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.

Effect of Cardioselective Beta Blocker on Lisinopril Treated Isolated Rabbit’s Heart

“…In this study it was investigated that altered responses of metoprolol on lisinopril treated heart. [22][23][24][25][26][27] and hence proved by our data. The force of contraction of cardiac muscles and heart rate both are decreased by chronic administration of lisinopril and then metoprolol i.e.…”

The effectiveness and relative effectiveness of intravenous inotropic drugs acting through the adrenergic pathway in patients with heart failure—a meta‐regression analysis

“…Beta‐blockers will reduce the inotropic response to beta‐agonists, which may reduce both any benefit or harm from these agents. There is evidence [70–72] that chronic oral dosing with selective beta 1 ‐blockers leads to up‐regulation in beta 2 ‐receptor density which may last for several days beyond the last dose. The clinical significance of this is unclear.…”

Prevention of Heart Failure in Rats by Trimetazidine Treatment: A Consequence of Accelerated Phospholipid Turnover?

“…This desensitization is associated with a downregulation of ␤-adrenergic receptors (ARs) (Bristow et al, 1982) that is involved in the progression from the compensated cardiac hypertrophy status to the heart failure status as reported in human and experimental animal models (Böhm et al, 1997;Joseph and Gilbert 1998;Anderson et al, 1999). The reduction of cardiac ␤-AR site number is usually considered to parallel the evolution of the disease and, particularly, the dramatic alteration in cardiac membrane homeostasis capacity.…”