The Impact Of Sildenafil On Monocrotaline-induced Pulmonary Hypertension In Rats

Objective:This study was designed to investigate the impact and mechanism of sildenafil on monocrotaline-induced pulmonary hypertension in rats.Methods:Thirty Adult male Wistar rats were randomized into three groups:pulmonary hypertension(PH)group induced by injection of a single dose of subcutaneous 60 mg/kg monocrotaline(MCT);intervention group administered Sildenafil(25mg/kg)orally once daily for 4 weeks after MCT injection and control group(saline injected).After 2 weeks,the parameters of mean pulmonary arterial pressure and systemic arterial pressure of each rat were monitored.The wall area(WA)%and vessel lumen area(VA)%of the pulmonary artery was measured microscopically.The ratio of right ventricular mass to left ventricular plus septal mass[RV/(LV+S)]was measured. Pulmonary artery and right ventricular myocardial tissue were examined histologically.The levels of cGMP in the plasma were measured by radioimmunoassay and colorimetric analysis.Results:Sildenafil significantly attenuated the aggravation of pulmonary artery pressure(29.96±2.03 mmHg vs.37.35±2.15 mmHg,P＜0.01)while mean systemic arterial pressure was not markedly lowered between the three groups.WA(%)in the interventional group was reduced more significantly compared with the PH group(49.68±2.35%vs.58.85±6.00%P＜0.01)while (VA)%was markedly increased in the interventional group compare with that in the PH group(50.32±2.35%vs.41.15±6.00%,P＜0.01).The ratio of right ventricular mass to left ventricular plus septal mass in the interventional group had decreased as compared with PH group(30.49±2.14%vs.39.04±2.66%,P＜0.01).Histological examination revealed that sildenafil inhibited pulmonary arterial proliferation and the remodeling of right myocardium in MCT-induced HP rats.The treatment of sildenafil significantly increased the level of plasma cGMP(20.88±1.54 pmol/ml vs.11.53±0.66 pmol/ml,P＜0.01).Conclusions:The data demonstrate that sildenafil can reduce the pressure in the pulmonary artery and downregulate the remodeling of pulmonary artery and right myocardium induced by MCT,which is associated with sildenafil-stimulated increase of cGMP in the plasma.