The effect of long-term resveratrol treatment on relaxation to estrogen in aortae from male and female rats: role of nitric oxide and superoxide.
Resveratrol, which is found in several foods, has vasorelaxing and estrogen-like activities. The aim of the present study was to determine whether the relaxation to estrogen is differently modified between male and female genders after long-term resveratrol treatment. To test this, we compared endothelium-dependent and -independent relaxations to estrogen in the aortae of control and resveratrol-treated male and female rats. Nitric oxide and superoxide levels were also evaluated to explain the mechanism of action of resveratrol. Concentration-response curves to estrogen (10(-10)-10(-4) M) were obtained in aortic rings with and without endothelium from control or long-term resveratrol-treated (50 mg/l in drinking water for 21 days) male and female rats. Estrogen produced mainly endothelium-dependent relaxation in aortic rings of rats, with a higher potency in females than males. Resveratrol treatment increased both endothelium-dependent and -independent relaxations to estrogen especially in aortae from males. The relaxations to estrogen in the aortae of resveratrol-treated rats were inhibited, almost to the same extent as those of control, by pretreatment with ICI 182,780 (10(-6) M), an estrogen receptor antagonist. In both genders, resveratrol treatment increased basal nitric oxide and nitrite/nitrate productions and decreased both basal and NAD(P)H-induced superoxide productions in the aortae. In addition, plasma estrogen levels were found decreased in long-term resveratrol-treated animals of both genders. The improvement in the relaxations to estrogen observed in resveratrol-treated animals could be related to elevated nitric oxide and/or decreased superoxide productions and possibly mediated by classical estrogen receptors. The modulating effect of resveratrol on estrogen responsiveness may differ between male and female.
Soylemez
S
S
Department of Pharmacology, Faculty of Pharmacy, Gazi University, Etiler, Ankara, Turkey.
Gurdal
H
H
Sepici
A
A
Akar
F
F
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D001835:Body Weight / Q000187:drug effects; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000502:physiology; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D000077267:Fulvestrant; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000077185:Resveratrol; D012737:Sex Factors; D013267:Stilbenes / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D004965:Estrogen Antagonists; D004967:Estrogens; D013267:Stilbenes; D014665:Vasodilator Agents; D013481:Superoxides; D000077267:Fulvestrant; D009569:Nitric Oxide; D004958:Estradiol; D000077185:Resveratrol