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

Abstract

In this article, we review the basic biology, signal transduction pathways, and clinical pharmacology associated with cardiac beta-adrenergic receptors (beta-ARs) in the context of the use of beta-blocking agents in patients with chronic congestive heart failure. Adrenergic receptors, particularly the beta-AR subtypes (beta(1)-AR and beta(2)-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 beta-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 down- regulation and desensitization of myocardial beta-ARs, and potentially, significant myocardial damage. A number of recent clinical trials have demonstrated a marked mortality benefit from using beta-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.