Regulation of endothelial nitric oxide synthase and asymmetric dimethylarginine by matrine attenuates isoproterenol-induced acute myocardial injury in rats

Abstract

Objectives This study was designed to investigate the cardioprotective effects of matrine on regulation of endothelial nitric oxide synthase (eNOS) and asymmetric dimethylarginine (ADMA) in isoproterenol-induced acute myocardial ischaemic rats. Methods Male Sprague-Dawley rats were pretreated with matrine (200, 100 and 50 mg/kg) orally for 10 days. Acute myocardial injury was induced in rats by subcutaneous injection of isoproterenol. Serum and haemodynamic parameters, histopathological variables and expression of protein levels were analysed. Key findings Oral administration of matrine (200, 100 and 50 mg/kg) significantly attenuated isoproterenol-induced cardiac necrosis and left ventricular dysfunction. Matrine treatment restored impaired ventricular Akt and eNOS protein expression with concomitant increased phosphorylation of Akt (Ser473) and eNOS (Ser1177), and also restored glycogen synthase kinase 3β activity, as indicated by increased phosphorylation at Ser 9. Moreover, treatment with matrine had no effect on the isoproterenol-induced elevated protein arginine methyltransferase 1 protein expression, but could significantly normalize the reduced dimethylarginine dimethylaminohydrolase 2 expression and attenuate the increased serum level of ADMA. The expression of catechol-o-methyltransferase and monoamine oxidase did not differ among all groups (all P > 0.05). Conclusions Our results suggested that matrine protects against isoproterenol-induced myocardial ischaemia via eNOS and ADMA pathway. © 2012 Royal Pharmaceutical Society.