Iptakalim rescues human pulmonary artery endothelial cells from hypoxia-induced nitric oxide system dysfunction

Zong,Feng; Zuo,Xiang-Rong; Wang,Qiang; Zhang,Shi-Jiang; Xie,Wei-Ping; Wang,Hong

doi:10.3892/etm.2011.414

Iptakalim rescues human pulmonary artery endothelial cells from hypoxia-induced nitric oxide system dysfunction

Authors:
- Feng Zong
- Xiang-Rong Zuo
- Qiang Wang
- Shi-Jiang Zhang
- Wei-Ping Xie
- Hong Wang
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Affiliations: Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China, Department of Cardiothoracic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
Published online on: December 14, 2011 https://doi.org/10.3892/etm.2011.414
Pages: 535-539

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Abstract

The aim of this study was to assess whether hypoxia inhibits endothelial nitric oxide synthase (eNOS) activity and nitric oxide (NO) production, and whether iptakalim may rescue human pulmonary artery endothelial cells (HPAECs) from hypoxia-induced NO system dysfunction. HPAECs were cultured under hypoxic conditions in the absence or presence of 0.1, 10 and 1,000 µM iptakalim or the combination of 10 µM iptakalim and 1, 10 and 100 µM glibenclamide for 24 h, and the eNOS activity and NO levels were measured in the conditioned medium from the HPAEC cultures. The eNOS activity and NO levels were reduced significantly in the conditioned medium from HPAEC cultures under hypoxic conditions. Pre-treatment with 10 µM iptakalim normalized the reduction of the eNOS activity and NO levels caused by hypoxia in the conditioned medium from HPAEC cultures. Iptakalim raised the eNOS activity and NO levels under hypoxic conditions, but was blocked by the KATP channel blocker, glibenclamide. Our results indicate that hypoxia impairs NO system function, whereas the ATP-sensitive K+ channel opener, iptakalim, may rescue HPAECs from hypoxia-induced NO system dysfunction.

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