The Endothelium in Cardiovascular Disease

Transcription

1 Thomas F. Luscher (Ed.) The Endothelium in Cardiovascular Disease Pathophysiology, Clinical Presentation and Pharmacotherapy

2 Springer Berlin Heidelberg New York Barcelona Budapest Hong Kong London Milan Paris Tokyo

3 Thomas F. Luscher (Ed.) The Endothelium in Cardiovascular Disease Pathophysiology, Clinical Presentation and Pharmacotherapy With 75 Figures Springer

4 Professor Dr. med. Thomas F. Luscher Abteilung Kardiologie, Inselspital 3010 Bern Switzerland Library of Congress Cataloging-tn-Publication Data The endothelium In c,rdlov.scular disease; pathophysiology, clinical presentation. and phar~acology I T.F. Luscher (ed.). p. em. Includes bibliographical references and index. ISBN-13: (a 1 k. paper) 1. Vascular endothallum--pathophyslology. 2. Endothellns- -P.thophySiOlogy. 3. NitrIC oxlde--pathophyslology. I. LUSCher. Thomas F. <Thomas FelIX) [DNLM; 1. Endoth;lium. Vascular-- physiopathology. 2. Endothel ins--physloiogy. 3. Endothallns-- antagonists & InhIbItors. 4. EndothelIum-Derived Aalaxlng Factor. 5. CardIovascular Dlseases--physlopathology, WG 500 E5S RC669.9.E SI6.1--dc20 ONLM/OLC For LIbrary of Congress CIP This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other way, and storage in data banks. Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September 9, 1965, in its current version, and permission for use must always be obtained from Springer-Verlag. Violations are liable for prosecution under the German Copyright Law. Springer-Verlag Berlin Heidelberg 1995 Softcover reprint of the hardcover 1st edition 1995 The use of general descriptive names, registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free of general use. Product liability: The publishers cannot guarantee the accuracy of any information about dosage and application contained in this book. In every individual case the user must check such information by consulting the relevant literature. Book production: PRO EDIT GmbH, D Heidelberg Cover design: Springer-Verlag, Design & Production SPIN: / Printed an acid-free paper

5 Preface Already described by Malpighi several hundred years ago, the endothelium has long been considered to be like inert wallpaper covering the inner lumen of all blood vessels. Its role in the regulation of permeability in the microcirculation was recognized later, but only recently has the important regulatory role of endothelial cells in the circulation been appreciated. In the 1970S Moncada and Vane observed that endothelial cells are a source of prostacyclin, a substance which inhibits platelet aggregation and causes vascular relaxation. Full recognition of the endothelium as an important cardiovascular regulator, however, did not come until Robert Furchgott's seminal paper in 1980 describing endothelium-derived relaxing factor produced within the cells. The nature of this endothelium-derived relaxing factor was not certain for several years. In 1987 Moncada and coworkers demonstrated that nitric oxide may account for the biological activity of the endothelium-derived relaxing factor described by Robert Furchgott. Since then the amount of literature on the endothelium as a regulator of vascular tone and growth as well as platelet function and coagulation has exploded. It is now clear that endothelial cells not only produce nitric oxide and prostacyclin, but most likely also an as yet unidentified hyperpolarizing factor. Furthermore, endothelial cells have been shown to produce potent constrictor factors such as endothelin-1, a 21-amino acid peptide, cyclooxygenase products such as prostaglandin H2 and thromboxane A2, and possibly also components of the renin -angiotensin system. The capacity for producing relaxing and contracting factors establishes the endothelium as an important regulator of vascular tone. Most interestingly, several of these substances also affect circulating blood cells such as platelets and monocytes. Indeed, platelets release substances which can stimulate the endothelium to produce nitric oxide and prostacyclin. Nitric oxide and prostacyclin, on the other hand, are able to deactivate platelets and prevent aggregation and adhesion on the cells. Hence, nitric oxide and prostacyclin may play an important protective role in the vessel wall. More recently it has been suggested that nitric oxide also acts as an inhibitor of proliferation and migration of vascular smooth muscle cells. Due to its strategic anatomical position between ilie circulating blood and vascular smooth muscle, the endothelium is a primary target and mediator of cardiovascular disease. Indeed, endothelial dysfunction has been described in a variety of disease states such as hypercholesteremia, hypertension, diabetes, and atherosclerosis. As certain of these dysfunctions of the endothelium occur rather early in the disease process, pharmacological modulation of its function may be a pro-

6 VI Preface mising approach to prevent the development of various forms of cardiovascular disease. In this monography a number of well-known clinicians and scientists in the field of endothelial cell research have contributed chapters covering different aspects of endothelial cell physiology, dysfunction, and perspectives of pharmacotherapy. It is the aim of the editor to stimulate further research in this area and to offer the notion that endothelial mediators and their modulation are now ready to be used not only in basic cardiovascular research but also in clinical research and practice. Bern, May 8, 1995 THOMAS F. LOSCHER

7 Contents The Endothelium as a Regulator of Vascular Tone and Growth T. F. LUSCHER and G. NOLL Effects of Physical and Pharmacological Interventions on Circulating Endothelin-l Levels in Humans A. MORGANTI, F. GHIO, and G. GAZZANO The Role of Endothelin in Congestive Heart Failure A. L. CLAVELL and J. C. BURNETT, Jr. Endothelin as a Regulator of Vascular Tone in Man: Studies in Upper Limb Resistance and Capacitance Vessels D. J. WEBB, W. G. HAYNES, and C. J. FERRO Systemic and Endocrine Effects of Endothelin in Humans H. VIERHAPPER Endothelin in Hypertension and Vascular Hypertrophy: Experimental Studies E. L. SCHIFFRIN Role of Endogenous Endothelin in Myocardial Ischemia and Nitric Oxide-Deficient Hypertension.... V. RICHARD, M. HOGlE, and C. THUILLEZ 74 Endothelin and Renal Function: From Theory to Therapy T. J. RABELINK and P. MORRISON The Endothelium and the Pathogenesis of Chronic Vascular Diseases: The Protective Role of Calcium Antagonists H. HALLER 97 Insulin and the Regulation of the Cardiovascular System: Role of the L-arginine Nitric Oxide Pathway and the Sympathetic Nervous System U. SCHERRER

8 VIII Contents Endothelin Receptor Antagonists as New Tools to Inhibit Endothelin induced Vasoconstriction in Humans: Comparison with Calcium Channel Blockers. 129 R. R. WENZEL and T. F. LUSCHER Endothelial Dysfunction: Clinical Applicability of Calcium Antagonist Drugs H. L. ELLIOTT Endothelin in Hypertension and Diabetes Mellitus A. FERNANDEZ-CRUZ, R. PATINO, J. IBARRA, L. FERNANDEZ, M. ROLDAN, J. MOYA, and R. FERNANDEZ-DURANGO Endothelium-Dependent Vasodilation in the Peripheral Circulation in Humans In Vivo: Effects of Hypertension and Aging S. TADDEI and A. SALVETTI Endothelin and Pulmonary Hypertension D. J. STEWART and D. LANGLEBEN Subject Index

9 List of Contributors DR. J. C. BURNETT and Physiology Cardiovascular Diseases and Internal Medicine, Mayo Clinic, 200 First Street Southwest, Rochester, MI 55905, USA DR. A. 1. CLA VELL Cardiovascular Diseases and Internal Medicine, Mayo Clinic, 200 First Street Southwest, Rochester, MI 55905, USA DR. H. L. ELLIOTT University of Glasgow, Department of Medicine and Therapeutics, Gardiner Institute - Western Infirmary, Glasgow G116NT, U.K. DR. 1. FERNANDEZ Cardiovascular Preventive Center, Department ofinternal Medicine, DR. A. FERNANDEZ-CRUZ Cardiovascular Preventive Center, Department ofinternal Medicine, DR. R. FERNANDEZ-DuRANGO Cardiovascular Preventive Center, Department of Internal Medicine, DR. C. J. FERRO Clinical Research Centre, Department of Medicine, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, U.K. DR. G. GAZZANO Centro di Fisiologia Clinica e Ipertensione, Ospedale Maggiore, Via F. Sforza, 35, Milano, Italy

10 X List of Contributors DR. F. GHIO Centro di Fisiologia Clinica e Ipertensione, Ospedale Maggiore, Via F. Sforza, 35, Milano, Italy Dr. H. Haller Franz-V olhard -Klinik, U niversitatsklinikum Rudolf Virchow, WiltbergstraBe 50, Berlin, Germany DR. W. G. HAYNES Clinical Research Centre, Department of Medicine, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, U.K. DR. M. HOGJE Service de Pharmacologie, Hopital de Bois Guillaume, CHU de Rouen, Rouen Cedex, France DR. J. IBARRA Cardiovascular Preventive Center, Department of Internal Medicine, DR. D. LANGLEBEN 3755 chemin Cote-Ste-Catherine, Cardiology Division, Jewish General Hospital, Montreal, PQ H3T 1E2, Canada DR. T. F. LOSCHER Cardiology, University Hospital, Inselspital, 3010 Bern, Switzerland DR. A. MORGANTI Centro di Fisiologia Clinica e Ipertensione, Ospedale Maggiore, Via F. Sforza, 35, Milano, Italy DR. P. MORRISON U-Gene Research, Bolognalaan 40, 3508 CJ Utrecht, The Netherlands DR. J. MOYA Cardiovascular Preventive Center, Department ofinternal Medicine, DR.G. NOLL Cardiology, University Hospital, Inselspital, 3010 Bern, Switzerland DR. R. PATINO Cardiovascular Preventive Center, Department ofinternal Medicine,

11 List of Contributors XI DR. T. J. RABELINK Department of Nephrology and Hypertension (F03.226), University Hospital Utrecht, P.o. Box 85500, 3508 GA Utrecht, The Netherlands DR. V. RICHARD Service de Pharmacologie, Hopital de Bois Guillaume, CHU de Rouen, Rouen Cedex, France DR. M. ROLDAN Department of Ophthalmology, DR. A. SALVETTI I. Clinica Medica, University of Pis a, Via Roma, 67, Pisa, Italy DR. U. SCHERRER Assistant Department ofinternal Medicine, BH , CHUV, 1011 Lausanne, Switzerland DR. E. L. SCHIFFRIN Clinical Research Institute of Montreal, 110, Pine Avenue West, Montreal, Quebec H2W 1R7, Canada DR. D. J. STEWART Head, Cardiology Division, Room 712B, St. Michael Hospital, 30, Bond Street, Toronto, Ontario M5B lw8, Canada DR. S. TADDEI I. Clinica Medica, University of Pisa, Via Roma, 67, Pisa, Italy DR. C. THUILLEZ Service de Pharmacologie, Hopital de Bois Guillaume, CHU de Rouen, Rouen Cedex, France DR. H. VIERHAPPER Associate Clinical Division of Endocrinology and Metabolism, University Clinic for Internal Medicine III, Wiihringer GiirteI18-20, 1090 Wien, Austria DR. D. J. WEBB Senior Lecturer Clinical Research Center, Department of Medicine, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, U.K. DR. R. R. WENZEL Cardiology, University Hospital, Inselspital, 3010 Bern, Switzerland