The phytoestrogen genistein produces acute nitric oxide-dependent dilation of human forearm vasculature with similar potency to 17β-estradiol

Background-Genistein, a phytoestrogen, may have estrogenic cardioprotective actions. We investigated whether genistein influences endothelium-dependent vasodilation in forearm vasculature of healthy human subjects and compared the effects of genistein with those of 17 beta -estradiol. Methods and Results-The brachial arterial was cannulated with a 27-gauge needle for drug infusion. Forearm blood flow responses were measured with strain-gauge plethysmography, Genistein (10 to 300 nmol/min, each dose for 6 minutes) produced a dose-dependent increase in forearm blood flow from 3.4+/-0.3 to 9.6+/-1.3 mL . min(-1). 100 mL forearm(-1) (mean+/-SEM) in men (n=9, P<0.0001 by ANOVA). The mean forearm venous concentration of genistein during infusion of the highest dose was 1.8+/-0.3 mol/L in 6 additional men. Genistein produced a similar increase in blood flow in premenopausal women. Daidzein, another phytoestrogen, was ineffective, but equimolar concentrations of 17 beta -estradiol caused similar vasodilation to genistein, Responses to genistein and 17 beta -estradiol were inhibited to the same degree by the NO synthase inhibitor N-G-monomethyl-L-arginine. A threshold dose of genistein potentiated the endothelium-dependent vasodilator acetylcholine but not the endothelium-independent vasodilator nitroprusside. Conclusions-Genistein causes L-arginine/NO-dependent vasodilation in forearm vasculature of human subjects with similar potency to 17 beta -estradiol and potentiates endothelium-dependent vasodilation to acetylcholine.