CONTROL OF THE CARDIOVASCULAR AND RESPIRATORY SYSTEMS IN HEALTH AND DISEASE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY Editorial Board: NATHAN BACK, State University of New York at Buffalo IRUN R. COHEN, The Weizmann Institute of Science DAVID KRITCHEVSKY, Wistar Institute ABEL LAJTHA, N. S. Kline Institute for Psychiatric Research RODOLFO PAOLETTI, University of Milan Recent Volumes in this Series Volume 375 DIET AND CANCER: Molecular Mechanisms of Interactions Edited under the auspices of the American Institute for Cancer Research Volume 376 GLYCOIMMUNOLOGY Edited by Azita Alavi and John S. Axford Volume 377 TISSUE RENIN-ANGIOTENSIN SYSTEMS: Current Concepts of Local Regulators in Reproductive and Endocrine Organs Edited by Amal K. Mukhopadhyay and Mohan K. Raizada Volume 378 DENDRITIC CELLS IN FUNDAMENTAL AND CLINICAL IMMUNOLOGY, Volume 2 Edited by Jacques Banchereau and Daniel Schmitt Volume 379 SUBTILISIN ENZYMES: Practical Protein Engineering Edited by Richard Bott and Christian Betzel Volume 380 CORONA- AND RELATED VIRUSES: Current Concepts in Molecular Biology and Pathogenesis Edited by Pierre J. Talbot and Gary A. Levy Volume 381 CONTROL OF THE CARDIOVASCULAR AND RESPIRATORY SYSTEMS IN HEALTH AND DISEASE Edited by C. Tissa Kappagoda and Marc P. Kaufman Volume 382 MOLECULAR AND SUBCELLULAR CARDIOLOGY: Effects of Structure and Function Edited by Samuel Sideman and Rafael Beyar Volume 383 IMMUNOBIOLOGY OF PROTEINS AND PEPTIDES VIII: Manipulation or Modulation of the Immune Response Edited by M. Zouhair Atassi and Garvin S. Bixler, Jr. A Continuation Order Plan is available for this series. A continuation order will bring delivery of each new volume immediately upon publication. Volumes are billed only upon actual shipment. For further information please contact the publisher. CONTROL OF THE CARDIOVASCULAR AND RESPIRATORY SYSTEMS IN HEALTH AND DISEASE Edited by C. Tissa Kappagoda and Marc P. Kaufman University of California, Davis Davis, California SPRINGER SCIENCE+BUSINESS MEDIA, LLC Library of Congress Cataloging-in-Publication Data Control of the cardiovascular and respiratory systems in health and disease / edited by C. Tissa Kappagoda and Marc P. Kaufman. p. cm. — (Advances in experimental medicine and biology ; v. 381) "Proceedings of the Symposium on Control of the Cardiovascular and Respiratory Systems in Health and Disease, held April 8-9, 1994, at the University of California", Davis, California—T.p. verso. Includes bibliographical references and index. ISBN 978-1-4613-5773-5 ISBN 978-1-4615-1895-2 (eBook) DOI 10.1007/978-1-4615-1895-2 1. Respiration—Regulation—Congresses. 2. Heart—Contraction¬ -Regulation—Congresses. 3. Cardiopulmonary system—Congresses. 4. Lungs—Innervation—Congresses. 5. Heart—Innervation- -Congresses. I. Kappagoda, C. T. II. Kaufman, Marc P. III. Symposium on Control of the Cardiovascular and Respiratory Systems in Health and Disease (1994 ; University of California, Davis) IV. Series. [DNLM: 1. Cardiovascular System—physiology—congresses. 2. Respiratory Systems—phyology—congresses. 3. Neurotransmitters- -congresses. WG 102 C764 1995] QP123.C67 1995 612. 1—dc20 DNLM/DLC for Library of Congress 95-37629 CIP Proceedings of the Symposium on Control of the Cardiovascular and Respiratory Systems in Health and Disease, held April 8—9, 1994, at the University of California, Davis, Davis, California ISBN 978-1-4613-5773-5 © 1995 Springer Science+Business Media New York Originally published by Plenum Press, New York in 1995 Softcover reprint of the hardcover 1st edition 1995 10 98765432 1 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 PREFACE On April 8-9, 1994, a symposium entitled Control of the Cardiovascular and Respiratory Systems in Health and Disease was held at the University of California Davis Medical Center in Sacramento. The purpose of this symposium was to honor the careers of Professors Hazel M. and John C.G. Coleridge. Participants in this symposium came from throughout the world. Their attendance at the symposium was a symbol of great respect and affection for the honorees. The Professors Coleridge have made many important contribu tions to the scientific literature concerning neural control of the cardiovascular and respira tory systems. In addition, they have made remarkable contributions to the lives of other scientists working in this field of investigation. Some of us have known them as mentors, counselors, friends, and supervisors; others have known them as co-investigators. Most importantly, all of us have known them as friends. This book, which contains the proceedings of the symposium, is dedicated to Hazel and John Coleridge. C. T. Kappagoda M. P. Kaufman v ACKNOWLEDGMENTS We wish to acknowledge the financial support of the following agencies for making this symposium a reality: • Astra Merck Group (Tarek Ackad, M.D., Ph.D.) • Boehringer Ingelheim Pharmaceuticals, Inc. (Ms. Kathryn B. Lucas and Mr. Allan Holloway) • Bristol-Myers Squibb (David L. Cram, Jr., Pharm.D.) • Marion/Merrrell Dow, Inc. (Mr. Brian Scheffield) • Merck and Company (Mr. Johnathan Sakakibara) • Pfizer Laboratories (Mr. Thomas Werth) • Smith Kline Beecham and Company (Ms. Eileen Abbott) • The Upjohn Company (Mr. Thomas Nannizzi) • Zeneca Pharmaceutical Group (Mr. Jack W. Britts) In addition we would also like to acknowledge the superb organizational skills of Ms. Shirley Martin, who was responsible for handling the logistics relating to the sympo sium, as well as Rhonda McBride and Elizabeth Walker for their clerical assistance. Finally, we would like to thank John C. Longhurst, M.D., Ph.D., Chief of Cardiovascular Medicine, University of California, Davis, for extending the facilities of the division to ensure a successful conclusion to this project. vii CONTENTS 1. Interactions of Neurotransmitters and Endothelial Cells in Determining Vascular Tone ................................................. . John T. Shepherd 2. Some Recent Advances in Studies on J Receptors ......................... 15 A. S. Paintal 3. Pathophysiology of Bronchial Asthma .................................. 27 John Widdicombe 4. Upper Airway Influences on Breathing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 37 Giuseppe Sant' Ambrogio 5. Activation of Protein Kinase C Mediates Insulin Regulation of the Na-K Pump in Cultured Skeletal Muscle ...................................... 47 S. R. Sampson 6. Aortic and Abdominal Glomera ....................................... , 57 A.Howe 7. Postnatal Development of Hypoglossal Motoneuron Intrinsic Properties. . . . . .. 63 Albert J. Berger, Douglas A. Bayliss, Mark C. Bellingham, Masashi Umemiya, and Felix Viana 8. Central Nervous Mechanisms Responsible for Cardio-Respiratory Homeostasis 73 K. M. Spyer 9. Neuroendocrine Regulation of Vascular Capacitance ....................... 81 F. Karim 10. The Microphysiology of Lung Liquid Clearance .......................... 95 Jahar Bhattacharya II. Cardiac Receptor Activity in Heart Failure: Implications for the Control of Sympathetic Nervous Outflow .................................... 109 Irving H. Zucker, Wei Wang, and Harold D. Schultz ix x Contents 12. Atrial Receptors and Heart Volumes .................................... 125 R. J. Linden 13. Aspects of Coronary Vasomotor Regulation .............................. 135 Julien 1. E. Hoffman, Giovanni Piedimonte, Andrew J. Maxwell, Jay A. Nadel, Shiro Iwanaga, and Waleed K. Husseini 14. Graded Restriction of Blood Flow in Exercising Leg Muscles: A Human Model 147 Hilding Bjurstedt and Ola Eiken 15. Cardiovascular Reflexes from Ventricular and Coronary Receptors ........... 157 Roger Hainsworth 16. Mechanisms of Release of Atrial Natriuretic Factor in Vivo .................. 175 J. R. Ledsome and K. A. King 17. Exercise Pressor Reflex: Studies on the Effect of Skeletal Muscle Fiber Type and Spinal Cord Transmission .................................... 187 L. Britt Wilson and Jere H. Mitchell 18. A Lifetime of Research in Integrative Physiology ......................... 199 Hazel M. Coleridge and John C. G. Coleridge Short Communications 19. Mechanisms Underlying Spinal Neuromodulation of the Exercise Pressor Reflex ........................................................ 209 Charles L. Stebbins 18. The Role of Vasopressin and Angiotensin II in the Hemodynamic Response to Dynamic Exercise .............................................. 215 J. David Symons and Charles L. Stebbins Index ................................................................. 223 1 INTERACTIONS OF NEUROTRANSMITTERS AND ENDOTHELIAL CELLS IN DETERMINING VASCULAR TONE John T. Shepherd Mayo Clinic and Mayo Foundation Rochester, Minnesota INTRODUCTION My interest in research on the cardiovascular system began in 1948. I had joined the Department of Physiology at the Queen's University of Belfast with the title of "Demonstra tor", indicating that my responsibilities were to supervise the practical classes. This provided a paid opportunity to spend one year preparing for the basic science section of the examina tions to qualify as a Fellow of the Royal College of Surgeons of England. The chairman of the department was Henry Barcroft, later FRS, who had brought the method of venous occlusion plethysmography to the department, for the measurement of blood flow in human limbs. In his first studies, Barcroft demonstrated the presence of sympathetic nerves to the human forearm muscle blood vessels. After the second World War started in 1939, fainting was noted to occur in certain blood donors. Sir Thomas Lewis had concluded that vagal slowing of the heart was the primary cause of the sudden decrease in arterial blood pressure. Barcroft and Edholm decided to use plethysmography to study the circulation to the leg muscles, using conscientious objectors to the war who were willing volunteers for the studies. Venous blood was withdrawn until the subjects fainted. At the time of the faint, despite the marked decrease in arterial blood pressure, the blood flow to the leg muscles increased, demonstrating that the resistance vessels had dilated. This did not occur if the sympathetic nerves were interrupted; the dilatation was too large to be attributed solely to a decrease in sympathetic vasoconstrictor activity. Barcroft and Edholm concluded, therefore, that vasodilator nerves to skeletal muscles were activated during the faint; since these muscles form about 40 per cent of the body mass, this could explain the decrease in arterial blood pressure. The nature of the vasodilator nerves remains to be elucidated (see Barcroft and Swan 1953). Gunshot wounds of major arteries were common in the war, necessitating ligation of major vessels. At the same time, surgeons frequently did a surgical sympathectomy on the assumption that this would enhance the collateral circulation. Therefore, Barcroft asked me to investigate whether these vessels had a sympathetic innervation in humans, and offered me a tenure appointment as Lecturer in the Department. Control of the Cardiovascular and Respiratory Systems in Health and Disease Edited by C. T. Kappagoda and M. P. Kaufman, Plenum Press, New York, 1995 2 J. T. Shepherd By measuring the changes in blood flow to the calf of the leg in normal subjects during temporary mechanical occlusion of one femoral artery, before and after sympathetic blockade using a newly developed drug, tetraethylammonium bromide, I succeeded in showing that, in the leg with the femoral artery occluded, the collateral flow increased after blockade, both at rest and after exercise of the leg. I submitted these studies for the Master of Surgery degree of the: Queen's University. The external examiner was a vascular surgeon and fortunately, a leading advocate of surgical sympathectomy, so I received a gold medal. This was my only contribution to surgery, since I had succumbed to the lure and challenges of an Investigator's career. Barcroft comforted me by saying that if I stayed around long enough, he felt certain that physiologists would soon receive a living wage! Henry Barcroft left The Queen's University in 1948 to accept the Chair of Physiology at St. Thomas Hospital Medical School in London, and was succeeded in Queen's by David Greenfield from St. Mary's Hospital Medical School in London. At that time Ian Roddie and Robert Whelan had joined the department; Autar Paintal, then working at the University of Edinburgh, had demonstrated the A and B receptors in the cat atria and found that type Bare stretch receptors responding to changes in atrial filling (1953). These studies were the stimulus for us to test the effect of increasing central venous pressure on the reflex control of the forearm muscle resistance vessels by passively raising the legs of the horizontal subject. This caused an increase in blood flow in the skeletal muscles of the forearm due to a decrease in sympathetic vasoconstrictor activity; I was the best responder because of my long legs. Since the arterial blood pressure did not change, we concluded that this was due to a reflex mediated by "stimulation of rec'~ptors in a low-pres sure area of the intrathoracic vascular bed" (Roddie and Shepherd 1956; Roddie, Shepherd and Whelan 1957). Some years later, David Greenfield took a sabbatical leave at the Cardiovascular Research Institute at the University of California in San Francisco. Here he developed a lower body box with a seal around the waist and attached it to a vacuum cleaner for the application of negative pressure. With negative pressures of 1: 5-20 mm/Hg, which did not cause changes in arterial blood pressure, the forearm muscle vessels reflexly constricted, consistent with deactivation of mechanoreceptors in the cardiopulmonary area. Since then, the "Greenfield suck-box" has become the standard method for investigation of these receptors in humans (Brown et al 1966). An important impetus to the further studies of these cardiopulmonary mechanore ceptors in humans was the demonstration by Coleridge et al (1964) in clog's ventricles, that some of these receptors are mechanoreceptors, capable of signalling changes in the inotropic state of the ventricles as well as changes in its volume. Some of these receptors are subserved by myelinated vagal afferents (Paintal 1955; Brown 1965) and others, including the heart and lungs, unmyelinated (C fiber) afferents (Coleridge et al 1964; Baker et al 1979; Thoren et al 1976). As the papers in this symposium indicate, the search continues to understand the signal transduction processes responsible for activation, not only of the cardiopulmonary, but also the arterial mechanoreceptors and skeletal muscle ergoreceptors, and the transmitters involved in the processing of the information received from these receptors by the centers in the brain, with the resultant translation of the afferent inputs from the peripheral sensors into the appropriate alterations in autonomic outflow. THE VASCULAR NEUROEFFECTOR JUNCTION The final determinant of the response of the cardiovascular system occurs at the effector organs, where the neurotransmitters released from the nerve endings and their