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
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
收藏
页码:225 / 232
页数:7
相关论文
共 57 条
[21]  
Steinberg S.F., The molecular basis for distinct beta-adrenergic receptor subtype actions in cardiomyocytes, Circ Res, 85, pp. 1101-1111, (1999)
[22]  
Communal C., Singh K., Sawyer D.B., Colucci W.S., Opposing effects of beta(1)-and beta(2)-adrenergic receptors on cardiac myocyte apoptosis : role of a pertussis toxin-sensitive G protein, Circulation, 100, pp. 2210-2212, (1999)
[23]  
Milano C.A., Allen L.F., Rockman H.A., Et al., Enhances myocardial function in transgenic mice overexpressing the b2-adrenergic receptor, Science, 264, pp. 582-586, (1994)
[24]  
Koch W., Rockman H., Samama P., Et al., Cardiac function in mice overexpressing the b-adrenergic receptor kinase or a bARK inhibitor, Science, 268, pp. 1350-1353, (1995)
[25]  
Bisognano J., Pende A., Tremmel K.D., Et al., Preliminary characterization of a transgenic mouse overexpressing the human b1-adrenergic receptor, J Invest Med, 45, (1997)
[26]  
Bisognano J., Weinberger H.D., Bohlmeyer T.J., Et al., Myocardial-directed overexpression of the human b1-adrenergic receptor in transgenic mice, J Mol Cell Cardiol, (2000)
[27]  
Engelhardt S., Hein L., Wiesmann F., Lohse M.J., Progressive hypertrophy and heart failure in beta1-adrenergic receptor transgenic mice, Proc Natl Acad Sci U S A, 96, pp. 7059-7064, (1999)
[28]  
Iwase M., Uechi M., Vatner D.E., Et al., Cardiomyopathy induced by cardiac Gs alpha overexpression, Am J Physiol, 272, (1997)
[29]  
Asai K., Yang G.P., Geng Y.J., Et al., Beta-adrenergic receptor blockade arrests myocyte damage and preserves cardiac function in the transgenic G(salpha) mouse, J Clin Invest, 104, pp. 551-558, (1999)
[30]  
Joseph J., Gilbert E.M., The sympathetic nervous system in chronic heart failure, Prog Cardiovasc Dis, 41, pp. 9-16, (1998)