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(Hypertension. 2008;51:1088.)
© 2008 American Heart Association, Inc.

Go Red Original Articles

Wine Polyphenols Improve Endothelial Function in Large Vessels of Female Spontaneously Hypertensive Rats

Rocío López-Sepúlveda; Rosario Jiménez; Miguel Romero; Maria José Zarzuelo; Manuel Sánchez; Manuel Gómez-Guzmán; Félix Vargas; Francisco O’Valle; Antonio Zarzuelo; Francisco Pérez-Vizcaíno; Juan Duarte

From the Department of Pharmacology (R.L.-S., R.J., M.R, M.J.Z., M.S., M.G.-G., A.Z., J.D.), School of Pharmacy, University of Granada; the Department of Physiology (F.V.), School of Medicine, University of Granada; the Department of Pathological Anatomy (F.O.), School of Medicine, University of Granada; and the Department of Pharmacology (F.P.-V.), School of Medicine, University Complutense of Madrid, CIBERES, Spain.

Correspondence to Juan Duarte, Department of Pharmacology, School of Pharmacy, University of Granada, 18071 Granada, Spain. E-mail jmduarte{at}ugr.es

Red wine polyphenols (RWPs) have been reported to prevent hypertension and endothelial dysfunction. Several individual RWPs exert estrogenic effects. We analyzed the possible in vivo protective effects on blood pressure and endothelial function of RWPs in female spontaneously hypertensive rats (SHR) and its relationship with ovarian function. RWPs (40 mg/kg by gavage) were orally administered for 5 weeks. Ovariectomized rats showed both increased isoprostaglandin F₂ excretion and aortic superoxide production and reduced relaxant response to acetylcholine and contraction to the endothelial nitric oxide synthase (eNOS) inhibitor L-NAME measured in the aorta but similar blood pressure, as compared with sham-operated rats. Moreover, in ovariectomized rats aortic eNOS expression was unchanged, whereas caveolin-1, angiotensin II receptor (AT)-1, and the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits p22^phox and p47^phox expression was increased compared with sham-operated rats. In both ovariectomized and sham-operated SHR, RWPs reduced systolic blood pressure, urinary isoprostaglandin F₂ excretion, and aortic O₂^– production, improving the endothelium-dependent relaxant response to acetylcholine in SHR. These changes were associated with unchanged aortic eNOS expression, whereas caveolin-1 was increased and the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits p22^phox and p47^phox expression was reduced. RWPs had no effect on the AT-1 overexpression found in ovariectomized animals. All these results suggest that a chronic treatment with RWPs reduces hypertension and vascular dysfunction through reduction in vascular oxidative stress in female SHR in a manner independent of the ovarian function.

Key Words: red wine polyphenols • spontaneously hypertensive rat • endothelial dysfunction • NADPH oxidase • ovariectomy