title: Myocardial contractile dysfunction induced by ovariectomy requires AT1 receptor activation in female rats.
abstract: OBJECTIVE
  Estrogen deficiency induces myocardial contractile dysfunction and increases cardiovascular disease risk. However, the mechanism underlying this response is unclear. Our aim was to investigate whether AT(1)receptor blockade would prevent ovariectomy-induced myocardial contractile dysfunction.
  
  
  METHODS
  Female rats (8 weeks old, 280 g) that underwent bilateral ovariectomy were randomly assigned to receive daily treatment with losartan (OVX + LOS, 15 mg/kg, s.c., in 0.9 % NaCl), placebo (OVX), estrogen replacement (OVX + E2, 1 mg/ kg, once a week, i.m.) and SHAM for 58 days.
  
  
  RESULTS
  Losartan and estrogen treatment 1) prevented ovariectomy-induced weight gain and slight hypertrophy, 2) restored the positive inotropic responses to Ca(2+) and isoproterenol in the isolated papillary muscle in the OVX group, 3) prevented the reduction in SERCA2a levels and the increase in phospholamban (PLB) expression in the OVX group, 4) abolished the increase in superoxide anion that was increased in the OVX group, and 5) normalized the increase in p22(phox) expression after ovariectomy. Estrogen treatment but not losartan restored the increase in serum angiotensin converting enzyme activity in the OVX group.
  
  
  CONCLUSIONS
  This study demonstrated that myocardial contractile dysfunction induced by ovariectomy and expression of key Ca(2+)-handling proteins were prevented by losartan treatment and that AT(1) receptor activation is involved in this response.
authors: Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES, Brazil. rogeriofaustinoribeiro@hotmail.com
authors: Rogerio Faustino
authors: RF
authors: Ribeiro
authors: Brunella M M
authors: BM
authors: Pavan
authors: Felipe F
authors: FF
authors: Potratz
authors: Jonaina
authors: J
authors: Fiorim
authors: Maylla Ronacher
authors: MR
authors: Simoes
authors: Fernanda Moura Vargas
authors: FM
authors: Dias
authors: Filipe Lugon Moulin
authors: FL
authors: Lima
authors: Aurelia Araujo
authors: AA
authors: Fernandes
authors: Dalton Valentim
authors: DV
authors: Vassallo
authors: Ivanita
authors: I
authors: Stefanon
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D004967:Estrogens / Q000172:deficiency; D005260:Female; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008315:Malondialdehyde / Q000097:blood; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D019255:NADPH Oxidases / Q000378:metabolism; D009929:Organ Size; D010052:Ovariectomy; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000378:metabolism*
chemical_list: D000318:Adrenergic beta-Agonists; D004967:Estrogens; D044140:Receptor, Angiotensin, Type 1; D013481:Superoxides; D008315:Malondialdehyde; D019255:NADPH Oxidases; C515768:Cyba protein, rat; D007703:Peptidyl-Dipeptidase A; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D007545:Isoproterenol; D002118:Calcium