title: Iptakalim, a novel ATP-sensitive potassium channel opener, inhibits pulmonary arterial smooth muscle cell proliferation by downregulation of PKC-α.
abstract: 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 abolished by glibenclamide, a selective KATP 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.
authors.affiliation: Department of Respiratory Medicine; ; Critical Care Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China;
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Zuo
authors.forename: Feng
authors.initials: F
authors.lastname: Zong
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.forename: Weiping
authors.initials: W
authors.lastname: Xie
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
keywords: hypoxia; iptakalim; proliferation; protein kinase C-α (PKC-α); pulmonary arterial smooth muscle cells (PASMCs); pulmonary hypertension
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