The phytoestrogen genistein produces acute nitric oxide-dependent dilationof human forearm vasculature with similar potency to 17 beta-estradiol

Background-Genistein, a phytoestrogen, may have estrogenic cardioprotective actions. We investigated whether genistein influences endothelium-dependen t vasodilation in forearm vasculature of healthy human subjects and compare d the effects of genistein with those of 17 beta -estradiol. Methods and Results-The brachial arterial was cannulated with a 27-gauge ne edle for drug infusion. Forearm blood flow responses were measured with str ain-gauge plethysmography, Genistein (10 to 300 nmol/min, each dose for 6 m inutes) 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 du ring infusion of the highest dose was 1.8+/-0.3 <mu>mol/L in 6 additional m en. Genistein produced a similar increase in blood flow in premenopausal wo men. Daidzein, another phytoestrogen, was ineffective, but equimolar concen trations of 17 beta -estradiol caused similar vasodilation to genistein, Re sponses to genistein and 17 beta -estradiol were inhibited to the same degr ee by the NO synthase inhibitor N-G-monomethyl-L-arginine. A threshold dose of genistein potentiated the endothelium-dependent vasodilator acetylcholi ne but not the endothelium-independent vasodilator nitroprusside. Conclusions-Genistein causes L-arginine/NO-dependent vasodilation in forear m vasculature of human subjects with similar potency to 17 beta -estradiol and potentiates endothelium-dependent vasodilation to acetylcholine.