Anti-proliferating effect of iptakalim, a novel KATP channel opener, in cultured rabbit pulmonary arterial smooth muscle cells

ATP-sensitive potassium (KATP) channels of pulmonary arterial smooth muscle cells (SMCs) have been implicated in pulmonary hypertension. Iptakalim, designed and synthesized by ourselves, is a newly selective KATP channel opener. Here, we explored the effects of iptakalim on the rise of cytoplasmic free Ca2+ concentration ([Ca2+]cyt) induced by endothelin-1 (ET-1) and on the proliferation of cultured rabbit pulmonary arterial SMCs. The results showed that iptakalim inhibited the [Ca2+]cyt increase. The enhanced [3H]thymidine incorporation was inhibited and the transition of cells from static phase (G0/G1) to DNA synthesis (S) and mitotic phase (G2/M) was held back by iptakalim in a concentration-dependent manner. Glyburide abolished the inhibitory effect of iptakalim. In conclusion, we have shown that iptakalim had an inhibitory effect on [Ca2+]cyt increase and the proliferation of pulmonary arterial SMCs induced by endothelin-1 through activation of KATP channels. These findings suggest that iptakalim might be a promising candidate for the treatment of pulmonary arterial remodeling in pulmonary hypertension.