Hypoxic pulmonary vasoconstriction: mechanisms of oxygen-sensing.
Hypoxic pulmonary vasoconstriction: mechanisms of oxygen-sensing.
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DOI：
10.1097/aco.0b013e3283421201
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发表时间：
2011-02
期刊：
影响因子：
--
通讯作者：
Mahmoud A
中科院分区：
文献类型：
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作者：
Evans AM;Hardie DG;Peers C;Mahmoud A
缺氧性肺血管收缩（HPV）是由肺动脉平滑肌和内皮细胞对缺氧的内在反应驱动的。它们是一组专门的 O2 感应细胞的代表，其定义是它们对 pO2 相对较小的变化具有敏锐的敏感性，这些细胞已经进化到调节呼吸和循环功能，以将 O2 供应维持在生理限度内。本文的目的是讨论最近对缺氧反应耦合机制的研究，并据此对当前的工作假设进行批判性评估。最先进的技术现已证实，在暴露于缺氧时，所有氧气感应细胞（包括肺动脉平滑肌细胞）的线粒体氧化磷酸化都会受到抑制。此后，有证据表明，“气体递质”一氧化碳和硫化氢、活性氧或相反的还原细胞氧化还原对的主要效应器的作用。考虑到最近支持和反对这些提议的证据，我们认为另一种机制可能是关键，即抑制线粒体氧化磷酸化后激活 AMP 激活蛋白激酶 (AMPK)。 HPV 通过将血流从缺氧区域转移到富含氧气的区域来支持肺部的通气-灌注匹配。然而，在肺气肿和囊性纤维化等疾病中，广泛传播的 HPV 会导致缺氧性肺动脉高压，最终导致右心衰竭。因此，确定支撑缺氧反应耦合的精确机制将促进对相关病理生理学基本过程的理解，并提供改进的治疗方法。
Hypoxic pulmonary vasoconstriction (HPV) is driven by the intrinsic response to hypoxia of pulmonary arterial smooth muscle and endothelial cells. These are representatives of a group of specialised O2-sensing cells, defined by their acute sensitivity to relatively small changes in pO2, which have evolved to modulate respiratory and circulatory function in order to maintain O2 supply within physiological limits. The aim of this article is to discuss recent investigations into the mechanism(s) of hypoxia-response coupling and, in light of these, provide a critical assessment of current working hypotheses. Upon exposure to hypoxia state-of-the-art technologies have now confirmed that mitochondrial oxidative phosphorylation is inhibited in all O2-sensing cells, including pulmonary arterial smooth muscle cells. Thereafter, evidence has been presented to indicate a role as principal effector for the “gasotransmitters” carbon monoxide and hydrogen sulphide, reactive oxygen species or, in marked contrast, reduced cellular redox couples. Considering recent evidence in favour and against these proposals we suggest that an alternative mechanism may be key, namely the activation of AMP-activated protein kinase (AMPK) consequent to inhibition of mitochondrial oxidative phosphorylation. HPV supports ventilation-perfusion matching in the lung by diverting blood flow away from oxygen-deprived areas towards regions rich in O2. However, in diseases such as emphysema and cystic fibrosis, widespread HPV leads to hypoxic pulmonary hypertension and ultimately right heart failure. Determining the precise mechanism(s) that underpins hypoxia-response coupling will therefore advance understanding of the fundamental processes contributing to related pathophysiology and provide for improved therapeutics.