Effects of Ang-(1-7) on hyperplasia of pulmonary vascular smooth muscle cells in pulmonary arterial hypertension rats

BACKGROUND: Ang-(1-7) is considered one of the biologically active products of renin-angiotensin system. Ang-(1-7) might inhibit the vascular smooth muscle cells. However, effects of Ang-(1-7) in different vascular beds are different. Effects of Ang-(1-7) on the model of pulmonary artery hypertension induced by monocrotaline (MTC) are unknown. OBJECTIVE: To investigate the therapeutic effect of Ang-(1-7) on proliferation of the pulmonary vascular smooth muscle cells in rat model of pulmonary arterial hypertension. METHODS: Adult SD rats were randomly divided into three groups: control group, MCT group and MCT+Ang-(1-7) group. Rats in MCT group and MCT+ Ang-(1-7) group received 60 mg/kg MCT injection subcutaneously and after 24 hours received either saline or 24 ug/kg/h of Ang-(1-7) injection via osmotic minipumps for 2 and 4 weeks. These rats in control group were firstly injected saline subcutaneously and then received saline injection via osmotic minipumps for two and four weeks. Right ventricular systolic pressure (RVSP) was measured. The animals' hearts were measured to calculate the ratio of right ventricle to left ventricle plus septum (RV/LV+S), right ventricle mass to body weight (RV/BW) and left ventricle plus septum mass to body weight (LV+S/BW). Percentage of wall thickness (WT%) and percentage of wall area (WA%) of pulmonary arterioles were evaluated. Immunohistochemical stains were used to identifyα-actin and proliferation cells nuclear antibody (PCNA) distribution in pulmonary arteries. RESULTS AND CONCLUSION: At 2 weeks after injection, no significant difference was found between MCT and control group in RVSP and RVHI. Compared with control group, WT%, WA% and the positive ratio of PCNA were significantly increased and α-actin was significantly decreased in MCT group. At 4 weeks after injection, compared with control group, RVSP, RVHI, WT%, WA % and the positive ratio of PCNA were significantly increased and α-actin was significantly decreased in MCT group. However, no significant difference was found between MCT+Ang-(1-7) group and control group among the above parameters (P > 0.05). MCT-induced pulmonary arteriolar remodeling is prior to the increase of pulmonary arterial pressure in rats. Ang-(1-7) might inhibit the vascular smooth muscle cells in rat model of pulmonary arterial hypertension.