title: Adrenal adrenoceptors in heart failure.
abstract: Heart failure (HF) is a chronic clinical syndrome characterized by the reduction in left ventricular (LV) function and it represents one of the most important causes of morbidity and mortality worldwide. Despite considerable advances in pharmacological treatment, HF represents a severe clinical and social burden. Sympathetic outflow, characterized by increased circulating catecholamines (CA) biosynthesis and secretion, is peculiar in HF and sympatholytic treatments (as β-blockers) are presently being used for the treatment of this disease. Adrenal gland secretes Epinephrine (80%) and Norepinephrine (20%) in response to acetylcholine stimulation of nicotinic cholinergic receptors on the chromaffin cell membranes. This process is regulated by adrenergic receptors (ARs): α2ARs inhibit CA release through coupling to inhibitory Gi-proteins, and β ARs (mainly β2ARs) stimulate CA release through coupling to stimulatory Gs-proteins. All ARs are G-protein-coupled receptors (GPCRs) and GPCR kinases (GRKs) regulate their signaling and function. Adrenal GRK2-mediated α2AR desensitization and downregulation are increased in HF and seem to be a fundamental regulator of CA secretion from the adrenal gland. Consequently, restoration of adrenal α2AR signaling through the inhibition of GRK2 is a fascinating sympatholytic therapeutic strategy for chronic HF. This strategy could have several significant advantages over existing HF pharmacotherapies minimizing side-effects on extra-cardiac tissues and reducing the chronic activation of the renin-angiotensin-aldosterone and endothelin systems. The role of adrenal ARs in regulation of sympathetic hyperactivity opens interesting perspectives in understanding HF pathophysiology and in the identification of new therapeutic targets.
authors: Department of Medical Translational Sciences, University of Naples Federico II Naples, Italy.
authors: Claudio
authors: C
authors: de Lucia
authors: Department of Medical Translational Sciences, University of Naples Federico II Naples, Italy.
authors: Grazia D
authors: GD
authors: Femminella
authors: Department of Medical Translational Sciences, University of Naples Federico II Naples, Italy.
authors: Giuseppina
authors: G
authors: Gambino
authors: Department of Medical Translational Sciences, University of Naples Federico II Naples, Italy.
authors: Gennaro
authors: G
authors: Pagano
authors: Department of Medical Translational Sciences, University of Naples Federico II Naples, Italy.
authors: Elena
authors: E
authors: Allocca
authors: Department of Medical Translational Sciences, University of Naples Federico II Naples, Italy ; Salvatore Maugeri Foundation, IRCCS, Scientific Institute of Telese Terme Telese Terme, Italy.
authors: Carlo
authors: C
authors: Rengo
authors: Department of Medical Translational Sciences, University of Naples Federico II Naples, Italy.
authors: Candida
authors: C
authors: Silvestri
authors: Department of Medical Translational Sciences, University of Naples Federico II Naples, Italy.
authors: Dario
authors: D
authors: Leosco
authors: Department of Medical Translational Sciences, University of Naples Federico II Naples, Italy ; Salvatore Maugeri Foundation, IRCCS, Scientific Institute of Telese Terme Telese Terme, Italy.
authors: Nicola
authors: N
authors: Ferrara
authors: Salvatore Maugeri Foundation, IRCCS, Scientific Institute of Telese Terme Telese Terme, Italy.
authors: Giuseppe
authors: G
authors: Rengo
keywords: GRK2; adrenal gland; adrenergic system; catecholamine; functional recovery; heart failure; β-adrenergic receptor