Sildenafil Prevents And Reverses The Development Of Pulmonary Hypertension In Pneumonectomy Combining To Monocrotaline Treated Rats

Objective: To investigate the protective and reverse effects of sildenafil on pulmonary hypertension in pneumonectomy combining to monocrotaline treated rats.Methods: All 50 Male SD rats (8 weeks old), 10 were sham operated, the other rats were treated with monocrotaline(60mg·kg^-1)one week after pneumonectomy and divided into 2 groups. In the prevention group, 20 monocrotaline-treated and 10 sham-treated rats were used. One day after the injection of monocrotaline, the animals were randomly divided into two sub-groups (n =10 each), and given a single daily administration of either Sodium Chloride as the vehicletreated group, or sildenafil (1.7mg·kg^-1·d^-1) for 3 weeks. The shamtreated rats (n = 10) received vehicle. In therapeutic study, Three weeks after the injection of monocrotaline, the animals were randomly divided into two groups, and orally given Sodium Chloride as the vehicle (n = 10) or sildenafil (1.7mg·kg^-1·d^-1, n =10;) once daily for 3 weeks . The sham-treated rats (n=10) received the vehicle. One day after the final drug administration, hemodynamic variables were measured .The mean pulmonary arterial pressure (mPAP) and right ventricle/left ventricle and septum [RV/(LV+S)] were measured and the small pulmonary arterial morphologic changes were observed with morphmetric analysis under microscopes in two groups. Orcein elastic fiber stained to detect the elastic fiber on small pumlonary arterial. The expression of endothelin-1 A type receptor (ET-1_AR) on small pumlonary arterial were measured with immunohistochemistry. The ET-1 level in plasma was measured with radioimmunity.Results: In the prevention group, Compared to sham-treated rats, monocrotaline-treated rats receiving vehicle showed a marked increase in right pulmonary arterial pressure at 3 weeks after monocrotaline injection, demonstrating the presence of pulmonary hypertension .These rats also showed increases in RV, RV/BW and RV/(LV+ S) values, indicating marked right ventricular hypertrophy.The level of mPAP, [RV/(LV+S)], small pumlonary arterial morphologic and elastic fiber changes were highly improved in sildenafil group(P<0.05). The expression of endothelin-1 A type receptor (ET_A-R) on small pumlonary arterial were significently reduced in sildenafil group (P<0.05). The ET-1 level in plasma were increased in sildenafil group, but not reach the significant.The same finding was observed in therapeutic study. Emphysema, interstitial pneumonia were significantly improved in sildenafil group in both group.