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

Abstract

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 17β-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 μmol/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 17β-estradiol caused similar vasodilation to genistein. Responses to genistein and 17β-estradiol were inhibited to the same degree by the NO synthase inhibitor NG-monomethyl-L-arginine. A threshold dose of genistein potentiated the endothelium-dependent vasodilator acetylcholine but not the endothelium-independent vasodilator nitroprusside. Conclusion - Genistein causes L-arginine/NO-dependent vasodilation in forearm vasculature of human subjects with similar potency to 17β-estradiol and potentiates endothelium-dependent vasodilation to acetylcholine.