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Provedor de dados:  BJMBR
País:  Brazil
Título:  CPU0213, a novel endothelin type A and type B receptor antagonist, protects against myocardial ischemia/reperfusion injury in rats
Autores:  Wang,Z.Y.
Zhang,W.
Li,X.Z.
Han,Y.
Chen,Y.P.
Liu,Z.
Xie,L.P.
Ji,Y.
Lu,X.
Data:  2011-11-01
Ano:  2011
Palavras-chave:  Endothelin receptor antagonist
Myocardial ischemia/reperfusion injury
Akt
ENOS
Resumo:  The efficacy of endothelin receptor antagonists in protecting against myocardial ischemia/reperfusion (I/R) injury is controversial, and the mechanisms remain unclear. The aim of this study was to investigate the effects of CPU0123, a novel endothelin type A and type B receptor antagonist, on myocardial I/R injury and to explore the mechanisms involved. Male Sprague-Dawley rats weighing 200-250 g were randomized to three groups (6-7 per group): group 1, Sham; group 2, I/R + vehicle. Rats were subjected to in vivo myocardial I/R injury by ligation of the left anterior descending coronary artery and 0.5% sodium carboxymethyl cellulose (1 mL/kg) was injected intraperitoneally immediately prior to coronary occlusion. Group 3, I/R + CPU0213. Rats were subjected to identical surgical procedures and CPU0213 (30 mg/kg) was injected intraperitoneally immediately prior to coronary occlusion. Infarct size, cardiac function and biochemical changes were measured. CPU0213 pretreatment reduced infarct size as a percentage of the ischemic area by 44.5% (I/R + vehicle: 61.3 ± 3.2 vs I/R + CPU0213: 34.0 ± 5.5%, P < 0.05) and improved ejection fraction by 17.2% (I/R + vehicle: 58.4 ± 2.8 vs I/R + CPU0213: 68.5 ± 2.2%, P < 0.05) compared to vehicle-treated animals. This protection was associated with inhibition of myocardial inflammation and oxidative stress. Moreover, reduction in Akt (protein kinase B) and endothelial nitric oxide synthase (eNOS) phosphorylation induced by myocardial I/R injury was limited by CPU0213 (P < 0.05). These data suggest that CPU0123, a non-selective antagonist, has protective effects against myocardial I/R injury in rats, which may be related to the Akt/eNOS pathway.
Tipo:  Info:eu-repo/semantics/article
Idioma:  Inglês
Identificador:  http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2011001100011
Editor:  Associação Brasileira de Divulgação Científica
Relação:  10.1590/S0100-879X2011007500119
Formato:  text/html
Fonte:  Brazilian Journal of Medical and Biological Research v.44 n.11 2011
Direitos:  info:eu-repo/semantics/openAccess
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