Cyclosporine A reverses the development of pulmonary hypertension induced by monocrotaline in rats

Objective:To explore the effect and the mechanism of cyclosporine A(CsA) on pulmonary hypertension induced by monocrotaline(MCT) in rats.Methods: Thirty six Sprague-Dawley male rats were randomly divided into normal control group(n=8),MCT model group(n=12),low dose CsA(0.33mg·kg-1)(n=8) and high dose CsA group(n=8).A single dose of MCT(50mg·kg-1) was subcutaneously injected to induce pulmonary hypertension.CsA was administered 14～21 days after MCT injection when pulmonary hypertension had already been established.Hemodynamic parameters were measured by Powerlab on day 22.The heart was separated into the right ventricle(RV) and the left ventricle with septum,and weighed separately.RVHI was measured as RV/(LV+septum);the lung weight(LW)/body weight(BW) were calculated.Left lung leafs were stained with haematoxylin-eosin,and examined under a light microscope.Immunohistochemical analysis was performed on paraffin-embedded left lung tissue using the anti-PCNA(proliferating cell nuclear antigen) primary antibody.Results: CsA(0.33 and 1mg·kg-1) significantly inhibited the progression of pulmonary artery pressure,the increase of the RVHI and the ratio of lung weight/body weight(P0.05 or P0.01) after MCT-induced pulmonary hypertension.Histological examination revealed that CsA effectively prevented pulmonary arterial medial thickening(P0.05 or P0.01),and attenuated inflammation.CsA effectively reduced the PCNA expression in pulmonary artery smooth muscle cells(PASMC)(P0.05 or P0.01).The effects of 1mg·kg-1 CSA were more significant.Conclusions: CsA reverses the development of pulmonary hypertension induced by MCT in rats.The mechanism may be related to reduction of the proliferation of PASMC and inhibition of the lung inflammation.