title: Mechanism of salutary effects of estrogen on cardiac function following trauma-hemorrhage: Akt-dependent HO-1 up-regulation.
abstract: OBJECTIVE
  Because administration of 17beta-estradiol following trauma-hemorrhage improves cardiovascular responses, we investigated whether the salutary effects of 17beta-estradiol on cardiac function are mediated via Akt-dependent heme oxygenase-1 up-regulation under those conditions.
  
  
  METHODS
  Experimental animal study.
  
  
  METHODS
  University laboratory.
  
  
  METHODS
  Male Sprague-Dawley rats.
  
  
  METHODS
  Rats underwent trauma-hemorrhage (mean blood pressure approximately 40 mm Hg for 90 mins) followed by fluid resuscitation. Before resuscitation, rats received either vehicle, 17beta-estradiol (1 mg/kg), or 17beta-estradiol plus the phosphoinositide 3-kinase inhibitor wortmannin (1 mg/kg). At 2 hrs after trauma-hemorrhage or sham operation, the rats were killed.
  
  
  RESULTS
  Cardiac function, heart tissue myeloperoxidase activity, cardiac and circulatory cytokine levels, cardiac intercellular adhesion molecule-1, and chemokine levels were measured. Cardiac Akt and heme oxygenase-1 were also determined. We found that 17beta-estradiol prevented the trauma-hemorrhage-induced impairment in cardiac function and increase in cardiac myeloperoxidase activity. Cardiac and systemic interleukin-6 and tumor necrosis factor-alpha levels as well as cardiac intercellular adhesion molecule-1, cytokine-induced neutrophil chemoattractant-1, and macrophage inflammatory protein-2 contents were increased following trauma-hemorrhage, which were normalized by 17beta-estradiol. Administration of 17beta-estradiol following trauma-hemorrhage restored cardiac Akt phosphorylation and further increased heme oxygenase-1 expression. Coadministration of wortmannin following trauma-hemorrhage abolished the previous effects by 17beta-estradiol.
  
  
  CONCLUSIONS
  These results suggest that the 17beta-estradiol-meditated improvement in cardiac function following trauma-hemorrhage occurs via Akt-dependent heme oxygenase-1 up-regulation.
authors.affiliation: Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, USA.
authors.forename: Jun-Te
authors.initials: JT
authors.lastname: Hsu
authors.forename: Wen-Hong
authors.initials: WH
authors.lastname: Kan
authors.forename: Chi-Hsun
authors.initials: CH
authors.lastname: Hsieh
authors.forename: Mashkoor A
authors.initials: MA
authors.lastname: Choudhry
authors.forename: Kirby I
authors.initials: KI
authors.lastname: Bland
authors.forename: Irshad H
authors.initials: IH
authors.lastname: Chaudry
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000188:drug therapy*; D015854:Up-Regulation; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D018925:Chemokines; D016207:Cytokines; D004967:Estrogens; D047428:Protein Kinase Inhibitors; D004958:Estradiol; D009195:Peroxidase; D051547:Heme Oxygenase-1; D051057:Proto-Oncogene Proteins c-akt; D000077191:Wortmannin