title: Polyphenols restore endothelial function in DOCA-salt hypertension: role of endothelin-1 and NADPH oxidase.
abstract: Red wine polyphenols (RWPs) have been reported to exert beneficial effects in preventing cardiovascular diseases, such as hypertension. We studied the effects of chronic treatment with RWPs and apocynin, an inhibitor of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, on blood pressure, endothelial function, and oxidative status in deoxycorticosterone acetate (DOCA)-salt-induced hypertension. Rats were administered RWPs (40 mg/kg) or apocynin (33 microg/kg) daily by gavage for 5 weeks. Plasma catechin levels were detected only after RWP treatment. RWPs and apocynin prevented both the increase in systolic blood pressure and the proteinuria induced by DOCA-salt. Plasma malonyldialdehyde levels, urinary iso-prostaglandin F(2alpha) excretion, aortic superoxide production, and aortic NADPH oxidase activity were found to be increased in animals of the DOCA group. RWP and apocynin treatments reduced these parameters in DOCA-salt rats, having no effect on control rats. However, only RWPs reduced the increase in plasma endothelin-1 (ET-1) levels and aortic p22(phox) gene overexpression found in DOCA-salt animals. RWPs and apocynin also improved the blunted endothelium-dependent relaxation response to acetylcholine in noradrenaline-precontracted aortic rings. All these results suggest that chronic treatment with RWPs prevents hypertension and vascular dysfunction. RWPs prevent vascular oxidative stress by inhibiting NADPH oxidase activity and/or by reducing ET-1 release.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Spain.
authors.forename: Rosario
authors.initials: R
authors.lastname: Jiménez
authors.forename: Rocío
authors.initials: R
authors.lastname: López-Sepúlveda
authors.forename: María
authors.initials: M
authors.lastname: Kadmiri
authors.forename: Miguel
authors.initials: M
authors.lastname: Romero
authors.forename: Rocío
authors.initials: R
authors.lastname: Vera
authors.forename: Manuel
authors.initials: M
authors.lastname: Sánchez
authors.forename: Félix
authors.initials: F
authors.lastname: Vargas
authors.forename: Francisco
authors.initials: F
authors.lastname: O'Valle
authors.forename: Antonio
authors.initials: A
authors.lastname: Zarzuelo
authors.forename: Montserrat
authors.initials: M
authors.lastname: Dueñas
authors.forename: Celestino
authors.initials: C
authors.lastname: Santos-Buelga
authors.forename: Juan
authors.initials: J
authors.lastname: Duarte
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure; D003900:Desoxycorticosterone; D019332:Endothelin-1 / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005419:Flavonoids / Q000097:blood / Q000494:pharmacology*; D015870:Gene Expression; D006973:Hypertension / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D019255:NADPH Oxidases / Q000502:physiology*; D010636:Phenols / Q000097:blood / Q000494:pharmacology*; D059808:Polyphenols; D011507:Proteinuria / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D012965:Sodium Chloride
chemical_list: D000098:Acetophenones; D019332:Endothelin-1; D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; D017382:Reactive Oxygen Species; D003900:Desoxycorticosterone; D012965:Sodium Chloride; C056165:acetovanillone; D019255:NADPH Oxidases