Effect Of Inhaled S-nitrosocysteine On Pulmonary Hypertension, Pulmonary Vascular Remolding, And Survival Rates In A Rat Model Of Monocrotaline-induced Pulmonary Hypertension

Objects:To explore the effect of inhaled S-nitrosocysteine(CSNO) on reducing pulmonary artery pressure in a rat model of monocrotaline-induced pulmonary hypertension,and if inhaled S-nitrosocysteine can retard the pathological progress of pulmonary hypertension, delay pulmonary vascular and right ventricular remolding, and reduce mortality.Methods:Forty male SD rats were randomly into three groups:(1)Acute treatment group(n=20):inducing pulmonary hypertension in rats by a single subcutaneous injection of monocrotaline(MCT), on the 25 th day, the rats underwent right heart catheterization, meanwhile, kept inhaling S-nitrosocysteine(CSNO) for 20 minutes, observing the pulmonary artery pressure change.(2)Chronic treatment group(n=10):inducing pulmonary hypertension in rats by a single subcutaneous injection of monocrotaline(MCT), on the 26 th day, using transthoracic echocardiography to evaluate pulmonary artery pressure, then beginning to make the rats inhaleS-nitrosocysteine(CSNO) twice a day, 5 days a week, 20 minutes at a time.(3)Chronic control group(n=10):inducing pulmonary hypertension in rats by a single subcutaneous injection of monocrotaline(MCT), on the 26 th day, using transthoracic echocardiography to evaluate pulmonary artery pressure, then beginning to make the rats inhale distilled water twice a day, 5 days a week, 20 minutes at a time. During therapy, observing the mortality of rats in chronic treatment group and chronic control group, and using transthoracic echocardiography to evaluate pulmonary artery pressure of the two groups every week. After two to three weeks, measuring right ventricular pressure of the two groups by invasive method. Then the rats were executed, their hearts and lungs were removed for histopathological and immunohistochemical examinations, observing the differences of hemodynamics, cardiac structure and pulmonary vascular structure between the two groups.Results :(1) With the inhalation of CSNO, the rats pulmonary artery pressures decreasing. In the 20 th minute, compared with before medication,the pulmonary artery pressures of rats in acute treatment group were significantly lower(P<0.05).(2)From the fourth week, the difference of mortality rates between chronic treatment group and chronic control group gradually appeared. Compared with chronic control group, the mortality rates of rats in chronic treatment group were significantly lower(P<0.05).(3)After 2 weeks of treatment,compared with chronic control group,the right ventricular transverse diameter and the anteroposterior diameter of the right ventricular outflow tract of rats in chronic treatment group were significantly reduced(P<0.05); RV/(LV + IVS) and RVWT in rats of the two groups were no significant difference(P>0.05).(4)After 2 weeks of treatment,WT%, WA% and proliferation PCNA in rats of the two groups were no significant difference(P>0.05).Conclusion:CSNO inhalation can depress the pulmonary artery pressure in rats of monocrotaline-induced pulmonary hypertension. The mortality rates of rats can be significantly reduced by long-term treatments, probably through retarding the pathological progress of pulmonary hypertension and delaying pulmonary vascular and right ventricular remolding.