Zuo Xiangrong, Zong Feng, Wang Hui, Wang Qiang, Xie Weiping, Wang Hong
Department of Respiratory Medicine; ; Critical Care Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China;
J Biomed Res. 2011 Nov;25(6):392-401. doi: 10.1016/S1674-8301(11)60052-3.
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.
伊伐卡林是一种新型的ATP敏感性钾（KATP）通道开放剂，它可抑制肺动脉平滑肌细胞（PASMCs）的增殖和肺血管重塑。然而，其潜在机制仍不清楚。在本研究中，我们发现伊伐卡林在大鼠肺动脉高压模型中可显著降低慢性低氧时的肺动脉压力，抑制肺动脉重塑和PKC-α的过度表达。伊伐卡林可降低低氧诱导的PKC-α表达，并在体外以剂量依赖的方式显著消除低氧对PASMC增殖的影响。此外，这些作用被选择性KATP通道拮抗剂格列本脲所消除。这些结果表明，伊伐卡林通过下调PKC-α的表达来抑制低氧诱导的PASMC增殖和肺血管重塑。伊伐卡林可作为一种有前景的新型治疗低氧性肺动脉高压的药物。
