Oxymatrine Attenuates Monocrotaline-induced Pulmonary Hypertension Via Regulation Akt/eNOS Signaling And Asymmetric Dimethylarginine Metabolism

Objectives The purpose of this study was to investigate the effect and potential mechanism of oxymatrine on monocrotaline-induced pulmonary hypertension in rats.Methods Pulmonary hypertension was induced in rats by a single-dose injection of monocrotaline (60mg/kg). Daily administration with oxymatrine (25, 50 and 100 mg/kg, respectively) was started on the day following monocrotaline injection for 28 days. Hemodynamic parameters and right ventricular hypertrophy and morphological features were evaluated. The plasma level of cTn-I were assessed.Key findings Administration of oxymatrine (25, 50 and 100 mg/kg, respectively) significantly attenuated both the hemodynamic and structural abnormalities of monocrotaline-induced pulmonary hypertension and right ventricular hypertrophy. Oxymatrine administration improved moncrotaline-induced increased serum level of cTn-I. However, HR did not differ among all groups (P>0.05).Conclusions We conclude that daily administration of oxymatrine potently attenuates monocrotaline-induced pulmonary hypertension, right ventricular hypertrophy and pulmonary vascular remodeling in rats. The underlying mechanism responsible for this effect may be partly related to reduce cTn-I level in serum and inhibit pulmonary vascular reconstruction.Objectives To elucidate the molecular mechanisms of oxymatrine against pulmonary hypertension induced by monocrotaline, the signal pathway of Akt/eNOS, PRMT1/ADMA/DDAH2 were investigated.Methods Pulmonary hypertension was induced in rats by a single-dose injection of monocrotaline (60mg/kg). The protein content of Akt/p-Akt(Ser473), eNOS/p-eNOS(Ser1177), PRMT1, DDAH2 in lung tissue were measured by the method of Western blot.Key findings Compared with the control, the protein level of Akt, eNOS were significantly reduced, and the content of ADMA was markedly increased and DDAH2 decreased in MCT-induced pulmonary hypertension group. Daily administration of oxymatrine could reverse the down-regulation of Akt, eNOS and enhance the phosphorylation of AktSer473 and eNOSSer1177, significant reduced the content of ADMA and increased level of DDAH2. The level of PRMT1 had no difference among all groups (all P>0.05).Conclusions We conclude that the molecular mechanism of the effect of oxymatrine on MCT-induced pulmonary hypertension were regulated via Akt/eNOS signal transduction pathway, and increased the content of DDAH2, then the metabolism of ADMA were enhanced, the level of nitric oxide may be restored.