Metabolic and Cardiovascular Effects of Ghrelin

Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor, is synthesized as a preprohormone and then proteolytically processed to yield a 28-amino acid peptide. This peptide was originally reported to induce growth hormone release; large evidence, however, has indicated many other physiological activities of ghrelin, including regulation of food intake and energy balance, as well as of lipid and glucose metabolism. Ghrelin receptors have been detected in the hypothalamus and the pituitary, but also in the cardiovascular system, where ghrelin exerts beneficial hemodynamic activities. Ghrelin administration acutely improves endothelial dysfunction by increasing nitric oxide bioavailability and normalizes the altered balance between endothelin-1 and nitric oxide within the vasculature of patients with metabolic syndrome. Other cardiovascular effects of ghrelin include improvement of left ventricular contractility and cardiac output, as well as reduction of arterial pressure and systemic vascular resistance. In addition, antinflammatory and antiapoptotic actions of ghrelin have been reported both in vivo and in vitro. This review summarizes the most recent findings on the metabolic and cardiovascular effects of ghrelin through GH-dependent and -independent mechanisms and the possible role of ghrelin as a therapeutic molecule for treating cardiovascular diseases.