Objective To study the effects of iptakalim, a novel ATP-sensitive potassium channel opener, on the mRNA and protein expression level of eNOS in primary cultured human pulmonary arterial endothelial cells( HPAECs) in-duced by endothelin-1 ( ET-1) . Methods By Western-blot analysis, the protein expression level of eNOS was measured in primary cultured HPAECs. By RT-PCR analysis, the mRNA expression level of eNOS was measured in primary cultured HPAECs. The control group received no intervention, and the other groups were incubated with ET-1, ET-1+iptakalim, pinacidil or glibenclamide. Results The results demonstrated that ET-1 downregulated the mRNA and protein expression level of eNOS. Iptakalim inhibited ET-1-induced downregulation of the mRNA and protein expression level of eNOS in a concentration-dependent manner. Glibenclamide, a selective KATP channel antagonist, could antagonize the effects of iptakalim. Conclusions Pulmonary vascular endothelial dysfunction is induced by chronic hypoxia,and the level of NO, the mRNA and protein expression of eNOS are decreased. Iptakalim can improve the vascular endothelial dysfunction, in-crease the expression of eNOS and the level of NO,decrease pulmonary artery pressure and will be a most promising new compound to treat pulmonary arterial hypertension.%目的：研究新型ATP敏感性钾通道（ KATP ）开放剂埃他卡林（ IPT）对内皮素-1（ ET-1）诱导的原代培养人肺动脉内皮细胞（ HPAECs）内皮型一氧化氮合酶（ eNOS） mRNA和蛋白表达水平的影响。方法原代培养HPAECs，对照组不予干预，实验组分别加入ET-1，ET-1＋IPT、KATP开放剂吡那地尔（ PIN）或KATP阻断剂格列本脲（ GLI）等孵育。用RT-PCR技术，分析各组eNOS mRNA表达；采用Western-blot技术，分析各组eNOS蛋白表达。结果 ET-1使HPAECs eNOS mRNA和蛋白表达水平下调。 IPT呈浓度依赖性抑制ET-1的作用。 GLI逆转IPT的作用。结论长期低氧导致肺血管内皮细胞功能障碍，一氧化氮（ NO）生成减少、eNOS mRNA和蛋白水平表达下降，而IPT可改善内皮细胞功能障碍，增加eNOS的表达和NO的释放，从而降低肺动脉压力，可能成为较有前途的治疗肺动脉高压（ PAH）的新型化合物。
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