Effects of beta-blockade on beta-adrenergic receptors and signal transduction

Abstract

Recent work on the effects of beta-blockers on the beta-adrenergic receptor-adenylate cyclase pathway has led to an increased understanding of the influence of chronic beta-blockade on signal transduction mediated by the beta-adrenergic receptor. In chronic congestive cardiac failure the beta-adrenergic receptor is downregulated, and small doses of beta-blockers have reversed this trend. Since adrenergic receptor density during beta-blockade tends to return toward normal levels, it has been hypothesized that the adrenergic system could then participate in inotropic support during periodic increases in local neurotransmitter release or elevation of circulating catecholamines produced by exercise or other activities, despite the presence of a competitive beta-blocking agent. Preliminary clinical results appear to support this hypothesis. In addition, the role of guanine nucleotide regulatory proteins in chronic congestive heart failure has recently been examined, but the results are conflicting. Whether an increase in the quantity or function of the guanine nucleotide inhibitory protein (Gi) is responsible at least in part for the decline in catecholamine-stimulated adenylate cyclase activity in chronic congestive heart failure remains controversial. Recent evidence also suggests that chronic beta-blockade may enhance coupling of the beta-receptor to the guanine nucleotide stimulatory protein. This could be an additional benefit of chronic beta-blockade in patients with congestive heart failure.