The time-dependent effect of ProvinolsTM on brain NO synthase activity in L-NAME-induced hypertension

Red wine polyphenols have been reported to possess beneficial properties for preventing cardiovascular diseases but their neuroprotective effects during chronic L-NAME treatment have not been elucidated. The aim of this study was to analyze a time course of Provinols (TM) effects on brain NO synthase activity and oxidative damage in L-NAME-induced hypertension. Male Wistar rats, 12 weeks old, were divided into six groups: control groups, groups treated with N-G-nitro-L-arginine methyl ester (L-NAME, 40 mg/kg/day) for 4 or 7 weeks and groups receiving Provinols (TM) (40 mg/kg/day) plus L-NAME for 4 or 7 weeks. At the end of the treatment, marker of membrane oxidative damage conjugated dienes (CD) in the brain and NO synthase activity in the cerebral cortex, cerebellum and brainstem were determined. L-NAME treatment for 4 or 7 weeks led to the increase in blood pressure, elevation of CD concentration and decrease of NO synthase activity in the brain parts investigated. Provinols (TM) partially prevented blood pressure rise and elevation of CD concentration. Comparing to the L-NAME treated group, Provinols (TM) increased NO synthase activity after 4 weeks of treatment. However, the prolonged Provinols (TM) treatment for 7 weeks had no effect on NO synthase activity decreased by L-NAME treatment. In conclusion, Provinols (TM) partially prevents L-NAME induced hypertension via the different mechanisms depending on the duration of treatment. Prevention of oxidative damage in the brain with modulating effect on NO synthase activity is suggested.