Hormones and the Heart in Health and Disease

260 Pages·1999·7.92 MB·English

by  David G. Gardner

HORMONES AND THE HEART IN HEALTH AND DISEASE
CONTEMPORARY ENDOCRINOLOGY
P. Michael Conn,
SERIES EDITOR
22. Gene Engineering in Endocrinology, edited by MARGARET A. SHUPNIK, 2000
21. Hormones and the Heart in Health and Disease, edited by LEONARD SHARE, 1999
20. Endocrinology ofA ging, edited by JOHN E. MORLEY AND LUCRETIA VAN DEN BERG, 2000
19. Human Growth Hormone: Research and Clinical Practice, edited by Roy G. SMITH
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18. Menopause: Endocrinology and Management, edited by DAVID B. SEIFER AND
ELIZABETH A. KENNARD, 1999
17. The IGF System: Molecular Biology, Physiology, and Clinical Applications,
edited by RON G. ROSENFELD AND CHARLES T. ROBERTS, JR., 1999
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ETIENNE-EMILE BAULIEU, MICHAEL SCHUMACHER, AND PAUL ROBEL, 1999
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14. Hormone Resistance Syndromes, edited by J LARRY JAMESON, 1999
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AMI LAWS, 1999
11. Endocrinology ofB reast Cancer, edited by ANDREA MANNI, 1999
10. Molecular and Cellular Pediatric Endocrinology, edited by
STUART HANDWERGER, 1999
9. The Endocrinology ofP regnancy, edited by FULLER W BAZER, 1998
8. Gastrointestinal Endocrinology, edited by GEORGE H. GREELEY, JR., 1999
7. Clinical Management ofD iabetic Neuropathy, edited by ARISTIDIS VEVES, 1998
6. G Proteins, Receptors, and Disease, edited by ALLEN M. SPIEGEL, 1998
5. Natriuretic Peptides in Health and Disease, edited by WILLIS K. SAMSON
AND ELLIS R. LEVIN, 1997
4. Endocrinology of Critical Disease, edited by K. PATRICK OBER, 1997
3. Diseases oft he Pituitary: Diagnosis and Treatment, edited by
MARGARET E. WIERMAN, 1997
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1. Endocrinology oft he Vasculature, edited by JAMES R. SOWERS, 1996
HORMONES AND THE
HFART IN HFALTH
AND DISFASE
Edited by
LEONARD SHARE
University ofT ennessee, Memphis, TN
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Hormones and the heart in health and disease/edited by Leonard Share
p. cm.-{Contemporary endocrinology; 20)
Includes index.
ISBN 978-1-4757-5420-9 ISBN 978-1-59259-708-6 (eBook)
DOI 10.1007/978-1-59259-708-6
1. Heart-Physiology. 2.Autocrine mechanisms. 3. Atrial natriuretic peptides-Physiological effect.
4. Endothelins-Physiological effect. 5. Hormones-Physiological effect. 6. Catecholamines-Physiological
effect. 1. Share, Leonard. II. Series: Contemporary endocrinology (Totowa, NJ); 20.
[DNLM: 1. Heart-physiology. 2. Peptides-physiology. 3. Hormones-physiology.
WG 202E561 1999]
QP111.4E53 1999
612.1 '73--{ic21
DNLM/DLC
for Library of Congress 99-10459
CIP
PREFACE
The maintenance of arterial blood pressure and the distribution of blood flow to the
various organs of the body depends on the control oft he pumping action of the heart and
of the resistance of the vascular beds in the individual organs in accordance with their
metabolic needs. These controls are achieved through the integrated actions of circulat
ing hormones, humoral factors that are synthesized and released in the heart and blood
vessels, and the autonomic nervous system. The heart, however, is not only the target for
the direct and indirect actions of a number of hormones and humoral factors, it is also an
endocrine organ in the traditional sense, synthesizing and secreting into the circulation
chemical factors that act at distant sites. In this treatise, Hormones and the Heart in Health
and Disease, we interpret "endocrinology" broadly and consider traditional hormones as
well as autocoids that are secreted by the heart or that act on it. In this overview, the
relevant chapters are indicated in parentheses.
The discovery of atrial natriuretic peptide (ANP; atrial natriuretic factor, ANF) in the
1980s indicated that the heart does indeed function as an endocrine organ in the classic
sense. ANP (Chapter I) is synthesized in the heart and secreted into the circulation for
actions on the kidney, where it is a potent natriuretic agent, and on the vasculature, where
it causes vasodilation. ANP can also affect myocardial contractility.
The heart, among several other organs, can also synthesize the recently discovered
peptide humoral factors adrenomedullin (Chapter 2) and urocortin (Chapter 3).
Adrenomedullin synthesis is stimulated by volume and pressure overload and may be
released into the circulation under these circumstances. Adrenomedullin is a potent
vasodilator that can also affect myocardial function. Urocortin is a newly discovered
member of the ACTH family of peptides. The demonstration that it causes potent and
long-lasting vasodilation and an increase in myocardial contractility suggests that it may
be a particularly important cardiovascular hormone.
The heart is the direct target for several circulating hormones. Of particular interest in
heart failure is the renin-angiotensin-aldosterone system (Chapter 4). Elevated circulat
ing angiotensin II, as well as angiotensin II produced locally in the heart, can adversely
affect myocardial function. This is of particular importance in the failing heart. Elevated
plasma concentrations of aldosterone, a mineralocorticoid, as well as glucocorticoids,
can also exert negative effects on the heart via structural remodeling and electrolyte
disturbances (Chapter 5). The heart can also synthesize corticosteroids, and these may
exhibit autocrine and paracrine actions.
The autonomic nervous system plays a major role in determining the pumping action
of the heart (Chapter 6). The sympathetic nervous system and catecholamines exert
positive inotropic and chronotropic actions on the heart. These effects are opposed by
acetylcholine released from vagal nerve endings and neuropeptide Y released from sym
pathetic nerve endings. Understanding these interactions is key to understanding the
participation of the heart in cardiovascular regulation.
Vasopressin is not only the antidiuretic hormone, it is also a potent vasoconstrictor. It
has also been demonstrated that vasopressin at physiologically relevant plasma concen
trations can decrease heart rate and cardiac output (Chapter 7), and that these actions
occur at vasopressin levels that are too low to increase arterial blood pressure. These
v
vi Preface
effects of vasopressin largely result from its central actions on the sympathetic nervous
system and on baroreflex sensitivity.
Insulin (Chapter 8) contributes to both the acute and chronic regulation ofthe mechani
cal function of the heart. The importance ofthe long-term actions of insulin on the heart
is indicated by the cardiomyopathy that occurs in diabetes mellitus. Much is known about
the cellular basis for this action ofi nsulin and about its actions on myocardial metabolism.
The components oft he kallikrein-kinin system necessary for the generation of brady
kinin are present in the heart and vascular tissue (Chapter 9). Kinins probably act prima
rily as paracrine agents (local hormones), exerting important cardioprotective actions
through the release of various autocoids. The cardioprotective action of angiotensin
converting enzyme (ACE) inhibitors may be due in part to inhibition of the enzymes that
degrade kinins. The well-known autocoids, endothelin (Chapter 10), nitric oxide (Chap
ter 11), and eicosanoids (Chapter 12), are also synthesized in the heart and modulate
cardiac performance under physiological and pathophysiological conditions. Endothelin
is a potent constrictor oft he coronary vasculature and can affect myocardial contractility
and hypertrophy. Nitric oxide, on the other hand, is a potent vasodilator. It can also affect
myocardial contractility and can influence myocardial metabolism. The synthesis of
eicosanoids in the heart can be stimulated by activating both the adrenergic and cholin
ergic nervous systems and by several circulating and locally generated humoral factors.
The eicosanoids exert important modulatory effects on the heart in physiological and
pathophysiological circumstances.
It is well known that the incidence of heart disease is lower in premenopausal women
than in men. The possibility that estrogen exerts a cardioprotective action is of consid
erable interest physiologically and clinically (Chapter 13). This cardioprotective effect
ofe strogen may result in part from its actions on coronary artery endothelium and smooth
muscle and on lipid metabolism. On the other hand, there is evidence that testosterone in
men is a risk factor for coronary artery disease (Chapter 14). This may be related to the
observation that testosterone treatment in men can reduce the plasma concentration of
high-density lipoprotein cholesterol.
It is the intent oft his treatise to survey and evaluate the hormonal and autocrine factors
that modulate cardiac performance in health and disease.
Dr. JayM. Sullivan, the author ofC hapter 13,EstrogenandtheHeart, died on February
22, 1999 at the age of 62. He was Chief of the Division of Cardiovascular Diseases of
the Department ofM edicine at the University ofT ennessee, Memphis, and he was known
for his work on salt sensitivity in hypertension and the role of estrogen in protecting
against cardiovascular disease. He will be missed greatly as a physician and scholar and,
for those of us who knew him, as a colleague and friend.
Leonard Share, PHD
CONTENTS
Preface ........................................................................................................ v
Contributors .............................................................................................. ix
1 Natriuretic Peptides and the Heart.. .................................................. 1
David G. Gardner, Branka Kovacic-Milivojevic, Faquan Liang,
and Songcang Chen
2 Adrenomedullin and the Heart ....................................................... 21
Willis K. Samson
3 Cardiac and Vascular Actions ofUrocortin ................................... 39
David G. Parkes and Clive N. May
4 The Renin-Angiotensin System and the Heart ............................... 53
Haralambos Gavras and Irene Gavras
5 Adrenocortical Hormones and the Heart: A Steroidogenic
Endocrine Organ as Well as Target Organ? ............................. 69
Celso E. Gomez-Sanchez
6 Catecholamines and the Heart ........................................................ 81
Matthew N. Levy
7 Vasopressin and the Heart ............................................................ 103
Vernon S. Bishop and Max G. Sanderford
8 Insulin and the Heart ..................................................................... 115
Roger W Brownsey, Brian Rodrigues, Subodh Verma,
and John H. McNeill
9 Kinins in the Heart ........................................................................ 137
Oscar A. Carretero
10 Endothelin and the Heart .............................................................. 159
David P. Brooks and Eliot H. Ohlstein
11 Nitric Oxide and the Heart ............................................................ 175
Robert D. Bernstein, Fabio A. Recchia, Gabor Kaley,
and Thomas H. Hintze
12 Contribution of Eicosanoids in the Heart ..................................... 195
Kafait U. Malik
13 Estrogen and the Heart .................................................................. 219
Jay M Sullivan
14 Androgen and Estrogen Effects on Plasma Lipids in Men .......... 235
Carrie J. Bagatell and William J. Bremner
Index ....................................................................................................... 253
Vll
CONTRIBUTORS
CARRIE J. BAGATELL, MD· Puget Sound Veterans Medical Center, Seattle, WA
ROBERT D. BERNSTEIN, BA • Department ofP hysiology, New York Medical College,
Valhalla, NY
VERNON S. BISHOP, PHD· Department ofP hysiology, The University of Texas Health
Science Center, San Antonio, TX
WILLIAM J. BREMNER, MD, PHD • Department ofM edicine, Seattle VA Medical Center,
Seattle, WA
DAVID P. BROOKS, PHD • Department ofR enal Pharmacology, SmithKline Beecham,
King ofP russia, PA
ROGER W. BROWNSEY, PHD • Department ofB iochemistry and Molecular Biology,
The University ofB ritish Columbia, Vancouver, BC, Canada
OSCAR A. CARRETERO, MD· Hypertension and Vascular Research Division,
Henry Ford Hospital, Detroit, MI
SONGCANG CHEN, MD· Metabolic Research Unit, University of California,
San Francisco, CA
DAVID G. GARDNER, MD· Metabolic Research Unit, University of California,
San Francisco, CA
HARALAMBOS GAVRAS, MD • Hypertension and Atherosclerosis Section,
Boston University School ofM edicine, Boston, MA
IRENE GAVRAS, MD • Hypertension and Atherosclerosis Section, Boston University
School ofM edicine, Boston, MA
CELSO E. GOMEZ-SANCHEZ, MD • Harry S Truman Memorial Veterans Hospital,
Columbia, MO
THOMAS H. HINTZE, PHD • Department ofP hysiology, New York Medical College,
Valhalla, NY
GABOR KALEY, PHD • Department ofP hysiology, New York Medical College,
Valhalla, NY
BRANKA KOVACIC-MILIVOJEVIC, PHD· Metabolic Research Unit, University of
California, San Francisco, CA
MATTHEW N. LEVY, MD • Department ofI nvestigative Medicine, Mt. Sinai
Medical Center, Cleveland, OH
F AQUAN LIANG, MD, PHD • Metabolic Research Unit, University of California,
San Francisco, CA
KAFAIT U. MALIK, PHD, DSc· Department ofP harmacology University of Tennessee,
Memphis, TN
CLIVE N. MAY, PHD· Howard Florey Institute ofP hysiology and Medicine,
University ofM elbourne, Parksville, Australia
JOHN H. McNEILL, PHD • Department ofP harmaceutical Sciences, The University
ofB ritish Columbia, Vancouver, BC, Canada
ELIOT H. OHLSTEIN, PHD • Department of Cardiovascular Pharmacology, SmithKline
Beecham, King ofP russia, PA
DAVID G. PARKES, PHD· Department Physiology, Amylin Pharmaceuticals Inc.,
San Diego, CA
ix
x Contributors
FABIO A. RECCHIA, MD, PHD • Department ofP hysiology, New York Medical College,
Valhalla, NY
BRIAN RODRIGUES, PHD • Department ofP harmaceutical Sciences, The University of
British Columbia, Vancouver, BC, Canada
WILLIS K. SAMSON, PHD • Department ofP hysiology, University ofN orth Dakota
School ofM edicine and Health Sciences, Grand Forks, ND
MAX G. SANDERFORD, MS • Department ofP hysiology, The University of Texas
Health Science Center, San Antonio, TX
LEONARD SHARE, PHD· Department ofP hysiology, The University of Tennessee,
Memphis, TN
JAY M. SULLIVAN, MD (DECEASED)· Department ofM edicine, Division of
Cardiovascular Diseases, The University of Tennessee, Memphis, TN
SUBODH VERMA, PHD • Department ofP harmaceutical Sciences, The University of
British Columbia, Vancouver, BC, Canada