Lee Y H, Seo J H, Kang B S
Department of Physiology, Yonsei University College of Medicine, Seoul, Korea.
Yonsei Med J. 1998 Jun;39(3):261-7. doi: 10.3349/ymj.1998.39.3.261.
Although hypoxic pulmonary vasoconstriction (HPV) has been recognized by many researchers, the precise mechanism remains unknown. As isolated pulmonary arteries will constrict in vitro in the response to hypoxia, the oxygen sensor/transduction mechanism must reside in the pulmonary arterial smooth muscle or in the endothelium, or in both. Unfortunately, much of the current evidence is conflicting, especially as to the dependency of HPV on the endothelium and the role of a K+ channel. Therefore, this experiment was attempted to clarify the dependency of HPV on the endothelium and the role of a K+ channel on HPV in rat pulmonary artery. The effects of hypoxia were investigated in isolated main pulmonary arteries precontracted with norepinephrine. Vascular rings were suspended for isometric tension recording in an organ chamber filled with a Krebs-Henseleit solution. Hypoxia was induced by gassing the chamber with 95% N2 + 5% CO2 and this was maintained for 20 min. Hypoxia elicited a vasoconstriction in arteries with endothelium. Mechanical disruption of the endothelium abolished HPV. There was no difference between the amplitude of the HPV induced by two consecutive hypoxic challenges and the effect of normoxic and hyperoxic control Krebs-Henseleit solution on a subsequent response to hypoxia. Inhibition of NO synthesis by treatment with N(omega)-nitro-L-arginine reduced HPV, but inhibition of a cyclooxygenase pathway by treatment with indomethacin had no effect on HPV. Blockades of a tetraetylammonium chloride-sensitive K+ channel abolished HPV. Verapamil, a Ca2+ entry blocker reduced HPV. In conclusion, these results suggest that HPV was dependent on the endothelium and that HPV can be considered to be induced by inhibition of the mechanisms of NO-dependent vasodilation such as the opening of a K+ channels.
尽管许多研究人员已经认识到缺氧性肺血管收缩（HPV），但其确切机制仍然未知。由于离体肺动脉在体外会对缺氧产生收缩反应，氧传感器/转导机制必定存在于肺动脉平滑肌或内皮细胞中，或者两者都有。不幸的是，目前的许多证据相互矛盾，特别是关于HPV对内皮细胞的依赖性以及钾通道的作用。因此，本实验旨在阐明大鼠肺动脉中HPV对内皮细胞的依赖性以及钾通道对HPV的作用。在预先用去甲肾上腺素预收缩的离体主肺动脉中研究了缺氧的影响。将血管环悬挂在充满克雷布斯 - 亨泽莱特溶液的器官浴槽中进行等长张力记录。通过向浴槽中通入95% N₂ + 5% CO₂诱导缺氧，并维持20分钟。缺氧引起有内皮的动脉血管收缩。内皮细胞的机械损伤消除了HPV。两次连续缺氧刺激诱导的HPV幅度与常氧和高氧对照克雷布斯 - 亨泽莱特溶液对随后缺氧反应的影响之间没有差异。用N（ω）-硝基-L-精氨酸处理抑制一氧化氮合成可降低HPV，但用吲哚美辛处理抑制环氧化酶途径对HPV没有影响。阻断对氯化四乙铵敏感的钾通道消除了HPV。维拉帕米，一种钙通道阻滞剂，降低了HPV。总之，这些结果表明HPV依赖于内皮细胞，并且HPV可以被认为是由抑制一氧化氮依赖性血管舒张机制（如钾通道开放）诱导的。
