title: 17beta-Estradiol modulates vasoconstriction induced by endothelin-1 following trauma-hemorrhage.
abstract: Although endothelin-1 (ET-1) induces vasoconstriction, it remains unknown whether 17beta-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-beta 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.
authors.affiliation: Center for Surgical Research and Dept. of Surgery, Univ. of Alabama at Birmingham, 1670 University Blvd., Volker Hall, Rm. G094, Birmingham, AL 35294-0019, USA.
authors.forename: Zheng F
authors.initials: ZF
authors.lastname: Ba
authors.forename: Ailing
authors.initials: A
authors.lastname: Lu
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Shimizu
authors.forename: László
authors.initials: L
authors.lastname: Szalay
authors.forename: Martin G
authors.initials: MG
authors.lastname: Schwacha
authors.forename: Loring W
authors.initials: LW
authors.lastname: Rue
authors.forename: Kirby I
authors.initials: KI
authors.lastname: Bland
authors.forename: Irshad H
authors.initials: IH
authors.lastname: Chaudry
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D019332:Endothelin-1 / Q000008:administration & dosage*; D004958:Estradiol / Q000008:administration & dosage*; D006470:Hemorrhage / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects*; D014950:Wounds, Penetrating / Q000503:physiopathology
chemical_list: D004338:Drug Combinations; D019332:Endothelin-1; D004958:Estradiol