Cardioprotective Effect Of Oxymatrine On Chronic Heart Failure Via The Regulation Of ADMA/Nitric Oxide Pathway In Rats

Objectives This study was designed to investigate if oxymatrine could prevent theisoproterenol-induced chronic heart failure in rats and whether cardioprotective effectinvolved in regulating of asymmetric dimethylarginine (ADMA) metabolism and nitric oxidepathway.Methods Male Sprague-Dawley rats were given oxymatrine (100,50and25mg·kg-1)orally for14days. Chronic heart failure was induced in rats by subcutaneous injection ofisoproterenol (5mg·kg-1·d-1) at the8thday for1week. Myocardial injury marker enzymes(cTn I), haemodynamic parameters (+LVdp/dtmax、LVSP、-LVdp/dtmax、SAP、MAP、heart rateet al.) and histopathological variables were analysed. Serum levels of ADMA, nitric oxide(NO), Endothelin-1(ET-1) and myocardial tissue levels of NO were detected. The proteincontent of protein-arginine methyltransferases1(PRMT1), dimethylargininedimethylaminohydrolase2(DDAH2), endothelial nitric oxide synthase (eNOS) in myocardialtissue were measured by the method of Western blot.Result Oral administration oxymatrine (100and50mg·kg-1) significantly attenuatedserum content of cTn I (P<0.01), improved left ventricle systolic and diastolic function andleft ventricular remodeling (P<0.01), reduced the ISO-induced myocardial pathologicalchanges compared with ISO group. Compared with the control, the serum levels of ADMA,NO, ET-1was significantly increased, myocardial tissue level of NO was significantlyreduced, the content of PRMT1was markedly increased and DDAH2decreased and theprotein level of eNOS was significantly reduced in ISO-induced chronic heart failure gourp. Oxymatrine (100and50mg·kg-1) significantly reduced serum content of ADMA and ET-1(P<0.01), increased heart tissue level of NO (P<0.01), normalize the reduced DDAH2andeNOS expression (P<0.01), but had no effect on the isoproterenol-induced upregulated serumcontent of NO and protein PRMT1expression (P>0.05).Conclusions Our results suggest that oxymatrine exerted cardioprotective effect onisoproterenol-induced chronic heart failure in rats and its action of mechanism involved inmodulating the cardiac ADMA metabolism and NO pathway.