What Is the Role of β-Adrenergic Signaling in Heart Failure?

Abstract

This review addresses open questions about the role of β-adrenergic receptors in cardiac function and failure. Cardiomyocytes express all three β-adrenergic receptor subtypes—β 1 , β 2 , and, at least in some species, β 3 . The β 1 subtype is the most prominent one and is mainly responsible for positive chronotropic and inotropic effects of catecholamines. The β 2 subtype also increases cardiac function, but its ability to activate nonclassical signaling pathways suggests a function distinct from the β 1 subtype. In heart failure, the sympathetic system is activated, cardiac β-receptor number and function are decreased, and downstream mechanisms are altered. However, in spite of a wealth of data, we still do not know whether and to what extent these alterations are adaptive/protective or detrimental, or both. Clinically, β-adrenergic antagonists represent the most important advance in heart failure therapy, but it is still debated whether they act by blocking or by resensitizing the β-adrenergic receptor system. Newer experimental therapeutic strategies aim at the receptor desensitization machinery and at downstream signaling steps.