The Phytoestrogen Genistein Produces Acute Nitric Oxide–Dependent Dilation of Human Forearm Vasculature With Similar Potency to 17β-Estradiol

Adult Male Nitroprusside Cardiotonic Agents Dose-Response Relationship, Drug Estradiol Phytoestrogens Middle Aged Nitric Oxide Genistein Isoflavones Acetylcholine Forearm 03 medical and health sciences 0302 clinical medicine Blood Vessels Humans Female Nitric Oxide Donors Estrogens, Non-Steroidal Plant Preparations Enzyme Inhibitors
DOI: 10.1161/01.cir.103.2.258 Publication Date: 2012-06-12T00:09:32Z
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 inhibitorNG-monomethyl-l-arginine. A threshold dose of genistein potentiated the endothelium-dependent vasodilator acetylcholine but not the endothelium-independent vasodilator nitroprusside.Conclusions—Genistein causesl-arginine/NO-dependent vasodilation in forearm vasculature of human subjects with similar potency to 17β-estradiol and potentiates endothelium-dependent vasodilation to acetylcholine.
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