DOI: 10.5176/2345-783X_PHARMA13.14
Authors: Fawzy Elbarbry, Agnieszka Balkwiec and Anke Vermehren Schmaedick
Abstract:
We investigated the effects of sulforaphane (SF), the main active isothiocyanate in cruciferous vegetables, on modulation of arachidonic acid (AA) metabolism in the kidney and its effect on arterial blood pressure, using spontaneously hypertensive rats (SHR) as a model. Rats were treated for 6 weeks with either vehicle (control) or SF (20 or 40 mg/kg) added to drinking water. 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 (sEH), which is responsible for the degradation of the vasodilator metabolites such as epoxyeicosatetraenoic acids. We found that treatment with SF leads to significant reductions in both, the expression and activity of renal CYP4A isozymes, as well as the activity of soluble epoxide hydrolase (sEH). Consistent with these data, we have found that SF prevents development of hypertension by significantly reducing the rise in MAP of developing SHRs. This is the first demonstration that SF modulates the metabolism of AA by both P450 enzymes and sEH in SHR rats. This may represent a novel mechanism by which SF protects SHR rats against the progressive rise in blood pressure
Keywords: SHR, CYP4A, she, Hypertension, 20-HETE, EETs
Updating...