Iptakalim, a novel ATP-sensitive potassium channel opener, inhibits pulmonary arterial smooth muscle cell proliferation by downregulation of PKC-α  

作　　者：Xiangrong Zllo Feng Zong Hui Wang Qiang Wang Weiping Xie Hong Wang 

机构地区：[1]Department of Respiratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China [2]Critical Care Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China

出　　处：《The Journal of Biomedical Research》2011年第6期392-401,共10页生物医学研究杂志（英文版）

基　　金：supported by the National Natural Science Foundation of China (No.30971319);the "Six Talent Peak" Project of Jiangsu Province (No.08-B);the grant from Open Project Program of the Key Disciplines of the Public Health Department of Jiangsu Province (No. XK13_200902)

摘　　要：Iptakalim is a new ATP-sensitive potassium （KATp） channel opener, and it inhibits the proliferation of pulmonary arterial smooth muscle cells （PASMCs） and pulmonary vascular remodeling. However, the underlying mechanism remains unclear. In the present study, we found that iptakalim significantly decreased pulmonary artery pressure, inhibited pulmonary ariery remodeling and PKC-α overexpression in chronic hypoxia in a rat pulmonary hypertension model. Iptakalim reduced hypoxia-induced expression of PKC-α, and abolished the effect of hypoxia on PASMC proliferation significantly in a dose-dependent manner in vitro. Moreover, these effects were abol- ished by glibenclamide, a selective KArp channel antagonist. These results indicate that iptakalim inhibits PASMC proliferation and pulmonary vascular remodeling induced by hypoxia through downregulating the expression of PKC-α. Iptakalim can serve as a novel promising treatment for hypoxic pulmonary hypertension.Iptakalim is a new ATP-sensitive potassium （KATp） channel opener, and it inhibits the proliferation of pulmonary arterial smooth muscle cells （PASMCs） and pulmonary vascular remodeling. However, the underlying mechanism remains unclear. In the present study, we found that iptakalim significantly decreased pulmonary artery pressure, inhibited pulmonary ariery remodeling and PKC-α overexpression in chronic hypoxia in a rat pulmonary hypertension model. Iptakalim reduced hypoxia-induced expression of PKC-α, and abolished the effect of hypoxia on PASMC proliferation significantly in a dose-dependent manner in vitro. Moreover, these effects were abol- ished by glibenclamide, a selective KArp channel antagonist. These results indicate that iptakalim inhibits PASMC proliferation and pulmonary vascular remodeling induced by hypoxia through downregulating the expression of PKC-α. Iptakalim can serve as a novel promising treatment for hypoxic pulmonary hypertension.

关 键 词：IPTAKALIM pulmonary arterial smooth muscle cells （PASMCs） pulmonary hypertension protein kinase C-α （PKC-α） hypoxia proliferation 

分 类 号：Q55[生物学—生物化学] S858.316.2[农业科学—临床兽医学]