Integration of hypoxic dilation signaling pathways for skeletal muscle resistance arteries
Integration of hypoxic dilation signaling pathways for skeletal muscle resistance arteries
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DOI：
10.1152/ajpregu.00741.2001
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发表时间：
2002-08-01
影响因子：
2.8
通讯作者：
Lombard, JH
中科院分区：
文献类型：
--
作者：
Frisbee, JC;Maier, KG;Lombard, JH
通过测量增量缺氧后的扩张、血管平滑肌超极化和代谢产物的产生来确定介质对大鼠股薄肌阻力动脉缺氧扩张的贡献。一氧化氮（NO）合酶抑制消除反应轻度缺氧，而考克斯抑制受损反应更严重的缺氧77%。阻断20-羟基二十碳四烯酸（20-HETE）会损害对中度缺氧的反应。只有NO系统完整，反应维持轻度缺氧（88%正常）介导的K（Ca）通道。当只有考克斯途径是完整的，对中度至重度缺氧的反应在很大程度上保留（正常的79%）介导的K（ATP）通道。血管反应中度缺氧保留只有20-HETE系统完整介导的K（Ca）通道。NO的产生增加了5.6倍，轻度缺氧，更大的缺氧没有进一步的影响。随着缺氧的增加，20-HETE水平下降到对照值的40%。轻度缺氧时6-keto-PGF（1 α）水平无变化，但重度缺氧时升高4.6倍。这些结果表明，血管对进行性缺氧的反应性代表NO产生（轻度缺氧）、PGI（2）产生（重度缺氧）和20-HETE水平降低（中度缺氧）的整合。
Mediator contributions to hypoxic dilation of rat gracilis muscle resistance arteries were determined by measuring dilation, vascular smooth muscle hyperpolarization, and metabolite production after incremental hypoxia. Nitric oxide (NO) synthase inhibition abolished responses to mild hypoxia, whereas COX inhibition impaired responses to more severe hypoxia by 77%. Blocking 20-hydroxyeicosatetraenoic acid (20-HETE) impaired responses to moderate hypoxia. With only NO systems intact, responses were maintained with mild hypoxia (88% normal) mediated via K(Ca) channels. When only COX pathways were intact, responses to moderate-severe hypoxia were largely retained (79% of normal) mediated via K(ATP) channels. Vessel responses to moderate hypoxia were retained with only 20-HETE systems intact mediated via K(Ca) channels. NO production increased 5.6-fold with mild hypoxia; greater hypoxia was without further effect. With increased hypoxia, 20-HETE levels fell to 40% of control values. 6-keto-PGF(1alpha) levels were not altered with mild hypoxia, but increased 4.6-fold with severe hypoxia. These results suggest vascular reactivity to progressive hypoxia represents an integration of NO production (mild hypoxia), PGI(2) production (severe hypoxia), and reduced 20-HETE levels (moderate hypoxia).