Polyphenols restore endothelial function in DOCA-salt hypertension: role of endothelin-1 and NADPH oxidase.
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.
Jiménez
Rosario
R
Department of Pharmacology, School of Pharmacy, Spain.
López-Sepúlveda
Rocío
R
Kadmiri
María
M
Romero
Miguel
M
Vera
Rocío
R
Sánchez
Manuel
M
Vargas
Félix
F
O'Valle
Francisco
F
Zarzuelo
Antonio
A
Dueñas
Montserrat
M
Santos-Buelga
Celestino
C
Duarte
Juan
J
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
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