Cerebral microvascular dilation during hypotension and decreased oxygen tension: a role for nNOS
Cerebral microvascular dilation during hypotension and decreased oxygen tension: a role for nNOS
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DOI：
10.1152/ajpheart.00190.2007
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发表时间：
2007-10-01
影响因子：
4.8
通讯作者：
Bohlen, H. Glenn
中科院分区：
文献类型：
--
作者：
Bauser-Heaton, Holly D.;Bohlen, H. Glenn
内皮细胞 (eNOS) 和神经元一氧化氮合酶 (nNOS) 是通过一氧化氮 (NO) 调节脑血管的重要贡献者。然而，大脑中一氧化氮的直接体内测量尚未用于剖析它们的相对作用，特别是与脑组织氧合相关的作用。我们发现，在体内，当浴氧张力或动脉压降低时，大鼠脑小动脉在小动脉周围氧张力（Po-2）降低的情况下增加了NO浓度（[NO]）和直径。使用这些高度选择性阻断 nNOS 的方案，我们测试了这样的假设：脑组织 nNOS 可以在休息时和血管周围氧张力降低期间（例如低血压或局部氧气供应减少期间）向小动脉捐赠 NO。浴操作导致的小动脉周围 Po-2 下降增加了 [NO] 和血管直径，这与低血压期间 Po-2 类似下降时的反应相当。为了确定nNOS是否提供了大部分血管壁NO，用高选择性抑制剂N-(4S)-(4-氨基-5-[氨基乙基]氨基戊基)-N'-硝基胍局部抑制nNOS。阻断后，静息 [NO]、Po-2 和直径下降，并且 Po-2 降低或低血压期间 [NO] 的增加完全消失。然而，nNOS 阻断后，侧支小动脉闭塞过程中血流介导的扩张确实保持完整，并且血管壁 [NO] 增加至与正常值相似的 80%。因此，在小动脉周围氧张力降低期间（例如低血压期间），nNOS 主要增加 NO，但 eNOS 是流动剪切机制中 NO 的主要来源。
Endothelial (eNOS) and neuronal nitric oxide synthase (nNOS) are implicated as important contributors to cerebral vascular regulation through nitric oxide (NO). However, direct in vivo measurements of NO in the brain have not been used to dissect their relative roles, particularly as related to oxygenation of brain tissue. We found that, in vivo, rat cerebral arterioles had increased NO concentration ([NO]) and diameter at reduced periarteriolar oxygen tension (Po-2) when either bath oxygen tension or arterial pressure was decreased. Using these protocols with highly selective blockade of nNOS, we tested the hypothesis that brain tissue nNOS could donate NO to the arterioles at rest and during periods of reduced perivascular oxygen tension, such as during hypotension or reduced local availability of oxygen. The decline in periarteriolar Po-2 by bath manipulation increased [NO] and vessel diameter comparable with responses at similarly decreased Po-2 during hypotension. To determine whether the nNOS provided much of the vascular wall NO, nNOS was locally suppressed with the highly selective inhibitor N-(4S)-(4-amino-5-[aminoethyl]aminopentyl)-N '-nitroguanidine. After blockade, resting [NO], Po-2, and diameters decreased, and the increase in [NO] during reduced Po-2 or hypotension was completely absent. However, flow-mediated dilation during occlusion of a collateral arteriole did remain intact after nNOS blockade and the vessel wall [NO] increased to similar to 80% of normal. Therefore, nNOS predominantly increased NO during decreased periarteriolar oxygen tension, such as that during hypotension, but eNOS was the dominant source of NO for flow shear mechanisms.