title: Resveratrol improves vascular function in patients with hypertension and dyslipidemia by modulating NO metabolism.
abstract: Epidemiological studies have demonstrated that the Mediterranean diet, which is rich in resveratrol, is associated with a significantly reduced risk of cardiovascular disease. However, the molecular mechanisms that underlie the beneficial effects of resveratrol on cardiovascular function remain incompletely understood. Therefore, we set out to identify the molecular target(s) mediating the protective action of resveratrol on vascular function. To this end, we performed vascular reactivity studies to evaluate the effects of resveratrol on superior thyroid artery obtained from 59 patients with hypertension and dyslipidemia. We found that resveratrol evoked vasorelaxation and reduced endothelial dysfunction through the modulation of NO metabolism via (1) an 5' adenosine monophosphate-activated protein kinase-mediated increase in endothelial NO synthase activity; (2) a rise in tetrahydrobiopterin levels, which also increases endothelial NO synthase activity; and (3) attenuation of vascular oxidative stress, brought about by overexpression of manganese superoxide dismutase via an nuclear factor erythroid-derived 2-like 2-dependent mechanism. The effects of resveratrol on acetylcholine vasorelaxation were also tested in vessels from patients with nonhypertensive nondyslipidemia undergoing thyroid surgery. In this setting, resveratrol failed to exert any effect. Thus, our finding that resveratrol reduces endothelial dysfunction, an early pathophysiological feature and independent predictor of poor prognosis in most forms of cardiovascular disease, supports the concept that the risk of vascular events could be further reduced by adherence to a set of dietary and behavioral guidelines.
authors.affiliation: Vascular Physiopathology Unit, University of Naples Federico II, Naples, Italy.
authors.forename: Albino
authors.initials: A
authors.lastname: Carrizzo
authors.forename: Annibale
authors.initials: A
authors.lastname: Puca
authors.forename: Antonio
authors.initials: A
authors.lastname: Damato
authors.forename: Marina
authors.initials: M
authors.lastname: Marino
authors.forename: Elio
authors.initials: E
authors.lastname: Franco
authors.forename: Franco
authors.initials: F
authors.lastname: Pompeo
authors.forename: Anna
authors.initials: A
authors.lastname: Traficante
authors.forename: Fabio
authors.initials: F
authors.lastname: Civitillo
authors.forename: Luigi
authors.initials: L
authors.lastname: Santini
authors.forename: Valentina
authors.initials: V
authors.lastname: Trimarco
authors.forename: Carmine
authors.initials: C
authors.lastname: Vecchione
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D001708:Biopterins / Q000031:analogs & derivatives / Q000097:blood; D050171:Dyslipidemias / Q000503:physiopathology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000503:physiopathology*; D051267:NF-E2-Related Factor 2 / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010766:Phosphorylation; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D013267:Stilbenes; D001708:Biopterins; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D013482:Superoxide Dismutase; C003402:sapropterin; D000109:Acetylcholine; D000077185:Resveratrol
keywords: endothelial cells; nitric oxide; nutrition assessment; oxidative stress; vessel