Adrenal adrenoceptors in heart failure: fine-tuning cardiac stimulation

Chronic heart failure (HF) is characterized by sympathetic hyperactivity reflected by increased circulating catecholamines (CAs), which contributes significantly to its morbidity and mortality. Therefore, sympatholytic treatments, that is, treatments that reduce sympathetic hyperactivity, are being pursued currently for the treatment of HF. Secretion of CAs from the adrenal gland, which is a major source of CAs, is regulated by α2-adrenoceptors (α2ARs), which inhibit, and by β-adrenoceptors (βARs), which enhance CA secretion. All ARs are G-protein-coupled receptors (GPCRs), whose signaling and function are regulated tightly by the family of GPCR kinases (GRKs). Despite the enormous potential of adrenal ARs for the regulation of sympathetic outflow, elucidation of their properties has only begun recently. Here, recent advances regarding the roles of adrenal ARs in the regulation of sympathetic outflow in HF and the regulatory properties of ARs are discussed, along with the potential benefits and challenges of harnessing their function for HF therapy.