention strategies for the human disease. Current concepts of pulmonary hypertension (PH) assign a primary pathogenetic role to the pulmonary endothelial cell in both human PH and that induced by MCT. Recently, a genetic lesion in the Bone Morphogenic Protein Receptor (BMPR) has been identified in humans with pulmonary hypertension The overall objective of this grant is to characterize the effects of MCT on the biology of the pulmonary endothelial cell and relate them to the initiating mechanisms of PH. Our previous work has demonstrated that several proteins with potential functional significance for endothelial cells have selective covalent interactions with the reactive intermediate of MCT metabolism, monocrotaline pyrrole (MCTP). This leads to our hypothesis that protein targets of MCT initiate vascular remodeling by altering endothelial cell function similar to endothelial dysfunction in persons with genetic susceptibility to primary pulmonary hypertension. Our specific aims are to further characterize the protein targets of MCT, to determine the functional significance of protein binding in endothelial cells, to evaluate proteins
Studies 17
regulating endothelial cell barrier function as potential MCT targets and to determine whether the MCT model alters the BMPR signal pathway affected in humans with PH. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BLOOD FLOW, CONTRACTILE AND METABOLIC FUNCTION IN LVH Principal Investigator & Institution: Davila-Roman, Victor G.; Associate Professor of Medicine, Anesthe; Internal Medicine; Washington University Lindell and Skinker Blvd St. Louis, MO 63130 Timing: Fiscal Year 2001; Project Start 01-APR-1998; Project End 31-MAR-2003 Summary: Hypertension, a disease that affects more than 50 million Americans, is the most common cause of left ventricular hypertrophy (LVH). Over 20 percent of patients with hypertension have LVH, and its presence is associated with a 50 percent increase in cardiovascular morbidity, and a risk of mortality from cardiovascular disease that is four to six times greater than the risk from hypertension alone. Because of this, regression of LVH with antihypertensive medication has become a goal of treatment. The precise mechanisms by which cardiac hypertrophy in arterial hypertension increases cardiac morbidity and mortality remain unknown. Although it is known that structural abnormalities of the myocardium and the microcirculation in LVH result in decreased coronary flow reserve, the relation between these and abnormalities in contractile, and metabolic function are unknown. It is also unkown whether regression of LVH induced by pharmacologic intervention decreases the risk of subsequent cardiovascular disease. Hence, understanding the mechanisms responsible for the transition from hypertrophy to heart failure, and elucidating whether reversal of LVH with antihypertensive medication results in salutary effects to the coronary circulation and cardiac function and whether it is associated with reduced morbidity and mortality from cardiovascular disease is of great importance. The working hypotheses of this proposal are: a) that hypertensive LVH is associated with decreased coronary artery reserve, and that this is associated with abnormalities in metabolic and contractile function; and b) that pharmacologic therapy with ACE inhibitors result in normalization of the left ventricular mass and improvements in myocardial blood flow reserve, myocardial metabolism, and systolic function. We propose to prove these hypotheses by use of novel approaches and methods, most of which have been developed and validated at our institution. These methods include imaging techniques that allow measurements of left ventricular mass with echocardiography, myocardial blood flow by positron emission tomography (PET) with 15 O- water, global contractile function with magnetic resonance imaging (MRI) with and without tissue-tagging by stressstrain relations, and myocardial metabolism measured by PET with 11 C-acetate and 11 C- palmitate. Measurements at baseline and after one year of treatment with ACE inhibitors will be performed in patients with LVH induced by hypertension and with either normal or decreased left ventricular function. Results of these studies are designed to determine the benefits of normalization of arterial blood pressure and left ventricular mass with antihypertensive medication. We have previously used and validated these methods and preliminary studies from our institution suggests that the cardiac imaging approach outlined in this proposal is rational and feasible. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BOLD MRI: APPLICATION TO INTRARENAL OXYGENATION Principal Investigator & Institution: Prasad, Pottumarthi V.; Evanston Northwestern Healthcare 2650 Ridge Ave Evanston, IL 60201
18 Hypertension
Timing: Fiscal Year 2003; Project Start 01-FEB-1998; Project End 31-JAN-2008 Summary: (provided by applicant): Hypertension, also known as high blood pressure, affects one in four adults in the United States, and is a major risk factor for stroke, heart attack and kidney disease. It is sometimes called the "silent killer" because it often has no symptoms. Progress towards preventing and curing hypertension has been impeded by a lack of thorough understanding of its underlying pathophysiology. Significant progress made over the last decade in vascular biology has allowed for better understanding of many of the underlying mechanisms, which then has led to development of novel drug treatments for hypertension. Many now believe that kidney plays an important role in the pathophysiology of hypertension. Specifically, it is thought that renal medullary blood flow has a direct influence on hypertension. It is still a topic of debate as to the alterations in the kidney being the cause or the consequence of hypertension. In either case, availability of a non-invasive method to probe blood flow at a regional level within the kidney would allow for verifying many of the hypotheses to be tested in humans. Based on previous experience with blood oxygenation level dependent (BOLD) magnetic resonance imaging (MRI) technique to the kidney, we hypothesize that the technique would be sensitive to changes in medullary blood flow. More specifically, we believe that the technique in combination with suitable endothelium-dependent vasoactive agents would allow for renal microvascular reactivity studies to be performed in a non-invasive way. Vascular reactivity studies look for responses in the vessel walls to vasoactive substances or physiological paradigms that elicit an endogenous vasoactive response. It is believed that these functional changes at the microvascular level take place much earlier than the development of hypertension and if detected early enough, may be reversed with novel therapeutic approaches. In this proposal, we will perform experiments that will validate our hypothesis in several forms of hypertension in previously well established animal models and then extend them to human kidneys. Animal models will allow for direct comparison of BOLD MRI measurements against invasive laser probe assessments. Our human studies are designed to test the hypothesis that subjects at risk for developing hypertension will exhibit reduced renal microvascular reactivity. Successful outcome will provide better understanding of pathophysiology of human hypertension. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BRAIN AND CARDIAC ANGIOTENSIN II IN HYPERTENSION Principal Investigator & Institution: Berecek, Kathleen H.; Professor; Physiology and Biophysics; University of Alabama at Birmingham Uab Station Birmingham, AL 35294 Timing: Fiscal Year 2001; Project Start 01-DEC-1983; Project End 31-MAR-2004 Summary: The major goal is to identify mechanisms underlying the prolonged antihypertensive and cardio-protective effects of early, short- term ACE inhibitor therapy or single intracardiac injection of the angiotensin II AT1 receptor subtype antisense cDNA (AT1 R-AS) to SHR. This goal is based on previous studies by us and other investigators showing that early, short-term therapy with captopril (CAP) or early, single-application of AT1 R-AS to SHR attenuated hypertension not only in treated rats but in their offspring as well. The major hypothesis to be tested is that Ang II is a permissive factor necessary for expression of the hypertensive phenotype and that early perturbation of this peptide, particularly in brain or heart, either by decreasing its synthesis and/or effecting its receptors would prevent expression of hypertension in treated rats as well as their offspring. There are four Specific Aims to this project. Aim I: To determine whether or not the prolonged antihypertensive effect of early, short-term CAP therapy in SHR is due to chronically attenuated production of Ang II and/or its
Studies 19
receptors which is passed on to offspring of treated rats and/or due to accumulation of antihypertensive agents such as bradykinin (BK), Ang (1-7) or nitric oxide (NO) which are passed on to offspring of treated rats. Aim II: To determine whether or not the prolonged antihypertensive effect of early CAP treatment down-regulates the AT1 receptor subtype (AT1 R) in brain and, with it, produces an attenuation of Ang II mediated modulation of the sympathetic nervous system. Aim III: To determine whether the prolonged antihypertensive effect of early CAP treatment down-regulates AT1 R in heart and, with it, produces an attenuation of Ang II mediated effects on cardiovascular structural remodeling. Aim IV: To determine whether or not early AT1 R antisense therapy in SHR mimics changes in brain and cardiac receptors and their function observed with early, short-term CAP therapy. We will perform histological, morphological, biochemical, molecular biological and functional studies to address there hypotheses. The proposal addresses an important cardiovascular problem, that of the role of brain and cardiac renin-angiotensin systems in the development of hypertension and its sequelae and why early perturbation of these systems with early, short-term ACE therapy or a single early application of AT1 R-AS leads to a permenant effect not only in the development of hypertension in SHR subjected to these treatments but also in their offspring. These studies are highly novel and could help to define new strategies not only for the treamtent of hypertension but its prevention as well. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CARDIOVASCULAR REGULATION--AUTONOMIC/METABOLIC MECHANISMS Principal Investigator & Institution: Biaggioni, Italo; Professor of Medicine and Pharmacology; Vanderbilt University 3319 West End Ave. Nashville, TN 372036917 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): Local metabolic factors play an important role in modulating vascular smooth muscle tone, and interact with the autonomic nervous system to contribute to cardiovascular regulation. Nitric oxide (NO) is arguably one of the most important of these metabolic factors. Experimental evidence suggests that endothelial-derived NO exerts tonic vasodilatory effects even under resting conditions. Neuronal-derived NO acts centrally to inhibit sympathetic tone, and on presynaptic aderenergic neurons to inhibit norepinephrine release. There is substantial evidence that several disease states are characterized by ?NO deficiency?, including hypercholesterolemia, smoking and, potentially, hypertension. It is though that this NO deficiency contributes to the adverse cardiovascular events that characterizes these patient populations. Experimental systemic blockade of NO synthesis leads to an increase in blood pressure, indicating its importance on cardiovascular regulation. In normal subjects, however, the pressor effect of systemic NO inhibition is modest because of the restraining effect of the baroreflex. It is difficult, therefore, to gauge the importance of NO on blood pressure regulation because of the 'close loop' characteristics of autonomic regulation. Similarly, the relative contribution of neuronal NO and endothelial NO to blood pressure control remains unclear. It would be advantageous, therefore, to develop a human model where the increase in blood pressure produced by systemic NOS inhibition reflects selective endothelial NO inhibition, unrestrained by baroreflex buffering. Patients with pure autonomic failure represent such a human model. Similarly, we can induce transient autonomic failure by blocking neurotransmission at the level of autonomic ganglia with trimethaphan. We propose to use these models to test the hypothesis that endothelial nitric oxide is an important modulator of blood pressure under normal conditions, and that its impairment
20 Hypertension
contributes to hypertension. We will inhibit NO synthesis with L-arginine analogs to determine its effect on normal subjects, normotensive offspring of hypertensive parents, patients with essential hypertension, and patients with pure autonomic failure. About half of patients with pure autonomic failure paradoxically develop hypertension driven by increased vascular resistance. We also propose a proof-of-concept study to determine if modulation of NO mechanisms with L-citrulline and Larginine provide a novel therapeutic option in this human model of hypertension. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CEREBROVASCULAR HYPERTENSION
CHANGES
IN
PREGNANCY
AND
Principal Investigator & Institution: Cipolla, Marilyn J.; Neurology; University of Vermont & St Agric College 340 Waterman Building Burlington, VT 05405 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2007 Summary: (provided by applicant): Eclampsia is a serious complication of pregnancy that occurs when hypertension develops with neurologic symptoms, including headaches, nausea, visual disturbances and convulsions. While numerous organs are affected by hypertension in pregnancy, cerebrovascular involvement is the direct cause of death in approximately 40 percent of patients. The major cerebrovascular changes that occur have been shown to be similar to hypertensive encephalopathy in which acute elevations in blood pressure (i.e., acute hypertension) overcome the myogenic vasoconstriction of the cerebral arteries and arterioles causing autoregulatory failure, hyperperfusion and edema. Because women who develop eclampsia in general are normotensive prior to pregnancy, there is evidence that pregnancy affects the cerebral circulation in a way that makes the vessels susceptible to autoregulatory failure and hyperperfusion during acute hypertension. The long-term objective of this proposal is to investigate how pregnancy affects the structure and function of the cerebral circulation focusing on diameter regulation in response to changes in pressure (myogenic reactivity) and how those changes affect vascular permeability that promotes edema. Aim 1 will use isolated and pressurized posterior cerebral arteries from pregnant and nonpregnant rats to determine the pressure at which forced dilatation occurs and investigate underlying mechanisms of pregnancy-induced alterations in diameter regulation, including vascular smooth muscle actin and endothelial cell influences (e.g., nitric oxide and prostaglandins). In addition, since hypertension alone has been shown to cause significant remodeling and reactivity changes in the cerebral circulation, Aim 1 will also investigate how elevated mean arterial pressure during pregnancy affects myogenic activity and diameter regulation in a rat model of hypertension in pregnancy (nitric oxide inhibition). Acute hypertension and eclampsia are associated with significant edema formation due to disruption of the normally impermeable cerebral endothelium. Therefore, Aim 2 will investigate pregnancyinduced changes in endothelial cell permeability during acute hypertension, including enhanced fluid phase endocytosis (transcellular flux) and tight junction disruption (paracellular flux). The influence of pregnancy on permeability during forced dilatation will be determined using a combination of techniques, including clearance of fluorescent tracers and transmission electron microscopy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CIRCUMVENTRICULAR ORGANS: GENDER AND HYPERTENSION Principal Investigator & Institution: Hay, Meredith; Director and Associate Professor; None; University of Missouri Columbia 310 Jesse Hall Columbia, MO 65211
Studies 21
Timing: Fiscal Year 2001; Project Start 15-FEB-2000; Project End 31-JAN-2004 Summary: It has been proposed that estrogen delays and or prevents the onset of hypertension and may function to keep women "cardiovascularly younger" than men of the same age. Similar observations have been made in experimental hypertensive animals, however, the underlying mechanisms of estrogen's protective effects are incompletely understood. Given the importance of estrogen replacement therapy in women's health, it is clear that an understanding of the cellular mechanisms underlying estrogen's cardiovascular protective effects is critical for continuing development of clinical therapies for the treatment of hypertension in women. Angiotensin II (Ang II) is an important factor in some forms of both clinical and experimental hypertension. Chronic intravenous infusions of low levels of Ang II in experimental animals result in an increase in blood pressure that involves an increased neurogenic contribution to the maintenance of blood pressure which is prevented by prior lesioning of the area postrema (3,6,33,57,95). It is thought that circulating Ang II acts on area postrema neurons to maintain the hypertension. The proposed studies will test the general hypothesis that estrogen protects against the Ang II induced hypertension by inhibiting the actions of Ang II on area postrema neurons. To test this hypothesis and to characterize the effects of estrogen (17beta-estradiol) on area postrema neurons, Ang II induced increases in blood pressure and baroreflex modulation, this proposal will utilize whole-cell patch clamp recordings from isolated area postrema neurons, in vivo single unit recordings of area postrema neurons and hemodynamic measurements in conscious animals to address the following 4 major and distinct aims. 1) To evaluate area postrema membrane properties following exposure to 17beta-estradiol. 2) To determine the effects of acute and chronic 17beta-estradiol on area postrema calcium handling. 3) To determine the effect of 17beta-estradiol on activation of area postrema neurons. 4) To evaluate the effects of acute and chronic 17beta-estradiol on Ang II hypertension. Determination of the effects of estrogen on CNS mechanisms underlying Ang II dependent hypertension will have a significant impact on our understanding of the cardiovascular benefits of estrogen replacement therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EFFECTS HYPERTENSION
OF
BMPRII
MUTATIONS
IN
PULMONARY
Principal Investigator & Institution: Rodman, David M.; Professor; Medicine; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, CO 800450508 Timing: Fiscal Year 2003; Project Start 19-SEP-2003; Project End 31-JUL-2007 Summary: (provided by applicant): Primary pulmonary hypertension (PPH) is a potentially lethal disorder characterized by pulmonary vasoconstriction and vascular remodeling involving abnormal proliferation of fibroblasts, smooth muscle and endothelial cells. In the year 2000, mutations in the type 2 bone morphogenic protein receptor (BMPR2) were identified as the genetic basis for familial PPH and about 30% of sporadic PPH. BMP signaling had not previously been connected to pulmonary hypertension, and the mechanistic linkage is unknown. We hypothesize that in normal individuals the BMP pathway acts to down-regulate both inflammatory cytokinemediated positive feedback loops and vascular smooth muscle cell proliferation. Insufficient BMP pathway activity in individuals with BMPR2 mutations leads to insufficient damping of these auto-regulatory loops, resulting in the PPH phenotype. We provide preliminary evidence in cell culture systems supporting this hypothesis and have constructed a unique series of transgenic mice to further test the hypothesis. These
22 Hypertension
mice express a human dominant-negative BMPR2 (dnBMPR2) using the tetracycline gene switch system, allowing both spatial and temporal control of expression. We have successfully bred smooth muscle cell and epithelial cell specific dnBMPR2 expressing mice, and are constructing endothelial cell specific mice at this time. Using our in vitro and transgenic models we will test the following three specific aims: 1: Test the hypothesis that the BMP pathway is a negative modulator of the cytokine interleukin-6 (IL-6) in PA SMC, leading to reduced IL-6-mediated signaling and proliferation. 2: Test the hypothesis that loss of PA SMC BMPR2 function in SM22-dnBMPR2 transgenic mice leads to an exaggerated pulmonary hypertensive response in vivo. 3: Test the hypothesis that loss of BMPR2 function in lung cell types other than SMC also contributes to the development of pulmonary hypertension. Upon completion of our studies, we will have tested the hypothesis that the link between BMP signaling and pulmonary hypertension involves both regulation of the critical cytokine, IL-6, as well as modulation of smooth muscle cell proliferation. We will have also tested the role of four pulmonary cell types, smooth muscle, endothelium, airway epithelium and macrophages in the link between BMPR2 and pulmonary hypertension. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CONTROL
ENDOGENOUS
OPIOIDS,
PAIN
AND
BLOOD
PRESSURE
Principal Investigator & Institution: Mccubbin, James A.; Professor and Chair; Psychology; Clemson University 300 Brackett Hall Clemson, SC 296345702 Timing: Fiscal Year 2001; Project Start 01-AUG-1989; Project End 31-JUL-2003 Summary: This proposal is for continuation of our ongoing research on opioid abnormalities and blood pressure reactivity in persons at risk for hypertension. We are gradually becoming aware that regulation of both blood pressure and pain sensitivity is altered in pre-hypertensive populations. For example, persons at risk for hypertension have decreased opioid inhibition of blood pressure responses to stress. Paradoxically, they also show antinociceptive effects consistent with exaggerated opioid function. The scientific meaningfulness, both basic and clinical, of the links between pain sensitivity alterations and blood pressure dysregulation remains to be clarified. Recent studies by ourselves and others have emphasized the importance of opioids in regulation of 1) neuroendocrine and blood pressure responses to stress in hypertension development, 2) behavioral responses to pain, and 3) the relationship between pain sensitivity and blood pressure. The purpose of this continuation proposal is to further examine the role of endogenous opioids in blood pressure dysregulation by studies of circulatory and behavioral responses to aversive stimuli in persons at enhanced risk for hypertension. This will be accomplished by comparison of the effects of opioid blockade with naltrexone on pain sensitivity and blood pressure reactivity in young men and women with mildly elevated casual blood pressure. We hypothesize that abnormalities of both blood pressure control and pain sensitivity in the early stages of hypertension development are linked to altered opioid peptide function. Persons at risk for hypertension will show exaggerated opioid inhibition of pain sensitivity in the face of diminished opioid inhibition of blood pressure reactivity. Improved understanding of the opioidergic basis of altered pain sensitivity and blood pressure control will clarify the poorly characterized etiology of essential hypertension and possibly offer new preventive, diagnostic and therapeutic strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
Studies 23
•
Project Title: ESOPHAGEAL VARICES BY B-ADRENERGIC BLOCKERS Principal Investigator & Institution: Groszmann, Roberto J.; Internal Medicine; Yale University 47 College Street, Suite 203 New Haven, CT 065208047 Timing: Fiscal Year 2001; Project Start 20-APR-1993; Project End 31-MAR-2003 Summary: Cirrhosis is the fifth leading cause of death in the United States in individuals under the age of 65, the productive years of life. It affects men and women equally, and impacts on all races and socio- economical levels. Portal hypertension is the main complication of cirrhosis, regardless of etiology. Gastroesophageal varices and variceal hemorrhage are a direct consequence of portal hypertension and account in large part for the high mortality of cirrhosis. Non-selective beta- adrenergic blockers decrease portal pressure and have been shown to prevent the first variceal hemorrhage in patients with cirrhosis and varices. Early portal hypotensive therapy, before the patients develop varices, would be beneficial not only because it may prevent or delay the formation of varices (and variceal hemorrhage) but because it may prevent or delay the development of other complications of portal hypertension, such a ascites. This ongoing multi-center, prospective, randomized, placebo-controlled, double-blind trial was designed with the primary aim of investigating if early therapy with timolol, a nonselective beta-adrenergic blocker, can prevent or delay the development of varices in patients with cirrhosis and portal hypertension. Secondary aims will examine whether timolol prevents or delays other complications of portal hypertension such as ascites and porto-systemic encephalopathy, as well as liver transplantation or death. Patients with cirrhosis, without varices on endoscopy and with portal hypertension (portal pressure greater than 6 mmHg) are included in the study. This grant application was funded in April of 1993 and patient randomization began in August of 1993. Patient accrual took longer than originally estimated, however it is now certain that the number of 190 patients required for the study will have been randomized by the end of the current funding period (March 1998), since at the writing of this proposal 158 patients had already been randomized. In calculating sample size, we assumed a rate of development of varices of 50 percent at 4 years in the control arm, to be reduced to 30 percent in the timolol arm. So far our observed rates for development of varices are consistent with our planned estimates. However, we have now estimated that a minimum follow-up of 4 years (after last patient is recruited) is necessary to ensure high statistical power (80 percent at the 2-sided 0.05 level). The trial is highly significant for the promise it holds for the treatment of cirrhosis of all etiologies and for an understanding of the natural history of the disease. The four centers involved are widely renown for their studies in this area and have collaborated productively in the past, including the only published double-blind trial of propranolol in the prevention of first variceal hemorrhage in patients with cirrhosis and varices. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ESTROGEN AND SODIUM MODULATE HYPERTENSION IN AGING RATS Principal Investigator & Institution: Hinojosa-Laborde, Carmen; Associate Professor; Physiology; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, TX 78229 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-JAN-2007 Summary: (provided by applicant): The Dahl salt sensitive (S) rat will be studied as an animal model of post-menopausal hypertension to investigate the mechanisms responsible for the hypertension. The pressor systems that will be evaluated are the
24 Hypertension
renin-angiotensin system (RAS) and the sympathetic nervous system (SNS). The role of estrogen, aging, and salt intake as modulators of these pressor systems via their effects on the nitric oxide (NO) system will be investigated. The first specific hypothesis is that the aging process with the accompanying loss of estrogen activity is associated with a down regulation of the nitric oxide system resulting in hypertension. To test this hypothesis, Specific Aim 1 of this study is to monitor blood pressure and the level of activation of the NO system in intact, ovariectomized (OVX), and OVX+estrogen-treated Dahl salt sensitive and Dahl salt-resistant (R) female rats as they age from 3 month to 2022 months of age. The second specific hypothesis is that the factors maintaining the hypertension associated with the loss of estrogen activity in Dahl S rats is determined by the level of salt intake. OVX performed at young, middle and old age will cause an increase in blood pressure, but the rise will be attenuated with increasing age. However, the level of blood pressure and the activity of the pressor systems contributing to hypertension will be higher pre-OVX because of the effects of aging on the RAS and SNS. Two specific aims will address this hypothesis. Specific Aim 2 will be to establish that the Dahl S elderly and OVX females maintained on low salt intake will become hypertensive as a result of an activation of the RAS. Estrogen administration will maintain activation of the NO system to suppress the RAS. Blockade of NO formation in low salt animals will increase RAS function, especially in the OVX+estrogen animals. Specific Aim 3 is to determine that high salt fed Dahl S elderly and OVX animals will develop a hypertension that is dependent on the activation of the SNS. As with the low salt animals, estrogen supplement will suppress the SNS stimulation through a NOmediated mechanism. Together these studies will provide evidence that the arterial pressure of the Dahl S rat is sensitive to the removal of estrogen through OVX or aging suggesting a useful model of post-menopausal hypertension. By investigating the relationship of estrogen, NO and salt, important new information will be gained in the mechanisms whereby estrogen provides protection against hypertension. Importantly, a greater understanding will be obtained addressing why the protection disappears with the aging process. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ESTROGEN REDUCES VENOUS TONE IN EARLY HYPERTENSION Principal Investigator & Institution: Martin, Douglas S.; Basic Biomedical Sciences; University of South Dakota 414 E Clark St Vermillion, SD 57069 Timing: Fiscal Year 2001; Project Start 15-SEP-2000; Project End 31-JUL-2004 Summary: (Verbatim from the application): Recent data from our laboratory indicated that venous tone is increased in the developmental stages of spontaneous hypertension in the rat. Since the increase in blood pressure in the initial stages of hypertension is characterized by an elevation of cardiac output, veins appear to play an important role in the initiation of the hypertensive process. The development of hypertension is sexually dimorphic. Considerable evidence suggests that estrogen attenuates the development of hypertension. Estrogen has been shown to affect vascular smooth muscle via both endothelial dependent and independent mechanisms and to modulate peripheral and central nervous system function. Veins possess functional estrogen receptors, high estrogen states are associated with changes in venous tone and estrogen modulates neural activity in brain regions involved in the control of venous tone. Thus, estrogen may modulate venoconstrictor tone during the developmental stages of hypertension via effects on venous smooth muscle and/or via effects on sympathetic outflow to veins. Accordingly, the proposed research is aimed at testing the general hypothesis that estrogen reduces venoconstrictor tone during the developmental stages
Studies 25
of spontaneous hypertension. The specific aims of the research will be to determine if I) Estrogen reduces sympathetic venoconstrictor tone in young female SHR. II) Estrogen reduces venous tone via effects on venous smooth muscle responsiveness via an effect on the nitric oxide system, calcium channels or potassium channels. III) Estrogen alters the expression of key proteins involved in the control of venous tone. Experiments will be performed in spontaneously hypertensive (SHR) rats at 6-10 weeks of age, a time point when previous studies have shown elevated venous tone in SHR rats. MAP, HR, and mean circulatory filling pressure, an index of integrated venomotor tone will be measured in conscious rats to determine the effects of estrogen on overall venous tone. Isolated portal and mesenteric veins will be used to assess the effects of estrogen on venous smooth muscle responsiveness and the mechanisms underlying these effects. Western blot techniques will be used to determine if estrogen affects venous tone by altering expression of key protein involved in venous control systems. These studies are expected to show that estrogen attenuates the development of hypertension by reducing venomotor tone and thereby, reduces a major factor contributing to the increase in cardiac output and blood pressure that initiates the hypertensive process. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ETIOLOGY OF NEPHROPATHY AND HYPERTENSION IN AASK PATIENT Principal Investigator & Institution: Lipkowitz, Michael S.; Medicine; Mount Sinai School of Medicine of Nyu of New York University New York, NY 10029 Timing: Fiscal Year 2001; Project Start 01-AUG-2000; Project End 31-JUL-2005 Summary: (adapted from the application) We will study the etiology of hypertension and nephropathy in the majority of the 1094 African-American patients in the AfricanAmerican Study of Kidney Disease in Hypertension (AASK). The AASK study is an NIH sponsored clinical multicenter trial comparing the effect of two levels of blood pressure control and three antihypertensive regimens on progression of hypertensive nephropathy in African Americans. There is a disproportionate number of African Americans with hypertensive target organ damage, suggesting a genetic susceptibility in this population; paradoxically, few studies have been performed to evaluate such genetic predisposition to disease in this high risk population. The patients of the AASK study offer a unique opportunity to prospectively determine the genetic factors involved in hypertension and hypertensive target organ damage within a high risk and understudied population. The proposed studies will immortalize white blood cells from patients to provide a renewable source of tissue and DNA from this unique study group, and follow two approaches in assessing the etiology of hypertension, nephropathy, and their sequelae: 1. Studies are proposed to determine whether polymorphisms in candidate genes for hypertension, renal failure, and cardiac disease, including renin-angiotensin system genes, insulin resistance (beta3-adrenergic receptor and lipoprotein lipase) genes, Liddle's syndrome (beta and gammaENaC) genes, and others are related to hypertension or renal failure, severity/rate of progression of renal disease, severity/refractoriness of hypertension, electrocardiographic left ventricular hypertrophy, cardiovascular morbidity and mortality, and overall morbidity and mortality. 2. Additional studies will employ a new technique, mapping by admixture linkage disequilibrium (MALD), which uses the linkage disequilibrium caused by recent admixture of founder populations to localize genes linked to a particular phenotype within a 5-20 centiMorgan region in a genome-wide screen. By utilizing microsatellite markers from the carefully phenotyped patients of the AASK Study it should be
26 Hypertension
possible to identify regions of interest containing genes associated with hypertension, renal failure, and the outcomes described above for candidate genes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FEEDBACK CONTROL BY H3 RECEPTORS IN HYPERTENSIVE Principal Investigator & Institution: Washington, Benny; Tennessee State University 3500 Centennial Blvd Nashville, TN 37203 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2006 Summary: H3 histamine receptors provide feedback inhibition of synthesis and release of histamine from the hypothalamus, as well as, inhibition of the release of other neurotransmitters, such as acetylcholine from intestinal cholinergic nerves, and norepinephrine from the retina and cerebral cortex. Preliminary data indicate that the ability of H3 receptors to regulate feedback inhibition of histamine release in spontaneously hypertension rats is age-dependent. Our central hypothesis is sustained hypertension enhances H3-receptor's ability to regulate the synthesis and release of histamine in the CNS. To test this hypothesis we will: 1) assess changes in the evokedrelease of histamine in the CNS (hypothalamus); 2) investigate quantitatively, changes in H3-histaminergic receptors in the CNS (hypothalamus); and 3) identify changes in the expression of H3 receptor mRNAs in the CNS (hypothalamus) using RT-PCR during the progression of hypertension. The proposed studies will be conducted in the CNS of spontaneously hypertensive (SHR) phenotypes and compared with normotensive (WKY) rats-accepted models for essential hypertension during the progession of hypertension. The results/data obtained will define the role of histamine in the development of hypertension and the function of the H3 receptor in upregulation or downregulation of histamine. The information generated from this investigation will also provide important insights into the pathophysiological causes of hypertension and could offer an opportunity to develop potential new drugs for the management of hypertension. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: FETAL ORIGINS OF ADULT HYPERTENSION IN MICROSWINE Principal Investigator & Institution: Bagby, Susan P.; Professor of Medicine; Oregon Health & Science University Portland, OR 972393098 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2007 Summary: A growing body of human epidemiologic evidence links intrauterine growth retardation (IUGR) and adult "Syndrome X": hypertension, obesity, diabetes, coronary artherosclerosis, and risk of renal failure. In preliminary studies in microswine, maternal isocaloric protein restriction (0.5% vs. 14%) during nephrogenesis (last 1/3 gestation +3 weeks post- natally) yields IUGR at 3 weeks, rapid catch-up growth to 123% of control body weight (overweight), adult hypertension, reduced nephron number by histology, and normal GFR suggesting single-nephron hyperfiltration. Renal cortical AT1 and AT2 receptors by quantitative autoradiography are abnormal in both 3-week and 6-month old offspring of low-protein sows but in unique ways. We hypothesize that excess appetite/body image size generate excess protein load for the low number of nephrons, driving sustained intrarenal renin/AngII (RAS) activation to achieve nitrogen balance via single-nephron hyperfiltration. This RAS response is predicted to amplify the Na retention and extracellular fluid volume (ECV) excess expected with fewer nephrons, yielding hypertension. In a microswine model of maternal protein restriction/IUGR, studies in offspring will address: 1) whether IUGR modifies the activation state of
Studies 27
circulating vs. intrarenal RAS at key developmental stages (preterm; 2-weeks postnatal; 3-month pre- hypertensive juvenile; and 6-month adult), including mRNA, protein, and activity levels for renin, angiotensinogen, ACE, AngII, and AT1/AT2 receptors at LowProtein vs. Normal-protein offspring on ad lib normal diet; 2) whether IUGR enhances postnatal homeostatic responses of blood pressure (BP), ECV, Na balance, and circulating vs. intrarenal RAS components in vivo to dietary sodium manipulation to AngII blockade; 3) whether IUGR amplifies AT1 signaling efficacy in vitro in cultured vascular smooth muscle at each developmental stage; and 4) whether global caloric restriction to limit adult bodyweight to 75% of Normal-protein controls in IUGR offspring attenuates adult BP, body fat mass, ECV, and intrarenal RAS components. Results are relevant to etiologic mechanisms of hypertension and to the preventive management of IUGR-exposed children at risk for adult cardiovascular and renal disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GAMMA-MSH AND SODIUM METABOLISM Principal Investigator & Institution: Humphreys, Michael H.; Professor; Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): Variations in dietary sodium intake initiate integrated adjustments in neural and hormonal systems regulating sodium excretion by the kidneys in order to maintain overall sodium balance. These adjustments remain incompletely understood despite intensive study. In addition, a complex relationship exists between sodium balance and blood pressure such that high dietary sodium intake provokes hypertension in susceptible individuals. Studies from our laboratory have identified a previously unrecognized hormonal system which participates in the maintenance of sodium balance on a high sodium intake. This system involves the synthesis of the prohormone proopiomelanocortin (POMC) in the pituitary, and its processing into the secreted natriuretic peptide gamma-melanocyte stimulating hormone (gamma-MSH). This system is activated by a high sodium diet in rats, mice, and humans, and fails to respond to sodium loading in rodents with genetic forms of hypertension. We shall characterize the hypertension seen with dietary sodium loading in mice with gamma-MSH deficiency due to targeted disruption of the proconvertase 2 gene, necessary for processing of POMC into gamma-MSH, and establish that the hypertension is corrected by infusion of gamma-MSH. We shall also evaluate the consequences of inhibition of gamma-MSH release from the pituitary by dopaminergic stimulation in rats fed a high sodium diet, and test the effects of sodium loading in mice lacking melanocortin receptors with which gamma-MSH interacts. In addition, we shall characterize the nature and location of renal melanocortin receptors, and determine if their expression is altered by a high sodium diet. We shall determine if gamma-MSH acts centrally to inhibit sympathetic nervous outflow and lower blood pressure in hypertensive PC2 -/- mice on the high sodium diet. Finally, we shall examine the effects of high vs low sodium diets on blood pressure and plasma gamma-MSH concentration in normal subjects and patients with mild essential hypertension studied in a General Clinical Research Center to determine if this system functions in humans in a manner parallel to that in rodents and evaluate if individuals with salt-sensitive hypertension demonstrate blunted activation of the system. These studies should extend our understanding of the integrated regulation of sodium balance when challenged with a high sodium intake, and the relationship between sodium intake and the development
28 Hypertension
of hypertension, by providing mechanistic insight into a novel and previously unrecognized system activated by high dietary sodium intake. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENES OF HYPERTENSION IN AFRICAN AMERICANS Principal Investigator & Institution: Kotchen, Theodore A.; Professor of Medicine; Medicine; Medical College of Wisconsin Po Box26509 Milwaukee, WI 532264801 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2007 Summary: (provided by applicant): We hypothesize that we will be able to identify genes contributing to hypertension in African Americans by focusing on the physiological pathways that determine arterial pressure. Over the past 6 years, we have extensively characterized African Americans for phenotypes related to cardiovascular and renal function. Based on recently completed genome scans, we have identified several chromosomal regions likely to contain genes influencing hypertension-related phenotypes in hypertensive, African American sib pairs. For several phenotypes, overlapping QTLs have also been identified in related studies in a genetically isolated French Canadian population and/or in homologous chromosomal regions in the F2 cross of Dahl-salt sensitive x normotensive Brown Norway rats. We now propose to extensively phenotype 500 hypertensive and 500 normotensive African American subjects to conduct a genetic association study, using a SNP genomic scan approach. To achieve a clear separation of blood pressures from hypertensive subjects, normotensive subjects will be selected from the lower third of the population-based blood pressure distribution. Hypertensive (BMI), and age. Inclusion of phenotypes is based on their relevance to the pathophysiology of hypertension and prior evidence of "heritability." Candidate genes for SNP analysis will be selected within chromosomal regions of two QTLs that we have previously demonstrated to be linked to hypertension-related phenotypes--a QTL for body mass index on chromosome 1 and a QTL for microalbuminuria on chromosome 18. SNP analyses will be carried out in 15 percent of the genes within each of these QTLs, and genes will be selected on the basis of their relevance to hypertension, including documented sequence conservation for blood pressure related QTLs with rat or mouse. The final goal of the project is to determine if distinct clusters of blood pressure related phenotypes can be identified that will permit stratification of hypertensive individuals into distinct subgroups to facilitate the analysis of the genetic determinants of hypertension and/or provide mechanistic leads to genes contributing to these traits. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENETIC DETERMINANTS OF HYPERTENSION, LVH, AND CHF Principal Investigator & Institution: Dries, Daniel L.; Internal Medicine; University of Texas Sw Med Ctr/Dallas Dallas, TX 753909105 Timing: Fiscal Year 2002; Project Start 17-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): The endogenous cardiac hormonal system (CHS) moderates blood pressure, the development of left-ventricular hypertrophy (LVH) in response to hypertension, and delays progression of systolic heart failure. The "afferentlimb" of the CHS refers to the ability of the myocardium to release atrial and brain natriuretic peptide (ANP and BNP) in response to pressure overload, and the "efferentlimb" describes the biological action of these hormones in target tissue. Plasma levels of cGMP are tightly correlated with the efferent actions of the cardiac hormones providing a validated method to measure the efferent function of the CHS in humans. We
Studies 29
hypothesize that gene-environment interactions involving genes related to critical components of the afferent and efferent cardiac hormonal signaling pathways, and gene-gene interactions between these genotypes and the ACE-gene, contribute to interindividual variation in susceptibility to hypertensive heart disease. Moreover, differences in the frequencies of these alleles in special populations may explain the increased susceptibility of African-Americans to LVH, development of heart failure, and progression of established heart failure. In order to address these hypotheses, we will identify patients with untreated hypertension and LVH in a random population sample of approx. 3,000 subjects. We will then compare the afferent and efferent function of the CHS in African- American and Caucasian subjects with untreated hypertension and leftventricular hypertrophy, and identify phenotypes characterized by reduced function of either the afferent or efferent function of the CHS. We will sequence these subjects to identify sequence variants in candidate genes critical to the cardiac hormonal signaling pathways (the gene for ANP, BNP, the type A and C cardiac hormone receptors, and corin). We will then study the association of these genotypes with prevalent hypertension, cardiac MRIdetermined LVH, and prevalent hypertensive cardiomyopathy in the two ethnic cohorts. In addition we will analyze the association of these genotypes with prognosis in patients with advanced systolic heart failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC EXPRESSION OF RISK GENES IN HYPERTENSION Principal Investigator & Institution: Seely, Ellen W.; Professor; Brigham and Women's Hospital 75 Francis Street Boston, MA 02115 Timing: Fiscal Year 2001; Project Start 25-JUN-2001; Project End 31-MAY-2005 Summary: (Verbatim from the application): Hypertension is a major contributor to cardiovascular disease, the leading cause of death in US women. Most studies of hypertension have focused on men. Women have a lower incidence of hypertension until age 50 at which time, the incidence of hypertension in women becomes greater than that in men. Since age 50 is the average age of menopause in US women, this observation suggests that ovarian steroids, present in the premenopausal state, mask genetic predisposition to hypertension and that with loss of these steroids at menopause, genetic predisposition to hypertension becomes manifest. We have shown that a specific intermediate phenotype of essential hypertension is associated with polymorphisms of the angiotensinogen gene which result in greater tissue activity of the renin-angiotensin-aldosterone system (RAAS) as a possible cause of hypertension. This phenotype is uncommon in premenopausal women compared to age-matched men but the frequency of this phenotype increases at menopause becoming equal in men and women. Estradiol has major effects on many of the genes of the RAAS and therefore is a prime candidate for modulating the expression of genotype and being responsible for the change in phenotype frequency in pre versus postmenopausal women. The overall objectives of this proposal are to: 1) demonstrate a difference in frequency of specific polymorphisms of genes of the RAAS in premenopausal hypertensive women as compare to hypertensive postmenopausal women and men, 2) test the hypothesis that the administration of estradiol to postmenopausal hypertensive women with these specific polymorphisms in RAAS genes will alter the intermediate phenotype and lower blood pressure, 3) examine activity of the tissue RAAS according to specific genotypes in these three groups. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
30 Hypertension
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Project Title: GENETIC LINKAGES IN CALCIUM OXALATE STONE DISEASE Principal Investigator & Institution: Mandel, Neil S.; Professor; Medicine; Medical College of Wisconsin Po Box26509 Milwaukee, WI 532264801 Timing: Fiscal Year 2003; Project Start 15-AUG-2003; Project End 31-MAY-2008 Summary: (provided by applicant): Kidney stone disease is a substantial health problem associated with significant pain, suffering, and economic costs. 5% to 15% of the population will have a symptomatic episode of a stone by the age of 70 and at least 50% of these individuals will have recurrent disease. To date, the only well-defined genetic abnormalities leading to hyperoxaluria and calcium oxalate stone disease have been described for primary and secondary hyperoxaluria and associated with specific enzyme errors. However, the familial tendency of idiopathic calcium oxalate stone disease coupled with the common trend for stone recurrence have led to the speculation that many idiopathic calcium oxalate stone formers may have a genetic predisposition for their stone disease. We propose to explore the genetic linkages underlying idiopathic hyperoxaluria and calcium oxalate stone disease, utilizing and applying to stone disease the methods and genetic observations from existing animal models currently being used to explore the genetic basis of hypertension. The application of genomic methods to stone disease is new. The proposed studies will allow us to define the genetic linkages that mediate critical mechanistic events in idiopathic calcium oxalate stone disease including the initiation, progression, and physiologic consequences of hyperoxaluria, crystalluria, and calcium oxalate crystal retention. We will use available genomic rat resources to explore both the genetic linkages in calcium oxalate stone disease and the genetic linkages between calcium oxalate stone disease and hypertension. Three specific major breeding colonies will be used: 1) The Dahl SS rat that demonstrates salt sensitive hypertension, 2) A colony of Brown Norway rats that are about 62% consomic with the Dahl SS rat, and 3) Consomic strains of Dahl SS rats that have one chromosome at a time introgressed into the Dahl SS genetic background from the Brown Norway rat, creating a rat that is about 98% consomic with the parent Dahl rat. Our working hypothesis is that there are specific genetic linkages that are associated with idiopathic hyperoxaluria and calcium oxalate stone disease and that the pathophysiology of stone disease associated with hypertension is different from stone disease absent hypertension. There are three Specific Aims. Specific Aim I: To determine what the associative effect of hypertension and hyperoxaluria is on urine chemistry and how these associated challenges influence the potential for calcium oxalate stone disease. Specific Aim II: To define the specific tissue injury associated with hypertensive and with hyperoxaluric challenges and to correlate these findings with effective calcium oxalate crystal attachment and stone maturation. Specific Aim III: To identify the chromosomes that harbor genes that control major susceptibility and resistance to hyperoxaluria, calcium oxalate crystalluria, and stone disease using a chromosomal replacement panel of consomic Dahl SS rats. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENETIC STUDIES OF MINERALOCORTICOID FUNCTION Principal Investigator & Institution: Geller, David S.; Internal Medicine; Yale University 47 College Street, Suite 203 New Haven, CT 065208047 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-JAN-2005 Summary: (adapted from the application) Hypertension is one of the most common diseases in America--being present in a 20% of the population. It is also one of the leading causes of morbidity and mortality in the United States, via its effects on heart,
Studies 31
cerebrovascular and renal disease. Despite its prevalence, the underlying cause(s) of hypertension remain poorly understood. It is clear that there are environmental and hereditary genetic factors that predispose to the development of hypertension; identification of the genetic factors is made difficult, however, by the small effects of many genes coupled with overlying environmental factors. One approach to this problem has been to study single gene disorders that primarily affect blood pressure. The determinants of the molecular bases of glucocorticoid-remediable aldosteronism, Liddle's syndrome, Bartter's syndrome, Gitelman's syndrome and others has done to [sic] much to increase our understanding of renal physiology and the kidneys role in blood pressure regulation. In this project, we describe the discovery of a new form of mendelian hypertension caused by activating mutation in the mineralocorticoid receptor, the effector molecule for aldosterone in the distal nephron. Through characterization of the affected kindred and in vitro analysis of the mutant receptor, we will discern the mechanism by which the mutation activates mineralocorticoid receptor function. It is anticipated that this information will yield insight into normal receptor function, which may prove useful in drug design. By creating a mouse model of the disease, we hope to generate a mechanism to study the effects of a wide variety of steroid agonists and antagonists in vivo, and also to gain insight into the effects of the activated mineralocorticoid receptor in tissues other than the kidney. This project is designed to provide training in molecular and human genetics for the Principal Investigator and to enable him to develop a career in academic Nephrology with a focus on the molecular genetics of hypertension and renal disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC STUDY ENDOTHELIAL FUNCTION (PILOT)
OF
ARTERIAL
COMPLIANCE
AND
Principal Investigator & Institution: Li, Rongling; Morehouse School of Medicine Atlanta, GA 30310 Timing: Fiscal Year 2002; Project Start 30-SEP-1987; Project End 31-JUL-2006 Summary: (provided by applicant): The objective of this pilot study is to develop and implement standardized methods for investigating both genetic and environmental determinants of endothelial function and arterial compliance (elasticity) in African Americans. African Americans have stiffer arteries and a higher prevalence of hypertension compared to other ethnic groups in the US. Specific genetic makeup and environmental factors may work together to influence the susceptibility. The specific aims of this pilot study are: 1) to develop standardized methods for collecting and validating family data from African-American hypertensive and normotensive probands, their family members and first-degree relatives; 2) to assess the difference in allele and genotype frequency, endothelial function, vascular compliance and blood pressure within and between the two sets of families; 3) to compare the distribution of genetic, behavioral, physical, psychosocial, biochemical and other environmental risk factors in families with or without high family risk of hypertension; and 4) to estimate preliminarily genetic and environmental determinants to familial clustering of risk factors, endothelial dysfunction, arterial stiffness and hypertension. The study will use family-based case-control design. We propose to recruit 5 African- American families in which probands (40% females) and at least one of their parents have hypertension, and 5 African-American families with probands (40% females) and both parents to be free of hypertension. Married individuals aged 30-50, who have both parents alive and at least two children and two siblings, will be included as probands in this study. An interviewer-administered questionnaire will be utilized to obtain information on
32 Hypertension
participants. demographic, behaviors, lifestyles, medical history, and family history of cardiovascular disease, socioeconomic status and other cardiovascular risk factors. Participants will have physical examinations, and measurements of arterial compliance and brachial endothelial function. Blood samples will be obtained to determine genotypes of endothelial nitric oxide synthase (eNOS) and angiotensin-converting enzyme (ACE), blood chemistry, hematology and lipid profiles, and to establish cell lines for future genetic studies of arterial disease. Statistical analyses will be conducted to estimate the main effects of genetic and environmental risks for arterial stiffness and their interactions among gene-gene and gene-environmental factors, such as smoking or physical inactivity, controlling for other cardiovascular risk factors. This study has the potential to provide insights into strategies for recruiting multi-generational families within the African-American community and the etiology and pathogenesis of arterial disease which will allow the development of effective strategies for early prevention of arterial disease, and its sequelae in an under-studied and under- served population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETICS OF SALT SENSITIVITY IN AFRICAN AMERICANS Principal Investigator & Institution: Douglas, Janice G.; Professor; Medicine; Case Western Reserve University 10900 Euclid Ave Cleveland, OH 44106 Timing: Fiscal Year 2001; Project Start 15-MAY-2000; Project End 31-MAR-2005 Summary: The prevalence, morbidity, and mortality of arterial hypertension are disproportionately high in the African-American population. Essential hypertension is a polygenic and heterogeneous disorder. In particular, African-Americans display an amplified blood pressure response to salt. The cellular and molecular mechanisms of salt-sensitive hypertension in humans remain poorly defined and our knowledge of potential genetic mechanisms remains incomplete. We recently observed an augmented blood pressure response to a salt challenge in healthy non-obese African- Americans females as compared to Whites. African-Americans also had significantly higher intracellular Na and depressed activity of the Na pump (86 Rb uptake)as compared to Whites suggesting these may be important phenotypic markers of salt-sensitive hypertension. In fact, an increase in intracellular Na was positively correlated with the increases in systolic blood pressure following one week of low salt vs one week of high salt diet in African-Americans but not in Whites. The inverse relationship was noted for the Na pump in African-Americans. The proposed study will carry out genetic studies of sibships with at least two hypertensive embers ascertained from the AfricanAmerican population. Emphasizing model- free approaches to genetic linkage analysis based upon hypertensive sibling pairs, candidate genes that have been associated with salt-sensitive hypertension in either human or animal studies will be evaluated with respect to these intermediate phenotypes, and blood pressure responses to a salt challenge. The aims of this proposal are: l) To characterize the intermediate phenotypes of salt sensitivity, intracellular Na, sodium pump activity, and protein expression in a cohort of 500 hypertensive siblings in 160 sibships and to genotype these individuals; wherever possible, parents of these subjects will also be genotyped in order to better establish identity by descent relationships. 2) To assess linkage of the various candidate loci with intermediate phenotypes relating to the magnitude of blood pressure change with a salt challenge using univariate and multivariate approaches. The overall aim of this project is to improve our understanding of the genetic basis and phenotypic characterization of salt-sensitive hypertension in African Americans. To this end, careful analytic attention will be paid to the development of improved phenotype
Studies 33
definition, as well as to the consideration of gene-gene and gene-environment interaction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETICS OF VASCULAR REMODELING IN HYPERTENSION Principal Investigator & Institution: Berk, Bradford C.; Professor & Chairman; Medicine; University of Rochester Orpa - Rc Box 270140 Rochester, NY 14627 Timing: Fiscal Year 2001; Project Start 01-JUN-1999; Project End 31-MAY-2003 Summary: An important long-term goal in the approach to treating atherosclerosis and hypertension is to understand the mechanisms that regulate the structure of blood vessels; a process we will term "vascular remodeling." Hypertension is a major risk factor for development of atherosclerosis (strong correlation between fatty streak formation and BP) and for clinical events (strong correlation between unstable angina, myocardial infarction, stroke and BP). Our major hypothesis is that hypertension is a major risk factor for atherosclerosis because the ability of the vessel to compensate for plaque burden (a process that requires outward vascular remodeling) is inhibited in hypertensive patients. We also suggest that impaired remodeling in hypertensives is due to 1) direct effects of elevated blood pressure, and 2) pressure-independent genes associated with essential hypertension that modulate the ability of the vessel to remodel. To gain insight into the mechanisms by which hypertension influences vascular remodeling we will selectively breed normotensive and hypertensive inbred rat strains that differ in their ability to remodel and perform a genetic analysis. Our preliminary data document significant differences in lumen diameter induced by blood flow among inbred rat strains. Our hypothesis is that among rats with genetic hypertension (e.g. SHR, SHR-SP, and Genetically Hypertensive rat of New Zealand (GH) there will be additional genetic determinants that modulate remodeling in response to physiologic stimuli such as flow. The use of genetic linkage analysis in the proposed project represents a novel approach to understanding the mechanisms that regulate vascular structure. Its advantage is that it is based on recombination probability, and requires no prior knowledge of the mechanisms to find the gene(s) that contribute to the process. We have developed and published a reproducible and quantitative model for flow-dependent vascular remodeling. Using this model to study inbred rat strains we have made the exciting preliminary observation that the remodeling abilities of Brown Norway (BN, high) and GH (low) strains differ by more than 2 standard deviations. Based on these data our major goal is to perform a BN x GH cross and total genomic scan to identify major genes that alter the ability of vessels to remodel in hypertension. Aim 1: Characterize the time course of flow- induced remodeling in the carotid arteries of Brown Norway rats (BN, high remodelers) and Genetically hypertensive rats (GH, low remodelers). Aim 2: Intercross GH and BN to obtain 200 F2 progeny that express a range of remodeling and blood pressure phenotypes. Aim 3: Genotype P0 and F2 rats and use interval mapping to determine the chromosomal location of the quantitative trait loci (QTL) that are responsible for flowinduced remodeling and blood pressure. Aim 4. Create a congenic strain of GH rats containing genes associated with high remodeling ability. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HEME-HEME OXYGENASE-CARBON MONOXIDE SYSTEM IN HYPERTENSION Principal Investigator & Institution: Johnson, Fruzsina K.; Tulane University of Louisiana New Orleans, LA 70118
34 Hypertension
Timing: Fiscal Year 2002; Project Start 20-SEP-2002; Project End 31-AUG-2007 Summary: Carbon monoxide (CO) can be endogenously formed during the enzymatic degradation of heme by heme oxygenase (HO). Although CO is generally regarded as a vasodilator, by its inhibitory effect on nitric oxide synthase it is also a vasoconstrictor. On high salt diet Dahl salt-sensitive rats (DS) develop hypertension that is accompanied by decreased NO formation. This project will investigate the role of the vascular hemeHOCO system in endothelial dysfunction during salt-induced hypertension in DS rats. The following specific aims will be addressed: Aim1: Characterize the temporal changes in various indeces of the HO system, arteriolar NO function, and cardiorenal pathologies in DS and salt-resistant (DR) rats on high and low salt diets. Aim2: Determine the effects of genetic predisposition for salt-sensitivity, high salt diet, and hypertension on various indeces of the HO system, arteriolar NO function, and cardiorenal pathologies in DS and DR rats. Aim3: Establish the effects of altered HO system function on artedolar NO function, and cardiorenal pathologies in DS and DR rats on high and low salt diets. Methods: Some animals will receive antinhypertensive treatment, others pressor treatment. Some groups will be treated with heme-L-lysinate, others with zinc protoporphyrin IX to increase or decrease endogenous CO formation, respectively. HbCO will be measured with a clinical grade analyzer (OSM3). Vascular HO-1 protein content will be studied by Western-blotting and immunohistochemistry (ABC method). NO function will be examined in isolated skeletal muscle arterioles by studying responses to a NO synthase inhibitor, an endothelium-dependent vasodilator, and a NO donor. Internal diameter of pressurized arterioles will be measured with a microscope and a video caliper. Objectives: These studies will provide information on temporal changes in HO function, cardiorenal pathologies and arteriolar NO function during salt-induced hypertension. Furthermore, they will evaluate the factors (genetic salt-sensitivity, high salt diet, and/or hypertension) contributing to HO-mediated NO dysfunction during salt-induced hypertension in DS rats. They will also examine the effects of altered endogenous CO formation on arteriolar NO function and cardiorenal injury in DS rats during salt-induced hypertension. Understanding the pathological basis of endothelial dysfunction may help to develop causetargeted therapy resulting in prolonged survival of hypertensive patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HEPARIN ON HYPOXIC PULMONARY HYPERTENSION AND REMODELING Principal Investigator & Institution: Hales, Charles A.; Professor of Medicine; Massachusetts General Hospital 55 Fruit St Boston, MA 02114 Timing: Fiscal Year 2001; Project Start 01-JUL-1987; Project End 31-MAY-2005 Summary: Thickening of the media with intrusion on the vascular lumen contributes substantially to the pulmonary hypertension seen in primary or secondary pulmonary hypertension. Heparin has been shown to be antiproliferative and antihypertrophic for systemic and pulmonary artery smooth muscle cells (PASMC) in vitro and has been variably effective at inhibiting in vivo remodeling in several systemic and pulmonary models. We have found that commercial heparin lots vary widely in their antiproliferative activity. However, an effective antiproliferative heparin in vitro for PASMC proliferation can prevent hypoxic pulmonary hypertension in mice, rats and guinea pigs and can reverse it in guinea pigs even in the presence of continued hypoxia. We have also shown that heparin's ability to inhibit PASMC proliferation and in vivo pulmonary hypertension correlates with its ability to prevent mitogen stimulation of the Na+/H+ antiporter. We have found that highly specific antagonists of the Na+/H+
Studies 35
antiporter such as dimethyl amiloride (DMA) can inhibit PASMC proliferation in response to growth factors in vitro and can substantially prevent hypoxic pulmonary hypertension and remodeling in rats. As we dissect the chemistry of antiproliferative heparins we have shown, among other things, that the protein core is unimportant and that 3-0-sulfate is not an important feature in full-length heparin. We have made new heparin derivatives by O-acetylating heparin with butanoyl and hexanoyl which are more potent antiproliferative agents on PASMC than native heparins and are nonanticoagulant. We have found that in PASMC heparin stimulates the production of the cell cyclin kinase inhibitors p21 and p27 which are inhibitors of cell proliferation in other cells. With this progress we hope to continue our pursuit of an effective treatment for pulmonary hypertension with the following specific aims: 1) Continue examining strongly versus weakly antiproliferative heparins in order to discover the reasons for the differences with a goal of amplifying the antiproliferative potency and perhaps divorcing it from the anticoagulative and osteopenic properties. 2) Determine in the pig, as a preclinical trial in a large mammal, if heparin or heparin fragments or the Na+/H+ inhibitor DMA are effective at preventing hypoxic pulmonary hypertension and 3) Determine if heparin's mechanism of action in preventing SMC proliferation is via stimulation of the cyclin kinase inhibitors p21 and p27. Thus, this proposal may lead to new therapeutic agents for humans with pulmonary hypertension and may elucidate a new understanding of how heparin prevents PASMC growth. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HYPERTENSION / ATHEROSCLEROSIS PARADIGMS Principal Investigator & Institution: Herrera, Victoria L.; Profesor of Medicine; Medicine; Boston University Medical Campus 715 Albany St, 560 Boston, MA 02118 Timing: Fiscal Year 2001; Project Start 15-AUG-1999; Project End 31-JUL-2003 Summary: Clinical and experimental data demonstrate unequivocally that hypertension accelerates atherosclerosis. This is an intriguing pathogenic phenomenon since the interaction is quite unambiguous for two complex diseases marked by clinical and genetic heterogeneity. Currently, the mechanisms underlying this interaction have not been elucidated. Strategic animal models are needed to mechanistically dissect pathogenesis. We have developed a transgenic hyperlipidemia- genetic hypertensive rat model by hepatic over-expression of human cholesteryl ester transfer protein (hCETP) in Dahl salt-sensitive (S) rats. Transgene high copy number in Tg[hCETP]53 Dahl S rats elicits aortic, coronary and intramyocardial atherosclerotic lesions and decreased life spans compared with no lesions in non-transgenic Dahl S controls and minor medial changes in Tg[hCETP]25 Dahl S rats with transgene moderate copy number. In this research proposal, we will investigate whether synergistic decrease of NO activity induced by both hypertension and atherosclerosis results in enhanced activated endothelial molecular and cellular changes which are then differentially amplified. as enhanced pro-inflammatory and pro-thrombotic changes leading to progressive vascular disease. The following specific aims will be studied: 1) Determined whether the endothelium of hypertensive, markedly hyperlipidemic Tg[hCETP]53 Dahl S rats exhibit exaggerated endothelial cell activation (marked by enhanced and/or sustained up- regulation of ICAM-1 and P-selectin gene expression and increased monocyte adhesion compared with control age-matched normotensive, markedly hyperlipidemic Tg[hCETP]53 Dahl salt-resistant (R) male rats, and control non-transgenic age-matched hypertensive, normolipidemic Dahl S rats. 2) Determine whether exaggerated activation results in amplified dysregulation through enhanced pro-inflammatory response (marked by increased TNF-alpha expression and increased NF-kappaB activation in
36 Hypertension
endothelial cells, macrophages) and/or pro-thrombotic response (marked by tissue factor TF expression in endothelial cells, macrophages, intimal smooth muscle cells)-distinct from corresponding arteries in control normotensive, markedly hyperlipidemic Tg[hCETP]53 Dahl R rats as well as in control hypertensive, normo-lipidemic Dahl S rats. 3) Define the hierarchical relationship of hypertension hyperlipidemia and decreased NO activity on the acceleration of atherosclerosis by determining which manipulation, high salt diet, Western Type Diet, or NO-inhibitor L-NA treatment will cause Tg[hCETP]25 Dahl S rats to exhibit similar atherosclerotic lesion phenotype similar to Tg[hCETP]53 Dahl S rats. 4) Define the mechanistic role of endothelial NO pathway in the interaction of hypertension and atherosclerosis; sufficient versus essential but not sufficient versus modifying but not essential by early, mid-point, and late-onset L-arginine treatment of Tg[hCETP]53 Dahl S rats and determine whether the acceleration of atherosclerosis by hypertension is differentially attenuated, if not significantly resolved. This research proposal will provide key information on mechanisms that underlie the acceleration of atherosclerosis by hypertension which will identify new strategies for intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INTEGRINS
HYPERTENSION
AND
ARTERIAL
INJURY--A
ROLE
FOR
Principal Investigator & Institution: Meininger, Gerald A.; Regents Professor and Associate Head; Medical Physiology; Texas A&M University Health Science Ctr College Station, TX 77843 Timing: Fiscal Year 2001; Project Start 15-AUG-1999; Project End 31-JUL-2003 Summary: The overall goal of this project is to test the prevailing hypothesis that hypertension and arteriosclerosis may be linked through a mechanism that involves oxidative stress. Our working hypothesis is that oxidative stress in hypertension and atherosclerosis acts to induce similar alterations in the expression of specific integrins and extracellular matrix (ECM) proteins that are responsible for changes in vasomotor function and vascular smooth muscle (VSM) phenotype. Our recent studies have established a novel link between VSM and endothelial integrins and the control of vascular tone. In addition, preliminary data indicates that oxidative stress can alter the expression of at least one of the VSM integrins linked to vasomotor activity and an ECM protein that is a ligand for this receptor. These altered integrin/matrix interactions may predispose the arterial wall to development of vascular pathology. This project incorporates a model of renal hypertension and atherogenesis that will be studied at various stages of disease development in large, intermediate and microvascular sized arterial vessels. Assessments will be made of the redox status, integrin and ECM profiles and vascular reactivity to soluble and insoluble integrin-binding ligands. These ligands will include synthetic Arginine-Glycine-Aspartic Acid (RGD) containing peptides and type I collagen and osteopontin, which are up-regulated following vascular injury. Our strategy is combining studies of intact vessels, cellular, biochemical and molecular approaches will provide a powerful approach for testing our hypothesis and systematically integrating our results, The specific aims are: Aim 1: Characterize the vasomotor response for large intermediate and small arterial vessels to known integrinbinding peptides, type I collagen and osteopontin at varius stages of development for a rat model of renal hypertension and/or imposed oxidative stress (allylamine treated). Vasoactivity will be correlated with measurements of redox status and integrin/ECM profiles. Aim 2: Characterize the vascular redox status and mechanisms leading to the development of oxidative stress in models of renal hypertension and atherogenesis and
Studies 37
evaluate the role of NFkappaB as a common signal transduction pathway. Aim 3. Characterize and evaluate changes in vascular ECM/integrin expression at the gene and protein levels that are associated with renal hypertension or oxidative stress and to define the influence of oxidative stress on extracellular matrix and integrin gene expression. These studies will provide new information that will advance our understanding vascular function in hypertension and atherosclerosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HYPERTENSION AND COLLAGEN: EFFECT OF AC-SDKP Principal Investigator & Institution: Rhaleb, Nour-Eddine; Internal Medicine; Case Western Reserve Univ-Henry Ford Hsc Research Administraion Cfp-046 Detroit, MI 48202 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2006 Summary: (provided by applicant): Hypertension causes left ventricular hypertrophy (LVH) and increased LV interstitial and perivascular collagen deposition. Increased cardiac collagen may alter function in hypertrophied hearts. Angiotensin converting enzyme inhibition(ACEi) has been shown to reverse LVH in hypertension. This effect has been attributed to blockade of angiotensin II (Ang II) formation and kinin degradation. We have shown that N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP), another natural substrate for ACE, prevents LV monocyte/macrophage infiltration and fibrosis without altering blood pressure (BP) or LVH in hypertension. We believe this is the first demonstration that Ac-SDKP affects cardiac fibrosis; however, the mechanism(s) or receptor(s) by which Ac-SDKP affords cardioprotection are not known, nor whether Ac-SDKP contributes to the cardioprotective effects of ACEi. We hypothesize that (1) Ac-SDKP has an anti-inflammatory and antifibrotic effect on the heart in hypertension via specific receptor(s) linked to a cascade of signal transduction, including MAP kinase, protein kinase C (PKC), NF-kB and TGF-beta, and (2) the effect of ACEi on the heart is mediated in part by Ac-SDKP. In aim new analogues of AcSDKP and SDK fragments will be synthesized and tested to identify (1) an ACE-resistant analogue with an inhibitory effect similar to Ac-SDKP that can be radiolabeled and used to characterize Ac-SDKP receptor(s), and (2) an antagonist that specifically blocks the inhibitory effect of Ac-SDKP. In aim II we will determine whether (1) the effect of AcSDKP is linked to suppression of TGF-beta, CTGF and Smad expression, and (2) the effect of TGF-beta on collagen type I and/or III expression is affected by Ac-SDKP. We will also examine whether Ac-SDKP inhibits p38 and PKC activation in fibroblasts. In aim IV we will determine whether in vivo Ac-SDKP (1) inhibits inflammatory cell infiltration in the LV, p42/p44, p38 and/or PKC activity, NF-kB,TGF-beta, CTGF and Smads, (2) regresses cardiac fibroblast proliferation, collagen expression and synthesis, (3) increases matrix metalloproteinase activity, and (4) decreases cardiac expression of collagen I and III in rats with long-term hypertension. In aim IV we will examine whether the effect of ACE inhibitionon LV collagen deposition is mediated by Ac-SDKP. This project will provide important new information on the on the cardioprotective effect of ACEi in hypertension and the mechanism of action of Ac-SDKP. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HYPERTENSION IN AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE Principal Investigator & Institution: Schrier, Robert W.; Professor; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, CO 800450508
38 Hypertension
Timing: Fiscal Year 2001; Project Start 21-APR-2001; Project End 31-JUL-2001 Summary: Hypertension occurs commonly and early in the natural history of autosomal dominant polycystic kidney disease (ADPKD). Hypertension (HBP) has been shown to have an adverse effect on both patients and renal outcome in ADPKD. Moreover, left ventricular hypertrophy (LVH), a known risk factor for cardiovascular mortality and sudden death, occurs frequently in HBP ADPKD patients. At present it is not clear what is the optimal level of blood pressure reduction in HBP ADPKD patients to minimize loss of renal function or to reverse lVH. Given that hypertension is the most important treatable variable to affect renal and patients outcome in ADPKD, this project will determine in prospective longitudinal fashion the appropriate level of blood pressure control in HBP ADPKD patients. Secondly, since lVH also occurs in normotensive ADPKD patients, factors other than HBP or the ADPKD gene may play a role in the development of lVH in ADPKD patients. Given that activation of the renin-angiotensinaldosterone axis is important in ADPKD and that the deletion polymorphism of the angiotensin converting enzyme gene is associated with LVH, normotensive and HBP ADPKD patients with and without LVH will be studied with regard to the frequency of this genotype. As well, given that hypertension in the unaffected parent is associated with earlier and more frequent HBP in ADPKD patients, the frequency of the angiotensinogen gene variant M235T will also be studied with regard to onset of hypertension and frequency of preeclampsia in ADPKD patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HYPERTENSION, OXIDATIVE STRESS AND RACE Principal Investigator & Institution: Guo, Zhongmao; Meharry Medical College 1005-D B Todd Blvd Nashville, TN 37208 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JUL-2006 Summary: Data from humans and animal models suggest that oxidative stress might play a part in the pathogenesis of hypertension. For example, patients and animals suffering from hypertension have been shown to increase reactive oxygen species (ROS) production and decrease antioxidant capacity. ROS, e.g., superoxide and hydrogen peroxide, have been shown to induce contraction and proliferation of vascular smooth muscle cells in vitro. The research described in this pilot project will examine the relationship between hypertension and oxidative stress in African-Americans. The goal of this study is to test the hypothesis that hypertension is associated with an increased oxidative stress, This project includes three specific aims: In specific aim 1, we will determine the relationship between hypertension and the concentration of plasma F2isoprostane (an in vivo oxidative stress marker) and the production of blood hydrogen peroxide and superoxide. In specific aim 2, we will determine the relationship between hypertension and the activities of major antioxidant enzymes, including superoxide dismutases, catalase and glutathione peroxidases, in blood. In specific aim 3, we will determine the relationship between hypertension and the activities of ROS-generating enzymes, including xanthine oxidase and NADH/NADPH oxidase, in blood, if the hypothesis described above is correct, hypertensive patients will show a higher level of F2-isoprostanes, a higher production of ROS, higher activities of ROS-generating enzymes and/or lower activities of antioxidant enzymes than normotensive subjects. In this pilot project, we will focus on African-Americans because hypertension is more prevalent in African-Americans than that in Caucasians. However, no unifying hypothesis as to the genetic mechanisms responsible for the excess prevalence of hypertension among African-Americans has emerged. If results from this pilot project show that hypertension is associated with an increased oxidative stress, we will
Studies 39
propose a study to compare the oxidative status of different populations, e.g., AfricanAmericans and Caucasians with or without hypertension, to test if the high prevalence of hypertension in African-Americans is associated with a high level of oxidative stress. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HYPOTHALAMIC ROLE IN HYPERTENSION Principal Investigator & Institution: Stern, Javier E.; Assistant Professor; Pharmacology and Toxicology; Wright State University Colonel Glenn Hwy Dayton, OH 45435 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 31-MAY-2006 Summary: (provided by applicant): This proposal focuses on the role of preautonomic neurons in the paraventncular nucleus (PVN) of the hypothalamus in the pathophysiology of hypertensive disorders. Hyperactivity of the sympathetic nervous system is commonly present in patients with essential hypertension, and the level of autonomic disbalance is a major determinant of patients' prognosis. By virtue of reciprocal connections with afferent visceroceptive and efferent motor autonomic centers, the PVN stands as a potential neural substrate underlying altered sympathetic drive in hypertension. Accumulating evidence implicates the PVN as an important component in the neuronal circuit involved in the pathophysiology of hypertension. In general, the cellular mechanisms involved in altered neuronal excitability during hypertension remain unknown. Since the PVN contains both preautonomic parasympathetic and sympathetic neurons, we propose to use it as a model to study altered cellular mechanisms contributing to unbalanced autonomic outflow, characteristic of hypertension. We hypothesize that the cellular properties of PVN preautonomic neurons innervating functionally different autonomic targets are differentially altered in hypertension, contributing to altered autonomic drive. Our preliminary data shows our ability to conduct experiments to test these hypotheses, and supports and altered function of these neurons in hypertension. Using a multifaceted approach combining in vitro electrophysiological recordings with immunohistochemical and in situ hybridization techniques we will answer the following questions: 1) What are the main intrinsic and extrinsic factors controlling neuronal excitability in PVN preautonomic neurons? 2) Are the cellular properties of PVN preautonomic neurons involved in the control of the parasympathetic and sympathetic autonomic function differentially affected during hypertension? 3) What are the cellular mechanisms underlying altered excitability during hypertension? Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: IDENTIFICATION HYPERTENSION
OF
GENES
INVOLVED
IN
HUMAN
Principal Investigator & Institution: Sheffield, Val C.; Professor; University of Iowa Iowa City, IA 52242 Timing: Fiscal Year 2001; Project Start 01-FEB-2001; Project End 31-JAN-2006 Summary: The primary goal of this project is to identify genes and loci involved in hypertension and related phenotypes. Identification of genes involved in Mendelian disorders can rely heavily on genetic mapping and positional cloning strategies cloning strategies. However, identification of genes involved in complex inherited disorders (such as hypertension) by positional cloning alone is not likely to be highly successful. The multiple genes contributing to a complex phenotypes can allow genetic mapping, but prevent refinement of loci because recombinants cannot be unequivocally resolved from the influences of unlinked loci. Thus, identifications involved in complex
40 Hypertension
phenotypes requires the use of all available information and a combination of research approaches. Such information includes the temporal-spatial expression patterns of genes, studies of gene function, knowledge of sequence polymorphism of genes, data obtained from physiological studies in animal models, as well as positional information gained from genetic studies in humans and animal models. In this study, we will take a multifaceted approach to the identification of genes and loci potentially involved in hypertension and hypertension-related phenotypes. In specific aim 1, we will use expression data from rat models of hypertension and gene-expression profiles, along with human and rat positional data to identify high- probability candidate genes for human gene-expression profiles, along with human and rat positional data to identify high-probability candidate genes for human hypertension. Inj specific aim 2, the human orthologues of the high-probability candidate genes identified in specific aim I will be isolated and evaluated for allelic association with hypertension in human populations. In specific aim 3, we will verify and refine putative loci influencing body size phenotypes and blood pressure, and in aim 4, we will identify a gene causing a human Mendelian disorder influencing blood pressure. The study design is built upon our past successes and resource development. We will take full advantage of existing genomic resources, as well as resources that are rapidly becoming available including: the complete draft sequence of the human genome; the discovery efforts of our NIH-funded "Rat Gene Discovery and Mapping Program" at the University of Iowa; human/rat syntenic maps; extensive rat and human cDNA libraries enriched for full -length clones; microarray hybridization capabilities with a comprehensive set and human cDNA libraries enriched for full-length clones; microarray hybridization capabilities with a comprehensive set of rat ESTs; and efficient sequencing team; expertise in all facets of genotyping and genetic mapping; outstanding information management expertise; wellcharacterized rat hypertension models; and carefully-phenotyped human subjects. All of these resources will be used toward ensuring the successful completion of this project. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMPROVING ADHERENCE TO BLOOD PRESSURE GUIDELINES Principal Investigator & Institution: Carter, Barry L.; Professor; Clinical and Administrative Pharmacy; University of Iowa Iowa City, IA 52242 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): Blood pressure (BP) control in the U.S. is poor despite six sets of guidelines generated over the last 30 years. Poor adherence to guidelines may be due to inadequate systems to track and monitor patients and inadequate therapy adjustments by physicians. While various strategies exist to assist physicians with improving guideline adherence and achieving better BP control, a consistently effective approach to solving the problem has not been found. The longrange goal of the principal investigator is to develop and evaluate collaborative relationships between physicians and pharmacists that improve pharmaco-therapy. This will be a five-year, multi-center, study to evaluate the impact of physician/pharmacist collaborative teams on adherence to hypertension guidelines (JNC-VI) in six community-based family practice sites. There will be two study phases. Phase I comprises a needs assessment to identify barriers to guideline adherence and design intervention implementation refinement strategies. Phase II will be a prospective, randomized trial to assess the impact of physician/pharmacist collaborative teams on hypertension guideline adherence and BP control. The specific aims of Phase I are to: 1) identify the scope and nature of physician and patient variables that may contribute to
Studies 41
poor guideline adherence and 2) to refine the intervention implementation strategy and design tools for assessing guideline adherence and barriers to adherence. The specific aims of Phase II are: 1) to determine if there is a change in guideline adherence and knowledge of hypertension when physicians are involved in physician/pharmacist teams and 2) to determine if physician/pharmacist teams can achieve better BP control compared to usual care. We expect that the improvement in guideline adherence and reduction in BP with this intervention will significantly impact patients with hypertension. Because there are more than 37 million Americans with uncontrolled hypertension, this model has to potential to become an important strategy to help achieve the BP goals for Healthy People 2010. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMPROVING HYPERTENSION
THE
TREATMENT
AND
CONTROL
OF
Principal Investigator & Institution: Margolis, Karen L.; Minneapolis Medical Research Fdn, Inc. 600 Hfa Bldg Minneapolis, MN 55404 Timing: Fiscal Year 2001; Project Start 01-JUN-1999; Project End 31-MAY-2004 Summary: Candidate: Karen Margolis, M.D., M.P.H., is a member of the Berman Center for Outcomes and Clinical Research at the Minneapolis Medical Research Foundation, and staff physician at Hennepin County Medical Center, a teaching hospital affiliated with the University of Minnesota. Dr. Margolis is interested in finding interventions which bring patients, physicians and the system of care together to implement effective medical care, specifically in the area of cardiovascular disease prevention. Career Objectives. Dr. Margolis' immediate career objectives include: (1) advanced course work in epidemiology, biostatistics, health services research, study design and analysis; (2) work with the Berman Center multi-center clinical trials and prospective studies; (3) work with mentor to develop and evaluate research direction, skills and experience; (4) obtain funding for and implement pilot and full-scale studies of randomized trial of physician incentives for improving the control of hypertension in a managed care organization; and (5) develop other related research projects. Dr. Margolis' long-term career objectives include attaining independence as an investigator in the field of patient-oriented cardiovascular disease prevention research and incorporating the theme of physician and patient adoption of effective interventions in a system of care for the prevention of cardiovascular disease morbidity and mortality. Research Plan. During the five year period of the award, Dr. Margolis plans to undertake at least one major clinical trial preceded by a pilot study for that trial. The clinical trial and pilot study are entitled "Program for Improving the Treatment and Control of Hypertension (PITCH)" and will involve testing the hypothesis that clinics in a managed care organization receiving funding to design their own program for improving the control of hypertension will have a higher percentage of hypertensives with controlled blood pressure compared to both clinics given similar funding for financial incentives (provided directly to physicians based on performance) and control clinics given no financial incentives. Dr. Margolis also has planned several other related projects which include: (1) study of patient attitudes towards physician financial incentives and satisfaction with care in PITCH; (2) study of impact of physician financial incentives in PITCH on medical care other than hypertension; and (3) the role of patient health state preferences in acceptance of hypertension treatment and control of hypertension. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
42 Hypertension
•
Project Title: INDUCED HYPERTENSION FOR ACUTE ISCHEMIC STROKE Principal Investigator & Institution: Wityk, Robert J.; Neurology and Neurosurgery; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAR-2005 Summary: (provided by the applicant): Thrombolysis using intravenous tissue Plasminogen Activator (rtPA) is the only proven therapy for Acute Ischemic Stroke, but it is only appropriate for some patients. The long-term goal of this proposal is to investigate the use of induced Hypertension as an alternative means of Cerebral Reperfusion. The rationale assumes the presence of an Ischemic Penumbra, a region of hypoperfused brain that is still viable and able to be rescued. Until recently, delineation of the Ischemic Penumbra in clinical practice has been impractical. Diffusion-Weighted MRI (DWI) allows early detection of Ischemic injury and Perfusion-Weighted MRI (PWI) shows areas of relative Cerebral Hypoperfusion. The DWI/PWI mismatch (in patients with PWI > DWI) can be functionally defined as the Ischemic Penumbra. Pharmacological elevation of blood pressure may increase cerebral blood flow to this region, and allow recovery of function. Before a double-blind, placebo-controlled clinical trial can be undertaken; several scientific issues need to be addressed. We propose a pilot clinical trial using DWI/PWI to investigate the physiology of induced Hypertension, and also study whether MRI can be used as a means of selecting patients likely to respond to treatment, as improved selection will allow more efficient trials later. Patients presenting within 12 hours of onset of stroke will be treated with a protocol of intravenous phenylephrine to increase mean arterial pressure to a maximum of 30% over baseline. Patients will have DWI/PWI studies performed before and during induced Hypertension, as well as 1-month follow-up. Serial neurological assessments (including the NIH stroke scale) will be performed by an investigator blinded to the imaging studies. The specific aims of this proposal are to: 1) determine the proportion of patients who have clinical improvement or serious adverse events related to induced Hypertension; 2) determine if the presence of DWI/PWI mismatch identifies patients likely to respond to induced Hypertension. We hypothesize that patients with mismatch are more likely to respond than are patients with other MRI patterns; and 3) correlate changes in neurological deficit with changes in MRI during induced Hypertension. An association of improved function, with reduction in the volume of mismatch, will support the proposed physiology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: INOS GENE TRANSFECTION IN PULMONARY HYPERTENSION Principal Investigator & Institution: Chicoine, Louis G.; Pediatrics; University of New Mexico Albuquerque Controller's Office Albuquerque, NM 87131 Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 31-MAR-2004 Summary: Pulmonary hypertension (PH) is a significant cause of morbidity and mortality affecting a broad range of patients. Neonatal pulmonary hypertension is the second leading cause for admission to neonatal intensive care units for respiratory support. In adults, PH causes significant morbidity and mortality in patients with chronic obstructive pulmonary disease. In all patients, PH is characterized by cellular proliferation and altered vasoreactivity in the pulmonary vascular bed. The objectives of this proposal are to evaluate the vasodilator efficacy and toxicity of NO produced by virally mediated inducible nitric oxide synthase (iNOS) gene transfection in the lung and to determine the effect of virally transfected iNOS on the pathogenesis of PH. The general hypothesis is that virally transfected iNOS will result in sufficient NO formation
Studies 43
to modulate pulmonary vasoconstriction and attenuate pulmonary vascular changes associated with pulmonary hypertension, but insufficient NO formation to result in toxicity. Utilizing human iNOS gene and, as a control, the E. coli lac Z reporter gene coding for beta-galactosidase (beta-gal) adenovirus constructs our goals set forth in this proposal are: 1) to optimize iNOS gene delivery and expression in the rat lung, 2) to determine the role of transfected iNOS on the development of pulmonary hypertension, and 3) to compare intravascular and intratracheal delivery of the iNOS gene in terms of gene expression, vascular reactivity and toxicity. These goals are addressed in the following specific aims: Specific Aim number 1: Assess the effectiveness of adenovirusmediated iNOS gene transfection in attenuating acute pulmonary vasoconstrictor responses. Specific Aim number 2: Assess iNOS gene transfection-mediated effects on the development of chronic hypoxia-induced pulmonary hypertension. Specific Aim number 3: Assess the efficacy and toxicity of intravascularly and intratracheally administered adenoviral iNOS constructs. The methods will involve using adenovirus constructs containing the gene for iNOS or beta-gal that will be administered intravascularly; the lungs will then be studied to determine vascular reactivity, NO production, and localization of transfected iNOS. Some rats will be transfected and exposed to chronic hypoxia. Finally, intravascular and intratracheal delivery will be compared in terms of gene localization and toxicity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISMS FOR CARDIOVASCULAR CONTROL EARLY IN DIABETES Principal Investigator & Institution: Brands, Michael W.; Associate Professor; Medical College of Georgia 1120 15Th St Augusta, GA 30912 Timing: Fiscal Year 2003; Project Start 01-JAN-1997; Project End 31-MAR-2007 Summary: (provided by applicant): We have shown that hyperglycemia at the onset of Type I diabetes causes significant hypertension if it is induced in rats with chronic blockade of nitric oxide synthesis. The hypertension is prevented by blocking angiotensin II, or the sympathetic nervous system; but our data suggest the two systems are linked in this response and may involve superoxide and thromboxane. Blood pressure and nitric oxide also track closely with GFR. The studies in this proposal will test the central hypothesis that nitric oxide protects against hypertension at the onset of diabetes by counteracting pressor actions of the sympathetic and renin-angiotensin systems. The Specific Aims are: 1) to test the hypothesis that nitric oxide protects against AngII-induced hypertension at the onset of diabetes by: a) chronically clamping (fixing) renin-angiotensin system activity at normal levels;b) blocking AngII action in rats with chronic intravenous and intrarenal i) ramipril and ii) iosartan; c) blocking AngII action in mice with ACE gene knockout; d) determining if gradual onset of diabetes causes the same renin secretion and blood pressure responses; e) determining whether low sodium intake increases the dependence of blood pressure on nitric oxide. 2) to test the hypothesis that the SNS contributes to the hypertensive response primarily through renal mechanisms. We will: a) determine the roles of a versus b receptors in mediating the renal, renin, and blood pressure responses:b) remove the renal nerves to test the role of the kidney in mediating the sympathetic pressor effect; c) determine if a decrease in ANG II is required for adrenergic blockade to prevent the hypertension; d) determine if the SNS effect is due to increases in SNS activity, or whether it plays a permissive role, 3) to test the hypothesis that nitric oxide counteracts AngII-dependent superoxide and thromboxane production to control blood pressure at the onset of diabetes. We will determine this by: a) "blocking" superoxide with a superoxide dismutase mimetic in rats
44 Hypertension
and gene overexpression in mice; b) quantifying the degree to which AngII determines whether superoxide significantly affects blood pressure: c) determining if thromboxane receptor blockade will decrease blood pressure if superoxide is not increased: d) determining whether knockout of superoxide dismutase 1 exacerbates the hypertensive response. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MENTORED DEVELOPMENT AW
PATIENT-ORIENTED
RESEARCH
CAREER
Principal Investigator & Institution: Gurubhagavatula, Indira Md; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, PA 19104 Timing: Fiscal Year 2001; Project Start 01-AUG-2000; Project End 31-JUL-2005 Summary: PROPOSAL (Adapted from the applicant's abstract): Characterized by intermittent airway closure during sleep, OSA is extremely prevalent, afflicting 2-4% of Americans. If left untreated, a large body of evidence convincingly shows that OSA can lead to daytime hypertension. In fact, 20-30% of patients with OSA will have hypertension, and 40% of patients with hypertension have occult OSA. The question then is how to identify patients who have OSA from among this high-risk population of individuals with hypertension. Polysomnography (PSG), the current diagnostic gold standard, is expensive and inconvenient. Several simple techniques to screen for OSA are available: questionnaires, craniofacial measurements, nocturnal oximetry and airflow monitoring devices. However, no one has compared their relative efficacies or costs in one unified population. The investigator proposes to compare these screening tools against full PSG's in a cohort of patients at high risk for OSA, i.e., outpatients with hypertension. Among the cases of OSA subsequently identified, the applicant next proposes to evaluate outcomes of treatment of OSA with continuous positive airway pressure (CPAP) in a randomized, placebo- controlled trial. The specific aims, therefore, are: 1) to compare the accuracy of several screening strategies for OSA in outpatients with hypertension; 2) to determine their relative economic costs; and 3) to determine the effect of CPAP therapy on blood pressure (BP) and sympathetic activity during sleep and awake states in OSA patients with hypertension. These projects are extraordinarily important. They have the potential to lead to dramatic changes in the approach to management of the patient with hypertension. Along with a complementary program of didactic training, they will constitute a strong foundation of experience for the applicant in her goal of becoming an independent clinical investigator. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MICROVESSEL HYPERTENSION
O2
RESPONSES
IN
SALT-SENSITIVE
Principal Investigator & Institution: Lombard, Julian H.; Professor; Physiology; Medical College of Wisconsin Po Box26509 Milwaukee, WI 532264801 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2007 Summary: (provided by applicant): Alterations in local blood flow control mechanisms may play a major role in the transition from an elevated cardiac output to a maintained elevation in vascular resistance in volume-expanded forms of hypertension. An enhanced constriction of arterioles, in response to increased O2, availability has been demonstrated in many forms of hypertension, but little is known regarding the mechanisms that mediate O2-induced constriction of microvessels. Cytochrome P450 (CYP450) 4A omega-hydroxylase, which catalyzes the formation of 20-HETE (a
Studies 45
vasoconstrictor metabolite of arachidonic acid), may act as an 02 sensor in the microcirculation. This study investigates the role of CYP450 4A omega-hydroxylase and 20-HETE in mediating O2-induced constriction of arterioles in the microcirculation of the Dahl S rat, a genetic model of salt sensitive hypertension, and in SS.BN13 consomic rats, in which chromosome 13 of the normotensive Brown Norway rat is substituted into the Dahl S genetic background. The SS.BN13 consomic rats are 98% identical to the Dahl S rat genetically, but do not exhibit elevated blood pressure in response to high salt diet. The overall hypothesis to be tested is that the enhanced response of arterioles to elevated PO2 in Dahl S hypertensive rats is due to one or a combination of 3 factors: increased 20-HETE production, increased sensitivity of arterioles to the vasoconstrictor effects of 20-HETE, and/or altered expression of CYP450 4A omega-hydroxylase. The effect of 20-HETE inhibition, on arteriolar responses to elevated PO2 will be determined in the in situ cremaster muscle of Dahl S and SS.BN13 rats on high salt (HS) and low salt (LS) diets. Cytochrome P450-4A omega-hydroxylase isoforms in arterioles and parenchymal cells of Dahl S rats and SS.BN13 rats on high and low salt diets will be assessed by RT-PCR and Western blotting, and changes in 20-HETE production in response to elevated PO2 will be measured in arterioles and parenchymal cells. Arteriolar constriction in response to exogenous 20-HETE will also be compared in the in situ microcirculation of Dahl S rats and SS.BN13 rats on high salt and low salt diets for various periods of time. These studies should provide an increased understanding of how the mechanisms that regulate vascular tone during changes in 02 availability, are altered during hypertension and during increases in dietary salt intake Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MORPHOLOGY AND FUNCTION OF BRAIN VESSELS Principal Investigator & Institution: Baumbach, Gary L.; Professor; Pathology; University of Iowa Iowa City, IA 52242 Timing: Fiscal Year 2003; Project Start 01-APR-1978; Project End 31-MAR-2007 Summary: (provided by applicant): Two provocative concepts have recently emerged in relation to mechanisms that contribute to altered cerebral vascular structure during chronic hypertension. First, superoxide, and its regulation by superoxide dismutase(s) (SOD), may play a critical role in regulating vascular structure by interacting with nitric oxide and by participating in cellular signaling and gene regulation. Second, the reninangiotensin system may play an important role in regulating vascular structure both by generating superoxide and by directly activating specific receptors. The overall objective of this proposal is to utilize novel molecular approaches to examine the roles of superoxide and the renin-angiotensin system in altered cerebral vascular structure in chronic hypertension. The proposed studies address two specific aims. The first aim is to clarify the influence of superoxide and SOD on cerebral vascular hypertrophy in chronic hypertension. To test the hypothesis that oxidative stress during chronic hypertension may contribute to cerebral vascular hypertrophy, effects of pressureoverload (induced by transverse aortic banding) will be examined using in vivo methods to assess vascular mechanics, histological methods to define hypertrophy, and biochemical methods to quantitate superoxide levels in carotid arteries and cerebral arterioles of genetically-altered mice that are deficient in the NADPH oxidase subunit, gp91phox, and that overexpress CuZn-SOD. Cerebral vessels also will be examined in these genetically- altered mice with arteriovenous fistulae to test the hypothesis that oxidative stress may contribute to cerebral vascular hypertrophy during increases in arterial pulse pressure, independently of increases in mean pressure. These studies will be among the first to use in vivo approaches to explore the influence of superoxide on
46 Hypertension
vascular structure. The second aim is to examine the role of angiotensin II in cerebral vascular remodeling during chronic hypertension. Vascular remodeling (defined as reduction in external diameter) plays an important role in hemodynamic alterations associated with essential hypertension in humans. Genetically altered mice that overexpress human renin (R+) and human angiotensinogen (A+) will be used to test the hypothesis that angiotensin II contributes to remodeling of cerebral arterioles independently of increases in arterial pressure. In addition, R+/A+ mice that are deficient in gp91phox will be generated to test the hypothesis that remodeling of cerebral arterioles in response to overproduction of angiotensin II may depend, at least partly, on the generation of superoxide. Finally, R+/A+ mice will be treated with blockers of angiotensin II type 1 and type 2 receptors to examine the hypothesis that remodeling of cerebral arterioles may be mediated by activation of one or both of these receptor types. These studies should provide important new insight into the mechanisms of vascular remodeling. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEDD4-DEPENDENT REGULATION OF ENAC IN HYPERTENSION Principal Investigator & Institution: Snyder, Peter M.; Associate Professor of Medicine; University of Iowa Iowa City, IA 52242 Timing: Fiscal Year 2001; Project Start 01-FEB-2001; Project End 31-JAN-2006 Summary: The epithelial Na+ channel (ENaC) is a distal target of the renin- angiotensinaldosterone pathway, where it is critically positioned to play an important role in blood pressure control. Gain-of-function mutations in ENaC cause Liddle's syndrome, an inherited form of hypertension. Conversely, loss-of-function mutations cause a genetic disorder of salt wasting and hypotension (pseudohypoaldosteronism type 1). Thus, an understanding of the function and regulation of this channel will provide important insights into human blood pressure variations and the pathogenesis of hypertension. In this project, we are responsive to Goal 2 of the RFA; "mechanistic studies on the consequence of genetic variation." In preliminary studies, we found that the interaction of ENaC with Nedd4, a ubiquitin protein-ligase, plays an important role in controlling Na+ absorption. Several findings suggest that a ubiquitin protein-ligase plays an important role in controlling Na+ absorption Several findings suggest that Nedd4 might play a critical role in the control of blood pressure. First, in preliminary studies we found that Nedd4 decreases ENaC Na+ current by targeting the channel for degradation. First, in preliminary studies we found that Nedd4 decreases ENaC Na+ current by targeting the channel for degradation. Second, the sequences in ENaC that bind to Ndd4 (PY motifs) are deleted or mutated in Liddle's syndromes. Third, we found that Liddle's syndrome mutations in the betaENaC subunit prevention Nedd4 from inhibiting the channel. Thus, the overall goal of this proposal is to understand the molecular mechanisms by which Nedd4 from inhibiting the channel. Thus, the overall goal of this proposal is to understand the molecular mechanisms by which Nedd4 inhibits ENaC, and to begin to define the role of this pathway in Liddle's syndrome and more common forms of hypertension. Thus, the overall goal of this proposal is to understand the molecular mechanisms by which Nedd4 inhibits ENaC, and to begin to define the role of this pathway in Liddle's syndrome and more common forms of hypertension. In the first two specific aims, we will investigate the molecular determinants for the inhibition of ENaC by Nedd4. Specific Aim 1 will focus on the role of a C2 domain in Nedd4 in the Ca2+- dependent inhibition of ENaC, and on the physical interaction between WW domains in Nedd4 and the PY motifs of ENaC. Specific Aim 2 will complement Aim 1, determining the sequences in ENaC that are
Studies 47
involved in the interaction and inhibition by Nedd4. Specifically, we will examine the role of the PY motifs that are targeted in Liddle's syndrome, and test the hypothesis that ubiquitination of ENaC is required for Nedd4- mediated inhibition. In Specific Aim 3, we will examine the functional consequences of natural genetic variation in ENaC found in hypertensive populations. This may provide important new insight into the role of ENaC and Nedd4 in human blood pressure variation and the pathogenesis of hypertension. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEURAL MECHANISMS OF LONG-TERM CARDIOVASCULAR CONTROL Principal Investigator & Institution: Osborn, John W.; Professor; Animal Science; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, MN 554552070 Timing: Fiscal Year 2001; Project Start 15-SEP-2000; Project End 31-JUL-2004 Summary: (Verbatim from Applicant's Abstract): Many forms of hypertension are exacerbated by increased dietary salt (salt-dependent hypertension) but the mechanisms are unknown. The overall objective of this proposal is to investigate the autonomic and hemodynamic mechanisms of salt-dependent hypertension. In preliminary experiments the applicants continuously monitored mean arterial pressure (MAP), heart rate (HR) and cardiac output (CO) in intact (SHAM) and sinoaortic denervated (SAD) rats consuming normal and high salt diets. Increasing dietary salt for two weeks resulted in an immediate and sustained increase in total peripheral resistance (TPR) in SHAM rats, but not hypertension since both HR and CO were decreased. In SAD rats, an equivalent salt-induced increase in TPR was observed, but CO and HR did not fall and saltdependent hypertension resulted. These results led to the following hypotheses and specific aims. Experiments in Specific Aim 1 will test the hypothesis that increased dietary salt stimulates release of neuropeptide-Y (NPY) from sympathetic vasomotor neurons to cause vasoconstriction in normotensive rats. In protocol 1, the response of hemodynamics (MAP, CO, HR and TPR) and plasma NPY to increased dietary salt in normal rats and rats chronically treated with the NPY Yl receptor antagonist BIPP 3266 will be measured. The effect of BIPP 3266 on the hemodynamic responses to salt will also be studied in rats chronically treated with alpha and beta-adrenergic antagonists, which have been shown to modulate the vasoconstrictor activity of NPY. In protocol 2, the effect of renal and splanchnic denervation on NPY mediated renal and mesenteric vasomotor responses to increased dietary salt respectively will be determined. In these same animals, the applicants will examine vascular Yl receptor MRNA expression using RT-PCR and correlate these findings with vascular sensitivity to NPY. Experiments in Specific Aim 2 will test the hypothesis that chronic salt induced decreases in cardiac output are mediated by baroreflex control of cardiac sympathetic and vagal tone. To test this hypothesis cardiac output, heart rate and arterial pressure will be monitored 24 hours/day in intact and baroreceptor denervated rats consuming normal and high salt diets. Power spectral analysis of heart rate will be preformed to assess the effect of increased salt on cardiac vagal and sympathetic activity throughout the experiment. In these same rats, the effect of long-term pharmacological blockade of M2 muscarinic receptors and beta l adrenergic receptors on cardiac vagal and sympathetic tone respectively (heart rate power spectra), cardiac output and arterial pressure will be examined before and during dietary salt loading. The applicants predict that impaired autonomic control of the heart will result in salt-dependent hypertension due to failure to buffer salt-induced vasoconstriction by a decrease in cardiac output. These experiments will provide important novel information on the role of the autonomic
48 Hypertension
nervous system in the long-term control of hemodynamics under conditions of increased dietary salt. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEW EXPERIMENTAL MODELS OF HYPERTENSION Principal Investigator & Institution: Kurtz, Theodore W.; Professor; Laboratory Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122 Timing: Fiscal Year 2002; Project Start 01-JAN-1997; Project End 31-DEC-2006 Summary: (provided by the applicant): The spontaneously hypertensive rat (SHR) is the most widely studied animal model of essential hypertension and has been a valuable tool for studying the pharmacology and physiology of blood pressure control. However, despite 30 years of research with this model, the primary mechanisms responsible for hypertension in the SHR remain undefined. Recently, we have succeeded in trapping a quantitative trait locus (QTL) for hypertension within a narrow segment of chromosome 8 in a unique congenic strain of SHR. In the current studies, we will exploit this congenic strain together with proven strategies of genome wide expression analysis and meiotic mapping to identify the molecular lesion(s) responsible for the effect of this region of chromosome 8 on blood pressure. We will pursue two alternative hypotheses using complementary strategies as follows: Hypothesis 1. A hypertension gene exists within the target segment of chromosome 8 that is differentially expressed between the SHR and the SHR congenic strain in one of the major organs suspected to be involved in the primary pathogenesis of spontaneous hypertension (brain, adrenal gland, or kidney). Accordingly, we will search for candidates for hypertension within the target chromosome segment by screening for genes that are differentially expressed between these organs of the SHR and the SHR congenic strain and that map back within the congenic segment of chromosome 8. Hypothesis 2. A hypertension gene exists within the target segment of chromosome 8 that is not differentially expressed between the SHR and the SHR congenic strain. To cover for this alternative possibility, we will also narrow the location of the hypertension gene by meiotic mapping analysis of a segregating F2 population derived from the SHR progenitor strain and the SHR congenic strain that carries the target region of chromosome 8 from the BN strain. Hypertension candidate genes will then be isolated using cDNA screening techniques to identify genes expressed in the brain, adrenal gland, or kidney that map within this chromosome region. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NMR STUDIES OF CYTOSOLIC METAL IONS AND OXIDATIVE STRESS Principal Investigator & Institution: Gupta, Raj K.; Professor; Physiology and Biophysics; Yeshiva University 500 W 185Th St New York, NY 10033 Timing: Fiscal Year 2003; Project Start 01-MAY-1982; Project End 31-AUG-2007 Summary: (provided by applicant): Our long-range goal is to elucidate the role of intracellular mineral ions (Na+, K+, free Mg2+ & free Ca2+) and oxidative stress in the pathophysiology of essential hypertension and type 2 diabetes. We seek to understand how the regulation of intracellular concentrations of essential metal ions and membrane lipids goes astray in health disorders, especially hypertension and diabetes. Our main research tool is NMR spectroscopy. Our laboratory played a key role in the development of NMR methods for measuring various intracellular cations and we also have
Studies 49
considerable expertise in the use of 1H NMR for analyzing membrane phospholipid composition and the degree of membrane fatty acid unsaturation (double bonds) and average chain length. Oxidative stress, which may play a contributory role in the pathogenesis of diabetes as well as hypertension, causes peroxidative degradation of membrane lipids resulting in a loss of fatty acid double bonds that can be quantitated by 1H NMR. The following specific aims will be pursued: (1) To investigate the mechanism of altered renal sodium homeostasis in salt-sensitive hypertension; (2) To demonstrate that oxidative stress, which results in overproduction of reactive oxygen species (ROS), can cause loss of unsaturation in fatty acyl chains of membrane phospholipids as measured by 'H NMR, and to test the hypothesis that peroxidative degradation of lipids as measured by loss of membrane fatty acid unsaturation during oxidative stress results in intracellular ionic changes similar to those seen in essential hypertension; (3) To investigate a possible protective role of magnesium against oxidative stress and whether there is a decrease in antioxidant capacity, as measured by glutathione (GSH) levels, in tissues exposed to low Mg environment; (4) To test the hypothesis that a deficit in membrane fatty acid unsaturation is associated with human essential hypertension and to investigate if there is an alteration in sphingomyelin-ceramide pathway in hypertension; (5) To find out if impairment of nitric oxide synthesis by inhibition of nitric oxide synthase, which causes hypertension in a normal rat, produces membrane lipid changes similar to those seen in essential hypertension; (6) To test the hypothesis that hyperglycemia causes peroxidative degradation,of membrane lipids as measured by 1H NMR, especially in vascular tissue, and, if so, whether hyperglycemia associated loss of fatty acid unsaturation and intracellular ionic alterations can be reversed by dietary antioxidants such as vitamin C and E; (7) To investigate increased vulnerability of hypertensive as well as hyperglycemic kidney and myocardium to ischemic damage and its relationship to increased perexidative degradation of membrane lipids; and (8) To design, develop and test a method for non-invasive measurement of "intracellular sodium using triple-quantum filtered (TQ)23 Na NMR. The proposed NMR investigations of intracellular ions and oxidative stress in hypertension and hyperglycemia condition may eventually lead to better strategies for the management of these health disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NONINVASIVE ASSESSMENT OF PRIMARY PULMONARY HYPERTENSION Principal Investigator & Institution: Shandas, Robin; Professor; Pediatrics; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, CO 800450508 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 31-MAY-2005 Summary: (Applicant's Abstract): This proposal addresses the problem of evaluating the efficacy of newly developed agents for the treatment of primary pulmonary hypertension. The use of catheter techniques to measure pulmonary vascular resistance severely limits routine evaluation of such treatments. We propose to develop, refine and test a non-invasive ultrasound based means of accurately evaluating pulmonary vascular resistance in children with primary pulmonary hypertension. The hypothesis for this project is based on the relationship between changes in downstream impedance within a fluid system and the characteristics of the pressure pulse propagation wave that develops within the arterial walls. We propose to show that downstream impedance affects the pulse propagation wave traveling within the main pulmonary artery and that changes in downstream impedance, as would occur with treatments such as inhaled nitric oxide or infused prostaclyin, can be followed by measuring pulse
50 Hypertension
propagation characteristics. Furthermore, we propose that the pressure pulse propagation in the main PA affects local velocities, and that such changes in local velocities can be quantified as a velocity propagation using non-invasive ultrasound color M-mode imaging. This should significantly aid in evaluating new treatments for primary pulmonary hypertension and thereby expand treatment options and improve quality of life for patients. The aims of this project, therefore, are: 1. Demonstrate analytically that a fundamentally rooted mathematical and physical foundation exists for using velocity data to extract pressure pulse propagation characteristics for pediatric primary pulmonary hypertension. 2. Develop and test a method for using color Mmode velocity data to predict downstream impedance using highly reproducible in vitro models. 3. Determine clinical utility of the color M-mode approach using existing clinical protocols studying the efficacy of nitric oxide and/or 100 percent 02 treatment in the catheterization laboratory to reduce pulmonary vascular resistance in children with primary pulmonary hypertension. 4. Determine whether color M-mode measured velocity propagation (Vel-prop) predicts pulmonary vascular resistance in the clinical situation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: OXIDATIVE STRESS AND GENETICS OF PREHYPERTENSION Principal Investigator & Institution: Nesbitt, Shawna D.; Internal Medicine; University of Texas Sw Med Ctr/Dallas Dallas, TX 753909105 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2005 Summary: (provided by applicant): High normal blood pressure in increasingly recognized as an important cardiovascular risk factor in part due to the likelihood of progression to hypertension. However, there is considerable heterogeneity in the risk of hypertension; some individuals progress while others maintain or regress. Thus, clinicians are unable to identify those at highest risk. Further, the effect of treatment of high normal blood pressure (BP) on the progression to hypertension is unknown. Consequently, my colleagues and I designed the Trial of Preventing Hypertension (TROPHY) as a prospective randomized placebo controlled trial of short-term monotherapy with the angiotensin receptor blocker (ARB) candesartan cilexitil in 809 subjects with high normal BP. Trophy provides a unique opportunity to study the mechanisms of the progression to hypertension. Emerging basic research emphasizes the role of superoxide (.O2-) as a major mechanism by which chronic exposure to low concentrations of angiotensin II (All) includes progressive hypertension. Via interaction with All receptors in the vessel wall, All activates NAD(P)H oxidases producing .O2and other reactive oxygen species that a) quench nitric oxide (NO), leading to NO deficient hypertension and b) stimulate signaling of vascular smooth muscle cell growth. TROPHY provides a new opportunity to translate this basic research from animal models to the clinical setting. Major Mechanistic Hypothesis: All receptor mediated generation of .O2- both quenches NO and stimulates vascular hypertrophy, and thereby constitutes the major mechanism of progression to hypertension from high normal BP. Specific Aims: Utilizing the TROPHY trial of 800 subjects on placebo or short-term ARB treatment we will: 1) in the placebo group, determine if individuals with high normal BP and high oxidative stress levels (F2 isoprostanes and glutathione ratio) are at high risk for progression to hypertension; 2) in the ARB group, determine if short-term treatment lowers oxidative stress levels compared to placebo and if the level of oxidative stress predicts failure to progress to hypertension; and 3) determine genetic sequence variants in the All, oxidative stress, and NO pathways associated with progression to hypertension or failure to progress to hypertension.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: OXIDATIVE STRESS AND SYMPATHETIC NERVE ACTIVITY Principal Investigator & Institution: Campese, Vito M.; Medicine; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, CA 90033 Timing: Fiscal Year 2003; Project Start 24-JAN-2003; Project End 31-DEC-2006 Summary: (provided by applicant): Hypertension is a common manifestation of renal disease and greatly contributes to its progression as well as to cardiovascular morbidity. Clearly, hypertension is an important etiology in the pathogenesis of renal failure. In the United States, hypertension is the primary cause of end-stage renal disease in approximately 29 percent of dialysis patients. In conjunction with other diseases such as diabetes and chronic glomerulonephritides, hypertension, when uncontrolled, hastens the progression of renal disease. Cardiovascular disease is the leading cause of death in patients receiving maintenance hemodialysis and hypertension is considered the most important factor responsible for cardiovascular events in these patients. Adequate BP control may reduce the progression of renal disease and cardiovascular morbidity in these patients, but often this is difficult to achieve with currently available drugs. The old paradigm is that hypertension in renal disease is the result of activation of the reninangiotensin system and/or volume expansion. Our studies strongly support the notion that a renal injury may result in activation of renal afferent pathways that integrate with the central nervous system, and lead to stimulation of efferent SNS activity and hypertension. Locally produced angiotensin II in the brain in response to these afferent stimuli seems to be responsible for SNS activation through inhibition of nitric oxide. Our hypothesis is that angiotensin-II activation of ROS may reduce NO availability in key brain region and result in increased SNS activity in a model of neurogenic hypertension caused by renal injury developed in our laboratory. To test this hypothesis we will pursue 3 specific Aims: 1. Test the hypothesis that locally produced Ang II mediates the activation of central SNS activity caused by phenol-renal injury. To this end, we will measure Ang II concentration in the dialysate collected from the PH using the microdialysis technique, and the expression of renin mRNA in the posterior hypothalamus. 2. Test the hypothesis that radical oxygen species (ROS) activated by Angiotensin II down-regulate nitric oxide production in the brain resulting in increased SNS activity. To this end, we will measure the concentration of reactive oxygen species (ROS) in the hypothalamus or rats with the phenol-renal injury or rats infused with Ang II in the lateral ventricle. In addition, we will evaluate the effects of anti-oxidants, or scavengers of ROS, and Ang II AT1 receptor antagonists on BP, sympathetic activation and ROS concentrations in the hypothalamic region. 3. Test the hypothesis that increased ROS production may result in NO inhibition and SNS activation in other forms of experimental hypertension, such as the DOCA-sait model, and the renovascular hypertension model. If our hypothesis were to be correct, administration of inhibitors of the renin-angiotensin system particularly if combined with antioxidants should result in better control of BP in these models. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: P450 EICOSANOIDS AND RENAL FUNCTION IN HYPERTENSION Principal Investigator & Institution: Roman, Richard J.; Professor; Physiology; Medical College of Wisconsin Po Box26509 Milwaukee, WI 532264801 Timing: Fiscal Year 2001; Project Start 01-JUL-1986; Project End 31-MAR-2005
52 Hypertension
Summary: (Adapted from the Investigator's Abstract): Recent studies have indicated that cytochrome P450 (CYP) metabolites of arachidonic acid (AA), in particular 20HETE, play a central role in the regulation of renal tubular and vascular function and the long-term control of arterial pressure. During the last funding period, this investigator identified a gene of the cytochrome P4504A family that is differentially expressed in the kidney of Dahl S and Lewis rats and that cosegregates with the development of hypertension in an F2 cross of Dahl S and Lewis rats. To further explore the role of this system in the control of renal function, they have developed (in collaboration with Dr. J. Rapp) congenic strains of rats in which overlapping segments of chromosome 5 of the Lewis rat, that include or exclude the P4504A region, have been introgressed into the Dahl S genetic background by greater than 8 generation of selective back-cross breedings. They now propose to determine whether the P4504A genes play a causal role on altering renal function and/or the development of hypertension and glomerulosclerosis in Dahl S rats by: 1) comparing blood pressure, renal function and the expression of P4504A enzymes in congenic strains of rats in which the P4504A alleles of normotensive Lewis rats have been introgressed into the Dahl S genetic background; 2) determining whether selective intrarenal blockade of the formation of 20-HETE can "rescue" the hypertensive and renal phenotypes in P4504A congenic Dahl S rats; 3) cloning and sequencing the 5'-flanking regions of the P4504A2 and 4A3 genes to determine whether there are sequence variants that can explain the differences in the expression of these genes in the outer medullas of the kidneys of Dahl S and Lewis rats. These studies will provide important new information regarding the role of P450 metabolites of AA in the regulation of renal function and will determine whether this pathway plays a primary or secondary role in the development of hypertension and/or glomerular disease in Dahl S rats. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HYPERTENSION
PHARMACOGENETIC
THERAPY
OF
PULMONARY
Principal Investigator & Institution: Li, Song; Pharmacology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2007 Summary: (provided by applicant): Pulmonary hypertension is a significant clinical entity severely affecting the longevity and quality of life for patients with either primary or secondary' forms of this disorder. Regardless of its underlying cause, pulmonary hypertension remains intractable to traditional pharmacotherapy. Recent basic genetic and preclinical pharmacological] studies suggest that newly developed agents modifying endothelin activity may have a potential role in pulmonary hypertension. Nonetheless, it is highly likely that general principles of pharmacology predictive of issues of non-specificity and adverse effects as well as target alterations leading to tachyphylaxis and desensitization will ultimately limit the use of new generation endothelin modifiers. In the current proposal, we suggest that advances in non-viral based genetic therapy may provide novel alternatives to traditional pharmacotherapy. In particular, delivery of antisense Oligodeoxynucleotides (ODN) to endothelin-1 lET-l) by immunoliposome can be used to down regulate pulmonary' endothelial ET-1 biosynthesis and similar application with RNA/DNA chimeric oligonucleotide may more permanently silence such expression. Accordingly, specific aims of this comprehensive proposal are: Aim 1: To develop an oligonucleotide-based approach to achieve efficient down-regulation of ET-1 in endothelial cells. ODN scanning arrays and ET-1 ELISA will be employed to identity - antisense ODNs that are highly efficient in
Studies 53
inhibiting the ET-1 expression in mouse lung endothelial cells. In addition, RNA/DNA chimeric oligonucleotides will be investigated as an approach to achieve a long-term silencing of ET-1 in pulmonary endothelium. Aim 2: To develop novel delivery, systems to achieve efficient delivery of oligonucleotide to pulmonary endothelium with reduced toxicity. Aim 3: To investigate the biological effect of tissue-specific down-regulation of ET-1 in normal mice and in mice with PHT. The current proposal will lead to a better understanding of the roles of ET-1 in mouse hypoxia-induced pulmonary hypertension and provide experimental and preclinical support for rational pharmacogenetic approach to pulmonary hypertensive disorders. Down regulation of ET-1 biosynthesis by pulmonary endothelium by immunoliposome-mediated delivery of ODN may by itself, or in combination with" direct pulmonary vasorelaxants (e.g. nitric oxide and oxygen), provide an approach to prevent the progressive pathological aspects of PHT and ameliorate return towards more normal pulmonary vascular structure and function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PILOT--DEPRESSION HYPERTENSIVES
&
TREATMENT
ADHERENCE
IN
Principal Investigator & Institution: Rojas, Mary; Mount Sinai School of Medicine of Nyu of New York University New York, NY 10029 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: Hypertension is a prevalent disorder. Treatment for hypertension usually requires a patient to take daily medications, reduce sodium intake and lose weight, adhere to routine follow-up visits, and undergo routine monitoring tests. Adherence to such regimens requires a great degree of patient motivation and perseverance, convictions that often require strong feelings of self-efficacy. Hypertensive patients who are also depressed may be less likely to summon the necessary self-discipline to follow such a complex health routine. Depression is also a prevalent disorder; approximately 9.5% of U.S. adults ages >=18 suffer from a depressive disorder in any given year. The relatively high prevalence of these 2 conditions suggest that it is likely that both hypertension and depression will occur concomitantly. Current research is lacking on the extent to which depression complicates hypertension and adherence to antihypertensive treatment regimens. Specific Aims: 1) To describe the prevalence of depression among controlled and uncontrolled hypertensive minority patients; 2) To describe the prevalence of treatment adherence among depressed and nondepressed hypertensive patients; 3) To explore associations between depression, treatment adherence, and blood pressure control; 4) To assess the feasibility of recruiting minority hypertensive patients to undergo screening for depression. We will take advantage of an ongoing AHRQ-EXCEED-funded randomized trial among minority patients with uncontrolled hypertension and utilize the recruitment procedures and tools to identify minority patients with diagnosed and treated hypertension. We will assess patients for depression, anti-hypertensive treatment adherence and perceived self-efficacy. We will survey 30 controlled and 30 uncontrolled hypertensive minority patients recruited from the waiting rooms of clinics in East and Central Harlem. This pilot study is an exploration of the relationship of depression, attitudes toward treatment of depression, hypertension treatment adherence, self-efficacy and blood pressure control. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
54 Hypertension
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Project Title: PILOT--DOPAMINE RECEPTOR ASSOCIATED PROTEINS AND HYPERTENSION Principal Investigator & Institution: Jones, John E.; University of Virginia Charlottesville Box 400195 Charlottesville, VA 22904 Timing: Fiscal Year 2002; Project Start 01-SEP-1997; Project End 31-AUG-2007 Summary: Genetic hypertension may be the result of abnormalities in the renal dopaminergic system. The renal autocrine/paracrine natriuretic function of dopamine, via the D1-like receptors (D1 and D5), is impaired in the spontaneously hypertensive rat. The impairment is not the result of a decrease in renal dopamine production nor is it due to abnormalities in the G proteins or effector proteins. We propose that the impairment resides within one or more intermediate components. Genetic changes occurring within the genes that encode D1-like receptor interacting proteins may lead to disruption of D1-like receptor mediated signal transduction and, in turn, result in increased risk for the development of hypertension. Specific aim 1 will identify and characterize the proteins that interact with the D1-like receptors in the kidney. We will employ the yeast two- hybrid system to identify genes encoding proteins that interact with the D1-like receptors. The D1 and D5 dopamine receptors will be divided into structural domains consisting of the amino terminal, carboxy terminal, extracellular and intracellular loops and each of the seven transmembrane segments. These domains will be used as molecular probes to detect interactions occurring with proteins expressed from a human kidney cDNA library. Protein-protein interactions will be verified using laser confocal microscopy and fluorescence resonance energy transfer techniques. Specific aim 2 will test the hypothesis that there are differences in the sequences of the D1-like receptor interacting proteins between normotensive and hypertensive individuals and that it is these differences that lead to hypertension. Genetic variants, especially those occurring within regions identified in specific aim 1 as potential sites of interaction with the D1-like receptor proteins or those that map to regions of the human genome associated with hypertension risk, will be studied further. We will screen for polymorphisms in genomic DNAs derived from control and hypertensive individuals representing several different ethnic groups including Asians, Africans, American Caucasians, and Italian Caucasians. Finally, specific aim 3 will determine if there are differences in the expression of D1-like receptor interacting proteins in young and adult kidney during maturation. A greater understanding of the proteins and protein networks associated with the regulation of the D1-like dopamine receptors will likely lead to greater insight into the roles these receptors play in the maintenance of blood pressure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PILOT--THE BETA 2 ADRENERGIC RECEPTOR AND GENETIC HYPERTENSION Principal Investigator & Institution: Xu, Jing; University of Virginia Charlottesville Box 400195 Charlottesville, VA 22904 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2007 Summary: Abnormalities of beta2-adrenergic receptor (beta2-AR) function have been found in human essential hypertension and animal models of genetic hypertension. Mice with disrupted beta2- AR genes and their regulators are in loci associated with hypertension and genetic variations of beta2-AR are associated with hypertension. Beta2-ARs increase cAMP production, Na+/K+ATPase activity, and sodium transport; a decrease in these actions can cause the increased vascular reactivity in hypertension,
Studies 55
However, a decrease in beta2-AR function in renal tubules should lead to sodium loss, which potentially could lead to a decrease in blood pressure, offsetting the effect on vascular reactivity. The overall hypothesis is that in the kidney beta2-AR single nucleotide polymorphisms (SNPs) do not lead to sodium loss because sodium/hydrogen exchanger (NHE)-3 activity is increased in the kidney. We hypothesize that renal NHE3 activity is increased in subjects with beta2-AR SNPs because of an increased binding affinity of variant beta2-ARs to the NHE regulatory factor (NHERF). This leads to a decrease in NHERF available to inhibit NHE3 activity. Specific aim 1 will determine whether the interaction between beta2-AR in a heterologous expression system. We will determine whether genetically hypertensive rats have beta2-ARs SNPs. Even if there are no beta2-AR SNPs in genetically hypertensive rats, the reported increase in beta2-ARs in the kidney in genetically hypertensive rats may still result in increased binding of NHERF with the same consequences as variant beta2-ARs. Therefore, we will also quantify beta2-ARs, NHERF, and NHE3 protein in renal tubules and determine whether the binding of beta2-ARs to NHERF is increased in genetically hypertensive rats. Preliminary data indicate that the activity of a G protein-coupled receptor kinase, GRK6, is increased in renal proximal tubule cells of spontaneously hypertensive rats (SHR) compared with their normotensive controls, Wistar-Kyoto (WKY) rats. Because GRK6 can phosphorylate both beta2-AR and NHERF, specific aim 2 will determine if GRK6 activity in renal proximal tubules is, indeed, increased in SHR. We will also determine if the phosphorylation of beta2-ARs and NHERF is increased in SHR and whether such an increase is caused by increased GRK6 activity. Finally, the mechanism of the increased GRK6 activity in SHRs will be determined. These studies should allow us to determine the role of aberrant beta2-AR regulation of NHERF in genetic hypertension. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PRENATAL AND PERINATAL PROGRAMMING OF ADULT HYPERTENSION Principal Investigator & Institution: Vehaskari, Vesa M.; Director; Pediatrics; Louisiana State Univ Hsc New Orleans New Orleans, LA 70112 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 31-MAY-2006 Summary: (provided by applicant): Low birth weight is a risk factor for the development of human essential hypertension. The goal of the project is to define the mechanisms by which prenatal and perinatal factors program later hypertension. An experimental rat model of adult hypertension associated with low birth weight has been validated by preliminary experiments and will be used for all studies. The hypothesis is that pre- and perinatal hormonal imprinting irreversibly alters the sodium handling characteristic of the maturing kidney, resulting in sodium retention, expansion of extracellular volume (ECV), and hypertension. The studies will focus on the renal reninangiotensin system (RAS) and the cortical collecting duct (CCD) which are critical regulators of sodium balance. The following potential mechanisms will be investigated: ECV will be measured to test the hypothesis that it is expanded during the development of hypertension. Persisting upregulation of intrarenal RAS and failure to regress normally after birth would lead to sodium retention. This will be examined by determining the intrarenal expression of the RAS components at different time points before and after the development of hypertension by molecular biology methods; renal and systemic angiotensin I and angiotensin II contents will also be measured. CCD sodium transport is hypothesized to be upregulated due to prenatal imprinting of the angiotensin II type 1 receptor, the 11-beta-hydroxysteroid dehydrogenase enzyme,
56 Hypertension
and/or the mineralocorticoid receptor in this nephron segment. Isolated CCDs will be used to study the sodium transport rate and the expression of the specific genes and proteins involved in the Na transport pathway. To assess the contribution of reduced Na filtration to the development of hypertension, total nephron number as well as whole kidney and single nephron filtration rate will be measured; also, the total nephron number will be manipulated using prenatal retinoic acid treatment. Based on preliminary experiments, the hypothesis that the development of prenatally programmed hypertension can be modified or prevented during a postnatal window will be tested. The effect of short-term postnatal dietary and phamacological manipulations on the long-term blood pressure profile will be investigated. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROSTACYCLIN SYNTHASE AND PROSTACYCLIN RECEPTOR IN PH Principal Investigator & Institution: Geraci, Mark W.; Director, Gene Array Facility; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, CO 800450508 Timing: Fiscal Year 2001; Project Start 17-SEP-2001; Project End 31-JUL-2006 Summary: (provided by applicant) Severe pulmonary hypertension, including primary pulmonary hypertension (PPH), is an important clinical problem with few clinical treatment options. The chronic, intravenous infusion of prostacyclin (PGI2) has been established as the treatment of choice for patients with PPH. It is now clear that longterm benefits occur which obviate the need for transplant in many cases. The physiological effects of prostacyclin on platelet behavior, vascular tone control, and cell proliferation are well established; however, we do not know whether prostacyclin effects the vascular remodeling in chronic pulmonary hypertension. Our overall hypothesis is that prostacyclin, through membrane-receptor dependent and independent mechanisms, is an important modulator of pulmonary vascular remodeling. We have demonstrated loss of the prostacyclin receptor (PGIR) protein in the smooth muscle cells of precapillary resistance arteries in patients with PPH. We postulate that impairment of the prostacyclin signal transduction contributes to pulmonary vascular remodeling. We have generated transgenic animals with selective pulmonary prostacyclin synthase (PGIS) overexpression. These animals are protected from the development of hypoxic pulmonary hypertension, and show no acute vasoconstriction or chronic vascular remodeling. In contrast, PGIR knockout (KO) mice, in response to hypoxia, develop rapid pulmonary hypertension accompanied by vascular remodeling. Microarray analysis of the lungs from the transgenic animals demonstrates a change in the global pattern of gene expression, which may be responsible for the "protected" phenotype, including changes in PPARs and COX-2. Our underlying concept is that PGI2 exhibits both membrane-receptor mediated and nuclear-receptor-mediated actions. These alternative mechanisms could include direct effects on gene expression, signaling pathways not yet recognized, or changes in the level of other eicosanoids. Our goal is to examine, using both animal models and cell systems, the effects of PGIS and PGIR on vascular smooth muscle cell (VSMO) growth and differentiation. In Specific Aim 1, we will determine whether pulmonary vascular tone and remodeling are mediated through the PGI2 receptor using bitransgenic mice with PGIS overexpression, but lacking PGIR. Specific Aim 2 is designed to define the effect of PGIS and PGIR on the growth and remodeling of vascular smooth muscle cells. The results of this work are designed to elucidate new potential therapeutic targets for
Studies 57
treating pulmonary hypertension, and broaden our understanding of vascular pathology in general. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PULMONARY HYPERTENSION FOLLOWING INTERMITTENT HYPOXIA Principal Investigator & Institution: Fagan, Karen A.; Medicine; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, CO 800450508 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2007 Summary: (provided by applicant): Pulmonary hypertension (PHTN) is common in diseases characterized by chronic hypoxia (CH) (i.e. COPD, IPF) and occurs in 15-40% of patients with sleep apnea. Intermittent hypoxia (IH) mimicking the hypoxiareoxygenation cycles of sleep apnea causes systemic hypertension and altered regulation of systemic vascular tone. However, the effect of intermittent hypoxia on the pulmonary circulation is unknown. Recently, patients with sleep apnea-induced PHTN were found to have exaggerated hypoxic pulmonary vasoconstriction. Unlike in chronic hypoxia, hypoxia in sleep apnea is not continuous, thus the mechanisms causing sleep apnea-induced PHTN are likely different from chronic hypoxia-induced PHTN. We therefore hypothesize that intermittent hypoxia leads to pulmonary hypertension by differential expression of genes important in regulating pulmonary vascular tone. Specifically, we hypothesize that oxidant stress in IH increases NOS and decreases SOD leading to PHTN through increased formation of peroxynitrite thus decreasing NO available for cellular effects such as attenuating vasoconstriction and mediating vasodilation. We further hypothesize that IH activates redox sensitive transcription factors leading to differential lung gone expression compared to CH. We will present data showing IH-induced PHTN in both rats and mice. We also will present data showing differential expression of NOS (nitric oxide synthase) and SOD (superoxide dismutase) in the lung following IH compared to CH, which may contribute to IHinduced PHTN through increased oxidant stress and decreased NO activity. This proposal will address the questions: 1) does repetitive hypoxia-reoxygenation causes pulmonary hypertension, 2) that despite increased NOS, NO appears to be insufficient to prevent IH-induced PHTN, 3) decreased SOD may contribute to IH-induced PHTN by increasing oxidant stress and formation of peroxynitrite, and 4) does IH leads to differential gene expression through activation of specific signaling pathways compared to CH. We will correlate physiologic measures of PHTN and pulmonary vascular tone with expression and activity of NOS and SOD, measurements of oxidant stress and NO, and activation of specific signaling pathways leading to altered gone expression in IH. This proposal, for the first time, will identify the consequences of IH in the pulmonary circulation. Understanding mechanisms contributing to the development of PHTN in IH may lead improved cardiovascular morbidity and mortality in this common disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PULMONARY HYPERTENSION IN SCD Principal Investigator & Institution: Johnson, Cage S.; Professor of Medicine; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, CA 90033 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-MAR-2008 Summary: Chronic lung disease and pulmonary hypertension are complications of the sickle diseases that are increasingly recognized and are associated with considerable morbidity and mortality. Standard therapy with oxygen and a hypertransfusion
58 Hypertension
regimen have not demonstrated efficacy in prolonging survival in such patients, indicating a need for new approaches to management. Both hydroxyurea and L-arginine have the potential for increasing endogenous production of NO within the pulmonary vasculature and may have beneficial effects on oxygenation and pulmonary vascular resistance in patients with chronic lung disease and pulmonary hypertension. In addition, hydroxyurea improves red blood cell hemorheological properties and microvascular blood flow and thus combined therapy may impact smooth muscle hyperplasia in damaged pulmonary microvasculature. We hypothesize that beneficial clinical responses may accrue to patients with sickle chronic lung disease and pulmonary hypertension as a result of increases in NO generated by oral administration of hydroxyurea and/or L-arginine. We further hypothesize that these beneficial effects are consequent to modulation of vasoactive peptides (ET-1) and adhesion molecules (ICAM-I, V-CAM-I). The proposed research project is a phase II, randomized clinical trial designed to determine the effect of the NO donor L-arginine and hydroxyurea, either singly or in combination, on the biologic and clinical features of sickle cell disease patients with chronic lung disease and pulmonary hypertension. We further propose to characterize the effects of this treatment strategy on a broad range of RBC and hemorheologic properties in SCD,and to determine its efficacy in ameliorating chronic lung disease and pulmonary hypertension in these patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION ON SODIUM PUMPS IN THE KIDNEY Principal Investigator & Institution: Mcdonough, Alicia A.; Professor; Physiology and Biophysics; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, CA 90033 Timing: Fiscal Year 2001; Project Start 01-JUL-1984; Project End 31-JUL-2002 Summary: (Adapted from the applicant's abstract) - Previous results from the principle investigator's laboratory and other have shown that a rapid increase in mean arterial blood pressure inhibits salt and fluid reabsorption in the renal proximal tubule. The resulting increase in volume flow to the thick ascending limp of the loop of Henle provokes an increased sodium reabsorption and Na, k-ATPase activity to limit the increase in volume flow to the distal tubule and increase in Na-K-2Cl co- transporter. A defect in the proximal tubular or thick ascending limb of the loop of Henle (TALH) responses could be responsible for the reduced pressure natriuresis that is that is the hallmark of hypertension. The overall goal of the research is to test the hypothesis that the "downstream shift" of sodium reabsorption from proximal tubule (PT) to the TALH during acute hypertension is due to inhibition of PT sodium transporters, specifically NHE-3 and Na, K-ATPase), and that similar changes are evident in chronic genetic hypertension. There are three specific aims. Specific Aim 1 aims to determine the cellular mechanisms responsible for the decrease in proximal tubular sodium transport during acute hypertension. The principal investigator will investigate the mechanism of sodium pump inhibition and whether or not apical sodium transporters are themselves inhibited or move to sub-apical endosomal compartments. Specific Aim 2 is to determine the cellular mechanisms responsible for the increase in TALH sodium transport during acute hypertension Four questions will be addressed, namely, what is the mechanisms for sodium pump activation; is NHE-3 and/or NKCC2 activated or moved to the apical membrane; does a change in volume flow without hypertension activate sodium pump activity; and is cytochrome P450 arachidonic acid metabolism required for the response? Specific Aim 3 is to test the hypothesis that the cellular mechanisms responsible for the downstream shift in sodium reabsorption during acute
Studies 59
hypertension are evident in genetic models of hypertension. For these studies, the principal investigator will use spontaneously hypertensive rats known to have defective proximal tubular sodium transport regulation, and Milan hypertensive rats known to have elevated thick ascending limp Na, K- ATPase. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RENAL DOPAMINE-1 RECEPTOR DEFECT IN HYPERTENSION Principal Investigator & Institution: Jose, Pedro A.; Professor of Pediatrics; Pediatrics; Georgetown University Washington, DC 20057 Timing: Fiscal Year 2001; Project Start 25-JUL-1991; Project End 31-MAR-2005 Summary: (Verbatim from the application): There are abnormalities in dopamine (DA) production and receptor function in genetic hypertension: some DA receptor genes and their regulators are in loci linked to hypertension. Data generated during the previous funding period show that in mice disruption of the D dopamine receptor. one of the two D1 -like receptors, produces hypertension via a multireceptor cascade. The absence of the D5 receptor increases hypothalamic oxytocin (OT) secretion, sensitizes central V1 vasopressm receptors. activates central non-NMDA receptors and stimulates the sympathetic nervous system. D5 receptor disruption also leads to the generation of reactive oxygen species (ROS) that participate in the increase in BP. Renal tubular effects of D1 -like agonists are also impaired in D5 receptor mutant mice. Abnormalities in the D5 receptor may have functional significance in human essential hypertension because certain single nucleotide polymorphisms (SNPs) of the D5 receptor do not generate cAMP. SNPs of G protein-coupled receptor kinase 4y (GRK4y) and protein phosphatase 2A regulatory subunit, B56a, acting on the D1 receptor in the renal proximal tubule and medullary thick ascending limb cause a subset of genetic hypertension. Thus, D1 and D5 receptor dysfunction produces hypertension by renal and non-renal mechanisms. The overall objective of this proposal is to determine the mechanisms by which dysfunction of the D5 receptor increases system blood pressure. There are 4 specific aims: the first 2 deal with D5 receptor interactions with other G protein-coupled receptors while the last 2 deal with D5 receptor regulation of ROS production. Specific aim 1 will test the hypothesis that disruption of both D1 and D5 receptors results in a greater impairment in the ability to excrete a sodium load and greater increase in BP than disruption of either DA receptor alone, Specific aim 2 will determine the precise roles of oxytocin and V1 receptors in generating the hypertension in the D5 knockout mice. Specific aim 3 will determine the role of ROS in the pathogenesis of hypertension in D5 receptor mutant mice. The induction of heme oxvgenase- I (HO- 1) normalized BP in D5 receptor mutant mice. We will test the hypothesis that hypertension in D5 receptor mutant mice is caused, in part, by increased generation of ROS because of the mutant D5 receptor. per Se. and/or activation of OT/V1 receptors. Specific aim 4 will test the hypothesis that desensitized D5 and D1 receptors and certain D5 receptor SNPs couple to Ga13 instead of Gsa resulting in increased generation of ROS and renal Sodium transport. These studies should shed light into the relative contributions of a genetic D5 receptor abnormality and other G protein-coupled receptors (OT and V1) in the pathogenesis of genetic hypertension. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: RENAL HYPERTENSION
HUMORAL
FACTORS
IN
RENAL
FUNCTION
&
Principal Investigator & Institution: Romero, Juan C.; Professor/Physiology & Biophysics; Mayo Clinic Rochester 200 1St St Sw Rochester, MN 55905
60 Hypertension
Timing: Fiscal Year 2001; Project Start 01-JUN-1979; Project End 31-JUL-2004 Summary: (Adapted from the Investigator's Abstract): The goal is to investigate the mechanisms by which the renin-angiotensin system (RAS) causes changes in intrarenal perfusion and tubular filtration-reabsorption dynamics. Renal artery stenosis in swine is predicted to stimulate angiotensin II (Ang II) production that stimulates superoxide isoprostane and endothelin (ET) production. Regional production of these vasoconstrictor agents will cause cortical ischemia with relative preservation of medullary perfusion. Electron beam computerized tomography (EBCT), a non-invasive x-ray, 3-dimentional tomographer (Imatron c-150) with high temporal resolution, has been developed recently and will be used to define changes in intrarenal blood flow and tubular flow patterns. A computerized analysis of vascular casts of microfil will help localize changes in the microcirculation. Aim # 1 examines changes in intrarenal hemodynamics and relate them with components of the RAS / oxidative stress cascade and ET in the stenotic and contralateral kidneys of pigs with 2-kidney-1-clip Goldblatt hypertension. Aim # 2 determines if reestablishing blood flow to the stenotic kidney normalizes renal blood flow and its intrarenal distribution in both the stenotic and control kidneys. Unclipping is expected to rapidly normalize arterial pressure is related to changes in the RAS and pressure natriuresis. Aim # 3 assesses intrarenal hemodynamics and status of the RAS/oxidative stress cascades in humans with focal unilateral renovascular stenosis. The human results are compared with measures in the swine model of 2-kidney-1 kidney clip hypertension.Aim # 4 examines swine with 2 kidney and 1 kidney clip hypertension with interventions to dissect causal relations between the RAS and / or oxidative stress and intrarenal flows. Aim # 5 is to characterize hypertension in swine produced by low dose Ang II infusion and the roles of oxidative stress and ET in the pathogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RISK OF HEART DISEASE/CANCER IN AFRICAN AMERICANS Principal Investigator & Institution: Robinson, Elwood L.; Professor; North Carolina Central University 160 Alexander-Dunn Bidg. Durham, NC 27707 Timing: Fiscal Year 2002; Project Start 01-JUN-1977; Project End 31-DEC-2005 Summary: The long-term goal of this study is to provide both cross-sectional and longitudinal data on psychosocial, behavioral and psychophysiological risk factors for cardiovascular disease and cancer in alumni of North Carolina Central (NCCU) in Durham, NC. This study represents one of the first examinations of the relationship between SES, age and gender and health risk factors in college-educated African Americans, and how these risk factors and their association may change over time. The primary purpose of this initial study is to conduct a telephone survey of 3,000 male and female NCCU alumni from three cohorts to examine social, behavioral, and psychological processes that mediate the well- known association between SES and hypertension. This study will also explore the association of age, gender and psychosocial factors with cardiovascular reactivity in a smaller subsample of 300 alumni. Finally, this study will investigate the association of SES, age and gender with cancer (in older persons), and with cancer-related risk factors and health behaviors. The following specific hypotheses will be tested: 1. Lower SES will be associated with a higher prevalence of hypertension and cancer (in older persons), and more hypertension and cancer risk factors. Lower SES will also be relate to fewer behaviors associated with cancer prevention and detection. 2. There will be age differences in the influence of SES on hypertension prevalence, and on hypertension and cancer risk factors, such that the SES effect will be stronger in the middle-aged than in elderly
Studies 61
respondents. 3. Psychological, behavioral and psychophysiological factors will mediate or moderate the association between SES and hypertension and cancer in adult blacks. These factors include social support, religious participation, residential environment, health care utilization, smoking physical activity, alcohol intake, dietary patterns, John Henryism, perceived stress/racism, optimism, depression, cancer knowledge/attitudes, screens behaviors and anger. Thus, we hope to show that the association of SES and hypertension and cancer can be partially explained by these variables. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RODENT MODEL OF SEVERE PULMONARY HYPERTENSION Principal Investigator & Institution: Tuder, Rubin M.; Associate Professor; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, CO 800450508 Timing: Fiscal Year 2001; Project Start 17-SEP-2001; Project End 31-JUL-2006 Summary: (provided by applicant): This project replaces the R01 grant: "VEGF protects against pulmonary vascular remodeling". Endothelial cell (EC) dysfunction plays an important role in the development of severe pulmonary hypertension (SPH). We have proposed that one of the most characteristic cellular features of SPH is the finding of EC clusters (tumorlets) in medium-size pulmonary arteries. Since these proliferated ECs express markers of angiogenesis, we have postulated that this EC growth occurs due to disordered angiogenesis. The VEGF receptor 2 (VEGFR-2) regulates several fundamental properties of ECs that impact on EC survival and nitric oxide and prostacyclin. We hypothesize that VEGF has a central role in the maintenance of the pulmonary endothelium. In this revised proposal, we seek to demonstrate that the blockade of the VEGFR-2 in combination with chronic hypoxia or monocrotaline causes severe pulmonary hypertension. We postulate that the combination of VEGFR-2 blockade and chronic hypoxia promotes death of normal pulmonary ECs and the selection of an abnormal, apoptosis-resistant, proliferating EC. Our experimental approach is based on in vivo studies with mice and rats with hypoxia- and monocrotaline-induced pulmonary hypertension (PH), ex vivo, in isolated perfused rat lungs, and, in vitro, using endothelial and lung smooth muscle cell cultures. Specifically, we propose to answer whether: 1. VEGF receptor blockade with SU5416 or ZK202650 in rats exposed to normoxia, or chronic hypoxia, or monocrotaline causes severe pulmonary hypertension associated with EC proliferation; and 2. The combination of VEGF receptor 2 blockade and chronic hypoxia leads to EC injury and EC death prior to the development of EC proliferation and SPH. Since we have successfully completed many of the originally planned experiments, we now propose experiments to confirm the specificity of our findings with SU5416 with a second, chemically unrelated VEGF receptor blocker, ZK202650, and we further probe the impact of abnormal VEGF/VEGF receptor signaling in the development of pulmonary hypertension in the transgenic mice expressing only the 188 amino-acid form of VEGF(VEGF188/188 mice) (Aim 1). In addition, we develop a novel approach to test whether apoptosis of normal lung ECs induces an apoptosis-resistant EC and SPH (Aim 2). This rodent model shares several of the key cellular and molecular features with human SPH. This proposal will allow us to better understand the natural history of human SPH associated with EC proliferation (secondary PH, project I and how alterations in pulmonary EC function affect pulmonary vascular tone and VSMC growth and hypertrophy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
62 Hypertension
•
Project Title: ROLE HYPERTENSION
OF
NA+
TRANSPORTER
GENES
IN
ESSENTIAL
Principal Investigator & Institution: Ruiz-Opazo, Nelson; Asociate Professor; Medicine; Boston University Medical Campus 715 Albany St, 560 Boston, MA 02118 Timing: Fiscal Year 2002; Project Start 15-JAN-1998; Project End 31-MAR-2006 Summary: (provided by applicant): Although there has been significant progress in the investigation of the genetic basis of hypertension, much work remains to be done against the cumulative backdrop of persistent clinical mandates. In essence, essential hypertension remains a highly prevalent disease and remains a major risk factor for the top causes of mortality in the USA: coronary artery disease, heart failure, arrhythmias. stroke and renal disease. It has become clear that (1) gene interaction must be factored into the genetic analysis of complex genetic diseases, (e.g., essential hypertension); and that (2) gene interaction analysis in well-controlled animal model experiments coupled to prioritized subsequent testing in genetically isolated human populations provides a robust experimental strategy. These realizations along with insights, observations, as well as experimental approach validation obtained in the previous research proposal, provide us with the clinical and scientific mandates to investigate the following hypothesis: The unidirectional gene interaction of a1 Na,K-ATPase (a1NK) and Na,K,2C1-cotransporter (NKC) genes increasing susceptibility to hypertension identified in Dahl S rats by an intercross linkage analysis reflects an in vivo molecular interdependence of these transporters and as such it should be amenable to in vivo testing via strategic transgenic experiments. Accordingly, the following specific aims are prioritized for this continuing research proposal: Aim I: Determine the in vivo biological significance of the genetic correlation of the renal-specific Na,K,2Cl-cotransporter gene with hypertension in Dahl S rats. Aim II: Determine the in vivo biological significance of the statistical interactive correlation of a1NK and NKC genes on salt-sensitive hypertension by developing dual transgenic (bigenic) Tg[Ra 1NK x nkc-F)] and Tg[Ra 1NK x nkc-A)] Dahl S rats. The successful completion of this research program will define a) the alNa,K-ATPase and the bumetanide-sensitive Na,K,2Cl-cotransporter as bona fide hypertension susceptibility genes in Dahl S rats; and b) will pave the way for the direct assessment of the role of these genes in hypertension susceptibility in different human populations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE ARTERIOPATHY
OF
NOTCH3
SIGNALING
IN
HYPERTENSIVE
Principal Investigator & Institution: Pollman, Matthew J.; Medicine; Morehouse School of Medicine Atlanta, GA 30310 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-MAY-2007 Summary: (provided by applicant): The pathogenesis of hypertension-induced target organ damage is related to long-term changes in vessel function and structure determined by signaling pathways governing cell growth, programmed cell death, inflammation and matrix modulation. Within the spectrum of identified arteriopathies, CADASIL is a heritable syndrome of systemic small vessel disease predisposing to stroke and vascular dementia. The etiological basis for this syndrome is mutations within one of the Notch family of genes, Notch3. We have recently extended this clinical observation by studying hypertensive vessels and documenting the up-regulation of Notch3 expression in association with maladaptive vascular remodeling. Taken together, these clinical and animal model data support our central hypothesis that
Studies 63
Notch3 is a major determinant of vascular structure. Although it is well established that the vascular complications of hypertension are associated with pathological hypertrophy and matrix deposition, the molecular basis of this phenomenon remains poorly defined. Our preliminary data provides provocative new links between the pathology of hypertensive arteriopathy, the putative mediator TGF-beta1 and the Notch3 transcriptional pathway. The proposed project will test the central hypothesis that Notch3 signaling is a critical determinant of maladaptive hypertensive vascular remodeling by up-regulating a key downstream molecular mediator of VSMC hypertrophy and matrix production--TGF-beta1-through the activation of an RBP-Jkand HRT2-dependent transcriptional pathway. The hypothesis will be tested in vitro and in vivo by systematically implementing both a loss- and gain-of- function strategy, while addressing two fundamental questions: 1) What are the downstream determinants of hypertrophy and matrix production modulated by Notch3 in VSMC and 2) What is the biological significance of Notch3 signaling as a functional and structural determinant of maladaptive hypertensive vascular remodeling and target organ damage in vivo? Specifically, we will: Aim 1: Define the essential role of the Notch3RBP-Jk--HRT2 signaling pathway as a determinant of TGF-beta1 expression in cultured VSMC. Aim 2: Determine the functional role of a gain of Notch3 signaling in promoting maladaptive vascular remodeling and target organ damage in the context of secondary hypertension in Notch3 transgenic mice. Aim 3: Determine the essential mediator role of Notch3 signaling in promoting maladaptive hypertensive vascular remodeling and target organ damage in the context of secondary hypertension in Notch3 null mice. Aim 4: Determine the essential mediator role of Notch3 signaling in promoting maladaptive hypertensive vascular remodeling and target organ damage in the context of genetic hypertension in Notch3 null mice. The successful completion of the aims of this proposal are anticipated to provide novel mechanistic insights into the determinants of maladaptive vascular remodeling that may have important clinical implications for preventing hypertension-induced target organ damage. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE OF TGF-ALPHA IN PULMONARY VASCULAR DISEASE Principal Investigator & Institution: Le Cras, Timothy D.; Assistant Professor; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, OH 45229 Timing: Fiscal Year 2003; Project Start 10-APR-2003; Project End 31-MAR-2007 Summary: (provided by applicant): Pulmonary hypertension plays a major role in the morbidity and mortality of a number of acute and chronic lung diseases including bronchopulmonary dysplasia. While clinical studies have implicated transforming growth factor-alpha (TGF-alpha) in the pathogenesis of these diseases, the role of TGFalpha, its cellular targets, and the signaling pathways involved are unclear. Preliminary data accompanying this application demonstrate that epithelial expression of TGF-alpha causes severe reductions in pulmonary artery number, vascular remodeling, and pulmonary hypertension as early as 2 weeks of age in transgenic mice. We also have preliminary evidence to suggest that this is mediated in part by autocrine signaling through EGF receptors on distal epithelial cells, and reductions in vascular endothelial growth factor-A (VEGF-A). Using both in vitro and in vivo approaches, this proposal will test the central hypothesis that epithelial expression of TGF-alpha disrupts vascular growth and causes vascular remodeling and pulmonary hypertension through EGF receptor-dependent autocrine-paracrine signaling. In the first phase we will define when pulmonary growth is disrupted by TGF-alpha, whether acute or chronic expression of TGF-alpha is necessary, and whether TGF-alpha causes vascular remodeling and
64 Hypertension
pulmonary hypertension independent of reductions in vascular growth (Specific Aim 1). In the second phase we will define the role of indirect signaling through the epithelium versus direct signaling to the vascular endothelium (Specific Aim 2) using a dominant negative (mutant) EGF receptor to block TGF-alpha signaling in specific cellular compartments. In the third phase we will define whether TGF-alpha, regulates expression of VEGF-A in type II epithelial cells in vitro and in vivo, and whether reductions in VEGF-A contribute to the pathogenesis of pulmonary vascular disease (Specific Aim 3). The overall goal of this proposal is to define the timing, cellular targets, and mechanism by which TGF-alpha disrupts pulmonary vascular growth and causes pulmonary hypertension and vascular remodeling. This information will serve as a basis for developing therapeutic strategies aimed at improving lung growth and preventing pulmonary hypertension in premature babies and adults. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE OF URIC ACID IN HYPERTENSION AND RENAL DISEASE Principal Investigator & Institution: Johnson, Richard; Associate Professor; Medicine; Baylor College of Medicine 1 Baylor Plaza Houston, TX 77030 Timing: Fiscal Year 2002; Project Start 01-JAN-2002; Project End 31-DEC-2006 Summary: (provided by applicant): The presence of an elevated serum uric acid is strongly associated with hypertension and renal disease. Despite the association and the ease with which to treat this condition, it remains unknown if the elevated uric acid has a pathogenic role in cardiovascular disease or whether it simply represents a 'marker' for other associated risk factors. Epidemiological studies have been unable to resolve this issue, and experimental studies have been thwarted by the absence of an animal model of mild hyperuricemia and by a paucity of cell culture studies. In preliminary data we have developed a model of mild hyperuricemia in rats and have found that they develop hypertension after several weeks through a crystal independent mechanism in which an afferent arteriolopathy develops in association with alterations in the renin angiotensin, cyclooxygenase-2 and nitric oxide pathways in the kidney. Mild hyperuricemia also results in interstitial renal disease, and hyperuricemia exacerbates renal injury in two different animal models. Our central hypothesis is that hyperuricemia induces hypertension and renal disease acutely by stimulating COX-2 in vascular smooth muscle cells and in the macula densa, which subsequently stimulates renin production, inhibits macula densa nitric oxide synthase, and raises blood pressure. Hyperuricemia also causes a primary afferent arteriolopathy that we hypothesize is mediated by local PDGF expression, and we postulate that once the arteriolopathy is established that salt-sensitive hypertension will persist even if the uric acid levels are corrected. In aim 1 we will examine the role of COX2 in our model, and will examine the kinetics of its expression and the effect of inhibition of COX2 on the alterations in renin, nitric oxide synthase, blood pressure and renal lesions. In aim 2 we will study the mechanism by which uric acid induces the arteriolopathy in our rats, and we will concentrate on the role of PDGF; furthermore, we will determine if the arteriolopathy provides a mechanism by which hypertension will be self-sustained despite correction of the hyperuricemia. In aim 3 we will initiate studies of the cellular mechanism by which uric acid stimulates PDGF and COX2 in cultured vascular smooth muscle cells and macula densa cells, with emphasis on the role of the recently cloned urate channel and on the MAP kinase cascade. Given that there are over 20 million individuals with hyperuricemia in the United States, and that 25-50% of all hypertensive individuals are hyperuricemic, we believe that studies examining the role of hyperuricemia in hypertension and cardiovascular disease are strongly indicated. We believe that the
Studies 65
preliminary data, coupled with the studies proposed, provide the first insights into a potential pathogenic mechanism by which uric acid induces hypertension and renal disease in rats, and may well provide important insights into the role of hyperuricemia in hypertension, cardiovascular and renal disease in man. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SCOR: MOLECULAR GENETICS OF HYPERTENSION Principal Investigator & Institution: Lifton, Richard P.; Chairman, Department of Genetics; Genetics; Yale University 47 College Street, Suite 203 New Haven, CT 065208047 Timing: Fiscal Year 2001; Project Start 01-FEB-1996; Project End 31-JAN-2006 Summary: The Yale Specialized Center of Research in Hypertension focuses on identification of the inherited abnormalities that contribute to high blood pressure and its consequences. To date, we have identified mutations in 4 genes that raise blood pressure, 8 genes that lower blood pressure, linkage for two more Mendelian hypertensive disease, and linkage for blood pressure in the general population. These findings have demonstrated the key role of renal salt homeostasis in determination of blood pressure variation in humans, and have begun to identify molecular mechanisms underlying relationships between blood pressure and bone density. In the current proposal, we propose a series of investigations that will extend these studies. Taking genes in which we have shown mutations alter blood pressure, we examine the impact of variants in these genes on blood pressure and related phenotypes in the Framingham Heart Study. We also search for a gene accounting for a substantial fraction of blood pressure variance in this population, and search for genes contributing to a common complication of hypertension, end stage renal disease. We continue our identification of Mendelian traits that affect blood pressure, and pursue the clinical consequences of these mutations. Finally, since virtually all known causes of hypertension act via a common pathway of increased activity of the amiloride-sensitive epithelial sodium channel, we investigate the signaling pathway that regulates the activity of this channel. These studies will continue to provide key information regarding the causes and consequences of hypertension in humans that have clinical and therapeutic implications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: SCOR-MOLECULAR GENETICS OF HYPERTENSION Principal Investigator & Institution: Sigmund, Curt D.; Professor; Internal Medicine; University of Iowa Iowa City, IA 52242 Timing: Fiscal Year 2001; Project Start 01-FEB-2001; Project End 31-JAN-2006 Summary: The application proposes to renew a Specialized Center of Research (SCOR) in the Molecular Genetics of Hypertension in the University of Iowa Cardiovascular Center. The overall theme is "Molecular and Physiologic Mechanisms of Genetic Hypertension in Humans and Experimental Animals." This initiative, which we have been planning for the past 18 months to fund 6 projects and one scientific core. The center brings together a cadre of investigators including outstanding molecular geneticists (Val Sheffield, Bento Soares and Curt Sigmund at Iowa and John Rapp in Ohio); molecular biologists (Peter Snyder and John Engelhardt); a genetic epidemiologist and biostatistician (Trudy Burns); and leading hypertension physiologists (Allyn Mark, John Stokes, Robin Davisson, Gerald DiBona, and Joseph Hill) to pursue the three broad goals of the Hypertension Molecular Genetics SCOR.
66 Hypertension
The strengths of the proposal include: (1) study of two distinctive human populations including nuclear families from the Muscatine population study of obesity and blood pressure; and Bedouin families from a homogenous population in Southern Israel with a high incidence of obesity; (2) a leading human and rat molecular genetics laboratory with capability for high throughput gene identification, sequencing of cDNAs, and generation and analysis of cDNA microarrays; (3) coordinated pursuit of chromosomal quantitative trait loci, physiologic and cellular intermediate phenotypes, and candidate genes in rat models of genetically salt-sensitive hypertension; (4) pursuit of functional data on the consequences of genetic variation in genes encoding the epithelial sodium channel; and (5) use of transgenic mice, tissue-specific knockout mice and mutant mouse strains to test the role of tissue-specific renin- angiotensin systems in hypertension and cardiac hypertrophy, and to study fundamental mechanisms in obesity-induced hypertension. These investigators have established vibrant collaborations within our SCOR and with investigators studying the genetics of hypertension at other institutions. This coalition of leading molecular geneticists and hypertension physiologists in the Iowa SCOR holds promise for continued substantial contribution to advancing knowledge of the molecular genetics of hypertension. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STRUCTURE/FUNCTION OF THE MICROCIRCULATIOM Principal Investigator & Institution: Schmid-Schonbein, Geert W.; Professor; Applied Mechanics & Engr Scis; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, CA 92093 Timing: Fiscal Year 2001; Project Start 01-SEP-1978; Project End 31-MAR-2003 Summary: (Adapted from the application) The hypertensive syndrome is accompanied by a broad range of microvascular dysfunctions. The mechanisms responsible for development of cardiovascular complications in hypertension, however, have remained speculative. The applicant's hypothesis is that in addition to the definitive elevation of the blood pressure a key feature of hypertension is a shift in free radical formation at the tissue level which involves an adrenal/renal pathway. An oxidative stress on one hand leads to elevation of the arteriolar resistance while on the other hand it triggers a multitude of pathophysiological consequence, especially at the level of the microcirculation. Introduction of advanced microvascular techniques has enabled the investigators to identify higher levels of free radical production in-vivo in several models of hypertension together with a shift in the state of activation and interaction of cells in the circulation. The objective of this study is to investigate the mechanisms for the enhanced free radical production and outline its consequences for adjustments of microvascular function. In specific terms, the investigators propose to examine (I) the role of adrenal glucocorticoids and specific oxidases in free radical production, (II) mechanisms by which cell death, including apoptosis, are induced by oxidative stress relative to microvascular rarefaction (a loss of the smallest terminal arterioles and selected capillaries) and its modulation through the involvement of adrenal glucocorticoids, free radical production, and nitric oxide suppression, (III) the modification in the shear stress response of circulating leukocytes and endothelial cells in hypertensives as a consequence of glucocorticoids, and (IV) the basis for the reduced capacity of circulating leukocytes in hypertensives to respond to chemotactic stimuli, reduced adhesion to microvascular endothelium and the consequences for the migratory response. Several well-documented hypertensive models (spontaneously hypertensive rat, Dahl genetic salt-dependent hypertensive model, nitric oxide synthase gene knockout mouse) will be examined in a specific context in order to bring to light
Studies 67
common pathophysiological pathways which undermine the microcirculation in various forms of hypertension. Such a program will serve to clarify the pathogenesis of hypertension and is expected to stimulate the design of novel approaches for interventions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SYMPATHETIC NERVOUS SYSTEM REGULATION OF CELL ADHESION Principal Investigator & Institution: Mills, Paul J.; Professor; Psychiatry; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, CA 92093 Timing: Fiscal Year 2001; Project Start 01-AUG-1997; Project End 31-MAR-2005 Summary: Observations from the literature suggest that the SNS affects leukocyte endothelial interaction through at least four pathways: 1) circulating leukocyte cell adhesion molecule expression, particularly, increased CD11a expression; 2) elevated endothelial cell adhesion molecule expression (as indexed by elevated circulating levels of sCD54); 3) increased formation of leukocyte-platelet aggregates, which in turn enhance leukocyte adhesion to the endothelium; and 4) increased production of proinflammatory cytokines, particularly IL-6 and TNF-alpha, that in turn enhance the expression of leukocyte and endothelial cell adhesion molecules. The potential disease implications of these findings are not well understood. We have also gathered preliminary data suggesting that subjects with hypertension, as compared to subjects with normal blood pressure, exhibit exaggerated responses in each of these four pathways. Hypertensives show: 1) increased density of lymphocyte CD11a at rest and in response to stressors; 2) elevated resting and stressor-induced levels of circulating soluble sCD54; 3) increased SNS-induced formation of leukocyte-platelet aggregates in circulation; and 4) increased production of proinflammatory cytokines. This project will examine these pathways, particularly the effect of sCD54 on in vitro leukocyte adhesion in hypertension, the effects of platelet activation on leukocyte adhesion in hypertension, and the potential role of adhesion molecule-inducing proinflammatory cytokines on increased adhesion in hypertension. We propose to study 40 hypertensive and 40 normotensive women and men prior to and following an exhaustive exercise task and an infusion of the beta-adrenergic agonist isoproterenol. The overarching hypothesis of the proposal is that hypertension combined with sympathetic activation results in enhanced effects on leukocyte, platelet and endothelial adhesion that are of likely clinical significance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: TGF-BETA1, RENAL DISEASE AND HYPERTENSION Principal Investigator & Institution: August, Phyllis; Professor of Medicine; Medicine; Weill Medical College of Cornell Univ New York, NY 10021 Timing: Fiscal Year 2001; Project Start 01-JUN-2000; Project End 31-MAY-2005 Summary: Dr. Phyllis August's application for a K24 is based on her accomplishments as an investigator in patient oriented research, her significant track record of mentoring young investigators, and the research plan that explores an exciting new area of investigation in hypertension and renal disease in humans. Dr. August's past research has focused on hypertension and renal disease, especially hypertensive disorders in pregnancy. She has made original and significant discoveries with respect to regulation of blood pressure and calcium metabolism in normal and hypertensive pregnancy, and recently discovered that transforming growth factor-beta1 (TGF-beta1) is
68 Hypertension
hyperexpressed in hypertensives. Also, TGF- beta1 was hyperexpressed in Africa Americans with hypertension and/or renal disease compared to their Caucasian counterparts. The research proposed for this award explores the role of TGF-beta1 hyperexpression in the pathogenesis of renal disease and hypertension. The objective of this research is to test the hypothesis that hyperexpression of TGF-beta1, a multifunctional cytokine clearly shown to induce renal disease in experimental models, is a risk factor for the progression of renal disease to end stage renal disease (ESRD) in humans. That TGF-beta1 overexpression is more frequent in African Americans, a population at greater risk for ESRD than Caucasians, and that TGF-beta1 expression is determined by TGF-beta1 DNA polymorphisms will be explored in this study with conceptually interrelated clinical and laboratory studies. Dr. August will have the primary responsibility for these studies in the next 5 years. Studies suitable for beginning investigators to develop research careers are also proposed and include, 1) investigation of TGF-beta1 as a therapeutic target for angiotensin II receptor blockade, 2) characterization of placental cytokine gene expression profiles in normal and hypertensive pregnancy, 3) clinical studies of human renovascular hypertension. Further goals include obtaining additional training in research methodology, biostatistics, and genetic epidemiology. A long-term goal is to further develop the research program in hypertensive disorders of pregnancy by training young investigators. The resources and environment at Cornell including the laboratory expertise of Dr. Suthanthiran, the broad based patient population available via the Hypertension Center and by the applicant's joint appointment in Obstetrics, the established clinical research programs (including GCRC) together provide the necessary environment to conduct the proposed research and provide mentoring to new investigators. The K24 award will provide invaluable protected time for the development of the above research protocols, for obtaining new research skills, and for ensuring the mentoring of new investigators who will continue to conduct patient oriented research in the field of kidney disease, hypertension, and hypertension in pregnancy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE ANGIOTENSINOGEN GENE AND HUMAN HYPERTENSION Principal Investigator & Institution: Jorde, Lynn B.; Professor; Human Genetics; University of Utah 200 S University St Salt Lake City, UT 84112 Timing: Fiscal Year 2003; Project Start 27-JAN-2003; Project End 31-DEC-2006 Summary: (provided by applicant): Essential hypertension affects at least 25 percent of American adults, and it is a primary risk factor for heart failure, stroke, and kidney disease. Many, but not all, studies have shown that variants of the angiotensinogen gene (AGT) affect the risk of hypertension, but association studies conducted to date have been compromised by genetic heterogeneity and by the inherent complexity of hypertension as a phenotype. To overcome these difficulties, we will sequence or genotype a 14.4 kb region including AGT in more than 1,600 individuals sampled from populations throughout the world. This will permit us to explore fully the extent of allelic heterogeneity, haplotype variation, and potential for population stratification in the AGT gene. Approximately 600 of these individuals are clinically uncharacterized and will represent a broad range of worldwide human variation. Another 500 subjects are members of 40 Utah pedigrees that are part of the CEPH collection. These unique families have been heavily characterized genetically, and they are now being phenotyped for variables that include anthropometrics, blood chemistries, blood pressure measures, and plasma and urinary angiotensinogen. We will address the issue
Studies 69
of genetic heterogeneity by testing associations between multi-SNP AGT haplotypes, angiotensinogen levels, and blood pressure. In addition, linkage disequilibrium patterns will be assessed to determine the density and nature of SNPs best suited for localizing a gene underlying a complex trait. We will address the issue of phenotypic heterogeneity in hypertension by performing extensive SNP typing on a set of 400 hypertensives and 100 normotensives collected by Dr. Gordon Williams. These clinically well-characterized subjects have been tested for their response to infused angiotensin-II under high and low sodium intake. This direct probe provides a hypertension endophenotype that is closer to the function of the AGT gene, yielding a more realistic and informative assessment of the relationship between AGT haplotype variation and hypertension risk. A phylogenetic analysis of AGT sequence variation in our worldwide sample will help to assess population stratification in association studies. In addition, this sample will allow us to test the hypothesis that the ancestral T235 AGT allele provided a selective advantage in the sodium-poor environment of sub-Saharan Africa. The results of this analysis may help to explain why African-Americans have elevated rates of hypertension. In summary, our extensive analysis of AGT variation in more than 1,600 subjects will clarify the role of this gene in essential hypertension and will test specific hypotheses about the evolution of AGT. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TRANSGENIC STUDY VASCULAR ROLE OF NEUROPEPTIDE Y Principal Investigator & Institution: Michalkiewicz, Michael; Physiology; West Virginia University P. O. Box 6845 Morgantown, WV 265066845 Timing: Fiscal Year 2001; Project Start 15-DEC-1998; Project End 31-MAR-2001 Summary: Neuropeptide Y (NPY) with its multiple receptor subtypes is emerging as an important sympathetic regulator of cardiovascular and metabolic functions. Very potent vasoconstrictor and appetite stimulating activities of NPY suggest the physiological importance of this peptide and its involvement in the pathogenesis of hypertension and obesity. Antagonizing specific NPY activities may offer new avenues for treatment these diseases. This project tests the hypothesis that endogenous NPY by activating its own receptor increases vascular tone directly or indirectly by modulating adrenergic transmission to the blood vessels and that an increased chronic expression of the NPY gene will cause the development of hypertension. To test this hypothesis the NPY transgenic of Sprague Dawley rats were generated in which endogenous NPY is overexpressed under its natural promoter allowing for physiological regulation in the constitutive sites. These animals develop persistent hypertension with mildly elevated body weight. Using this model, the role of NPY and its newly discovered receptors in the long-term regulation of cardiovascular functions will be determined. Four Specific Aims are proposed: (1) Analyze the pattern of NPY overexpression at the protein and mRNA levels in the NPY transgenic male and female rats with particular emphasis on the constitutive sites of endogenous NPY production involved in the cardiovascular regulation; (2a) Determine the effect of NPY overexpression on arterial blood pressure and vascular resistance in male and female rats; and (2b) using available specific NPY receptor antagonists, identify the NPY receptor(s) involved in the development of the hypertension in the NPY transgenic rats; (3) Determine the effect of NPY overexpression on the adrenergic transmission to blood vessels by measuring a) pressor responsiveness to an adrenergic agonist norepinephrine (alpha1/alpha2); and b) (alpha1/ alpha2) responsiveness of the submandibular gland blood flow to supramaximal nerve stimulation; (4) Evaluate the contribution of increased food consumption and body weight to the development of the hypertension in the NPY
70 Hypertension
transgenic rats using a pair feeding approach. This studies will determine the role of endogenous NPY and its receptors in a long-term regulation of blood pressure and the mechanisms of the cooperation between the sympathetic neurotransmitters. The NPY overexpressing rats with well defined mutation of the NPY gene will provide a new transgenic animal model of hypertension; such a model should also be very useful for development of new therapies for treating this diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TREATMENT INTENSITIES
OF
HYPERTENSION
WITH
TWO
EXERCISE
Principal Investigator & Institution: Posner, Joel D.; Medicine; Mcp Hahnemann University Broad & Vine Sts Philadelphia, PA 19102 Timing: Fiscal Year 2001; Project Start 15-JUN-1997; Project End 31-MAY-2004 Summary: (Adapted from Investigator's Abstract) Arterial hypertension affects over 50 million Americans. While drug treatment is effective, exercise would be safer, might be cheaper, and would bring added health benefits if it could replace drugs in controlling hypertension. The aims of this study are to: 1) determine if two 18 month long endurance training programs, one of high intensity and one of moderate intensity, can replace medication as a treatment for mild essential hypertension, 2) determine if a moderate intensity endurance training program is as effective as or more effective than a high intensity program in allowing mild essential hypertensives to discontinue antihypertensive medication, 3) determine if physiological, psychological, and compliance variables predict success in allowing mild essential hypertensives to discontinue antihypertensive medication. The investigators propose a randomized controlled trial. Known hypertensives (n=162) whose diastolic blood pressures rises to between 90 and 104 within four months of discontinuing medication under careful observation will have their pressures controlled with enalapril. Half the subjects will be female and half male, and their racial characteristics will generally reflect that of our managed care population (about 20% black). V02 peak will be measured during cycle ergometry. Eligible subjects will be randomly assigned to 18 months participation in one of three groups: 1) high intensity endurance training (35 minutes 3 times/week at heart rate at 70-85% of V02 peak), 2) moderate intensity endurance training (35 minutes 3 times/week at heart rate of 50-70 of V02 peak), and 3) contact control. Enalapril will be forward or back titrated or discontinued to maintain a normal blood pressure. After 12 months participation, medication will be withdrawn under careful supervision from all subjects still taking it. They will test the hypotheses that: 1) a greater number of subjects undergoing either or both of the two 18 month exercise training programs will be able to stop antihypertensive medication than non-exercising controls, 2) moderate and high intensity endurance training are equally effective in replacing drugs in the treatment of mild essential hypertension, and 3) subjects that are successful at withdrawing antihypertensive medication will have: greater improvements in V02 peak, better initial psychological status or greater improvements in psychological status, and greater compliance with the exercise training program. The investigators state that this study will be a critical test of whether endurance training can replace medication in an important number of patients as a treatment for hypertension. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TULANE COBRE IN HYPERTENSION AND RENAL BIOLOGY Principal Investigator & Institution: Navar, L. Gabriel.; Professor and Chairman; Physiology; Tulane University of Louisiana New Orleans, LA 70118
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Timing: Fiscal Year 2002; Project Start 20-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Hypertension is a leading cause of death and disability affecting 50 million people in the United States and responsible for 200,000 deaths annually. Because hypertension and associated cardiovascular diseases are particularly prevalent in Louisiana, Tulane Health Sciences Center established a Hypertension and Renal Center of Excellence, which consists of investigators in the School of Medicine and the School of Public Health and Tropical Medicine. The close linkage between hypertension and renal research is due to the growing recognition that many forms of hypertension result from abnormalities in kidney function due either to primary renal disease or to abnormal hormonal or environmental influences on the kidney that affect renal hemodynamics or tubular transport function. Disorders of sodium reabsorption by the renal tubules may lead to inadequate urinary excretion of salt, and derangements in vascular control mechanisms contribute to various forms of hypertension. Inappropriate activation of the renin-angiotensin system also leads to sodium retention and the development of hypertension with ensuing progressive renal and vascular injury. The objectives of this proposal are to provide an enriched mentoring environment to our junior faculty investigators so that they can achieve independent status and national competitiveness and to augment and strengthen biomedical research capacity at Tulane and the state of Louisiana in hypertension and associated renal and cardiovascular disease. The individual projects ranging from basic studies on development and function of the kidney to clinical and epidemiologic studies have been designed and will be performed by the junior faculty investigators who will be mentored by senior experienced faculty. Projects designated for initial support include investigations on the roles of angiotensin receptors in the control of the renal microvasculature and in kidney development and the roles of the newly described Heme-Heme oxygenase-carbon monoxide system and of cytochrome P450 metabolites in experimental and clinical hypertension. Epidemiologic studies will evaluate the effects of lifestyle modification (exercise) on hypertension in order to reduce blood pressure-related cardiovascular and renal disease in general but with emphasis on African-Americans. Accordingly, this COBRE will provide pivotal support needed to increase the number of competitive scientists in Louisiana in a disease specific area of extremely high biomedical relevance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: URIC ACID IN CHILDHOOD HYPERTENSION Principal Investigator & Institution: Feig, Daniel I.; Pediatrics; Baylor College of Medicine 1 Baylor Plaza Houston, TX 77030 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): An association between hyperuricemia and hypertension has been observed repeatedly since the 1870s. Generally the link was dismissed as having no causal role because of an assumption that the increase in serum uric acid was merely a surrogate for decreased glomerular filtration rate. Recently the association has been reevaluated because of results from several large clinical trials that implicate hyperuricemia as an independent risk factor for poor cardiovascular outcomes. Our own data demonstrates a close correlation between serum uric acid and primary hypertension in children. Furthermore, data from experiments using a model of mild hyperuricemia in rats reveal that the hyperuricemia alone is (1) sufficient to lead to hypertension and (2) exacerbates the progressive renal injury associated with either Cyclosporin A nephrotoxicity or surgical 5/6 nephrectomy. In the animal model, the mechanisms involved in these processes include uric acid mediated activation of
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cyclooxygenase-II, activation of the renin angiotensin system and down regulation of renal nitric oxide synthase. If these animal studies can be generalized to human populations, control of mild hyperuricemia will provide a new approach to management of hypertension as well as a novel therapeutic target for the prevention of progressive renal disease and cardiovascular morbidity. We propose to test whether the use of the xanthine oxidase inhibitor allopurinol, a uric acid lowering drug, will (1) ameliorate primary hypertension in children and (2) control hypertension in renal transplant recipients receiving cyclosporin or tacrolimus. We will further investigate the physiological mechanism by which serum uric acid levels are elevated in hypertensive children and the biochemical mechanisms by which elevated serum uric acid lead to increased blood pressure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: VASCULAR CONSEQUENCES OF SYMPATHETIC NEURAL ACTIVATION IN OBESITY Principal Investigator & Institution: Haynes, William G.; Associate Professor; University of Iowa Iowa City, IA 52242 Timing: Fiscal Year 2003; Project Start 21-JAN-2003; Project End 31-DEC-2007 Summary: The mechanisms underlying the association between obesity and hypertension are unclear, but increased sympathetic neural drive to skeletal muscle circulation and kidney has been implicated. This insight has been derived from direct intraneural recordings of sympathetic nerve activity and regional norepinephrine turnover. It has been assumed that the increases in sympathetic nerve activity (SNA) directly translate into elevated sympathetic vasoconstrictor tone, but these assumptions have not been rigorously tested. We have recently obtained preliminary data using maximal alpha-adrenergic receptor blockade of the forearm vasculature that demonstrates no increase in sympathetic vascular tone in normotensive obese humans despite increased muscle SNA. This suggests that there is dissociation between sympathetic neural outflow and sympathetically mediated vasoconstrictor tone. Interestingly, we also have preliminary data indicating that in obese hypertensive humans, increased muscle SNA is associated with increased sympathetic vasoconstrictor tone. This suggests that a predisposition to hypertension interacts with obesity to permit the increased SNA to be expressed as increased sympathetic vascular tone. This project will test the hypothesis that the vasoconstrictor effects of SNA are attenuated in obesity but preserved in obese humans with a predisposition to hypertension, with these specific aims: 1) What are the effects of hypertension, obstructive sleep apnea and visceral adiposity on the resistance vessel expression of elevated SNA? 2) Is endothelial nitric oxide generation responsible for attenuated effects of SNA on vascular tone in obese compared to lean normotensive humans, and is the modulating influence of nitric oxide attenuated in obese hypertensive humans? 3) What are the effects of different dietary components on SNA and sympathetically mediated vasoconstrictor tone in obese normotensive and hypertensive subjects? Sympathetic nerve traffic to skin and skeletal muscle will be assessed by microneurography. Sympathetic vasoconstrictor tone will be assessed by the vasodilator response of skin (laser Doppler flux) and skeletal muscle (oxygenation measured by near infra-red oximetry) to intra-arterial infusion of an alpha-adrenergic antagonist. These studies should provide new insights into the cardiovascular effects of obesity and the factors that predispose to obesity-related hypertension. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: VASCULAR MODULATION
EXTRACELLULAR
SUPEROXIDE
DISMUTASE
Principal Investigator & Institution: Fukai, Tohru; Emory University 1784 North Decatur Road Atlanta, GA 30322 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (provided by the applicant): Extracellular superoxide dismutase (ecSOD), a major form of SOD expressed in the vasculature, is a "secretory" copper-containing enzyme and plays an important role in regulating blood pressure and endothelial function by modulating the levels of O2 in the extracellular space. Particularly, in angiotensin H-induced hypertension model, the excessive 02 is observed in the vessel wall and the hypertension is ameliorated by treatment with membrane-targeted forms of SOD. Moreover, we have found that blood pressure and 02 production in the vessel were highly elevated in ecSOD-deficient mice infused with angiotensin II. Thus, ecS0D is a potentially important modulator of oxidative phenomena in the pathogenesis of hypertension. Recently, it has been shown that copper chaperones (CCS) are critical for copper transport and delivery to copper containing enzymes. Our preliminary data strongly suggests that CCS with signal peptide (CCS-SP) which targets to Golgi plays an important role in the transport of copper to ecSOD, which is required for full activity of the ecSOD. We will propose the following specific aim to address how ecSOD activity is controlled by copper transport system such as CCS and copper transporter in the yeast system, vascular cells and in vivo model of hypertension. In aim 1, we will characterize a role of copper transport system for full expression of ecSOD activity using the yeast system. First, by generating several CCS-SP cDNA constructs including the truncated form, we will determine which region is critical for copper loading-to ecSOD. Second, we will determine if copper loading to ecSOD requires MNK, a copper transporter in the trans-Golgi network, using the yeast strain deficient in MNK. In aim 2, we will identify endogenous copper chaperone for ecSOD in human aortic smooth muscle cells (HASM) that highly expresses ecSOD, by using the highly conserved region of CCS as a probe that have detected novel CCS-like transcript and protein in HASM. Next, we will determine if copper delivery to ecSOD requires MTNK in mammalian cells, by using the murine MNK-mutant fibroblast and aorta from MNK-mutant mice. In aim 3, we will examine the role of copper transport system for ecSOD in blood pressure, vascular O2 production and endothelial function in angiotensin II induced hypertension by using MNK-mutant mice. These studies will provide new insight into a copper transport system for ecSOD as a novel modulator of oxidative stress linked to the pathogenesis of hypertension and as essential to anti-oxidant therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and
3 4
Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.
With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age.
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unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “hypertension” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for hypertension in the PubMed Central database: •
[beta]-Blockers as first-line therapy for hypertension. by Heckman GA, Papaioannou A, Parkinson W, Patterson CA. 2000 Nov 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=80403
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A De novo Missense Mutation of the [beta] Subunit of the Epithelial Sodium Channel Causes Hypertension and Liddle Syndrome, Identifying a Proline-Rich Segment Critical for Regulation of Channel Activity. by Hansson JH, Schild L, Lu Y, Wilson TA, Gautschi I, Shimkets R, Nelson-Williams C, Rossier BC, Lifton RP. 1995 Dec 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=40428
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A genetic defect resulting in mild low-renin hypertension. by Wilson RC, DaveSharma S, Wei JQ, Obeyesekere VR, Li K, Ferrari P, Krozowski ZS, Shackleton CH, Bradlow L, Wiens T, New MI. 1998 Aug 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=21485
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A genetically clamped renin transgene for the induction of hypertension. by Caron KM, James LR, Kim HS, Morham SG, Lopez ML, Gomez RA, Reudelhuber TL, Smithies O. 2002 Jun 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=123053
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A new era in hypertension research: discussing the findings of ALLHAT. by Furberg CD. 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=64822
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A Review of the Adverse Effects of Peripheral Alpha-1 Antagonists in Hypertension Therapy. by Bryson CL MD, Psaty BM MD PhD. 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=134479
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Activation of the Fas/Fas ligand pathway in hypertensive renal disease in Dahl/Rapp rats. by Sanders PW, Wang PX. 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=64784
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Acute hemodynamic effects of inhaled nitric oxide, dobutamine and a combination of the two in patients with mild to moderate secondary pulmonary hypertension. by Vizza CD, Rocca GD, Roma DA, Iacoboni C, Pierconti F, Venuta F, Rendina E, Schmid G, Pietropaoli P, Fedele F. 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96124
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Acute visual loss after initiation of antihypertensive therapy: case report. by Mainville N, Connolly WE. 2003 Aug 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=180657
5
The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.
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Adipocyte-derived leucine aminopeptidase genotype and response to antihypertensive therapy. by Hallberg P, Lind L, Michaelsson K, Kurland L, Kahan T, Malmqvist K, Ohman KP, Nystrom F, Liljedahl U, Syvanen AC, Melhus H. 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=212555
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Alterations in the regulation of androgen-sensitive Cyp 4a monooxygenases cause hypertension. by Holla VR, Adas F, Imig JD, Zhao X, Price E Jr, Olsen N, Kovacs WJ, Magnuson MA, Keeney DS, Breyer MD, Falck JR, Waterman MR, Capdevila JH. 2001 Apr 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=33189
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Aminopeptidase A inhibitors as potential central antihypertensive agents. by Reaux A, Fournie-Zaluski MC, David C, Zini S, Roques BP, Corvol P, Llorens-Cortes C. 1999 Nov 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23962
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Anorexigen-induced pulmonary hypertension and the serotonin (5-HT) hypothesis: lessons for the future in pathogenesis. by Eddahibi S, Adnot S. 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=64820
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Arterial expression of 5-HT2B and 5-HT1B receptors during development of DOCAsalt hypertension. by Banes AK, Watts SW. 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=201025
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Atherosclerotic ischemic renal disease. Diagnosis and prevalence in an hypertensive and/or uremic elderly population. by Coen G, Calabria S, Lai S, Moscaritolo E, Nofroni I, Ronga G, Rossi M, Ventroni G, Sardella D, Ferrannini M, Zaccaria A, Cianci R. 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150566
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Benign intracranial hypertension secondary to nasal fluticasone propionate. by Bond DW, Charlton CP. 2001 Apr 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=30587
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Bone morphogenetic proteins, genetics and the pathophysiology of primary pulmonary hypertension. by Caestecker MD, Meyrick B. 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=59576
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Cardiovascular Effects of Fermented Milk Containing Angiotensin-Converting Enzyme Inhibitors Evaluated in Permanently Catheterized, Spontaneously Hypertensive Rats. by Fuglsang A, Nilsson D, Nyborg NC. 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=126801
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Changes in left ventricular structure and function in patients with white coat hypertension: cross sectional survey. by Muscholl MW, Hense HW, Brockel U, Doring A, Riegger GA, Schunkert H. 1998 Aug 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28649
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Chronic Control of High Blood Pressure in the Spontaneously Hypertensive Rat by Delivery of Angiotensin Type 1 Receptor Antisense. by Iyer SN, Lu D, Katovich MJ, Raizada MK. 1996 Sep 3; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38537
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Clinical Trials in Hypertension. by Springer AJ. 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101190
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Combination treatment effective option for hypertensive, diabetic patients with microalbuminuria. by Chen BH. 2001 Mar 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=80906
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Conditional and targeted overexpression of vascular chymase causes hypertension in transgenic mice. by Ju H, Gros R, You X, Tsang S, Husain M, Rabinovitch M. 2001 Jun 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=34692
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Correction of Hypertension by Normalization of Endothelial Levels of Fibroblast Growth Factor and Nitric Oxide Synthase in Spontaneously Hypertensive Rats. by Cuevas P, Garcia-Calvo M, Carceller F, Reimers D, Zazo M, Cuevas B, Munoz-Willery I, Martinez-Coso V, Lamas S, Gimenez-Gallego G. 1996 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38172
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Cost effectiveness analysis of improved blood pressure control in hypertensive patients with type 2 diabetes: UKPDS 40. by [No authors listed]; 1998 Sep 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28661
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Cyclosporine A-induced hypertension involves synapsin in renal sensory nerve endings. by Zhang W, Li JL, Hosaka M, Janz R, Shelton JM, Albright GM, Richardson JA, Sudhof TC, Victor RG. 2000 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=16939
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Defective G Protein Activation of the cAMP Pathway in Rat Kidney During Genetic Hypertension. by Chatziantoniou C, Ruan X, Arendshorst WJ. 1995 Mar 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42331
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Defects in caveolin-1 cause dilated cardiomyopathy and pulmonary hypertension in knockout mice. by Zhao YY, Liu Y, Stan RV, Fan L, Gu Y, Dalton N, Chu PH, Peterson K, Ross J Jr, Chien KR. 2002 Aug 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=123264
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Delivery of Angiotensin II Type 1 Receptor Antisense Inhibits Angiotensin Action in Neurons from Hypertensive Rat Brain. by Lu D, Raizada MK. 1995 Mar 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42329
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Dissection of a Quantitative Trait Locus for Genetic Hypertension on Rat Chromosome 10. by Kreutz R, Hubner N, James MR, Bihoreau M, Gauguier D, Lathrop GM, Ganten D, Lindpaintner K. 1995 Sep 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41050
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Diuretics: again the first step in the treatment of most patients with hypertension. by Fuchs FD. 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=59527
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Do hypertensive patients with average cholesterol levels benefit from atorvastatin therapy? by Hackam DG. 2003 Jun 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=161615
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Does Superoxide Underlie the Pathogenesis of Hypertension? by Nakazono K, Watanabe N, Matsuno K, Sasaki J, Sato T, Inoue M. 1991 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=52864
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Down-regulation of the expression of endothelial NO synthase is likely to contribute to glucocorticoid-mediated hypertension. by Wallerath T, Witte K, Schafer SC, Schwarz PM, Prellwitz W, Wohlfart P, Kleinert H, Lehr HA, Lemmer B, Forstermann U. 1999 Nov 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23952
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Dual Inhibition of Angiotensin-Converting Enzyme and Neutral Endopeptidase by the Orally Active Inhibitor Mixanpril: A Potential Therapeutic Approach in Hypertension. by Fournie-Zaluski MC, Gonzalez W, Turcaud S, Pham I, Roques BP, Michel JB. 1994 Apr 26; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=43725
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Effect of Increasing Doses of Angiotensin II Infused into Normal and Hypertensive Wistar Rats on Low Density Lipoprotein and Fibrinogen Uptake by Aortic Walls. by Cardon-Sanclemente LE, Medina R, Born GV. 1994 Apr 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=43561
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Endogenous Biosynthesis of Arachidonic Acid Epoxides in Humans: Increased Formation in Pregnancy-Induced Hypertension. by Catella F, Lawson JA, Fitzgerald DJ, FitzGerald GA. 1990 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=54435
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Episodic coronary artery vasospasm and hypertension develop in the absence of Sur2 KATP channels. by Chutkow WA, Pu J, Wheeler MT, Wada T, Makielski JC, Burant CF, McNally EM. 2002 Jul 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151064
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Evaluation of computer based clinical decision support system and risk chart for management of hypertension in primary care: randomised controlled trial. by Montgomery AA, Fahey T, Peters TJ, MacIntosh C, Sharp DJ. 2000 Mar 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27312
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Evidential hypertension. by Wright JM. 2002 Jan 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=99235
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Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. by Maynard SE, Min JY, Merchan J, Lim KH, Li J, Mondal S, Libermann TA, Morgan JP, Sellke FW, Stillman IE, Epstein FH, Sukhatme VP, Karumanchi SA. 2003 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151901
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First-line drugs for hypertension. by Spence JD. 2001 Jan 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=80672
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First-line drugs for hypertension. by Wright JM. 2001 Jan 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=80673
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Functional Heterogeneity of Bone Morphogenetic Protein Receptor-II Mutants Found in Patients with Primary Pulmonary Hypertension. by Nishihara A, Watabe T, Imamura T, Miyazono K. 2002 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=124142
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G protein-coupled receptor kinase 4 gene variants in human essential hypertension. by Felder RA, Sanada H, Xu J, Yu PY, Wang Z, Watanabe H, Asico LD, Wang W, Zheng S, Yamaguchi I, Williams SM, Gainer J, Brown NJ, Hazen-Martin D, Wong LJ, Robillard JE, Carey RM, Eisner GM, Jose PA. 2002 Mar 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122616
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Gene Targeting Approaches to Complex Genetic Diseases: Atherosclerosis and Essential Hypertension. by Smithies O, Maeda N. 1995 Jun 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41675
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Generalizability of guidelines and physicians' adherence. Case study on the Sixth Joint National Commitee's guidelines on hypertension. by Pedone C, Lapane KL. 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=183849
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Genetic Determinants of Human Hypertension. by Lifton RP. 1995 Sep 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41004
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Genetic disruption of [gamma]-melanocyte --stimulating hormone signaling leads to salt-sensitive hypertension in the mouse. by Ni XP, Pearce D, Butler AA, Cone RD, Humphreys MH. 2003 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152936
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Genetically determined chloride-sensitive hypertension and stroke. by Tanaka M, Schmidlin O, Yi SL, Bollen AW, Morris RC Jr. 1997 Dec 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=25108
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Genomic approaches to research in pulmonary hypertension. by Geraci MW, Gao B, Hoshikawa Y, Yeager ME, Tuder RM, Voelkel NF. 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=59578
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Heterozygous deficiency of hypoxia-inducible factor --2[alpha] protects mice against pulmonary hypertension and right ventricular dysfunction during prolonged hypoxia. by Brusselmans K, Compernolle V, Tjwa M, Wiesener MS, Maxwell PH, Collen D, Carmeliet P. 2003 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=155039
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How well can blood pressure be controlled? Progress report on the Systolic Hypertension in Europe Follow-Up Study (Syst-Eur 2). by Thijs L, Staessen JA, Beleva S, Birkenhager WH, Bulpitt CJ, Celis H, Fletcher AE, Kermova R, Leonetti G, Laks T, Mantov S, Nachev C, Sarti C, Tuomilehto J, Fagard RH. 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=64833
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Hypertension and [alpha]-adrenergic blockers: preliminary ALLHAT results. by Chen BH. 2000 Aug 22; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=80393
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Hypertension and prolonged vasoconstrictor signaling in RGS2-deficient mice. by Heximer SP, Knutsen RH, Sun X, Kaltenbronn KM, Rhee MH, Peng N, Oliveira-dosSantos A, Penninger JM, Muslin AJ, Steinberg TH, Wyss JM, Mecham RP, Blumer KJ. 2003 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151918
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Hypertension in the Parsi community of Bombay: a study on prevalence, awareness and compliance to treatment. by Bharucha NE, Kuruvilla T. 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=140316
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Hypertension, cardiac hypertrophy, and sudden death in mice lacking natriuretic peptide receptor A. by Oliver PM, Fox JE, Kim R, Rockman HA, Kim HS, Reddick RL, Pandey KN, Milgram SL, Smithies O, Maeda N. 1997 Dec 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=25105
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Hypertension: [beta] testing. by Kotlikoff M, Hall I. 2003 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=182214
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Hypertensive diseases of pregnancy and risk of hypertension and stroke in later life: results from cohort study. by Wilson BJ, Watson MS, Prescott GJ, Sunderland S, Campbell DM, Hannaford P, Smith WC. 2003 Apr 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153466
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Implications of recent hypertension trials for the generalist physician: whom do we treat, and how? by Green L. 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=59591
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Increase in blood glucose concentration during antihypertensive treatment as a predictor of myocardial infarction: population based cohort study. by Dunder K, Lind L, Zethelius B, Berglund L, Lithell H. 2003 Mar 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152364
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Inhaled nitric oxide in persistent pulmonary hypertension of the newborn refractory to high-frequency ventilation. by Al-Alaiyan S, Neiley E. 1999; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=29006
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Inhaled nitric oxide reverses cell-free hemoglobin-induced pulmonary hypertension and decreased lung compliance. Preliminary results. by Figueiredo LF, Mathru M, Jones JR, Solanki D, Kramer GC. 1997; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28996
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Inverse Changes in Erythroid Cell Volume and Number Regulate the Hematocrit in Newborn Genetically Hypertensive Rats. by Boylan JW, Liew JB, Feig PU. 1991 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=52818
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Low NO bioavailability in CCl4 cirrhotic rat livers might result from low NO synthesis combined with decreased superoxide dismutase activity allowing superoxide-mediated NO breakdown: A comparison of two portal hypertensive rat models with healthy controls. by Van de Casteele M, van Pelt JF, Nevens F, Fevery J, Reichen J. 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=155038
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Modulation of the molecular composition of large conductance, Ca2 + activated K + channels in vascular smooth muscle during hypertension. by Amberg GC, Bonev AD, Rossow CF, Nelson MT, Santana LF. 2003 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=182211
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Mutations in the CYP11B1 Gene Causing Congenital Adrenal Hyperplasia and Hypertension Cluster in Exons 6, 7, and 8. by Curnow KM, Slutsker L, Vitek J, Cole T, Speiser PW, New MI, White PC, Pascoe L. 1993 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46550
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NCX-1000, a NO-releasing derivative of ursodeoxycholic acid, selectively delivers NO to the liver and protects against development of portal hypertension. by Fiorucci S, Antonelli E, Morelli O, Mencarelli A, Casini A, Mello T, Palazzetti B, Tallet D, del Soldato P, Morelli A. 2001 Jul 17; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=37532
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Negative regulators of sodium transport in the kidney: Key factors in understanding salt-sensitive hypertension? by Rossier BC. 2003 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152592
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Newly diagnosed hypertension. by A'Court C. 2002 Jun 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=115217
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Non-dipper treated hypertensive patients do not have increased cardiac structural alterations. by Cuspidi C, Michev I, Meani S, Valerio C, Bertazzoli G, Magrini F, Zanchetti A. 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153424
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Nonlinear indicial response of complex nonstationary oscillations as pulmonary hypertension responding to step hypoxia. by Huang W, Shen Z, Huang NE, Fung YC. 1999 Mar 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26697
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Nonnarcotic analgesic use and the risk of hypertension. by O'Brien BD. 2003 May 27; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=155965
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Obesity drug sibutramine (Meridia): hypertension and cardiac arrhythmias. by Wooltorton E. 2002 May 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=111085
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Obstructive sleep apnoea syndrome as a risk factor for hypertension: population study. by Lavie P, Herer P, Hoffstein V. 2000 Feb 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27290
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Omapatrilat normalizes renal function curve in spontaneously hypertensive rats. by Morazo P, Fortepiani LA, Clara Ortiz M, Atucha NM, Garcia-Estan J. 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=57752
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Orlistat associated with hypertension. by Persson M, Vitols S. 2000 Jul 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27428
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Oxidation of tetrahydrobiopterin leads to uncoupling of endothelial cell nitric oxide synthase in hypertension. by Landmesser U, Dikalov S, Price SR, McCann L, Fukai T, Holland SM, Mitch WE, Harrison DG. 2003 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152929
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Patients' decisions about whether or not to take antihypertensive drugs: qualitative study. by Benson J, Britten N. 2002 Oct 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=129637
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Patients' views about taking antihypertensive drugs: questionnaire study. by Benson J, Britten N. 2003 Jun 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=161632
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Phenylpropanolamine, stroke and hypertension. by Kuchel O. 2001 Mar 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=80813
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Predictors of normotension on withdrawal of antihypertensive drugs in elderly patients: prospective study in second Australian national blood pressure study cohort. by Nelson MR, Reid CM, Krum H, Muir T, Ryan P, McNeil JJ. 2002 Oct 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128950
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Prevention of renovascular and cardiac pathophysiological changes in hypertension by angiotensin II type 1 receptor antisense gene therapy. by Martens JR, Reaves PY, Lu D, Katovich MJ, Berecek KH, Bishop SP, Raizada MK, Gelband CH. 1998 Mar 3; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=19454
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Pulmonary Hypertension Syndrome in Broilers Caused by Enterococcus faecalis. by Tankson JD, Thaxton JP, Vizzier-Thaxton Y. 2001 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=98767
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Purification of Parathyroid Hypertensive Factor from Plasma of Spontaneously Hypertensive Rats. by Benishin CG, Lewanczuk RZ, Pang PK. 1991 Jul 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=52085
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Randomised controlled trial of dual blockade of renin-angiotensin system in patients with hypertension, microalbuminuria, and non-insulin dependent diabetes: the candesartan and lisinopril microalbuminuria (CALM) study. by Mogensen CE, Neldam S, Tikkanen I, Oren S, Viskoper R, Watts RW, Cooper ME. 2000 Dec 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27545
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Rational Prescribing in Primary Care (RaPP-trial). A randomised trial of a tailored intervention to improve prescribing of antihypertensive and cholesterol-lowering drugs in general practice [ISRCTN48751230]. by Fretheim A, Oxman AD, Treweek S, Bjorndal A. 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152643
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Relation between insufficient response to antihypertensive treatment and poor compliance with treatment: a prospective case-control study. by Nuesch R, Schroeder K, Dieterle T, Martina B, Battegay E. 2001 Jul 21; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=34727
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RGS2: a "turn-off" in hypertension. by Le TH, Coffman TM. 2003 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151929
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Salt-sensitive hypertension: if only it were as simple as rocket science. by Reudelhuber TL. 2003 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152948
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Should hypertension be treated with angiotensin-converting-enzyme inhibitors, calcium-channel blockers or diuretics? by Myers KA. 2003 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=151997
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Spontaneously hypertensive rats: further evaluation of age-related memory performance and cholinergic marker expression. by Hernandez CM, Hoifodt H, Terry AV Jr. 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=161744
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Survival in treated hypertension: follow up study after two decades. by Andersson OK, Almgren T, Persson B, Samuelsson O, Hedner T, Wilhelmsen L. 1998 Jul 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28606
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The 2001 Canadian hypertension recommendations: take-home messages. by Campbell NR, Drouin D, Feldman RD. 2002 Sep 17; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=122031
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The management of hypertension in Canada: a review of current guidelines, their shortcomings and implications for the future. by McAlister FA, Campbell NR, Zarnke K, Levine M, Graham ID. 2001 Feb 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=80782
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The potential savings of using thiazides as the first choice antihypertensive drug: cost-minimisation analysis. by Fretheim A, Aaserud M, Oxman AD. 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=201005
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The rat STSL locus: characterization, chromosomal assignment, and genetic variations in sitosterolemic hypertensive rats. by Yu H, Pandit B, Klett E, Lee MH, Lu K, Helou K, Ikeda I, Egashira N, Sato M, Klein R, Batta A, Salen G, Patel SB. 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165443
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The value of industry-sponsored studies of initial antihypertensive therapies. by Caro JJ, Payne K. 2001 Jun 26; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=81187
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Thresholds for taking antihypertensive drugs in different professional and lay groups: questionnaire survey. by Steel N. 2000 May 27; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27388
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Transforming growth factor-[beta]1 hyperexpression in African-American hypertensives: A novel mediator of hypertension and /or target organ damage. by Suthanthiran M, Li B, Song JO, Ding R, Sharma VK, Schwartz JE, August P. 2000 Mar 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=16265
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Upregulation of nitric oxide synthase in mice with severe hypoxia-induced pulmonary hypertension. by Fagan KA, Morrissey B, Fouty BW, Sato K, Harral JW, Morris KG Jr, Hoedt-Miller M, Vidmar S, McMurtry IF, Rodman DM. 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=59521
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Up-Regulation of Pressure-activated Ca2+-permeable Cation Channel in Intact Vascular Endothelium of Hypertensive Rats. by Hoyer J, Kohler R, Haase W, Distler A. 1996 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38316
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Use of antihypertensive medications in pregnancy and the risk of adverse perinatal outcomes: McMaster Outcome Study of Hypertension In Pregnancy 2 (MOS HIP 2). by Ray JG, Vermeulen MJ, Burrows EA, Burrows RF. 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=60658
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Using thresholds based on risk of cardiovascular disease to target treatment for hypertension: modelling events averted and number treated. by Baker S, Priest P, Jackson R. 2000 Mar 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27311
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Vaccination for protection of retinal ganglion cells against death from glutamate cytotoxicity and ocular hypertension: Implications for glaucoma. by Schori H, Kipnis J, Yoles E, WoldeMussie E, Ruiz G, Wheeler LA, Schwartz M. 2001 Mar 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=30665
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Validation of Heart Failure Events in the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) Participants Assigned to Doxazosin and Chlorthalidone. by Piller LB, Davis BR, Cutler JA, Cushman WC, Wright JT Jr, Williamson JD, Leenen FH, Einhorn PT, Randall OS, Golden JS, Haywood LJ. 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149403
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Vasoactive intestinal peptide as a new drug for treatment of primary pulmonary hypertension. by Petkov V, Mosgoeller W, Ziesche R, Raderer M, Stiebellehner L, Vonbank K, Funk GC, Hamilton G, Novotny C, Burian B, Block LH. 2003 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154449
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When should hypertension be treated? The different perspectives of Canadian family physicians and patients. by McAlister FA, O'Connor AM, Wells G, Grover SA, Laupacis A. 2000 Aug 22; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=80373
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Xanthine oxidase activity associated with arterial blood pressure in spontaneously hypertensive rats. by Suzuki H, DeLano FA, Parks DA, Jamshidi N, Granger DN, Ishii H, Suematsu M, Zweifach BW, Schmid-Schonbein GW. 1998 Apr 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22563
The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with hypertension, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “hypertension” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for hypertension (hyperlinks lead to article summaries):
PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.
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A 25-year clinical history of portopulmonary hypertension associated with latent myeloproliferative disorder. Author(s): Ito H, Adachi Y, Arimura Y, Endo T, Hinoda Y, Imai K. Source: Journal of Gastroenterology. 2003; 38(5): 488-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12768393&dopt=Abstract
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A descriptive analysis of hypertension and affiliated therapies in a military retiree population (ages 40-85 years) at Camp Lejeune, North Carolina. Author(s): Johnson BW, Davies WG, Hardy DW, Varga J, Gallagher KL, Ryan MT, Jones RM. Source: Military Medicine. 2003 May; 168(5): 424-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12775183&dopt=Abstract
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A meta-analysis of the effects of treatment on left ventricular mass in essential hypertension. Author(s): Klingbeil AU, Schneider M, Martus P, Messerli FH, Schmieder RE. Source: The American Journal of Medicine. 2003 July; 115(1): 41-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12867233&dopt=Abstract
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A model analysis of costs of blood pressure destabilization and edema associated with rofecoxib and celecoxib among older patients with osteoarthritis and hypertension in a Medicare Choice population. Author(s): Becker RV, Burke TA, McCoy MA, Trotter JP. Source: Clinical Therapeutics. 2003 February; 25(2): 647-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12749519&dopt=Abstract
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A novel mechanism for pulmonary arterial hypertension? Author(s): Cooke JP. Source: Circulation. 2003 September 23; 108(12): 1420-1. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14504250&dopt=Abstract
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A nurse-led initiative to screen and treat hypertension. Author(s): Terry J. Source: Community Nurse. 2000 May; 6(4): 23-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12778519&dopt=Abstract
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A simple case of hypertension? Author(s): Nageh T, Swann AD, Walker DM. Source: The British Journal of General Practice : the Journal of the Royal College of General Practitioners. 2003 May; 53(490): 392-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12830568&dopt=Abstract
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A six-month randomized clinical trial comparing the IOP-lowering efficacy of bimatoprost and latanoprost in patients with ocular hypertension or glaucoma. Author(s): Robin AL. Source: American Journal of Ophthalmology. 2003 June; 135(6): 921-2; Author Reply 9223. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12788149&dopt=Abstract
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A study of hepatopulmonary syndrome among patients of cirrhosis of liver and portal hypertension. Author(s): Hira HS, Kumar J, Tyagi SK, Jain SK. Source: Indian J Chest Dis Allied Sci. 2003 July-September; 45(3): 165-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12866633&dopt=Abstract
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Abdominal adiposity, age, education level and therapy associated with uncontrolled hypertension. Author(s): de Resende SM, Velasquez-Melendez G. Source: Journal of Human Hypertension. 2003 May; 17(5): 365-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12756411&dopt=Abstract
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Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance: the STOP-NIDDM trial. Author(s): Chiasson JL, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso M; STOPNIDDM Trial Research Group. Source: Jama : the Journal of the American Medical Association. 2003 July 23; 290(4): 486-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12876091&dopt=Abstract
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Acetaminophen and hypertension: a causal association or pain mediated? Author(s): Brotman DJ. Source: Archives of Internal Medicine. 2003 May 12; 163(9): 1113-4; Author Reply 1115-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12742815&dopt=Abstract
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Acute endothelin A receptor antagonism improves pulmonary and systemic haemodynamics in patients with pulmonary arterial hypertension that is primary or autoimmune and related to congenital heart disease. Author(s): Apostolopoulou SC, Rammos S, Kyriakides ZS, Webb DJ, Johnston NR, Cokkinos DV, Kremastinos DT. Source: Heart (British Cardiac Society). 2003 October; 89(10): 1221-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12975426&dopt=Abstract
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Acute hemodynamic effects and home therapy using a novel pulsed nasal nitric oxide delivery system in children and young adults with pulmonary hypertension. Author(s): Ivy DD, Parker D, Doran A, Parker D, Kinsella JP, Abman SH. Source: The American Journal of Cardiology. 2003 October 1; 92(7): 886-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14516902&dopt=Abstract
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Acute intermittent porphyria: an unusual cause of malignant hypertension. Author(s): Singh V, Sud K, Kohli HS, Gupta KL, Sakhuja V. Source: J Assoc Physicians India. 2003 February; 51: 225-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12725276&dopt=Abstract
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Acute renal failure due to hypertension: malignant hypertension in an adolescent. Author(s): Tanaka H, Tateyama T, Suzuki K, Nakahata T, Kudo M, Takahashi Y, Ito E, Waga S. Source: Pediatrics International : Official Journal of the Japan Pediatric Society. 2003 June; 45(3): 342-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12828593&dopt=Abstract
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Aeolus myth: chronic obstructive lung disease and nocturnal lumbosacral pain in association with lumbar spinal stenosis and pulmonary hypertension. Author(s): LaBan MM, Kucway EJ. Source: American Journal of Physical Medicine & Rehabilitation / Association of Academic Physiatrists. 2003 September; 82(9): 660-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12960906&dopt=Abstract
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Aldosterone antagonism and hypertension. Author(s): Conti CR. Source: Clin Cardiol. 2003 May; 26(5): 209-10. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12769246&dopt=Abstract
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Ambulatory blood pressure measurement is now indispensable to the good clinical management of hypertension. Author(s): O'Brien E. Source: Cardiovasc J S Afr. 2003 May-June; 14(3): 113-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12844194&dopt=Abstract
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Analgesics and hypertension: causality or correlation? Author(s): Glaser JH. Source: Archives of Internal Medicine. 2003 May 12; 163(9): 1114; Author Reply 1115-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12742817&dopt=Abstract
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Angiopoietin-1 and pulmonary hypertension: cause or cure? Author(s): Rudge JS, Thurston G, Yancopoulos GD. Source: Circulation Research. 2003 May 16; 92(9): 947-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12750304&dopt=Abstract
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Angiotensin-converting-enzyme inhibitors and diuretics for hypertension. Author(s): Esnault VL. Source: The New England Journal of Medicine. 2003 July 3; 349(1): 90-3; Author Reply 90-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12846229&dopt=Abstract
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Angiotensin-converting-enzyme inhibitors and diuretics for hypertension. Author(s): Reese AM, Talbert RL, Bussey HI. Source: The New England Journal of Medicine. 2003 July 3; 349(1): 90-3; Author Reply 90-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12846228&dopt=Abstract
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Angiotensin-converting-enzyme inhibitors and diuretics for hypertension. Author(s): Krut LH. Source: The New England Journal of Medicine. 2003 July 3; 349(1): 90-3; Author Reply 90-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12846227&dopt=Abstract
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Angiotensin-converting-enzyme inhibitors and diuretics for hypertension. Author(s): Davis BR, Wright JT Jr, Cutler JA. Source: The New England Journal of Medicine. 2003 July 3; 349(1): 90-3; Author Reply 90-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12846226&dopt=Abstract
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Angiotensin-converting-enzyme inhibitors and diuretics for hypertension. Author(s): Pickering TG. Source: The New England Journal of Medicine. 2003 July 3; 349(1): 90-3; Author Reply 90-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12840099&dopt=Abstract
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Angiotensinogen and angiotensin II type 1 receptor gene polymorphism in patients with autosomal dominant polycystic kidney disease: effect on hypertension and ESRD. Author(s): Lee KB, Kim UK. Source: Yonsei Medical Journal. 2003 August 30; 44(4): 641-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12950120&dopt=Abstract
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Antibiotics in primary prevention of myocardial infarction among elderly patients with hypertension. Author(s): Brassard P, Bourgault C, Brophy J, Kezouh A, Rainville B, Xhignesse M, Suissa S. Source: American Heart Journal. 2003 May; 145(5): E20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12766754&dopt=Abstract
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Antihypertensive efficacy and safety of olmesartan medoxomil compared with amlodipine for mild-to-moderate hypertension. Author(s): Chrysant SG, Marbury TC, Robinson TD. Source: Journal of Human Hypertension. 2003 June; 17(6): 425-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12764406&dopt=Abstract
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Are current strategies for treating hypertension effective? Author(s): Sica DA. Source: Journal of Clinical Hypertension (Greenwich, Conn.). 2003 May-June; 5(3 Suppl 2): 23-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12826767&dopt=Abstract
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Are left ventricular mass, geometry and function related to vascular changes and/or insulin resistance in long-standing hypertension? ICARUS: a LIFE substudy. Author(s): Olsen MH, Hjerkinn E, Wachtell K, Hoieggen A, Bella JN, Nesbitt SD, Fossum E, Kjeldsen SE, Julius S, Ibsen H. Source: Journal of Human Hypertension. 2003 May; 17(5): 305-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12756402&dopt=Abstract
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Are there differences in risk factor profiles and frequency of CT/MRI-based infarcts among African American stroke patients with and without hypertension? A report from the African American Antiplatelet Stroke Prevention Study (AAASPS). Author(s): Whittley CY, Gorelick PB, Raman R, Harris J, Richardson D. Source: Journal of the National Medical Association. 2003 June; 95(6): 423-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12856908&dopt=Abstract
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Arm position and blood pressure: a risk factor for hypertension? Author(s): Mourad A, Carney S, Gillies A, Jones B, Nanra R, Trevillian P. Source: Journal of Human Hypertension. 2003 June; 17(6): 389-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12764401&dopt=Abstract
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Assessing CHD and hypertension in minority ethnic communities. Author(s): Memon M, Abbas F, Memon B. Source: Nurs Times. 2003 April 22-28; 99(16): 26-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12739278&dopt=Abstract
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Assessment of the novel selective aldosterone blocker eplerenone using ambulatory and clinical blood pressure in patients with systemic hypertension. Author(s): White WB, Carr AA, Krause S, Jordan R, Roniker B, Oigman W. Source: The American Journal of Cardiology. 2003 July 1; 92(1): 38-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12842242&dopt=Abstract
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Association between hyperhomocysteinemia and primary pulmonary hypertension. Author(s): Arroliga AC, Sandur S, Jacobsen DW, Tewari S, Mustafa M, Mascha EJ, Robinson K. Source: Respiratory Medicine. 2003 July; 97(7): 825-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12854633&dopt=Abstract
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Association between supine hypertension and orthostatic hypotension in autonomic failure. Author(s): Goldstein DS, Pechnik S, Holmes C, Eldadah B, Sharabi Y. Source: Hypertension. 2003 August; 42(2): 136-42. Epub 2003 June 30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12835329&dopt=Abstract
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Associations of aortic and mitral regurgitation with body composition and myocardial energy expenditure in adults with hypertension: the Hypertension Genetic Epidemiology Network study. Author(s): Palmieri V, Bella JN, Arnett DK, Oberman A, Kitzman DW, Hopkins PN, Rao DC, Roman MJ, Devereux RB; Hypertension Genetic Epidemiology Network study. Source: American Heart Journal. 2003 June; 145(6): 1071-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12796765&dopt=Abstract
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Atrial fibrillation: hypertension as a causative agent, risk factor for complications, and potential therapeutic target. Author(s): Healey JS, Connolly SJ. Source: The American Journal of Cardiology. 2003 May 22; 91(10A): 9G-14G. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12781903&dopt=Abstract
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Atrial septostomy in the treatment of severe pulmonary arterial hypertension. Author(s): Reichenberger F, Pepke-Zaba J, McNeil K, Parameshwar J, Shapiro LM. Source: Thorax. 2003 September; 58(9): 797-800. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12947142&dopt=Abstract
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Back to the salt mines-- endothelial dysfunction in hypertension and compensatory role of endothelium-derived hyperpolarizing factor (EDHF). Author(s): Katusic ZS. Source: The Journal of Physiology. 2002 August 15; 543(Pt 1): 1. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12181276&dopt=Abstract
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Balance and gait in older adults with systemic hypertension. Author(s): Hausdorff JM, Herman T, Baltadjieva R, Gurevich T, Giladi N. Source: The American Journal of Cardiology. 2003 March 1; 91(5): 643-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12615286&dopt=Abstract
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Baroreflex sensitivity in essential and secondary hypertension. Author(s): Mussalo H, Vanninen E, Ikaheimo R, Laitinen T, Laakso M, Lansimies E, Hartikainen J. Source: Clinical Autonomic Research : Official Journal of the Clinical Autonomic Research Society. 2002 December; 12(6): 465-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12598951&dopt=Abstract
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Bartter's/Gitelman's syndrome: a model for the relationships between hypertension, angiotensin II, oxidative stress and remodeling. Author(s): Calo LA, Davis PA, Semplicini A. Source: Clinical Nephrology. 2003 May; 59(5): 393-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12779105&dopt=Abstract
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Benign intracranial hypertension and thyreostimulin suppression hormonotherapy. Author(s): Serratrice J, Granel B, Conrath J, Dufour H, Disdier P, Henry JF, Weiller PJ. Source: American Journal of Ophthalmology. 2002 December; 134(6): 910-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12470764&dopt=Abstract
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Benign intracranial hypertension in a patient with chronic renal failure, precipitated by hemodialysis. Author(s): Shaw D, Priestman W, McIntyre CW. Source: Clinical Nephrology. 2002 December; 58(6): 458-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12508970&dopt=Abstract
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Benign intracranial hypertension in association with acute lymphoblastic leukemia. Author(s): Sastry J, Karandikar SS, English MW. Source: Pediatric Hematology and Oncology. 2003 March; 20(2): 157-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12554527&dopt=Abstract
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Beraprost sodium for pulmonary hypertension with congenital heart disease. Author(s): Suzuki H, Sato S, Tanabe S, Hayasaka K. Source: Pediatrics International : Official Journal of the Japan Pediatric Society. 2002 October; 44(5): 528-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12225555&dopt=Abstract
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Beraprost therapy for pulmonary arterial hypertension. Author(s): Barst RJ, McGoon M, McLaughlin V, Tapson V, Rich S, Rubin L, Wasserman K, Oudiz R, Shapiro S, Robbins IM, Channick R, Badesch D, Rayburn BK, Flinchbaugh R, Sigman J, Arneson C, Jeffs R; Beraprost Study Group. Source: Journal of the American College of Cardiology. 2003 June 18; 41(12): 2119-25. Erratum In: J Am Coll Cardiol. 2003 August 6; 42(3): 591. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12821234&dopt=Abstract
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Beyond hypertension: unraveling the causes of intracerebral hemorrhage. Author(s): Rosand J, Greenberg SM. Source: Stroke; a Journal of Cerebral Circulation. 2002 May; 33(5): 1195-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12532961&dopt=Abstract
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Bilateral adrenal masses in a patient with pregnancy-induced hypertension. Author(s): Eng S, Elias AN. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 2002 December; 79(3): 253-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12445994&dopt=Abstract
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Bilateral cannulation of internal jugular veins may worsen intracranial hypertension. Author(s): Stocchetti N, Longhi L, Valeriani V. Source: Anesthesiology. 2003 October; 99(4): 1017-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14508338&dopt=Abstract
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Bilateral cystic adenomatoid lung malformation type III--a rare differential diagnosis of pulmonary hypertension in neonates. Author(s): Banerjea MC, Wirbelauer J, Adam P, Trusen A, Marx A, Speer C. Source: Journal of Perinatal Medicine. 2002; 30(5): 429-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12442610&dopt=Abstract
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Bilateral renal embolization in the treatment of patients with renal insufficiency and arterial hypertension: report of a case of polycystic kidneys. Author(s): Basile A, Boullosa-Seoane E, Dominiguez-Viguera L, Certo A, Casal-Rivas M. Source: Radiol Med (Torino). 2002 May-June; 103(5-6): 555-7. English, Italian. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12207195&dopt=Abstract
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Bimatoprost 0.03% versus travoprost 0.004% in black Americans with glaucoma or ocular hypertension. Author(s): Noecker RJ, Earl ML, Mundorf T, Peace J, Williams RD. Source: Adv Ther. 2003 March-April; 20(2): 121-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12836812&dopt=Abstract
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Binswanger's disease: its association with hypertension and obstructive sleep apnea. Author(s): Matthews KD, Richter RW. Source: J Okla State Med Assoc. 2003 June; 96(6): 265-8; Quiz 269-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12858817&dopt=Abstract
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Biochemical endothelial markers and cardiovascular remodeling in refractory arterial hypertension. Author(s): Cittadino M, Goncalves de Sousa M, Ugar-Toledo JC, Rocha JC, Tanus-Santos JE, Moreno H Jr. Source: Clinical and Experimental Hypertension (New York, N.Y. : 1993). 2003 January; 25(1): 25-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12597522&dopt=Abstract
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Biofeedback of baroreflex sensitivity in patients with mild essential hypertension. Author(s): Overhaus S, Ruddel H, Curio I, Mussgay L, Scholz OB. Source: International Journal of Behavioral Medicine. 2003; 10(1): 66-78. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12581949&dopt=Abstract
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Biological factors are more important than socio-demographic and psychosocial conditions in relation to hypertension in middle-aged women. The Women's Health in the Lund Area (WHILA) study. Author(s): Lidfeldt J, Nyberg P, Nerbrand C, Ojehagen A, Samsioe G, Schersten B, Agardh CD. Source: Blood Pressure. 2002; 11(5): 270-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12458649&dopt=Abstract
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Birthweight, childhood growth and hypertension in adulthood. Author(s): Zhao M, Shu XO, Jin F, Yang G, Li HL, Liu DK, Wen W, Gao YT, Zheng W. Source: International Journal of Epidemiology. 2002 October; 31(5): 1043-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12435782&dopt=Abstract
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Blockade of the renin-angiotensin system in African Americans with hypertension and cardiovascular disease. Author(s): Saunders E, Gavin JR 3rd. Source: Journal of Clinical Hypertension (Greenwich, Conn.). 2003 January-February; 5(1 Suppl 1): 12-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12556668&dopt=Abstract
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Blockade of the renin-angiotensin system increases adiponectin concentrations in patients with essential hypertension. Author(s): Furuhashi M, Ura N, Higashiura K, Murakami H, Tanaka M, Moniwa N, Yoshida D, Shimamoto K. Source: Hypertension. 2003 July; 42(1): 76-81. Epub 2003 June 09. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12796280&dopt=Abstract
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Blood lead levels and hypertension. Author(s): Hense HW. Source: Jama : the Journal of the American Medical Association. 2003 July 23; 290(4): 460; Author Reply 461. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12876084&dopt=Abstract
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Blood lead levels and hypertension. Author(s): Heaney RP. Source: Jama : the Journal of the American Medical Association. 2003 July 23; 290(4): 460-1; Author Reply 461. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12876083&dopt=Abstract
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Blood lead, blood pressure, and hypertension in perimenopausal and postmenopausal women. Author(s): Nash D, Magder L, Lustberg M, Sherwin RW, Rubin RJ, Kaufmann RB, Silbergeld EK. Source: Jama : the Journal of the American Medical Association. 2003 March 26; 289(12): 1523-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12672769&dopt=Abstract
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Blood pressure and decline in kidney function: findings from the Systolic Hypertension in the Elderly Program (SHEP). Author(s): Young JH, Klag MJ, Muntner P, Whyte JL, Pahor M, Coresh J. Source: Journal of the American Society of Nephrology : Jasn. 2002 November; 13(11): 2776-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12397049&dopt=Abstract
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Blood pressure control and rates of edema following the administration of the cyclooxygenase-2 specific inhibitors celecoxib versus rofecoxib in patients with systemic hypertension and osteoarthritis. Author(s): Weaver A, Alderman M, Sperling R. Source: The American Journal of Cardiology. 2003 May 15; 91(10): 1291-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745131&dopt=Abstract
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Blood pressure increase and incidence of hypertension in relation to inflammationsensitive plasma proteins. Author(s): Engstrom G, Janzon L, Berglund G, Lind P, Stavenow L, Hedblad B, Lindgarde F. Source: Arteriosclerosis, Thrombosis, and Vascular Biology. 2002 December 1; 22(12): 2054-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12482834&dopt=Abstract
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Blood pressure reactivity to mental stress task as a determinant of sustained hypertension after 5 years of follow-up. Author(s): Armario P, del Rey RH, Martin-Baranera M, Almendros MC, Ceresuela LM, Pardell H. Source: Journal of Human Hypertension. 2003 March; 17(3): 181-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12624608&dopt=Abstract
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Blood pressure response after two-step exercise as a powerful predictor of hypertension: the Osaka Health Survey. Author(s): Tsumura K, Hayashi T, Hamada C, Endo G, Fujii S, Okada K. Source: Journal of Hypertension. 2002 August; 20(8): 1507-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12172311&dopt=Abstract
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Blood pressure-lowering effects of biofeedback treatment in hypertension: a metaanalysis of randomized controlled trials. Author(s): Nakao M, Yano E, Nomura S, Kuboki T. Source: Hypertens Res. 2003 January; 26(1): 37-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12661911&dopt=Abstract
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Blunted coronary vasoreactivity to insulin is an early alteration in hypertension. Author(s): Sundell J, Laine H, Luotolahti M, Nuutila P, Kalliokoski K, Raitakari O, Knuuti J. Source: Journal of Vascular Research. 2003 January-February; 40(1): 58-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12644726&dopt=Abstract
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BMPR2 germline mutations in pulmonary hypertension associated with fenfluramine derivatives. Author(s): Humbert M, Deng Z, Simonneau G, Barst RJ, Sitbon O, Wolf M, Cuervo N, Moore KJ, Hodge SE, Knowles JA, Morse JH. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2002 September; 20(3): 518-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12358323&dopt=Abstract
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Body mass index is the main risk factor for arterial hypertension in young subjects without major comorbidity. Author(s): Lukas A, Kumbein F, Temml C, Mayer B, Oberbauer R. Source: European Journal of Clinical Investigation. 2003 March; 33(3): 223-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12641540&dopt=Abstract
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Bone disorders, hypertension, and mitochondrial toxicity in HIV disease. Author(s): Newman MD. Source: Topics in Hiv Medicine : a Publication of the International Aids Society, Usa. 2003 January-February; 11(1): 10-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12717045&dopt=Abstract
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Bosentan for the treatment of pulmonary arterial hypertension. Author(s): Kenyon KW, Nappi JM. Source: The Annals of Pharmacotherapy. 2003 July-August; 37(7-8): 1055-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12841819&dopt=Abstract
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Brainstem mechanisms of hypertension: role of the rostral ventrolateral medulla. Author(s): Sved AF, Ito S, Sved JC. Source: Current Hypertension Reports. 2003 June; 5(3): 262-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12724060&dopt=Abstract
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Brimonidine Purite and bimatoprost compared with timolol and latanoprost in patients with glaucoma and ocular hypertension. Author(s): Netland PA, Michael M, Rosner SA, Katzman B, Macy JI. Source: Adv Ther. 2003 January-February; 20(1): 20-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12772815&dopt=Abstract
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Bronchopulmonary shunts in patients with chronic thromboembolic pulmonary hypertension: evaluation with helical CT and MR imaging. Author(s): Ley S, Kreitner KF, Morgenstern I, Thelen M, Kauczor HU. Source: Ajr. American Journal of Roentgenology. 2002 November; 179(5): 1209-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12388501&dopt=Abstract
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By the way, doctor. When I was first diagnosed with hypertension, my doctor (who knew that I was a competitive cyclist) prescribed an ACE inhibitor. I wondered for some time why he didn't prescribe diuretics, since all the articles I've read recommend that as a beginning step. Then I read in a bicycling magazine that ACE inhibitors are the only hypertension medicine that doesn't interfere with aerobic performance. Is that true? And did my doctor do the right thing? Author(s): Lee TH. Source: Harvard Health Letter / from Harvard Medical School. 2003 June; 28(8): 8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12835145&dopt=Abstract
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Calcium antagonists in the treatment of hypertension in patients with ischaemic heart disease. Author(s): Rosendorff C. Source: Expert Opinion on Pharmacotherapy. 2003 September; 4(9): 1535-41. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12943483&dopt=Abstract
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Calcium channel blockers as the treatment of choice for hypertension in renal transplant recipients: fact or fiction. Author(s): Baroletti SA, Gabardi S, Magee CC, Milford EL. Source: Pharmacotherapy. 2003 June; 23(6): 788-801. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12820820&dopt=Abstract
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Cardiac and vascular pathophysiology in hypertension. Author(s): Mayet J, Hughes A. Source: Heart (British Cardiac Society). 2003 September; 89(9): 1104-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12923045&dopt=Abstract
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Cardiovascular disease, hypertension, and lipids. Author(s): Watkins PJ. Source: Bmj (Clinical Research Ed.). 2003 April 19; 326(7394): 874-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12702626&dopt=Abstract
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Cardiovascular risk factors in children with obesity, hypertension and diabetes: lipoprotein(a) levels and body mass index correlate with family history of cardiovascular disease. Author(s): Glowinska B, Urban M, Koput A. Source: European Journal of Pediatrics. 2002 October; 161(10): 511-8. Epub 2002 August 30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12297895&dopt=Abstract
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Case 4: eruption on the face of a diabetic man suffering from retinopathy, hypertension, and nephropathy. Diagnosis: ciclosporin-associated hyperplastic folliculitis. Author(s): Harman KE, Higgins EM. Source: Clinical and Experimental Dermatology. 2003 May; 28(3): 341-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12780737&dopt=Abstract
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Central nervous system effects of moxonidine experimental sustained release formulation in patients with mild to moderate essential hypertension. Author(s): Kemme MJ, vd Post JP, Schoemaker RC, Straub M, Cohen AF, van Gerven JM. Source: British Journal of Clinical Pharmacology. 2003 June; 55(6): 518-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12814444&dopt=Abstract
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Change in cardiovascular risk profile by echocardiography in low- or medium-risk hypertension. Author(s): Schillaci G, De Simone G, Reboldi G, Porcellati C, Devereux RB, Verdecchia P. Source: Journal of Hypertension. 2002 August; 20(8): 1519-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12172313&dopt=Abstract
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Chocolate and blood pressure in elderly individuals with isolated systolic hypertension. Author(s): Taubert D, Berkels R, Roesen R, Klaus W. Source: Jama : the Journal of the American Medical Association. 2003 August 27; 290(8): 1029-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12941673&dopt=Abstract
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Classification of visual field abnormalities in the ocular hypertension treatment study. Author(s): Keltner JL, Johnson CA, Cello KE, Edwards MA, Bandermann SE, Kass MA, Gordon MO; Ocular Hypertension Treatment Study Group. Source: Archives of Ophthalmology. 2003 May; 121(5): 643-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12742841&dopt=Abstract
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Clinical and therapeutical follow-up of HIV-associated pulmonary hypertension: prospective study of 10 patients. Author(s): Recusani F, Di Matteo A, Gambarin F, D'Armini A, Klersy C, Campana C. Source: Aids (London, England). 2003 April; 17 Suppl 1: S88-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12870536&dopt=Abstract
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Clinical significance of normalization of uterine artery pulsatility index with maternal heart rate for the evaluation of uterine circulation in pregnancy-induced hypertension. Author(s): Ochi H, Kusanagi Y, Katayama T, Matsubara K, Ito M. Source: Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. 2003 May; 21(5): 459-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12768557&dopt=Abstract
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Clinical trials in isolated systolic hypertension in the elderly. Author(s): Garcia-Palmieri MR, Torrado JM. Source: P R Health Sci J. 2003 June; 22(2): 145-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12866138&dopt=Abstract
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Clinical trials: Evidence and unanswered questions--hypertension. Author(s): Celermajer DS. Source: Cerebrovascular Diseases (Basel, Switzerland). 2003; 16 Suppl 3: 18-24. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12740552&dopt=Abstract
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Colonic wall thickening in patients with cirrhosis and portal hypertension. Author(s): Quilez C, Palazon JM, Arenas J, Alonso S, Sanchez J, Belda G, Perez-Mateo M. Source: Rev Esp Enferm Dig. 2003 April; 95(4): 269-72, 265-8. English, Spanish. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12828526&dopt=Abstract
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Combination ACE inhibitors and angiotensin II receptor blockers for hypertension. Author(s): Finnegan PM, Gleason BL. Source: The Annals of Pharmacotherapy. 2003 June; 37(6): 886-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12773079&dopt=Abstract
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Combination therapy for hypertension: an update. Author(s): Moser M. Source: Journal of Clinical Hypertension (Greenwich, Conn.). 2003 July-August; 5(4): 247-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12939563&dopt=Abstract
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Commentary on "Embracing complexity: A consideration of hypertension in the very old". Author(s): Lowenthal DT. Source: The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 2003 July; 58(7): 664-5; Discussion 669-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12865488&dopt=Abstract
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Commentary on "Embracing complexity: A consideration of hypertension in the very old". Author(s): Hajjar RR. Source: The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 2003 July; 58(7): 661-2; Discussion 669-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12865486&dopt=Abstract
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Commentary on "Embracing complexity: A consideration of hypertension in the very old". Author(s): Aronow WS. Source: The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 2003 July; 58(7): 659-60; Discussion 669-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12865484&dopt=Abstract
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Commentary on "Embracing complexity: A consideration of hypertension in the very old". Author(s): Newman AB. Source: The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 2003 July; 58(7): 666-7; Discussion 669-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12865490&dopt=Abstract
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Commentary on "Embracing complexity: A consideration of hypertension in the very old". Author(s): Michel JP, Grab B, Perrenoud JJ. Source: The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 2003 July; 58(7): 665-6; Discussion 669-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12865489&dopt=Abstract
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Comparative effect of lercanidipine, felodipine, and nifedipine GITS on blood pressure and heart rate in patients with mild to moderate arterial hypertension: the Lercanidipine in Adults (LEAD) Study. Author(s): Romito R, Pansini MI, Perticone F, Antonelli G, Pitzalis M, Rizzon P. Source: Journal of Clinical Hypertension (Greenwich, Conn.). 2003 July-August; 5(4): 249-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12939564&dopt=Abstract
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Comparison of ambulatory blood pressure values in patients with glaucoma and ocular hypertension. Author(s): Yazici B, Usta E, Erturk H, Dilek K. Source: Eye (London, England). 2003 July; 17(5): 593-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12855965&dopt=Abstract
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Comparison of candesartan with lisinopril on ambulatory blood pressure and morning surge in patients with systemic hypertension. Author(s): Eguchi K, Kario K, Shimada K. Source: The American Journal of Cardiology. 2003 September 1; 92(5): 621-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12943892&dopt=Abstract
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Comparison of effects on systolic and diastolic left ventricular function of nebivolol versus atenolol in patients with uncomplicated essential hypertension. Author(s): Kamp O, Sieswerda GT, Visser CA. Source: The American Journal of Cardiology. 2003 August 1; 92(3): 344-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12888152&dopt=Abstract
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Comparison of patients with acute coronary syndrome with and without systemic hypertension. Author(s): Majahalme SK, Smith DE, Cooper JV, Kline-Rogers E, Mehta RH, Eagle KA, Bisognano JD. Source: The American Journal of Cardiology. 2003 August 1; 92(3): 258-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12888127&dopt=Abstract
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Comparison of the blood pressure-lowering effects and tolerability of Losartan- and Amlodipine-based regimens in patients with isolated systolic hypertension. Author(s): Volpe M, Junren Z, Maxwell T, Rodriguez A, Gamboa R, Gomez-Fernandez P, Ortega-Gonzalez G, Matadamas N, Rodriguez F, Dass B, Kyle C, Clarysse L, Bryce A, Moreno-Heredia E, Germano G, Gilles L, Smith RD, Sanderson JE; CDSP-944 Study Group. Source: Clinical Therapeutics. 2003 May; 25(5): 1469-89. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12867222&dopt=Abstract
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Compensatory mechanisms in patients with benign intracranial hypertension syndrome. Author(s): Gasparian SS, Serova NK, Sherbakova EY, Belova TN. Source: Acta Neurochir Suppl. 2002; 81: 31-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12171062&dopt=Abstract
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Complete remission of hypertension after successful living donation of a kidney with a large benign cyst. Author(s): Veroux P, Veroux M. Source: Transplantation. 2002 September 15; 74(5): 744. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12352897&dopt=Abstract
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Completely skewed X-inactivation in a mentally retarded young female with pseudohypoparathyroidism type IB and juvenile renin-dependent hypertension. Author(s): Demura M, Takeda Y, Yoneda T, Furukawa K, Tachi A, Mabuchi H. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 July; 88(7): 3043-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12843141&dopt=Abstract
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Compliance--and improving it--in hypertension. Author(s): Elliott WJ. Source: Manag Care. 2003 August; 12(8 Suppl Hypertension): 56-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12971594&dopt=Abstract
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Complications of hypertension as encountered by primary care physician. Author(s): Biswas S, Dastidar DG, Roy KS, Pal SK, Biswas TK, Ganguly SB. Source: J Indian Med Assoc. 2003 April; 101(4): 257-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12964646&dopt=Abstract
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Concurrent transcatheter closure of an apical muscular ventricular septal defect and a patent ductus arteriosus in a child with severe hyperkinetic pulmonary hypertension. Author(s): Joseph G, Muthunayagam JV, Mandalay A. Source: Pediatric Cardiology. 2003 January-February; 24(1): 47-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12574978&dopt=Abstract
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Continuity of care and recognition of diabetes, hypertension, and hypercholesterolemia. Author(s): Koopman RJ, Mainous AG 3rd, Baker R, Gill JM, Gilbert GE. Source: Archives of Internal Medicine. 2003 June 9; 163(11): 1357-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12796073&dopt=Abstract
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Contribution of salt intake to insulin resistance associated with hypertension. Author(s): Ogihara T, Asano T, Fujita T. Source: Life Sciences. 2003 June 20; 73(5): 509-23. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12770608&dopt=Abstract
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Coronary vasodilator capacity and hypertension-induced increase in left ventricular mass. Author(s): Kozakova M, de Simone G, Morizzo C, Palombo C. Source: Hypertension. 2003 February; 41(2): 224-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12574086&dopt=Abstract
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COX-2-specific inhibitors and the kidney: effect on hypertension and oedema. Author(s): Whelton A. Source: Journal of Hypertension. 2002 September; 20 Suppl 6: S31-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12683425&dopt=Abstract
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Current perspectives on arterial stiffness and pulse pressure in hypertension and cardiovascular diseases. Author(s): Safar ME, Levy BI, Struijker-Boudier H. Source: Circulation. 2003 June 10; 107(22): 2864-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12796414&dopt=Abstract
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Current treatment of patients with hypertension: therapeutic implications of INSIGHT. Author(s): Taddei S, Ghiadoni L, Salvetti A. Source: Drugs. 2003; 63(14): 1435-44. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12834362&dopt=Abstract
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Data access. Industry groups petition for data on salt and hypertension. Author(s): Kaiser J. Source: Science. 2003 May 30; 300(5624): 1350. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12775802&dopt=Abstract
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Decompressive laparotomy: a novel approach in the management of severe intracranial hypertension. Author(s): Miglietta MA, Salzano LJ, Chiu WC, Scalea TM. Source: The Journal of Trauma. 2003 September; 55(3): 551-4; Discussion 554-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14501902&dopt=Abstract
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Design and statistical aspects of the African American Study of Kidney Disease and Hypertension (AASK). Author(s): Gassman JJ, Greene T, Wright JT Jr, Agodoa L, Bakris G, Beck GJ, Douglas J, Jamerson K, Lewis J, Kutner M, Randall OS, Wang SR. Source: Journal of the American Society of Nephrology : Jasn. 2003 July; 14(7 Suppl 2): S154-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12819322&dopt=Abstract
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Detectable serum cardiac troponin T as a marker of poor prognosis among patients with chronic precapillary pulmonary hypertension. Author(s): Torbicki A, Kurzyna M, Kuca P, Fijalkowska A, Sikora J, Florczyk M, Pruszczyk P, Burakowski J, Wawrzynska L. Source: Circulation. 2003 August 19; 108(7): 844-8. Epub 2003 Aug 04. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12900346&dopt=Abstract
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Detection of incipient left ventricular hypertrophy in mild to moderate arterial hypertension with normal electrocardiogram and echocardiogram: a new use for signal-averaged electrocardiography. Author(s): Ginefra P, Barbosa EC, Barbosa PR, Bomfim AS, Boghossian SH, Salgado AA, Brasil FG, Freitas EA, Albanesi Filho FM. Source: Arquivos Brasileiros De Cardiologia. 2003 July; 81(1): 79-84, 73-8. Epub 2003 July 31. English, Portuguese. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12908075&dopt=Abstract
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Determinants of elevated pulse pressure in middle-aged and older subjects with uncomplicated systolic hypertension: the role of proximal aortic diameter and the aortic pressure-flow relationship. Author(s): Mitchell GF, Lacourciere Y, Ouellet JP, Izzo JL Jr, Neutel J, Kerwin LJ, Block AJ, Pfeffer MA. Source: Circulation. 2003 September 30; 108(13): 1592-8. Epub 2003 Sep 15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12975261&dopt=Abstract
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Determinants of poor hypertension management in the community. Author(s): Maziak W, Keil U, Doring A, Hense HW. Source: Journal of Human Hypertension. 2003 March; 17(3): 215-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12624614&dopt=Abstract
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Development of congestive heart failure in type 2 diabetic patients with microalbuminuria or proteinuria: observations from the DIABHYCAR (type 2 DIABetes, Hypertension, CArdiovascular Events and Ramipril) study. Author(s): Vaur L, Gueret P, Lievre M, Chabaud S, Passa P; DIABHYCAR Study Group (type 2 DIABetes, Hypertension, CARdiovascular Events and Ramipril) study. Source: Diabetes Care. 2003 March; 26(3): 855-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12610049&dopt=Abstract
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Devices and techniques for blood pressure measurement and criteria for hypertension adopted by Brazilian physicians: exploratory study. Author(s): Mion D Jr, Pierin AM, Lessa I, Nobre F. Source: Arquivos Brasileiros De Cardiologia. 2002 December; 79(6): 597-600, 593-6. English, Portuguese. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12532243&dopt=Abstract
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Dexamethasone induction of hypertension and diabetes is PPAR-alpha dependent in LDL receptor-null mice. Author(s): Bernal-Mizrachi C, Weng S, Feng C, Finck BN, Knutsen RH, Leone TC, Coleman T, Mecham RP, Kelly DP, Semenkovich CF. Source: Nature Medicine. 2003 August; 9(8): 1069-75. Epub 2003 July 06. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12847522&dopt=Abstract
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Diabetes and hypertension in severe obesity and effects of gastric bypass-induced weight loss. Author(s): Sugerman HJ, Wolfe LG, Sica DA, Clore JN. Source: Annals of Surgery. 2003 June; 237(6): 751-6; Discussion 757-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12796570&dopt=Abstract
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Diabetes, hypertension and birth injuries: a complex interrelationship. Author(s): Iffy L, Djordjevic MM, Apuzzio JJ, Martin JD, Sama JC. Source: Med Law. 2003; 22(2): 207-19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12889640&dopt=Abstract
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Diagnosing secondary hypertension. Author(s): Onusko E. Source: American Family Physician. 2003 January 1; 67(1): 67-74. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12537168&dopt=Abstract
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Diagnosis and evaluation of pulmonary hypertension. Author(s): Budev MM, Arroliga AC, Jennings CA. Source: Cleve Clin J Med. 2003 April; 70 Suppl 1: S9-17. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12716138&dopt=Abstract
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Diagnosis and management of gestational hypertension and preeclampsia. Author(s): Sibai BM. Source: Obstetrics and Gynecology. 2003 July; 102(1): 181-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12850627&dopt=Abstract
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Diagnosis and treatment of hypertension in children and adolescents. Author(s): Peters RM, Flack JM. Source: Journal of the American Academy of Nurse Practitioners. 2003 February; 15(2): 56-63. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12640940&dopt=Abstract
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Diagnosis of portopulmonary hypertension in candidates for liver transplantation: a prospective study. Author(s): Colle IO, Moreau R, Godinho E, Belghiti J, Ettori F, Cohen-Solal A, Mal H, Bernuau J, Marty J, Lebrec D, Valla D, Durand F. Source: Hepatology (Baltimore, Md.). 2003 February; 37(2): 401-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12540791&dopt=Abstract
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Dietary markers of hypertension associated with pulse pressure and arterial compliance in black South African children: the THUSA Bana Study. Author(s): Schutte AE, Van Rooyen JM, Huisman HW, Kruger HS, Malan NT, De Ridder JH. Source: Cardiovasc J S Afr. 2003 March-April; 14(2): 81-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12748745&dopt=Abstract
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Dietary protein and hypertension: where do we stand? Author(s): Martin DS. Source: Nutrition (Burbank, Los Angeles County, Calif.). 2003 April; 19(4): 385-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679176&dopt=Abstract
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Dietary risk markers that contribute to the aetiology of hypertension in black South African children: the THUSA BANA study. Author(s): Schutte AE, van Rooyen JM, Huisman HW, Kruger HS, Malan NT, De Ridder JH; Transition and Health During Urbanisation in South Africa in Children; Bana: Children. Source: Journal of Human Hypertension. 2003 January; 17(1): 29-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12571614&dopt=Abstract
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Dietary salt and hypertension: a scientific issue or a matter of faith? Author(s): Robertson JI. Source: Journal of Evaluation in Clinical Practice. 2003 February; 9(1): 1-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12558698&dopt=Abstract
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Differential influence of family history of hypertension and premature myocardial infarction on systolic blood pressure and left ventricular mass trajectories in youth. Author(s): Dekkers JC, Treiber FA, Kapuku G, Snieder H. Source: Pediatrics. 2003 June; 111(6 Pt 1): 1387-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12777557&dopt=Abstract
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Digestive endoscopy and portal hypertension. North Italian Endoscopic Club. Author(s): Cestari R, Minelli L, Lanzini A, Missale G, Ravelli P, Salerni B. Source: Ital J Gastroenterol. 1996 November; 28 Suppl 2: 18-33. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14509962&dopt=Abstract
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Diminished renal kallikrein responses to mineralocorticoid stimulation in African Americans: determinants of an intermediate phenotype for hypertension. Author(s): Wong CM, O'Connor DT, Martinez JA, Kailasam MT, Parmer RJ. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 2003 April; 16(4): 281-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12670744&dopt=Abstract
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Dispersion method of excessive portal hypertension (shear stress) and changes of portal pressure and flow after living-related liver transplantation with a splenorenal shunt: a case report. Author(s): Hara Y, Sato Y, Yamamoto S, Nakatsuka H, Takeishi T, Hirano K, Kobayashi T, Watanabe T, Hatakeyama K. Source: Transplantation Proceedings. 2003 February; 35(1): 414-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12591466&dopt=Abstract
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Do community based self-reading sphygmomanometers improve detection of hypertension? A feasibility study. Author(s): Hamilton W, Round A, Goodchild R, Baker C. Source: Journal of Public Health Medicine. 2003 June; 25(2): 125-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12848401&dopt=Abstract
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Do hypertension and diuretic treatment in pregnancy increase the risk of schizophrenia in offspring? Author(s): Sorensen HJ, Mortensen EL, Reinisch JM, Mednick SA. Source: The American Journal of Psychiatry. 2003 March; 160(3): 464-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12611826&dopt=Abstract
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Does a prolonged QT peak identify left ventricular hypertrophy in hypertension? Author(s): Wong KY, Lim PO, Wong SY, MacWalter RS, Struthers AD, MacDonald TM. Source: International Journal of Cardiology. 2003 June; 89(2-3): 179-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767541&dopt=Abstract
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Does orthostatic hypotension predict the occurrence of nocturnal arterial hypertension in the elderly patient? Author(s): Carmona J, Amado P, Vasconcelos N, Almeida L, Santos I, Alves J, Nazare J. Source: Rev Port Cardiol. 2003 May; 22(5): 607-15. English, Portuguese. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12940176&dopt=Abstract
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Doppler tissue imaging reveals systolic dysfunction in patients with hypertension and apparent "isolated" diastolic dysfunction. Author(s): Poulsen SH, Andersen NH, Ivarsen PI, Mogensen CE, Egeblad H. Source: Journal of the American Society of Echocardiography : Official Publication of the American Society of Echocardiography. 2003 July; 16(7): 724-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12835658&dopt=Abstract
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Doxycycline induced intracranial hypertension. Author(s): Lochhead J, Elston JS. Source: Bmj (Clinical Research Ed.). 2003 March 22; 326(7390): 641-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12649241&dopt=Abstract
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Drug treatment of hypertension. Conclusion of editorial is somewhat flawed. Author(s): Hackam DG. Source: Bmj (Clinical Research Ed.). 2003 April 5; 326(7392): 764. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12676853&dopt=Abstract
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Drug treatment of hypertension: implications of ALLHAT. Author(s): Williams B. Source: Heart (British Cardiac Society). 2003 June; 89(6): 589-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12748205&dopt=Abstract
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Drug treatment of mild hypertension in elderly--we should be cautious in some patients. Author(s): Singh AK, Singh M. Source: J Assoc Physicians India. 2002 October; 50: 1340; Author Reply 1340-1. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12568237&dopt=Abstract
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Drug-induced hypertension. Author(s): Handler J. Source: Journal of Clinical Hypertension (Greenwich, Conn.). 2003 January-February; 5(1): 83-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12556663&dopt=Abstract
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Drugs that interrupt the renin-angiotensin system should be among the preferred initial drugs to treat hypertension. Author(s): Moore MA. Source: Journal of Clinical Hypertension (Greenwich, Conn.). 2003 March-April; 5(2): 137-44. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12671327&dopt=Abstract
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Early posttransplantation hypertension and poor long-term renal allograft survival in pediatric patients. Author(s): Mitsnefes MM, Khoury PR, McEnery PT. Source: The Journal of Pediatrics. 2003 July; 143(1): 98-103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12915832&dopt=Abstract
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Eclampsia in Southern Alberta: is there a role for seizure prophylaxis in all women with gestational hypertension? Author(s): Foong SC, Pollard JK. Source: J Obstet Gynaecol Can. 2003 May; 25(5): 385-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12738979&dopt=Abstract
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Economics of suboptimal drug use: cost-savings of using JNC-recommended medications for management of uncomplicated essential hypertension. Author(s): Xu KT, Moloney M, Phillips S. Source: Am J Manag Care. 2003 August; 9(8): 529-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12921230&dopt=Abstract
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Effect of a hypertension teaching protocol on patient and staff satisfaction in a rural community health center. Author(s): Stanton MP, Nix GS. Source: Lippincott's Case Management : Managing the Process of Patient Care. 2003 May-June; 8(3): 125-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12777973&dopt=Abstract
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Effect of beta-blockers on peripheral skin microcirculation in hypertension and peripheral vascular disease. Author(s): Ubbink DT, Verhaar EE, Lie HK, Legemate DA. Source: Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. 2003 September; 38(3): 535-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12947273&dopt=Abstract
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Effect of nitroglycerin inhalation on patients with pulmonary hypertension undergoing mitral valve replacement surgery. Author(s): Yurtseven N, Karaca P, Kaplan M, Ozkul V, Tuygun AK, Aksoy T, Canik S, Kopman E. Source: Anesthesiology. 2003 October; 99(4): 855-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14508317&dopt=Abstract
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Effect of orally active prostacyclin analogue on survival in patients with chronic thromboembolic pulmonary hypertension without major vessel obstruction. Author(s): Ono F, Nagaya N, Okumura H, Shimizu Y, Kyotani S, Nakanishi N, Miyatake K. Source: Chest. 2003 May; 123(5): 1583-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12740277&dopt=Abstract
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Effects of enalapril on left ventricular mass and diastolic function in essential hypertension: special reference to duration of hypertension. Author(s): Oki T, Fukuda N, Iuchi A, Tabata T, Sasaki M, Kawahara K, Ishimoto T, Tominaga T, Okushi H, Fujimoto T, Ito S. Source: Journal of Cardiac Failure. 1995 December; 1(5): 365-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12836711&dopt=Abstract
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Effects of exercise and weight loss on hypertension. Author(s): Beilin LJ, Burke V, Puddey IB. Source: Jama : the Journal of the American Medical Association. 2003 August 20; 290(7): 887; Author Reply 887-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12928461&dopt=Abstract
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Effects of exercise and weight loss on hypertension. Author(s): Yeo S. Source: Jama : the Journal of the American Medical Association. 2003 August 20; 290(7): 886; Author Reply 886-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12928460&dopt=Abstract
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Effects of exercise and weight loss on hypertension. Author(s): McCarthy WJ, Arpawong TE, Dietsch BJ, Yancey AK. Source: Jama : the Journal of the American Medical Association. 2003 August 20; 290(7): 885; Author Reply 886-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12928458&dopt=Abstract
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Effects of exercise and weight loss on hypertension. Author(s): Blumenthal JA, Sherwood A, Bacon SL, Hinderliter A. Source: Jama : the Journal of the American Medical Association. 2003 August 20; 290(7): 885-6; Author Reply 886-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12928457&dopt=Abstract
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Effects of hemorheological factors on the development of hypertension in diabetic children. Author(s): Cam H, Pusuroglu K, Aydin A, Ercan M. Source: Journal of Tropical Pediatrics. 2003 June; 49(3): 164-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12848207&dopt=Abstract
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Effects of hypertension and obesity on endometrial thickness. Author(s): Serdar Serin I, Ozcelik B, Basbug M, Ozsahin O, Yilmazsoy A, Erez R. Source: European Journal of Obstetrics, Gynecology, and Reproductive Biology. 2003 July 1; 109(1): 72-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12818448&dopt=Abstract
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Effects of telmisartan and losartan on left ventricular mass in mild-to-moderate hypertension. A randomized, double-blind trial. Author(s): Martina B, Dieterle T, Sigle JP, Surber C, Battegay E. Source: Cardiology. 2003; 99(3): 169-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12824726&dopt=Abstract
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Effects of the Dietary Approaches to Stop Hypertension (DASH) diet on the pressurenatriuresis relationship. Author(s): Akita S, Sacks FM, Svetkey LP, Conlin PR, Kimura G; DASH-Sodium Trial Collaborative Research Group. Source: Hypertension. 2003 July; 42(1): 8-13. Epub 2003 May 19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12756219&dopt=Abstract
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Effects of the dual endothelin receptor antagonist bosentan in patients with pulmonary arterial hypertension: a 1-year follow-up study. Author(s): Sitbon O, Badesch DB, Channick RN, Frost A, Robbins IM, Simonneau G, Tapson VF, Rubin LJ. Source: Chest. 2003 July; 124(1): 247-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12853530&dopt=Abstract
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Efficacy and tolerability of fixed-dose combinations of telmisartan plus HCTZ compared with losartan plus HCTZ in patients with essential hypertension. Author(s): Lacourciere Y, Gil-Extremera B, Mueller O, Byrne M, Williams L. Source: Int J Clin Pract. 2003 May; 57(4): 273-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12800457&dopt=Abstract
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Efficacy of moderate hypothermia in patients with severe head injury and intracranial hypertension refractory to mild hypothermia. Author(s): Shiozaki T, Nakajima Y, Taneda M, Tasaki O, Inoue Y, Ikegawa H, Matsushima A, Tanaka H, Shimazu T, Sugimoto H. Source: Journal of Neurosurgery. 2003 July; 99(1): 47-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12854743&dopt=Abstract
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Efficacy of nephrectomy for the treatment of nephrogenic hypertension in a pediatric population. Author(s): Baez-Trinidad LG, Lendvay TS, Broecker BH, Smith EA, Warshaw BL, Hymes L, Kirsch AJ. Source: The Journal of Urology. 2003 October; 170(4 Pt 2): 1655-7; Discussion 1658. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14501684&dopt=Abstract
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Elevated plasma fibrinogen levels in patients with essential hypertension are related to vascular complications. Author(s): Lechi C, Gaino S, Zuliani V, Tommasoli RM, Faccini G, Fasson R, Arcaro G, Lechi A, Minuz P. Source: International Angiology : a Journal of the International Union of Angiology. 2003 March; 22(1): 72-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12771860&dopt=Abstract
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Elevated serum concentrations of androgens in women with pregnancy-induced hypertension. Author(s): Jirecek S, Joura EA, Tempfer C, Knofler M, Husslein P, Zeisler H. Source: Wiener Klinische Wochenschrift. 2003 March 31; 115(5-6): 162-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12741075&dopt=Abstract
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Embracing complexity: A consideration of hypertension in the very old. Author(s): Goodwin JS. Source: The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 2003 July; 58(7): 653-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12865483&dopt=Abstract
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Emerging therapies for pulmonary hypertension: striving for efficacy and safety. Author(s): Kao PN, Faul JL. Source: Journal of the American College of Cardiology. 2003 June 18; 41(12): 2126-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12821235&dopt=Abstract
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Endoscopic ligation of esophageal varices for prophylaxis of first bleeding in children and adolescents with portal hypertension: preliminary results of a prospective study. Author(s): Celinska-Cedro D, Teisseyre M, Woynarowski M, Socha P, Socha J, Ryzko J. Source: Journal of Pediatric Surgery. 2003 July; 38(7): 1008-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12861528&dopt=Abstract
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Evaluation of patient counseling on blood pressure control of out-patients with hypertension at Chulalongkorn Hospital. Author(s): Aramwit P, Assawawitoontip S. Source: J Med Assoc Thai. 2003 June; 86 Suppl 2: S496-500. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12930031&dopt=Abstract
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Evaluation of renal causes of hypertension. Author(s): Hartman RP, Kawashima A, King BF Jr. Source: Radiologic Clinics of North America. 2003 September; 41(5): 909-29. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14521201&dopt=Abstract
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Evidence-based treatment of hypertension. JNC 7 Guidelines provide an updated framework. Author(s): Lookinland S, Beckstrand RL. Source: Adv Nurse Pract. 2003 September; 11(9): 32-9; Quiz 39-40. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14521107&dopt=Abstract
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Exercise training counteracts the abnormal release of plasma endothelin-1 in normal subjects at risk for hypertension. Author(s): Tanzilli G, Barilla F, Pannitteri G, Greco C, Comito C, Schiariti M, Papalia U, Mangieri E. Source: Ital Heart J. 2003 February; 4(2): 107-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12762273&dopt=Abstract
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Expression of human herpesvirus 8 in primary pulmonary hypertension. Author(s): Cool CD, Rai PR, Yeager ME, Hernandez-Saavedra D, Serls AE, Bull TM, Geraci MW, Brown KK, Routes JM, Tuder RM, Voelkel NF. Source: The New England Journal of Medicine. 2003 September 18; 349(12): 1113-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13679525&dopt=Abstract
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Factor analysis of possible risks for hypertension in a black South African population. Author(s): Schutte AE, van Rooyen JM, Huisman HW, Kruger HS, de Ridder JH. Source: Journal of Human Hypertension. 2003 May; 17(5): 339-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12756407&dopt=Abstract
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Factors associated with uncontrolled hypertension in an affluent, elderly population. Author(s): Inciardi JF, McMahon K, Sauer BL. Source: The Annals of Pharmacotherapy. 2003 April; 37(4): 485-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12659600&dopt=Abstract
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Factors influencing arterial stiffness in systolic hypertension in the elderly: role of sodium and the renin-angiotensin system. Author(s): Safar ME, Benetos A. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 2003 March; 16(3): 249-58. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12620707&dopt=Abstract
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Fall in mean arterial pressure and fetal growth restriction in pregnancy hypertension: an updated metaregression analysis. Author(s): von Dadelszen P, Magee LA. Source: J Obstet Gynaecol Can. 2002 December; 24(12): 941-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12464992&dopt=Abstract
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Familial aggregation of diabetes and hypertension in a case-control study of colorectal neoplasia. Author(s): Brauer PM, McKeown-Eyssen GE, Jazmaji V, Logan AG, Andrews DF, Jenkins D, Marcon N, Saibil F, Cohen L, Stern H, Baron D, Greenberg G, Diamandis E, Kakis G, Singer W, Steiner G. Source: American Journal of Epidemiology. 2002 October 15; 156(8): 702-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12370158&dopt=Abstract
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Familial hyperkalemic hypertension: phenotypic analysis in a large family with the WNK1 deletion mutation. Author(s): Achard JM, Warnock DG, Disse-Nicodeme S, Fiquet-Kempf B, Corvol P, Fournier A, Jeunemaitre X. Source: The American Journal of Medicine. 2003 April 15; 114(6): 495-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12727582&dopt=Abstract
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Familial idiopathic intracranial hypertension. Author(s): Karaman K, Gverovic-Antunica A, Zuljan I, Vukojevic N, Zoltner B, Erceg I, Ivkosic A. Source: Croatian Medical Journal. 2003 August; 44(4): 480-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12950154&dopt=Abstract
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Familial/sporadic glucocorticoid resistance syndrome and hypertension. Author(s): Kino T, Vottero A, Charmandari E, Chrousos GP. Source: Annals of the New York Academy of Sciences. 2002 September; 970: 101-11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12381545&dopt=Abstract
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Family history of hypertension and type 2 diabetes in relation to preeclampsia risk. Author(s): Qiu C, Williams MA, Leisenring WM, Sorensen TK, Frederick IO, Dempsey JC, Luthy DA. Source: Hypertension. 2003 March; 41(3): 408-13. Epub 2003 February 17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12623936&dopt=Abstract
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Fibromuscular dysplasia in renovascular hypertension demonstrated by multislice CT: comparison with conventional angiogram and intravascular ultrasound. Author(s): Funabashi N, Komiyama N, Komuro I. Source: Heart (British Cardiac Society). 2003 June; 89(6): 639. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12748219&dopt=Abstract
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Fish consumption and hypertension incidence in African Americans and whites: the NHANES I Epidemiologic Follow-up Study. Author(s): Gillum RF, Mussolino ME, Madans JH. Source: Journal of the National Medical Association. 2001 April; 93(4): 124-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12653399&dopt=Abstract
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Fixed combination trandolapril/verapamil sustained-release: a review of its use in essential hypertension. Author(s): Muijsers RB, Curran MP, Perry CM. Source: Drugs. 2002; 62(17): 2539-67. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12421112&dopt=Abstract
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Fixed combinations of delapril plus indapamide vs fosinopril plus hydrochlorothiazide in mild to moderate essential hypertension. Author(s): Cremonesi G, Cavalieri L, Cikes I, Dobovisek J, Bacchelli S, Degli Esposti D, Costa FV, Borghi C, Ambrosioni E. Source: Adv Ther. 2002 May-June; 19(3): 129-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12201354&dopt=Abstract
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For the patient. Are vegetarians at less risk for obesity, diabetes, and hypertension? Obesity, diabetes, hypertension, and vegetarian status among Seventh-Day Adventists in Barbados: preliminary results. Author(s): Brathwaite N, Fraser HS, Modeste N, Broome H, King R. Source: Ethn Dis. 2003 Winter; 13(1): 148. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12723025&dopt=Abstract
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For the patient. The effectiveness of a community health worker outreach program on healthcare utilization of west Baltimore City Medicaid patients with diabetes, with or without hypertension. Author(s): Fedder DO, Chang RJ, Curry S, Nichols G. Source: Ethn Dis. 2003 Winter; 13(1): 146. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12723023&dopt=Abstract
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Forearm vasoconstriction to endothelin-1 is impaired, but constriction to sarafotoxin 6c and vasodilatation to BQ-123 unaltered, in patients with essential hypertension. Author(s): Ferro CJ, Haynes WG, Hand MF, Webb DJ. Source: Clinical Science (London, England : 1979). 2002 August; 103 Suppl 48: 53S-58S. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12193054&dopt=Abstract
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Forms of mineralocorticoid hypertension. Author(s): Ferrari P, Bonny O. Source: Vitam Horm. 2003; 66: 113-56. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12852254&dopt=Abstract
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Frequency and severity of tricuspid regurgitation determined by Doppler echocardiography in primary pulmonary hypertension. Author(s): Hinderliter AL, Willis PW 4th, Long WA, Clarke WR, Ralph D, Caldwell EJ, Williams W, Ettinger NA, Hill NS, Summer WR, de Boisblanc B, Koch G, Li S, Clayton LM, Jobsis MM, Crow JW; PPH Study Group. Source: The American Journal of Cardiology. 2003 April 15; 91(8): 1033-7, A9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12686360&dopt=Abstract
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Frequency doubling perimetry in ocular hypertension and chronic open angle glaucoma. Author(s): Cellini M, Torreggiani A. Source: Acta Ophthalmologica Scandinavica. Supplement. 2002; 236: 24-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12390120&dopt=Abstract
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Frequency doubling technology and high-pass resolution perimetry in glaucoma and ocular hypertension. Author(s): Kalaboukhova L, Lindblom B. Source: Acta Ophthalmologica Scandinavica. 2003 June; 81(3): 247-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12780403&dopt=Abstract
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Frequency of analgesic use and risk of hypertension in younger women. Author(s): Curhan GC, Willett WC, Rosner B, Stampfer MJ. Source: Archives of Internal Medicine. 2002 October 28; 162(19): 2204-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12390063&dopt=Abstract
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From linkage to genes in human hypertension. Author(s): Melander O. Source: Journal of Hypertension. 2002 November; 20(11): 2135-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12409946&dopt=Abstract
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From theory into practice: arterial haemodynamics in clinical hypertension. Author(s): O'Rourke MF. Source: Journal of Hypertension. 2002 October; 20(10): 1901-15. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12359961&dopt=Abstract
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Function of the serotonin 5-hydroxytryptamine 2B receptor in pulmonary hypertension. Author(s): Launay JM, Herve P, Peoc'h K, Tournois C, Callebert J, Nebigil CG, Etienne N, Drouet L, Humbert M, Simonneau G, Maroteaux L. Source: Nature Medicine. 2002 October; 8(10): 1129-35. Epub 2002 September 16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12244304&dopt=Abstract
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Functional heterogeneity of bone morphogenetic protein receptor-II mutants found in patients with primary pulmonary hypertension. Author(s): Nishihara A, Watabe T, Imamura T, Miyazono K. Source: Molecular Biology of the Cell. 2002 September; 13(9): 3055-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12221115&dopt=Abstract
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Gamma-glutamyltransferase is a predictor of incident diabetes and hypertension: the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Author(s): Lee DH, Jacobs DR Jr, Gross M, Kiefe CI, Roseman J, Lewis CE, Steffes M. Source: Clinical Chemistry. 2003 August; 49(8): 1358-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12881453&dopt=Abstract
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Gastrectomy in combination with a distal splenorenal shunt in a patient with gastric cancer and portal hypertension: report of a case. Author(s): Kato T, Kato H, Kondo S, Okushiba S, Morikawa T. Source: Surgery Today. 2002; 32(8): 727-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12181726&dopt=Abstract
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Gastric motility in patients with presinusoidal portal hypertension. Author(s): Aprile LR, Meneghelli UG, Martinelli AL, Monteiro CR. Source: The American Journal of Gastroenterology. 2002 December; 97(12): 3038-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12492187&dopt=Abstract
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Gender and age differences in lifestyle factors related to hypertension in middle-aged civil service employees. Author(s): Hori Y, Toyoshima H, Kondo T, Tamakoshi K, Yatsuya H, Zhu S, Kawamura T, Toyama J, Okamoto N. Source: J Epidemiol. 2003 January; 13(1): 38-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12587612&dopt=Abstract
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Gender, age and deprivation differences in the primary care management of hypertension in Scotland: a cross-sectional database study. Author(s): Pears E, Hannaford PC, Taylor MW. Source: Family Practice. 2003 February; 20(1): 22-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12509366&dopt=Abstract
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Gender-specific correlates of leptin with hypertension-related phenotypes in African Americans. Author(s): El-Gharbawy AH, Kotchen JM, Grim CE, Kaldunski M, Hoffmann RG, Pausova Z, Hamet P, Kotchen TA. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 2002 November; 15(11): 989-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12441220&dopt=Abstract
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Gene expression profiling in hypertension research: a critical perspective. Author(s): Pravenec M, Wallace C, Aitman TJ, Kurtz TW. Source: Hypertension. 2003 January; 41(1): 3-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12511522&dopt=Abstract
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Gene polymorphisms of the renin-angiotensin-aldosterone system and essential arterial hypertension in childhood. Author(s): Petrovic D, Bidovec M, Peterlin B. Source: Folia Biol (Krakow). 2002; 50(1-2): 53-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12597535&dopt=Abstract
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Gene transfer of human guanosine 5'-triphosphate cyclohydrolase I restores vascular tetrahydrobiopterin level and endothelial function in low renin hypertension. Author(s): Zheng JS, Yang XQ, Lookingland KJ, Fink GD, Hesslinger C, Kapatos G, Kovesdi I, Chen AF. Source: Circulation. 2003 September 9; 108(10): 1238-45. Epub 2003 August 18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12925450&dopt=Abstract
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Gene-targeting studies of the renin-angiotensin system: mechanisms of hypertension and cardiovascular disease. Author(s): Gurley SB, Le TH, Coffman TM. Source: Cold Spring Harb Symp Quant Biol. 2002; 67: 451-7. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12858571&dopt=Abstract
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Genetic basis of essential hypertension in Tibetan. Author(s): Zhuang L, Cui C, Chen Y, Cen W, Qiu C, Xu Q, Liu Y, Zhu X, Fang M, Wu Z. Source: Zhonghua Yi Xue Za Zhi. 2002 August 10; 82(15): 1009-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12194787&dopt=Abstract
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Genetic influences in human hypertension. Author(s): Rutherford PA. Source: Journal of Hypertension. 2003 January; 21(1): 19-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544427&dopt=Abstract
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Genetic studies of pulmonary arterial hypertension. Author(s): Morse JH. Source: Lupus. 2003; 12(3): 209-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12708784&dopt=Abstract
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Genetic variants of WNK4 in whites and African Americans with hypertension. Author(s): Erlich PM, Cui J, Chazaro I, Farrer LA, Baldwin CT, Gavras H, DeStefano AL. Source: Hypertension. 2003 June; 41(6): 1191-5. Epub 2003 April 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12719438&dopt=Abstract
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Genetics and pulmonary hypertension. Author(s): Loyd JE. Source: Chest. 2002 December; 122(6 Suppl): 284S-286S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12475800&dopt=Abstract
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Genetics of essential hypertension: from families to genes. Author(s): Barlassina C, Lanzani C, Manunta P, Bianchi G. Source: Journal of the American Society of Nephrology : Jasn. 2002 November; 13 Suppl 3: S155-64. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12466306&dopt=Abstract
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Genetics of hypertension: the adducin paradigm. Author(s): Bianchi G, Tripodi G. Source: Annals of the New York Academy of Sciences. 2003 April; 986: 660-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12763916&dopt=Abstract
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Genetics of pulmonary hypertension: from bench to bedside. Author(s): Humbert M, Trembath RC. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2002 September; 20(3): 741-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12358355&dopt=Abstract
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Genetics of the kidney and hypertension. Author(s): Watson B Jr. Source: Current Hypertension Reports. 2003 June; 5(3): 273-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12724062&dopt=Abstract
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Genome scans for hypertension and blood pressure regulation. Author(s): Samani NJ. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 2003 February; 16(2): 167-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12559688&dopt=Abstract
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Genome-wide linkage analyses for hypertension genes in two ethnically and geographically diverse populations. Author(s): Kardia SL, Rozek LS, Krushkal J, Ferrell RE, Turner ST, Hutchinson R, Brown A, Sing CF, Boerwinkle E. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 2003 February; 16(2): 154-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12559685&dopt=Abstract
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Genome-wide mapping of human loci for essential hypertension. Author(s): Caulfield M, Munroe P, Pembroke J, Samani N, Dominiczak A, Brown M, Benjamin N, Webster J, Ratcliffe P, O'Shea S, Papp J, Taylor E, Dobson R, Knight J, Newhouse S, Hooper J, Lee W, Brain N, Clayton D, Lathrop GM, Farrall M, Connell J; MRC British Genetics of Hypertension Study. Source: Lancet. 2003 June 21; 361(9375): 2118-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12826435&dopt=Abstract
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Genomic medicine: exploring the basis of a new approach to endocrine hypertension. Author(s): Alesci S, Chrousos GP, Pacak K. Source: Annals of the New York Academy of Sciences. 2002 September; 970: 177-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12381553&dopt=Abstract
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Genotyping of essential hypertension single-nucleotide polymorphisms by a homogeneous PCR method with universal energy transfer primers. Author(s): Bengra C, Mifflin TE, Khripin Y, Manunta P, Williams SM, Jose PA, Felder RA. Source: Clinical Chemistry. 2002 December; 48(12): 2131-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12446468&dopt=Abstract
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Goal-oriented hypertension management: translating clinical trials to practice. Author(s): Singer GM, Izhar M, Black HR. Source: Hypertension. 2002 October; 40(4): 464-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12364348&dopt=Abstract
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Goldblatt's kidney, Hughes syndrome and hypertension. Author(s): Sangle S, D'Cruz D, Khamashta M, Tungekar MF, Abbs I, Hughes G. Source: Lupus. 2002; 11(11): 699-703. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12474999&dopt=Abstract
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G-protein beta3 subunit 825T allele and hypertension. Author(s): Siffert W. Source: Current Hypertension Reports. 2003 February; 5(1): 47-53. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12530935&dopt=Abstract
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Graded balloon atrial septostomy in severe pulmonary hypertension. Author(s): Tandon R. Source: Indian Heart J. 2002 May-June; 54(3): 326; Author Reply 326. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12216938&dopt=Abstract
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Growth and living conditions in childhood and hypertension in adult life: a longitudinal study. Author(s): Barker DJ, Forsen T, Eriksson JG, Osmond C. Source: Journal of Hypertension. 2002 October; 20(10): 1951-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12359972&dopt=Abstract
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Guidelines for treatment of hypertension in the elderly--2002 revised version. Author(s): Ogihara T, Hiwada K, Morimoto S, Matsuoka H, Matsumoto M, Takishita S, Shimamoto K, Shimada K, Abe I, Ouchi Y, Tsukiyama H, Katayama S, Imai Y, Suzuki H, Kohara K, Okaishi K, Mikami H. Source: Hypertens Res. 2003 January; 26(1): 1-36. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12661910&dopt=Abstract
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Haemodynamic comparison of amlodipine and atenolol in essential hypertension using the quantascope. Author(s): Tham TC, Herity N, Guy S, Silke B. Source: British Journal of Clinical Pharmacology. 1993 December; 36(6): 555-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12959272&dopt=Abstract
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Headache as a predictive factor of severe systolic hypertension in acute ischemic stroke. Author(s): Hong YH, Lee YS, Park SH. Source: The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques. 2003 August; 30(3): 210-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12945943&dopt=Abstract
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Help! Grandma's stroking: Balancing morbidity and mortality in the treatment of hypertension among the very old. Author(s): Denson S. Source: The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 2003 July; 58(7): 660-1; Discussion 669-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12865485&dopt=Abstract
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Hemodynamic and catecholamine responses during tracheal intubation using a lightwand device (Trachlight) in elderly patients with hypertension. Author(s): Kanaide M, Fukusaki M, Tamura S, Takada M, Miyako M, Sumikawa K. Source: Journal of Anesthesia. 2003; 17(3): 161-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12911202&dopt=Abstract
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Hemolytic anemia-associated pulmonary hypertension of sickle cell disease and the nitric oxide/arginine pathway. Author(s): Jison ML, Gladwin MT. Source: American Journal of Respiratory and Critical Care Medicine. 2003 July 1; 168(1): 3-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12826592&dopt=Abstract
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Homocysteine plasma concentration levels for the prediction of preeclampsia in women with chronic hypertension. Author(s): Zeeman GG, Alexander JM, McIntire DD, Devaraj S, Leveno KJ. Source: American Journal of Obstetrics and Gynecology. 2003 August; 189(2): 574-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14520237&dopt=Abstract
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How well are hypertension and albuminuria treated in type II diabetic patients? Author(s): Boero R, Prodi E, Elia F, Porta L, Martelli S, Ferraro L, Quarello F. Source: Journal of Human Hypertension. 2003 June; 17(6): 413-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12764404&dopt=Abstract
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Hybrid cell-gene therapy for pulmonary hypertension based on phagocytosing action of endothelial progenitor cells. Author(s): Nagaya N, Kangawa K, Kanda M, Uematsu M, Horio T, Fukuyama N, Hino J, Harada-Shiba M, Okumura H, Tabata Y, Mochizuki N, Chiba Y, Nishioka K, Miyatake K, Asahara T, Hara H, Mori H. Source: Circulation. 2003 August 19; 108(7): 889-95. Epub 2003 June 30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12835224&dopt=Abstract
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Hydralazine for treatment of severe hypertension in pregnancy: meta-analysis. Author(s): Magee LA, Cham C, Waterman EJ, Ohlsson A, von Dadelszen P. Source: Bmj (Clinical Research Ed.). 2003 October 25; 327(7421): 955-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14576246&dopt=Abstract
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Hyperhomocysteinemia but not MTHFR genotype is associated with young-onset essential hypertension. Author(s): Garfunkel VA, Porto PI, Garcia SI, Dieuzeide G, Kirszner T, Plotquin Y, Spataro RJ, Gonzalez C, Pirola CJ. Source: Journal of Human Hypertension. 2003 May; 17(5): 361-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12756410&dopt=Abstract
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Hyperhomocysteinemia in menopausal hypertension: an added risk factor and a dangerous association for organ damage. Author(s): Noto R, Neri S, Molino G, Meli S, Noto P, Mauceri B, Cilio D, Rapisarda A, Noto Z. Source: Eur Rev Med Pharmacol Sci. 2002 July-August; 6(4): 81-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12729036&dopt=Abstract
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Hypertension and cancer mortality: is there a place for antioxidant interventions? Author(s): Korantzopoulos P, Papaioannides D. Source: Indian Heart J. 2003 January-February; 55(1): 95-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12760600&dopt=Abstract
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Hypertension and cognitive function: pathophysiologic effects of hypertension on the brain. Author(s): Manolio TA, Olson J, Longstreth WT. Source: Current Hypertension Reports. 2003 June; 5(3): 255-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12724059&dopt=Abstract
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Hypertension and diabetes mellitus. Author(s): Jayakumar RV. Source: J Indian Med Assoc. 2003 April; 101(4): 254-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12964645&dopt=Abstract
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Hypertension and heart failure sine heart failure. The ACC/AHA guidelines: a misadventure in the lexicography of cardiomyopathy and heart failure, particularly for the hypertensive. Author(s): Giles TD. Source: Journal of Clinical Hypertension (Greenwich, Conn.). 2003 July-August; 5(4): 280-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12939569&dopt=Abstract
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Hypertension and obesity. Author(s): Najman DM, Kapoor P, Serrano A, Tckachenko D. Source: Archives of Internal Medicine. 2003 May 12; 163(9): 1114-5; Author Reply 1115-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12742816&dopt=Abstract
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Hypertension and renal dysfunction: NHANES III. Author(s): Jones CA. Source: Journal of the American Society of Nephrology : Jasn. 2003 July; 14(7 Suppl 2): S71-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12819306&dopt=Abstract
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Hypertension and the cortisol-cortisone shuttle. Author(s): Quinkler M, Stewart PM. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 June; 88(6): 2384-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12788832&dopt=Abstract
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Hypertension and the prothrombotic state. Author(s): Nadar S, Lip GY. Source: Journal of the American College of Cardiology. 2003 May 21; 41(10): 1847; Author Reply 1847. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767675&dopt=Abstract
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Hypertension in diabetes. Author(s): Sahay BK, Sahay RK. Source: J Indian Med Assoc. 2003 January; 101(1): 12, 14-5, 44. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12841500&dopt=Abstract
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Hypertension in older urban Native-American primary care patients. Author(s): Rhoades DA, Buchwald D. Source: Journal of the American Geriatrics Society. 2003 June; 51(6): 774-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12757563&dopt=Abstract
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Hypertension in the athlete. Author(s): Sachtleben T, Fields KB. Source: Curr Sports Med Rep. 2003 April; 2(2): 79-83. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12831663&dopt=Abstract
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Hypertension prevalence and blood pressure levels in 6 European countries, Canada, and the United States. Author(s): Wolf-Maier K, Cooper RS, Banegas JR, Giampaoli S, Hense HW, Joffres M, Kastarinen M, Poulter N, Primatesta P, Rodriguez-Artalejo F, Stegmayr B, Thamm M, Tuomilehto J, Vanuzzo D, Vescio F. Source: Jama : the Journal of the American Medical Association. 2003 May 14; 289(18): 2363-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12746359&dopt=Abstract
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Hypertension prevalence and stroke mortality across populations. Author(s): Staessen JA, Kuznetsova T, Stolarz K. Source: Jama : the Journal of the American Medical Association. 2003 May 14; 289(18): 2420-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12746368&dopt=Abstract
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Hypertension update: lessons from the literature. Author(s): Ong HT. Source: Med J Malaysia. 2002 December; 57(4): 510-4. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12733181&dopt=Abstract
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Hypertension, diabetes, and longitudinal changes in intraocular pressure. Author(s): Hennis A, Wu SY, Nemesure B, Leske MC; Barbados Eye Studies Group. Source: Ophthalmology. 2003 May; 110(5): 908-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12750088&dopt=Abstract
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Hypertension, obesity, and the renin-angiotensin system: a tale of tight associations. Author(s): Sibley S. Source: Minn Med. 2003 January; 86(1): 46-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12585560&dopt=Abstract
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Hypertension: a review of therapeutic options. Author(s): Carter BL. Source: Manag Care. 2003 August; 12(8 Suppl Hypertension): 34-44. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12971591&dopt=Abstract
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Hypertension: prevalence and economic implications. Author(s): Dalzell MD. Source: Manag Care. 2003 August; 12(8 Suppl Hypertension): 6-11. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12971587&dopt=Abstract
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Hypertension: treating the patient as well as the blood pressure. Author(s): Jackson G. Source: Int J Clin Pract. 2003 June; 57(5): 357. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12846335&dopt=Abstract
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Identifying at-risk patients through community pharmacy-based hypertension and stroke prevention screening projects. Author(s): Mangum SA, Kraenow KR, Narducci WA. Source: Journal of the American Pharmaceutical Association (Washington,D.C. : 1996). 2003 January-February; 43(1): 50-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12585751&dopt=Abstract
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Idiopathic intracranial hypertension in the pediatric population. Author(s): Ng YT, Bodensteiner JB. Source: Journal of Child Neurology. 2003 June; 18(6): 440; Author Reply 440. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12886985&dopt=Abstract
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Idiopathic intracranial hypertension: associations with coagulation disorders and polycystic-ovary syndrome. Author(s): Glueck CJ, Iyengar S, Goldenberg N, Smith LS, Wang P. Source: The Journal of Laboratory and Clinical Medicine. 2003 July; 142(1): 35-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12878984&dopt=Abstract
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Image of the month. Superior mesenteric arteriovenous fistula and portal hypertension. Author(s): Revilla Jde L, Herreros de Tejada A, Garrido A. Source: Gastroenterology. 2003 September; 125(3): 653, 1000. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12949709&dopt=Abstract
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Immediate and long-term hemodynamic and clinical effects of sildenafil in patients with pulmonary arterial hypertension receiving vasodilator therapy. Author(s): Bhatia S, Frantz RP, Severson CJ, Durst LA, McGoon MD. Source: Mayo Clinic Proceedings. 2003 October; 78(10): 1207-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14531479&dopt=Abstract
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Immune cell CD62L and CD11a expression in response to a psychological stressor in human hypertension. Author(s): Mills PJ, Farag NH, Hong S, Kennedy BP, Berry CC, Ziegler MG. Source: Brain, Behavior, and Immunity. 2003 August; 17(4): 260-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12831828&dopt=Abstract
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Implementing a shared-care approach to improve the management of patients with pulmonary arterial hypertension. Author(s): Mughal MM, Mandell B, James K, Stelmach K, Minai OA. Source: Cleve Clin J Med. 2003 April; 70 Suppl 1: S28-33. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12716140&dopt=Abstract
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Improvement of microcirculation and healing of venous hypertension and ulcers with Crystacide. Evaluation of free radicals, laser Doppler flux and PO2. A prospectiverandomized-controlled study. Author(s): Belcaro G, Cesarone MR, Nicolaides AN, Geroulakos G, Di Renzo A, Milani M, Ricci A, Brandolini R, Dugall M, Ruffini I, Cornelli U, Griffin M. Source: Angiology. 2003 May-June; 54(3): 325-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12785025&dopt=Abstract
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In vivo adaptive response of the peripheral conduit artery in patients with borderline systolic hypertension. Author(s): Tao J, Jin Y, Wang L, Tang A, Liao X, Yang Z, Ma H. Source: Chin Med J (Engl). 2003 March; 116(3): 333-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12781031&dopt=Abstract
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Increased serum ferritin is common in men with essential hypertension. Author(s): Piperno A, Trombini P, Gelosa M, Mauri V, Pecci V, Vergani A, Salvioni A, Mariani R, Mancia G. Source: Journal of Hypertension. 2002 August; 20(8): 1513-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12172312&dopt=Abstract
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Infection-induced pulmonary hypertension crisis after Rastelli procedure. Author(s): Katoh Y, Nakajima Y, Yamagishi M, Mizobe T. Source: Paediatric Anaesthesia. 2003 June; 13(5): 461-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12791125&dopt=Abstract
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Inferior meso-caval shunt for portal hypertension with bleeding esophageal varices. Author(s): Khanna R, Mishra S, Khanna S, Khanna AK. Source: Indian J Gastroenterol. 2003 May-June; 22(3): 108-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12839390&dopt=Abstract
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Influence of antihypertensive medication on aldosterone and renin concentration in the differential diagnosis of essential hypertension and primary aldosteronism. Author(s): Seifarth C, Trenkel S, Schobel H, Hahn EG, Hensen J. Source: Clinical Endocrinology. 2002 October; 57(4): 457-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12354127&dopt=Abstract
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Inhibin-A and superimposed preeclampsia in women with chronic hypertension. Author(s): Zeeman GG, Alexander JM, McIntire DD, Byrd W, Leveno KJ. Source: Obstetrics and Gynecology. 2003 February; 101(2): 232-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12576244&dopt=Abstract
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Inhibition of 11beta-hydroxysteroid dehydrogenase type 1 lowers intraocular pressure in patients with ocular hypertension. Author(s): Rauz S, Cheung CM, Wood PJ, Coca-Prados M, Walker EA, Murray PI, Stewart PM. Source: Qjm : Monthly Journal of the Association of Physicians. 2003 July; 96(7): 481-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12881590&dopt=Abstract
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Initial management of ocular hypertension and primary open-angle glaucoma: an evaluation of the royal college of ophthalmologists' guidelines. Author(s): Choong YF, Devarajan N, Pickering A, Pickering S, Austin MW. Source: Eye (London, England). 2003 August; 17(6): 685-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12928677&dopt=Abstract
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Initial treatment of hypertension. Author(s): Berend K. Source: The New England Journal of Medicine. 2003 September 11; 349(11): 1090-1; Author Reply 1090-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12971366&dopt=Abstract
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Initial treatment of hypertension. Author(s): Porat G. Source: The New England Journal of Medicine. 2003 September 11; 349(11): 1090-1; Author Reply 1090-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12968097&dopt=Abstract
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Initial treatment of hypertension. Author(s): August P. Source: The New England Journal of Medicine. 2003 February 13; 348(7): 610-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12584370&dopt=Abstract
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Insulin resistance and its potential role in pregnancy-induced hypertension. Author(s): Seely EW, Solomon CG. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 June; 88(6): 2393-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12788833&dopt=Abstract
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Insulin resistance, hypertension, and coronary heart disease. Author(s): Reaven G. Source: Journal of Clinical Hypertension (Greenwich, Conn.). 2003 July-August; 5(4): 269-74. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12939567&dopt=Abstract
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Insulin resistance/compensatory hyperinsulinemia, essential hypertension, and cardiovascular disease. Author(s): Reaven GM. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 June; 88(6): 2399403. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12788834&dopt=Abstract
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Interactions between the renin-angiotensin system and dyslipidemia: relevance in the therapy of hypertension and coronary heart disease. Author(s): Singh BM, Mehta JL. Source: Archives of Internal Medicine. 2003 June 9; 163(11): 1296-304. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12796065&dopt=Abstract
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Intraoperative management of severe pulmonary hypertension during cardiac surgery with inhaled iloprost. Author(s): Rex S, Busch T, Vettelschoss M, de Rossi L, Rossaint R, Buhre W. Source: Anesthesiology. 2003 September; 99(3): 745-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12960562&dopt=Abstract
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Is the 'rule of halves' in hypertension still valid?--Evidence from the Chennai Urban Population Study. Author(s): Deepa R, Shanthirani CS, Pradeepa R, Mohan V. Source: J Assoc Physicians India. 2003 February; 51: 153-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12725257&dopt=Abstract
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Is there a pathogenetic role for uric acid in hypertension and cardiovascular and renal disease? Author(s): Johnson RJ, Kang DH, Feig D, Kivlighn S, Kanellis J, Watanabe S, Tuttle KR, Rodriguez-Iturbe B, Herrera-Acosta J, Mazzali M. Source: Hypertension. 2003 June; 41(6): 1183-90. Epub 2003 April 21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12707287&dopt=Abstract
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Isolated systolic hypertension: analysis of a significant sample of the Portuguese population. Author(s): Ramalhinho V. Source: Rev Port Cardiol. 2003 January; 22(1): 25-6. English, Portuguese. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12712808&dopt=Abstract
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Isolated systolic hypertension: data on a cohort of young subjects from a French working population (IHPAF). Author(s): Mallion JM, Hamici L, Chatellier G, Lang T, Plouin PF, De Gaudemaris R. Source: Journal of Human Hypertension. 2003 February; 17(2): 93-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12574786&dopt=Abstract
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Isolated systolic hypertension--epidemiology and impact in clinical practice. Author(s): Rocha E, Mello e Silva A, Gouveia-Oliveira A, Nogueira P. Source: Rev Port Cardiol. 2003 January; 22(1): 7-23. English, Portuguese. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12712807&dopt=Abstract
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Isovolume hypertonic solutes (sodium chloride or mannitol) in the treatment of refractory posttraumatic intracranial hypertension: 2 mL/kg 7.5% saline is more effective than 2 mL/kg 20% mannitol. Author(s): Vialet R, Albanese J, Thomachot L, Antonini F, Bourgouin A, Alliez B, Martin C. Source: Critical Care Medicine. 2003 June; 31(6): 1683-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12794404&dopt=Abstract
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JNC 7 express: new thinking in hypertension treatment. Author(s): Green L. Source: American Family Physician. 2003 July 15; 68(2): 228, 230. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12892344&dopt=Abstract
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JNC 7 urges aggressive management of hypertension. Author(s): Thompson CA. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2003 June 15; 60(12): 1206, 1209. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12845912&dopt=Abstract
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J-shaped relationship in hypertension. Author(s): Simon G. Source: Annals of Internal Medicine. 2003 January 7; 138(1): 78. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12513059&dopt=Abstract
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Key issues in the diagnosis and management of hypertension. Author(s): Yonga GO. Source: East Afr Med J. 2000 April; 77(4): 177-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12858898&dopt=Abstract
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Lack of association between angiotensin converting enzyme (ACE) genotype, serum ACE activity, and haemodynamics in patients with primary pulmonary hypertension. Author(s): Hoeper MM, Tacacs A, Stellmacher U, Lichtinghagen R. Source: Heart (British Cardiac Society). 2003 April; 89(4): 445-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12639879&dopt=Abstract
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Lack of association between angiotensin II type 1 receptor gene polymorphism and hypertension in Japanese. Author(s): Ono K, Mannami T, Baba S, Yasui N, Ogihara T, Iwai N. Source: Hypertens Res. 2003 February; 26(2): 131-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12627871&dopt=Abstract
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Lack of association between progressive supranuclear palsy and arterial hypertension: a clinicopathological study. Author(s): Colosimo C, Osaki Y, Vanacore N, Lees AJ. Source: Movement Disorders : Official Journal of the Movement Disorder Society. 2003 June; 18(6): 694-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12784275&dopt=Abstract
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Laparoscopic nephrectomy for renovascular hypertension in a 6-month-old infant. Author(s): Thomas PB, Hebra A, Chavin K. Source: Jsls. 2003 January-March; 7(1): 63-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12723001&dopt=Abstract
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L-arginine transport in humans with cortisol-induced hypertension. Author(s): Chin-Dusting JP, Ahlers BA, Kaye DM, Kelly JJ, Whitworth JA. Source: Hypertension. 2003 June; 41(6): 1336-40. Epub 2003 April 21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12707296&dopt=Abstract
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Left atrial mechanical function in patients with essential hypertension. Author(s): Erol MK, Yilmaz M, Acikel M, Karakelleoglu S. Source: Acta Cardiol. 2002 October; 57(5): 323-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12405568&dopt=Abstract
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Left ventricle is better suited as pulmonary ventricle in simple transposition with severe pulmonary hypertension. Author(s): Sharma R, Choudhary SK, Bhan A, Juneja R, Kothari SS, Saxena A, Venugopal P. Source: The Annals of Thoracic Surgery. 2002 November; 74(5): 1612-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12440617&dopt=Abstract
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Left ventricular concentric geometry as a risk factor in gestational hypertension. Author(s): Novelli GP, Valensise H, Vasapollo B, Larciprete G, Altomare F, Di Pierro G, Casalino B, Galante A, Arduini D. Source: Hypertension. 2003 March; 41(3): 469-75. Epub 2003 February 17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12623945&dopt=Abstract
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Left ventricular hypertrophy is associated with reduced vasodilatory capacity in the brachial artery in patients with longstanding hypertension. A LIFE substudy. Author(s): Olsen MH, Wachtell K, Hermann KL, Bella JN, Dige-Petersen H, Rokkedal J, Ibsen H. Source: Blood Pressure. 2002; 11(5): 285-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12458651&dopt=Abstract
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Left ventricular mass change during treatment and outcome in patients with essential hypertension. Author(s): Koren MJ, Ulin RJ, Koren AT, Laragh JH, Devereux RB. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 2002 December; 15(12): 1021-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12460696&dopt=Abstract
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Left ventricular remodeling and renal function in never-treated essential hypertension. Author(s): Fesler P, Du Cailar G, Ribstein J, Mimran A. Source: Journal of the American Society of Nephrology : Jasn. 2003 April; 14(4): 881-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12660322&dopt=Abstract
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Leptin and the central neural mechanisms of obesity hypertension. Author(s): Rahmouni K, G Haynes W. Source: Drugs Today (Barc). 2002 December; 38(12): 807-17. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12582470&dopt=Abstract
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Lifestyle modifications to prevent hypertension. Author(s): Logan AG. Source: Jama : the Journal of the American Medical Association. 2003 February 19; 289(7): 843; Author Reply 843-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12588260&dopt=Abstract
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Lifestyle modifications to prevent hypertension. Author(s): McGuffin M. Source: Jama : the Journal of the American Medical Association. 2003 February 19; 289(7): 843; Author Reply 843-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12588259&dopt=Abstract
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Linkage analysis of five candidate genes and essential hypertension in 106 Chinese nuclear families. Author(s): He X, Wang G, Huang W, Ding-Liang Z. Source: Journal of Human Hypertension. 2003 January; 17(1): 69-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12571619&dopt=Abstract
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Lipid lowering in hypertension and heart protection: observations from the AngloScandinavian Cardiac Outcomes Trial (ASCOT) and the Heart Protection Study. Author(s): Nadar S, Lim HS, Beevers DG, Lip GY. Source: Journal of Human Hypertension. 2002 December; 16(12): 815-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12522461&dopt=Abstract
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Lipid peroxidation is not increased in patients with untreated mild-to-moderate hypertension. Author(s): Cracowski JL, Baguet JP, Ormezzano O, Bessard J, Stanke-Labesque F, Bessard G, Mallion JM. Source: Hypertension. 2003 February; 41(2): 286-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12574096&dopt=Abstract
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Living transplantation using a kidney with a large cyst as curative treatment of donor's hypertension. Author(s): Veroux P, Veroux M, Puliatti C, Macarone M, Sorbello M, Valvo MC, Cappello D. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2002 December; 17(12): 2258-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12454244&dopt=Abstract
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Local cardiac renin-angiotensin system: hypertension and cardiac failure. Author(s): Varagic J, Frohlich ED. Source: Journal of Molecular and Cellular Cardiology. 2002 November; 34(11): 1435-42. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12431442&dopt=Abstract
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Long-lasting improvement of arterial hypertension after surgical treatment of a foramen magnum meningioma: case report. Author(s): Worner BA, Rahim T, Lange M, Fink U, Oeckler R. Source: Surgical Neurology. 2002 September-October; 58(3-4): 189-92; Discussion 193. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12480212&dopt=Abstract
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Long-term treatment with oral sildenafil in addition to continuous IV epoprostenol in patients with pulmonary arterial hypertension. Author(s): Stiebellehner L, Petkov V, Vonbank K, Funk G, Schenk P, Ziesche R, Block LH. Source: Chest. 2003 April; 123(4): 1293-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12684325&dopt=Abstract
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Long-time survival with HIV-related pulmonary arterial hypertension: a case report. Author(s): Alp S, Schlottmann R, Bauer TT, Schmidt WE, Bastian A. Source: Aids (London, England). 2003 July 25; 17(11): 1714-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12853763&dopt=Abstract
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Loosening the cuff: important new advances in modeling antihypertensive treatment effects in genetic studies of hypertension. Author(s): Palmer LJ. Source: Hypertension. 2003 February; 41(2): 197-8. Erratum In: Hypertension. 2003 March; 41(3): E3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12574080&dopt=Abstract
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Low birth weight as a risk factor for hypertension. Author(s): Lackland DT, Egan BM, Ferguson PL. Source: Journal of Clinical Hypertension (Greenwich, Conn.). 2003 March-April; 5(2): 133-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12671326&dopt=Abstract
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Low dose acetylsalicylic acid in prevention of pregnancy-induced hypertension and intrauterine growth retardation in women with bilateral uterine artery notches. Author(s): Smith JH. Source: Bjog : an International Journal of Obstetrics and Gynaecology. 2002 December; 109(12): 1421-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12510691&dopt=Abstract
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Low dose acetylsalicylic acid in prevention of pregnancy-induced hypertension and intrauterine growth retardation in women with bilateral uterine artery notches. Author(s): Coomarasamy A, Gee H, Khan KS. Source: Bjog : an International Journal of Obstetrics and Gynaecology. 2002 December; 109(12): 1420-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12504994&dopt=Abstract
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Low dose acetylsalicylic acid in prevention of pregnancy-induced hypertension and intrauterine growth retardation in women with bilateral uterine artery notches. Author(s): Somerset D. Source: Bjog : an International Journal of Obstetrics and Gynaecology. 2002 December; 109(12): 1420. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12504993&dopt=Abstract
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Low-density lipoprotein subfractions and cardiovascular risk in hypertension: relationship to endothelial dysfunction and effects of treatment. Author(s): Felmeden DC, Spencer CG, Blann AD, Beevers DG, Lip GY. Source: Hypertension. 2003 March; 41(3): 528-33. Epub 2003 February 24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12623954&dopt=Abstract
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Lower cognitive function in the presence of obesity and hypertension: the Framingham heart study. Author(s): Elias MF, Elias PK, Sullivan LM, Wolf PA, D'Agostino RB. Source: International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity. 2003 February; 27(2): 260-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12587008&dopt=Abstract
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Lymphocyte subpopulations in pregnancy complicated by hypertension. Author(s): Mahmoud F, Omu A, Abul H, El-Rayes S, Haines D. Source: Journal of Obstetrics and Gynaecology : the Journal of the Institute of Obstetrics and Gynaecology. 2003 January; 23(1): 20-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12623476&dopt=Abstract
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Malignant hypertension and hypertensive encephalopathy in primary aldosteronism caused by adrenal adenoma. Author(s): Bortolotto LA, Cesena FH, Jatene FB, Silva HB. Source: Arquivos Brasileiros De Cardiologia. 2003 July; 81(1): 97-100, 93-6. Epub 2003 July 31. English, Portuguese. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12908077&dopt=Abstract
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Malignant hypertension as a presenting symptom of Takayasu arteritis. Author(s): Wolak T, Szendro G, Golcman L, Paran E. Source: Mayo Clinic Proceedings. 2003 February; 78(2): 231-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12583535&dopt=Abstract
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Management of high blood pressure in African Americans: consensus statement of the Hypertension in African Americans Working Group of the International Society on Hypertension in Blacks. Author(s): Douglas JG, Bakris GL, Epstein M, Ferdinand KC, Ferrario C, Flack JM, Jamerson KA, Jones WE, Haywood J, Maxey R, Ofili EO, Saunders E, Schiffrin EL, Sica DA, Sowers JR, Vidt DG; Hypertension in African Americans Working Group of the International Society on Hypertension in Blacks. Source: Archives of Internal Medicine. 2003 March 10; 163(5): 525-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12622600&dopt=Abstract
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Management of hypertension and screening of renal complications by GPs in diabetic type 2 patients (France--2001). Author(s): Fagnani F, Souchet T, Labed D, Gaugris S, Hannedouche T, Grimaldi A. Source: Diabetes & Metabolism. 2003 February; 29(1): 58-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12629449&dopt=Abstract
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Management of hypertension in light of the new national guidelines. Author(s): Moser M. Source: Manag Care. 2003 August; 12(8 Suppl Hypertension): 12-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12971588&dopt=Abstract
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Management of pulmonary hypertension: physiological and pharmacological considerations for anesthesiologists. Author(s): Fischer LG, Van Aken H, Burkle H. Source: Anesthesia and Analgesia. 2003 June; 96(6): 1603-16. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12760982&dopt=Abstract
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Management of refractory hypertension. Author(s): Ram CV. Source: American Journal of Therapeutics. 2003 March-April; 10(2): 122-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12629590&dopt=Abstract
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Managing hypertension in patients with stroke. Are you prepared for labetalol infusion? Author(s): Harrington C. Source: Critical Care Nurse. 2003 June; 23(3): 30-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12830778&dopt=Abstract
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Managing hypertension. Author(s): Stanton AV. Source: The Practitioner. 2003 September; 247(1650): 712-5, 717-8, 721-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13677709&dopt=Abstract
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Managing hypertension: measurement and prevention. Author(s): Hurst R. Source: Nurs Times. 2002 September 17-23; 98(38): 38-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12355920&dopt=Abstract
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Managing hypertension--a real challenge in the new millennium. Author(s): Biswas TK, Biswas S. Source: J Indian Med Assoc. 2003 April; 101(4): 250. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12964643&dopt=Abstract
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Massive spontaneous perirenal hematoma and accelerated hypertension in a patient with polyarteritis nodosa. Author(s): Minardi D, Dessi-Fulgheri P, Sarzani R, Onesta M, Mucaj A, Branchi A, Giangiacomi M, Mantovani P, Muzzonigro G. Source: Urologia Internationalis. 2003; 70(3): 227-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12660463&dopt=Abstract
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Measuring hypertension control: NCQA and beyond. Author(s): Miller NH. Source: Manag Care. 2003 August; 12(8 Suppl Hypertension): 51-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12971593&dopt=Abstract
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Measuring the habitat as an indicator of socioeconomic position: methodology and its association with hypertension. Author(s): Galobardes B, Morabia A. Source: Journal of Epidemiology and Community Health. 2003 April; 57(4): 248-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12646538&dopt=Abstract
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Membrane fluidity and hypertension. Author(s): Tsuda K, Nishio I. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 2003 March; 16(3): 259-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12620708&dopt=Abstract
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Mendelian hypertension with brachydactyly as a molecular genetic lesson in regulatory physiology. Author(s): Luft FC, Toka O, Toka HR, Jordan J, Bahring S. Source: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 2003 October; 285(4): R709-14. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12959913&dopt=Abstract
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Mesalazine-associated benign intracranial hypertension in a patient with ulcerative colitis. Author(s): Rosa N, Giamundo A, Jura A, Iaccarino G, Romano A. Source: American Journal of Ophthalmology. 2003 July; 136(1): 212-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12834704&dopt=Abstract
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Mesenteric venous thrombosis causing jejunal stricture: secondary to hypercoagulable states and primary portal hypertension. Author(s): Chandra S, Dutta U, Das R, Vaiphei K, Nagi B, Singh K. Source: Digestive Diseases and Sciences. 2002 September; 47(9): 2017-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12353848&dopt=Abstract
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Metabolic abnormalities (hypertension, hyperglycemia and overweight), lifestyle (high energy intake and physical inactivity) and endometrial cancer risk in a Norwegian cohort. Author(s): Furberg AS, Thune I. Source: International Journal of Cancer. Journal International Du Cancer. 2003 May 10; 104(6): 669-76. Erratum In: Int J Cancer. 2003 May 10; 104(6): 799. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12640672&dopt=Abstract
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Microalbuminuria and hypertension with focus on type 1 and type 2 diabetes. Author(s): Mogensen CE. Source: Journal of Internal Medicine. 2003 July; 254(1): 45-66. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12823642&dopt=Abstract
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Microalbuminuria in hypertension. Author(s): Palatini P. Source: Current Hypertension Reports. 2003 June; 5(3): 208-14. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12724052&dopt=Abstract
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Microalbuminuria is closely related to impaired arterial elasticity in untreated patients with essential hypertension. Author(s): Tsioufis C, Tzioumis C, Marinakis N, Toutouzas K, Tousoulis D, Kallikazaros I, Stefanadis C, Toutouzas P. Source: Nephron. Clinical Practice [electronic Resource]. 2003; 93(3): C106-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12660419&dopt=Abstract
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Midtrimester triple-test levels in women with chronic hypertension and altered renal function. Author(s): Shenhav S, Gemer O, Sherman DJ, Peled R, Segal S. Source: Prenatal Diagnosis. 2003 February; 23(2): 166-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12575027&dopt=Abstract
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Might losartan reduce sudden cardiac death in diabetic patients with hypertension? Author(s): Aronow WS. Source: Lancet. 2003 August 23; 362(9384): 591-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12944056&dopt=Abstract
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Mild renal dysfunction and subclinical cardiovascular damage in primary hypertension. Author(s): Leoncini G, Viazzi F, Parodi D, Vettoretti S, Ratto E, Ravera M, Tomolillo C, Del Sette M, Bezante GP, Deferrari G, Pontremoli R. Source: Hypertension. 2003 July; 42(1): 14-8. Epub 2003 May 19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12756221&dopt=Abstract
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Moderate-term effect of epoprostenol on severe portopulmonary hypertension. Author(s): Kato H, Katori T, Nakamura Y, Kawarasaki H. Source: Pediatric Cardiology. 2003 January-February; 24(1): 50-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12574979&dopt=Abstract
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Modified endoscopic optic nerve decompression in idiopathic intracranial hypertension. Author(s): Gupta AK, Ganth MG, Gupta A. Source: The Journal of Laryngology and Otology. 2003 June; 117(6): 501-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12818064&dopt=Abstract
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Multicenter, open-label evaluation of hyperemia associated with use of bimatoprost in adults with open-angle glaucoma or ocular hypertension. Author(s): Abelson MB, Mroz M, Rosner SA, Dirks MS, Hirabayashi D. Source: Adv Ther. 2003 January-February; 20(1): 1-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12772813&dopt=Abstract
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Multiple actions of angiotensin II in hypertension: benefits of AT1 receptor blockade. Author(s): Schiffrin EL, Touyz RM. Source: Journal of the American College of Cardiology. 2003 September 3; 42(5): 911-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12957442&dopt=Abstract
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Myocardial ultrasonic backscatter in hypertension: relation to aldosterone and endothelin. Author(s): Kozakova M, Buralli S, Palombo C, Bernini G, Moretti A, Favilla S, Taddei S, Salvetti A. Source: Hypertension. 2003 February; 41(2): 230-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12574087&dopt=Abstract
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Negative regulators of sodium transport in the kidney: key factors in understanding salt-sensitive hypertension? Author(s): Rossier BC. Source: The Journal of Clinical Investigation. 2003 April; 111(7): 947-50. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12671041&dopt=Abstract
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Nephron number and primary hypertension. Author(s): Querfeld U, Niaudet P. Source: The New England Journal of Medicine. 2003 April 24; 348(17): 1717-9; Author Reply 1717-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12713000&dopt=Abstract
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Nephron number and primary hypertension. Author(s): O'Neill WC. Source: The New England Journal of Medicine. 2003 April 24; 348(17): 1717-9; Author Reply 1717-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12712999&dopt=Abstract
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Nephron number and primary hypertension. Author(s): Johnson RJ, Rodriguez-Iturbe B, Herrera-Acosta J. Source: The New England Journal of Medicine. 2003 April 24; 348(17): 1717-9; Author Reply 1717-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12711751&dopt=Abstract
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Nephron number in patients with primary hypertension. Author(s): Keller G, Zimmer G, Mall G, Ritz E, Amann K. Source: The New England Journal of Medicine. 2003 January 9; 348(2): 101-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12519920&dopt=Abstract
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Nephrotic proteinuria as a result of essential hypertension. Author(s): Obialo CI, Hewan-Lowe K, Fulong B. Source: Kidney & Blood Pressure Research. 2002; 25(4): 250-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12424428&dopt=Abstract
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Neurovascular compression associated with trigeminal neuralgia and systemic arterial hypertension: surgical treatment. Author(s): Sendeski M, Aguiar PH, Zanetti MV, Teixeira MJ, Cescato VA. Source: Stereotactic and Functional Neurosurgery. 2002; 79(3-4): 284-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12890987&dopt=Abstract
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New developments in the treatment of hypertension: are some antihypertensives more equal than others? Author(s): Gansevoort RT, Gans RO. Source: The Netherlands Journal of Medicine. 2003 May; 61(5 Suppl): 13-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12918545&dopt=Abstract
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Nicardipine to control neonatal hypertension during extracorporeal membrane oxygen support. Author(s): McBride BF, White CM, Campbell M, Frey BM. Source: The Annals of Pharmacotherapy. 2003 May; 37(5): 667-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12708943&dopt=Abstract
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Nitric oxide and portal hypertension. Author(s): Gonzalez-Abraldes J, Garcia-Pagan JC, Bosch J. Source: Metabolic Brain Disease. 2002 December; 17(4): 311-24. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12602508&dopt=Abstract
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Nitric oxide, cholesterol oxides and endothelium-dependent vasodilation in plasma of patients with essential hypertension. Author(s): Moriel P, Sevanian A, Ajzen S, Zanella MT, Plavnik FL, Rubbo H, Abdalla DS. Source: Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Medicas E Biologicas / Sociedade Brasileira De Biofisica . [et Al.]. 2002 November; 35(11): 1301-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12426629&dopt=Abstract
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No evidence that panic attacks are associated with the white coat effect in hypertension. Author(s): Davies SJ, Jackson PR, Ramsay LE, Ghahramani P, Palmer RL, Hippisley-Cox J. Source: Journal of Clinical Hypertension (Greenwich, Conn.). 2003 March-April; 5(2): 145-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12671328&dopt=Abstract
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Nonfunctioning islet cell tumor presenting with ascites and portal hypertension. Author(s): Dalvi AN, Rege SA, Bapat MR, Abraham P, Joshi AS, Bapat RD. Source: Indian J Gastroenterol. 2002 November-December; 21(6): 227-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12546175&dopt=Abstract
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Noninvasive delivery of inhaled nitric oxide therapy for late pulmonary hypertension in newborn infants with congenital diaphragmatic hernia. Author(s): Kinsella JP, Parker TA, Ivy DD, Abman SH. Source: The Journal of Pediatrics. 2003 April; 142(4): 397-401. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12712057&dopt=Abstract
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Noninvasive study of endothelial function in white coat hypertension. Author(s): Gomez-Cerezo J, Rios Blanco JJ, Suarez Garcia I, Moreno Anaya P, Garcia Raya P, Vazquez-Munoz E, Barbado Hernandez FJ. Source: Hypertension. 2002 September; 40(3): 304-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12215471&dopt=Abstract
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Nonnarcotic analgesic use and the risk of hypertension in US women. Author(s): Dedier J, Stampfer MJ, Hankinson SE, Willett WC, Speizer FE, Curhan GC. Source: Hypertension. 2002 November; 40(5): 604-8; Discussion 601-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12411450&dopt=Abstract
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Non-pharmacological treatment of hypertension in primary health care: a 2-year open randomized controlled trial of lifestyle intervention against hypertension in eastern Finland. Author(s): Kastarinen MJ, Puska PM, Korhonen MH, Mustonen JN, Salomaa VV, Sundvall JE, Tuomilehto JO, Uusitupa MI, Nissinen AM; LIHEF Study Group. Source: Journal of Hypertension. 2002 December; 20(12): 2505-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12473876&dopt=Abstract
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Non-pharmacological treatment of hypertension in women. Author(s): Costa FV. Source: Journal of Hypertension. 2002 May; 20 Suppl 2: S57-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12183854&dopt=Abstract
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Nonselective beta-blockers plus nitrates in portal hypertension: an open question. Author(s): Merkel C. Source: Hepatology (Baltimore, Md.). 2003 June; 37(6): 1254-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12774001&dopt=Abstract
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Not so benign intracranial hypertension. Author(s): Digre KB. Source: Bmj (Clinical Research Ed.). 2003 March 22; 326(7390): 613-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12649214&dopt=Abstract
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NSAIDs and hypertension. Author(s): Aisen PS, Schafer K, Grundman M, Thomas R, Thal LJ. Source: Archives of Internal Medicine. 2003 May 12; 163(9): 1115; Author Reply 1115-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12742818&dopt=Abstract
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Nurse-recorded and ambulatory blood pressure predicts treatment-induced reduction of left ventricular hypertrophy equally well in hypertension: results from the Swedish irbesartan left ventricular hypertrophy investigation versus atenolol (SILVHIA) study. Author(s): Nystrom F, Malmqvist K, Ohman KP, Kahan T. Source: Journal of Hypertension. 2002 August; 20(8): 1527-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12172314&dopt=Abstract
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Nutritional supplementation with Chlorella pyrenoidosa for mild to moderate hypertension. Author(s): Merchant RE, Andre CA, Sica DA. Source: Journal of Medicinal Food. 2002 Fall; 5(3): 141-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12495586&dopt=Abstract
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Obesity hypertension in children: a problem of epidemic proportions. Author(s): Sorof J, Daniels S. Source: Hypertension. 2002 October; 40(4): 441-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12364344&dopt=Abstract
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Obesity, diabetes, hypertension, and vegetarian status among Seventh-Day Adventists in Barbados: preliminary results. Author(s): Brathwaite N, Fraser HS, Modeste N, Broome H, King R. Source: Ethn Dis. 2003 Winter; 13(1): 34-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12723010&dopt=Abstract
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Obesity, hypertension, and insulin resistance. Author(s): Bloomgarden ZT. Source: Diabetes Care. 2002 November; 25(11): 2088-97. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12401761&dopt=Abstract
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Obesity, insulin resistance, diabetes, and cardiovascular risk in children: an American Heart Association scientific statement from the Atherosclerosis, Hypertension, and Obesity in the Young Committee (Council on Cardiovascular Disease in the Young) and the Diabetes Committee (Council on Nutrition, Physical Activity, and Metabolism). Author(s): Steinberger J, Daniels SR; American Heart Association Atherosclerosis, Hypertension, and Obesity in the Young Committee (Council on Cardiovascular Disease in the Young); American Heart Association Diabetes Committee (Council on Nutrition, Physical Activity, and Metabolism). Source: Circulation. 2003 March 18; 107(10): 1448-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12642369&dopt=Abstract
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Obstructive jaundice in a case of portal hypertension. Author(s): Chawla A, Maheshwari M, Parmar H. Source: The British Journal of Radiology. 2003 September; 76(909): 667-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14500285&dopt=Abstract
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Obstructive sleep apnea syndrome: its relationship with hypertension. Author(s): Krieger AC, Redeker NS. Source: The Journal of Cardiovascular Nursing. 2002 October; 17(1): 1-11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12358089&dopt=Abstract
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Ocular flutter in a patient with intracranial hypertension following cerebral venous thrombosis. Author(s): Shetty T. Source: Neurology. 2003 February 11; 60(3): 525; Author Reply 525. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12578949&dopt=Abstract
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Ocular flutter in a patient with intracranial hypertension following cerebral venous thrombosis. Author(s): Ploner CJ, Kupsch A. Source: Neurology. 2002 September 24; 59(6): 959. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12297595&dopt=Abstract
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Ocular Hypertension Treatment Study (OHTS) commentary. Author(s): Lee BL, Wilson MR; Ocular Hypertension Treatment Study (OHTS). Source: Current Opinion in Ophthalmology. 2003 April; 14(2): 74-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12698045&dopt=Abstract
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Ocular hypertension treatment study results could be misconstrued. Author(s): Weene LE. Source: Archives of Ophthalmology. 2003 July; 121(7): 1070; Author Reply 1070. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860828&dopt=Abstract
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Omapatrilat: still a promise in salt-sensitive hypertension? Author(s): Tojo A, Fujita T, Wilcox CS. Source: Journal of Hypertension. 2003 January; 21(1): 31-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544430&dopt=Abstract
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One-year, randomized study comparing bimatoprost and timolol in glaucoma and ocular hypertension. Author(s): Higginbotham EJ, Schuman JS, Goldberg I, Gross RL, VanDenburgh AM, Chen K, Whitcup SM; Bimatoprost Study Groups 1 and 2. Source: Archives of Ophthalmology. 2002 October; 120(10): 1286-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12365906&dopt=Abstract
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Ophthalmic features of idiopathic intracranial hypertension. Author(s): Hung HL, Kao LY, Huang CC. Source: Eye (London, England). 2003 August; 17(6): 793-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12928704&dopt=Abstract
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Optimal treatment of hypertension and cardiovascular risk reduction in African Americans: treatment approaches for outpatients. Author(s): Wright JT Jr, Douglas J. Source: Journal of Clinical Hypertension (Greenwich, Conn.). 2003 January-February; 5(1 Suppl 1): 18-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12556669&dopt=Abstract
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Optimal treatment of hypertension in African Americans. Reaching and maintaining target blood pressure goals. Author(s): Bakris GL, Ferdinand KC, Douglas JG, Sowers JR. Source: Postgraduate Medicine. 2002 October; 112(4): 73-4, 77-80, 83-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12400150&dopt=Abstract
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Oral beta-blockers for mild to moderate hypertension during pregnancy. Author(s): Magee LA, Duley L. Source: Cochrane Database Syst Rev. 2003; (3): Cd002863. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12917933&dopt=Abstract
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Oral L-arginine improves endothelial dysfunction in patients with essential hypertension. Author(s): Lekakis JP, Papathanassiou S, Papaioannou TG, Papamichael CM, Zakopoulos N, Kotsis V, Dagre AG, Stamatelopoulos K, Protogerou A, Stamatelopoulos SF. Source: International Journal of Cardiology. 2002 December; 86(2-3): 317-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12419572&dopt=Abstract
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Oral sildenafil as long-term adjunct therapy to inhaled iloprost in severe pulmonary arterial hypertension. Author(s): Ghofrani HA, Rose F, Schermuly RT, Olschewski H, Wiedemann R, Kreckel A, Weissmann N, Ghofrani S, Enke B, Seeger W, Grimminger F. Source: Journal of the American College of Cardiology. 2003 July 2; 42(1): 158-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12849677&dopt=Abstract
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Orlistat improves blood pressure control in obese subjects with treated but inadequately controlled hypertension. Author(s): Bakris G, Calhoun D, Egan B, Hellmann C, Dolker M, Kingma I; orlistat and resistant hypertension investigators. Source: Journal of Hypertension. 2002 November; 20(11): 2257-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12409965&dopt=Abstract
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Orthodeoxia without platypnea from interatrial defect associated with persistent left superior vena cava in the absence of pulmonary hypertension. Author(s): Maniscalco M, Dialetto G, Tufano G, Romano A, Sofia M. Source: Respiration; International Review of Thoracic Diseases. 2003 March-April; 70(2): 207-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12740520&dopt=Abstract
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Osteopathic manipulative medicine in the treatment of hypertension: an alternative, conventional approach. Author(s): Spiegel AJ, Capobianco JD, Kruger A, Spinner WD. Source: Heart Disease. 2003 July-August; 5(4): 272-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12877760&dopt=Abstract
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Outcome in 91 consecutive patients with pulmonary arterial hypertension receiving epoprostenol. Author(s): Kuhn KP, Byrne DW, Arbogast PG, Doyle TP, Loyd JE, Robbins IM. Source: American Journal of Respiratory and Critical Care Medicine. 2003 February 15; 167(4): 580-6. Epub 2002 November 21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12446266&dopt=Abstract
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Outcomes of treating hypertension in the elderly: a short commentary on current issues. Author(s): Weber MA. Source: The American Journal of Geriatric Cardiology. 2003 January-February; 12(1): 148. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12502910&dopt=Abstract
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Outcomes with nifedipine GITS or Co-amilozide in hypertensive diabetics and nondiabetics in Intervention as a Goal in Hypertension (INSIGHT). Author(s): Mancia G, Brown M, Castaigne A, de Leeuw P, Palmer CR, Rosenthal T, Wagener G, Ruilope LM; INSIGHT. Source: Hypertension. 2003 March; 41(3): 431-6. Epub 2003 February 17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12623939&dopt=Abstract
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Overestimation of pulmonary artery occlusion pressure in pulmonary hypertension due to partial occlusion. Author(s): Leatherman JW, Shapiro RS. Source: Critical Care Medicine. 2003 January; 31(1): 93-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12545000&dopt=Abstract
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Oxidant stress in pre-eclampsia and essential hypertension. Author(s): Kumar CA, Das UN. Source: J Assoc Physicians India. 2002 November; 50: 1372-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12583464&dopt=Abstract
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Oxidative stress in juvenile essential hypertension. Author(s): Turi S, Friedman A, Bereczki C, Papp F, Kovacs J, Karg E, Nemeth I. Source: Journal of Hypertension. 2003 January; 21(1): 145-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544446&dopt=Abstract
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Oxidative stress in kidney transplant patients with calcineurin inhibitor-induced hypertension: effect of ramipril. Author(s): Calo LA, Davis PA, Giacon B, Pagnin E, Sartori M, Riegler P, Antonello A, Huber W, Semplicini A. Source: Journal of Cardiovascular Pharmacology. 2002 October; 40(4): 625-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12352326&dopt=Abstract
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Oxidative stress in patients with primary pulmonary hypertension. Author(s): Irodova NL, Lankin VZ, Konovalova GK, Kochetov AG, Chazova IE. Source: Bulletin of Experimental Biology and Medicine. 2002 June; 133(6): 580-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12447471&dopt=Abstract
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Oxygen-15 positron-emission tomography for predicting selective delivery of a chemotherapeutic agent to hepatic cancers during angiotensin II-induced hypertension. Author(s): Koh T, Taniguchi H, Yamagishi H. Source: Cancer Chemotherapy and Pharmacology. 2003 April; 51(4): 349-58. Epub 2003 March 05. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12721763&dopt=Abstract
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Pathogenesis and consequences of essential hypertension. Author(s): Rao MS. Source: J Indian Med Assoc. 2003 April; 101(4): 251-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12964644&dopt=Abstract
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Pathological lesions causing pulmonary hypertension after closure of a ventricular septal defect. Author(s): Maeda K, Yamaki S, Nishiyama M, Murakami Y, Takahashi Y, Takamoto S. Source: Jpn J Thorac Cardiovasc Surg. 2003 September; 51(9): 430-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14529159&dopt=Abstract
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Pathophysiological insights from a case of reversible pulmonary arterial hypertension. Author(s): Mukerjee D, Kingdon E, Vanderpump M, Coghlan JG. Source: Journal of the Royal Society of Medicine. 2003 August; 96(8): 403-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12893860&dopt=Abstract
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Patient knowledge and awareness of hypertension is suboptimal: results from a large health maintenance organization. Author(s): Alexander M, Gordon NP, Davis CC, Chen RS. Source: Journal of Clinical Hypertension (Greenwich, Conn.). 2003 July-August; 5(4): 254-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12939565&dopt=Abstract
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Pharmacological modulation of platelet function in hypertension. Author(s): Blann AD, Nadar S, Lip GY. Source: Hypertension. 2003 July; 42(1): 1-7. Epub 2003 June 02. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12782643&dopt=Abstract
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Pharmacological rationale for the use of somatostatin and analogues in portal hypertension. Author(s): Reynaert H, Geerts A. Source: Alimentary Pharmacology & Therapeutics. 2003 August 15; 18(4): 375-86. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12940922&dopt=Abstract
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Plasma homocysteine levels in Indian patients with essential hypertension and their siblings. Author(s): Jain S, Ram H, Kumari S, Khullar M. Source: Renal Failure. 2003 March; 25(2): 195-201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12739826&dopt=Abstract
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Polymorphism in the promoter region of the insulin-like growth factor I gene is related to carotid intima-media thickness and aortic pulse wave velocity in subjects with hypertension. Author(s): Schut AF, Janssen JA, Deinum J, Vergeer JM, Hofman A, Lamberts SW, Oostra BA, Pols HA, Witteman JC, van Duijn CM. Source: Stroke; a Journal of Cerebral Circulation. 2003 July; 34(7): 1623-7. Epub 2003 June 05. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12791939&dopt=Abstract
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Portopulmonary hypertension in decompensated cirrhosis with refractory ascites. Author(s): Benjaminov FS, Prentice M, Sniderman KW, Siu S, Liu P, Wong F. Source: Gut. 2003 September; 52(9): 1355-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12912870&dopt=Abstract
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Portopulmonary hypertension: an increasingly important complication of cirrhosis. Author(s): Blendis L, Wong F. Source: Gastroenterology. 2003 August; 125(2): 622-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12891571&dopt=Abstract
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Positional change in blood pressure and 8-year risk of hypertension: the CARDIA Study. Author(s): Thomas RJ, Liu K, Jacobs DR Jr, Bild DE, Kiefe CI, Hulley SB. Source: Mayo Clinic Proceedings. 2003 August; 78(8): 951-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12911043&dopt=Abstract
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Potential causes of secondary hypertension. Author(s): Schapera CH. Source: American Family Physician. 2003 July 1; 68(1): 42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12887112&dopt=Abstract
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Preliminary characterisation of the promoter of the human p22(phox) gene: identification of a new polymorphism associated with hypertension. Author(s): Moreno MU, San Jose G, Orbe J, Paramo JA, Beloqui O, Diez J, Zalba G. Source: Febs Letters. 2003 May 8; 542(1-3): 27-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12729892&dopt=Abstract
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Prevalence, treatment, and control of hypertension in chronic hemodialysis patients in the United States. Author(s): Agarwal R, Nissenson AR, Batlle D, Coyne DW, Trout JR, Warnock DG. Source: The American Journal of Medicine. 2003 September; 115(4): 291-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12967694&dopt=Abstract
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Preventing heart disease by controlling hypertension: impact of hypertensive subtype, stage, age, and sex. Author(s): Wong ND, Thakral G, Franklin SS, L'Italien GJ, Jacobs MJ, Whyte JL, Lapuerta P. Source: American Heart Journal. 2003 May; 145(5): 888-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12766749&dopt=Abstract
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Prevention of hypertension and its complications: theoretical basis and guidelines for treatment. Author(s): Flack JM, Peters R, Shafi T, Alrefai H, Nasser SA, Crook E. Source: Journal of the American Society of Nephrology : Jasn. 2003 July; 14(7 Suppl 2): S92-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12819310&dopt=Abstract
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Primary hypertension-induced cerebellar encephalopathy causing obstructive hydrocephalus. Case report. Author(s): Verrees M, Fernandes Filho JA, Suarez JI, Ratcheson RA. Source: Journal of Neurosurgery. 2003 June; 98(6): 1307-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12816279&dopt=Abstract
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Primary pulmonary hypertension may be a heterogeneous disease with a second locus on chromosome 2q31. Author(s): Rindermann M, Grunig E, von Hippel A, Koehler R, Miltenberger-Miltenyi G, Mereles D, Arnold K, Pauciulo M, Nichols W, Olschewski H, Hoeper MM, Winkler J, Katus HA, Kubler W, Bartram CR, Janssen B. Source: Journal of the American College of Cardiology. 2003 June 18; 41(12): 2237-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12821254&dopt=Abstract
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Primary pulmonary hypertension. Author(s): Runo JR, Loyd JE. Source: Lancet. 2003 May 3; 361(9368): 1533-44. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12737878&dopt=Abstract
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Progression of uncontrolled hypertension and implications for managing its sequelae. Author(s): Kannel WB. Source: Manag Care. 2003 August; 12(8 Suppl Hypertension): 26-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12971590&dopt=Abstract
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Proximal pulmonary arterial and intrapulmonary radiologic features of Eisenmenger syndrome and primary pulmonary hypertension. Author(s): Perloff JK, Hart EM, Greaves SM, Miner PD, Child JS. Source: The American Journal of Cardiology. 2003 July 15; 92(2): 182-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860221&dopt=Abstract
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Psychosocial factors and risk of hypertension: the Coronary Artery Risk Development in Young Adults (CARDIA) study. Author(s): Yan LL, Liu K, Matthews KA, Daviglus ML, Ferguson TF, Kiefe CI. Source: Jama : the Journal of the American Medical Association. 2003 October 22; 290(16): 2138-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14570949&dopt=Abstract
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Pulmonary arterial hypertension in previously splenectomized patients with betathalassemic disorders. Author(s): Atichartakarn V, Likittanasombat K, Chuncharunee S, Chandanamattha P, Worapongpaiboon S, Angchaisuksiri P, Aryurachai K. Source: International Journal of Hematology. 2003 August; 78(2): 139-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12953808&dopt=Abstract
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Pulmonary arterial hypertension--the primary pulmonary hypertension syndromes. Author(s): Hey JC, Scharf SM. Source: Isr Med Assoc J. 2003 April; 5(4): 298-303. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14509142&dopt=Abstract
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Pulmonary hypertension in patients with end-stage renal disease. Author(s): Yigla M, Nakhoul F, Sabag A, Tov N, Gorevich B, Abassi Z, Reisner SA. Source: Chest. 2003 May; 123(5): 1577-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12740276&dopt=Abstract
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Pulmonary hypertension in pregnancy. Author(s): Kelley SE. Source: J Ark Med Soc. 2000 September; 97(3): 98-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12876809&dopt=Abstract
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Pulmonary hypertension in systemic sclerosis. Author(s): Denton CP, Black CM. Source: Rheumatic Diseases Clinics of North America. 2003 May; 29(2): 335-49, Vii. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12841298&dopt=Abstract
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Pulmonary hypertension in the setting of acquired systemic arteriovenous fistulas. Author(s): Bhatia S, Morrison JF, Bower TC, McGoon MD. Source: Mayo Clinic Proceedings. 2003 July; 78(7): 908-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12839088&dopt=Abstract
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Pulmonary hypertension: new perspectives. Author(s): Nauser TD, Stites SW. Source: Congestive Heart Failure (Greenwich, Conn.). 2003 May-June; 9(3): 155-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12826774&dopt=Abstract
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Pulmonary venous flow in pure mitral stenosis and sinus rhythm--does pulmonary hypertension alter pulmonary venous flow velocity? Author(s): Ha JW, Chung N, Goh CW, Jang KJ, Kang SM, Rim SJ, Jang Y, Shim WH, Cho SY, Kim SS. Source: Echocardiography (Mount Kisco, N.Y.). 2003 February; 20(2): 129-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12848677&dopt=Abstract
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Quality control of the blood pressure phenotype in the European Project on Genes in Hypertension. Author(s): Kuznetsova T, Staessen JA, Kawecka-Jaszcz K, Babeanu S, Casiglia E, Filipovsky J, Nachev C, Nikitin Y, Peleska J, O'Brien E. Source: Blood Pressure Monitoring. 2002 August; 7(4): 215-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12198337&dopt=Abstract
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Quality of hypertension treatment and risk of stroke in the general population. Author(s): Klungel OH. Source: Journal of Hypertension. 2002 October; 20(10): 1949-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12359971&dopt=Abstract
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Quality of life on randomized treatment for isolated systolic hypertension: results from the Syst-Eur Trial. Author(s): Fletcher AE, Bulpitt CJ, Thijs L, Tuomilehto J, Antikainen R, Bossini A, Browne J, Duggan J, Kawecka-Jaszcz K, Kivinen P, Sarti C, Terzoli L, Staessen JA; SystEur Trial Investigators. Source: Journal of Hypertension. 2002 October; 20(10): 2069-79. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12359987&dopt=Abstract
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Quantitative relationship between severity of pulmonary hypertension and LV diastolic function has been established. Author(s): Barasch E, Moustapha A, Kaushik V, Diaz S, Kang SH. Source: Journal of the American College of Cardiology. 2003 March 19; 41(6): 1066; Author Reply 1066-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12651061&dopt=Abstract
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Questioning race-based hypertension management. Author(s): Denberg TD. Source: Archives of Internal Medicine. 2003 July 28; 163(14): 1744-5; Author Reply 1745. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12885694&dopt=Abstract
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Questions remain regarding patients with aortic stenosis and severe pulmonary hypertension. Author(s): Rahimtoola SH. Source: Journal of the American College of Cardiology. 2003 May 21; 41(10): 1847-8; Author Reply 1848. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767677&dopt=Abstract
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QUICKI is a useful index of insulin sensitivity in subjects with hypertension. Author(s): Chen H, Sullivan G, Yue LQ, Katz A, Quon MJ. Source: American Journal of Physiology. Endocrinology and Metabolism. 2003 April; 284(4): E804-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12678026&dopt=Abstract
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Randomized clinical trial comparing intraocular pressure-lowering efficacy of bimatoprost and latanoprost in patients with ocular hypertension or glaucoma. Author(s): Eisenberg D. Source: American Journal of Ophthalmology. 2003 July; 136(1): 217; Author Reply 217-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12834708&dopt=Abstract
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Randomized, comparative, double-blind study of amlodipine vs. nicardipine as a treatment of isolated systolic hypertension in the elderly. Author(s): Mounier-Vehier C, Jaboureck O, Emeriau JP, Bernaud C, Clerson P, Carre A. Source: Fundamental & Clinical Pharmacology. 2002 December; 16(6): 537-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12685513&dopt=Abstract
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Reduced activity of the kallikrein-kinin system predominates over renin-angiotensin system overactivity in all conditions of sodium balance in essential hypertensives and family-related hypertension. Author(s): Sanchez R, Nolly H, Giannone C, Baglivo HP, Ramirez AJ. Source: Journal of Hypertension. 2003 February; 21(2): 411-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12569273&dopt=Abstract
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Reduced heart rate variability in hypertension: associations with lifestyle factors and plasma renin activity. Author(s): Virtanen R, Jula A, Kuusela T, Helenius H, Voipio-Pulkki LM. Source: Journal of Human Hypertension. 2003 March; 17(3): 171-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12624607&dopt=Abstract
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Refractory hypertension and sleep apnoea: effect of CPAP on blood pressure and baroreflex. Author(s): Logan AG, Tkacova R, Perlikowski SM, Leung RS, Tisler A, Floras JS, Bradley TD. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2003 February; 21(2): 241-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12608436&dopt=Abstract
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Refractory hypertension: recognition of psychiatric comorbidity. Author(s): Handler J. Source: Journal of Clinical Hypertension (Greenwich, Conn.). 2003 May-June; 5(3): 235-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12826793&dopt=Abstract
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Regression of electrocardiographic left ventricular hypertrophy by losartan versus atenolol: The Losartan Intervention for Endpoint reduction in Hypertension (LIFE) Study. Author(s): Okin PM, Devereux RB, Jern S, Kjeldsen SE, Julius S, Nieminen MS, Snapinn S, Harris KE, Aurup P, Edelman JM, Dahlof B; Losartan Intervention for Endpoint reduction in hypertension Study Investigations. Source: Circulation. 2003 August 12; 108(6): 684-90. Epub 2003 July 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12885747&dopt=Abstract
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Regression of left ventricular hypertrophy after treatment of hypertension: comparison of directed M-echocardiography with magnetic resonance imaging in quantification of serial mass changes. Author(s): Tse HF, Cheung BM, Ng W, Chan JK, Devereux RB, Lau CP. Source: Journal of Cardiac Failure. 2003 April; 9(2): 122-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12751133&dopt=Abstract
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Relation of C-reactive protein and fibrinogen to coronary artery calcium in subjects with systemic hypertension. Author(s): Kullo IJ, McConnell JP, Bailey KR, Kardia SL, Bielak LF, Peyser PA, Sheedy PF 2nd, Boerwinkle E, Turner ST. Source: The American Journal of Cardiology. 2003 July 1; 92(1): 56-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12842247&dopt=Abstract
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Relationship between eicosanoids and endothelin-1 in the pathogenesis of erythropoietin-induced hypertension in uremic rats. Author(s): Rodrigue ME, Moreau C, Lariviere R, Lebel M. Source: Journal of Cardiovascular Pharmacology. 2003 March; 41(3): 388-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12605017&dopt=Abstract
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Relationship between visceral fat accumulation and hypertension in obese men. Author(s): Watanabe J, Tochikubo O. Source: Clinical and Experimental Hypertension (New York, N.Y. : 1993). 2003 April; 25(3): 199-208. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12716082&dopt=Abstract
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Relationship of light to moderate alcohol consumption and risk of hypertension in Japanese male office workers. Author(s): Nakanishi N, Makino K, Nishina K, Suzuki K, Tatara K. Source: Alcoholism, Clinical and Experimental Research. 2002 July; 26(7): 988-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12170108&dopt=Abstract
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Relationship of urinary sodium/potassium excretion and calcium intake to blood pressure and prevalence of hypertension among older Chinese vegetarians. Author(s): Kwok TC, Chan TY, Woo J. Source: European Journal of Clinical Nutrition. 2003 February; 57(2): 299-304. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12571663&dopt=Abstract
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Relevance of the plasma renin hormonal control system that regulates blood pressure and sodium balance for correctly treating hypertension and for evaluating ALLHAT. Author(s): Laragh JH, Sealey JE. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 2003 May; 16(5 Pt 1): 407-15. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745204&dopt=Abstract
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Renal and cardiovascular responses to water immersion in essential hypertension: is there a role for the opioidergic system? Author(s): Coruzzi P, Parati G, Brambilla L, Brambilla V, Gualerzi M, Novarini A, Mancia G, Castiglioni P, Di Rienzo M. Source: Nephron. Physiology [electronic Resource]. 2003; 94(3): P51-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12902616&dopt=Abstract
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Renal sodium retention in portal hypertension and hepatorenal reflex: from practice to science. Author(s): Jimenez-Saenz M, Soria IC, Bernardez JR, Gutierrez JM. Source: Hepatology (Baltimore, Md.). 2003 June; 37(6): 1494; Author Reply 1494-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12774029&dopt=Abstract
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Renin-angiotensin gene polymorphism in children with uremia and essential hypertension. Author(s): Papp F, Friedman AL, Bereczki C, Haszon I, Kiss E, Endreffy E, Turi S. Source: Pediatric Nephrology (Berlin, Germany). 2003 February; 18(2): 150-4. Epub 2002 December 18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12579405&dopt=Abstract
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Renin-angiotensin-aldosterone system and G-protein beta-3 subunit gene polymorphisms in salt-sensitive essential hypertension. Author(s): Pamies-Andreu E, Ramirez-Lorca R, Stiefel Garcia-Junco P, Muniz-Grijalbo O, Vallejo-Maroto I, Garcia Morillo S, Miranda-Guisado ML, Ortiz JV, Carneado de la Fuente J. Source: Journal of Human Hypertension. 2003 March; 17(3): 187-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12624609&dopt=Abstract
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Renin-angiotensin-aldosterone system loci and multilocus interactions in youngonset essential hypertension. Author(s): Porto PI, Garcia SI, Dieuzeide G, Gonzalez C, Pirola CJ. Source: Clinical and Experimental Hypertension (New York, N.Y. : 1993). 2003 February; 25(2): 117-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12611423&dopt=Abstract
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Renovascular hypertension secondary to spontaneous renal artery dissection and treatment with stenting. Author(s): Bilge AK, Nisanci Y, Yilmaz E, Umman B, Hunerel D, Ozsaruhan O. Source: Int J Clin Pract. 2003 June; 57(5): 435-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12846352&dopt=Abstract
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Research into policy. Hypertension and diabetes mellitus in the Caribbean. Author(s): Forrester TE. Source: The West Indian Medical Journal. 2003 June; 52(2): 164-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12974071&dopt=Abstract
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Response of the right ventricle to acute pulmonary vasodilation predicts the outcome in patients with advanced heart failure and pulmonary hypertension. Author(s): Gavazzi A, Ghio S, Scelsi L, Campana C, Klersy C, Serio A, Raineri C, Tavazzi L. Source: American Heart Journal. 2003 February; 145(2): 310-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12595849&dopt=Abstract
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Response to travoprost in black and nonblack patients with open-angle glaucoma or ocular hypertension. Author(s): Netland PA, Robertson SM, Sullivan EK, Silver L, Bergamini MV, Krueger S, Weiner AL, Davis AA; Travoprost Study Groups. Source: Adv Ther. 2003 May-June; 20(3): 149-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12956257&dopt=Abstract
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Results of the betaxolol versus placebo treatment trial in ocular hypertension. Author(s): Kamal D, Garway-Heath D, Ruben S, O'Sullivan F, Bunce C, Viswanathan A, Franks W, Hitchings R. Source: Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Fur Klinische Und Experimentelle Ophthalmologie. 2003 March; 241(3): 196-203. Epub 2003 February 19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12644943&dopt=Abstract
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Reversible pulmonary hypertension and thalidomide therapy for multiple myeloma. Author(s): Younis TH. Source: British Journal of Haematology. 2003 April; 121(1): 191-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12670354&dopt=Abstract
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Reversible segmental portal hypertension--an unusual presentation of abdominal tuberculosis in a renal transplant recipient. Author(s): Varma PP, Seth AK, Kumar RS. Source: J Assoc Physicians India. 2003 February; 51: 218-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12725273&dopt=Abstract
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Risk of hypertension among women in the EPIC-Potsdam Study: comparison of relative risk estimates for exploratory and hypothesis-oriented dietary patterns. Author(s): Schulze MB, Hoffmann K, Kroke A, Boeing H. Source: American Journal of Epidemiology. 2003 August 15; 158(4): 365-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12915502&dopt=Abstract
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Role of endothelin-1 in hypertension. Author(s): Iglarz M, Schiffrin EL. Source: Current Hypertension Reports. 2003 April; 5(2): 144-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12642014&dopt=Abstract
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Role of kidney in hypertension. Author(s): Tripathi S, Tripathi K. Source: J Indian Med Assoc. 2003 April; 101(4): 260-2, 264-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12964647&dopt=Abstract
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Role of para-esophageal collateral veins in patients with portal hypertension based on the results of endoscopic ultrasonography and liver scintigraphy analysis. Author(s): Irisawa A, Obara K, Bhutani MS, Saito A, Shishido H, Shibukawa G, Takagi T, Yamamoto G, Seino O, Shishido F, Kasukawa R, Sato Y. Source: Journal of Gastroenterology and Hepatology. 2003 March; 18(3): 309-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12603532&dopt=Abstract
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Safety and efficacy of sibutramine in overweight Hispanic patients with hypertension. Author(s): Fanghanel G, Cortinas L, Sanchez-Reyes L, Gomez-Santos R, Campos-Franco E, Berber A. Source: Adv Ther. 2003 March-April; 20(2): 101-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12836810&dopt=Abstract
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Second International Symposium on Obesity and Hypertension: genetics and molecular mechanisms, 25-27 October 2001, Berlin, Germany. Author(s): Sharma AM. Source: International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity. 2002 October; 26(10): 1283-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12355322&dopt=Abstract
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Self-reported stress and subsequent hospital admissions as a result of hypertension, varicose veins and haemorrhoids. Author(s): Metcalfe C, Davey Smith G, Macleod J, Heslop P, Hart C. Source: Journal of Public Health Medicine. 2003 March; 25(1): 62-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12669921&dopt=Abstract
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Serious perinatal complications of non-proteinuric hypertension: an international, multicentre, retrospective cohort study. Author(s): Magee LA, von Dadelszen P, Bohun CM, Rey E, El-Zibdeh M, Stalker S, Ross S, Hewson S, Logan AG, Ohlsson A, Naeem T, Thornton JG, Abdalla M, Walkinshaw S, Brown M, Davis G, Hannah ME. Source: J Obstet Gynaecol Can. 2003 May; 25(5): 372-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12738978&dopt=Abstract
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Seventh report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7): resetting the hypertension sails. Author(s): Lenfant C, Chobanian AV, Jones DW, Roccella EJ; Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Source: Hypertension. 2003 June; 41(6): 1178-9. Epub 2003 May 19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12756222&dopt=Abstract
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Severe acidosis in a patient with type 2 diabetes mellitus, hypertension, and renal failure. Author(s): Kumar A, Nugent K, Kalakunja A, Pirtle F. Source: Chest. 2003 May; 123(5): 1726-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12740293&dopt=Abstract
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Severe portopulmonary hypertension in congenital hepatic fibrosis. Author(s): Hsu CM, Chiu CT, Lien JM, Ng KF. Source: Chang Gung Med J. 2003 March; 26(3): 193-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12790224&dopt=Abstract
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Severity of human hypertension in relation to the age in which high blood pressure makes its presumptive appearance. Author(s): Cugini P, Ferrari P, De Rosa R, Caliumi C, Delfini E, Colotto M, Fontana S, Mandolini C, Manetti L, Letizia C. Source: Clin Ter. 2003 January-February; 154(1): 21-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12854280&dopt=Abstract
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Shifting trends in the pharmacologic treatment of hypertension in a Nigerian tertiary hospital: a real-world evaluation of the efficacy, safety, rationality and pharmacoeconomics of old and newer antihypertensive drugs. Author(s): Adigun AQ, Ishola DA, Akintomide AO, Ajayi AA. Source: Journal of Human Hypertension. 2003 April; 17(4): 277-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12714973&dopt=Abstract
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Signaling molecules in pulmonary hypertension. Author(s): Hoeper MM. Source: The New England Journal of Medicine. 2003 May 22; 348(21): 2151; Author Reply 2151. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12761375&dopt=Abstract
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Sildenafil as a treatment for pulmonary hypertension. Author(s): Carroll WD, Dhillon R. Source: Archives of Disease in Childhood. 2003 September; 88(9): 827-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12937112&dopt=Abstract
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Sildenafil for long-term treatment of nonoperable chronic thromboembolic pulmonary hypertension. Author(s): Ghofrani HA, Schermuly RT, Rose F, Wiedemann R, Kohstall MG, Kreckel A, Olschewski H, Weissmann N, Enke B, Ghofrani S, Seeger W, Grimminger F. Source: American Journal of Respiratory and Critical Care Medicine. 2003 April 15; 167(8): 1139-41. Epub 2003 January 24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12684251&dopt=Abstract
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Sildenafil for treatment of lung fibrosis and pulmonary hypertension: a randomised controlled trial. Author(s): Ghofrani HA, Wiedemann R, Rose F, Schermuly RT, Olschewski H, Weissmann N, Gunther A, Walmrath D, Seeger W, Grimminger F. Source: Lancet. 2002 September 21; 360(9337): 895-900. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12354470&dopt=Abstract
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Sildenafil in secondary pulmonary hypertension. Author(s): Cubillos-Garzon LA, Casas JP, Morillo CA. Source: International Journal of Cardiology. 2003 May; 89(1): 101-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12727014&dopt=Abstract
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Sitaxsentan in pulmonary arterial hypertension. Author(s): Apostolopoulou SC, Rammos S. Source: Chest. 2003 May; 123(5): 1772; Author Reply 1772-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12740304&dopt=Abstract
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Six-month randomized clinical trial comparing intraocular pressure-lowering efficacy of bimatoprost and latanoprost in patients with ocular hypertension or glaucoma. Author(s): Fellenbaum PS. Source: American Journal of Ophthalmology. 2003 August; 136(2): 392; Author Reply 392-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12888081&dopt=Abstract
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Small intestinal motility disturbances and bacterial overgrowth in patients with liver cirrhosis and portal hypertension. Author(s): Gunnarsdottir SA, Sadik R, Shev S, Simren M, Sjovall H, Stotzer PO, Abrahamsson H, Olsson R, Bjornsson ES. Source: The American Journal of Gastroenterology. 2003 June; 98(6): 1362-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12818282&dopt=Abstract
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Socioeconomic aspects of spousal concordance for hypertension, obesity, and smoking in a community of Rio de Janeiro, Brazil. Author(s): Bloch KV, Klein CH, de Souza e Silva NA, Nogueira Ada R, Salis LH. Source: Arquivos Brasileiros De Cardiologia. 2003 February; 80(2): 179-86, 171-8. Epub 2003 February 25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12640511&dopt=Abstract
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Splicing mutation of the prostacyclin synthase gene in a family associated with hypertension. Author(s): Nakayama T, Soma M, Watanabe Y, Hasimu B, Kanmatsuse K, Kokubun S, Morrow JD, Oates JA. Source: Advances in Experimental Medicine and Biology. 2003; 525: 165-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12751759&dopt=Abstract
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Study design of HOMED-BP: hypertension objective treatment based on measurement by electrical devices of blood pressure. Author(s): Fujiwara T, Matsubara M, Ohkubo T, Imai Y. Source: Clinical and Experimental Hypertension (New York, N.Y. : 1993). 2003 April; 25(3): 143-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12716076&dopt=Abstract
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Study finds hypertension incidence is rising. Author(s): Levenson D. Source: Rep Med Guidel Outcomes Res. 2003 July 25; 14(14): 1-2, 6-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12931696&dopt=Abstract
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Subjects with essential hypertension are more sensitive to the inhibition of 11 betaHSD by liquorice. Author(s): Sigurjonsdottir HA, Manhem K, Axelson M, Wallerstedt S. Source: Journal of Human Hypertension. 2003 February; 17(2): 125-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12574791&dopt=Abstract
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Surgical and radiological management of renovascular hypertension in a developing country. Author(s): Kumar A, Dubey D, Bansal P, Sanjeevan KV, Gulati S, Jain S, Sharma K. Source: The Journal of Urology. 2003 September; 170(3): 727-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12913683&dopt=Abstract
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Susceptibility genes for hypertension and renal failure. Author(s): Freedman BI. Source: Journal of the American Society of Nephrology : Jasn. 2003 July; 14(7 Suppl 2): S192-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12819327&dopt=Abstract
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Symposium reporter 2003. New therapeutic options in the management of hypertension to heart failure. Orlando, Florida, USA, March 6, 2003. Author(s): Cohn JN, Velazquez EJ, Musher J. Source: Journal of the American Medical Directors Association. 2003; : 1-16, Quiz 17. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12924409&dopt=Abstract
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Symptomatic aortic stenosis: does systemic hypertension play an additional role? Author(s): Antonini-Canterin F, Huang G, Cervesato E, Faggiano P, Pavan D, Piazza R, Nicolosi GL. Source: Hypertension. 2003 June; 41(6): 1268-72. Epub 2003 April 21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12707297&dopt=Abstract
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Symptoms and the distress they cause: comparison of an aldosterone antagonist and a calcium channel blocking agent in patients with systolic hypertension. Author(s): Hollenberg NK, Williams GH, Anderson R, Akhras KS, Bittman RM, Krause SL. Source: Archives of Internal Medicine. 2003 July 14; 163(13): 1543-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860576&dopt=Abstract
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Systematic review of the prevention of delayed ischemic neurological deficits with hypertension, hypervolemia, and hemodilution therapy following subarachnoid hemorrhage. Author(s): Treggiari MM, Walder B, Suter PM, Romand JA. Source: Journal of Neurosurgery. 2003 May; 98(5): 978-84. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12744357&dopt=Abstract
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Systemic lupus erythematosus-associated pulmonary hypertension: good outcome following sildenafil therapy. Author(s): Molina J, Lucero E, Luluaga S, Bellomio V, Spindler A, Berman A. Source: Lupus. 2003; 12(4): 321-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12729058&dopt=Abstract
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Systolic hypertension in hemodialysis patients. Author(s): Agarwal R. Source: Seminars in Dialysis. 2003 May-June; 16(3): 208-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12753679&dopt=Abstract
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Targeting sources of superoxide and increasing nitric oxide bioavailability in hypertension. Author(s): Elmarakby AA, Williams JM, Pollock DM. Source: Curr Opin Investig Drugs. 2003 March; 4(3): 282-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12735229&dopt=Abstract
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The aggressive treatment of hypertension. Author(s): Ramanan SV. Source: Lancet. 2003 May 3; 361(9368): 1510. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12737860&dopt=Abstract
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The alteration of the pulmonary artery flow spectrum with pulmonary hypertension. Author(s): Guogan W, Baiping C, Hanying L, Rusheng C. Source: Chinese Medical Sciences Journal = Chung-Kuo I Hsueh K'o Hsueh Tsa Chih / Chinese Academy of Medical Sciences. 1999 December; 14(4): 220-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12894895&dopt=Abstract
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The burden of uncontrolled hypertension: morbidity and mortality associated with disease progression. Author(s): Cushman WC. Source: Journal of Clinical Hypertension (Greenwich, Conn.). 2003 May-June; 5(3 Suppl 2): 14-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12826766&dopt=Abstract
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The dilemma of immediate preoperative hypertension: to treat and operate, or to postpone surgery? Author(s): Weksler N, Klein M, Szendro G, Rozentsveig V, Schily M, Brill S, Tarnopolski A, Ovadia L, Gurman GM. Source: Journal of Clinical Anesthesia. 2003 May; 15(3): 179-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12770652&dopt=Abstract
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The economic impact of hypertension. Author(s): Elliott WJ. Source: Journal of Clinical Hypertension (Greenwich, Conn.). 2003 May-June; 5(3 Suppl 2): 3-13. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12826765&dopt=Abstract
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The ethnic characteristics and prevalence of diabetes mellitus, hypertension and hyperlipidaemia in patients who underwent coronary artery bypass grafting in Hospital Universiti Kebangsaan Malaysia. Author(s): Chiam P, Abdullah F, Chow HK, Adeeb SM, Yousafzai MS. Source: Med J Malaysia. 2002 December; 57(4): 460-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12733171&dopt=Abstract
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The hypertension management program: identifying opportunities for improvement. Author(s): Maue SK, Jackson JH 4th, Weiss BA, Rivo ML, Jhaveri V, Lennert B. Source: Journal of Clinical Hypertension (Greenwich, Conn.). 2003 May-June; 5(3 Suppl 2): 33-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12826768&dopt=Abstract
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The JNC 7 hypertension guidelines. Author(s): Phillips B. Source: Jama : the Journal of the American Medical Association. 2003 September 10; 290(10): 1314; Author Reply 1314-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12966119&dopt=Abstract
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The JNC 7 hypertension guidelines. Author(s): Majernick TG, Madden N. Source: Jama : the Journal of the American Medical Association. 2003 September 10; 290(10): 1314; Author Reply 1314-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12966118&dopt=Abstract
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The JNC 7 hypertension guidelines. Author(s): Murthy GD. Source: Jama : the Journal of the American Medical Association. 2003 September 10; 290(10): 1313; Author Reply 1314-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12966117&dopt=Abstract
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The JNC 7 hypertension guidelines. Author(s): Brotman DJ, Frost SD. Source: Jama : the Journal of the American Medical Association. 2003 September 10; 290(10): 1313-4; Author Reply 1314-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12966116&dopt=Abstract
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The JNC 7 hypertension guidelines. Author(s): Caspi O. Source: Jama : the Journal of the American Medical Association. 2003 September 10; 290(10): 1313; Author Reply 1314-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12966115&dopt=Abstract
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The JNC 7 hypertension guidelines. Author(s): Sackner-Bernstein J. Source: Jama : the Journal of the American Medical Association. 2003 September 10; 290(10): 1312; Author Reply 1314-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12966114&dopt=Abstract
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The JNC 7 hypertension guidelines. Author(s): Nelson MR. Source: Jama : the Journal of the American Medical Association. 2003 September 10; 290(10): 1312; Author Reply 1314-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12966113&dopt=Abstract
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The JNC 7 hypertension guidelines. Author(s): Ong HT. Source: Jama : the Journal of the American Medical Association. 2003 September 10; 290(10): 1312; Author Reply 1314-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12966112&dopt=Abstract
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The latest hypertension guidelines. Author(s): Hurley ML. Source: Rn. 2003 August; 66(8): 43-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13677682&dopt=Abstract
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The new hypertension guidelines from JNC 7: is the devil in the details? Author(s): Textor SC, Schwartz GL, Frye RL. Source: Mayo Clinic Proceedings. 2003 September; 78(9): 1078-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12962161&dopt=Abstract
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The nineteenth pregnancy in a patient with cor pulmonale and severe pulmonary hypertension: a management challenge. Author(s): Al-Mobeireek AF, Almutawa J, Alsatli RA. Source: Acta Obstetricia Et Gynecologica Scandinavica. 2003 July; 82(7): 676-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12790853&dopt=Abstract
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The psychosocial determinants of hypertension. Author(s): Kaplan MS, Nunes A. Source: Nutr Metab Cardiovasc Dis. 2003 February; 13(1): 52-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12772438&dopt=Abstract
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The relationship between catecholamines levels in mother and fetus, and pathogenesis of pregnancy-induced hypertension. Author(s): Zhang W, Zhao Y, Yin Y. Source: Chin Med J (Engl). 2003 July; 116(7): 1108-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12890395&dopt=Abstract
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The role of magnesium sulphate in the treatment of persistent pulmonary hypertension of the newborn. Author(s): Saidy KM, Itto BA. Source: Saudi Med J. 2003 July; 24(7): 801-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12883626&dopt=Abstract
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Thiazides could achieve major cost savings in uncomplicated hypertension. Author(s): Mayor S. Source: Bmj (Clinical Research Ed.). 2003 September 6; 327(7414): 521. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12958099&dopt=Abstract
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Thiazides first-line treatment for hypertension. Author(s): McCormack J, Rangno R, Wright JM. Source: Can Fam Physician. 2003 July; 49: 879. English, French. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12901483&dopt=Abstract
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Tibetan patients with essential hypertension caused by underlying oxidative metabolism dysfunction and depressed nitric oxide synthesis. Author(s): Li D, Wang X, Fu Z, Yu J, Da W, Peng S, Wang X. Source: Chin Med J (Engl). 2003 February; 116(2): 309-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12775254&dopt=Abstract
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Transient neurologic deficits associated with carbamazepine-induced hypertension. Author(s): Marini AM, Choi JY, Labutta RJ. Source: Clinical Neuropharmacology. 2003 July-August; 26(4): 174-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12897634&dopt=Abstract
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Treatment of chronic hypertension for the prevention of stroke. Author(s): Naidech AM, Weisberg LA. Source: Southern Medical Journal. 2003 April; 96(4): 359-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12916554&dopt=Abstract
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Treatment of pulmonary arterial hypertension: a step forward. Author(s): Sharma S. Source: Chest. 2003 July; 124(1): 8-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12853493&dopt=Abstract
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Treatment of severe pulmonary hypertension with inhaled iloprost. Author(s): Leuchte HH, Baumgartner RA, Behr J. Source: Annals of Internal Medicine. 2003 August 19; 139(4): 306. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12965995&dopt=Abstract
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Trends in prevalence, awareness, treatment, and control of hypertension in the United States, 1988-2000. Author(s): Hajjar I, Kotchen TA. Source: Jama : the Journal of the American Medical Association. 2003 July 9; 290(2): 199206. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12851274&dopt=Abstract
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Unclear and present danger. More vigilant hypertension treatment needed. Author(s): Diehl Y. Source: Adv Nurse Pract. 2002 October; 10(10): 73-6, 78. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12424888&dopt=Abstract
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Uncontrolled hypertension as a risk for coronary artery disease: patient characteristics and the role of physician intervention. Author(s): Hyman DJ, Pavlik VN. Source: Current Atherosclerosis Reports. 2003 March; 5(2): 131-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12573199&dopt=Abstract
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Uncontrolled hypertension due to volume overload contributes to higher left ventricular mass index in CAPD patients. Author(s): Koc M, Toprak A, Tezcan H, Bihorac A, Akoglu E, Ozener IC. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2002 September; 17(9): 1661-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12198220&dopt=Abstract
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Understanding primary pulmonary hypertension. Author(s): Berkowitz DS, Coyne NG. Source: Critical Care Nursing Quarterly. 2003 January-March; 26(1): 28-34. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12669944&dopt=Abstract
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Undertreatment of hypertension: a dozen reasons. Author(s): Gupta K, Gupta S. Source: Archives of Internal Medicine. 2002 October 28; 162(19): 2246-7; Author Reply 2247-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12390071&dopt=Abstract
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Unexplained pulmonary hypertension is associated with systolic arterial hypertension in patients undergoing routine Doppler echocardiography. Author(s): Finkelhor RS, Yang SX, Bosich G, Bahler RC. Source: Chest. 2003 March; 123(3): 711-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12628867&dopt=Abstract
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Unexplained systemic hypertension after closure of ductus arteriosus. Author(s): Litwin SB. Source: Asian Cardiovascular & Thoracic Annals. 2002 December; 10(4): 379. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12538299&dopt=Abstract
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Unexplained systemic hypertension after closure of ductus arteriosus. Author(s): Aydogan U. Source: Asian Cardiovascular & Thoracic Annals. 2002 December; 10(4): 378. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12538298&dopt=Abstract
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Unrecognized internal jugular vein obstruction: cause of fatal intracranial hypertension after tracheostomy? Author(s): Schummer W, Schummer C, Niesen WD. Source: Journal of Neurosurgical Anesthesiology. 2002 October; 14(4): 313-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12357090&dopt=Abstract
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Untreated hypertension among Australian adults: the 1999-2000 Australian Diabetes, Obesity and Lifestyle Study (AusDiab). Author(s): Briganti EM, Shaw JE, Chadban SJ, Zimmet PZ, Welborn TA, McNeil JJ, Atkins RC; Australian Diabetes, Obesity and Lifestyle Study (AusDiab). Source: The Medical Journal of Australia. 2003 August 4; 179(3): 135-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12885281&dopt=Abstract
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Unusual cause of intraoperative hypertension and tachycardia. Author(s): Unnikrishnan KP, Sinha PK, Neema PK. Source: Anesthesia and Analgesia. 2003 October; 97(4): 1196. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14500184&dopt=Abstract
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Update from the International Society on Hypertension in Blacks. Author(s): McCullough PA. Source: Reviews in Cardiovascular Medicine. 2002 Fall; 3(4): 192-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12650156&dopt=Abstract
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Urbanisation--the Hamlin's tune and hypertension. Author(s): Chakrabortti SCh. Source: J Indian Med Assoc. 2002 September; 100(9): 546. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12455384&dopt=Abstract
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Use of inhaled iloprost in a case of pulmonary hypertension during pediatric congenital heart surgery. Author(s): Muller M, Scholz S, Kwapisz M, Akinturk H, Thul J, Hempelmann G. Source: Anesthesiology. 2003 September; 99(3): 743-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12960561&dopt=Abstract
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Usefulness and limits of transthoracic echocardiography in the evaluation of patients with primary and chronic thromboembolic pulmonary hypertension. Author(s): Ghio S, Raineri C, Scelsi L, Recusani F, D'armini AM, Piovella F, Klersy C, Campana C, Vigano M, Tavazzi L. Source: Journal of the American Society of Echocardiography : Official Publication of the American Society of Echocardiography. 2002 November; 15(11): 1374-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12415231&dopt=Abstract
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Using the arteriolar Pressure Attenuation Index to predict ocular hypertension progression to open-angle glaucoma. Author(s): Cohen SL, Lee PP, Herndon LW, Challa P, Overbury O, Allingham RR. Source: Archives of Ophthalmology. 2003 January; 121(1): 33-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12523882&dopt=Abstract
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Uterine artery velocimetry in patients with gestational hypertension. Author(s): Frusca T, Soregaroli M, Platto C, Enterri L, Lojacono A, Valcamonico A. Source: Obstetrics and Gynecology. 2003 July; 102(1): 136-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12850619&dopt=Abstract
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Utility of ambulatory blood pressure monitoring for diagnosis of hypertension in liver allograft recipients. Author(s): Otero-Anton E, Padin E, Tome S, Gonzalez-Quintela A, Calvo C, Hermida RC, Ayala DE, Castroagudin JF, Delgado M, Varo E. Source: Transplantation Proceedings. 2003 March; 35(2): 718. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12644109&dopt=Abstract
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Utility of computed tomographic renal angiogram in the management of childhood hypertension. Author(s): Vade A, Agrawal R, Lim-Dunham J, Hartoin D. Source: Pediatric Nephrology (Berlin, Germany). 2002 September; 17(9): 741-7. Epub 2002 July 30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12215828&dopt=Abstract
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Uveal effusion and angle-closure glaucoma in primary pulmonary hypertension. Author(s): Krohn J, Bjune C. Source: American Journal of Ophthalmology. 2003 May; 135(5): 705-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12719080&dopt=Abstract
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Validation of the Microlife BP 3BTO-A oscillometric blood pressure monitoring device according to a modified British Hypertension Society protocol. Author(s): Cuckson AC, Reinders A, Shabeeh H, Shennan AH; British Hypertension Society. Source: Blood Pressure Monitoring. 2002 December; 7(6): 319-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12488652&dopt=Abstract
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Validation of the short form of the Spanish Hypertension Quality of Life Questionnaire (MINICHAL). Author(s): Badia X, Roca-Cusachs A, Dalfo A, Gascon G, Abellan J, Lahoz R, Varela C, Velasco O; MINICHAL Group. Source: Clinical Therapeutics. 2002 December; 24(12): 2137-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12581551&dopt=Abstract
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Validity of the JNC VI recommendations for the management of hypertension in a general population of Japanese elderly: the Hisayama study. Author(s): Arima H, Tanizaki Y, Kiyohara Y, Tsuchihashi T, Kato I, Kubo M, Tanaka K, Ohkubo K, Nakamura H, Abe I, Fujishima M, Iida M. Source: Archives of Internal Medicine. 2003 February 10; 163(3): 361-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12578518&dopt=Abstract
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Valsartan/hydrochlorothiazide: a review of its pharmacology, therapeutic efficacy and place in the management of hypertension. Author(s): Wellington K, Faulds DM. Source: Drugs. 2002; 62(13): 1983-2005. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12215069&dopt=Abstract
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Value of rilmenidine therapy and its combination with perindopril on blood pressure and left ventricular hypertrophy in patients with essential hypertension (VERITAS). Author(s): Farsang C, Lengyel M, Borbas S, Zorandi A, Dienes BS; VERITAS Investigators. Source: Current Medical Research and Opinion. 2003; 19(3): 205-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12803735&dopt=Abstract
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Variant of pre-clinical Cushing's syndrome: hypertension and hypokalemia associated with normoreninemic normoaldosteronism. Author(s): Yamakita N, Murai T, Miyamoto K, Matsunami H, Ikeda T, Sasano H, Mune T, Yasuda K. Source: Hypertens Res. 2002 July; 25(4): 623-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12358151&dopt=Abstract
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Variation at the aldosterone synthase (CYP11B2) locus contributes to hypertension in subjects with a raised aldosterone-to-renin ratio. Author(s): Lim PO, Macdonald TM, Holloway C, Friel E, Anderson NH, Dow E, Jung RT, Davies E, Fraser R, Connell JM. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 September; 87(9): 4398-402. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12213905&dopt=Abstract
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Variceal bleeding and portal hypertension: has there been any progress in the last 12 months? Author(s): Seewald S, Mendoza G, Seitz U, Salem O, Soehendra N. Source: Endoscopy. 2003 February; 35(2): 136-44. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12561007&dopt=Abstract
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Vascular abnormalities in salt-sensitive hypertension. Author(s): de la Sierra A. Source: Current Hypertension Reports. 2003 April; 5(2): 93-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12642006&dopt=Abstract
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Vascular disease, hypertension, and prevention: "from endothelium to clinical events". Author(s): Hirsch AT. Source: Journal of the American College of Cardiology. 2003 July 16; 42(2): 377-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875780&dopt=Abstract
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Vasoactive intestinal peptide as a new drug for treatment of primary pulmonary hypertension. Author(s): Petkov V, Mosgoeller W, Ziesche R, Raderer M, Stiebellehner L, Vonbank K, Funk GC, Hamilton G, Novotny C, Burian B, Block LH. Source: The Journal of Clinical Investigation. 2003 May; 111(9): 1339-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12727925&dopt=Abstract
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Vasoactive modulators during and after craniotomy: relation to postoperative hypertension. Author(s): Olsen KS, Pedersen CB, Madsen JB, Ravn LI, Schifter S. Source: Journal of Neurosurgical Anesthesiology. 2002 July; 14(3): 171-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12172288&dopt=Abstract
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Vasoconstricting effect of angiotensin II in human hand veins: influence of aging, diabetes mellitus and hypertension. Author(s): Harada K, Ohmori M, Fujimura A. Source: Hypertens Res. 2002 September; 25(5): 683-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12452319&dopt=Abstract
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Venous hypertension following average arterious-venous fistula for haemodialysis. Author(s): Kojecky Z, Utikal P, Sekanina Z, Kocher M, Buriankova E. Source: Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2002 December; 146(2): 77-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12572902&dopt=Abstract
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Verification of 525 coding SNPs in 179 hypertension candidate genes in the Japanese population: identification of 159 SNPs in 93 genes. Author(s): Okuda T, Fujioka Y, Kamide K, Kawano Y, Goto Y, Yoshimasa Y, Tomoike H, Iwai N, Hanai S, Miyata T. Source: Journal of Human Genetics. 2002; 47(8): 387-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12181638&dopt=Abstract
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Visual evoked potentials in patients with Graves' ophthalmopathy complicated by ocular hypertension and suspect glaucoma or dysthyroid optic neuropathy. Author(s): Ambrosio G, Ferrara G, Vitale R, De Marco R. Source: Documenta Ophthalmologica. Advances in Ophthalmology. 2003 March; 106(2): 99-104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12678273&dopt=Abstract
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Visual field testing in patients with ocular hypertension and localized RNFL defects. Author(s): Rossetti L, Miglior S, Incarnato N, Fogangnolo P, Orzalesi N. Source: Acta Ophthalmologica Scandinavica. Supplement. 2002; 236: 27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12390122&dopt=Abstract
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Visual-field loss with optic nerve drusen and ocular hypertension: a case report. Author(s): Spalding JM. Source: Optometry. 2002 January; 73(1): 24-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12363235&dopt=Abstract
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Vitamin A in the cerebrospinal fluid of patients with and without idiopathic intracranial hypertension. Author(s): Warner JE, Bernstein PS, Yemelyanov A, Alder SC, Farnsworth ST, Digre KB. Source: Annals of Neurology. 2002 November; 52(5): 647-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12402264&dopt=Abstract
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Vitamin C hypertension. Author(s): Temple RJ. Source: American Journal of Therapeutics. 2003 May-June; 10(3): 234-5; Author Reply 235. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12756434&dopt=Abstract
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Vitamin E prevents extensive lipid peroxidation in patients with hypertension. Author(s): Brockes C, Buchli C, Locher R, Koch J, Vetter W. Source: British Journal of Biomedical Science. 2003; 60(1): 5-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12680623&dopt=Abstract
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What defines an adolescent as having hypertension? Author(s): Materson BJ. Source: Journal of Hypertension. 2003 January; 21(1): 13-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544425&dopt=Abstract
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What is the meaning of LIFE? Implications of the Losartan Intervention for Endpoint reduction in hypertension trial for heart failure physicians. Author(s): Massie BM. Source: Journal of Cardiac Failure. 2002 August; 8(4): 197-201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12397565&dopt=Abstract
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When can the practicing physician suspect white coat hypertension? Statement from the Working Group on Blood Pressure Monitoring of the European Society of Hypertension. Author(s): Verdecchia P, O'Brien E, Pickering T, Staessen JA, Parati G, Myers M, Palatini P; European Society of Hypertension Working Group on Blood Pressure Monitoring. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 2003 January; 16(1): 87-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12517690&dopt=Abstract
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White coat effect and white coat hypertension in pediatric patients. Author(s): Matsuoka S, Kawamura K, Honda M, Awazu M. Source: Pediatric Nephrology (Berlin, Germany). 2002 November; 17(11): 950-3. Epub 2002 October 29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12432440&dopt=Abstract
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White coat hypertension and nursing care. Author(s): Alves LM, Nogueira MS, Veiga EV, de Godoy S, Carnio EC. Source: Can J Cardiovasc Nurs. 2003; 13(3): 29-34. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14508916&dopt=Abstract
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White coat hypertension in treated hypertensives: a three year follow-up study. Author(s): MacDonald MB, Laing GP, Wilson MP, Wilson TW. Source: Can J Cardiovasc Nurs. 2003; 13(2): 24-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12802835&dopt=Abstract
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White coat hypertension in Zimbabwean African women. Author(s): Bhagat K. Source: East Afr Med J. 2000 August; 77(8): 452-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12862073&dopt=Abstract
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White coat hypertension: understanding the concept and examining the significance. Author(s): Tsai PS. Source: Journal of Clinical Nursing. 2002 November; 11(6): 715-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12427175&dopt=Abstract
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White coat hypertension'--should it be treated or not? Author(s): Pickering T. Source: Cleve Clin J Med. 2002 August; 69(8): 584-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12184466&dopt=Abstract
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White-coat effect in normotension and hypertension. Author(s): Zakopoulos NA, Kotsis VT, Pitiriga VCh, Toumanidis ST, Lekakis JP, Nanas SN, Vemmos KN, Stamatelopoulos SF, Moulopoulos SD. Source: Blood Pressure Monitoring. 2002 October; 7(5): 271-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12409886&dopt=Abstract
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White-coat hypertension and normotension in the League of Hypertension of the Hospital das Clinicas, FMUSP: prevalence, clinical and demographic characteristics. Author(s): Segre CA, Ueno RK, Warde KR, Accorsi TA, Miname MH, Chi CK, Pierin AM, Mion Junior D. Source: Arquivos Brasileiros De Cardiologia. 2003 February; 80(2): 117-26. Epub 2003 February 25. English, Portuguese. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12640506&dopt=Abstract
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Why beta-blockers are not cardioprotective in elderly patients with hypertension. Author(s): Grossman E, Messerli FH. Source: Current Cardiology Reports. 2002 November; 4(6): 468-73. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12379165&dopt=Abstract
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Why not prescribe the best drugs for hypertension now? Author(s): Wong SY, McInnes GT, MacDonald TM. Source: Journal of Human Hypertension. 2003 July; 17(7): 505-11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12821958&dopt=Abstract
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Why we can't translate clinical trials into clinical practice in hypertension. Author(s): Resnick LM. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 2003 May; 16(5 Pt 1): 421-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745206&dopt=Abstract
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CHAPTER 2. NUTRITION AND HYPERTENSION Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and hypertension.
Finding Nutrition Studies on Hypertension The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail:
[email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “hypertension” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.
7
Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.
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The following is a typical result when searching for recently indexed consumer information on hypertension: •
Authorized health claims. Source: FDA-consumer (USA). (Nov-December 1998). volume 32(6) page 19-21. calcium osteodystrophy sodium hypertension diet fats neoplasms saturated fats cholesterol heart diseases risk dietary fibres solubility cereals grain fruits vegetables folic acid dental caries sugar alcohols 0362-1332
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Diet for keeping blood pressure down. Source: Tufts-University-diet-and-nutrition-letter (USA). (July 1996). volume 14(5) page 6. diet blood pressure hypertension weight reduction alcoholic beverages physical activity potassium sodium chloride common salt 0747-4105
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Effects of individual fatty acids on chronic diseases. Author(s): Penn State University. Source: Jonnalagadda, S.S. Mustad, V.A. Yu, S. Etherton, T.D. Kris Etherton, P.M. Nutrition-today (USA). (June 1996). volume 31(3) page 90-106. fatty acids food consumption diet fats nutrients nutrient intake heart diseases hypertension neoplasms diabetes thrombosis chronic course immune response saturated fatty acids unsaturated fatty acids risk 0029-666X
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For men only: a primer on your unique nutrition concerns. Source: Helm, J. Environmental-nutrition (USA). (June 1997). volume 20(6) page 1, 4-5. men nutritional requirements diet foods neoplasms prostate hypertension adipose tissues overweight osteodystrophy disease control iron folic acid pyridoxine proteins zinc 0893-4452
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Genetic variation and nutrition. 2. Genetic variation, nutrition, and chronic diseases. Author(s): Center for Genetics Nutrition and Health, Washington, DC. Source: Simopoulos, A.P. Nutrition-today (USA). (October 1995). volume 30(5) page 194206. genotype environment interaction overweight carcinomas autoimmune diseases chronic course genetic variation pathogenesis risk hypertension diet families genetic disorders disease control recommended dietary allowances diabetes osteodystrophy 0029-666X
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Good news about what to eat to take control of your blood pressure. Source: Walsh, J. Environmental-nutrition (USA). (December 1998). volume 21(12) page 1, 6. diet food intake common salt hypertension clinical trials human nutrition 0893-4452
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One nation, under pressure. Source: Liebman, B. Nutrition-action-health-letter (USA). (Jul-August 1995). volume 22(6) page 1, 4-9. blood pressure hypertension risk therapeutic diets sodium weight reduction physical activity 0885-7792
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Reexamining cholesterol and sodium recommendations. Source: Callaway, W. Nutrition-today (USA). (October 1994). volume 29(5) page 32-36. cholesterol sodium recommended dietary allowances diet blood lipids cardiovascular diseases hypertension case studies 0029-666X
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Scouting for sodium: and other nutrients important to blood pressure. Source: Kurtzweil, P. FDA-consumer (USA). (September 1994). volume 28(7) page 18-22. usa sodium blood pressure hypertension therapeutic diets nutrition labelling 0362-1332
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The fetal origins of adult disease. Author(s): University of Southampton, Southampton, England.
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Source: Barker, D.J.P. Nutrition-today (USA). (June 1996). volume 31(3) page 108-114. embryonic development mothers human nutrition malnutrition overweight adults heart diseases birth weight diabetes hypertension cardiovascular diseases muscles growth infants body measurements placenta multiple births 0029-666X •
To shake or not to shake: EN takes another look at salt. Source: Ternus, M. Environmental-nutrition (USA). (September 1996). volume 19(9) page 1, 4. sodium chloride common salt nutritive value osteodystrophy flavour enhancers hypertension risk nutrient excesses meal patterns dietary guidelines age recommended dietary allowances calcium absorption nutrient intake men women 08934452
Additional consumer oriented references include: •
Array of drugs tames hypertension. Lessening the pressure. Source: Kurtzweil, P FDA-Consum. 1999 Jul-August; 33(4): 18-23 0362-1332
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Calcium and hypertension: does a relationship exist. Source: Thomson, A.B.R. Nutr-Today. Baltimore, Md. : Williams & Wilkins. July/August 1989. volume 24 (4) page 21-26. 0029-666X
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Diabetes and hypertension. Source: Beach, R.S. Diabetes-Forecast. Alexandria, Va. : American Diabetes Association. April 1989. volume 42 (4) page 54-60. charts. 0095-8301
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I am undergoing treatment for hypertension and have been taking 200 mg of vitamin E daily for the past few years. I read that even lower doses might raise my risk of having a hemorrhagic stroke. Is this true? Source: Goldfinger, S E Harv-Health-Lett. 1999 January; 24(3): 3 1052-1577
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I have mild hypertension and my doctor recommended I eat bananas and drink orange juice. Why? Source: Anonymous Johns-Hopkins-Med-Lett-Health-After-50. 1999 August; 11(6): 8 1042-1882
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I recently read that potassium supplements can reduce blood pressure. What is your opinion? I have borderline hypertension, which I'm trying to control with diet and exercise. Source: Robb Nicholson, C Harv-Womens-Health-Watch. 1999 January; 6(5): 8 1070910X
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Magnesium and other nutrient deficiencies as possible causes of hypertension and low birthweight. Source: Wynn, A Wynn, M Nutr-Health. 1988; 6(2): 69-88 0260-1060
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Recommendations updated for hypertension. Source: Anonymous Harv-Health-Lett. 1998 January; 23(3): 6-7 1052-1577
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Reduced cardiovascular morbidity and mortality in hypertensive diabetic patients on first-line therapy with an ACE inhibitor compared with a diuretic/beta-blocker-based treatment regimen: a subanalysis of the Captopril Prevention Project. Author(s): Department of Medicine, University of Kuopio, Kuopio, Finland.
[email protected] Source: Niskanen, L Hedner, T Hansson, L Lanke, J Niklason, A Diabetes-Care. 2001 December; 24(12): 2091-6 0149-5992
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The brown eyes are from Dad, the hypertension from Mom. Source: Warshaw, H. Environ-Nutr. New York, N.Y. : Environmental Nutrition, Inc. October 1990. volume 13 (10) page 1, 6. 0893-4452
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Urinary transforming growth factor-beta excretion in patients with hypertension, type 2 diabetes, and elevated albumin excretion rate: effects of angiotensin receptor blockade and sodium restriction. Author(s): University of Melbourne, Department of Medicine at Austin, Victoria, Australia. Source: Houlihan, C A Akdeniz, A Tsalamandris, C Cooper, M E Jerums, G Gilbert, R E Diabetes-Care. 2002 June; 25(6): 1072-7 0149-5992
The following information is typical of that found when using the “Full IBIDS Database” to search for “hypertension” (or a synonym): •
Immunoreactivity and inhibition of angiotensin I converting enzyme and lactococcal oligopeptidase by peptides from cheese. Author(s): Agricultural Univ. of Norway, As. Dept. of Food Science Polish Academy of Sciences, Poznan (Poland). Inst. of Food Science Source: Stepaniak, L. SorhAugust, T. Jedrychowski, L. Wroblewska, B. Italian-Journalof-Food-Science (Italy). (2001). volume 13(4) page 373-381. cheese hypertension inhibition immunological techniques analytical methods lactococcus lactis enzymes enzymatic analysis hplc peptides 1120-1770
Additional physician-oriented references include: •
A comparative clinical study of latanoprost and isopropyl unoprostone in Japanese patients with primary open-angle glaucoma and ocular hypertension. Author(s): Department of Opthalmology and Visual Science, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan. Source: Tsukamoto, H Mishima, H K Kitazawa, Y Araie, M Abe, H Negi, A J-Glaucoma. 2002 December; 11(6): 497-501 1057-0829
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A nested case-control study on the high-normal blood pressure as a risk factor of hypertension in Korean middle-aged men. Author(s): Department of Preventive Medicine, Cheju National University College of Medicine, Cheju, Korea.
[email protected] Source: Bae, J M Ahn, Y O J-Korean-Med-Sci. 2002 June; 17(3): 328-36 1011-8934
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Activation of hypothalamic angiotensin receptors produces pressor responses via cholinergic inputs to the rostral ventrolateral medulla in normotensive and hypertensive rats. Source:
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Altered vascular function in fetal programming of hypertension. Author(s): Research Center, Hopital Sainte-Justine, Department of Pediatrics and Pharmacology, Universite de Montreal, Montreal, Canada. Source: Lamireau, D Nuyt, A M Hou, X Bernier, S Beauchamp, M Gobeil, F Jr Lahaie, I Varma, D R Chemtob, S Stroke. 2002 December; 33(12): 2992-8 1524-4628
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Antihypertensive effect of sesamin. IV. Inhibition of vascular superoxide production by sesamin. Author(s): Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Takatsuki, Japan.
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Source: Nakano, D Itoh, C Takaoka, M Kiso, Y Tanaka, T Matsumura, Y Biol-PharmBull. 2002 September; 25(9): 1247-9 0918-6158 •
Antihypertensive effects of valsartan/hydrochlorothiazide combination in essential hypertension. Source: Schmidt, A Adam, S A Kolloch, R Weidinger, G Handrock, R Blood-Press. 2001; 10(4): 230-7 0803-7051
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Blood pressure response to antihypertensive agents related to baseline blood pressure. Author(s): Cardiovascular Unit, Department of Medicine, Bangkok Metropolitan Administration Medical College and Vajira Hospital, Bangkok 10300, Thailand. Source: Sermswan, A Uboldejpracharak, Y Suthichaiyakul, T Sukontasarn, A Buranakitcharoen, P J-Med-Assoc-Thai. 2002 October; 85(10): 1113-20 0125-2208
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Cardiovascular effects of the essential oil of Mentha x villosa in DOCA-salthypertensive rats. Author(s): Departamento de Fisiologia e Farmacologia, Centro de Ciencias Biologicas, Universidade Federal de Pernambuco, Recife-PE, Brasil.
[email protected] Source: Lahlou, S Carneiro Leao, R F Leal Cardoso, J H Phytomedicine. 2002 December; 9(8): 715-20 0944-7113
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Combination therapy with an angiotensin-converting enzyme (ACE) inhibitor and a calcium antagonist: beyond the renoprotective effects of ACE inhibitor monotherapy in a spontaneous hypertensive rat with renal ablation. Author(s): Department of Internal Medicine and Rehabilitation Science, Tohoku University Graduate School of Medicine, Sendai, Japan.
[email protected] Source: Kanazawa, M Kohzuki, M Yoshida, K Kurosawa, H Minami, N Saito, T Yasujima, M Abe, K Hypertens-Res. 2002 May; 25(3): 447-53 0916-9636
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Combination treatment with a calcium channel blocker and an angiotensin blocker in a rat systolic heart failure model with hypertension. Author(s): Department of Pharmacology, Osaka City University Medical School, Japan. Source: Namba, M Kim, S Zhan, Y Nakao, T Iwao, H Hypertens-Res. 2002 May; 25(3): 461-6 0916-9636
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Comparison of latanoprost, brimonidine and a fixed combination of timolol and dorzolamide on circadian intraocular pressure in patients with primary open-angle glaucoma and ocular hypertension. Author(s): University Eye Clinic, San Paolo Hospital, Milan. Source: Orzalesi, N Rossetti, I Bottoli, A Invernizzi, T Fumagalli, E Fogagnolo, P ActaOphthalmol-Scand-Suppl. 2002; 236: 55 1395-3931
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Darusentan: an effective endothelinA receptor antagonist for treatment of hypertension. Source:
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Decreased 4-aminopyridine sensitive K+ currents in endothelial cells from hypertensive rats. Author(s): Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Source: Sadanaga, T Ohya, Y Ohtsubo, T Goto, K Fujii, K Abe, I Hypertens-Res. 2002 July; 25(4): 589-96 0916-9636
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Differential effects of a long-acting angiotensin converting enzyme inhibitor (temocapril) and a long-acting calcium antagonist (amlodipine) on ventricular ectopic beats in older hypertensive patients. Author(s): Department of Internal Medicine, Nishiarita Kyoritsu Hospital, Saga, Japan.
[email protected] Source: Eguchi, K Kario, K Shimada, K Hypertens-Res. 2002 May; 25(3): 329-33 09169636
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Effect of acute portal hypertension on gut mucosa. Author(s): Second Department of Surgery, Kinki University School of Medicine, 377-2 Ohno-Higashi, Osaka, Sayama, Osaka 589-8511, Japan. Source: Hashimoto, N Ohyanagi, H Hepatogastroenterology. 2002 Nov-December; 49(48): 1567-70 0172-6390
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Effect of long-term intake of milk products on blood pressure in hypertensive rats. Author(s): Institute of Biomedicine, Pharmacology, Biomedicum Helsinki, University of Helsinki, Finland.
[email protected] Source: Sipola, M Finckenberg, P Korpela, R Vapaatalo, H Nurminen, M L J-Dairy-Res. 2002 February; 69(1): 103-11 0022-0299
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Effect of renin-angiotensin system activation by dietary sodium restriction and upright position on plasma leptin concentration in patients with essential hypertension. Author(s): Department of Nephrology, Endocrinology and Metabolic Diseases, Silesian Medical University, Katowice, Poland. Source: Adamczak, M Kokot, F Chudek, J Wiecek, A Med-Sci-Monit. 2002 July; 8(7): CR473-7 1234-1010
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Effects of angiotensin converting enzyme inhibitor and calcium antagonist on endothelial function in patients with essential hypertension. Author(s): Department of Internal Medicine, Soonchunhyang University, College of Medicine, Seoul, Korea.
[email protected] Source: On, Y K Kim, C H Oh, B H Lee, M M Park, Y B Hypertens-Res. 2002 May; 25(3): 365-71 0916-9636
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Effects of atorvastatin on aortic pulse wave velocity in patients with hypertension and hypercholesterolaemia: a preliminary study. Author(s): Department of Internal Medicine, Broussaia Hospital, Paris, France. Source: Raison, J Rudnichi, A Safar, M E J-Hum-Hypertens. 2002 October; 16(10): 705-10 0950-9240
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Effects of caloric restriction on development of the proximal growth plate and metaphysis of the caput femoris in spontaneously hypertensive rats: microscopic and computer-assisted image analyses. Author(s): Department of Respiratory and Digestive Medicine, Nagasaki University School of Medicine, Nagasaki City 852-8102, Japan.
[email protected] Source: Kawahara, T Shimokawa, I Tomita, M Hirano, T Shindo, H Microsc-Res-Tech. 2002 November 15; 59(4): 306-12 1059-910X
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Effects of four antihypertensive monotherapies on cardiac mass and function in hypertensive patients with left ventricular hypertrophy: randomized prospective study. Author(s): Department of Internal Medicine, Split University Hospital and School of Medicine, Split, Croatia.
[email protected] Source: Rakic, D Rumboldt, Z Bagatin, J Polic, S Croat-Med-J. 2002 December; 43(6): 6729 0353-9504
Nutrition 181
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Effects of Ginkgo biloba extract (EGb 761) on cerebral thrombosis and blood pressure in stroke-prone spontaneously hypertensive rats. Author(s): Laboratory of Physiology, Faculty of Nutrition, Kobe Gakuin University, Kobe, Japan.
[email protected] Source: Sasaki, Y Noguchi, T Yamamoto, E Giddings, J C Ikeda, K Yamori, Y Yamamoto, J Clin-Exp-Pharmacol-Physiol. 2002 November; 29(11): 963-7 0305-1870
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Effects of L-carnosine on renal sympathetic nerve activity and DOCA-salt hypertension in rats. Author(s): Niigata University School of Medicine, Asahimachidoori, Japan.
[email protected] Source: Niijima, A Okui, T Matsumura, Y Yamano, T Tsuruoka, N Kiso, Y Nagai, K Auton-Neurosci. 2002 May 31; 97(2): 99-102 1566-0702
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Effects of policosanol on older patients with hypertension and type II hypercholesterolaemia. Author(s): Surgical Medical Research Center, Havana City, Cuba. Source: Castano, G Mas, R Fernandez, J C Fernandez, L Illnait, J Lopez, E Drugs-R-D. 2002; 3(3): 159-72 1174-5886
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Effects of stress and behavioral interventions in hypertension: the rise and fall of omapatrilat. Author(s): Integrative and Behavioral Cardiovascular Health Program, Zena and Michael Wiener Cardiovascular Institute, Mt. Sinai School of Medicine, New York, NY 10029, USA. Source: Pickering, T G J-Clin-Hypertens-(Greenwich). 2002 Sep-October; 4(5): 371-3 1524-6175
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Efficacy and safety of a therapeutic interchange from high-dose calcium channel blockers to a fixed-dose combination of amlodipine/benazepril in patients with moderate-to-severe hypertension. Source: Caro, J J Lee, K Curr-Hypertens-Repage 2002 December; 4(6): 417-8 1522-6417
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Emerging medical therapies for pulmonary arterial hypertension. Author(s): Institute of Cardiology, University of Bologna, Italy. Source: Galie, N Manes, A Branzi, A Prog-Cardiovasc-Dis. 2002 Nov-December; 45(3): 213-24 0033-0620
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Endothelium-dependent vasorelaxation induced by L-carnitine in isolated aorta from normotensive and hypertensive rats. Author(s): Department of Pharmacology, Faculty of Pharmacy, University of Seville, C/ Profesor Garcia Gonzalez s/n, 41012-Seville, Spain.
[email protected] Source: Herrera, M D Bueno, R De Sotomayor, M A Perez Guerrero, C Vazquez, C M Marhuenda, E J-Pharm-Pharmacol. 2002 October; 54(10): 1423-7 0022-3573
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Ethnopharmacobotany in Tuscany: plants used as antihypertensives. Author(s): Dipartimento di Agronomia e Gestione dell'Agroecosistema via S. Michele degli Scalzi, 2-56100, Pisa, Italy. Source: Uncini Manganelli, R E Chericoni, S Baragatti, B Fitoterapia. 2000 August; 71 Suppl 1: S95-100 0367-326X
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Fluvastatin remodels resistance arteries in genetically hypertensive rats, even in the absence of any effect on blood pressure. Author(s): Department of Pharmacology and Toxicology, School of Medical Sciences, University of Otago, Dunedin, New Zealand.
[email protected] 182 Hypertension
Source: Ledingham, J M Laverty, R Clin-Exp-Pharmacol-Physiol. 2002 October; 29(10): 931-4 0305-1870 •
Hemostasis imbalance in experimental hypertension. Author(s): INSERM U479, Faculte Xavier Bichat, Paris, France. Source: Corseaux, D Ollivier, V Fontaine, V Huisse, M G Philippe, M LoueDecember, L Vranckx, R Ravanat, C Lanza, F Angles Cano, E Guillin, M C Michel, J B Mol-Med. 2002 April; 8(4): 169-78 1076-1551
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High salt intake inhibits nitric oxide synthase expression and aggravates hypertension in rats with chronic renal failure. Author(s): Department of Medicine, Keck School of Medicine University of Southern California, Los Angeles, USA.
[email protected] Source: Campese, V M Mozayeni, P Ye, S Gumbard, M J-Nephrol. 2002 Jul-August; 15(4): 407-13 1120-3625
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HMG-CoA reductase inhibitor has protective effects against stroke events in strokeprone spontaneously hypertensive rats. Author(s): Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
[email protected] Source: Kawashima, S Yamashita, T Miwa, Y Ozaki, M Namiki, M Hirase, T Inoue, N Hirata, K Yokoyama, M Stroke. 2003 January; 34(1): 157-63 1524-4628
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Hypertension and insulin disorders. Author(s): Division of Internal Medicine, Ajina Tsuchiya Hospital, 4-51-1 Ajina Hatsukaichi, Japan.
[email protected] Source: Imazu, M Curr-Hypertens-Repage 2002 December; 4(6): 477-82 1522-6417
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Hypertensive cardiovascular disease: risk reduction by dietary calcium and dairy foods. Source: McCarron, D.A. Reusser, M.E. Sciences-des-Aliments (France). (2002). volume 22(4) page 415-421. Numero special: Dairy Products, Nutrition and Health. P11. calcium diet milk products hypertension human nutrition health 0240-8813
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Initial treatment of hypertension. Author(s): Weill Medical College of Cornell University and the Lang Research Center, New York Hospital Medical Center of Queens, New York, USA. Source: August, P N-Engl-J-Med. 2003 February 13; 348(7): 610-7 1533-4406
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Insights into Dahl salt-sensitive hypertension revealed by temporal patterns of renal medullary gene expression. Author(s): Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
[email protected] Source: Liang, M Yuan, B Rute, E Greene, A S Olivier, M Cowley, A W Jr PhysiolGenomics. 2003 February 6; 12(3): 229-37 1531-2267
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Is lead exposure the principal cause of essential hypertension? Author(s): Nephrology Division, The Burns and Allen Research Institute, Cedars-Sinai Medical Center, Los Angeles 90048, USA.
[email protected] Source: Gonick, H C Behari, J R Med-Hypotheses. 2002 September; 59(3): 239-46 03069877
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Isradipine treatment of hypertension in children: a single-center experience. Author(s): Division of Pediatric Nephrology, Montefiore Medical Center, Bronx, NY 10467, USA.
[email protected] Source: Flynn, J T Warnick, S J Pediatr-Nephrol. 2002 September; 17(9): 748-53 0931-041X
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Mecamylamine (Inversine): an old antihypertensive with new research directions. Author(s): Center for Aging and Brain Repair, Department of Neurosurgery, University of South Florida College of Medicine, Tampa 33613, USA.
[email protected] Source: Shytle, R D Penny, E Silver, A A Goldman, J Sanberg, P R J-Hum-Hypertens. 2002 July; 16(7): 453-7 0950-9240
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Molecular and cellular basis of pulmonary vascular remodeling in pulmonary hypertension. Author(s): Respiratory Medicine Unit, Department of Medicine, Addenbrooke's Hospital, University of Cambridge School of Clinical Medicine, Cambridge, UK. Source: Jeffery, T K Morrell, N W Prog-Cardiovasc-Dis. 2002 Nov-December; 45(3): 173202 0033-0620
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Non pharmacologic therapy and lifestyle factors in hypertension. Author(s): Department of Medicine, University of Western Australia, Royal Perth Hospital, Australia. Source: Beilin, L J Burke, V Cox, K L Hodgson, J M Mori, T A Puddey, I B Blood-Press. 2001; 10(5-6): 352-65 0803-7051
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Nutritional supplementation with Chlorella pyrenoidosa for mild to moderate hypertension. Author(s): Department of Anatomy and Internal Medicine, Virginia Commonwealth University, Medical College of Virginia, Richmond, VA 23298-0709, USA.
[email protected] Source: Merchant, R E Andre, C A Sica, D A J-Med-Food. 2002 Fall; 5(3): 141-52 1096620X
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Participation of renal and circulating endothelin in salt-sensitive essential hypertension. Author(s): Department of Medicine, College of Human Medicine, Michigan State University, Medical Education and Research Center of Grand Rapids, 49503, USA.
[email protected] Source: Elijovich, F Laffer, C L J-Hum-Hypertens. 2002 July; 16(7): 459-67 0950-9240
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Pulmonary hypertension associated with connective tissue disease. Author(s): Pulmonary Hypertension Center, University of Colorado Health Sciences Center, Denver, CO, USA. Source: Fagan, K A Badesch, D B Prog-Cardiovasc-Dis. 2002 Nov-December; 45(3): 22534 0033-0620
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Pulmonary hypertension in systemic sclerosis: bete noire no more? Source: Varga, J Curr-Opin-Rheumatol. 2002 November; 14(6): 666-70 1040-8711
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Recent developments in the treatment of obesity-related hypertension. Author(s): Franz Volhard Clinic - HELIOS-Klinikum Berlin Buch, Charite, Medical Faculty of the Humboldt University Berlin, Max Delbruck Center for Molecular Medicine, Germany. Source: Pischon, T Sharma, A M Curr-Opin-Nephrol-Hypertens. 2002 September; 11(5): 497-502 1062-4821
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Responsiveness, affinity constants and beta-adrenoceptor reserves for isoprenaline on aortae from normo-, pre- and hypertensive rats. Author(s): Cardiovascular Pharmacology Group, Faculty of Medicine and Health Science, The University of Auckland, New Zealand. Source: Chen, Y Y Doggrell, S A J-Pharm-Pharmacol. 2002 April; 54(4): 515-22 0022-3573
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Role of bacterial cell wall proteinase in anti hypertension. Author(s): (Chr. Hansen A/S, Hoersholm (Danemark)) Source: Flambard, B. Sciences-des-Aliments (France). (2002). volume 22(1-2) page 209222. P11. lactic acid bacteria cell walls proteases medicinal properties hypertension 02408813
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Role of blood pressure monitoring in non-pharmacological management of hypertension. Author(s): Division of Hypertension and Nephrology, National Cardiovascular Centre, Suita, Osaka, Japan. Source: Kawano, Y Blood-Press-Monit. 2002 February; 7(1): 51-4 1359-5237
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Subjects with essential hypertension are more sensitive to the inhibition of 11 betaHSD by liquorice. Source: Sigurjonsdottir, H A Manhem, K Axelson, M Wallerstedt, S J-Hum-Hypertens. 2003 February; 17(2): 125-31 0950-9240
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The effect of amlodipine on exercise-induced pulmonary hypertension and right heart function in patients with chronic obstructive pulmonary disease. Author(s): Klinik Wehrawald, BfA Schwarzenbacher Strasse 3 79682 Todtmoos, Germany.
[email protected] Source: Franz, I W Van Der Meyden, J Schaupp, S Tonnesmann, U Z-Kardiol. 2002 October; 91(10): 833-9 0300-5860
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The effect of the combination of Mediterranean diet and leisure time physical activity on the risk of developing acute coronary syndromes, in hypertensive subjects. Author(s): Cardiology Department, School of Medicine, University of Athens, Greece. Source: Pitsavos, C Panagiotakos, D B Chrysohoou, C Kokkinos, P F Skoumas, J Papaioannou, I Stefanadis, C Toutouzas, P J-Hum-Hypertens. 2002 July; 16(7): 517-24 0950-9240
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Use of atorvastatin in hyperlipidemic hypertensive renal transplant recipients. Author(s): Department of Molecular Medicine, Karolinska Institutet, L3 Karolinska Hospital, 171 76 Stockholm, Sweden.
[email protected] Source: KrMarch, R T Ferraris, J R Ramirez, J A Sorroche, P Legal, S Cayssials, A PediatrNephrol. 2002 July; 17(7): 540-3 0931-041X
Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •
healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0
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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov
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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov
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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/
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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/
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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/
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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/
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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/
Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html
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Google: http://directory.google.com/Top/Health/Nutrition/
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Healthnotes: http://www.healthnotes.com/
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Open Directory Project: http://dmoz.org/Health/Nutrition/
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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/
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WebMDHealth: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
The following is a specific Web list relating to hypertension; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •
Vitamins Vitamin B6 Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin C Source: Healthnotes, Inc. www.healthnotes.com Vitamin C Source: Prima Communications, Inc.www.personalhealthzone.com
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Minerals ACE Inhibitors (Angiotensin-Converting Enzyme Inhibitors) Source: Prima Communications, Inc.www.personalhealthzone.com
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Angiotensin-Converting Enzyme (ACE) Inhibitors Source: Healthnotes, Inc. www.healthnotes.com Angiotensin-Converting Enzyme (ACE) Inhibitors Source: Integrative Medicine Communications; www.drkoop.com Calcium Source: Healthnotes, Inc. www.healthnotes.com Calcium Source: Prima Communications, Inc.www.personalhealthzone.com Calcium-Channel Blockers Source: Healthnotes, Inc. www.healthnotes.com HMG-CoA Reductase Inhibitors (Statins) Source: Integrative Medicine Communications; www.drkoop.com L-Carnitine Source: Healthnotes, Inc. www.healthnotes.com Magnesium Source: Healthnotes, Inc. www.healthnotes.com Magnesium Source: Integrative Medicine Communications; www.drkoop.com Magnesium Source: Prima Communications, Inc.www.personalhealthzone.com Potassium Source: Healthnotes, Inc. www.healthnotes.com Potassium Source: Integrative Medicine Communications; www.drkoop.com Potassium Source: Prima Communications, Inc.www.personalhealthzone.com Potassium Chloride Source: Healthnotes, Inc. www.healthnotes.com Spironolactone Source: Healthnotes, Inc. www.healthnotes.com Zinc Source: Healthnotes, Inc. www.healthnotes.com Zinc Source: Integrative Medicine Communications; www.drkoop.com
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Food and Diet Artichoke Source: Healthnotes, Inc. www.healthnotes.com Atkins Diet Source: Healthnotes, Inc. www.healthnotes.com Avocado Source: Healthnotes, Inc. www.healthnotes.com Beets Source: Healthnotes, Inc. www.healthnotes.com Chocolate Source: Healthnotes, Inc. www.healthnotes.com Coffee Source: Healthnotes, Inc. www.healthnotes.com Diabetes Source: Healthnotes, Inc. www.healthnotes.com Garlic Alternative names: Allium sativum Source: Healthnotes, Inc. www.healthnotes.com Garlic Source: Prima Communications, Inc.www.personalhealthzone.com Garlic Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,786,00.html Hypertension Source: Healthnotes, Inc. www.healthnotes.com Jerusalem Artichoke Source: Healthnotes, Inc. www.healthnotes.com Kohlrabi Source: Healthnotes, Inc. www.healthnotes.com Low Back Pain Source: Healthnotes, Inc. www.healthnotes.com Low-Fat Diet Source: Healthnotes, Inc. www.healthnotes.com Low-Salt Diet Source: Healthnotes, Inc. www.healthnotes.com
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Natural Sweeteners Source: Healthnotes, Inc. www.healthnotes.com Nutritional Yeast Source: Integrative Medicine Communications; www.drkoop.com Nutritional Yeast Alternative names: Brewer's Yeast Source: Integrative Medicine Communications; www.drkoop.com Omega-3 Fatty Acids Source: Integrative Medicine Communications; www.drkoop.com Omega-3 fatty acids Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,992,00.html Parsnips Source: Healthnotes, Inc. www.healthnotes.com Porcini Mushrooms Source: Healthnotes, Inc. www.healthnotes.com Radishes Source: Healthnotes, Inc. www.healthnotes.com Rutabagas Source: Healthnotes, Inc. www.healthnotes.com Salmon Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,102,00.html Shiitake Mushrooms Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,308,00.html Special Diets Index Source: Healthnotes, Inc. www.healthnotes.com Tea Source: Healthnotes, Inc. www.healthnotes.com The Dean Ornish Diet Source: Healthnotes, Inc. www.healthnotes.com Tyramine-Free Diet Source: Healthnotes, Inc. www.healthnotes.com
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Vegetarian Diet Source: Healthnotes, Inc. www.healthnotes.com Weight Loss and Obesity Source: Healthnotes, Inc. www.healthnotes.com Winter Squash Source: Healthnotes, Inc. www.healthnotes.com Yams Source: Healthnotes, Inc. www.healthnotes.com
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CHAPTER 3. ALTERNATIVE MEDICINE AND HYPERTENSION Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to hypertension. At the conclusion of this chapter, we will provide additional sources.
The Combined Health Information Database The Combined Health Information Database (CHID) is a bibliographic database produced by health-related agencies of the U.S. federal government (mostly from the National Institutes of Health) that can offer concise information for a targeted search. The CHID database is updated four times a year at the end of January, April, July, and October. Check the titles, summaries, and availability of CAM-related information by using the “Simple Search” option at the following Web site: http://chid.nih.gov/simple/simple.html. In the drop box at the top, select “Complementary and Alternative Medicine.” Then type “hypertension” (or synonyms) in the second search box. We recommend that you select 100 “documents per page” and to check the “whole records” options. The following was extracted using this technique: •
Using the Body To Heal the Body: Exercise and Disease Intervention Source: Alternative and Complementary Therapies. 4(3): 169-172. June 1998. Summary: This journal article discusses the multiple health benefits of exercise, highlighting the work in this area by Dr. L. Goldberg and D. L. Elliot at the Human Performance Laboratory, Division of Health Promotion and Sports Medicine, Oregon Health Sciences University in Portland. Drs. Goldberg and Elliot have focused their work on the effects of exercise in hypertension, neuromuscular diseases, certain metabolic conditions, and obesity. Clinicians at the Human Performance Laboratory offer patients a choice of testing options, and develop individualized exercise plans specifying exercise mode, intensity, duration, frequency, and progression. They also help patients develop strategies to overcome potential barriers to plan compliance. Exercise, along with diet, stress reduction, and social support, also is an integral component of the Opening Your Heart Program developed by Dr. D. Ornish at the Preventive Medicine Research Center in Sausalito, California. Dr. Ornish emphasizes
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that exercise does not have to be vigorous to be beneficial, noting that consistency is more important than intensity. In addition to its benefits in heart disease, recent research suggests a role for exercise in reducing cancer risk and improving function in older age. The article includes a list of recommended readings and 14 references. •
Herbal Medicines: Poison or Potions? Source: Journal of Laboratory and Clinical Medicine. 139(6): 343-8. June 2002. Summary: This journal article provides a wide variety of information on herbal medicines, including the reasons for their use, safety issues, beneficial effects, adverse effects, and the role that physicians can play in helping patients make informed treatment decisions. The article gives examples of adverse effects from specific herbs, including: Herbal Ecstasy and Parkinson's syndrome; Chinese medications with undeclared prescription drugs; Indian herbal medications with lead contamination; valerian withdrawal syndrome; adverse reactions of St. John's wort; mu tong and nephropathy; saw palmetto and liver disease; dong quai and hypertension; and kombucha mushroom and coagulation disorders. 1 table. 38 references. 6 pages.
National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to hypertension and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “hypertension” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to hypertension: •
A preliminary fast may potentiate response to a subsequent low-salt, low-fat vegan diet in the management of hypertension - fasting as a strategy for breaking metabolic vicious cycles. Author(s): McCarty MF. Source: Medical Hypotheses. 2003 May; 60(5): 624-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12710893&dopt=Abstract
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Acupuncture in hypertension. Author(s): Townsend RR. Source: Journal of Clinical Hypertension (Greenwich, Conn.). 2002 May-June; 4(3): 229. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12045377&dopt=Abstract
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Acute effect of tetrandrine pulmonary targeting microspheres on hypoxic pulmonary hypertension in rats. Author(s): Cheng D, Chen W, Mo X. Source: Chin Med J (Engl). 2002 January; 115(1): 81-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11930667&dopt=Abstract
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Anti-hypertensive effect of water extract of danshen on renovascular hypertension through inhibition of the renin angiotensin system. Author(s): Kang DG, Yun YG, Ryoo JH, Lee HS. Source: The American Journal of Chinese Medicine. 2002; 30(1): 87-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12067101&dopt=Abstract
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Aqueous extract of Monascus purpureus M9011 prevents and reverses fructoseinduced hypertension in rats. Author(s): Hsieh PS, Tai YH. Source: Journal of Agricultural and Food Chemistry. 2003 July 2; 51(14): 3945-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12822928&dopt=Abstract
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Benign intracranial hypertension in association with acute lymphoblastic leukemia. Author(s): Sastry J, Karandikar SS, English MW. Source: Pediatric Hematology and Oncology. 2003 March; 20(2): 157-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12554527&dopt=Abstract
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Biofeedback and hypertension: a deja vu experience. Comments on Yucha's "Problems inherent in assessing biofeedback efficacy studies". Author(s): Blanchard EB. Source: Applied Psychophysiology and Biofeedback. 2002 March; 27(1): 107-9; Discussion 111-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12001883&dopt=Abstract
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Biofeedback of baroreflex sensitivity in patients with mild essential hypertension. Author(s): Overhaus S, Ruddel H, Curio I, Mussgay L, Scholz OB. Source: International Journal of Behavioral Medicine. 2003; 10(1): 66-78. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12581949&dopt=Abstract
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Blood pressure lowering effect of an olive leaf extract (Olea europaea) in L-NAME induced hypertension in rats. Author(s): Khayyal MT, el-Ghazaly MA, Abdallah DM, Nassar NN, Okpanyi SN, Kreuter MH. Source: Arzneimittel-Forschung. 2002; 52(11): 797-802. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12489249&dopt=Abstract
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Blood pressure-lowering effects of biofeedback treatment in hypertension: a metaanalysis of randomized controlled trials. Author(s): Nakao M, Yano E, Nomura S, Kuboki T. Source: Hypertens Res. 2003 January; 26(1): 37-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12661911&dopt=Abstract
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Cardiovascular, antihyperlipidemic and antioxidant effects of oleanolic and ursolic acids in experimental hypertension. Author(s): Somova LO, Nadar A, Rammanan P, Shode FO. Source: Phytomedicine : International Journal of Phytotherapy and Phytopharmacology. 2003 March; 10(2-3): 115-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12725563&dopt=Abstract
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Case study examining the efficacy of a multi-modal psychotherapeutic intervention for hypertension. Author(s): Borckardt JJ. Source: Int J Clin Exp Hypn. 2002 April; 50(2): 189-201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11939278&dopt=Abstract
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Cerebral blood flow during plateau waves in a patient with benign intracranial hypertension--case report. Author(s): Kabeya R, Inao S, Tadokoro M, Nishino M, Yoshida J. Source: Neurol Med Chir (Tokyo). 2000 May; 40(5): 287-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11980098&dopt=Abstract
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Chronic administration of a tyrosine kinase inhibitor restores functional and morphological changes of the basilar artery during chronic hypertension. Author(s): Kitayama J, Kitazono T, Ooboshi H, Ago T, Ohgami T, Fujishima M, Ibayashi S. Source: Journal of Hypertension. 2002 November; 20(11): 2205-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12409959&dopt=Abstract
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Chronic administration of aqueous extract of Hibiscus sabdariffa attenuates hypertension and reverses cardiac hypertrophy in 2K-1C hypertensive rats. Author(s): Odigie IP, Ettarh RR, Adigun SA. Source: Journal of Ethnopharmacology. 2003 June; 86(2-3): 181-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12738084&dopt=Abstract
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Comparison of different methods evaluating the functional and structural abnormalities in hypertension. Author(s): Ficzere A, Csiba L. Source: European Neurology. 2002; 48(2): 71-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12186996&dopt=Abstract
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Compliance and blood pressure control in women with hypertension. Author(s): Bobb-Liverpool B, Duff EM, Bailey EY. Source: The West Indian Medical Journal. 2002 December; 51(4): 236-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12632640&dopt=Abstract
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Considering the whole patient with hypertension: the ethos of pharmaceutical care. Author(s): Coleman CA, Bleidt B. Source: Ethn Dis. 2002 Fall; 12(4): S3-72-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12477159&dopt=Abstract
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Dietary vitamin E and C supplementation prevents fructose induced hypertension in rats. Author(s): Vasdev S, Gill V, Parai S, Longerich L, Gadag V. Source: Molecular and Cellular Biochemistry. 2002 December; 241(1-2): 107-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12482032&dopt=Abstract
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Docosahexaenoic acid attenuated hypertension and vascular dementia in strokeprone spontaneously hypertensive rats. Author(s): Kimura S, Saito H, Minami M, Togashi H, Nakamura N, Ueno K, Shimamura K, Nemoto M, Parvez H. Source: Neurotoxicology and Teratology. 2002 September-October; 24(5): 683-93. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12200199&dopt=Abstract
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Drug-induced hypertension. Author(s): Handler J. Source: Journal of Clinical Hypertension (Greenwich, Conn.). 2003 January-February; 5(1): 83-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12556663&dopt=Abstract
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Effect of calcium antagonist on cerebral blood flow and oxygen metabolism in patients with hypertension and chronic major cerebral artery occlusion: a positron emission tomography study. Author(s): Ogasawara K, Noda A, Yasuda S, Kobayashi M, Yukawa H, Ogawa A. Source: Nuclear Medicine Communications. 2003 January; 24(1): 71-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12501022&dopt=Abstract
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Effect of vitamin C on pulmonary hypertension and muscularisation of pulmonary arterioles in broilers. Author(s): Xiang RP, Sun WD, Wang JY, Wang XL. Source: British Poultry Science. 2002 December; 43(5 Suppl): 705-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12555895&dopt=Abstract
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Effect of vitamin C supplementation on oxidative DNA damage in an experimental model of lead-induced hypertension. Author(s): Attri J, Dhawan V, Mahmood S, Pandhi P, Parwana HK, Nath R.
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Source: Annals of Nutrition & Metabolism. 2003; 47(6): 294-301. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14520025&dopt=Abstract •
Effects of Cudrania tricuspidata water extract on blood pressure and renal functions in NO-dependent hypertension. Author(s): Kang DG, Hur TY, Lee GM, Oh H, Kwon TO, Sohn EJ, Lee HS. Source: Life Sciences. 2002 April 19; 70(22): 2599-609. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12269387&dopt=Abstract
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Effects of docosahexaenoic acid on vascular pathology and reactivity in hypertension. Author(s): Engler MM, Engler MB, Pierson DM, Molteni LB, Molteni A. Source: Experimental Biology and Medicine (Maywood, N.J.). 2003 March; 228(3): 299307. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12626775&dopt=Abstract
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Effects of progressive muscle relaxation on blood pressure and psychosocial status for clients with essential hypertension in Taiwan. Author(s): Sheu S, Irvin BL, Lin HS, Mar CL. Source: Holistic Nursing Practice. 2003 January-February; 17(1): 41-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12597674&dopt=Abstract
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Effects of purified eicosapentaenoic and docosahexaenoic acids on glycemic control, blood pressure, and serum lipids in type 2 diabetic patients with treated hypertension. Author(s): Woodman RJ, Mori TA, Burke V, Puddey IB, Watts GF, Beilin LJ. Source: The American Journal of Clinical Nutrition. 2002 November; 76(5): 1007-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12399272&dopt=Abstract
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Effects of Qigong on blood pressure, blood pressure determinants and ventilatory function in middle-aged patients with essential hypertension. Author(s): Lee MS, Lee MS, Choi ES, Chung HT. Source: The American Journal of Chinese Medicine. 2003; 31(3): 489-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12943180&dopt=Abstract
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Effects of Salvia miltiorrhiza extracts on rat hypoxic pulmonary hypertension, heme oxygenase-1 and nitric oxide synthase. Author(s): Chen Y, Ruan Y, Li L, Chu Y, Xu X, Wang Q, Zhou X. Source: Chin Med J (Engl). 2003 May; 116(5): 757-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875696&dopt=Abstract
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Efficacy and safety of a therapeutic interchange from high-dose calcium channel blockers to a fixed-dose combination of amlodipine/benazepril in patients with
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moderate-to-severe hypertension. Author(s): Caro JJ, Lee K. Source: Current Hypertension Reports. 2002 December; 4(6): 417-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12419166&dopt=Abstract •
Ethnopharmacological survey of medicinal plants used for the treatment of diabetes mellitus, hypertension and cardiac diseases in the south-east region of Morocco (Tafilalet). Author(s): Eddouks M, Maghrani M, Lemhadri A, Ouahidi ML, Jouad H. Source: Journal of Ethnopharmacology. 2002 October; 82(2-3): 97-103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12241983&dopt=Abstract
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For the patient. Are vegetarians at less risk for obesity, diabetes, and hypertension? Obesity, diabetes, hypertension, and vegetarian status among Seventh-Day Adventists in Barbados: preliminary results. Author(s): Brathwaite N, Fraser HS, Modeste N, Broome H, King R. Source: Ethn Dis. 2003 Winter; 13(1): 148. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12723025&dopt=Abstract
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Hypertension and blood pressure among meat eaters, fish eaters, vegetarians and vegans in EPIC-Oxford. Author(s): Appleby PN, Davey GK, Key TJ. Source: Public Health Nutrition. 2002 October; 5(5): 645-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12372158&dopt=Abstract
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Hypertension and holistic care. Author(s): Donnelly GF. Source: Holistic Nursing Practice. 2001 July; 15(4): V. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12120498&dopt=Abstract
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Hypertension induced by St. John's Wort - a case report. Author(s): Zullino D, Borgeat F. Source: Pharmacopsychiatry. 2003 January; 36(1): 32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12649772&dopt=Abstract
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Increased coronary vascular resistance cannot be reduced by inhibiting sympathetic overactivity in hypertension. Author(s): Sundell J, Laine H, Luotolahti M, Nuutila P, Knuuti J. Source: Journal of Vascular Research. 2002 September-October; 39(5): 456-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12297708&dopt=Abstract
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Increased renal vascular sensitivity to angiotensin II in hypertension is due to decreased response to prostaglandins. Author(s): Palmgren E, Widgren B, Aurell M, Herlitz H. Source: Journal of Hypertension. 2003 May; 21(5): 969-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12714872&dopt=Abstract
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Increases in hypertension and blood pressure during pregnancy with increased bone lead levels. Author(s): Rothenberg SJ, Kondrashov V, Manalo M, Jiang J, Cuellar R, Garcia M, Reynoso B, Reyes S, Diaz M, Todd AC. Source: American Journal of Epidemiology. 2002 December 15; 156(12): 1079-87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12480651&dopt=Abstract
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Inhaled ethyl nitrite gas for persistent pulmonary hypertension of the newborn. Author(s): Moya MP, Gow AJ, Califf RM, Goldberg RN, Stamler JS. Source: Lancet. 2002 July 13; 360(9327): 141-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12126827&dopt=Abstract
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Is lead exposure the principal cause of essential hypertension? Author(s): Gonick HC, Behari JR. Source: Medical Hypotheses. 2002 September; 59(3): 239-46. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12208146&dopt=Abstract
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Is there a role for stress management in reducing hypertension in African Americans? Author(s): Kondwani KA, Lollis CM. Source: Ethn Dis. 2001 Fall; 11(4): 788-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11763303&dopt=Abstract
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Lay beliefs about high blood pressure in a low- to middle-income urban AfricanAmerican community: an opportunity for improving hypertension control. Author(s): Wilson RP, Freeman A, Kazda MJ, Andrews TC, Berry L, Vaeth PA, Victor RG. Source: The American Journal of Medicine. 2002 January; 112(1): 26-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11812403&dopt=Abstract
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Leaf methanol extract of Bidens pilosa prevents and attenuates the hypertension induced by high-fructose diet in Wistar rats. Author(s): Dimo T, Rakotonirina SV, Tan PV, Azay J, Dongo E, Cros G. Source: Journal of Ethnopharmacology. 2002 December; 83(3): 183-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12426085&dopt=Abstract
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Lifestyle modifications to prevent hypertension. Author(s): McGuffin M.
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Source: Jama : the Journal of the American Medical Association. 2003 February 19; 289(7): 843; Author Reply 843-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12588259&dopt=Abstract •
Magnesium supplementation and deoxycorticosterone acetate--salt hypertension: effect on arterial mechanical properties and on activity of endothelin-1. Author(s): Berthon N, Laurant P, Hayoz D, Fellmann D, Brunner HR, Berthelot A. Source: Canadian Journal of Physiology and Pharmacology. 2002 June; 80(6): 553-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12117304&dopt=Abstract
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Mechanism of garlic (Allium sativum) induced reduction of hypertension in 2K-1C rats: a possible mediation of Na/H exchanger isoform-1. Author(s): Al-Qattan KK, Khan I, Alnaqeeb MA, Ali M. Source: Prostaglandins, Leukotrienes, and Essential Fatty Acids. 2003 October; 69(4): 217-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12907130&dopt=Abstract
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Medically supervised water-only fasting in the treatment of borderline hypertension. Author(s): Goldhamer AC, Lisle DJ, Sultana P, Anderson SV, Parpia B, Hughes B, Campbell TC. Source: Journal of Alternative and Complementary Medicine (New York, N.Y.). 2002 October; 8(5): 643-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12470446&dopt=Abstract
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Medically supervised water-only fasting in the treatment of hypertension. Author(s): Ciurleo A, Marchese M. Source: Journal of Manipulative and Physiological Therapeutics. 2002 February; 25(2): 138-9; Author Reply 139. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11896385&dopt=Abstract
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Natural approach to hypertension. Author(s): Khosh F, Khosh M. Source: Alternative Medicine Review : a Journal of Clinical Therapeutic. 2001 December; 6(6): 590-600. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11804549&dopt=Abstract
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Nondrug interventions in hypertension prevention and control. Author(s): Labarthe D, Ayala C. Source: Cardiology Clinics. 2002 May; 20(2): 249-63. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12119799&dopt=Abstract
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Non-pharmacological treatment of hypertension in women. Author(s): Costa FV.
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Source: Journal of Hypertension. 2002 May; 20 Suppl 2: S57-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12183854&dopt=Abstract •
Nutritional supplementation with Chlorella pyrenoidosa for mild to moderate hypertension. Author(s): Merchant RE, Andre CA, Sica DA. Source: Journal of Medicinal Food. 2002 Fall; 5(3): 141-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12495586&dopt=Abstract
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Obesity, diabetes, hypertension, and vegetarian status among Seventh-Day Adventists in Barbados: preliminary results. Author(s): Brathwaite N, Fraser HS, Modeste N, Broome H, King R. Source: Ethn Dis. 2003 Winter; 13(1): 34-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12723010&dopt=Abstract
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Osteopathic manipulative medicine in the treatment of hypertension: an alternative, conventional approach. Author(s): Spiegel AJ, Capobianco JD, Kruger A, Spinner WD. Source: Heart Disease. 2003 July-August; 5(4): 272-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12877760&dopt=Abstract
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Oxygen-15 positron-emission tomography for predicting selective delivery of a chemotherapeutic agent to hepatic cancers during angiotensin II-induced hypertension. Author(s): Koh T, Taniguchi H, Yamagishi H. Source: Cancer Chemotherapy and Pharmacology. 2003 April; 51(4): 349-58. Epub 2003 March 05. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12721763&dopt=Abstract
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Practice-based randomized controlled-comparison clinical trial of chiropractic adjustments and brief massage treatment at sites of subluxation in subjects with essential hypertension: pilot study. Author(s): Plaugher G, Long CR, Alcantara J, Silveus AD, Wood H, Lotun K, Menke JM, Meeker WC, Rowe SH. Source: Journal of Manipulative and Physiological Therapeutics. 2002 May; 25(4): 221-39. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12021741&dopt=Abstract
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Preventive effect of a chicken extract on the development of hypertension in strokeprone spontaneously hypertensive rats. Author(s): Matsumura Y, Kita S, Ono H, Kiso Y, Tanaka T. Source: Bioscience, Biotechnology, and Biochemistry. 2002 May; 66(5): 1108-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12092823&dopt=Abstract
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Promising hypotensive effect of hawthorn extract: a randomized double-blind pilot study of mild, essential hypertension. Author(s): Walker AF, Marakis G, Morris AP, Robinson PA. Source: Phytotherapy Research : Ptr. 2002 February; 16(1): 48-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11807965&dopt=Abstract
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Randomized, double-blind, placebo-controlled trial of coenzyme Q10 in isolated systolic hypertension. Author(s): Burke BE, Neuenschwander R, Olson RD. Source: Southern Medical Journal. 2001 November; 94(11): 1112-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11780680&dopt=Abstract
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Rapeseed oil ingestion and exacerbation of hypertension-related conditions in stroke prone spontaneously hypertensive rats. Author(s): Naito Y, Nagata T, Takano Y, Nagatsu T, Ohara N. Source: Toxicology. 2003 May 3; 187(2-3): 205-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12699909&dopt=Abstract
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Relationship of urinary sodium/potassium excretion and calcium intake to blood pressure and prevalence of hypertension among older Chinese vegetarians. Author(s): Kwok TC, Chan TY, Woo J. Source: European Journal of Clinical Nutrition. 2003 February; 57(2): 299-304. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12571663&dopt=Abstract
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Relaxation training as complementary therapy for mild hypertension control and the implications of evidence-based medicine. Author(s): Yung P, French P, Leung B. Source: Complementary Therapies in Nursing & Midwifery. 2001 May; 7(2): 59-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11855773&dopt=Abstract
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Risk of gestational hypertension in relation to folic acid supplementation during pregnancy. Author(s): Hernandez-Diaz S, Werler MM, Louik C, Mitchell AA. Source: American Journal of Epidemiology. 2002 November 1; 156(9): 806-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12396998&dopt=Abstract
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Role of blood pressure monitoring in non-pharmacological management of hypertension. Author(s): Kawano Y. Source: Blood Pressure Monitoring. 2002 February; 7(1): 51-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12040244&dopt=Abstract
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Roles of tyrosine kinase-, 1-phosphatidylinositol 3-kinase-, and mitogen-activated protein kinase-signaling pathways in ethanol-induced contractions of rat aortic smooth muscle: possible relation to alcohol-induced hypertension. Author(s): Yang ZW, Wang J, Zheng T, Altura BT, Altura BM. Source: Alcohol (Fayetteville, N.Y.). 2002 August; 28(1): 17-28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12377357&dopt=Abstract
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Serotonin-induced contraction in mesenteric resistance arteries: signaling and changes in deoxycorticosterone acetate-salt hypertension. Author(s): Watts SW. Source: Hypertension. 2002 March 1; 39(3): 825-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11897772&dopt=Abstract
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Soy milk lowers blood pressure in men and women with mild to moderate essential hypertension. Author(s): Rivas M, Garay RP, Escanero JF, Cia P Jr, Cia P, Alda JO. Source: The Journal of Nutrition. 2002 July; 132(7): 1900-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12097666&dopt=Abstract
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Status and management of hypertension in Greece: role of the adoption of a Mediterranean diet: the Attica study. Author(s): Panagiotakos DB, Pitsavos CH, Chrysohoou C, Skoumas J, Papadimitriou L, Stefanadis C, Toutouzas PK. Source: Journal of Hypertension. 2003 August; 21(8): 1483-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12872041&dopt=Abstract
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Status of lifestyle modifications in hypertension. Author(s): Chhabra MK, Lal A, Sharma KK. Source: J Indian Med Assoc. 2001 September; 99(9): 504-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12018559&dopt=Abstract
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Supplementation of L-arginine improves hypertension and lipid metabolism but not insulin resistance in diabetic rats. Author(s): Kawano T, Nomura M, Nisikado A, Nakaya Y, Ito S. Source: Life Sciences. 2003 October 24; 73(23): 3017-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14519450&dopt=Abstract
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The 10trans,12cis isomer of conjugated linoleic acid suppresses the development of hypertension in Otsuka Long-Evans Tokushima fatty rats. Author(s): Nagao K, Inoue N, Wang YM, Hirata J, Shimada Y, Nagao T, Matsui T, Yanagita T.
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Source: Biochemical and Biophysical Research Communications. 2003 June 20; 306(1): 134-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12788078&dopt=Abstract •
The effect of magneto-treated blood autotransfusion on central hemodynamic values and cerebral circulation in patients with essential hypertension. Author(s): Alizade IG, Karayeva NT. Source: Saudi Med J. 2002 May; 23(5): 517-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12070571&dopt=Abstract
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The JNC 7 hypertension guidelines. Author(s): Caspi O. Source: Jama : the Journal of the American Medical Association. 2003 September 10; 290(10): 1313; Author Reply 1314-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12966115&dopt=Abstract
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The nurse's role and skills in hypertension care: a review. Author(s): Bengtson A, Drevenhorn E. Source: Clinical Nurse Specialist Cns. 2003 September; 17(5): 260-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14501307&dopt=Abstract
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The role of lifestyle management in the overall treatment plan for prevention and management of hypertension. Author(s): Davis MM, Jones DW. Source: Semin Nephrol. 2002 January; 22(1): 35-43. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11785067&dopt=Abstract
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The sympathetic nervous system: the muse of primary hypertension. Author(s): DeQuattro V, Feng M. Source: Journal of Human Hypertension. 2002 March; 16 Suppl 1: S64-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11986898&dopt=Abstract
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The treatment of adults with essential hypertension. Author(s): Dosh SA. Source: The Journal of Family Practice. 2002 January; 51(1): 74-80. Review. Erratum In: J Fam Pract 2002 April; 51(4): 377. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11927069&dopt=Abstract
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Thermo-visual evaluation of the Yin-Tang acupuncture point for intracranial hypertension syndrome. Author(s): Ovechkin A, Kim KS, Lee JW, Lee SM.
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Source: The American Journal of Chinese Medicine. 2003; 31(3): 455-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12943176&dopt=Abstract •
Transcendental meditation, hypertension and heart disease. Author(s): King MS, Carr T, D'Cruz C. Source: Aust Fam Physician. 2002 February; 31(2): 164-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11917830&dopt=Abstract
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Treatment of Hypertension with Alternative Therapies (THAT) Study: a randomized clinical trial. Author(s): Goertz CH, Grimm RH, Svendsen K, Grandits G. Source: Journal of Hypertension. 2002 October; 20(10): 2063-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12359986&dopt=Abstract
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Why not prescribe the best drugs for hypertension now? Author(s): Wong SY, McInnes GT, MacDonald TM. Source: Journal of Human Hypertension. 2003 July; 17(7): 505-11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12821958&dopt=Abstract
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Yoga practices and hypertension. Author(s): Yeolekar ME. Source: J Assoc Physicians India. 2002 May; 50(5): 631-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12186114&dopt=Abstract
Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •
Alternative Medicine Foundation, Inc.: http://www.herbmed.org/
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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats
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Chinese Medicine: http://www.newcenturynutrition.com/
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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html
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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm
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Google: http://directory.google.com/Top/Health/Alternative/
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Healthnotes: http://www.healthnotes.com/
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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine
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Open Directory Project: http://dmoz.org/Health/Alternative/
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HealthGate: http://www.tnp.com/
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WebMDHealth: http://my.webmd.com/drugs_and_herbs
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/
The following is a specific Web list relating to hypertension; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •
General Overview Age-Related Cognitive Decline Source: Healthnotes, Inc. www.healthnotes.com Angina Source: Healthnotes, Inc. www.healthnotes.com Atherosclerosis and Heart Disease Prevention Source: Prima Communications, Inc.www.personalhealthzone.com Athletic Performance Source: Healthnotes, Inc. www.healthnotes.com Bell's Palsy Source: Healthnotes, Inc. www.healthnotes.com Bone Infection Source: Integrative Medicine Communications; www.drkoop.com Canker Sores Source: Healthnotes, Inc. www.healthnotes.com Capillary Fragility Source: Healthnotes, Inc. www.healthnotes.com Cardiac Arrhythmia Source: Healthnotes, Inc. www.healthnotes.com Cardiomyopathy Source: Healthnotes, Inc. www.healthnotes.com Cardiovascular Disease Overview Source: Healthnotes, Inc. www.healthnotes.com Congestive Heart Failure Source: Healthnotes, Inc. www.healthnotes.com Diabetes Source: Prima Communications, Inc.www.personalhealthzone.com
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Diabetes Mellitus Source: Integrative Medicine Communications; www.drkoop.com Edema Source: Healthnotes, Inc. www.healthnotes.com Erectile Dysfunction Source: Healthnotes, Inc. www.healthnotes.com Fainting Source: Integrative Medicine Communications; www.drkoop.com Gastritis Source: Healthnotes, Inc. www.healthnotes.com Gestational Hypertension Source: Healthnotes, Inc. www.healthnotes.com Gout Source: Healthnotes, Inc. www.healthnotes.com Heart Attack Source: Healthnotes, Inc. www.healthnotes.com Heart Attack Source: Integrative Medicine Communications; www.drkoop.com Hepatitis Source: Healthnotes, Inc. www.healthnotes.com High Blood Pressure Source: Integrative Medicine Communications; www.drkoop.com High Cholesterol Source: Healthnotes, Inc. www.healthnotes.com High Cholesterol Source: Integrative Medicine Communications; www.drkoop.com High Cholesterol Source: Prima Communications, Inc.www.personalhealthzone.com High Homocysteine Source: Healthnotes, Inc. www.healthnotes.com High Triglycerides Source: Healthnotes, Inc. www.healthnotes.com HIV and AIDS Support Source: Healthnotes, Inc. www.healthnotes.com
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Hypercholesterolemia Source: Integrative Medicine Communications; www.drkoop.com Hyperkalemia Source: Integrative Medicine Communications; www.drkoop.com Hypertension Source: Integrative Medicine Communications; www.drkoop.com Hypertension Source: Integrative Medicine Communications; www.drkoop.com Hypertension Alternative names: High Blood Pressure Source: Prima Communications, Inc.www.personalhealthzone.com Indigestion, Heartburn, and Low Stomach Acidity Source: Healthnotes, Inc. www.healthnotes.com Insulin Resistance Syndrome Source: Healthnotes, Inc. www.healthnotes.com Liver Cirrhosis Source: Healthnotes, Inc. www.healthnotes.com Macular Degeneration Source: Healthnotes, Inc. www.healthnotes.com Menopause Source: Healthnotes, Inc. www.healthnotes.com Menopause Source: Integrative Medicine Communications; www.drkoop.com Mitral Valve Prolapse Source: Healthnotes, Inc. www.healthnotes.com Myocardial Infarction Source: Integrative Medicine Communications; www.drkoop.com Obesity Source: Integrative Medicine Communications; www.drkoop.com Osteomyelitis Source: Integrative Medicine Communications; www.drkoop.com Potassium, Excess in Blood Source: Integrative Medicine Communications; www.drkoop.com Preeclampsia Source: Healthnotes, Inc. www.healthnotes.com
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Preeclampsia Source: Integrative Medicine Communications; www.drkoop.com Pregnancy and Postpartum Support Source: Healthnotes, Inc. www.healthnotes.com Pulmonary Hypertension Source: Integrative Medicine Communications; www.drkoop.com Raynaud's Phenomenon Source: Integrative Medicine Communications; www.drkoop.com Retinopathy Source: Healthnotes, Inc. www.healthnotes.com Scleroderma Source: Integrative Medicine Communications; www.drkoop.com Stroke Source: Healthnotes, Inc. www.healthnotes.com Stroke Source: Integrative Medicine Communications; www.drkoop.com Syncope Source: Integrative Medicine Communications; www.drkoop.com Varicose Veins Source: Prima Communications, Inc.www.personalhealthzone.com •
Alternative Therapy Acupuncture Source: Healthnotes, Inc. www.healthnotes.com Apitherapy Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,669,00.html Chiropractic Source: Healthnotes, Inc. www.healthnotes.com Chiropractic Source: Integrative Medicine Communications; www.drkoop.com Homeovitics Alternative names: homoeovitics Source: The Canoe version of A Dictionary of Alternative-Medicine Methods, by Priorities for Health editor Jack Raso, M.S., R.D. Hyperlink: http://www.canoe.ca/AltmedDictionary/h.html
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Light Therapy Source: Healthnotes, Inc. www.healthnotes.com Mind&Body Medicine Source: Integrative Medicine Communications; www.drkoop.com Raktamoksha Source: The Canoe version of A Dictionary of Alternative-Medicine Methods, by Priorities for Health editor Jack Raso, M.S., R.D. Hyperlink: http://www.canoe.ca/AltmedDictionary/r.html Trager approach Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,741,00.html Yoga Source: Integrative Medicine Communications; www.drkoop.com •
Chinese Medicine Dilong Alternative names: Earthworm; Pheretima Source: Chinese Materia Medica Duzhong Alternative names: Eucommia Bark; Cortex Eucommiae Source: Chinese Materia Medica Fangji Alternative names: Fourstamen Stephania Root; Radix Stephaniae Tetrandrae Source: Chinese Materia Medica Gancao Jingao Alternative names: Liquorice Extract; Gancao JingaoExtractum Glycyrrhizae
Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Hyperlink: http://www.newcenturynutrition.com/cgilocal/patent_herbs_db/db.cgi?db=default&Chinese=Gancao%20Jingao&mh=10&sb =---&view_records=View+Records Gegen Alternative names: Kudzuvine Root; Radix Puerariae Source: Chinese Materia Medica Gouguye Alternative names: Chinese Holly Leaf; Folium Ilicis Cornutae Source: Chinese Materia Medica
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Gouteng Alternative names: Gambir Plant; Ramulus Uncariae cum Uncis Source: Chinese Materia Medica Luobumaye Alternative names: Dogbane Leaf; Folium Apocyni Veneti Source: Chinese Materia Medica Qingnao Jiangya Pian Alternative names: Qingnao Jiangya Tablets Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Hyperlink: http://www.newcenturynutrition.com/cgilocal/patent_herbs_db/db.cgi?db=default&Chinese=Qingnao%20Jiangya%20Pian& mh=10&sb=---&view_records=View+Records Sangjisheng Alternative names: Chinese Taxillus Herb; Herba Taxilli Source: Chinese Materia Medica Wuzhuyu Alternative names: Medicinal Evodia Fruit; Fructus Evodiae Source: Chinese Materia Medica Xiakucao Alternative names: Common Selfheal Fruit-Spike; Spica Prunellae Source: Chinese Materia Medica Yinyanghuo Alternative names: Epimedium Herb; Herba Epimedii Source: Chinese Materia Medica •
Homeopathy Argentum nitricum Source: Healthnotes, Inc. www.healthnotes.com Aurum metallicum Source: Healthnotes, Inc. www.healthnotes.com Belladonna Source: Healthnotes, Inc. www.healthnotes.com Calcarea carbonica Source: Healthnotes, Inc. www.healthnotes.com Glonoinum Source: Healthnotes, Inc. www.healthnotes.com Lachesis Source: Healthnotes, Inc. www.healthnotes.com
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Natrum muriaticum Source: Healthnotes, Inc. www.healthnotes.com Nux vomica Source: Healthnotes, Inc. www.healthnotes.com Phosphorus Source: Healthnotes, Inc. www.healthnotes.com Plumbum Source: Healthnotes, Inc. www.healthnotes.com Sanguinaria Source: Healthnotes, Inc. www.healthnotes.com •
Herbs and Supplements Acebutolol Source: Healthnotes, Inc. www.healthnotes.com ALA Source: Integrative Medicine Communications; www.drkoop.com Alpha2-Adrenergic Agonists Source: Integrative Medicine Communications; www.drkoop.com Alpha-Linolenic Acid (ALA) Source: Integrative Medicine Communications; www.drkoop.com American Ginseng Alternative names: Panax quinquefolium Source: Integrative Medicine Communications; www.drkoop.com Amiloride Source: Healthnotes, Inc. www.healthnotes.com Amino Acids Overview Source: Healthnotes, Inc. www.healthnotes.com Amlodipine Source: Healthnotes, Inc. www.healthnotes.com Ananas comosus Source: Integrative Medicine Communications; www.drkoop.com Angelica sinensis Source: Integrative Medicine Communications; www.drkoop.com Angiotensin II Receptor Blockers Source: Healthnotes, Inc. www.healthnotes.com
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Aortic Glycosaminoglycans Source: Prima Communications, Inc.www.personalhealthzone.com Arginine Source: Healthnotes, Inc. www.healthnotes.com Asian Ginseng Alternative names: Panax ginseng Source: Healthnotes, Inc. www.healthnotes.com Asian Ginseng Alternative names: Panax ginseng Source: Integrative Medicine Communications; www.drkoop.com Astragalus Alternative names: Astragalus membranaceus, Astragalus membranaceus var. mongholicus, Huang-qi, Milk-Vetch Root Source: Integrative Medicine Communications; www.drkoop.com Astragalus Source: Prima Communications, Inc.www.personalhealthzone.com Astragalus membranaceus Source: Integrative Medicine Communications; www.drkoop.com Astragalus mongholicus Alternative names: Astragalus membranaceus, Astragalus membranaceus var. mongholicus, Huang-qi, Milk-Vetch Root Source: Integrative Medicine Communications; www.drkoop.com Atenolol Source: Healthnotes, Inc. www.healthnotes.com Benazepril Source: Healthnotes, Inc. www.healthnotes.com Berberis Alternative names: Barberry; Berberis sp. Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Beta-Adrenergic Blockers Source: Healthnotes, Inc. www.healthnotes.com Beta-Blockers Source: Integrative Medicine Communications; www.drkoop.com Beta-Blockers Source: Prima Communications, Inc.www.personalhealthzone.com Beta-Carotene Source: Prima Communications, Inc.www.personalhealthzone.com
Alternative Medicine 213
Betaxolol Source: Healthnotes, Inc. www.healthnotes.com Bilberry Alternative names: Vaccinium myrtillus Source: Healthnotes, Inc. www.healthnotes.com Bilberry Alternative names: Vaccinium myrtillus, European Blueberry, Huckleberry Source: Integrative Medicine Communications; www.drkoop.com Bilberry Source: Prima Communications, Inc.www.personalhealthzone.com Bisoprolol Source: Healthnotes, Inc. www.healthnotes.com Black Haw Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Blue Cohosh Alternative names: Caulophyllum thalictroides Source: Healthnotes, Inc. www.healthnotes.com Blue-Green Algae Source: Healthnotes, Inc. www.healthnotes.com Borago Alternative names: Borage; Borago officinalis Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Brahmi Alternative names: Centella asiatica , Centella, March Pennywort, Indian Pennywort, Hydrocotyle, Brahmi (Sanskrit), Luei Gong Gen (Chinese)(Note: Gotu kola should not be confused with kola nut.) Source: Integrative Medicine Communications; www.drkoop.com Brewer's Yeast Alternative names: Nutritional Yeast Source: Integrative Medicine Communications; www.drkoop.com Bromelain Source: Healthnotes, Inc. www.healthnotes.com Bromelain Alternative names: Ananas comosus, Bromelainum Source: Integrative Medicine Communications; www.drkoop.com Bromelainum Source: Integrative Medicine Communications; www.drkoop.com
214 Hypertension
Caffeine Source: Healthnotes, Inc. www.healthnotes.com Candesartan Source: Healthnotes, Inc. www.healthnotes.com Captopril Source: Healthnotes, Inc. www.healthnotes.com Carnosine Source: Healthnotes, Inc. www.healthnotes.com Carvedilol Source: Healthnotes, Inc. www.healthnotes.com Centella Alternative names: Gotu Kola; Centella asiatica (Linn.) Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Centella Source: Integrative Medicine Communications; www.drkoop.com Centella asiatica Alternative names: Centella asiatica , Centella, March Pennywort, Indian Pennywort, Hydrocotyle, Brahmi (Sanskrit), Luei Gong Gen (Chinese)(Note: Gotu kola should not be confused with kola nut.) Source: Integrative Medicine Communications; www.drkoop.com Chinese Angelica Source: Integrative Medicine Communications; www.drkoop.com Clonidine Source: Healthnotes, Inc. www.healthnotes.com Clonidine Alternative names: Catapres Source: Prima Communications, Inc.www.personalhealthzone.com Coenzyme Q10 Source: Healthnotes, Inc. www.healthnotes.com Coenzyme Q10 Source: Integrative Medicine Communications; www.drkoop.com Coenzyme Q10 (CoQ10) Source: Prima Communications, Inc.www.personalhealthzone.com Coleus Alternative names: Coleus forskohlii Source: Healthnotes, Inc. www.healthnotes.com
Alternative Medicine 215
Coleus forskohlii Source: Prima Communications, Inc.www.personalhealthzone.com CoQ10 Source: Integrative Medicine Communications; www.drkoop.com Corydalis Alternative names: Corydalis turtschaninovii, Corydalis yanhusuo Source: Healthnotes, Inc. www.healthnotes.com Crataegus Alternative names: Hawthorn; Crataegus oxyacantha L. Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Crataegus laevigata Source: Integrative Medicine Communications; www.drkoop.com Crataegus monogyna Source: Integrative Medicine Communications; www.drkoop.com Cyclosporine Source: Healthnotes, Inc. www.healthnotes.com Cysteine Source: Integrative Medicine Communications; www.drkoop.com Danggui Alternative names: Angelica sinensis, Chinese Angelica, Dang Gui, Danngui, Dong Qua, Tang Kuei, Tan Kue Bai zhi(Note: Dong quai should not be confused with Angelica root or Angelica seed.) Source: Integrative Medicine Communications; www.drkoop.com Dehydroepiandrosterone (DHEA) Source: Healthnotes, Inc. www.healthnotes.com DHA Source: Integrative Medicine Communications; www.drkoop.com Diltiazem Source: Healthnotes, Inc. www.healthnotes.com Diuretics Source: Healthnotes, Inc. www.healthnotes.com Docosahexaenoic Acid Source: Healthnotes, Inc. www.healthnotes.com Docosahexaenoic Acid (DHA) Source: Integrative Medicine Communications; www.drkoop.com
216 Hypertension
Dong Quai Alternative names: Angelica sinensis Source: Healthnotes, Inc. www.healthnotes.com Dong Quai Alternative names: Angelica sinensis, Chinese Angelica, Dang Gui, Danngui, Dong Qua, Tang Kuei, Tan Kue Bai zhi(Note: Dong quai should not be confused with Angelica root or Angelica seed.) Source: Integrative Medicine Communications; www.drkoop.com Dorzolamide Source: Healthnotes, Inc. www.healthnotes.com Doxazosin Source: Healthnotes, Inc. www.healthnotes.com Eicosapentaenoic Acid (EPA) Source: Integrative Medicine Communications; www.drkoop.com Eleuthero Source: Healthnotes, Inc. www.healthnotes.com Enalapril Source: Healthnotes, Inc. www.healthnotes.com EPA Source: Integrative Medicine Communications; www.drkoop.com Ephedra Source: Healthnotes, Inc. www.healthnotes.com European Blueberry Source: Integrative Medicine Communications; www.drkoop.com Felodipine Source: Healthnotes, Inc. www.healthnotes.com Fennel Source: Healthnotes, Inc. www.healthnotes.com Fiber Source: Healthnotes, Inc. www.healthnotes.com Fibric Acid Derivatives Source: Integrative Medicine Communications; www.drkoop.com Flaxseed Alternative names: Linum usitatissimum, Linseed Source: Integrative Medicine Communications; www.drkoop.com Ginkgo Biloba Source: Integrative Medicine Communications; www.drkoop.com
Alternative Medicine 217
Ginseng, American Alternative names: Panax quinquefolium Source: Integrative Medicine Communications; www.drkoop.com Ginseng, Asian Alternative names: Panax ginseng Source: Integrative Medicine Communications; www.drkoop.com Glucosamine Source: Healthnotes, Inc. www.healthnotes.com Glutathione Source: Healthnotes, Inc. www.healthnotes.com Glycyrrhiza glabra Source: Integrative Medicine Communications; www.drkoop.com Glycyrrhiza1 Alternative names: Licorice; Glycyrrhiza glabra L. Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Gotu Kola Alternative names: Centella asiatica Source: Healthnotes, Inc. www.healthnotes.com Gotu Kola Alternative names: Centella asiatica , Centella, March Pennywort, Indian Pennywort, Hydrocotyle, Brahmi (Sanskrit), Luei Gong Gen (Chinese)(Note: Gotu kola should not be confused with kola nut.) Source: Integrative Medicine Communications; www.drkoop.com Gotu Kola Source: Prima Communications, Inc.www.personalhealthzone.com Grape Seed Alternative names: Vitis vinifera Source: Integrative Medicine Communications; www.drkoop.com Guanfacine Source: Healthnotes, Inc. www.healthnotes.com Gymnema Alternative names: Gurmar; Gymnema sylvestre Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Hawthorn Alternative names: Crataegus laevigata, Crataegus oxyacantha, Crataegus monogyna Source: Healthnotes, Inc. www.healthnotes.com
218 Hypertension
Hawthorn Alternative names: Crataegus monogyna, Crataegus laevigata Source: Integrative Medicine Communications; www.drkoop.com Hawthorn Source: Prima Communications, Inc.www.personalhealthzone.com Hawthorn Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Hawthorn Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10035,00.html Hibiscus Alternative names: Hibiscus, Roselle; Hibiscus sp. Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Huang-qi Source: Integrative Medicine Communications; www.drkoop.com Huckleberry Source: Integrative Medicine Communications; www.drkoop.com Huperzine A Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10038,00.html Hydralazine Source: Healthnotes, Inc. www.healthnotes.com Hydralazine Alternative names: Apresoline Source: Prima Communications, Inc.www.personalhealthzone.com Hydrocotyle Source: Integrative Medicine Communications; www.drkoop.com Indapamide Source: Healthnotes, Inc. www.healthnotes.com Indian Pennywort Source: Integrative Medicine Communications; www.drkoop.com Irbesartan Source: Healthnotes, Inc. www.healthnotes.com
Alternative Medicine 219
Kudzu Alternative names: Pueraria lobata Source: Healthnotes, Inc. www.healthnotes.com Labetalol Source: Healthnotes, Inc. www.healthnotes.com Lemon Balm Alternative names: Melissa officinalis Source: Healthnotes, Inc. www.healthnotes.com Licorice Alternative names: Glycyrrhiza glabra, Glycyrrhiza uralensis Source: Healthnotes, Inc. www.healthnotes.com Licorice Alternative names: Glycyrrhiza glabra, Spanish Licorice Source: Integrative Medicine Communications; www.drkoop.com Linden Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Linseed Source: Integrative Medicine Communications; www.drkoop.com Linum usitatissimum Source: Integrative Medicine Communications; www.drkoop.com Liquorice Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Lisinopril Source: Healthnotes, Inc. www.healthnotes.com Loop Diuretics Source: Healthnotes, Inc. www.healthnotes.com Losartan Source: Healthnotes, Inc. www.healthnotes.com Ma Huang Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Maidenhair Tree Source: Integrative Medicine Communications; www.drkoop.com Maitake Source: Prima Communications, Inc.www.personalhealthzone.com
220 Hypertension
Marsh Pennywort Alternative names: Centella asiatica , Centella, March Pennywort, Indian Pennywort, Hydrocotyle, Brahmi (Sanskrit), Luei Gong Gen (Chinese)(Note: Gotu kola should not be confused with kola nut.) Source: Integrative Medicine Communications; www.drkoop.com Melatonin Source: Healthnotes, Inc. www.healthnotes.com Melatonin Source: Integrative Medicine Communications; www.drkoop.com Methyldopa Source: Healthnotes, Inc. www.healthnotes.com Methyldopa Alternative names: Aldomet Source: Prima Communications, Inc.www.personalhealthzone.com Metoprolol Source: Healthnotes, Inc. www.healthnotes.com Milk-Vetch Root Source: Integrative Medicine Communications; www.drkoop.com Mistletoe Alternative names: Viscum album Source: Healthnotes, Inc. www.healthnotes.com Mixed Amphetamines Source: Healthnotes, Inc. www.healthnotes.com Moexipril Source: Healthnotes, Inc. www.healthnotes.com Nadolol Source: Healthnotes, Inc. www.healthnotes.com Nettle Source: Prima Communications, Inc.www.personalhealthzone.com Nifedipine Source: Healthnotes, Inc. www.healthnotes.com Nonsteroidal Anti-inflammatory Drugs (NSAIDs) Source: Integrative Medicine Communications; www.drkoop.com Olive Leaf Alternative names: Olea europa Source: Healthnotes, Inc. www.healthnotes.com
Alternative Medicine 221
Oral Hypoglycemics Source: Prima Communications, Inc.www.personalhealthzone.com Panax Alternative names: Ginseng; Panax ginseng Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Panax ginseng Source: Integrative Medicine Communications; www.drkoop.com Panax quinquefolium Source: Integrative Medicine Communications; www.drkoop.com Phenothiazine Derivatives Source: Integrative Medicine Communications; www.drkoop.com Phenylalanine Source: Integrative Medicine Communications; www.drkoop.com Pimpinella Alternative names: Anise; Pimpinella anisum (L) Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Prazosin Source: Healthnotes, Inc. www.healthnotes.com Propranolol Source: Healthnotes, Inc. www.healthnotes.com Psyllium Alternative names: Plantago ovata, Plantago ispaghula Source: Healthnotes, Inc. www.healthnotes.com Pueraria Alternative names: Kudzu; Pueraria lobata Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Quinapril Source: Healthnotes, Inc. www.healthnotes.com Ramipril Source: Healthnotes, Inc. www.healthnotes.com Reishi Alternative names: Ganoderma lucidum Source: Healthnotes, Inc. www.healthnotes.com Ribes Alternative names: Black Currant; Ribes nigrum L. Source: Alternative Medicine Foundation, Inc. www.amfoundation.org
222 Hypertension
Selegiline Source: Healthnotes, Inc. www.healthnotes.com Siberian ginseng Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,821,00.html Silybum Alternative names: Milk Thistle; Silybum marianum (L.) Gaertn. Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Spanish Licorice Source: Integrative Medicine Communications; www.drkoop.com Stevia Alternative names: Sweetleaf; Stevia rebaudiana Bertoni Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Sulfonylureas Source: Integrative Medicine Communications; www.drkoop.com Symphytum Alternative names: Comfrey; Symphytum officinale L. Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Tang Kuei Source: Integrative Medicine Communications; www.drkoop.com Taurine Source: Healthnotes, Inc. www.healthnotes.com Taurine Source: Prima Communications, Inc.www.personalhealthzone.com Terazosin Source: Healthnotes, Inc. www.healthnotes.com Thiazide Diuretics Source: Healthnotes, Inc. www.healthnotes.com Thiazide Diuretics Source: Integrative Medicine Communications; www.drkoop.com Thiazide Diuretics Source: Prima Communications, Inc.www.personalhealthzone.com Thioxanthene Derivatives Source: Integrative Medicine Communications; www.drkoop.com Timolol Source: Healthnotes, Inc. www.healthnotes.com
Alternative Medicine 223
Triamterene Source: Healthnotes, Inc. www.healthnotes.com Tribulus Puncture Alternative names: Puncture Vine, Goathead; Tribulus terrestris L. Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Tricyclic Antidepressants (TCAs) Source: Integrative Medicine Communications; www.drkoop.com Trigonella Alternative names: Fenugreek; Trigonella foenum graecum L. Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Triotann-S Pediatric Source: Healthnotes, Inc. www.healthnotes.com Uncaria asian Alternative names: Asian species; Uncaria sp. Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Uva ursi Alternative names: Arctostaphylos uva-ursi Source: Healthnotes, Inc. www.healthnotes.com Vaccinium myrtillus Source: Integrative Medicine Communications; www.drkoop.com VacciniumB Alternative names: Bilberry; Vaccinium myrtillus L. Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Valerian Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Valsartan Source: Healthnotes, Inc. www.healthnotes.com Vasodilators Source: Integrative Medicine Communications; www.drkoop.com Verapamil Source: Healthnotes, Inc. www.healthnotes.com Vitis vinifera Source: Integrative Medicine Communications; www.drkoop.com Wood Betony Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca
224 Hypertension
Yarrow Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Yohimbe Alternative names: Pausinystalia yohimbe Source: Healthnotes, Inc. www.healthnotes.com Yohimbe Source: Prima Communications, Inc.www.personalhealthzone.com
General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.
225
CHAPTER 4. DISSERTATIONS ON HYPERTENSION Overview In this chapter, we will give you a bibliography on recent dissertations relating to hypertension. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “hypertension” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on hypertension, we have not necessarily excluded nonmedical dissertations in this bibliography.
Dissertations on Hypertension ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to hypertension. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •
A Bioanthropological Perspective of Hypertension in Arab-americans in the Metropolitan Detroit Area (michigan) by Hassoun, Rosina Jean, Phd from University of Florida, 1995, 413 pages http://wwwlib.umi.com/dissertations/fullcit/9607520
•
A Biocultural Analysis of Blood Pressure Variation among the Black Caribs and Creoles of St. Vincent, West Indies (hypertension) by Hutchinson, Janice Faye, Phd from University of Kansas, 1984, 295 pages http://wwwlib.umi.com/dissertations/fullcit/8424370
•
A Comparison of Power Spectral Analysis of Heart Rate Variability and Baroreceptor Sensitivity in Healthy, Caucasian and African American Men and Women (africanamerican, Gender Differences, Hypertension) by Horodyski, Marybeth Harman, Edd from Columbia University Teachers College, 1993, 132 pages http://wwwlib.umi.com/dissertations/fullcit/9320980
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•
A Hypertension Control Pilot Study for the African-american Elderly by Walker, Chantay Cheri, Phd from University of Alabama at Birmingham, 1998, 163 pages http://wwwlib.umi.com/dissertations/fullcit/9839864
•
A Phenomenological Approach to Compliance to Prescribed Antihypertensive Medications in Puerto Ricans by Rivera-villegas, Pedro Antonio, Phd from Southern Illinois University at Carbondale, 1995, 170 pages http://wwwlib.umi.com/dissertations/fullcit/9614971
•
A Study of the Defensive Styles Associated with Essential Hypertension and Peptic Ulcer by Belfrage, James E; Phd from York University (canada), 1978 http://wwwlib.umi.com/dissertations/fullcit/NK38481
•
A Study of the Effectiveness of a Stress Management Program on Hypertension by Bosley, Florida Mae, Phd from Washington University, 1982, 118 pages http://wwwlib.umi.com/dissertations/fullcit/8223765
•
A Study of the Impact of Level of Activity and Nutrition As It Affects Hypertension in Elderly African-americans at Two Senior Centers in Atlanta, Georgia by Maddox, Janice Helen Williams, Phd from The Union Institute, 1998, 109 pages http://wwwlib.umi.com/dissertations/fullcit/9828440
•
A Study of Three Models of Hypertension Genetic, Mineralocorticoid and Ethanolinduced by Chan, Thomas C. K; Phd from The University of British Columbia (canada), 1983 http://wwwlib.umi.com/dissertations/fullcit/NK65040
•
Acute Hypertension Inhibits Drinking Behavior but Not Vasopressin Release Stimulated by Angiotensin Ii or Hyperosmolality by Stocker, Sean David; Phd from University of Pittsburgh, 2002, 151 pages http://wwwlib.umi.com/dissertations/fullcit/3054339
•
Alcohol-induced Hepatomegaly Possible Role in Portal Hypertension by Britton, Robert S; Phd from University of Toronto (canada), 1984 http://wwwlib.umi.com/dissertations/fullcit/NK66805
•
Aldosterone Metabolism in Normal Subjects and in Patients with Benign Essential Hypertension by Grose, John H; Phd from Mcgill University (canada), 1973 http://wwwlib.umi.com/dissertations/fullcit/NK15863
•
Alterations in Endothelin Receptor Subtypes in the Pathogenesis of Hypertensioninduced Ventricular Cell Hypertrophy by Lee, Grahad Robert; Phd from Queen's University of Belfast (northern Ireland), 2002, 447 pages http://wwwlib.umi.com/dissertations/fullcit/f683937
•
Alterations in the Renal Vasculature during the Development of Hypertension by Smeda, John S; Phd from Mcmaster University (canada), 1984 http://wwwlib.umi.com/dissertations/fullcit/NK65447
•
An Assessment of the Effects of Health Education Modalities on Hypertension Clinic Outpatients. by Cryer, Dennis Craig, Phd from The University of Utah, 1975, 150 pages http://wwwlib.umi.com/dissertations/fullcit/7528871
•
An Evaluation of a Hypertension Screening and Intervention Program for High School Students. by Latham, Gail Fowler, Edd from Duke University, 1979, 210 pages http://wwwlib.umi.com/dissertations/fullcit/7922758
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•
An Examination of Social and Demographic Variables and Treatment Adherence in Male Veterans with Primary Hypertension by Totin, Martha J. Psyd from Chicago School of Professional Psychology, 2002, 110 pages http://wwwlib.umi.com/dissertations/fullcit/3049748
•
An Examination of the Efficacy of Eeg Biofeedback on the Treatment of Essential Hypertension: a Presentation and Implementation of a Comprehensive Protocol for Treating the Disorder by Peterson, Dana Timothy; Phd from Rosemead School of Psychology, Biola University, 2002, 83 pages http://wwwlib.umi.com/dissertations/fullcit/3076457
•
An Examination of the Hypothesis That Structural Changes Which Occur in Hypertension, Are a Result of the Increase in Arterial Pressure by Pang, Stephen Ching-ng; Phd from Memorial University of Newfoundland (canada), 1982 http://wwwlib.umi.com/dissertations/fullcit/NK63611
•
Ancient Environments and Modern Disease: the Case of Hypertension among Afroamericans by Wilson, Thomas Woodrow, Phd from Bowling Green State University, 1987, 204 pages http://wwwlib.umi.com/dissertations/fullcit/8728411
•
Biocultural Correlates of Pregnancy Induced Hypertension. by Poland, Marilyn Laken, Phd from Wayne State University, 1978, 92 pages http://wwwlib.umi.com/dissertations/fullcit/7816071
•
Biological Effects and Genetic Analysis of Thermosensitivity in Hypertension by Malo, Danielle; Phd from Mcgill University (canada), 1989 http://wwwlib.umi.com/dissertations/fullcit/NL52180
•
Biomedicine and Ideology: a Social History of the Conceptualization and Treatment of Essential Hypertension in the United States by Greenlee, Edwin J., Phd from Temple University, 1989, 305 pages http://wwwlib.umi.com/dissertations/fullcit/8920251
•
Blood Pressure, Blood Pressure Development and Potential Risk Factors for Hypertension with Special Reference to Metabolic Factors and Kidney Function by Kristjansson, Karl; Meddr from Goteborgs Universitet (sweden), 2002, 104 pages http://wwwlib.umi.com/dissertations/fullcit/f660673
•
Calcitonin Gene-related Peptide and Its Novel Receptors in Hypoxic Pulmonary Hypertension by Qing, Xin; , Phd from The University of Wisconsin - Madison, 2002, 172 pages http://wwwlib.umi.com/dissertations/fullcit/3060616
•
Calcium Uptake and Enzymatic Activities of Subcellular Fractions from Cardiovascular System of Normotensive and Hypertensive Rats (calcium Regulation and Hypertension) by Wei, Jiann-wu; Phd from University of Alberta (canada), 1976 http://wwwlib.umi.com/dissertations/fullcit/NK27754
•
Cardiac Remodeling and Systolic Function in Response to Hypertension (htn), Diabetes (d), and Hypertension-diabetes (h-d) by Bernal, Juan Mario; Ms from The University of Alabama at Birmingham, 2002, 61 pages http://wwwlib.umi.com/dissertations/fullcit/1411126
•
Catecholamine Synthesising Enzymes in the Programming of Hypertension by Mild Protein Restriction during Gestation by Copin, Nane; Phd from University of Southampton (united Kingdom), 2002 http://wwwlib.umi.com/dissertations/fullcit/f293089
228 Hypertension
•
Cerebrovascular Permeability in Experimental Hypertension by Nag, Sukriti; Phd from Queen's University at Kingston (canada), 1978 http://wwwlib.umi.com/dissertations/fullcit/NK37531
•
Change and Hypertension in the Population of Marakei Atoll, Kiribati by Lewis, David Eldrige, Jr., Phd from The University of Arizona, 1981, 374 pages http://wwwlib.umi.com/dissertations/fullcit/8126169
•
Characterization of Sympathetic Ganglion Sensitivity to Substance P in a Genetic and a Non-genetic Rat Model of Hypertension by Tompkins, John Daniel; Phd from East Tennessee State University, 2003, 77 pages http://wwwlib.umi.com/dissertations/fullcit/3083442
•
Childhood Hypertension - Knowledge and Health Beliefs of Sixth Graders and Their Parent(s) by Jarvis, Linda Louise, Edd from Boston University, 1986, 219 pages http://wwwlib.umi.com/dissertations/fullcit/8612174
•
Christian Meditation and Biofeedback Training As Psychotherapeutic Agents in the Treatment of Essential Hypertension by Bynum, Jack Lynn, Edd from Southwestern Baptist Theological Seminary, 1980 http://wwwlib.umi.com/dissertations/fullcit/f1026822
•
Culture Change, Stress and Epidemiological Transition in Bangladesh: an Anthropological Study of Chronic Degenerative Disorders (diabetes and Hypertension) among Rural and Urban Populations by Choudhury, Ahmed Fazle Hasan, Phd from Southern Illinois University at Carbondale, 1987, 261 pages http://wwwlib.umi.com/dissertations/fullcit/8728266
•
Determinants of Loss of Control of Hypertension by Casson, Richard Ian; Msc from Queen's University at Kingston (canada), 2002, 106 pages http://wwwlib.umi.com/dissertations/fullcit/MQ65608
•
Dietary Adherence among Rural African-american Elders with Hypertension: an Ethnographic Approach by Schoenberg, Nancy Ellen, Phd from University of Florida, 1994, 249 pages http://wwwlib.umi.com/dissertations/fullcit/9607124
•
Distribution of Regional Blood Flow and Vascular Resistance in Experimental Renal Hypertension by Allotey, John B. K; Phd from Mcgill University (canada), 1977 http://wwwlib.umi.com/dissertations/fullcit/NK33228
•
Dynamic Competition and Product Innovation Within the Prescription Antihypertensive Market by Bonk, Robert John, Phd from Philadelphia College of Pharmacy and Science, 1995, 225 pages http://wwwlib.umi.com/dissertations/fullcit/9527843
•
Effectiveness of Biofeedback Assisted Relaxation Treatment of Essential Hypertension in the Elderly by Schonfeld, Ginny M., Edd from University of Toronto (canada), 1992, 236 pages http://wwwlib.umi.com/dissertations/fullcit/NN78827
•
Effectiveness of Patient Education for Improving Compliance in Hypertension Therapy. by Lambert, Martin Lee, Jr., Phd from The University of Tennessee, 1978, 115 pages http://wwwlib.umi.com/dissertations/fullcit/7903437
Dissertations 229
•
Effects of Aerobic Fitness Level and Parental History of Hypertension on Cardiovascular Reactivity to Mental Arithmetic (psychological Stress, Blood Pressure) by Nixon, Patricia Ann, Phd from University of Pittsburgh, 1986, 79 pages http://wwwlib.umi.com/dissertations/fullcit/8701978
•
Effects of Swim Training on Blood Pressure and Other Cardiovascular Risk Factors in Individuals with Hypertension by Tanaka, Hirofumi, Phd from The University of Tennessee, 1995, 115 pages http://wwwlib.umi.com/dissertations/fullcit/9609322
•
Elastin and Elastase in the Pathogenesis of Pulmonary Hypertension in the Rat Monocrotaline Model by Todorovich-hunter, Livia; Phd from University of Toronto (canada), 1989 http://wwwlib.umi.com/dissertations/fullcit/NL54570
•
Essential Hypertension in Urban Adolescents: the Epidemiology of Obesity and Physical Fitness by Wilson, Susan Louise, Phd from Southern Methodist University, 1982, 253 pages http://wwwlib.umi.com/dissertations/fullcit/8216732
•
Essential Hypertension, Family Functioning, and Family Therapy by Duhamel, Fabie; Phd from University of Calgary (canada), 1987 http://wwwlib.umi.com/dissertations/fullcit/NL37983
•
Evaluation of the Reliability and Validity of the Hypertension Education Level Test by Martin, Barbara Clare, Edd from Southern Illinois University at Edwardsville, 1987, 71 pages http://wwwlib.umi.com/dissertations/fullcit/8725340
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Expectancy of Control Beliefs and Health Value As Predisposing Influences in Hypertension Information Preferences among Elderly Hypertensives and Nonhypertensives by Pastoriza Maldonado, Alida, Edd from Columbia University Teachers College, 1985, 174 pages http://wwwlib.umi.com/dissertations/fullcit/8510161
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Family Functioning and Hypertension in a Black Population. by Frate, Dennis Anthony, Phd from University of Illinois at Urbana-champaign, 1978, 280 pages http://wwwlib.umi.com/dissertations/fullcit/7913458
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Genetic Factors Contributing to Hypertension: with Emphasis on Hypertension in Type 2 Diabetes by Bengtsson, Kristina; Phd from Lunds Universitet (sweden), 2002, 136 pages http://wwwlib.umi.com/dissertations/fullcit/f660769
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Haemodynamic Profiling for Diagnosing and Treating Hypertension by Daniel, G. S. H; Phd from Dalhousie University (canada), 1984 http://wwwlib.umi.com/dissertations/fullcit/NK66111
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Hypertension and Social Support: the Medical Anthropology of Older, Urban Samoans by Du Bois, Barbara Constance, Phd from University of Hawaii, 1987, 447 pages http://wwwlib.umi.com/dissertations/fullcit/8812139
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Hypertension and Social Support: the Medical Anthropology of Older, Urban Samoans by Dubois, Barbara Constance, Phd from University of Hawaii, 1987 http://wwwlib.umi.com/dissertations/fullcit/f149893
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Hypertension and the Department of Transportation by Walls, George Samuel, Iii; Mph from The University of Texas Graduate Sch. of Biomedical Sci. at Galveston, 2002, 14 pages http://wwwlib.umi.com/dissertations/fullcit/1408249
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Hypertension and the Elderly: Managing Invisible Disease (compliance) by Wheeler, Robinetta Theresa, Phd from University of California, San Francisco, 1985, 216 pages http://wwwlib.umi.com/dissertations/fullcit/8513672
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Hypertension in a Defined Population: the Skaraborg Hypertension and Diabetes Project (sweden) by Bog-hansen, Erik; Phd from Lunds Universitet (sweden), 2002, 143 pages http://wwwlib.umi.com/dissertations/fullcit/f692817
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Hypertension in St. Lucia: Social and Cultural Dimensions. by Dressler, William Wymer, Phd from The University of Connecticut, 1978, 366 pages http://wwwlib.umi.com/dissertations/fullcit/7913008
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Hypertension: an Analysis of Detroit Afro-american Health Patterns (michigan) by Bailey, Eric Jon, Phd from Wayne State University, 1988, 194 pages http://wwwlib.umi.com/dissertations/fullcit/8903218
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Hypnosis Utilizing Ericksonian Techniques in the Treatment of Essential Hypertension by Kerr, Deborah Ann, Phd from University of Alberta (canada), 1988 http://wwwlib.umi.com/dissertations/fullcit/f44565
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Hypnosis Utilizing Ericksonian Techniques in the Treatment of Essential Hypertension by Kerr, Deborah Ann; Phd from University of Alberta (canada), 1988 http://wwwlib.umi.com/dissertations/fullcit/NL42916
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Immediate Early Gene Expression in the Central Nervous System in Portal Hypertension: Functional and Immunohistochemical Studies by Song, Daisheng; Phd from University of Calgary (canada), 2002, 175 pages http://wwwlib.umi.com/dissertations/fullcit/NQ77039
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In Vivo and in Vitro Studies of Cardiocytes in Genetic Hypertension by Walter, Susan Valerie; Phd from Mcgill University (canada), 1986 http://wwwlib.umi.com/dissertations/fullcit/NL38377
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Insurance Medicine: from Eyeballing to Thorough Check-up (hypertension, Aids, Immune Deficiency) by Brown, Frances Rakower, Phd from City University of New York, 1995, 210 pages http://wwwlib.umi.com/dissertations/fullcit/9530856
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Intermediate and Long Term Effects of Progressive Relaxation Training upon Senior Center Participants (hypertension) by Bloomberg, Sandra Lee, Phd from The University of Utah, 1984, 123 pages http://wwwlib.umi.com/dissertations/fullcit/8418726
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Interrelationships of the Sympathetic Nervous System, Vascular Reactivity and Electrolytes in Experimental Hypertension in Rabbits by Ayitey-smith, Edward; Phd from University of Ottawa (canada), 1971 http://wwwlib.umi.com/dissertations/fullcit/NK18121
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Job Stress and Health among Women Clerical Workers (occupational Stress, United States, Secretaries, Hypertension, Ulcers) by Balshem, Martha Levittan, Phd from Indiana University, 1985, 222 pages http://wwwlib.umi.com/dissertations/fullcit/8526982
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Lay Perceptions of Medication-taking among Women with Hypertension by Hoekelman, Margaret Campbell; Phd from University of Kentucky, 2000, 288 pages http://wwwlib.umi.com/dissertations/fullcit/9996027
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Mama Always Said: the Transmission of Health Care Beliefs among Three Generations of Rural Black Women (hypertension, South, Folk Medicine) by Randalldavid, Elizabeth Wilson, Phd from University of Florida, 1985, 237 pages http://wwwlib.umi.com/dissertations/fullcit/8523886
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Mapping Genes for Complex Traits: Obesity, Diabetes, Hypertension, and Dyslipidemia on the Pacific Island of Kosrae by Shmulewitz, Dvora; Phd from The Rockefeller University, 2002, 165 pages http://wwwlib.umi.com/dissertations/fullcit/3053194
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Mechanism of Augmented Alpha 2 Adrenergic Receptor Contraction in Aorta from Chronic Nitric Oxide Synthase Inhibited Hypertensive Rats by Carter, Rebecca W. Phd from The University of New Mexico, 2002, 142 pages http://wwwlib.umi.com/dissertations/fullcit/3058933
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Mechanisms Linking Ses to Hypertension: Findings from Three Longitudinal Studies among the Pre-retirement-age and Older Populations by Lu, Ranyan , Phd from University of Southern California, 1998, 313 pages http://wwwlib.umi.com/dissertations/fullcit/9930507
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Metabolism of Pregnenolone and Its Sulphate in Normotensive Control Subjects and Patients with Benign Essential Hypertension by Tan, Eng Lay; Phd from Mcgill University (canada), 1973 http://wwwlib.umi.com/dissertations/fullcit/NK16013
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Migration and Hypertension: an Ethnography of Disease Risk in an Urban Samoan Community (medical Ecology) by Janes, Craig Robert, Phd from Univ. of Calif., San Francisco with the Univ. of Calif., Berkeley, 1984, 406 pages http://wwwlib.umi.com/dissertations/fullcit/8425947
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Mitochondrial Dysfunction in Pulmonary Hypertension Syndrome in Broiler Chickens by Cawthon, David Randall; Phd from University of Arkansas, 2002, 149 pages http://wwwlib.umi.com/dissertations/fullcit/3067032
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Mortality, Survivorship and Longevity in American Samoa, 1950 to 1981 (cardiovascular, Hypertension, Diabetes, Obesity, Cancer) by Crews, Douglas Earl, Phd from The Pennsylvania State University, 1985, 176 pages http://wwwlib.umi.com/dissertations/fullcit/8516013
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Mutations in Wnk Kinases Cause Human Hypertension by Wilson, Frederick Hugh; Phd from Yale University, 2002, 207 pages http://wwwlib.umi.com/dissertations/fullcit/3046252
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'my Blood Boils': Folk Models of Hypertension and Compliance among Older New Orleans Black Women (louisiana) by Heurtin-roberts, Suzanne Marie, Phd from Univ. of Calif., San Francisco with the Univ. of Calif., Berkeley, 1988, 266 pages http://wwwlib.umi.com/dissertations/fullcit/8828124
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National Estimate of Cost of Illness for Hypertension and Non-persistence with Drug Therapy Using the Medical Expenditure Panel Survey by Graden, Suzanne Elaine; Phd from The Ohio State University, 2003, 183 pages http://wwwlib.umi.com/dissertations/fullcit/3088853
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Nutrition Intervention for Hypertension during Health Care Visits in Community Health Care Clinics by Mattfeldt-beman, Mildred Kay, Phd from Saint Louis University, 1992, 136 pages http://wwwlib.umi.com/dissertations/fullcit/9233814
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Observation of the Effects of Thermal Biofeedback Assisted by Autogenic Relaxation in Patients with Borderline or Mild Hypertension (biofeedback) by Chiraseveenuprapund, Anuluck, Edd from Boston University, 1994, 156 pages http://wwwlib.umi.com/dissertations/fullcit/9422504
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Patients' Knowledge and Beliefs about Hypertension and Their Reported Compliance with Treatment Regimens As Related to Blood Pressure Control. by Wolle, Joan M., Phd from University of Maryland College Park, 1977, 174 pages http://wwwlib.umi.com/dissertations/fullcit/7808197
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Peripheral Dopaminergic Mechanisms in Experimental Hypertension by Racz, Karoly; Phd from Mcgill University (canada), 1985 http://wwwlib.umi.com/dissertations/fullcit/NL31110
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Pharmacogenetic Studies of Antihypertensive Treatment: with Special Reference to the Renin-angiotensin-aldosterone System by Kurland, Lisa; Phd from Uppsala Universitet (sweden), 2002, 57 pages http://wwwlib.umi.com/dissertations/fullcit/f661009
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Physiological Factors in Micro-embolic Renal Ischemic Hypertension by Mersereau, William A; Advdeg from Mcgill University (canada), 1969 http://wwwlib.umi.com/dissertations/fullcit/NK04592
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Physiological Significance of the 5-ht(2b) and 5-ht(1b) Receptors in Deoxycorticosterone Acetate-salt Hypertension by Banes, Amy Kissiah Lynn; Phd from Michigan State University, 2002, 175 pages http://wwwlib.umi.com/dissertations/fullcit/3064200
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Preventive Health Care Planning As a Public Service in the Seattle Inner-city, with Special Reference to Hypertension Detection and Control. by Spratlen, Lois Price, Phd from University of Washington, 1976, 126 pages http://wwwlib.umi.com/dissertations/fullcit/7700624
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Program Development in Hypertension Patient Education Programs by Coyle-perkins, Geraldine Anne, Edd from Temple University, 1985, 129 pages http://wwwlib.umi.com/dissertations/fullcit/8521061
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Psychosocial Life-style Stressors and the African American Hypertensive by Cloud, Linda Diane, Phd from University of Missouri - Kansas City, 1995, 145 pages http://wwwlib.umi.com/dissertations/fullcit/9531450
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Pulmonary Disease in Scleroderma: Combined Interstitial Lung Disease and Pulmonary Hypertension and Predictors of Pulmonary Hypertension by Chang, Betty; Phd from The Johns Hopkins University, 2003, 72 pages http://wwwlib.umi.com/dissertations/fullcit/3068129
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Race, Class, and Health: Health Behavior and Hypertension in Black and White Americans by Duelberg, Sonja I., Phd from University of Illinois at Urbana-champaign, 1993, 158 pages http://wwwlib.umi.com/dissertations/fullcit/9411607
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Retinal Microvascular Abnormalities and Their Relationships with Hypertension, Cardiovascular Disease and Mortality by Wong, Tien Yin; Phd from The Johns Hopkins University, 2002, 264 pages http://wwwlib.umi.com/dissertations/fullcit/3046580
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Role Involvement, Social Identity, and Compliance with Hypertension Medical Regimens by Myjer, D'arcy Aubrey Roger, Phd from Yale University, 1988, 347 pages http://wwwlib.umi.com/dissertations/fullcit/9009417
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Role of Angiotensin in Glucocorticoid-associated Hypertension by Deng, Min; , Ms from University of Missouri - Kansas City, 2002, 87 pages http://wwwlib.umi.com/dissertations/fullcit/1410849
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Self-regard in Hypertension: a Study of Selected Quality of Life and General Attitude Variables of Hypertensive Patients by Beto, Judith A., Phd from The University of Chicago, 1990 http://wwwlib.umi.com/dissertations/fullcit/T-31177
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Socio-cultural Influences on the Pregnancy Experience: an Analysis of the Differences between Hypertensive and Normotensive Women by Lewis, Charlene Sturgess, Phd from Northwestern University, 1980, 287 pages http://wwwlib.umi.com/dissertations/fullcit/8026854
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Socioeconomic Status Configurations and the Distribution of Hypertension. by Davis, Charles George, Phd from The University of Michigan, 1975, 110 pages http://wwwlib.umi.com/dissertations/fullcit/7609380
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Sodium, the Sympathetic Nervous System and the Development of Hypertension in the Spontaneously Hypertensive Rat by Toal, Corey B; Phd from University of Toronto (canada), 1985 http://wwwlib.umi.com/dissertations/fullcit/NK66016
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Speaking of Illness: Popular Conceptions of Hypertension in American Culture by Blumhagen, Dan William, Phd from University of Washington, 1982, 270 pages http://wwwlib.umi.com/dissertations/fullcit/8218202
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Stress Inoculation Training with Hypertensive Firemen (cognitive Behavior, Relaxation Therapy) by Smith, Steve Benedict, Phd from University of Kentucky, 1985, 229 pages http://wwwlib.umi.com/dissertations/fullcit/8523934
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Stress, Social Inequality, and Culture Change: an Anthropological Approach to Human Psychophysiology (hypertension, Sociality) by Blakey, Michael Louis, Phd from University of Massachusetts, 1985, 288 pages http://wwwlib.umi.com/dissertations/fullcit/8602613
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Structural, Biophysical and Biochemical Properties of Arterial Smooth Muscle in Hypertension by Packer, Carol Subah; Phd from The University of Manitoba (canada), 1987 http://wwwlib.umi.com/dissertations/fullcit/NL37143
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Temporal Processing Deficit in Glaucoma and Ocular Hypertension by Stelmach, Lew B; Phd from University of Alberta (canada), 1985 http://wwwlib.umi.com/dissertations/fullcit/NL22931
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Test of the Effectiveness of a Hypertension Health Instruction Unit on Knowledge in a Minority Elderly Population at a Senior Citizen Center by Trowell-harris, Irene, Edd from Columbia University Teachers College, 1983, 153 pages http://wwwlib.umi.com/dissertations/fullcit/8322249
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Tetrahydrobiopterin-dependent Vasodilation Is Impaired in Experimental Hypertension by Mitchell, Brett M. Phd from Medical College of Georgia, 2003, 218 pages http://wwwlib.umi.com/dissertations/fullcit/3086344
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The Community Hypertension Management Project a Multi-center, Randomized, Controlled Clinical Trial of Computer-assisted Hypertension Management in Primary Care by Mcalister, Neil Harding; Phd from University of Toronto (canada), 1986 http://wwwlib.umi.com/dissertations/fullcit/NL29350
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The Development and Evaluation of a Group Training Program to Teach Self Control Skills to People with Hypertension by Twichell, Kristi Baatz, Phd from The University of Wisconsin - Madison, 1982, 320 pages http://wwwlib.umi.com/dissertations/fullcit/8224070
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The Diffusion of Health Information: a Study of the Dissemination Patterns of Hypertension Information. by Murdock, Marianne, Phd from Southern Illinois University at Carbondale, 1978, 178 pages http://wwwlib.umi.com/dissertations/fullcit/7817538
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The Effect of a Medication Self-care Program on Knowledge of Medication, Health Locus of Control and Self-care Behavior among Black Elderly Hypertensive Women by Harper, Doreen Connor, Phd from University of Maryland College Park, 1980, 220 pages http://wwwlib.umi.com/dissertations/fullcit/8103883
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The Effect of Hypertensive Disorders in Pregnancy on Perinatal Outcomes: a Population-based Cohort Study by Allen, Victoria Mary; Msc from University of Toronto (canada), 2002, 96 pages http://wwwlib.umi.com/dissertations/fullcit/MQ68871
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The Effect of Knowledge about Hypertension and Cultural Background on Typicality Judgments about a Scripted Event by Flynn, Janet-beth Mccann, Phd from The Catholic University of America, 1990, 155 pages http://wwwlib.umi.com/dissertations/fullcit/9107488
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The Effect of Two Methods of Patient Teaching on Selected Health Behaviors in the Treatment for Hypertension by Kneeshaw, Muriel Frances, Edd from Columbia University Teachers College, 1981, 159 pages http://wwwlib.umi.com/dissertations/fullcit/8122962
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The Effects of a Health Education Intervention Program on the Management of Hypertensive Patients by Conley, Mark Isaac, Jr., Edd from Boston University School of Education, 1982, 202 pages http://wwwlib.umi.com/dissertations/fullcit/8220914
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The Effects of Aerobic Exercise on Cardiovascular Reactivity and Baroreflex Response in Women with Parental History of Hypertension by Buckworth, Janet, Phd from University of Georgia, 1993, 170 pages http://wwwlib.umi.com/dissertations/fullcit/9329754
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The Effects of Coping Desensitization Training on the Attenuation of Blood Pressure in Essential Hypertension by Sprague, David Wayne, Phd from The Pennsylvania State University, 1988, 181 pages http://wwwlib.umi.com/dissertations/fullcit/8826822
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The Effects of Health Education on the Compliance of Hypertensive Patients to Medical Regimens by Werner, Russell Thomas, Sr., Edd from Temple University, 1980, 158 pages http://wwwlib.umi.com/dissertations/fullcit/8014571
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The Effects of Relaxation Training and Biofeedback on Essential Hypertension. by Payson, James Boyd, Edd from East Texas State University, 1976, 189 pages http://wwwlib.umi.com/dissertations/fullcit/7709634
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The Effects of Thermal Feedback with Diaphragmatic Breathing in the Treatment of White-coat Hypertension in Japan (anxiety) by Saito, Atsuko, Phd from Southern Illinois University at Carbondale, 1989, 141 pages http://wwwlib.umi.com/dissertations/fullcit/9022832
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The Efficacy of Autogenic Training and Skin Temperature Biofeedback on Hypertension by Yeager, John Micheal, Edd from Boston University School of Education, 1982, 188 pages http://wwwlib.umi.com/dissertations/fullcit/8220978
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The Influence of Exercise Intensity on Postexercise Hypotension among Middle-aged Men with High Normal to Stage I Hypertension by Zellner, Scott Richard; Phd from The University of Connecticut, 2002, 74 pages http://wwwlib.umi.com/dissertations/fullcit/3076729
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The Influence of One-kidney Goldblatt Hypertension and Cold Acclimation on Adrenergically-induced Cardiovascular and Thermoregulatory Adjustments in Rats by Fyda, Doreen M; Phd from The University of Manitoba (canada), 1987 http://wwwlib.umi.com/dissertations/fullcit/NL37277
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The Post-exercise Blood Pressure Response to Acute Exercise in Borderline Hypertensive Women by Inbar, Galit, Phd from Indiana University, 1992, 212 pages http://wwwlib.umi.com/dissertations/fullcit/9310333
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The Prospective Testing of a Psychosocial Model of Preventive Health Service Utilization in a University Population Offered Hypertension Screening by Walker, Lawrence Ronald, Phd from Temple University, 1981, 289 pages http://wwwlib.umi.com/dissertations/fullcit/8124759
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The Relationship between Knowledge and Drug Compliance among Elderly Hypertensive Patients by Barley, Linda Rose, Edd from Columbia University Teachers College, 1980, 77 pages http://wwwlib.umi.com/dissertations/fullcit/8105853
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The Role of Human Profilin in Vascular Smooth Muscle Contractility and Hypertension by Al-kheraije, Khalid Ali; Phd from The Ohio State University, 2002, 148 pages http://wwwlib.umi.com/dissertations/fullcit/3048991
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The Roles of Lithium(+), Magnesium(2+), and Sodium Ions in Bipolar Disorder and Essential Hypertension: a Multinuclear Nmr and Fluorescence Study by Williams, Nicole Marie; Phd from Loyola University of Chicago, 2002, 152 pages http://wwwlib.umi.com/dissertations/fullcit/3056455
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Two Educational Approaches to a Primary Prevention Hypertension Lesson Series: a Comparative Analysis (patient Education, Nursing, Blood Pressure) by Kirkpatrick, Mary Kinsland, Edd from North Carolina State University, 1984, 155 pages http://wwwlib.umi.com/dissertations/fullcit/8500237
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Type 2 Diabetes in a Defined Population: the Skaraborg Hypertension and Diabetes Project (sweden) by Ostgren, Carl Johan; from Lunds Universitet (sweden), 2002, 105 pages http://wwwlib.umi.com/dissertations/fullcit/f692929
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Using Traction Force Microscopy to Study the Role of Fibroblast Contractility in Hypertensive Cardiac Dysfunction by Marganski, William Alec; Phd from Boston University, 2003, 144 pages http://wwwlib.umi.com/dissertations/fullcit/3084846
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Women with Hypertension: an Ethnographic Inquiry by Harmon, Adrienne Seccia, Phd from University of Illinois at Urbana-champaign, 1993, 449 pages http://wwwlib.umi.com/dissertations/fullcit/9329053
Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.
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CHAPTER 5. CLINICAL TRIALS AND HYPERTENSION Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning hypertension.
Recent Trials on Hypertension The following is a list of recent trials dedicated to hypertension.8 Further information on a trial is available at the Web site indicated. •
A 6-week safety & efficacy study of combination intraocular pressure-lowering therapy in patients with open-angle glaucoma or ocular hypertension Condition(s): Glaucoma, Open-Angle; Ocular Hypertension Study Status: This study is currently recruiting patients. Sponsor(s): Alcon Research Purpose - Excerpt: To compare the intraocular pressure(IOP)-lowering efficacy of morning or evening instillations of a combination IOP-lowering therapy in patients with open-angle glaucoma or ocular hypertension. Phase(s): Phase II Study Type: Interventional Contact(s): Alcon Clinical 817-568-6747
[email protected] Web Site: http://clinicaltrials.gov/ct/show/NCT00051194
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A 6-week safety and efficacy study of Travatan compared to Xalcom in subjects with open-angle glaucoma(OAG) or ocular hypertension(OHT) Condition(s): Glaucoma, Open-Angle; Ocular Hypertension Study Status: This study is currently recruiting patients. Sponsor(s): Alcon Research
8
These are listed at www.ClinicalTrials.gov.
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Purpose - Excerpt: To compare the safety and IOP-lowering efficacy of TRAVATAN and XALCOM in subjects with open-angle glaucoma or ocular hypertension. Phase(s): Phase IV Study Type: Interventional Contact(s): Alcon Clinical 817-568-6747
[email protected] Web Site: http://clinicaltrials.gov/ct/show/NCT00051155 •
A safety and efficacy study of Travoprost 0.004% compared to Latanoprost 0.005% in patients with open-angle glaucoma(OAG) or ocular hypertension(OHT) Condition(s): Glaucoma, Open-Angle; Ocular Hypertension Study Status: This study is currently recruiting patients. Sponsor(s): Alcon Research Purpose - Excerpt: To evaluate the safety and IOP-lowering efficacy of Travoprost (0.004%) compared to Latanoprost (0.005%) in patients with chronic open-angle glaucoma or ocular hypertension. Phase(s): Phase IV Study Type: Interventional Contact(s): Alcon Clinical 817-568-6747
[email protected] Web Site: http://clinicaltrials.gov/ct/show/NCT00051142
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A Transition Study From Flolan(r) to Remodulin(r) in Patients with Pulmonary Arterial Hypertension Condition(s): Pulmonary Arterial Hypertension; Pulmonary Hypertension Study Status: This study is currently recruiting patients. Sponsor(s): United Therapeutics Purpose - Excerpt: This trial is a study of Remodulin in patients with pulmonary arterial hypertension who have been transitioned from Flolan therapy. The study consists of Screening, Baseline and Treatment Phases. Patients meeting all inclusion/exclusion criteria during the Screening Phase will enter the Baseline Phase, during which baseline exercise capacity, vital signs, and clinical signs and symptoms of the disease will be assessed. After confirmation of all inclusion/exclusion criteria, patients will be assigned to study drug (Remodulin or placebo) and will enter the Treatment Phase. The Treatment Phase begins with a Dose Transition Period, during which patients will begin receiving subcutaneous study drug at a low dose determined by the patient's current dose of Flolan. The study drug dose will be increased gradually while the Flolan dose is decreased gradually over a period of up to 14 days. The dose changes will continue until Flolan therapy has been discontinued and the patient is stable on study drug. Patients who are transitioned off Flolan, who are stable on study drug will be discharged from the clinic, and will continue to receive study drug on an outpatient basis. The patient will return to the clinic at Weeks 4 and 8 for assessments. Patients will remain on study drug for 8 weeks from the first dose of study drug. At Week 8, final assessments will be conducted and the patient will be dismissed from the study. Patients who successfully complete Week 8 assessments may be offered Remodulin therapy or other therapy, at the investigator's discretion. Phase(s): Phase IV
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Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00058929 •
Inhaled Nitric Oxide and Transfusion Therapy for Patients with Sickle Cell Anemia and Secondary Pulmonary Hypertension Condition(s): Sickle Cell Anemia; Pulmonary Hypertension Study Status: This study is currently recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: This study will test whether inhaling nitric oxide gas mixed with room air can improve pulmonary hypertension (high blood pressure in the lungs) in patients with sickle cell anemia. It is estimated that 20 to 30 percent of patients with sickle cell anemia have moderate to severe pulmonary hypertension, a disease complication associated with higher rates of illness and death. Patients with sickle cell disease 18 years of age or older may be eligible to participate in one or more parts of this three-stage study. Candidates will be screened with a medical history, physical examination, electrocardiogram, echocardiogram and blood tests. Those enrolled will undergo the following tests and procedures: Stage 1: Patients will be tested to determine the cause of pulmonary hypertension. They will have an echocardiogram (ultrasound study of the heart); a test for asthma, with measurement of arterial blood oxygen levels; oxygen breathing study with measurement of arterial blood oxygen levels; chest X-ray; computed tomography (CT) scans of the lung with and without contrast material; magnetic resonance imaging (MRI) of the heart; 6-minute walk to measure the distance covered in that time at a comfortable pace; night-hawks oxygen measurement while sleeping; blood tests for HIV, hepatitis virus, lupus and arthritis and pregnancy; pulmonary ventilation/perfusion scan with evaluation of shunt fraction to the brain and kidney; and exercise studies will be performed to determine oxygen and carbon dioxide consumption and production and to measure the anaerobic threshold. Stage 2: Patients who proceed with stage 2 will have a detailed MRI evaluation of the heart and will be admitted to the Clinical Center intensive care unit for the following procedure: A small intravenous (IV) catheter (plastic tube) is placed in the patient arm and a longer tube, called a central line, in a deeper neck or leg vein. A long thin tube is then inserted through the vein into the heart and the lung artery to measure all blood pressures in the heart and lungs directly. Following baseline measurements the following medications will be delivered for two hours each, separated by a 30 minute wash-out period. The patients is then given oxygen to breathe for 2 hours, followed by infusion of prostacyclin, a blood pressure-lowering drug, for 2 hours; and finally inhaled nitric oxide for 2 hours. A small blood sample (3 tablespoons) of blood is drawn during the nitric oxide administration. Stage 3: For patients who complete stage II or III and do not respond to NO gas as determined by a decrease in mean or systolic pulmonary artery pressure of greater than 10% from baseline or a 10% increase in 6 minute walk distance, or are unable to receive it due to technical, regulatory (no free standing home structure for storage of NO gas, etc.) or personal lifestyle issues (some patient do not want to carry two tanks of gas - oxygen and NO - or have difficulty learning how to use the NO gas system), we will offer regular exchange transfusions and home oxygen for three months with a goal of maintaining hemoglobin levels of 8-10 and hemoglobin S levels of less than 40%. The monitoring of patients receiving exchange transfusions will be the same as for the patients receiving NO gas: Measurements will include pulmonary artery pressure measured by repeat right heart catheterization, other hemodynamic
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parameters, exercise tolerance by 6-minute walk, plasma adhesion molecule levels, neutrophil and monocyte mRNA gene profiles, and circulating erythroid progenitor cell a/a hemoglobin message and protein levels. This portion of the study is to be undertaken as an outpatient. Clinical follow-up will involve bi-weekly clinic visits with the principal investigator, associate investigators, or study nurse. At these clinic visits venous blood will be obtained for hemoglobin electrophoresis (including hemoglobin F and A2), CBC, ESR, C-reactive protein and standard chemistries. Research blood, for plasma and erythrocyte reactive nitrogen species and plasma adhesion molecule levels, will be collected with total blood drawn per day not to exceed 30 mL. Protocol nurse or principal investigator will record total weekly symptoms, emergency room visits, hospital admissions, and narcotic use. Echocardiograms and 6-minute walk will be repeated at two-week intervals. 32 mL of blood will be drawn prior to the exchange transfusion and a 4 and 8 weeks for neutrophil and monocyte mRNA expression chip profiling. Patients who develop any complication of their disease (i.e. vaso-occlusive crisis, acute chest syndrome, let ulcers, priapism, avascular necrosis of the femoral hip, asthma, etc.) will be strongly encouraged to directly come to the Clinical Center's 10D ICU for evaluation and direct admission by the 10D ICU physician on-call. If they are very ill they will be instructed to either call and ambulance or go to the nearest emergency room. If they are relatively stable, patients will be instructed to call the 10D ICU and speak with the physician on-call. We will follow patients according to the NO protocol with right heart catheterization at 3 months of therapy and serial echocardiograms. The effects of exchange transfusion will be statistically analyzed separately but in a similar fashion as delineated for NO treatment. All patients will complete Stage I and II of the study prior to entering into Exchange Transfusion therapy. Patients with greater than a 10% increase in six-minute walk distance or a 10% reduction in mean or systolic pulmonary artery pressures, who want to continue Exchange Transfusion therapy will have the option of continuing therapy. In these cases, blood draws and clinical follow-up will be reduced to bi-monthly intervals and when clinically indicated. The Clinical Center will continue to pay for these clinic visits and urgent care at the Clinical Center. The Transfusion Therapy and the Clinical Center care will continue until the study has terminated (anticipated three year study duration). Our physicians and social workers will work with patients to help them obtain appropriate insurance to cover Exchange Transfusion therapy. However, it is possible that circumstances may arise that prevent the patient from continuing this therapy after the study is terminated. Alternative Therapies Patients who have enrolled in the NO or transfusion treatment arm of the study who do not respond to the treatment (defined by a 10% reduction in mean or systolic pulmonary artery pressure measured by right heart catheterization or a 10% increase in 6-minute walk distance) will be eligible to receive the alternative therapy (NO or transfusion) or other FDA approved medications. These medications may include oxygen, prostacyclin (flolan or remodulin), L-arginine, bosentan or sidenafil. We will limit the number of patients who are treated with medication other than NO or exchange transfusion to 10 subjects. Such patients will be managed at the NIH, in collaboration with their primary medical providers, according to accepted current standards of care using only FDA approved medication. The effect of such treatments on estimated pulmonary artery pressures, measured by echocardiogram, and on 6-minute walk distance will be assessed at regular intervals (every 1-3 months while on protocol) and all adverse events reported to the IRB and DSMB as defined by the current protocol. Patients maintained on alternative therapies will not have research bloods drawn, all laboratory testing will be obtained only for clinical indications. Such patients may be managed on this protocol until the protocol is terminated, the medication used becomes FDA approved specifically for use in sickle
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cell disease, the patient wishes to end participation, or the patient wishes to enroll in another study for treatment of pulmonary hypertension. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00023296 •
Magnetic Resonance Imaging for Evaluating Kidney Function Condition(s): Healthy; Renovascular Hypertension Study Status: This study is currently recruiting patients. Sponsor(s): Warren G Magnuson Clinical Center (CC) Purpose - Excerpt: Renovascular hypertension (RVH) is a potentially curable disease affecting 0.5-5 percent of patients with hypertension. The current diagnostic work-up of RVH involves a complex algorithm which includes doppler ultrasound, captopril renography and conventional angiography. Because of the expense, risk and inconvenience of this workup, patients may not be correctly diagnosed. Advances in MR technology present the opportunity to develop a single comprehensive test. This would combine an MR angiogram that provides anatomic information about the renal arteries, and an MR renogram that provides information about the functional impact of a stenosis as a cause of hypertension. Our main purpose is to test MR renography with and without an oral angiotensin converting enzyme inhibitor (ACEI) combined with MR angiography against the reference standard of captopril radionuclide renography. Secondary goals of this study are to test whether hypoxia within ischemic kidneys affected by RVH is detectable by T2 weighted (Blood oxygen level dependent or BOLD) MRI. This is considered of value since such a test of oxygenation would further shorten and simplify the diagnostic MR test. Information gained from this study could lead to important changes in the diagnostic and pathophysiologic understanding of RVH. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006173
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Mechanism of Action of TRAVATAN 0.004% in Subjects with Glaucoma or Ocular Hypertension Condition(s): Glaucoma; Ocular Hypertension Study Status: This study is currently recruiting patients. Sponsor(s): Alcon Research Purpose - Excerpt: The primary objective of this study is to describe the effect of TRAVATAN 0.004% Ophthalmic Solution on aqueous humor dynamics in subjects with a clinical diagnosis of open angle glaucoma (OAG) or ocular hypertension (OHT). Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00061503
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Phase 3 study to evaluate IOP lowering therapy in open angle glaucoma and ocular hypertension C-01-69 Condition(s): Open-Angle Glaucoma; Ocular Hypertension Study Status: This study is currently recruiting patients. Sponsor(s): Alcon Research Purpose - Excerpt: To compare intraocular pressure lowering effectiveness of a combination drug vs. two individual drugs dosed alone. Phase(s): Phase III Study Type: Interventional Contact(s): Alcon Call Center 1-888-451-EYES (3937) alconlabs.com Web Site: http://clinicaltrials.gov/ct/show/NCT00047515
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Phase 3 study to evaluate IOP lowering therapy in open angle glaucoma and ocular hypertension C-01-70 Condition(s): Open-Angle Glaucoma; Ocular Hypertension Study Status: This study is currently recruiting patients. Sponsor(s): Alcon Research Purpose - Excerpt: To compare intraocular pressure lowering effectiveness of a combination drug vs. two individual drugs dosed alone. Phase(s): Phase III Study Type: Interventional Contact(s): Alcon Call Center 1-888-451-EYES (3937) alconlabs.com Web Site: http://clinicaltrials.gov/ct/show/NCT00047541
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Phase 3 study to evaluate IOP lowering therapy in open angle glaucoma and ocular hypertension C-02-41 Condition(s): Open-Angle Glaucoma; Ocular Hypertension Study Status: This study is currently recruiting patients. Sponsor(s): Alcon Research Purpose - Excerpt: To compare intraocular pressure lowering effectiveness of a combination drug vs. two individual drugs dosed alone. Phase(s): Phase III Study Type: Interventional Contact(s): Alcon Call Center 1-888-451-EYES (3937) alconlabs.com Web Site: http://clinicaltrials.gov/ct/show/NCT00047528
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Phase II safety and efficacy study to evaluate a glaucoma therapy in open-angle glaucoma or ocular hypertension patients Condition(s): Open-Angle Glaucoma; Ocular Hypertension Study Status: This study is currently recruiting patients. Sponsor(s): Alcon Research
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Purpose - Excerpt: The purpose of this study is to determine the safety and IOPlowering ability of a glaucoma therapy in patients with open-angle glaucoma or ocular hypertension. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00069706 •
Phase III Randomized Study of UT-15 in Patients with Primary Pulmonary Hypertension Condition(s): Pulmonary Hypertension Study Status: This study is currently recruiting patients. Sponsor(s): FDA Office of Orphan Products Development; United Therapeutics Purpose - Excerpt: Objectives: I. Determine the safety and efficacy of UT-15 in patients with severe symptomatic primary pulmonary hypertension. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004497
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Pulmonary Hypertension--Mechanisms and Family Registry Condition(s): Lung Diseases; Hypertension, Pulmonary Study Status: This study is currently recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To establish a registry of primary pulmonary hypertension (PPH), a lethal disease which causes progressive obstruction of small pulmonary arteries and to investigate basic mechanisms of the disease. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005357
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Secondary Pulmonary Hypertension in Adults with Sickle Cell Anemia Condition(s): Pulmonary Hypertension; Sickle Cell Anemia Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: The purpose of this study is to determine how often people with sickle cell anemia develop pulmonary hypertension-a serious disease in which blood pressure in the artery to the lungs is elevated. Men and women 18 years of age and older with sickle cell anemia may be eligible for this study. Participants will undergo an evaluation at Howard University's Comprehensive Sickle Cell Center in Washington, D.C. or at the National Institutes of Health in Bethesda, Maryland. It will include the following: -medical history -physical examination -blood collection (no more than 50 ml., or about 1/3 cup) to confirm the diagnosis of sickle cell anemia, sickle cell trait or
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beta-thalassemia (Some blood will be stored for future research testing on sickle cell anemia.) -echocardiogram (ultrasound test of the heart) to check the pumping action of the heart and the rate at which blood travels through the tricuspid valve. Following this evaluation, a study nurse will contact participants twice a month for 2 months and then once every 3 months for the next 3 years for a telephone interview. The interview will include questions about general health and recent health-related events, such as hospitalizations or emergency room visits. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00011648 •
Treatment of Pediatric Hypertension with Altace Trial Condition(s): Hypertension Study Status: This study is currently recruiting patients. Sponsor(s): King Pharmaceuticals; Wyeth-Ayerst Research Purpose - Excerpt: Ramipril is an ACE inhibitor that has been marketed in the US for the treatment of hypertension since 1991. It has been shown to be effective in reducing both systolic and diastolic blood pressure in adults when used once daily. ACE inhibitors are frequently used to treat hypertension in children, however ramipril has not been extensively tested in children, and information regarding the efficacy and safety would therefore be of benefit to children. This study is designed to demonstrate the efficacy and safety of ramipril in the treatment of hypertension in children ages 6 through 16 years. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00044265
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A Phase III Study of Brimonidine Tartrate Ophthalmic Solution, 0.15% in Patients with Open-Angle Glaucoma or Ocular Hypertension Condition(s): Open-Angle Glaucoma; Ocular Hypertension Study Status: This study is no longer recruiting patients. Sponsor(s): Alcon Research Purpose - Excerpt: The primary objective of this study is to compare the safety and efficacy of Brimonidine Tartrate Ophthalmic Solution, 0.15% in patients with open-angle glaucoma or ocular hypertension. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00061529
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A Study to Prevent Complications of High Blood Pressure Caused by Hepatitis in Patients with Cirrhosis Condition(s): Hypertension, Portal; Liver Cirrhosis; Esophageal and Gastric Varices
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Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Yale University Purpose - Excerpt: Objectives: I. Evaluate the efficacy of a certain drug in preventing intestinal complications in patients with cirrhosis and high blood pressure in the hepatic portal vein. II. Evaluate vein pressure measurements to predict the development of internal bleeding. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004641 •
GenHAT--Genetics of Hypertension Associated Treatments Condition(s): Cardiovascular Diseases; Heart Diseases; Hypertension; Coronary Disease; Myocardial Infarction Study Status: This study is no longer recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To examine whether the association between selected hypertensive genes and combined fatal coronary heart disease and nonfatal myocardial infarction in high-risk hypertensives is modified by the type of antihypertensive treatment, leading to differential risks of coronary heart disease. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006294
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Hypertension: Prediction of Biofeedback Success Condition(s): Essential Hypertension Study Status: This study is no longer recruiting patients. Sponsor(s): National Center for Complementary and Alternative Medicine (NCCAM) Purpose - Excerpt: Hypertension, present in more than 50 million Americans, increases the risk of cardiovascular disease and its associated complications. More persons are turning to alternative medicine to deal with their health problems. Biofeedback may reduce blood pressure and/or allow the reduction of antihypertensive medications in some patients, while having no adverse effects. Yet biofeedback therapy is timeintensive and technician-intensive. Therefore, it is critical to be able to predict which patients with essential hypertension are most likely to lower his/her blood pressure using these techniques. This research proposes to test three different means of predicting whether a hypertensive subject will or will not be successful in lowering his/her blood pressure using biofeedback. Sixty hypertensive subjects will be studied over a three-year period. The results of this study will enable those caring for hypertensive persons to recommend biofeedback in an individualized way, thereby promoting adherence. Phase(s): Phase I Study Type: Interventional
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Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00026065 •
Ocular Hypertension Treatment Study (OHTS) Condition(s): Ocular Hypertension; Glaucoma Study Status: This study is no longer recruiting patients. Sponsor(s): National Eye Institute (NEI) Purpose - Excerpt: To determine whether medical reduction of intraocular pressure prevents or delays the onset of glaucomatous visual field loss and/or optic disc damage in ocular hypertensive subjects judged to be at moderate risk for developing open-angle glaucoma. To produce natural history data to assist in identifying patients at most risk for developing open-angle glaucoma and those most likely to benefit from early medical treatment. To quantify risk factors for developing open-angle glaucoma among ocular hypertensive subjects. Phase(s): Phase III Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000125
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Phase II safety and efficacy study to evaluate a glaucoma therapy in open-angle glaucoma or ocular hypertension patients Condition(s): Open-Angle Glaucoma; Ocular Hypertension Study Status: This study is no longer recruiting patients. Sponsor(s): Alcon Research Purpose - Excerpt: To determine the safety and IOP-lowering ability of a test compound in patients with open-angle glaucoma or ocular hypertension. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00069719
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Safety and Efficacy of Sitaxsentan in the Treatment of Pulmonary Arterial Hypertension Condition(s): Pulmonary Hypertension Study Status: This study is no longer recruiting patients. Sponsor(s): ICOS-Texas Biotechnology; ICOS; Texas Biotechnology Corporation Purpose - Excerpt: This is a clinical research study designed to evaluate an investigational new medication called sitaxsentan for the treatment of pulmonary arterial hypertension (patients with NYHA functional class II, III or IV). The purpose of this study is to evaluate the safety and effectiveness of two different doses of sitaxsentan, compared to placebo (inactive treatment) for the treatment of pulmonary arterial hypertension. Patients who complete this trial may be eligible to take part in an
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extension trial (Protocol FPH01-X). Eligible patients who receive placebo in the 12-week study cross over to receive sitaxsentan for the extension trial. Phase(s): Phase II; Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00034307 •
Study of BSF 208075 evaluating exercise capacity in patients with pulmonary arterial hypertension Condition(s): Pulmonary Hypertension Study Status: This study is no longer recruiting patients. Sponsor(s): Myogen Purpose - Excerpt: The purpose of this study is to determine if treating patients suffering from moderate to severe pulmonary arterial hypertension with BSF 208075 will improve the patients' ability to exercise. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00046319
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The SILVER Study: Systolic Hypertension Interaction with Left Ventricular Remodeling Condition(s): Hypertension; Hypertrophy, Left Ventricular Study Status: This study is no longer recruiting patients. Sponsor(s): Alteon Inc. Purpose - Excerpt: The purpose of this study is to evaluate the safety and efficacy of ALT-711 in the treatment of isolated systolic hypertension in a formal study in patients with left ventricular hypertrophy. Eligible patients will be randomized to double-blind treatment once daily for 6 months with oral ALT-711 (210 mg) or placebo. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00045994
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Acupuncture and Hypertension Condition(s): Hypertension Study Status: This study is completed. Sponsor(s): National Center for Complementary and Alternative Medicine (NCCAM) Purpose - Excerpt: Although traditional Chinese medicine advocates the use of acupuncture not only to induce analgesia but also to treat essential hypertension, acupuncture's postulated antihypertensive efficacy in humans has not been subjected to rigorous Western scientific testing. Before advocating acupuncture as an effective
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complementary/alternative medicine strategy for essential hypertension, it is necessary to demonstrate that the beneficial effects of acupuncture are scientifically robust, longlasting, and explicable in terms of modern scientific mechanisms. In spontaneously hypertensive rats, acupuncture-like electrical stimulation of thinly myelinated (Group III) somatic afferents activates central endorphin (naloxone-sensitive) pathways that elicit long-lasting decreases in sympathetic nerve activity (SNA) and blood pressure. The ability to record SNA with microelectrodes in conscious humans provides a new opportunity to test this novel mechanistic hypothesis in patients undergoing electroacupuncture, a modification of the ancient technique that provides a quantifiable and reproducible stimulus to human skeletal muscle afferents. Using a randomized, double-blind placebo-controlled design, we will test the following major hypotheses: Electroacupuncture produces a long-lasting reduction in SNA, thereby providing a safe and effective complementary treatment of human hypertension. Given the enormous interest in acupuncture by our lay public, but the paucity of Western scientific data about its efficacy in cardiovascular disorders, our studies in normotensive and hypertensive humans should provide a conceptual framework for deciding whether to accept or reject the large body of Chinese (and Russian) literature advocating acupuncture as a safe and effective treatment of essential hypertension and other cardiovascular disorders (such as heart failure, and myocardial ischemia). Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00010478 •
Antecedents of Hypertension: Role of Race and Stress Condition(s): Cardiovascular Diseases; Heart Diseases; Hypertension Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To determine the role of environmental stressors in the development of hypertension in Black and white school-age children from hypertensive families. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005238
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Control of Hypertension by Non-Pharmacologic Means Condition(s): Cardiovascular Diseases; Heart Diseases; Hypertension; Vascular Diseases Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To determine whether blood pressure could be controlled by nutritional-hygienic, non-pharmacologic means in hypertensives treated with drugs in the Hypertension Detection and Follow-up Trial (HDFP). Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000498
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Dietary Intervention Study for Hypertension (DISH) Condition(s): Cardiovascular Diseases; Heart Diseases; Hypertension; Vascular Diseases Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: The primary objective of this multicenter cooperative clinical trial was to determine if dietary modification would enable drug controlled hypertensive patients to remain at 'goal blood pressures' after antihypertensive medication was withdrawn. The proposal made use of the HDFP hypertensive population who had five years of treatment for their hypertension. Additionally, the group of investigators proposed to determine if dietary treatment would permit patients not previously adequately controlled under the HDFP program to achieve normalization of blood pressure with a combination of dietary modification and drug treatment. The study also proposed to search for predictors (i.e., levels of hormonal agents such as plasma renin activity) of responsiveness to dietary manipulation among the hypertensive population as well as to identify psychological attributes that might be of importance in managing these patients. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000497
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Effects of Rosiglitazone on Blood Vessels in Patients with High Blood Pressure and High Cholesterol Condition(s): Hypercholestrolemia; Hypertension Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: Cells in the lining of blood vessels produce various substances that cause the vessels to dilate (relax) and constrict (tighten), thereby regulating blood flow. In patients with high blood pressure and high cholesterol, the blood vessels do not dilate properly. This study will investigate the effects of rosiglitazone-a drug used to improve the action of insulin in diabetic patients-on blood flow by examining its effects on endothelin (a substance that causes vessel constriction), and other substances produced by the vessel-lining cells. Adults with blood pressure recordings of 140/90 mmHg or higher on at least three separate days or with a blood cholesterol level of at least 240 mg/dl may be eligible for this study. Candidates will be screened with a medical history and physical examination, blood pressure recordings, blood and urine tests. This "crossover" study involves two separate treatment periods; that is, participants will take either rosiglitazone or placebo (an inactive look-alike pill) once a day for 8 weeks, then no drug for 4 weeks, and then the alternative treatment for the next 8 weeks. Patients will continue to take their high blood pressure medicines during the first 6 weeks of each treatment period. They will stop the medication 2 weeks before the following procedures, which are done at the end of each 8-week treatment period: Strain gauge plethysmography-A small catheter is placed through a needle into an artery at the bend of the arm for measuring blood pressure and drawing blood samples during the study. Pressure cuffs are placed on the wrist and upper arm, and a strain gauge (a rubber band device) is placed around the forearm to measure forearm blood flow. When the cuffs are inflated, blood flows into the arm, stretching the strain gauge at
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a rate proportional to the flow, and the measurement is recorded. Small doses of four drugs-acetylcholine, bradykinin, sodium nitroprusside and BQ-123-are given through the catheter. Acetylcholine slows the heart rate. Bradykinin stimulates the release of a substance that causes blood vessels to dilate and can lower blood pressure. Sodium nitroprusside causes blood vessels to dilate and is used to treat high blood pressure and heart failure. BQ-123 blocks the blood vessel-constricting activity of endothelin. Brachial ultrasound reactivity study-A baseline ultrasound image (picture produced using sound waves) of the brachial artery (artery located at the bend of the arm) is taken and blood flow measurements are recorded. Then, a pressure cuff is placed around the upper forearm, inflated for 5 minutes to stop blood flow to the forearm, and then released. Images of the artery and flow measurements are repeated. After a 15-minute rest, new baseline images are taken and flow measurements obtained. A small amount of nitroglycerin is then sprayed under the tongue and after 3 minutes, blood flow measurements and brachial artery images are recorded once more. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006071 •
Effects of Salt Intake on the Nervous Systems of Patients with Salt-Sensitive High Blood Pressure Condition(s): Hyperaldosteronism; Hypertension Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: Some patients with high blood pressure can experience an increase of blood pressure by 10 percent or more by taking in salt. These patients are referred to as having "salt-sensitive" (SS) hypertension. Previous studies conducted on patients with salt sensitive hypertension suggest that their portion of the nervous system responsible for maintaining normal blood pressure (autonomic nervous system) may respond differently to salt than patients with non-salt sensitive (NSS) hypertension. This study is designed to examine the response of the nervous system to high doses of salt in patients with salt-sensitive hypertension and patients with non-salt sensitive hypertension. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001176
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Epidemiology of Hypertensive Emergency Condition(s): Cardiovascular Diseases; Heart Diseases; Hypertension Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To test the hypotheses that hypertensive emergency was associated with non-compliance with antihypertensive medication, low level of contact with the medical care system, and alcohol abuse and cigarette smoking. Also, to describe the clinical characteristics of patients hospitalized with hypertensive emergency including morbidity, mortality, and cost, and the extent to which hypertensive emergency occured among previously diagnosed and treated hypertensives. Study Type: Observational
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Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005240 •
Genetic and Environmental Determinants of Hypertension Condition(s): Cardiovascular Diseases; Heart Diseases; Hypertension Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To determine the pathophysiology of different types of essential hypertension by identifying the discrete effects of major genes and environmental variables as determinants of the subtypes of essential hypertension. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005149
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Guidelines for Drug Therapy of Hypertension: Closing the Loop Condition(s): Hypertension Study Status: This study is completed. Sponsor(s): Department of Veterans Affairs; Department of Veterans Affairs Health Services Research and Development Service; Stanford University Purpose - Excerpt: Hypertension is a major risk factor for heart disease and stroke. Evidence-based guidelines support the use of specific drugs for patients with specific comorbidities to maximize the decrease in cardiovascular risk; yet, many physicians do not follow these guidelines in choosing drug therapy. The goal of this project was to evaluate methods of implementing clinical practice guidelines, using hypertension as a model. We hypothesized that providing patient-specific recommendations to clinicians at the time of clinic contact with hypertensive patients would substantially improve guideline concordance of drug therapy without adversely affecting (possibly improving) blood pressure control. Our long-term goal is to develop and evaluate methods of implementing clinical practice guidelines that build on current knowledge about the most effective approaches to changing clinician behavior, and to extend those methods to other cardiovascular diseases. This project, known as ATHENA, included two major components: (1) We conducted a randomized controlled trial of patientspecific recommendations about drug therapy for hypertension, delivered to primary care clinicians at the time of primary care clinic visits. The recommendations were based on VA Hypertension Guidelines. The trial included 36 clinicians and 4500 hypertensive patients enrolled in primary care clinics at VA Palo Alto Health Care System. We compared a general intervention to an individualized intervention. Both the general and the intervention groups of clinicians received extensive guideline education, as part of a VISN-mandated hypertension guideline implementation. Clinicians randomized to the individualized intervention received, in addition, computer-generated patient-specific recommendations about drug therapy of hypertension, delivered to the clinics with the encounter forms for each visit. (2) In the 2nd major component of the study, we collaborated with Stanford Medical Informatics to develop a hypertension decision support system (ATHENA DSS). ATHENA DSS combines detailed patient information from the VA electronic medical record (VistA) with hypertension guideline knowledge based on the VA and JNC 6 hypertension guidelines. A special feature of ATHENA DSS is that the knowledge in the system can be easily browsed and updated by clinician-
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managers, so that knowledge can be kept up to date with emerging clinical trial findings about best treatments. We developed an infrastructure to implement the system in a pop-up window in the CPRS-GUI in the primary care clinics at VA Palo Alto. We also conducted an offline test of the program logic by comparing the ATHENA DSS recommendations with those made by a physician for 100 randomly selected VA patients. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00012636 •
Hypertension Detection and Follow-up Program (HDFP) Condition(s): Cardiovascular Diseases; Heart Diseases; Hypertension; Vascular Diseases Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To determine the effectiveness of systematic, sustained, antihypertensive therapy in reducing morbidity and mortality from hypertension in a wide spectrum of persons with elevated blood pressure in 14 communities. During its course, the trial also obtained a direct measure of the prevalence, severity, and treatment status of representative white and black populations with high blood pressure in these 14 communities, and obtained an estimate of the extent of attainable reduction of complications of high blood pressure by an organized screening and blood pressure management program. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000485
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Hypertension Prevention Trial (HPT) Feasibility Study Condition(s): Cardiovascular Diseases; Heart Diseases; Hypertension; Obesity; Vascular Diseases Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To test the feasibility and the efficacy of nutritional interventions in the primary prevention of hypertension in individuals predisposed to the development of hypertension; specifically, to test the hypothesis that reduction of weight and/or decreased sodium intake in obese individuals, or decreased sodium intake with or without increased potassium intake (in men and women, regardless of weight) would prevent the elevation of blood pressure and the incidence of hypertension. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000501
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Hypertension screening and treatment program Condition(s): Hypertension
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Study Status: This study is completed. Sponsor(s): Department of Veterans Affairs; Department of Veterans Affairs Cooperative Studies Program Purpose - Excerpt: Hypertension is one of the most common medical problems in the United States and in the VA health care system. It has been well-documented that hypertension can be effectively treated. However, there remain important unresolved clinical questions in the area of antihypertensive treatment. For example, how much is mortality affected by visit compliance, blood pressure control and type of antihypertensive agent? Or, are some regimens associated with more morbidity than others? Or, are there inexpensive regimens that are as effective as more expensive regimens? The amount of data that is available from this demonstration project (currently 6,100 patients) will help address these questions. The answers to these questions should result in better care for veterans with hypertension. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00007592 •
Hypertensive and Normal Pregnancy--Calcium Metabolism and Renin-Angiotensin SCOR in Hypertension Condition(s): Cardiovascular Diseases; Heart Diseases; Hypertension; Eclampsia; PreEclampsia Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To study calcium metabolism and the renin-angiotensin system in hypertensive and normal pregnancy. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005456
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Hypertensive Treatment and Epidemiological Analyses Condition(s): Cardiovascular Diseases; Hypertension; Heart Diseases; Coronary Disease Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To determine the impact of the treatment of hypertension on the epidemiological analyses of blood pressure from observational studies. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005501
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Phase IV Study of Chronic Infusional Epoprostenol for Severe Primary Pulmonary Hypertension Condition(s): Hypertension, Pulmonary Study Status: This study is completed.
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Sponsor(s): National Center for Research Resources (NCRR); Baylor College of Medicine Purpose - Excerpt: Objectives: I. Provide epoprostenol (Flolan, prostaglandin I2) by chronic infusion to patients with severe primary pulmonary hypertension for whom no alternative therapy is available. II. Obtain additional safety information on continuous infusion epoprostenol. III. Obtain additional information on economic resource health consumption. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004754 •
Polyunsaturates and KCL to Control Mild Hypertension Condition(s): Cardiovascular Diseases; Heart Diseases; Hypertension; Vascular Diseases Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To test the efficacy of omega-3 fatty acids, magnesium, calcium, and potassium supplementation in untreated mild hypertensives and magnesium and potassium supplementation in treated hypertensives. Three clinical trials were conducted in sequence over a four year period. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000511
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Prevention of Hypertension: A Randomized Trial Condition(s): Cardiovascular Diseases; Heart Diseases; Hypertension; Vascular Diseases Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To determine whether improved nutrition to correct overweight and high sodium intake, and regular frequent moderate rhythmic exercise to improve cardio-pulmonary fitness and to slow heart rate could lower blood pressure and prevent development of hypertension in hypertension-prone individuals. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000495
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Role of Endothelin in the Regulation of Vascular Tone in Patients with Essential Hypertension Condition(s): Hypertension Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI)
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Purpose - Excerpt: Endothelin-1 (ET-1) is a powerful vasoconstricting peptide produced predominantly by vascular endothelial cells, that exerts its effect through the interaction with specific receptors, ETA and ETB, on the underlying smooth muscle cells. Previous studies in normal subjects have demonstrated an increase in forearm blood flow after ET-1 antagonism, suggesting a physiologic role of ET-1 in the regulation of basal vascular tone. However, whether ET-1-mediated tone is increased in hypertensive patients is unknown. The main purpose of this study will be to compare the forearm vascular responses to local infusion of ET-1 receptor antagonists between normotensive and hypertensive subjects in order to assess whether ET-1-mediated basal tone is increased in patients with hypertension. In addition, we propose to study the vascular responses to local ET-1 infusion to determine whether vascular smooth muscle sensitivity to this peptide is increased in hypertensive vessels. We will use both an ETA receptor antagonist, BQ-123, and an ETB receptor antagonist, BQ-788, in order to evaluate the relative contribution of the two receptor subtypes to the regulation of vascular tone. All drugs will be infused into the brachial artery and the responses of the forearm vasculature will be measured by means of strain gauge plethysmography. Because of the relative long-lasting effect of most of the substances to be infused, the study will be performed on two separate occasions. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001527 •
Sodium Transport: Genetics and Hypertension Condition(s): Cardiovascular Diseases; Heart Diseases; Hypertension Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: Originally, to determine whether genetic alterations in pathways of sodium ion transport in the red blood cells of children could predict their risk of developing primary hypertension in adulthood. In 1992, the objective was to determine the genetic basis of interindividual variation in the risk of essential hypertension in the population at large using the Rochester Family Heart Study. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005166
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Systolic Hypertension in the Elderly Program (SHEP) Condition(s): Cardiovascular Diseases; Cerebrovascular Disorders; Heart Diseases; Hypertension Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI); National Institute on Aging (NIA) Purpose - Excerpt: The primary objective was to assess whether long-term administration of antihypertensive therapy to elderly subjects with isolated systolic hypertension reduced the combined incidence of fatal and non-fatal stroke. The secondary objectives were to evaluate: the effect of long-term antihypertensive therapy on mortality from any cause in elderly people with isolated systolic hypertension;
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possible adverse effects of chronic use of antihypertensive drug treatment in this population; the effect of therapy on indices of quality-of-life; the natural history of isolated systolic hypertension in the placebo population. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000514 •
Telmisartan vs. valsartan missed dose Condition(s): Hypertension Study Status: This study is completed. Sponsor(s): Boehringer Ingelheim Pharmaceuticals Purpose - Excerpt: The primary objectives are to demonstrate that MICARDIS(r) (telmisartan) is statistically superior to Diovan(r) (valsartan) in reducing diastolic blood pressure (DBP) following a missed dose at the end of a 6 to 8-week treatment period as measured by the 24-hour ABPM mean and to demonstrate that MICARDIS(r) is statistically superior to Diovan(r) in reducing DBP during the last 6-hours of the 24-hour dosing interval as measured by ABPM following a dose of active study medication at the end of a 6 to 8-week treatment period. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00034840
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The Role of Cyclooxygenase Activity in the Endothelial Function of Hypertensive and Hypercholesterolemic Patients Condition(s): Healthy; Hypercholesterolemia; Hypertension Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: A layer of cells called the endothelium line the walls of blood vessels. These cells produce substances that control the tone of blood vessels and thus control blood flow through the vessel. This regulating activity of the endothelium is dysfunctional in several diseases of the heart and blood vessels, including high blood pressure and high levels of cholesterol. Previous research has pointed toward a decrease in the action of nitric oxide (NO) as the cause of this abnormality. Nitric oxide is a substance produced by the cells of the endothelium that plays a role in the relaxation of blood vessels. In this project researchers plan to study blood flow through the blood vessels in patients forearms after receiving four different drugs: sodium nitroprusside, acetylcholine, L-NMMA, and aspirin. These four drugs act on the blood vessels of the forearm through different mechanisms. Acetylcholine and sodium nitroprusside are drugs that open the blood vessels of the forearm and increase blood flow through the vessel. L-NMMA is a drug that blocks production of nitric oxide (NO). Aspirin's role in controlling blood flow is unknown. Patients participating in this research study will not directly benefit from it. However, the study will contribute to researchers understanding of diseases of the blood vessels and heart.
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Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001742 •
Treatment Effects on Platelet Calcium in Hypertensive and Depressed Patients Condition(s): Depression; Hypertension Study Status: This study is not yet open for patient recruitment. Sponsor(s): Department of Veterans Affairs Medical Research Service; SmithKline Beecham Purpose - Excerpt: This study aims to determine if treatment with an SSRI antidepressant medication, paroxetine, is associated with cellular calcium response to serotonin, platelet serotonin receptors, and improvement in mood in depressed patients with or without hypertension. It is hypothesized that platelets of hypertensive patients with depressive symptomatology with be hyper-responsive to serotonin. Additionally, treatment with an SSRI antidepressant is expected to produce a down-regulation of the serotonin receptor with an associated reduction in platelet cytosolic calcium response as well as improved mood. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00018759
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Urban African-American Community Hypertension Control Condition(s): Cardiovascular Diseases; Heart Diseases; Hypertension Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To investigate whether a health education program, developed in partnership with the community and delivered by nurse supervised community health workers (CHWs), lowered high blood pressure (HBP) in inner city African American adults. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005706
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Urinary Kallikrein and Hypertension: A Prospective Study Condition(s): Cardiovascular Diseases; Heart Diseases; Hypertension Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To determine whether low total urinary kallikrein activity was prospectively associated with new hypertension onset or elevated blood pressures. Study Type: Observational Contact(s): see Web site below
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Web Site: http://clinicaltrials.gov/ct/show/NCT00005261 •
White Coat Hypertension and Antihypertensive Treatment Effect - SCOR in Hypertension Condition(s): Cardiovascular Diseases; Heart Diseases; Hypertension Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To investigate the mechanisms of white coat hypertension and study it further as a risk factor for heart damage. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005316
Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “hypertension” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •
For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/
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For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html
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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/
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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm
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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm
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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm
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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp
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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm
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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/
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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm
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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm
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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm
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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm
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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm
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For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials
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CHAPTER 6. PATENTS ON HYPERTENSION Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “hypertension” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on hypertension, we have not necessarily excluded nonmedical patents in this bibliography.
Patents on Hypertension By performing a patent search focusing on hypertension, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an 9Adapted
from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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example of the type of information that you can expect to obtain from a patent search on hypertension: •
1,2,3,4-Tetrahydro-2-piperazinyl-naphthalenes for treating hypertension Inventor(s): Seiler; Max-Peter (Basel, CH) Assignee(s): Sandoz Ltd. (Basel, CH) Patent Number: 4,308,266 Date filed: September 7, 1979 Abstract: The present invention provides tetraline derivatives, useful for the treatment of hypertension, a process for their preparation and compositions containing these compounds. Excerpt(s): and ring B can contain 1, 2 or 3 double bonds... The compounds of formula I can exist in the form of enantiomers or in racemate form... In the aforementioned compounds all alkyl, alkoxy and alkanoyl groups which possess 3 or more carbon atoms, can be linear or branched. Web site: http://www.delphion.com/details?pn=US04308266__
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13-Aza prostaglandins for the treatment of glaucoma and ocular hypertension Inventor(s): Klimko; Peter G. (Fort Worth, TX) Assignee(s): Alcon Manufacturing, Ltd.. (Fort Worth, TX) Patent Number: 6,417,228 Date filed: October 29, 1999 Abstract: 13-Aza analogs of PGF.sub.2.alpha. and methods of their use in treating glaucoma and ocular hypertension are disclosed. Excerpt(s): The present invention relates to novel compounds and methods for the treatment of glaucoma and ocular hypertension. In particular, the present invention relates to the use of certain 13-aza analogs of F series prostaglandins to treat glaucoma and ocular hypertension... Glaucoma is a progressive disease which leads to optic nerve damage and, ultimately, total loss of vision. The causes of this disease have been the subject of extensive studies for many years, but are still not fully understood. The principal symptom of and/or risk factor for the disease is elevated intraocular pressure or ocular hypertension due to excess aqueous humor in the anterior chamber of the eye... The causes of aqueous humor accumulation in the anterior chamber are not fully understood. It is known that elevated intraocular pressure ("IOP") can be at least partially controlled by administering drugs which either reduce the production of aqueous humor within the eye, such as beta-blockers and carbonic anhydrase inhibitors, or increase the outflow of aqueous humor from the eye, such as miotics and sympathomimetics. Web site: http://www.delphion.com/details?pn=US06417228__
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3-Mercaptomethyl-2-oxo-1-pyrrolidine acetic acids and use for hypertension Inventor(s): Scott; William L. (Indianapolis, IN) Assignee(s): Eli Lilly and Company (Indianapolis, IN) Patent Number: 4,552,889 Date filed: June 9, 1983 Abstract: This invention provides for certain lactam derivatives, their pharmaceutical formulations, and a method of treating hypertension. Excerpt(s): The octapeptide angiotensin II is a potent pressor agent. It is formed from the decapeptide angiotensin I by the "converting enzyme" or angiotensinase. Converting enzyme has also been shown to degrade the nonapeptide bradykinin which is a vasodilator. Compounds which inhibit angiotensinase can therefore block both the formation of angiotensin II and prevent the degradation of bradykinin. By either or both of these mechanisms, inhibitors of angiotensinase are useful as antihypertensive agents both in animal models and clinically... European Patent Application Nos. 49,505 and 49,842, Biochemical And Biophysical Research Communications, 111 (1), 166 (1983), J. Med. Chem., 25, 250 (1982), and J. Med. Chem., 24, 104 (1981) all describe 3(mercaptomethyl)-N-lactamacetic acid derivatives which are said to be useful as antihypertensive agents by virtue of their ability to inhibit angiotensin converting enzyme... R.sub.3 is hydrogen or C.sub.1 -C.sub.3 alkyl. Web site: http://www.delphion.com/details?pn=US04552889__
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Aminoalkyl phenyl selenides for the treatment of hypertension and nervous system dysfunctions Inventor(s): Roberts; Steven F. (Atlanta, GA), Herman; Heath H. (Chamblee, GA), May; Sheldon W. (Atlanta, GA) Assignee(s): Georgia Tech Research Corporation (Atlanta, GA) Patent Number: 4,906,668 Date filed: October 13, 1987 Abstract: The preparation of aminoalkyl phenyl selenides and pharmaceutically acceptable salts thereof is disclosed which are useful for the treatment of hypertension and related vascular diseases and the treatment of nervous system dysfunctions. Excerpt(s): This invention relates to the synthesis of aminoalkyl phenyl selenides useful for the treatment of hypertension and nervous system dysfunctions... Phenolic arylseleno and aryl-thio compounds and other selenide and sulfide derivatives have been disclosed for use as photographic couplers. Lau, Phillip T. S., Arylthio (or seleno, or sulfonyl) Methyl-Substituted Phenolic Compounds As Photographic Couplers, Chem. Abstracts 80: 82391. Neither the structures, nor the use disclosed by Lau are related to the compositions of the present invention... May et al., U.S. Pat. No. 4,415,591 of Nov. 15, 1983, which patent is assigned in common herewith, the subject matter of which is incorporated herein by reference, discloses a method for treating hypertension involving the administration of aminoalkyl phenyl sulfide derivatives; there is also disclosed a method for evaluating the hypotensive potential of these compounds through the rate of enzymatic oxygenation by dopamine-beta-hydroxylase in the presence of an electron donor such as hexacyanoferrate (II) or ascorbic acid; and pharmaceutical compositions are also disclosed which comprise aminoalkyl phenyl sulfide or a salt thereof in amount
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effective for treatment of hypertension, a monoamine oxidase inhibitor and a nontoxic excipient. Web site: http://www.delphion.com/details?pn=US04906668__ •
Anandamide analog compositions and method of treating intraocular hypertension using same Inventor(s): Jarvinen; Tomi (Sompatie 3 I 6, 70200 Kuopio, FI), Urtti; Arto (8 Whittier Ct., Mill Valley, CA 94941), Jarvinen; Kristina (Sompatie 3 I 6, 70200 Kuopio, FI), Pate; David W. (Postbus 1397, 1000 BJ Amsterdam, NL) Assignee(s): none reported Patent Number: 5,977,180 Date filed: January 10, 1997 Abstract: Anandamide analogues useful for the treatment of intraocular hypertension, as well as ophthalmic compositions comprising the same and a cyclodextrin, and methods of use of these compounds to treat intraocular hypertension. Excerpt(s): The present invention relates to anandamide analogues useful for the treatment of intraocular hypertension, as well as ophthalmic compositions comprising the same and a cyclodextrin, and methods of use of said compositions to treat intraocular hypertension... Subjects who smoke marijuana have reduced intraocular pressure (Helper et al, J. Am. Med. Assoc., 217:1392 (1971)). The primary psychoactive ingredient in marijuana is known to be delta-9-tetrahydrocannabinol ("THC"). Human experiments involving intravenous administration of pure THC have confirmed the intraocular pressure reduction phenomenon seen with subjects who smoke marijuana (Cooler et al, South. Med. J., 70:954 (1977)). As a result, cannabinoids have been investigated as anti-glaucoma agents... However, use of systemic cannabinoids, such as THC, as anti-glaucoma agents is disadvantageous since they can cause significant adverse psychological and physiological side-effects. In addition, cannabinoids are lipophilic compounds that are very insoluble in water, thus hindering their application as topical ophthalmic pharmaceutical products. Web site: http://www.delphion.com/details?pn=US05977180__
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Antihypertensive agents and their use in treatment of hypertension Inventor(s): Trachewsky; Daniel (Oklahoma City, OK) Assignee(s): The Board of Regents of the University of Oklahoma (Norman, OK) Patent Number: 4,264,601 Date filed: June 12, 1979 Abstract: Riboflavin analogues, including both endo- and exocyclically substituted isoalloxazines which are competitive inhibitors of the enzyme flavokinase (EC 2.7.1.26) when administered in a non-toxic dosage, effectively reduce the blood pressure of a subject suffering from hypertension. Excerpt(s): The present invention relates generally to riboflavin analogues which are competitive inhibitors of the enzyme flavokinase (EC 2.7.1.26). In one aspect the invention relates to a method for reducing blood pressure of a subject suffering from
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hypertension by administering to such subject an effective, non-toxic dosage of riboflavin analogues which are competitive inhibitors of the enzyme flavokinase. More specifically, but not by way of limitation, the present invention relates to the use of endo- and exocyclically substituted isoalloxazine derivatives as antihypertensive agents for reducing the blood pressure of a subject having hypertension... It is generally known that expansion of body fluid volumes by renal retention of sodium results in an increase in the blood pressure of an individual. It is further known that certain riboflavin analogues function as competitive inhibitors of the enzyme flavokinase... I have hertofore reported at the 60th Annual Meeting of the Endocrine Society, held at Miami Beach, Florida during June 14-16, 1978, in a paper entitled "Aldosterone Stimulation of Riboflavin Incorporation into Rat Renal Flavin Coenzymes and the Effect of Inhibition by Riboflavin Analogues on Sodium Reabsorption" and published in the Journal of Clinical Investigation, Volume 62, Number 6, 1325-1333, December 1978, that the administration of aldosterone to adrenalectomized male Sprague-Dawley rats significantly increased the biosynthesis of renal flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) in the adrenalectomized male rats. It was further reported that aldosterone significantly decreased the excretion of sodium and increased the excretion of potassium. To determine if the increased biosynthesis of the flavin coenzymes were causing the alterations in urinary sodium and potassium output by aldosterone, the riboflavin analogues, 7,8-dimethyl-10-(2'-hydroxyethyl) isoalloxazine, and 7,8-dimethyl-10-formylmethyl isoalloxazine, were administered to the animals to diminish the conversion of the riboflavin to renal flavin mononucleotide (FMN) by competitively inhibiting the enzyme flavokinase. Web site: http://www.delphion.com/details?pn=US04264601__ •
Cerebral blood outflow maintenance during intracranial hypertension Inventor(s): Pranevicius; Mindaugas (48-76-th St., Brooklyn, NY 11209), Pranevicius; Osvaldas (48-76-th St., Brooklyn, NY 11209) Assignee(s): none reported Patent Number: 6,105,582 Date filed: January 13, 1999 Abstract: Method and apparatus for detecting and treating cerebral blood vessel collapse (54) during intracranial hypertension or vasospasm by affecting cerebral venous outflow pressure (61). Venous collapse is diagnosed by lowering jugular venous bulb pressure (61) and detecting significant, progressively increasing gradient between it and ICP (60). Rising jugular venous pressure initially the collapse is terminated and then ICP starts to increase. Increasing jugular venous pressure opens collapsed vascular segments by increasing intravascular pressure. There is no increase in ICP if jugular venous pressure is maintained below value that affects ICP. During life-threatening vascular collapse caused by a plateau wave or vasospasm venous outflow pressure is temporarily increased to a level necessary to terminate collapse regardless of ICP. This is accomplished by venous occlusion catheter placed into dominant jugular vein. Catheter has highly compliant inflatable balloon operating like Starling resistor for venous outflow pressure control. Quick control of venous pressure is achieved by withdrawing/injecting fluid through catheter tip. Operation catheter is controlled by controller, which also measures ICP and possibly CBF, S.sub.jv O.sub.2. Alternative venous outflow control measures are possible.
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Excerpt(s): This invention relates to blood flow control in organs with increased compartmental- tissue pressure and collapsible vessels, specifically in the brain... The concept of critical cerebral blood flow (CBF) under the conditions of increased intracranial pressure (ICP) are well known (1,2). Studies have correlated specific levels of regional cerebral blood flow (rCBF) with reproducible clinical end points such as EEG slowing up to the point of isoelectricity. Normal rCBF of 40-60 mL/100 g/ min will maintain ion pumps, membrane potential, and the overall cellular energy pool (3). Cellular electrical failure occurs at rCBF of 15 mL/ 100 g/min (2). Decrements in rCBF below this level do not correlate with clinical end points and associated with an adverse outcome (2). From an energy standpoint, rCBF