Objective:The present study was designed to investigate the protective effect of Iptakalim against hypoxia-induced apoptosis in human pulmonary arterial endothelial cells (HPAEC)and the potential mechanisms involved. Methods:After medicine and hypoxia treatment,the MTT assay was performed to measure cell viability. Hoechst 33342 was then used to detect apoptosis. Finally,the expression of phospho-JNK,JNK and caspase-3 was assayed by Western blot. Results:Our study showed that hypoxia significantly decreased the cell viability by inducing cellular apoptosis,while Iptakalim reversed the hypoxia-induced apoptosis, which can be blocked by 5-HD. Iptakalim and SP600125 consistently inhibited the phosphorylation of c-JNK and the expression of caspase-3 induced by hypoxia,and this effect was completely blocked by the 5-HD. Conclusion:Iptakalim protects the HPAEC from hypoxia-induced apoptosis by opening the KATP channels. The possible cellular mechanisms for this protective effect may involve the inhibition of phospho-JNK and the downstream cell death pathways.