Alpha-1-adrenergic receptors: Targets for agonist drugs to treat heart failure

Evidence from cell, animal, and human studies demonstrates that α1-adrenergic receptors mediate adaptive and protective effects in the heart. These effects may be particularly important in chronic heart failure, when catecholamine levels are elevated and β-adrenergic receptors are down-regulated and dysfunctional. This review summarizes these data and proposes that selectively activating α1-adrenergic receptors in the heart might represent a novel and effective way to treat heart failure. This article is part of a special issue entitled “Key Signaling Molecules in Hypertrophy and Heart Failure.”

Research Highlights► α1-ARs are Gq-coupled and activated by catecholamines. ► The 3 α1-subtypes, A, B, and D, have similar expression in human and mouse hearts. ► Cell, animal, and human studies reveal numerous beneficial effects of cardiac α1-ARs. ► Low α1- agonist doses have adaptive cardiac effects without changing blood pressure. ► α1-ARs might be new targets for agonist drugs to treat heart failure.