Cardiac α1A-adrenergic receptors: emerging protective roles in cardiovascular diseases

Abstract

α1-Adrenergic receptors (ARs) are catecholamine-activated G protein-coupled receptors (GPCRs) that are expressed in mouse and human myocardium and vasculature, and play essential roles in the regulation of cardiovascular physiology. Though α1-ARs are less abundant in the heart than β1-ARs, activation of cardiac α1-ARs results in important biologic processes such as hypertrophy, positive inotropy, ischemic preconditioning, and protection from cell death. Data from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) indicate that nonselectively blocking α1-ARs is associated with a twofold increase in adverse cardiac events, including heart failure and angina, suggesting that α1-AR activation might also be cardioprotective in humans. Mounting evidence implicates the α1A-AR subtype in these adaptive effects, including prevention and reversal of heart failure in animal models by α1A agonists. In this review, we summarize recent advances in our understanding of cardiac α1A-ARs.