Oxymatrine prevents the development of monocrotaline-induced pulmonary hypertension via regulation of the N G , N G -dimethyl-L-arginine metabolism pathways in rats

The purpose of this study was to investigate the potential effect of oxymatrine in monocrotaline-induced pulmonary hypertension and its possible influence on the N ,N -dimethyl-L-arginine (ADMA) metabolism pathway. Pulmonary hypertension was induced in rats by a single-dose injection of monocrotaline (60 mg/kg). Daily oral administration of oxymatrine (25, 50 and 100 mg/kg) was started on the day following the monocrotaline injection for 28 days. Oxymatrine (50 and 100 mg/kg) significantly attenuated monocrotaline-induced lung and right ventricular hypertrophy, right ventricular systolic pressure elevation, and right ventricular dysfunction. Oxymatrine also reduced the thickening of monocrotaline-induced pulmonary arterial medial wall. Meanwhile, oxymatrine normalized the level of pulmonary asymmetric ADMA and attenuated the upregulated expression of protein arginine methyltransferase 1 (PRMT1). Oxymatrine had no effect on the expression of protein arginine methyltransferase 2 (PRMT2) and N ,N -Dimethylarginine dimethylaminohydrolase 1 (DDAH1), which were upregulated in monocrotaline-induced pulmonary arterial hypertensive rats. However, the expression of the protein N ,N -Dimethylarginine dimethylaminohydrolase 2 (DDAH2) did not differ among all groups (all P﹥0.05). These results suggest that oxymatrine may offer protective effects on the development of pulmonary hypertension by ameliorating pulmonary remodeling and modulating the ADMA metabolism pathway.