The effect of long-term resveratrol treatment on relaxation to estrogen in aortae from male and female rats: role of nitric oxide and superoxide

Vascul Pharmacol. Aug-Sep 2008;49(2-3):97-105. doi: 10.1016/j.vph.2008.06.006. Epub 2008 Jul 4.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta, Thoracic / drug effects*
  • Aorta, Thoracic / metabolism
  • Aorta, Thoracic / physiology
  • Body Weight / drug effects
  • Drug Synergism
  • Endothelium, Vascular / physiology
  • Estradiol / analogs & derivatives
  • Estradiol / pharmacology
  • Estrogen Antagonists / pharmacology
  • Estrogens / pharmacology*
  • Female
  • Fulvestrant
  • In Vitro Techniques
  • Male
  • Nitric Oxide / metabolism
  • Rats
  • Rats, Wistar
  • Resveratrol
  • Sex Factors
  • Stilbenes / pharmacology*
  • Superoxides / metabolism
  • Time Factors
  • Vasodilation / drug effects*
  • Vasodilator Agents / pharmacology


  • Estrogen Antagonists
  • Estrogens
  • Stilbenes
  • Vasodilator Agents
  • Superoxides
  • Fulvestrant
  • Nitric Oxide
  • Estradiol
  • Resveratrol