Deactivation of the sympathetic nervous system in patients with chronic congestive heart failure

被引：6

作者：

Gilbert E.M. ^{[1
]}

Port J.D. ^{[2
]}

机构：

[1] Division of Cardiology, Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT

[2] Division of Cardiology and Department of Pharmacology, Department of Medicine, University of Colorado Health Sciences Center, Denver, CO 80262

来源：

Current Cardiology Reports | 2000年 / 2卷 / 3期

关键词：

Heart Failure; Chronic Heart Failure; Metoprolol; Carvedilol; Adrenergic Receptor;

D O I：

10.1007/s11886-000-0073-7

中图分类号：

学科分类号：

摘要：

In this article, we review the basic biology, signal transduction pathways, and clinical pharmacology associated with cardiac b-adrenergic receptors (b-ARs) in the context of the use of b-blocking agents in patients with chronic congestive heart failure. Adrenergic receptors, particularly the b-AR subtypes (b1-AR and b2-AR), are known to play a critical role in the modulation of cardiac function, providing for both "adaptive" and "maladaptive" compensatory changes. In the context of exercise or self-preservation, the adrenergic nervous system, acting via b-ARs permits an appropriately rapid, highly-dynamic increase in cardiac function. Conversely, in individuals with chronic congestive heart failure, the sustained, heightened activation of adrenergic nervous system, as manifested by increases in circulating catecholamines, results in downregulation and desensitization of myocardial b-ARs, and potentially, significant myocardial damage. A number of recent clinical trials have demonstrated a marked mortality benefit from using b-blocking agents such as metoprolol and carvedilol in patients with heart failure. The pharmacologic properties of several of these drugs and some of the specifics of their usefulness and limitations are discussed herein. Copyright © 2000 by Current Science Inc.

引用

页码：225 / 232

页数：7

共 57 条

[1] Bristow M.R., Ginsburg R., Umans V., Et al., Beta 1-and beta 2-adrenergic-receptor subpopulations in nonfailing and failing human ventricular myocardium: Coupling of both receptor subtypes to muscle contraction and selective beta 1-receptor down-regulation in heart failure, Circ Res, 59, pp. 297-309, (1986)
[2] Bristow M.R., Hershberger R.E., Port J.D., Et al., Beta 1-and beta 2-adrenergic receptor-mediated adenylate cyclase stimulation in nonfailing and failing human ventricular myocardium, Mol Pharmacol, 35, pp. 295-303, (1989)
[3] Cohn J.N., Levine T.B., Olivari M.T., Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure, N Engl J Med, 311, pp. 819-823, (1984)
[4] Port J.D., Malbon C.C., Integration of transmembrane signaling. Cross-talk among G-protein-linked receptors and other signal transduction pathways, Trends Cardiovasc Med, 3, pp. 85-92, (1993)
[5] Frielle T., Collins S., Daniel K., Et al., Cloning of the cDNA for the human b1-adrenergic receptor, Proc Natl Acad Sci U S A, 84, pp. 7920-7924, (1987)
[6] Kobilka B., Dixon R., Frielle T., Et al., CDNA for the human b2-adrenergic receptor: A protein with multiple membranespanning domains and encoded by a gene whose chromosomal location is shared with that of the receptor for platelet-derived growth factor, Proc Natl Acad Sci U S A, 84, pp. 46-50, (1988)
[7] Emorine L.J., Marullo S., Briend-Sutren M.M., Et al., Molecular characterization of the human beta 3-adrenergic receptor, Science, 245, pp. 1118-1121, (1989)
[8] Gauthier C., Tavernier G., Charpentier F., Et al., Functional beta3-adrenoceptor in the human heart [see comments], J Clin Invest, 98, pp. 556-562, (1996)
[9] Bristow M., Anderson F., Port J., Et al., Differences in b-adrenergic neuroeffector mechanisms in ischemic versus idiopathic dilated cardiomyopathy, Circulation, 84, pp. 1024-1039, (1991)
[10] Bristow M.R., Hershberger R.E., Port J.D., Et al., Beta-adrenergic pathways in nonfailing and failing human ventricular myocardium, Circulation, 82, (1990)

← 1 2 3 4 5 6 →