© 2000 by European Society of Cardiology
Copyright © 2000, European Society of Cardiology
Genistein supplementation and estrogen replacement therapy improve endothelial dysfunction induced by ovariectomy in rats
aInstitute of Pharmacology, School of Medicine, University of Messina, Via Consolare Valeria, Policlinico Gazzi Torre Biologica 5° Piano, 98125 Messina, Italy
bDepartment of Internal Medicine, School of Medicine, University of Messina, Via Consolare Valeria, Policlinico Gazzi Paoliglione C, 98125 Messina, Italy
cChair of Chemistry School of Medicine, School of Medicine, University of Messina, Via Consolare Valeria, Policlinico Gazzi Torre Biologica 5° Piano, 98125 Messina, Italy
* Corresponding author. Tel.: +39-90-221-3648; fax: +39-90-221-3300 squadrito{at}csnet.it
Background: We investigated the effect of genistein, a phytoestrogen derived from a soy diet with a flavonoid chemical structure, on endothelial dysfunction induced by estrogen deficiency in rats. Methods: Female mature Sprague–Dawley rats were subjected to a bilateral ovariectomy (OVX rats). Sham-operated animals (Sham OVX rats) were used as controls. Three weeks after surgery animals were randomized to the following treatments: genistein (0.2 mg/kg/day, s.c. for 4 weeks), 17β-estradiol (20 µg/kg/day, s.c. for 4 weeks) or their respective vehicles. Mean arterial blood pressure (MAP), heart rate (HR), total plasma cholesterol, plasma estradiol, plasma genistein levels and uterine weights were studied. Furthermore, we investigated acetylcholine (ACh 10 nM–10 µM) and sodium nitroprusside: (SN 15–30 nM) induced relaxation of aortic rings as well as NG-L-arginine (L-NMA: 10–100 µM) induced vasoconstriction in phenylephrine precontracted aortic segments and calcium-dependent nitric oxide synthase (cNOS) activity in homogenates of lungs taken from both sham OVX and OVX rats. Results: Untreated OVX rats had, compared with sham OVX animals, unchanged body weight, MAP, HR and plasma cholesterol. In contrast ovariectomy impaired endothelial responses, blunted L-NMA induced contraction (L-NMA 100 µM: Sham OVX=2.1±0.2 g/mg tissue; OVX=1.7±0.4 g/mg tissue) and reduced cNOS activity. Treatment with 17β-estradiol increased the hormone plasma levels, reverted the endothelial dysfunction and increased cNOS activity in lung homogenates. Genistein supplementation enhanced the circulating levels of the phytoestrogen and affected NOS activity and endothelial dysfunction to the same extent. Conclusions: Our data suggest that genistein and 17β-estradiol show overlapping effects on experimental endothelial dysfunction.
KEYWORDS Endothelial function; Hormones; Nitric oxide
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