17β-Estradiol modulates vasoconstriction induced by endothelin-1 following trauma-hemorrhage

Although endothelin- 1 ( ET- 1) induces vasoconstriction, it remains unknown whether 17 beta- estradiol ( E-2) treatment following trauma- hemorrhage alters these ET- 1-induced vasoconstrictive effects. In addition, the role of the specific estrogen receptor ( ER) subtypes ( ER-alpha and ER-beta) and the endothelium-localized downstream mechanisms of actions of E-2 remain unclear. We hypothesized that E-2 attenuates increased ET-1-induced vasoconstriction following trauma- hemorrhage via an ER-beta-mediated pathway. To study this, aortic rings were isolated from male Sprague-Dawley rats following trauma- hemorrhage with or without E-2 treatment, and alterations in tension were determined in vitro. Dose-response curves to ET- 1 were determined, and the vasoactive properties of E-2, propylpyrazole triol ( PPT, ER-alpha agonist), and diarylpropionitrile ( DPN, ER-beta agonist) were determined. The results showed that trauma- hemorrhage significantly increased ET- 1- induced vasoconstriction; however, administration of E-2 normalized ET- 1-induced vasoconstriction in trauma- hemorrhage vessels to the sham-operated control level. The ER-alpha agonist DPN counteracted ET- 1-induced vasoconstriction, whereas the ER-alpha agonist PPT was ineffective. Moreover, the vasorelaxing effects of E-2 were not observed in endothelium-denuded aortic rings or by pretreatment of the rings with a nitric oxide ( NO) synthase inhibitor. Cyclooxygenase inhibition with indomethacin had no effect on the action of E-2. Thus, E-2 administration attenuates ET- 1- induced vasoconstriction following trauma- hemorrhage via an ER-beta- mediated pathway that is dependent on endothelium- derived NO synthesis.