Effect of α1-adrenergic receptors in cardiac pathophysiology

Compelling evidence now exists that proves adrenergic blockade is at the center of neurohormonal antagonism in heart failure (HF). Catecholamines are well known to act through both β- and α-adrenergic receptors (ARs), which mediate their effects through distinct receptor pathways. β-AR blockers are commonly used in the treatment of HF and have distinct receptor affinity profiles. The recent COMET trial comparing 2 important β-blocking drugs showed a distinct advantage for carvedilol in decreasing the risk of mortality from HF. The mechanism of action for carvedilol differs from metoprolol tartrate in its ability to block both α- and β-ARs, leading to renewed interest in the potential role of α-ARs in the progression of HF. In contrast, however, the ALLHAT study discontinued use of doxazosin, an α1-receptor blocker because of an increase in cardiovascular events among patients using this drug. The results of these studies appear to be in contrast with respect to the role of α-ARs in regards to cardiovascular pathophysiology. Further study of the α-receptor and understanding the role of α-ARs in HF is necessary to understand the therapeutic effect of α-blockade. This article reviews our understanding of the α-AR in HF.