TY - JOUR
T1 - Genistein supplementation and estrogen replacement therapy improve endothelial dysfunction induced by ovariectomy in rats
AU - Squadrito, Francesco
AU - Altavilla, Domenica
AU - Squadrito, Giovanni
AU - Saitta, Antonino
AU - Cucinotta, Domenico
AU - Minutoli, Letteria
AU - Deodato, Barbara
AU - Ferlito, Marcella
AU - Campo, Giuseppe M.
AU - Bova, Antonio
AU - Caputi, Achile P.
PY - 2000/1/14
Y1 - 2000/1/14
N2 - 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 N(G)-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. Copyright (C) 2000 Elsevier Science B.V.
AB - 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 N(G)-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. Copyright (C) 2000 Elsevier Science B.V.
KW - Endothelial function
KW - Hormones
KW - Nitric oxide
UR - http://www.scopus.com/inward/record.url?scp=0033979106&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033979106&partnerID=8YFLogxK
U2 - 10.1016/S0008-6363(99)00359-4
DO - 10.1016/S0008-6363(99)00359-4
M3 - Article
C2 - 10728366
AN - SCOPUS:0033979106
SN - 0008-6363
VL - 45
SP - 454
EP - 462
JO - Cardiovascular research
JF - Cardiovascular research
IS - 2
ER -