Effect and mechanism of signal transduction pathway in urocortininduced cardiomyocytes hypertrophy in neonatal rat / 中国药理学与毒理学杂志

ABSTRACT

AIM To investigate the effects and mechanism of cardiomyocyte hypertrophy induced by urocortin. METHODS The cardiomyocytes were divided into 8 groups normal control, urocortin, staurosporine(Sta), verapamil(Ver), H89, urocortin+Sta, urocortin+Ver, and urocortin+H89 groups. The cardiomyocytes diameter was measured by computer photograph analysis system. The protein synthetic rate was obtained through measuring the incorporation of [~3H]-leucine into myocyte protein by liquid scintillation method. The total protein content was assayed by Lowry method. The expression of atrial natriuretic peptide (ANP) was determined by Western blot. [Ca~(2+)]_i transient was measured by Till image system by cell loading Fura-2/AM. RESULTSUrocortin group enhanced cardiomyocyte volume, protein synthesis, total protein content and expression of ANP by 30.9%, 36.3%, 35.5% and 34.7%;urocortin+Sta group decreased cardiomyocyte diameter, protein synthesis, total protein content and expression of ANP by 16.5%, 22.1%, 18.1% and 21.3%;urocortin+H89 group decreased the cardiomyocyte diameter, the protein synthesis,total protein content and expression of ANP by 16.6%, 21.5%, 19.5% and 20.6%;urocortin+Ver decreased the cardiomyocyte diameter, the protein synthesis, total protein content and the expression of ANP by 17.1%, 20.9%, 17.9% and 19.9%;Sta, H89 and Ver could decrease the [Ca~(2+)]_i transient induced by urocortin. CONCLUSION The hypertrophic effect of urocortin in rat neonatal cardiomyocytes is mediated via activation of protein kinase C and protein kinase A pathway and L-type calcium channels.