Objective To study the effect of chloride channel blocker(niflumic acid,NFA) on pulmonary hypertension induced by high pulmonary blood flow in rats.Methods Fifty male or female Sprague-Dawley rats were randomly divided into 5 groups:normal group,sham group,model group,drug 1 group,and drug 2 group,with 10 rats in each group.After subjected to an abdominal aorta-inferior vena cava shunt,all the rats were reared under the same condition for 11 weeks.Then,mean pulmonary artery pressure(mPAP) and right ventricular hypertrophy index(RVHI) of each rat were measured.In addition,arterial wall area/vessel area (W/V) and arterial wall thickness/vessel external diameter(T/D) of each rat were also measured.Results 1.The mPAP of model group [(25.79 ± 4.03) mmHg,1 mmHg =0.133 kPa] was significantly higher than those of normal group [(16.48 ± 1.70) mmHg],sham group [(17.03 ± 2.01) mmHg],drug 1 group [(21.78 ± 2.77) mmHg] and drug 2 group [(20.31 ± 2.15) mmHg] (F =18.983,P ＜0.01).Although the mPAP of drug 1 group was a little higher than drug 2 group,there was no significant difference (P ＞ 0.05).Compared with normal group and sham group,the mPAP of drug 1 group and drug 2 group increased(P ＜0.01,respectively).2.The W/V and T/D of model group were significantly higher than those of normal group,sham group,drug 1 group and drug 2 group (F =26.135,15.527,all P ＜ 0.001).The W/V and T/D of two drug groups showed no significant difference,but they were higher than those of normal group and sham group (P ＜ 0.01,respectively).Conclusions Chloride channel blocker NFA partly decrease mPAP of pulmonary hypertension indnced by high pulmonary blood flow in rats,and inhibit proliferation of vascular smooth muscle cells.These results suggest that NFA had part of therapeutic effect to pulmonary hypertension induced by high pulmonary blood flow.

Objective To study the pulmonary interstitial changes in pulmonary hypertension induced by high pulmonary blood flow.Methods Sixty-five male or female Sprague-Dawley rats (180-230 g) were used and randomly divided into 3 groups:normal group (n =20) ; sham group (n =20),only exposing the abdominal aorta and inferior vena cava about 10-20 minutes;model group(n =25),rats in this group were subjected to an abdominal aorta-inferior vena cava shunt to create animal models of high pulmonary.After operation,all the rats were reared under the same conditions for 11 weeks.Then,the systolic pulmonary artery pressure (sPAP) and mean pulmonary artery pressure (mPAP) of every rat were determined by means of homemade right heart catheterization.After that,the right ventricle (RV) was separated from the left ventricle (LV) and septum (S),then weighed.And right ventricular hypertrophy index (RVHI) was measured by the ratio of RV to LV + S [RV/(LV + S)].In addition,the morphological changes of pulmonary interstitial of rats were observed under optical microscope by means of hematoxylin-eosin (HE) staining.In the end,single pulmonary artery smooth muscle cell (PASMC) was isolated through acute enzyme separation.Then membrane capacitance (Cm) was recorded through in the method of patch clamp technique.Results 1.Compared with sham group and normal group,the sPAP,mPAP and RVHI of model group increased significantly(F =17.293,16.259,12.878,all P ＜ 0.01).2.In contrast to sham group and normal group,arterial wall area/vessel area(W/V) and arterial wall thickness/vessel external diameter(T/D) in model group increased significantly(F =85.717,22.795,all P ＜0.01).3.The membrane capacitance of model group was bigger than that of sham group and normal group(F =8.704,P ＜ 0.01).4.mPAP was positively correlated with W/V,T/D and Cm (r =0.669,0.662,0.663,all P ＜ 0.01).Conclusions Shunts from abdominal aorta-inferior vena cava in SD rats caused high pulmonary blood flow-induced pulmonary hypertension,and these rats appeared with pulmonary smooth muscle cells hypertrophy,pulmonary vascular wall thickening and inflammatory cells infiltration.