Red wine polyphenols prevent cardiovascular alterations in L-NAME-induced hypertension

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Abstract
Objective Red wine polyphenols have been reported to possess beneficial properties for preventing cardiovascular diseases but their effects on hemodynamic and functional cardiovascular changes during inhibition of nitric oxide (NO) synthesis have not been elucidated. Design The effects of the red wine polyphenols, Provinols, on arterial hypertension as well as left ventricular (LV) hypertrophy, myocardial fibrosis and vascular remodeling were investigated in rats during chronic inhibition of nitric oxide synthase (NOS) activity. Rats were divided into four groups: a control group, a group treated with NG-nitro-l-arginine methyl ester (L-NAME) (40 mg/kg per day), a group receiving Provinols (40 mg/kg per day) alone or Provinols plus L-NAME. Results Provinols markedly reduced the increase in both blood pressure and protein synthesis in the heart and aorta caused by chronic inhibition of NO synthesis. Provinols reduced myocardial fibrosis even though it did not affect LV hypertrophy. In addition, Provinols prevented aortic thickening and corrected the augmented reactivity of the aorta to norepinephrine and the attenuated endothelium-dependent relaxation to acetylcholine in NO-deficient rats. These alterations were associated with an increase of NOS activity, a moderate enhancement of endothelial NOS expression and a reduction of oxidative stress in the LV and aorta. Conclusion Our results provide evidence that Provinols partially prevents L-NAME-induced hypertension, cardiovascular remodeling and vascular dysfunction via the increase of NO-synthase activity and prevention of oxidative stress. Thus, the beneficial effects of plant polyphenols in prevention of hypertension may result from their complex influence on the NO balance in the cardiovascular system.