Objective: To investigate the therapeutic effect of angiotensin converting enzyme inhibitor on pulmonary vascular remodeling of pulmonary hypertension induced by high pulmonary blood flow.
Methods: An arterial-venous shunt was surgically created between abdominal aorta and inferior vena cava in the rat of all groups except the control group. Captopril was given to all of the rats. Six weeks after the operation,pulmonary artery systolic pressure (PASP), pulmonary artery diastolic pressure (PADP) and right ventricular systolic pressure (RVSP) were measured. The rats' hearts were weighted to calculate the ratio of right ventricle mass to left ventricle plus septum mass. Immunohistochemical stains were used to identify alpha-actin and PCNA distribution in pulmonary arteries. Morphometric parameters (vascular wall thickness and muscularization) were used to assess the remodeling of small pulmonary arteries.
Results: The PASP, PADP, RVSP, RV/(LV+S), RV/BW, and (LV + S)/BW of the rats in the shunt group were significantly greater than those of the control group. Muscularization of small pulmonary arteries and pulmonary artery medial hypertrophy (wall thickness) were evident in the shunt group. The proliferation index of the smooth muscle cells of the small and medium-sized pulmonary arteries was significantly higher and the alpha-actin IOD was significantly lower in the rats of the shunt group than those of the control. By contrast, the levels of PASP, PADP, RVSP, RV/(LV+S), RV/BW, (LV+ S)/BW, and muscularization were lower in the rats of captopril group than those of the control.
Conclusions: Captopril slows down pulmonary hypertension and remodeling development. Captopril and losartan may have preventive and therapeutic effects on pulmonary hypertension induced by congenital left-to-right shunts.