Background and Objective:The objective of this study was to investigate the effects of resveratrol (RES) on Arachidonic acid (AA) metabolism in the kidney and its effect on arterial blood pressure, using spontaneously hypertensive rats (SHR) as a model system. Methods: Rats were exposed to either drinking water alone (control) or RES (20 or 40 mg kgG 1 ) added to drinking water for 7 weeks. Mean Arterial Pressure (MAP) was measured at 7-day intervals throughout the study. At the end of treatment, rats were euthanized, followed by preparation of kidney microsomes to measure enzymes involved in regulation of vasoactive metabolites: CYP4A, the key enzyme in the formation of 20-hydroxyeicosatetraenoic acid and the soluble epoxide hydrolase, which is responsible for the degradation of the vasodilator metabolites such as epoxyeicosatetraenoic acids. Effect of RES on kidney expression of CYP4A was also investigated by immunoblotting. Results: Treatment with RES resisted the progressive rise in MAP in the developing SHR in a dose-dependent manner. Consistent with these data, RES treatment led to significant reductions in both, the expression and activity of renal CYP4A isozymes, as well as the activity of soluble epoxide hydrolase (sEH). Conclusion: The presented studies show that RES modulates the metabolism of AA by both P450 enzymes and sEH in SHR rats, which may represent a novel mechanism by which RES protects SHR rats against the progressive rise in blood pressure.
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