Zong Feng, Zuo Xiang-Rong, Wang Qiang, Zhang Shi-Jiang, Xie Wei-Ping, Wang Hong
Departments of Respiratory Medicine.
Exp Ther Med. 2012 Mar;3(3):535-539. doi: 10.3892/etm.2011.414. Epub 2011 Dec 14.
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 K(ATP) 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.
本研究旨在评估缺氧是否会抑制内皮型一氧化氮合酶（eNOS）活性及一氧化氮（NO）生成，以及伊普卡林是否可挽救人肺动脉内皮细胞（HPAECs）免受缺氧诱导的NO系统功能障碍。将HPAECs在缺氧条件下培养，分别添加或不添加0.1、10和1000 μM伊普卡林，或10 μM伊普卡林与1、10和100 μM格列本脲的组合，培养24小时，然后测定HPAECs培养条件培养基中的eNOS活性和NO水平。缺氧条件下HPAECs培养条件培养基中的eNOS活性和NO水平显著降低。用10 μM伊普卡林预处理可使HPAECs培养条件培养基中因缺氧导致的eNOS活性和NO水平降低恢复正常。伊普卡林可提高缺氧条件下的eNOS活性和NO水平，但被K(ATP)通道阻滞剂格列本脲阻断。我们的结果表明，缺氧会损害NO系统功能，而ATP敏感性钾（K(+)）通道开放剂伊普卡林可能挽救HPAECs免受缺氧诱导的NO系统功能障碍。
