Endothelial modulation of pulmonary vascular tone.
Endothelial modulation of pulmonary vascular tone.
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DOI：
10.1183/09031936.93.05060757
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发表时间：
1992-06
期刊：
影响因子：
--
通讯作者：
A. Dinh-Xuan
中科院分区：
文献类型：
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作者：
A. Dinh-Xuan
肺内皮细胞通常合成前列环素(PGI2)和一氧化氮(NO)，这两种物质都是强有力的血管扩张剂。尽管前列腺素I2主要用于治疗重度肺动脉高压患者，但其在肺循环生理学和病理生理学中的作用仍存在争议。NO现在被认为是内源性硝基血管扩张剂，在健康和疾病中调节肺血管张力的机制中可能比PGI2参与得更多。有证据表明，在常氧状态下，背景NO的释放有助于正常低肺血管张力的形成。虽然有理论依据假设缺氧减少了NO的合成，但缺乏后者似乎不能解释急性缺氧性肺血管收缩。相反，有证据表明，NO活性增加是为了调节对急性肺泡缺氧的肺血管升压反应。然而，关于NO的作用，更一致的是从慢性低氧条件下进行的研究收集的数据。实验数据和在人身上进行的研究都表明，慢性缺氧性肺动脉高压患者NO合成和/或释放受到损害。NO的产生受损，虽然降低了肺血管的松弛能力，但也有利于过度的肺血管收缩的发生。缺乏NO合成也可能允许血管壁内各种类型的细胞有丝分裂和增殖。我们假设肺内皮细胞的功能改变可能影响肺血管的反应性和生长。在这方面，在健康和疾病中，NO可能在调节肺血管张力和控制肺血管重构方面起着关键作用。
Pulmonary endothelial cells normally synthesize prostacyclin (PGI2) and nitric oxide (NO), which are both potent vasodilators. Although PGI2 is largely used to treat patients with severe pulmonary hypertension, its role in the physiology and pathophysiology of the pulmonary circulation is still debated. NO, which is now considered as the endogenous nitrovasodilator, is perhaps more involved than PGI2 in the mechanisms that modulate pulmonary vascular tone in health and disease. There is evidence to suggest that background release of NO contributes to the normally low pulmonary vascular tone in normoxia. Although there are theoretical grounds to hypothesize that hypoxia reduces the synthesis of NO, lack of the latter does not seem to account for the acute hypoxic pulmonary vasoconstriction. Instead, there is evidence to suggest that NO activity is increased in order to modulate the pulmonary vasopressor response to acute alveolar hypoxia. However, more consistent, concerning the role of NO, are data gathered from studies performed in chronic hypoxic conditions. Both experimental data and studies performed in man demonstrate impairment of NO synthesis and/or release in chronic hypoxic pulmonary hypertension. The impaired NO production, whilst reducing the ability of the pulmonary vasculature to relax, also favours the occurrence of excessive pulmonary vasoconstriction. Lack of NO synthesis might also permit mitogenesis and proliferation of various cell types within the vascular wall. We hypothesize that functional alterations of pulmonary endothelium are likely to affect both reactivity and growth of pulmonary vessels. In this respect, NO probably has a pivotal role in modulating pulmonary vascular tone and controlling pulmonary vascular remodelling in health and disease.