Genistein supplementation and estrogen replacement therapy improve endothelial dysfunction induced by ovariectomy in rats.
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), 17 beta-estradiol (20 micrograms/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 microM) and sodium nitroprusside: (SN 15-30 nM) induced relaxation of aortic rings as well as NG-L-arginine (L-NMA: 10-100 microM) 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 microM: Sham OVX = 2.1 +/- 0.2 g/mg tissue; OVX = 1.7 +/- 0.4 g/mg tissue) and reduced cNOS activity. Treatment with 17 beta-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 17 beta-estradiol show overlapping effects on experimental endothelial dysfunction.
Squadrito
F
F
Institute of Pharmacology, School of Medicine, University of Messina, Italy. squadrito@csnet.it
Altavilla
D
D
Squadrito
G
G
Saitta
A
A
Cucinotta
D
D
Minutoli
L
L
Deodato
B
B
Ferlito
M
M
Campo
G M
GM
Bova
A
A
Caputi
A P
AP
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta; D001794:Blood Pressure / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D004958:Estradiol / Q000097:blood / Q000627:therapeutic use; D015914:Estrogen Replacement Therapy; D005260:Female; D019833:Genistein / Q000097:blood / Q000627:therapeutic use*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008168:Lung / Q000201:enzymology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000032:analysis; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014599:Uterus / Q000033:anatomy & histology; D014665:Vasodilator Agents / Q000097:blood / Q000627:therapeutic use*
D014665:Vasodilator Agents; D009569:Nitric Oxide; D004958:Estradiol; D002784:Cholesterol; D019833:Genistein; D019001:Nitric Oxide Synthase; D000109:Acetylcholine