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Spatial and temporal patterns of nitric oxide diffusion and degradation drive emergent cerebrovascular dynamics.

一氧化氮扩散和降解的时空模式驱动紧急脑血管动力学。

  • 影响因子:4.35
  • DOI:10.1371/journal.pcbi.1008069
  • 作者列表:"Haselden WD","Kedarasetti RT","Drew PJ
  • 发表时间:2020-07-27
Abstract

:Nitric oxide (NO) is a gaseous signaling molecule that plays an important role in neurovascular coupling. NO produced by neurons diffuses into the smooth muscle surrounding cerebral arterioles, driving vasodilation. However, the rate of NO degradation in hemoglobin is orders of magnitude higher than in brain tissue, though how this might impact NO signaling dynamics is not completely understood. We used simulations to investigate how the spatial and temporal patterns of NO generation and degradation impacted dilation of a penetrating arteriole in cortex. We found that the spatial location of NO production and the size of the vessel both played an important role in determining its responsiveness to NO. The much higher rate of NO degradation and scavenging of NO in the blood relative to the tissue drove emergent vascular dynamics. Large vasodilation events could be followed by post-stimulus constrictions driven by the increased degradation of NO by the blood, and vasomotion-like 0.1-0.3 Hz oscillations could also be generated. We found that these dynamics could be enhanced by elevation of free hemoglobin in the plasma, which occurs in diseases such as malaria and sickle cell anemia, or following blood transfusions. Finally, we show that changes in blood flow during hypoxia or hyperoxia could be explained by altered NO degradation in the parenchyma. Our simulations suggest that many common vascular dynamics may be emergent phenomena generated by NO degradation by the blood or parenchyma.

摘要

: 一氧化氮 (NO) 是一种气体信号分子,在神经血管偶联中起重要作用。神经元产生的NO扩散到脑小动脉周围的平滑肌中,驱动血管舒张。然而,血红蛋白中NO降解的速率比脑组织中高几个数量级,尽管这可能如何影响NO信号传导动力学尚不完全清楚。我们使用模拟来研究NO生成和降解的空间和时间模式如何影响皮质中穿透性小动脉的扩张。我们发现NO产生的空间位置和容器的大小在决定其对NO的响应性方面都起着重要作用。血液中NO降解和清除相对于组织而言高得多的速率驱动了紧急的血管动力学。大的血管舒张事件之后可能是由血液增加的NO降解驱动的刺激后收缩,并且也可能产生类似血管运动的0.1-0.3Hz振荡。我们发现,这些动态可以通过血浆中游离血红蛋白的升高来增强,这发生在疟疾和镰状细胞性贫血等疾病中,或输血后。最后,我们发现缺氧或高氧期间血流的变化可以通过改变实质中的NO降解来解释。我们的模拟表明,许多常见的血管动力学可能是由血液或实质不降解产生的紧急现象。

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血红蛋白病方向

由于血红蛋白分子结构异常(异常血红蛋白病),或珠蛋白肽链合成速率异常(珠蛋白生成障碍性贫血,又称海洋性贫血)所引起的一组遗传性血液病。

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