Ghrelin Inhibits Vascular Superoxide Production in Spontaneously Hypertensive Rats

Background Ghrelin is a novel peptide involved in the control of appetite, but its role in vascular pathologies remains to be elucidated. Ghrelin was shown to decrease blood pressure (BP) and improve endothelial function. Its plasma levels are correlated with BP in humans. Mechanisms of these effects are unknown. Because oxidative stress and increased superoxide production by NAD(P)H oxidases (Nox) are critical in the pathogenesis of hypertension, we aimed to study the effects of ghrelin on vascular superoxide production and NAD(P)H oxidase activity in spontaneously hypertensive rats (SHR). Methods Aortic superoxide production and NAD(P)H oxidase activity were measured using lucigenin (5 μmol/L) chemiluminescence. Aortas from Wistar-Kyoto rats (WKY) were used as control. Direct superoxide scavenging properties of ghrelin were tested using xanthine–xanthine oxidase system. Results Both basal superoxide production and vascular NADPH oxidase activity were significantly higher in aortas from SHR, than from WKY. Preincubation of aortic segments from SHR or WKY with ghrelin caused concentration-dependent (from 50 pg/mL to 5 ng/mL) decrease of basal superoxide production. Vascular NAD(P)H oxidase activity was inhibited by ghrelin, abolishing the difference between SHR and basal WKY. Ghrelin did not affect superoxide release from the in vitro xanthine–xanthine oxidase system, indicating lack of direct superoxide scavenging properties or inhibitory effects on xanthine oxidase in vitro. Nitric oxide synthase (NOS) inhibition, using Nω-nitro-L-arginine methyl ester (L-NAME), partially blunted the effects of ghrelin on NADPH oxidase activity indicating potential role of nitric oxide. Conclusions Ghrelin inhibits vascular oxidative stress in SHR. This effect is likely related to the inhibition of vascular NAD(P)H oxidases.