Effect of Phosphodiesterase Inhibitor on PI3K-Akt-eNOS Pathway in Cardiomyocytes of Neonatal Rat

Objective:To investigate the effect of Cilostazol on phosphatidylinositol-3 kinase(PI3K) /Serine/threonine protein kinase(AKT)/endothelial nitric oxide synthase(eNOS) pathway in cardiomyocyte of neonatal SD rat.Methods:To observe the time-effect and dose-effect relationship of Cilostazol on nitric oxide(NO) concentration in cardiomyocytes of cultured neonatal rat.Expressions of Akt,phospho-Akt and eNOS,phospho-eNOS were detected by Western blot.Results:Cilostazol increased the endothelial NO production in a dose-and time-dependent manner in cardiomyocytes of cultured neonatal SD rat and also increased the expression of phosphorylation of Akt and eNOS in a concentration-dependent manner,with no alteration in the expression of total Akt and total eNOS in cultured cardiomyocytes.L-NAME,eNOS synthase inhibitor,and Wortmannin,PI3K inhibitor,blocked the Cilostazol-induced NO formation.Wortmannin also prevented the phosphorylation of eNOS and Akt induced by Cilostazol.Conclusion:Cilostazol increased the endothelial NO production by promoting PI3K-Akt-eNOS signal pathway.