Handbook of the Autonomic Nervous System in Health and Disease edited by

C. Liana Bolis University of Milan Milan, Italy, and AIREN WHO Collaborating Centre for Research and Training in Neuroscience Geneva, Switzerland

Julio Licinio David Geffen School of Medicine at UCLA Los Angeles, California, U.S.A.

Stefano Govoni University of Pavia Pavia, Italy

Marcel Dekker, Inc. TM

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New York • Basel

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Library of Congress Cataloging-in-Publication Data A catalog record for this book is available from the Library of Congress. ISBN: 0-8247-0842-3 This book is printed on acid-free paper. Headquarters Marcel Dekker, Inc. 270 Madison Avenue, New York, NY 10016 tel: 212-696-9000; fax: 212-685-4540 Eastern Hemisphere Distribution Marcel Dekker AG Hutgasse 4, Postfach 812, CH-4001 Basel, Switzerland tel: 41-61-260-6300; fax: 41-61-260-6333 World Wide Web http://www.dekker.com The publisher offers discounts on this book when ordered in bulk quantities. For more information, write to Special Sales/Professional Marketing at the headquarters address above. Copyright © 2003 by Marcel Dekker, Inc. All Rights Reserved. Neither this book nor any part may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, microfilming, and recording, or by any information storage and retrieval system, without permission in writing from the publisher. Current printing (last digit): 10 9 8 7 6 5 4 3 2 1 PRINTED IN THE UNITED STATES OF AMERICA

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NEUROLOGICAL DISEASE AND THERAPY Advisory Board Louis R. Caplan, M.D.

Jerome Murphy, M.D.

Professor of Neurology Harvard University School of Medicine Beth Israel Deaconess Medical Center Boston, Massachusetts

Professor of Neurology University of Missouri School of Medicine Chief of Neurology Children’s Mercy Hospital Kansas City, Missouri

William Koller, M.D. National Parkinson Foundation Miami, Florida

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John C. Morris, M.D. Friedman Professor of Neurology Co-Director, Alzheimer’s Disease Research Center Washington University School of Medicine St. Louis, Missouri

Kapil Sethi, M.D. Professor of Neurology Director, Movement Disorders Program Medical College of Georgia Augusta, Georgia

Mark Tuszynski, M.D., Ph.D. Associate Professor of Neurosciences Director, Center for Neural Repair University of California–San Diego La Jolla, California

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Clinical Neurovirology, edited by Avi Nath and Joseph R. Berger

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Preface

The autonomic nervous system (ANS) consists of an integrated neuronal network that reaches all organs and tissues and is essential for the maintenance of homeostasis. The ANS ensures rapid adjustment of biological functions that are crucial for survival, adaptation, and evolution. It integrates afferent information that originates from both the environment and the internal milieu and, through its efferent pathways, regulates the functions of various organs and systems according to the needs of the organism. Because of its role in the regulation of biological functions that are essential to life, the ANS was the subject of some of the earliest research work in neurology and neuroscience. The earliest recorded reference to the visceral nervous system was made by Galen in the second century. The considerable amount of neuroanatomical and neurophysiological work performed over the last 18 centuries has helped elucidate the structure and key functions of the ANS. However, much remains to be done. Recent progress in molecular medicine and imaging has led to new approaches in neuroscience research and has provided elegant descriptions of the ANS and its functions. Increasingly sophisticated approaches using the tools of contemporary biology have allowed the molecular dissection of the mechanisms through which the ANS ensures rapid and effective integration between the central nervous system and visceral inputs, thereby establishing and maintaining homeostasis. Dysregulation of such a key system is associated with disease either linked to a primary ANS dysfunction or as an element in the pathophysiology of complex disorders such as cardiovascular diseases, asthma, and depression. The role of the ANS in disease goes beyond primary and secondary dysfunction. Pharmacological approaches to important diseases are based on drugs that are agonists and an-

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tagonists of various components of ANS function. The treatment of conditions that are highly prevalent and represent public health problems worldwide involves the use of drugs that modulate ANS function. Such diseases include various types of cardiovascular disorders, such as hypertension, heart failure, arrhythmias, ischemia, and myocardial infarction, as well as conditions such as asthma, diabetes, urinary retention, and shock. Thus, a better understanding of ANS biology and further work in this field will lead to improved knowledge of biology, pathophysiology, and pathogenesis in general. It will also lead to more efficacious treatment for human diseases of major public health significance. The volume includes views from leading scientists in the field of ANS research dealing with both classical neuroanatomical and neurochemical issues. It also discusses some less traditional aspects of the molecular organization of the ANS and its participation in functions such as sleep, thermoregulation, and neuroendocrine and neuroimmune control in health and in disease, including novel data on the role of the ANS in depression. Of particular interest is the discussion by various contributors of the ANS and cardiovascular disease, including modern clinical techniques used to study and analyze ANS function in the affected patient. This book offers a comprehensive view of the status of current research on the autonomic nervous system, directions for future investigation, and implications for clinical medicine and public health. It is a progress report on ANS research and its implications for health and disease.

Copyright 2003 by Marcel Dekker, Inc. All Rights Reserved.

C. Liana Bolis Julio Licinio Stefano Govoni

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Contents

Preface Contributors 1.

Structural and Chemical Organization of the Autonomic Neuroeffector System Geoffrey Burnstock

2.

Immune Function and Regulation of the Autonomic Nervous System: A Molecular Point of View Serge Rivest

3.

Organ Specificity of Autonomic Nervous System Responses Shaun F. Morrison

4.

Plasticity in the Autonomic Nervous System: Responses of Adult Sympathetic Neurons to Injury Richard E. Zigmond

5.

The Adrenal Medulla: Physiology and Pathophysiology Graeme Eisenhofer, Monika Ehrhart-Bornstein, and Stefan R. Bornstein

6.

Autonomic Nervous System–Leptin Interactions: Impact on Metabolic Rate and Body Weight Regulation Bulent Yildiz, Metin Ozata, Ma-Li Wong, and Julio Licinio

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7.

The Autonomic Nervous System and Thermoregulation Quentin J. Pittman

8.

Phylogenesis of the Autonomic Nervous System from Fish to Mammals C. Liana Bolis, Andrea Zenone Dalla Valle, and Margherita Piccolella

9.

Clinical Studies of the Sympathetic Nervous System Murray Esler and Magdalena S. Rumantir

10.

Autonomic Regulation and Dysregulation of the Heart: Insights from Spectral Analysis of Cardiovascular Oscillations Massimo Pagani and Daniela Lucini

11.

Cardiovascular Autonomic Dysregulation Vilho V. Myllylä, Juha T. Korpelainen, Tarja H. Haapaniemi, Uolevi Tolonen, Timo H. Mäkikallio, Mikko P. Tulppo, Kyösti A. Sotaniemi, and Heikki V. Huikuri

12.

Uremic Cardiac Autonomic Neuropathy: Clinical Evaluation with Heart Rate Variability and Metaiodobenzylguanidine Chinori Kurata

13.

The Function of the Autonomic Nervous System in Hypertension Guido Grassi and Giuseppe Mancia

14.

Autonomic Control of the Airways Peter J. Barnes

15.

The Parasympathetic Nervous System in the Pathophysiology of the Gastrointestinal Tract Yvette Taché

16.

The Autonomic Nervous System in the Normal Control and Pathophysiology of the Exocrine–Endocrine Pancreas Osvaldo M. Tiscornia

17.

Diabetes and the Autonomic Nervous System Maria Grazia Natali-Sora and Guido Pozza

18.

Sympathetic Innervation of the Kidney in Health and Disease Lars Christian Rump, Kerstin Amann, and Eberhard Ritz

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19.

Nerve Control of Bladder Function Giorgio Gabella

20.

Sleep Regulation and the Autonomic Nervous System Harvey Moldofsky and Wah-Ping Luk

21.

Major Depression and the Autonomic Nervous System Gina Rinetti and Ma-Li Wong

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Contributors

Kerstin Amann, M.D. Professor, Department of Pathology, University of Erlangen, Erlangen, Germany Peter J. Barnes, D.M., D.Sc., F.R.C.P. Professor and Head, Department of Thoracic Medicine, National Heart & Lung Institute, Imperial College, London, United Kingdom C. Liana Bolis, M.D., Ph.D. Professor, Laboratory of Comparative Biology, Department of Pharmacological Sciences, University of Milan, Milan, Italy, and AIREN, Geneva, Switzerland Stefan R. Bornstein, M.D., Ph.D. Professor of Medicine and Associate Director, Department of Endocrinology, University of Düsseldorf, Düsseldorf, Germany Geoffrey Burnstock, Ph.D, D.Sc., F.A.A., F.R.C.S.(Hon.), F.R.C.S.(Hon.), F.Med.Sci., F.R.S. Autonomic Neuroscience Institute, Royal Free & University College Medical School, London, United Kingdom Andrea Zenone Dalla Valle, Ph.D. Research Fellow, Laboratory of Comparative Biology, Department of Pharmacological Sciences, University of Milan, Milan, Italy Monika Ehrhart-Bornstein, Ph.D. German Diabetes Institute, University of Düsseldorf, Düsseldorf, Germany

Copyright 2003 by Marcel Dekker, Inc. All Rights Reserved.

Graeme Eisenhofer, Ph.D. Staff Scientist, Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, U.S.A.

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Murray Esler, M.B.B.S., Ph.D., F.R.A.C.P. Associate Director, Baker Medical Research Institute, and Professor of Medicine, Monash University, Melbourne, Victoria, Australia Giorgio Gabella, M.D., D.Sc. Professor of Histology and Cytology, Department of Anatomy and Developmental Biology, University College London, London, United Kingdom Stefano Govoni, Ph.D. Professor of Pharmacology, Head, Department of Experimental and Applied Pharmacology, School of Pharmacy, University of Pavia, Pavia, Italy. Guido Grassi, M.D. Associate Professor, Department of Clinical Medicine, University of Milan-Bicocca, and San Gerardo Hospital, Monza (Milan), Italy Tarja H. Haapaniemi, M.D., Ph.D. Department of Neurology, University of Oulu, Oulu, Finland Heikki V. Huikuri, M.D.,Ph.D. Professor, Division of Cardiology, Department of Medicine, University of Oulu, Oulu, Finland Juha T. Korpelainen, M.D., Ph.D. Assistant Professor, Department of Neurology, University of Oulu, Oulu, Finland Chinori Kurata, M.D. General Manager, Yamaha Health Care Center, Hamamatsu, Japan Julio Licinio, M.D. Director, Interdepartmental Clinical Pharmacology Center, and Professor of Psychiatry and Medicine, Neuropsychiatric Institute, David Geffen School of Medicine at UCLA, Los Angeles, California, U.S.A. Daniela Lucini Centro di Ricerca sulla Terapia Neurovegetativa, University of Milan and L. Sacco Hospital, Milan, Italy Wah-Ping Luk, B.Sc. Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada Timo H. Mäkikallio, M.D., Ph.D. Division of Cardiology, Department of Internal Medicine, University of Oulu, Oulu, Finland

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Giuseppe Mancia, M.D. Professor of Medicine and Head, Department of Clinical Medicine, University of Milan-Bicocca, and San Gerardo Hospital, Monza (Milan), Italy Harvey Moldofsky, M.D., F.R.C.P.C. Director, Sleep Disorders Clinics, Centre for Sleep and Chronobiology, and Professor Emeritus, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada

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Shaun F. Morrison, Ph.D Senior Scientist, Neurological Sciences Institute, Oregon Health and Sciences University, Beaverton, Oregon, U.S.A. Vilho V. Myllylä, M.D., Ph.D. Professor of Neurology and Vice Rector, Department of Neurology, University of Oulu, Oulu, Finland Maria Grazia Natali-Sora, M.D. Department of Neurology, Vita-Salute San Raffaele University, Milan, Italy Metin Ozata, M.D. Associate Professor, Division of Endocrinology and Metabolism, Department of Medicine, Gulhane School of Medicine, Ankara, Turkey Massimo Pagani, M.D., F.A.C.C. Professor, Department of Medicine, University of Milan and L. Sacco Hospital, Milan, Italy Margherita Piccolella, Ph.D. Research Fellow, Laboratory of Comparative Biology, Department of Pharmacological Sciences, University of Milan, Milan, Italy Quentin J. Pittman, Ph.D. Professor of Physiology, Neuroscience Research Group, Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada Guido Pozza, M.D., Ph.D. Professor of Clinical Medicine, Vita-Salute San Raffaele University, Milan, Italy Gina Rinetti, M.D. Cousins Center for Psychoneuroimmunology, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, California, U.S.A. Eberhard Ritz, M.D., F.A.H.A, F.R.C.P., F.A.C.P. Professor of Medicine and Chief, Division of Nephrology, Department of Internal Medicine, Ruperto Carola University of Heidelberg, Heidelberg, Germany

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Serge Rivest, Ph.D. Professor and MRC Scientist, Laboratory of Molecular Endocrinology, CHUL Research Center, and Professor, Department of Anatomy and Physiology, Laval University, Quebec, Quebec, Canada

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Magdalena S. Rumantir, M.D., Ph.D. Research Associate, Human Neurotransmitter Research Laboratory, Baker Medical Research Institute and Monash University, Melbourne, Victoria, Australia Lars Christian Rump, M.D. Professor of Medicine and Chief, Division of Nephrology, Department of Internal Medicine, Ruhr-University Bochum, Bochum, Germany Kyösti A. Sotaniemi, M.D., Ph.D. Associate Professor and Head, Department of Neurology, University of Oulu, Oulu, Finland Yvette Taché, Ph.D. Associate Director, CURE: Digestive Diseases Research Center, VA Greater Los Angeles Healthcare System, and Professor, Division of Digestive Diseases, Department of Medicine, and Brain Research Institute, David Geffen School of Medicine at UCLA, Los Angeles, California, U.S.A. Osvaldo M. Tiscornia, M.D., F.A.C.G. Consultant Professor, Department of Gastroenterology, University of Buenos Aires, and Chairman, Pancreatic Studies Program, José de San Martin Clinical Hospital, Capital Federal Buenos Aires, Argentina Uolevi Tolonen, M.D., Ph.D. Associate Professor, Department of Clinical Neurophysiology, University of Oulu, Oulu, Finland Mikko P. Tulppo, Ph.D. Head, Exercise Laboratory, Merikoski Rehabilitation and Research Centre, Oulu, Finland Ma-Li Wong, M.D. Professor, Department of Psychiatry and Biobehavioral Sciences, and Director, Laboratory for Pharmacogenomics, Neuropsychiatric Institute, David Geffen School of Medicine at UCLA, Los Angeles, California, U.S.A. Bulent Yildiz, M.D. Postdoctoral Fellow, Departments of Psychiatry and Medicine and Laboratory for Pharmacogenomics, Neuropsychiatric Institute, David Geffen School of Medicine at UCLA, Los Angeles, California, U.S.A. Richard E. Zigmond, Ph.D. Professor, Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, Ohio, U.S.A.

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About the Editor

C. Liana Bolis is Professor of Comparative Endocrinology, Department of Pharmacological Science, University of Milan, Italy; Director of AIREN, Geneva, Switzerland; and Codirector of the Alert Bay Marine Laboratory, Cormoran Island, Canada. Dr. Bolis is the author, coauthor, editor, or coeditor of numerous journal articles, book chapters, and books. Dr. Bolis received the M.D. degree cum laude from the University of Milan, Italy, and several M.D. Honours Cause from the University of Marseille and Aix-en-Provence, France; the University of Dakar Medical School, Senegal; and the Moron University Medical School, Buenos Aires, Argentina. Dr. Bolis also received the Ph.D. Honours Cause in zoology from the University of Goteborg, Sweden, and the academic qualification of Honour Professor in neuroscience from the Beijing Medical University and from the Shanghai Medical University, P.R.C. Since 1996 she has been a member of the Pontifical Academia for life, Vatican City. Julio Licinio is Professor of Psychiatry and Biobehavioral Sciences and Medicine/Endocrinology, Director of the Interdepartmental Clinical Pharmacology Center and the Graduate Training Program in Translational Investigation, Associate Program Director of the General Clinical Research Center, and Codirector of the Laboratory of Pharmacogenomics, David Geffen School of Medicine at UCLA, Los Angeles, California. The author, coauthor, editor, or coeditor of numerous journal articles, book chapters, and books, he is the editor of The Pharmacogenomics Journal and Molecular Psychiatry. Dr. Licinio received the M.D. degree (1982) from the University of Bahia, Brazil. Stefano Govoni is Professor of Pharmacology and Chairman of the Department of Experimental and Applied Pharmacology, School of Pharmacy, University of Pavia, Italy. Dr. Govoni is the author, coauthor, or coeditor of numerous journal articles, book chapters, and books. Since 1974, he has worked in the field of neurobiology and neuropharmacology of brain aging. Dr. Govoni received the Ph.D. degree (1974) in pharmacology from the University of Milan, Italy.

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