Contributions of endothelial and neuronal nitric oxide synthases to cerebrovascular responses to hyperoxia
Contributions of endothelial and neuronal nitric oxide synthases to cerebrovascular responses to hyperoxia
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DOI：
10.1097/01.wcb.0000089601.87125.e4
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发表时间：
2003-10-01
影响因子：
6.3
通讯作者：
Huang, PL
中科院分区：
文献类型：
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作者：
Atochin, DN;Demchenko, IT;Huang, PL
高氧导致CBF短暂下降，随后上升。这些效应的介质尚不清楚。我们使用缺乏内皮型或神经型一氧化氮合酶（NOS）亚型的小鼠（eNOS（-/-）和nNOS（-/-）小鼠）来研究NOS亚型在介导高氧引起的脑血管张力变化中的作用。静息局部脑血流量（rCBF）在野生型（WT）、eNOS（-/-）小鼠和nNOS（-/-）小鼠之间没有差异。eNOS（-/-）小鼠表现出对N-G-硝基-L-精氨酸甲酯（L-NAME）、PAPA NONOate、乙酰胆碱（Ach）和SOD 1的脑血管反应性降低。WT和nNOS（-/-）小鼠对5 ATA高压氧（HBO 2）的反应显示rCBF在30分钟内下降，但eNOS（-/-）小鼠没有。HBO 2处理60分钟后，WT小鼠rCBF增加幅度大于eNOS（-/-）或nNOS（-/-）小鼠。WT和eNOS（-/-）小鼠在HBO 2 30分钟内的脑NO代谢物（NOx）减少，但45分钟后，NOx升高至对照水平以上，而nNOS（-/-）小鼠则没有变化。WT和eNOS（-/-）小鼠在HBO 2期间脑3 NT增加，但nNOS（-/-）小鼠没有变化。这些结果表明，调制eNOS衍生的NO的HBO 2是负责早期血管收缩反应，而晚期HBO 2诱导的血管舒张依赖于eNOS和nNOS。
Hyperoxia causes a transient decrease in CBF, followed by a later rise. The mediators of these effects are not known. We used mice lacking endothelial or neuronal nitric oxide synthase (NOS) isoforms (eNOS(-/-) and nNOS(-/-) mice) to study the roles of the NOS isoforms in mediating changes in cerebral vascular tone in response to hyperoxia. Resting regional cerebral blood flow (rCBF) did not differ between wild type (WT), eNOS(-/-) mice, and nNOS(-/-) mice. eNOS(-/-) mice showed decreased cerebrovascular reactivities to N-G-nitro-L-arginine methyl ester (L-NAME), PAPA NONOate, acetylcholine (Ach), and SOD1. In response to hyperbaric oxygen (HBO2) at 5 ATA, WT and nNOS(-/-) mice showed decreases in rCBF over 30 minutes, but eNOS(-/-) mice did not. After 60 minutes HBO2, rCBF increased more in WT mice than in eNOS(-/-) or nNOS(-/-) mice. Brain NO-metabolites (NOx) decreased in WT and eNOS(-/-) mice within 30 minutes of HBO2, but after 45 minutes, NOx rose above control levels, whereas they did not change in nNOS(-/-) mice. Brain 3NT increased during HBO2 in WT and eNOS(-/-) but did not change in nNOS(-/-) mice. These results suggest that modulation of eNOS-derived NO by HBO2 is responsible for the early vasoconstriction responses, whereas late HBO2-induced vasodilation depends upon both eNOS and nNOS.