Adrenal adrenoceptors in heart failure.

摘要: Heart failure (HF) is a chronic clinical syndrome characterized by the reduction in left ventricular (LV) function and it represents one of most important causes morbidity mortality worldwide. Despite considerable advances pharmacological treatment, HF severe social burden. Sympathetic outflow, increased circulating catecholamines (CAs) biosynthesis secretion, peculiar sympatholytic treatments (as β-blockers) are presently being investigated for treatment this disease. Adrenal gland secretes Epinephrine (80%) Norepinephrine (20%) response to acetylcholine stimulation nicotinic cholinergic receptors on chromaffin cell membranes. This process regulated adrenergic (ARs): α2ARs inhibit CA release through coupling inhibitory Gi-proteins, βARs (mainly β2ARs) stimulate stimulatory Gs-proteins. All ARs G-protein-coupled (GPCRs) GPCR kinases (GRKs) regulate their signaling function. GRK2-mediated α2AR desensitization downregulation seem be fundamental regulator secretion from adrenal gland. Consequently, restoration a2AR inhibition GRK2 fascinating therapeutic strategy HF. could have several significant advantages over existing pharmacotherapies (antiadrenergic, such as bAR-blockers) minimizing side-effects extra-cardiac tissues reducing activation renin–angiotensin–aldosterone endothelin systems. The role regulation sympathetic hyperactivity opens interesting perspectives understanding pathophysiology identifying new potential targets.