Division of Asthma, Allergy and Lung Biology, King's College London, United Kingdom.
Respir Physiol Neurobiol. 2010 Dec 31;174(3):165-74. doi: 10.1016/j.resp.2010.08.016. Epub 2010 Aug 27.
During alveolar hypoxia, hypoxic pulmonary vasoconstriction (HPV) maintains blood oxygenation near optimum via incompletely defined mechanisms. It is proposed that a hypoxia-induced rise in the intracellular concentration of reactive oxygen species (ROS) or an oxidising shift in the cytoplasmic redox state provides the signal which initiates the constriction of pulmonary arteries (PA), although this is controversial. Here, we review recent investigations demonstrating that hypoxia causes a rise in [ROS] in PA smooth muscle, and that ROS and antioxidants have effects on PA which would be predicted if cell oxidation causes contraction. We argue that intracellular Ca2+ release and Ca2+-sensitisation are the key effector mechanisms causing HPV, and discuss evidence that both processes are promoted by ROS or oxidative protein modifications. We conclude that while it is plausible that an increase in cytoplasmic [ROS] activates HPV effector mechanisms, proving this link will require the determination of whether hypoxia causes oxidative modifications of proteins involved in Ca2+ homeostasis and sensitisation.
在肺泡缺氧时，低氧性肺血管收缩（HPV）通过不完全定义的机制使血氧维持在最佳水平。据推测，缺氧引起的活性氧（ROS）的细胞内浓度升高或细胞质氧化还原状态的氧化偏移提供了启动肺血管（PA）收缩的信号，尽管这存在争议。在这里，我们回顾了最近的研究，这些研究表明缺氧会导致 PA 平滑肌中 [ROS]的升高，并且 ROS 和抗氧化剂对 PA 有影响，如果细胞氧化导致收缩，那么这种影响是可以预测的。我们认为细胞内 Ca2+释放和 Ca2+敏化是引起 HPV 的关键效应机制，并讨论了证据表明这两个过程都受到 ROS 或氧化蛋白修饰的促进。我们的结论是，虽然细胞质[ROS]的增加激活 HPV 效应机制是合理的，但要证明这一联系，需要确定缺氧是否会引起钙稳态和敏化相关蛋白的氧化修饰。
