Commentaries on viewpoint: A paradigm shift for local blood flow regulation.
Commentaries on viewpoint: A paradigm shift for local blood flow regulation.
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观点评论：局部血流调节的范式转变。
DOI：
10.1152/japplphysiol.01360.2013
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发表时间：
2014
期刊：
影响因子：
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通讯作者：
Secomb,TimothyW
中科院分区：
文献类型：
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作者：
Buerk,DonaldG;Hirai,DanielM;Roseguini,BrunoT;Silva,BrunoM;Vagula,MaryC;Roy,TuhinK;Secomb,TimothyW
致编辑：Golub 和 Pittman (5) 假设，NAD (P) H 氧化酶产生的 O2 与线粒体 O2 的变化协同作用，在调节局部血流方面的作用很可能是 NO 途径令人着迷的复杂生物学的一个促成因素。氧气产生的延迟增加可能解释了反应性充血后经常观察到的血流量下冲。然而，将主要作用归因于单一机制过于简单化，正如我在 NO (1) 的评论论文中所认识到的那样，并在显示 O2(4) 清除 NO 的理论效应的早期数学模型中证明了这一点，并且在更新的评论 (2, 3) 中更全面地讨论了需要纳入 NO 生物转运数学模型的发展。在我看来，NO 通量的单一“设定点”不太可能存在，因为许多其他机制（其中一些依赖于 NO 而另一些则不依赖）可以显着改变与 NO 相关的反馈信号。 NO 的间接影响，例如通过各种信号蛋白的亚硝基化，也可以改变血流调节的敏感性。此外，由于已知 NO 会抑制线粒体呼吸链，并且文献中有证据表明细胞色素氧化酶既可以充当 O2 还原酶，也可以充当 NO 氧化酶，因此在不知道代谢抑制和净 ATP 产生程度的情况下，很难精确定义组织缺氧。调节血流和新陈代谢的综合动态模型仍有待开发和实验验证。
TO THE EDITOR: The proposed role of O2 produced by NAD (P) H oxidase acting in concert with changes in mitochondrial O2 on regulating local blood flow hypothesized by Golub and Pittman (5) could very well be a contributing factor in the fascinatingly complex biology of the NO pathway. A delayed increase in O2 production might explain the frequently observed undershoot in blood flow after reactive hyperemia. However, it is far too simplistic to attribute a major role to a single mechanism, as recognized in my review paper on NO (1) and demonstrated in an earlier mathematical model showing theoretical effects of NO scavenging by O2(4) and more thoroughly discussed in updated reviews (2, 3) for developments that need to be incorporated into mathematical models for NO biotransport. In my view, it is unlikely that a single “set point” for NO flux exists, because many other mechanisms, some of which are dependent on NO whereas others are not, can significantly modify NO-related feedback signaling. Indirect effects of NO, for example by nitrosylation of various signaling proteins, can also alter the sensitivity of blood flow regulation. Furthermore, because NO is known to inhibit the mitochondrial respiration chain and there is evidence in the literature that cytochrome oxidase can act either as an O2 reductase or a NO oxidase, it is difficult to precisely define tissue hypoxia without knowing the extent of metabolic inhibition and net ATP production. A comprehensive, dynamic model for regulating blood flow and metabolism remains to be developed and experimentally verified.