THE SMOOTH MUSCLE OF THE ARTERY ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY Editorial Board: Nathan Back State University of New York at Buffalo N. R. Di Luzio Tulane University School of Medicine Bernard Halpern College de France and Institute of Immuno·Biology Ephraim Katchalski The Weizmann Institute of Science David Kritchevsky Wistar Institute Abel Lajtha New York State Research Institute for Neurochemistry and Drug Addiction Rodolfo Paoletti University of Milan Recent Volumes in this Series Volume 48 PROTEIN-METAL INTERACTWNS Edited by Mendel Friedman. 1974 Volume 49 NUTRITION AND MALNUTRITION: Identification and Measurement Edited by Alexander F. Roche and Frank Falkner. 1974 Volume 50 ION·SELECTIVE MICROELECTRODES Edited by Herbert J. Berman and Normand C. Hebert. 1974 Volume 51 THE CELL SURFACE: Immunological and Chemical Approaches Edited by Barry D. Kahan and Ralph A. Reisfeld .1974 Volume 52 HEPARIN: Structure, Function, and Clinical Implications Edited by Ralph A. Bradshaw and Stanford Wessler. 1975 Volume 53 CELL IMPAIRMENT IN AGING AND DEVELOPMENT Edited by Vincent J. Cristofalo and Emma Holeckova ·1975 Volume 54 BIOLOGICAL RHYTHMS AND ENDOCRINE FUNCTION Edited by Laurence W. Hedlund, John M. Franz, and Alexander D. Kenny 1975 Volume 55 CONCANAVALIN A Edited by Tushar K. Chowdhury and A. Kurt Weiss • 1975 Volume 56 BIOCHEMICAL PHARMACOLOGY OF ETHANOL Edited by Edward Majchrowicz • 1975 Volume 57 THE SMOOTH MUSCLE OF THE ARTERY Edited by Stewart Wolf and Nirholas T. Werthe.ssen. 1975 THE SMOOTH MUSCLE OF THE ARTERY Edited by Stewart Wolf The Marine Biomedical Institute The University of Texas Medical Branch at Galveston Galveston, Texas and Nicholas T. Werthessen Department of the Navy The Office of Naval Research Boston Branch Office Boston, Massachusetts PLENUM PRESS • NEW YORK AND LONDON Library of Congress Cataloging in Publication Data Main entry under title: The Smooth muscle of the artery. (Advances in experimental medicine and biology; v. 57) "Proceedings of a workshop conference ... held in Heidelberg, West Germany, October 29·31, 1973." Bibliography: p. Includes index. 1. Smooth muscles - Congresses. 2. Arteries - Muscles - Congresses. I. W oU, Stewart George, 1914· II. Werthessen, Nicholas Theodore, 1911· III. Series: [DNLM: 1. Arteries-Congresses. 2. Muscle, Smooth-Congresses. WI AD559 v. 57 / WE500 S667 1973] QP321.S68 612'.133 75·9773 ISBN·13:978·1·4613·4478·0 e· ISBN·13:978·1·4613·4476·6 DOl: 10.1007/978·1·4613·4476·6 Proceedings of a workshop conference on The Smooth Muscle of the Arterial Wall, held in Heidelberg, West Germany, October 29.31,1973 © 1975 Plenum Press, New York Softcover reprint of the hardcover 1st edition 1975 A Division of Plenum Publishing Corporation 227 West 17th Street, New York, N.Y. lOon United Kingdom edition published by Plenum Press, London A Division of Plenum Publishing Company, Ltd. Davis House (4th floor), 8 Scruhs Lane, Harlesden, London, NWI0 6SE, England All rights reserved No part of this book may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher Participants C.W.M.ADAMS, England H.C.McGILL, U.S.A. C.G.BECKER, U.S.A. C.R.MINICK, U.S.A. S. BJORKERUD, Sweden J.C.F.POOLE, England D.E.BOWYER, England L.ROBERT, France G.BURNSTOCK, Australia A.L.ROBERTSON, U.S.A. C.CHALDAKOV, Bulgaria S.RODBARD, U.S.A. A.S.DAOUD, U.S.A. R.ROSS, U.S.A. A.J.DAY, Australia G.ROTHBLAT, U.S.A. K.FISHER-DZOGA, U.S.A. J.C.RUEGG, Germany K. GOLENHOFEN, Germany G.SCHETTLER, Germany U.GROSCHEL-STEWART, Germany C.J.SCHWARTZ, Canada M.D.HAUST, Canada D.SINAPIUS, Germany H.F.HOFF, U.S.A. E.B.SMITH, Scotland A.HORSCH, Germany A.P.SOMLYO, U.S.A. L.A.KELLY, U.S.A. A.V.SOMLYO, U.S.A. H.KIRCHHEIM, Germany O.STEIN, Israel K.KJELDSEN, Denmark Y.STEIN, Israel H.J.KNIERIEM, Germany J.P.STRONG, U.S.A. V.A.KREYE, Germany G. WEBER, Italy D.KRITCHEVSKY, U.S.A. K. WEGENER , Germany P.D.LANG, Germany A.WEIZEL, Germany K.T.LEE, U.S.A. N.T.WERTHESSEN, U.S.A. P.J.LINDNER, Germany T.WIGHT, U.S.A. H.B.LOFLAND, U.S.A. R.W.WISSLER, U.S.A. D.McDERMOTT, U.S.A. S.WOLF, U.S.A. T.K.ZEMPLENYI, U.S.A. v Preface This volume contains the edited proceedings of a workshop conference, THE SMOOTH MUSCLE OF THE ARTERIAL WALL, held at Max Planck Haus, Heidelberg, West Germany, on the occasion of the dedication of the new Myocardial Infarct Institute of the Univer sity of Heidelberg. The conference was a sequel to one held three years earlier at Lindau, West Germany, on THE ARTERY AND THE PROCESS OF ARTERIO SCLEROSIS. The earlier conference examined available data and conflicting theories on the pathogenesis of arteriosclerosis. A major yield of this gathering was a consensus that smooth muscle cell proliferation in the sub-endothelial space is a fundamental feature of atherogenesis. It was, therefore, decided in a second conference to bring together existing knowledge of arterial smooth muscle and of the structure and function of smooth muscle in general. Accordingly an international and interdisciplinary group of experts were gathered together to assess current knowledge, to attempt reconciliation of disparate data and synthesis of widely scattered information and to identify critical areas of ignorance. As before, the conference was conducted in the form of a dialogue with only a minimal number of formal presentations. Grateful acknowledgement for financial support of the confer ence is extended to: The Government of Baden-Wurttemberg, West Germany The Marine Biomedical Institute of the University of Texas Medical Branch, Galveston, Texas The Office of Naval Research, Washington, D.C. The American Heart Association The Dow Chemical Company G. D. Searle and Company ~i viii PREFACE Firma Boehringer Mannheim Firma Maizena, Hamburg Firma Pfizer, Karlsruhe Firma Rhein Pharma, Plankstadt Firma Selinka, Werbeberatung, Ravensburg Special thanks are extended to the University of Heidelberg, to Professor Gotthard Schettler, and to the Max Planck Institute for their generous and gracious hospitality. The audiovisual responsibilities at the Conference were ably handled by Mr. Harold Druschel and Mr. Robert Robbins of the Depart ment of Medical Illustrations, University of Texas Medical Branch. The illustrations were prepared and some charts redrawn by Edmond S. Alexander and Carol Hoecker of the same department. Mrs. Joan Martin undertook the entire process of transcription, typing of edits, redaction and organization of the manuscript with the assist ance of Mrs. Diane Townsend, Miss Colleen Hogan, Mrs. Lucille Smith and Ms. Moira Martin. Acknowledgement is made to the following publications for permission to reproduce illustrations: Psychosomatic Medicine Journal of Psychosomatic Research Medical Clinics of North America Transactions of the American Clinical & Climato logical Society Journal of Medical Education Journal American Medical Association Revista Medica de Chile Williams and Wilkins Springer Verlag W. B. Saunders Company Journal Oklahoma State Medical Association Contents Welcoming Remarks and Reply • • • • • • • • • • • • • • • xi Chapter 1 STRUCTURAL CHARACTERISTICS, MECHANISMS OF CONTRACTION, INNERVATION, AND PROLIFERATION OF SMOOTH MUSCLE CELLS • • • • • • • • • • • 1 Chapter 2 METABOLIC CHARACTERISTICS OF SMOOTH MUSCLE INCLUDING SYNTHETIC AND SECRETORY FUNCTIONS AND THE CHEMISTRY OF CONTRACTION • • • • • • 81 Chapter 3 RELATIONSHIP OF ENDOTHELIUM TO SMOOTH MUSCLE· 180 Chapter 4 DEVELOPMENT OF THE ATHEROMATOUS LESION 254 Bibliography 327 Index . . . . . . . . . . . . . . . . . . . . . . . . . . 367 ix WELCOMING REMARKS Dr. Gotthard Schettler I am most pleased to have the opportunity. to welcome my colleagues and friends, the participants in this Conference. After the successful Lindau meeting three years ago we decided to continue with this multidisciplinary type of Conference. Since we had to organize the Third International Symposium on Atherosclerosis in Berlin it was impossible, and probably not justified at this time, to organize a meeting as long or as large as the former Lindau meeting. We therefore decided to continue in Heidelberg with a "Little Lindau Meeting", a meet ing which may be understood as a kind of satellite meeting of our Berlin Conference because our topic will be closely related to atherosclerosis research. However, it will concentrate on a particular topic. This workshop meeting with its intimate atmosphere will provide excellent opportunities for intensive personal contacts and uninhibited discussions. We feel that the flair of the oldest university in our country and Heidelberg itself will be an appropriate and adequate alternative for the ambience of Lake Constance. The slogan of our alma mater is "Semper apertus". Heidelberg has always been very open-minded. The political atmosphere is always exciting, sometimes hot. As in many other places we have had student violence in Heidelberg. However, as in most other places the situation has stabilized again and the academic youth of our university has returned to the principles of academic engagement and achievement. Our State Government has made strong efforts to further develop our university. Not far from this building you can see the new University campus of the Heidelberg University. Heidel- xi xii WELCOME berg has become a center in many fields; especially in physics, chemistry, biochemistry, astronomy and cybernetics. The philo sophical sciences, sociology, and the faculty of law have been internationally recognized for a long time and have produced a good number of highly respected authorities. The faculty of medicine is trying to keep up with inter national standards. The German Cancer Research Center as well as the Max-Planck Institutes of Heidelberg are well equipped to perform basic research and these institutes keep strong inter national contacts. This is also true for our medical institutes which are engaged in close cooperation with many foreign univer sities. Our small Myocardial Infarct Institute which opens officially today also provides the basis for strong cooperation in the field of coronary heart disease and we hope that this Institute will be an adequate place for scientists and students from abroad to perform research on a high level. Furthermore, we hope that this type of cooperation will provide the basis for initiating common research projects. Heidelberg is one of the very few places in Germany which was not destroyed during the second world war. It is an example of a city living on old traditions. The old castle and the center of the "Altstadt" have been a great attraction for many tourists from all countries. Therefore, Heidelberg seems to be a "must" for most European travel programs. This may also help us to attract more and more friends from science and research to visit and work with us in Heidelberg. Every fifth inhabitant of this city is from a foreign country and every sixth is from the United States. So I am certain most of you will have no problem getting along in your mother tongue while walking through the old part of the city. The barkeeper and "Schankwirte" especially will answer you in their particular Pfalzisch-English; in the same manner as they used to answer in Pfalzisch-French several hundred years ago when most of their guests came from France. You, my dear friends, are not asked to express your excite ment in the same way as the soldiers of Melac, who particularly enjoyed small fireworks in the castle and thereby created one of the most famous ruins. You are, however, welcome to relax in the over-whelming atmosphere of one of the charming wine-Stuben or student pubs. This advice, however, holds only if the scientific discussions are not going to be too exhausting. The "Roter Ochse" is a good example of one of these places. I tremendously regret that I am not able to demonstrate sabre fencing for you today, since dueling was such an important part of student life in Heidelberg during the last hundred years.