Effect of ambrisentan and bosentan on pulmonary vascular remodeling in rats with hypoxic pulmonary hypertension

AIM: To study the effect of ambrisentan and bosentan on pulmonary vascular remodeling in rats with hypoxic pulmonary hypertension(HPH) and to compare the effect of the two drugs.METHODS: Forty Sprague Dawley rats were randomly divided into five groups: control group,model group,ambrisentan group,bosentan group and placebo group(eight rats in each group).Rats in the control group were kept under a normal environment for 4 weeks and rats in other groups were kept under hypobaric hypoxia environment(8 h/day) for 4 weeks.For placebo group,ambrisentan group and bosentan group,sodium choride(2 ml),ambrisentan(5 mg/kg) and bosentan(125 mg/kg) were given,respectively,during the third week.After 4 weeks,mean pulmonary arterial pressure(mPAP) and right ventricular systoic pressure(RVSP) were measured.Indexes of wall thickness of pulmonary arterioles including the percentage of vascular wall thickness/vascular external diameter(WT%) and the percentage of vascular wall area/total vascular area(WA%) were determined by a computerized image analyzer.α-SMA protein expression in pulmonary arteriole was observed by immunohistochemistry.RESULTS: H/E staining revealed that the pulmonary vessel wall was thickened and the vessel lumina decreased in the model and placebo groups.Ambrisentan and bosentan reversed this change.Compared with those in the control group,mPAP,WT%,WA% and protein expression of α-SMA increased significantly in the model and placebo groups.No significant difference was observed in the expression of α-SMA and indexes between ambrisentan group and bosentan group.CONCLUSION: Ambrisentan and bosentan significantly decrease pulmonary artery pressure and reverse pulmonary vessel remodeling in rats with HPH.No significant difference has been found in the curative effect between ambrisentan and bosentan.