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(Circulation. 2005;112:2986-2992.)
© 2005 American Heart Association, Inc.

Vascular Medicine

Ghrelin Improves Endothelial Function in Patients With Metabolic Syndrome

Manfredi Tesauro, MD; Francesca Schinzari, MD; Micaela Iantorno, MD; Stefano Rizza, MD; Domenico Melina, MD; Davide Lauro, MD; Carmine Cardillo, MD

From the Dipartimento di Medicina Interna (M.T., M.I., S.R., D.L.), Università di Tor Vergata, and the Divisione di Terapia Medica, Complesso Integrato Columbus (F.S., D.M., C.C.), Università Cattolica del Sacro Cuore, Rome, Italy.

Correspondence to Dr Carmine Cardillo, Istituto di Patologia Speciale Medica e Semeiotica Medica, Università Cattolica del Sacro Cuore, Largo Gemelli 8, 00168 Roma, Italy. E-mail carmine.cardillo{at}rm.unicatt.it

Received April 7, 2005; revision received August 4, 2005; accepted August 10, 2005.

Background— Metabolic syndrome importantly accelerates the atherosclerotic process, the earliest event of which is endothelial dysfunction. Ghrelin, a gastric peptide with cardiovascular actions, has been shown to inhibit proatherogenic changes in experimental models. This study therefore investigated whether ghrelin administration might beneficially affect endothelial function in metabolic syndrome.

Methods and Results— Endothelium-dependent and -independent vasodilator responses to intra-arterial infusion of increasing doses of acetylcholine and sodium nitroprusside (SNP), respectively, were assessed by strain-gauge plethysmography before and after local administration of human ghrelin (200 µg/min). During saline, the vasodilator response to acetylcholine was significantly blunted (P=0.008) in patients with metabolic syndrome (n=12, 5 female) compared with controls (n=12, 7 female), whereas the vasodilator response to SNP was not different between groups (P=0.68). In patients with metabolic syndrome, basal plasma ghrelin was significantly lower than in controls (P=0.02). In these patients, ghrelin infusion markedly increased intravascular concentrations of the peptide (P<0.001) and resulted in a potentiation of the vasodilator response to acetylcholine (P=0.001 versus saline) but not to SNP (P=0.22). This effect was likely related to enhanced nitric oxide bioavailability because, in a group of patients with metabolic syndrome (n=6, 2 female), ghrelin had no effect on the vasodilator response to acetylcholine (P=0.78 versus saline) after nitric oxide inhibition by N^G-monomethyl-L-arginine.

Conclusions— These findings indicate that ghrelin reverses endothelial dysfunction in patients with metabolic syndrome by increasing nitric oxide bioactivity, thereby suggesting that decreased circulating levels of the peptide, such as those found in these patients, might play a role in the pathobiology of atherosclerosis.

Key Words: acetylcholine • endothelium • vasodilation

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