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(Hypertension. 2009;54:995.)
© 2009 American Heart Association, Inc.

Original Articles

Ghrelin Restores the Endothelin 1/Nitric Oxide Balance in Patients With Obesity-Related Metabolic Syndrome

Manfredi Tesauro; Francesca Schinzari; Valentina Rovella; Nicola Di Daniele; Davide Lauro; Nadia Mores; Augusto Veneziani; Carmine Cardillo

From the Department of Internal Medicine (M.T., V.R., N.D.D., D.L.), University of Tor Vergata, Rome, Italy; Departments of Internal Medicine (F.S., C.C.), Pharmacology (N.M.), and Surgery (A.V.), Catholic University Medical School, Rome, Italy.

Correspondence to 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

Obesity is associated with endothelial dysfunction related to decreased NO bioavailability, increased endothelin 1 vasoconstrictor activity, and decreased circulating ghrelin. Therefore, we tested whether exogenous ghrelin may have benefits to improve the balance between endothelin 1 and NO in patients with obesity-related metabolic syndrome. Vasoactive actions of endothelin 1 and NO were assessed in 8 patients with metabolic syndrome and 8 matched controls by evaluating forearm blood flow responses (strain-gauge plethysmography) to intra-arterial infusion of BQ-123 (endothelin A receptor antagonist; 10 nmol/min), followed by N^G-monomethyl-L-arginine (NO synthase inhibitor; 4 µmol/min), before and after infusion of ghrelin (200 ng/min). In the absence of ghrelin, the vasodilator response to BQ-123 was greater in patients than in controls (P<0.001), whereas infusion of N^G-monomethyl-L-arginine induced smaller vasoconstriction in patients than in controls (P=0.006). Importantly, exogenous ghrelin decreased the vasodilator response to BQ-123 (P=0.007 versus saline) and enhanced the magnitude of changes in forearm blood flow induced by N^G-monomethyl-L-arginine (P=0.003) in patients but not in controls (both P>0.05). The favorable effect of ghrelin on endothelin A–dependent vasoconstriction was likely related to the stimulation of NO production, because no change in the vascular effect of BQ-123 was observed after ghrelin (P=0.44) in 5 patients with metabolic syndrome during continuous infusion of the NO donor sodium nitroprusside (0.2 µg/min). In patients with metabolic syndrome, ghrelin has benefits to normalize the balance between vasoconstrictor (endothelin 1) and vasodilating (NO) mediators, thus suggesting that this peptide has important peripheral actions to preserve vascular homeostasis in humans.

Key Words: abdominal obesity • endothelin 1 • ghrelin • metabolic syndrome • NO

Related Article:

Exogenous Ghrelin on Nitric Oxide-Endothelin 1 Imbalance in Metabolic Syndrome: Can We Kill 2 Birds With 1 Stone?

Stefano Taddei and Agostino Virdis
Hypertension 2009 54: 960-961. [Extract] [Full Text] [PDF]

This article has been cited by other articles:

				S. Taddei and A. Virdis Exogenous Ghrelin on Nitric Oxide-Endothelin 1 Imbalance in Metabolic Syndrome: Can We Kill 2 Birds With 1 Stone? Hypertension, November 1, 2009; 54(5): 960 - 961. [Full Text] [PDF]