β-Adrenergic Signaling in Heart Failure

INTRODUCTION Activation of cardiac -adrenergic receptors (AR) represents the body's most powerful principle to increase cardiac contractility and heart rate [1]. Since the description of the AR as a distinct pharmacological entity [2] and the subdivision into 1-adrenergic and 2-adrenergic receptors by Lands and colleagues in 1967 [3], it has rapidly evolved into one of the most intensely studied receptor families. Pharmacological agents active at -adrenergic receptors were soon introduced into clinical practice. Before the 1980s, heart failure was regarded and treated primarily from the standpoint of reduced contractility and cardiac output. Hence, positive inotropic agents, including -receptor agonists, were used to treat heart failure patients with the result of inotropic benefit. Consequently, blockade of cardiac -adrenergic receptors was regarded as a contraindication in heart failure treatment due to its negative inotropic effect. In recent years, a dramatic change in the perception of cardiac -adrenergic signaling has occurred. Both experimental and clinical studies have shaped a novel picture of -adrenergic signaling, including the propagation of cardiomyocyte hypertrophy and apoptosis, and the progression of heart failure. As a direct result of this altered perception, -blockade in heart failure is now regarded as the single most effective therapeutic principle to treat chronic heart failure. This chapter will provide a brief overview about -adrenergic receptors in the heart, and focus on recent developments in the understanding of -adrenergic signaling and the use of -blockers in heart failure.