Cardiac α1A-Adrenergic Receptors: Adaptive Physiology to Therapeutic Targeting

The cardiovascular system is required to adapt continuously to fluctuations in physiological demands from exercise, stress, and hemodynamic load. The sympathetic nervous system (SNS) plays a central role in these adaptations through the release of norepinephrine (NE) and epinephrine (EPI). These endogenous catecholamines bind to adrenergic receptors (ARs) in the heart and blood vessels to regulate cardiac output and blood pressure. Adrenergic receptors are ligand-activated G-protein-coupled receptors (GPCRs) that most broadly are divided into α- and β-AR families. Cardiomyocytes predominantly express β1-ARs, with smaller populations of β2-ARs, α1-ARs. The physiological functions of the myocardial β1-AR and vascular smooth muscle α1-ARs have been explicated extensively. This review will focus on recent developments in our understanding of α1-AR biology in the heart, with a particular focus on recent data explicating the emerging cardioprotective effects of the α1A-AR subtype.