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

• DOI: 10.1161/01.cir.103.2.258
• Publication Date: 2012-06-12T00:09:32Z
• Authors: H. A. Walker; T. S. Dean; T. A. B. Sanders; G. Jackson; J. M. Ritter; P. J. Chowienczyk
• Keywords: 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

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.