Estrogen has protective effects against cardiovascular disease in pre-menopausal women which are decreased in diabetes and menopause. ER-a and ER-β mediate estrogen effects, but acute effects on vasculature are not completely understood. In this study, we investigated the contribution of estrogen receptors (ERs) a and β to vasorelaxation in thoracic aorta rings from control (C), diabetic (D), ovariectomized (O) and ovariectomized-diabetic (OD) rats. Diabetes was induced with streptozotocin (45mg/kg,iv.) and ovariectomy was performed with bilaterally operation. The experimental duration was 8 weeks. Direct relaxant effects of the selective ER agonists 4,4'4”-(4-propyl-[‘H']pyrazole-1,3,5-triyl)tris-phenol (PPT), 2,3-bis(4-hydroxyphenyl)-propionitril (DPN) and the nonselective ER agonist 17β-estradiol (E2) were determined after precontracted with phenylephrine. E2 and PPT produced dose-dependent relaxation (10-I3M-10-7M) with a similar profile. However, the maximal relaxation (Emax) to PPT was higher than that of E2 and was diminished in aorta from O and D groups, furthermore was abolished in aorta from OD group. Emax to DPN was weakened in all aortic groups in comparision with C group. These findings suggest that there is a predominant role of ER-a on estrogen-induced vasorelaxation which is altered along with hormonal status. Hence, the ER-a agonists may offer a new treatment option for the protection of cardiovascular disease.

Keywords: Estrogen receptor a, Estrogen receptor ß, Ovariectomy, Diabetes, Rat, Aorta