Mechanistic probing of gaseous signal transduction in microcirculation.
Mechanistic probing of gaseous signal transduction in microcirculation.
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DOI：
10.1089/152308603768295230
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发表时间：
2003-08
影响因子：
6.6
通讯作者：
M. Suematsu;Kazuhiro Suganuma;S. Kashiwagi
中科院分区：
文献类型：
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作者：
M. Suematsu;Kazuhiro Suganuma;S. Kashiwagi
一氧化氮（NO）和一氧化碳（CO）在体外作为可溶性鸟苷酸环化酶（sGC）的激活剂，后者作为肝脏的微血管松弛剂，肝脏是血红素氧合酶依赖性血红素降解和气体生成的主要器官。局部sGC活性的另一个重要决定因素是超氧阴离子，它可以清除NO和/或直接激活sGC。氧衍生物种的生物利用度及其功能结果的改变仍然未知，因为关于这些分子的数量和分布的信息几乎没有在体内检测过。我们最近的研究为多种气体在体内的复杂作用提供了证据。微循环NO的活体可视化显示，两种不同的来源，NO合成酶-1和-3，分别在小动脉和静脉壁上的NO维持中起主要作用。CO除了在肝脏微循环中有血管松弛作用外，还能在一氧化氮丰富的抵抗动脉中诱导血管收缩；血管平滑肌细胞中血红素氧化酶-1位点特异性过表达转基因小鼠的全身血压升高。这种气体之间的关系也已被证明机械生物探测sGC功能使用新的单克隆抗体。这篇文章的目的是提供一个进展的概述视觉评估的产生和接受的氧气衍生的气体介质在体内。
Nitric oxide (NO) and carbon monoxide (CO) serve as activators of soluble guanylate cyclase (sGC) in vitro, and the latter serves as a microvascular relaxant for the liver, a major organ for heme oxygenase-dependent heme degradation and gas generation. Another important determinant of local sGC activities is superoxide anion, which scavenges NO and/or activates sGC directly. Altered bioavailability of the oxygen-derived species and its functional outcomes remain unknown, because information on amounts and distribution of these molecules has hardly been examined in vivo. Our recent studies provided evidence for such complex actions of multiple gases in vivo. Intravital visualization of NO in microcirculation revealed that two distinct sources, NO synthase-1 and -3, play a major role in the maintenance of NO in arteriolar and venular walls, respectively. Besides its vasorelaxing action in the hepatic microcirculation, CO could induce vasoconstriction in the resistant artery where NO is abundantly available; systemic blood pressure was elevated in transgenic mice overexpressing heme oxygenase-1 site-specifically in vascular smooth muscle cells. Such a relationship between the gases has also been demonstrated by mechanistic bioprobing of sGC function using novel monoclonal antibodies. This article aims to provide an overview of advances in visual assessment of the generation and reception of oxygen-derived gaseous mediators in vivo.