title: Salutary effects of estrogen receptor-beta agonist on lung injury after trauma-hemorrhage.
abstract: Although 17beta-estradiol (E2) administration after trauma-hemorrhage attenuates lung injury in male rodents, it is not known whether the salutary effects are mediated via estrogen receptor (ER)-alpha or ER-beta. We hypothesized that the salutary effects of E2 lung are mediated via ER-beta. Male Sprague-Dawley rats underwent trauma-hemorrhage (mean blood pressure 40 mmHg for 90 min, then resuscitation). E2 (50 microg/kg), ER-alpha agonist propyl pyrazole triol (PPT; 5 microg/kg), ER-beta agonist diarylpropiolnitrile (DPN; 5 microg/kg), or vehicle (10% DMSO) was injected subcutaneously during resuscitation. At 24 h after trauma-hemorrhage or sham operation, bronchoalveolar fluid (BALF) was collected for protein concentration, LDH activity, and nitrate/nitrite and IL-6 levels. Moreover, lung tissue was used for inducible nitric oxide synthase (iNOS) mRNA/protein expression, nitrate/nitrite and IL-6 levels, and wet/dry weight ratio (n = 6 rats/group). One-way ANOVA and Tukey's test were used for statistical analysis. The results indicated that E2 downregulated lung iNOS expression after trauma-hemorrhage. Protein concentration, LDH activity, and nitrate/nitrite and IL-6 levels in BALF and nitrate/nitrite and IL-6 levels in the lung increased significantly after trauma-hemorrhage; however, administration of DPN but not PPT significantly improved all parameters. Moreover, DPN treatment attenuated trauma-hemorrhage-mediated increase in iNOS mRNA/protein expression in the lung. In contrast, no significant change in the above parameters was observed with PPT. Thus the salutary effects of E2 on attenuation of lung injury are mediated via ER-beta, and ER-beta-induced downregulation of iNOS likely plays a significant role in the DPN-mediated lung protection after trauma-hemorrhage.
authors.affiliation: Center for Surgical Research, University of Alabama at Birmingham, 1670 University Boulevard, Volker Hall, Rm. G094, Birmingham, AL 35294-0019, USA.
authors.forename: Huang-Ping
authors.initials: HP
authors.lastname: Yu
authors.forename: Ya-Ching
authors.initials: YC
authors.lastname: Hsieh
authors.forename: Takao
authors.initials: T
authors.lastname: Suzuki
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Shimizu
authors.forename: Mashkoor A
authors.initials: MA
authors.lastname: Choudhry
authors.forename: Martin G
authors.initials: MG
authors.lastname: Schwacha
authors.forename: Irshad H
authors.initials: IH
authors.lastname: Chaudry
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004195:Disease Models, Animal; D004958:Estradiol / Q000627:therapeutic use*; D047629:Estrogen Receptor beta / Q000819:agonists*; D006470:Hemorrhage / Q000209:etiology* / Q000517:prevention & control*; D006801:Humans; D015850:Interleukin-6 / Q000032:analysis; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008297:Male; D009566:Nitrates / Q000032:analysis; D009570:Nitriles / Q000627:therapeutic use*; D009573:Nitrites / Q000032:analysis; D010636:Phenols; D011422:Propionates / Q000627:therapeutic use*; D011720:Pyrazoles / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000150:complications*
chemical_list: C486182:2,3-bis(4-hydroxyphenyl)-propionitrile; D047629:Estrogen Receptor beta; D015850:Interleukin-6; D009566:Nitrates; D009570:Nitriles; D009573:Nitrites; D010636:Phenols; D011422:Propionates; D011720:Pyrazoles; C486184:4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol; D004958:Estradiol; D007770:L-Lactate Dehydrogenase