NITRIC OXIDE AND THE CARDIOVASCULAR SYSTEM

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1 NITRIC OXIDE AND THE CARDIOVASCULAR SYSTEM

2 CONTEMPORARY CARDIOLOGY Christopher P. Cannon, Series Editor Management of Acute Coronary Syndromes, edited by Christopher P. Cannon, 1999 Minimally Invasive Cardiac Surgery, edited by Mehmet C. Oz and Daniel J. Goldstein, 1999 Annotated Atlas of Electrocardiography: A Guide to Confident Interpretation edited by Thomas M. Blake, 1999 Platelet Glycoprotein IIb/IIIa Inhibitors in Cardiovascular Disease, edited by A. Michael Lincoff and Eric J. Topol, 1999 Nitric Oxide and the Cardiovascular System, edited by Joseph Loscalzo and Joseph A. Vita, 2000

3 NITRIC OXIDE AND THE CARDIOVASCULAR SYSTEM Edited by JOSEPH LOSCALZO, MD, PHD JOSEPH A. VITA, MD Boston University Medical Center, Boston, MA SPRINGER SCIENCE+BUSINESS MEDIA, LLC

4 2000 Springer Science+Business Media New York Originally published by Humana Press Inc in 2000 Softcover reprint of the hardcover 1st edition 2000 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. All articles, comments, opinions, conclusions, or recommendations are those of the author(s), and do not necessarily reflect the views of the publisher. Due diligence has been taken by the publishers, editors, and authors of this book to assure the accuracy of the information published and to describe generally accepted practices. The contributors herein have carefully checked to ensure that the drug selections and dosages set forth in this text are accurate and in accord with the standards accepted at the time of publication. Notwithstanding, as new research, changes in government regulations, and knowledge from clinical experience relating to drug therapy and drug reactions constantly occurs, the reader is advised to check the product information provided by the manufacturer of each drug for any change in dosages or for additional warnings and contraindications. This is of utmost importance when the recommended drug herein is a new or infrequently used drug. It is the responsibility of the treating physician to determine dosages and treatment strategies for individual patients. Further it is the responsibility of the health care provider to ascertain the Food and Drug Administration status of each drug or device used in their clinical practice. The publisher, editors, and authors are not responsible for errors or omissions or for any consequences from the application of the information presented in this book and make no warranty, express or implied, with respect to the contents in this publication. ISBN ISBN (ebook) DOI / Cover design by Patricia F. Cleary. This publication is printed on acid-free paper. ANSI Z (American National Standards Institute) Permanence of Paper for Printed Library Materials. Photocopy Authorization Policy: Authorization to photocopy items for internal or personal use, Springer Science+Business Media, LLC provided that the base fee of US $10.00 per copy, plus US $00.25 per page, is paid directly to the Copyright Clearance Center at 222 Rosewood Drive, Danvers, MA For those organizations that have been granted a photocopy license from the CCC Library of Congress Cataloging-in-Publication Data

5 PREFACE The field of nitric oxide biology has expanded considerably over the past decade with a growing appreciation of its many roles in a variety of cell and organ systems. Nitric oxide was first discovered in the cardiovascular system, and the importance of this discovery led to the award of the 1998 Nobel Prize in Physiology or Medicine to Robert Furchgott, Louis Ignarro, and Fred Murad, well-known cardiovascular investigators. With this history, it should come as no surprise that our understanding of the role of nitric oxide in biology and pathobiology is, perhaps, best developed as it relates to cardiovascular biology and disease. For this reason, we felt it would be both timely and relevant to review in detail the role of nitric oxide in cardiovascular biomedicine. To this end, we assembled a group of contributing authors with expertise in areas that include the chemistry of nitric oixide, the biochemistry of its synthesis, the molecular biology of nitric oxide synthases, the pharmacology of nitrovasodilators, and the role of nitric oxide in vascular diseases. With the recent expansion of the field in directions that range from the development of novel nitric oxide donors for the treatment of myocardial ischemia and thrombosis to the development of gene therapy approaches for the restoration of endothelial function in atherosclerosis, the application of nitric oxide biology to investigative and clinical arenas in cardiovascular medicine is, indeed, rapidly evolving. This comprehensive overview should prove useful for basic and clinical investigators alike, as well as practicing clinicians in the fields of cardiology, hematology, and vascular medicine. With a balanced presentation of basic and clinically relevant subject matter, this text will provide a compendium of information that may guide the reader through the foundations of the most recent developments in this rich and exciting field. ACKNOWLEDGMENT We thank Stephanie Tribuna for her assistance throughout the many phases of the development of this text, and Jalna Ross for her assistance in reference verification. Joseph Loscalzo, MD, PHD Joseph A. Vita, MD v

6 To Anita, Julia, Alex, Gina, Olivia, and Sam

7 CONTENTS Preface... v Contributors... ix PART I BIOLOGY OF NITRIC OXIDE The Biological Chemistry of Nitric Oxide... 3 Joseph Loscalzo 2 Cell and Molecular Biology of Nitric Oxide Synthases Olivier Feron and Thomas Michel 3 Cellular Signal Transduction and Nitric Oxide Stanley Heydrick 4 Regulation of Gene Expression by Nitric Oxide Ami A. Deora and Harry M. Lander 5 Cytotoxicity, Apoptosis, and Nitric Oxide Stefanie Dimmeler and Andreas M. Zeiher 6 Nitric Oxide and Ion Channels Victoria M. Bolotina 7 Role of Nitric Oxide in Vasomotor Regulation Richard A. Cohen 8 Nitric Oxide and Platelet-Mediated Hemostasis Elisabeth M. Battinelli and Joseph Loscalzo 9 Nitric Oxide Modulates Leukocyte Endothelial Cell Adhesion. 139 Wolfgang Cerwinka and D. Neil Granger 10 Nitric Oxide and Cardiomyocyte Function Jean-Luc Balligand and Paul J. Cannon 11 The Fibroblast and Nitric Oxide Peter Brecher 12 Nitric Oxide in Cardiac Electrophysiology Lü Fei and Douglas P. Zipes PART II CARDIOVASCULAR PATHOPHYSIOLOGY OF NITRIC OXIDE Nitric Oxide and Endothelial Dysfunction Gerard A. Dillon and Joseph A. Vita 14 Nitric Oxide and Hypertension M. Audrey Rudd, María R. Trolliet, and Joseph Loscalzo 15 Nitric Oxide and Pulmonary Hypertension John J. Leopore and Kenneth D. Bloch 16 Nitric Oxide in Atherosclerosis Robert T. Eberhardt and Joseph Loscalzo vii

8 viii Contents 17 Thrombotic Disorders and Nitric Oxide Insufficiency Jane E. Freedman and Joseph Loscalzo 18 Myocardial Nitric Oxide in Heart Failure Douglas B. Sawyer and Wilson S. Colucci 19 Shock States and Nitric Oxide Hartmut Ruetten and Christoph Thiemermann 20 Stroke and Nitric Oxide Nancy E. Stagliano and Paul L. Huang 21 The Role of Nitric Oxide in Ischemia-Reperfusion Allan M. Lefer and Reid Hayward PART III NITRIC OXIDE IN CARDIOVASCULAR THERAPEUTICS Nitrovasodilators John D. Horowitz 23 S-Nitrosothiols Jane A. Leopold and Joseph Loscalzo 24 Diazeniumdiolates (Formerly NONOates) in Cardiovascular Research and Potential Clinical Applications Joseph E. Saavedra, Anthony L. Fitzhugh, and Larry K. Keefer 25 Inhaled Nitric Oxide Therapy for Acute Respiratory Failure William Hurford and Warren M. Zapol 26 Antioxidants and Endothelium-Derived Nitric Oxide Action Annong Huang and John F. Keane`y, Jr. 27 Coating Arterial and Blood-Contacting Surfaces with NO -Donating Compounds John D. Folts and Joseph Loscalzo 28 Gene Therapy and Nitric Oxide Heiko E. von der Leyen 29 Nitric Oxide and Tissue Preservation in Transplantation David J. Pinsky and David M. Stern 30 L-Arginine: Its Role in Cardiovascular Therapy Andrew J. Maxwell and John P. Cooke Index

9 CONTRIBUTORS JEAN-LUC BALLIGAND, MD, PHD Department of Medicine, Pharmacology Unit, University of Louvain Medical School, Brussels, Belgium ELIZABETH M. BATTINELLI, MSC Whitaker Cardiovascular Institute and Evans Department KENNETH D. BLOCH, MD Cardiology Division and the Cardiovascular Research Center, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA VICTORIA BOLOTINA, PHD Vascular Biology Unit, Evans Department of Medicine, Boston University School of Medicine, Boston, MA PETER BRECHER, PHD Boston University School, of Medicine, Whitaker Cardiovascular Institute, Boston, MA PAUL J. CANNON, MD Department of Medicine, Division of Cardiology, Columbia University College of Physicians and Surgeons, New York, NY WOLFGANG CERWINKA, MD Department of Molecular and Cellular Physiology, Louisiana State University Medical Center, Shreveport, LA RICHARD A. COHEN, MD Vascular Biology Unit, Evans Department of Medicine, Boston University School of Medicine, Boston, MA WILSON S. COLUCCI, MD, FACC Myocardial Biology Unit, Boston University School of Medicine, and Cardiovascular Division, Department of Medicine, Boston University Medical Center, Boston, MA JOHN P. COOKE, MD, PHD Section of Vascular Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA AMI A. DEORA, PHD Department of Biochemistry, Cornell University Medical College, New York, NY GERARD DILLON, MD Evans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA STEFANIE DIMMELER, PHD Molecular Cardiology, Department of Internal Medicine IV, University of Frankfurt, Germany ROBERT T. EBERHARDT, MD Whitaker Cardiovascular Institute and Evans Department LÜ FEI, MD, PHD Krannert Institute of Cardiology, Department of Medicine, Indiana University School of Medicine, and the Roudebush Veterans Administration Medical Center, Indianapolis, IN OLIVIER FERON, PHD Pharmacology and Therapeutic Unit, Department of Medicine, University of Louvain Medical School, Brussels, Belgium ANTHONY L. FITZHUGH, MD Intramural Research Support Program, SAIC Frederick, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, MD JOHN D. FOLTS, PHD, FACC Coronary Thrombosis Research Laboratory, Department of Cardiology, University of Wisconsin Medical School, Madison, WI JANE E. FREEDMAN, MD Department of Clinical Pharmacology, Georgetown University, Washington, DC ix

10 x Contributors D. NEIL GRANGER, PHD Department of Molecular and Cellular Physiology, Louisiana State University Medical Center, Shreveport, LA REID HAYWARD, PHD Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA STANLEY HEYDRICK, PHD Boston University School of Medicine, Boston, MA JOHN D. HOROWITZ, MBBS, PHD Cardiology Unit, The Queen Elizabeth Hospital, Woodville, Australia ANNONG HUANG, PHD Evans Memorial Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA PAUL L. HUANG, MD, PHD Cardiovascular Research Center and Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA WILLIAM E. HURFORD, MD Department of Anesthesia and Critical Care, Massachusetts General Hospital, Boston, MA JOHN F. KEANEY, JR., MD Evans Memorial Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA LARRY K. KEEFER, PHD Chemistry Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, MD HARRY M. LANDER, PHD Department of Biochemistry, Cornell University Medical College, New York, NY ALLAN M. LEFER, PHD Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA JANE A. LEOPOLD, MD Whitaker Cardiovascular Institute and Evans Department JOHN J. LEPORE, MD Cardiology Division and the Cardiovascular Research Center, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA JOSEPH LOSCALZO, MD, PHD Whitaker Cardiovascular Institute and Evans Department ANDREW J. MAXWELL, MD Cooke Pharma, Belmont, CA THOMAS MICHEL, MD, PHD Cardiology Division, West Roxbury VA Medical Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA DAVID J. PINSKY, MD Divisions of Cardiology and Circulatory Physiology, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY M. AUDREY RUDD, PHD Whitaker Cardiovascular Institute and Evans Department HARTMUT RUETTEN, MD The William Harvey Research Institute, St. Bartholomew's and the Royal London School of Medicine and Dentistry, London, UK JOESPH E. SAAVEDRA, PHD Intramural Research Support Program, SAIC Frederick, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, MD DOUGLAS B. SAWYER, MD Myocardial Biology Unit, Boston University School of Medicine, and Cardiovascular Division, Department of Medicine, Boston University Medical Center, Boston, MA

11 Contributors xi NANCY E. STAGLIANO, PHD Cardiovascular Research Center and Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA DAVID M. STERN, MD Divisions of Cardiology and Circulatory Physiology, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY CHRISTOPH THIEMERMANN, MD The William Harvey Research Institute, St. Bartholomew's and the Royal London School of Medicine and Dentistry, London, UK MARÍA R. TROLLIET, PHD Whitaker Cardiovascular Institute and Evans Department JOSEPH A. VITA, MD Evans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA HEIKO E. VON DER LEYEN, MD, PHD Cardiogene AG, Erkrath, Germany, and Department Innere Medizin, Medizinische Hochschule, Hannover, Germany WARREN M. ZAPOL, MD Department of Anesthesia and Critical Care, Massachusetts General Hospital, Boston, MA ANDREAS M. ZEIHER, MD Molecular Cardiology, Department of Internal Medicine IV, University of Frankfurt, Germany DOUGLAS P. ZIPES, MD Krannert Institute of Cardiology, Department of Medicine, Indiana University School of Medicine, and the Roudebush Veterans Administration Medical Center, Indianapolis, IN

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