(Circulation. 2001;103:258.)
© 2001 American Heart Association, Inc.
Clinical Investigation and Reports |
The Phytoestrogen Genistein Produces Acute Nitric Oxide–Dependent Dilation of Human Forearm Vasculature With Similar Potency to 17ß-Estradiol
From the Department of Clinical Pharmacology (J.M.R., P.J.C.), Centre for Cardiovascular Biology and Medicine, and Department of Nutrition (T.S.D., T.A.B.S.), King’s College, London, UK; and Cardiothoracic Centre (H.A.W., G.J.), St Thomas’ Hospital, London, UK.
Correspondence to Dr P.J. Chowienczyk, Department of Clinical Pharmacology, St Thomas’ Hospital, Lambeth Palace Road, London SE1 7EH, UK. E-mail phil.chowienczyk{at}kcl.ac.uk
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 17ß-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 17ß-estradiol caused similar vasodilation to genistein. Responses to genistein and 17ß-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.
Conclusions—Genistein causes L-arginine/NO-dependent vasodilation in forearm vasculature of human subjects with similar potency to 17ß-estradiol and potentiates endothelium-dependent vasodilation to acetylcholine.
Key Words: genistein • vasodilation • hormones • endothelium • nitric oxide
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