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—β1, β2, and, at least in some species, β3. The β1 subtype is the most prominent one and is mainly responsible for positive chronotropic and inotropic effects of catecholamines. The β2 subtype also increases cardiac function, but its ability to activate nonclassical signaling pathways suggests a function distinct from the β1 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. N...