Genistein supplementation and estrogen replacement therapy improve endothelial dysfunction induced by ovariectomy in rats

Background: We investigated the effect of genistein, a phytoestrogen derive d from a soy diet with a flavonoid chemical structure, on endothelial dysfu nction induced by estrogen deficiency in rats. Methods: Female mature Sprag ue-Dawley rats were subjected to a bilateral ovariectomy (OVX rats). Sham-o perated animals (Sham OVX rats) were used as controls. Three weeks after su rgery animals were randomized to the following treatments: genistein (0.2 m g/kg/day, s.c. for 4 weeks), 17 beta-estradiol (20 mu g/kg/day, s.c. for 3 weeks) or their respective vehicles. Mean arterial blood pressure (MAP), he art rate (HR), total plasma cholesterol, plasma estradiol, plasma genistein levels and uterine weights were studied. Furthermore, we investigated acet ylcholine (ACh 10 nM-10 mu M) and sodium nitroprusside: (SN 15-30 nM) induc ed relaxation of aortic rings as well as NG-L-arginine (L-NMA: 10-100 mu M) induced vasoconstriction in phenylephrine precontracted aortic segments an d calcium-dependent nitric oxide synthase (cNOS) activity in homogenates of lungs taken from both sham OVX and OVX rats. Results: Untreated OVX rats h ad, compared with sham OVX animals, unchanged body weight, MAP, HR and plas ma cholesterol. In contrast ovariectomy impaired endothelial responses, blu nted L-NMA induced contraction (L-NMA 100 mu M: Sham OVX=2.1+/-0.2 g/mg tis sue; OVX=1.7+/-0.4 g/mg tissue) and reduced cNOS activity. Treatment with 1 7 beta-estradiol increased the hormone plasma levels, reverted the endothel ial dysfunction and increased cNOS activity in lung homogenates. Genistein supplementation enhanced the circulating levels of the phytoestrogen and af fected NOS activity and endothelial dysfunction to the same extent. Conclus ions: Our data suggest that genistein and 17 beta-estradiol show overlappin g effects on experimental endothelial dysfunction. (C) 2000 Elsevier Scienc e B.V. All rights reserved.