Effect of Ghrelin on the Cardiovascular System

SIMPLE SUMMARY: Ghrelin is an octanoylated peptide that was initially isolated from rat and human stomachs in the process of searching for an endogenous ligand to the orphan growth hormone secretagogue receptor (GHS-R), a G-protein-coupled receptor. Exogenous or endogenous ghrelin secreted from the stomach binds to GHS-R on gastric vagal nerve terminals, and the signals are transmitted to the central nervous system via the vagal afferent nerve to facilitate growth hormone (GH) secretion, feeding, sympathetic inhibition, parasympathetic activation, and anabolic effects. Ghrelin also binds directly to the pituitary GHS-R and stimulates GH secretion. Ghrelin has beneficial effects on the cardiovascular system, including cardioprotective effects such as anti-heart failure, anti-arrhythmic, and anti-inflammatory actions, and it enhances vascular activity via GHS-R-dependent stimulation of GH/IGF-1 (insulin-like growth factor-1) and modulation of the autonomic nervous system. The anti-heart failure effects of ghrelin could be useful as a new therapeutic strategy for chronic heart failure. ABSTRACT: Ghrelin, an n-octanoyl-modified 28-amino-acid-peptide, was first discovered in the human and rat stomach as an endogenous ligand for the growth hormone secretagogue receptor (GHS-R). Ghrelin-GHS-R1a signaling regulates feeding behavior and energy balance, promotes vascular activity and angiogenesis, improves arrhythmia and heart failure, and also protects against cardiovascular disease by suppressing cardiac remodeling after myocardial infarction. Ghrelin’s cardiovascular protective effects are mediated by the suppression of sympathetic activity; activation of parasympathetic activity; alleviation of vascular endothelial dysfunction; and regulation of inflammation, apoptosis, and autophagy. The physiological functions of ghrelin should be clarified to determine its pharmacological potential as a cardiovascular medication.