Background. We investigated the effects of sulforaphane (SF), the main active isothiocyanate in cruciferous vegetables, on arachidonic acid (AA) metabolism in the kidney and its effect on arterial blood pressure, using spontaneously hypertensive rats (SHR) as models. Methods. Rats were treated for 8 weeks with either drinking water alone (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, and kidneys were harvested to prepare microsomes and 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 SF on kidney expression of CYP4A was investigated by immunoblotting. Results. 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 treatment with SF resisted the progressive rise in MAP in the developing SHR in a dose-dependent manner. Conclusion. 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. 1. Background Hypertension affects about one in three adults in the United States and is a major predictor for coronary heart disease and stroke. Although there is still uncertainty about the pathophysiology of hypertension, many interrelated factors have been found to contribute to persistent blood pressure elevation [1]. Among the proposed factors are vascular resistance, oxidative stress, endothelial dysfunction, and salt sensitivity. Evidence from numerous studies indicate that arachidonic acid (AA) metabolites play an important role in the regulation of renal vascular tone, tubuloglomerular feedback, and sodium transport [2–4]. Therefore, we postulate that AA metabolites may participate in the pathogenesis of hypertension [2–4]. AA is metabolized by renal cytochrome P450 (CYP) enzymes to produce either hydroxyeicosatetraenoic acids (HETEs; particularly, 19- and 20-HETE) or epoxyeicosatetraenoic acids (EETs, Figure 1) [2, 3, 5, 6]. Figure 1: Metabolism of arachidonic acid by CYP enzymes and epoxide hydrolase. The sign “x” indicates the proposed
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