Effects of inhibitors of EDRF and EDHF on vasoreactivity of perfused rat lungs.
Effects of inhibitors of EDRF and EDHF on vasoreactivity of perfused rat lungs.
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EDRF 和 EDHF 抑制剂对灌注大鼠肺血管反应性的影响。
DOI：
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发表时间：
1991
影响因子：
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通讯作者：
I. Mcmurtry
中科院分区：
文献类型：
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作者：
K. Hasunuma;Takashi Yamaguchi;D. Rodman;R. O'Brien;I. Mcmurtry
最近的研究表明，离体大鼠肺动脉的内皮释放两种不同的因子，内皮源性舒张因子（EDRF）和超极化因子（EDHF），它们参与组胺和乙酰胆碱诱导的舒张。有证据表明灌注肺中存在 EDRF 血管反应性，但 EDHF（通过激活膜 K+ 通道使血管平滑肌超极化）的作用尚未报道。我们使用 EDRF 抑制剂、20 µM 血红蛋白、200 µM NG-单甲基-L-精氨酸和 2 mM L-刀豆氨酸、K+ 通道非选择性阻断剂、10 mM 四乙铵 (TEA) 和 ATP 敏感 K+ 通道抑制剂 20 µM 格列本脲，比较 EDRF 和 EDHF 在甲氯芬那酯处理、盐溶液灌注的大鼠肺的血管调节。三种 EDRF 抑制剂对基线灌注压影响很小或没有影响，但每种抑制剂都会增强对气道缺氧的峰值升压反应。两者均不能抑制 5 µM 组胺的肺血管舒张作用。 TEA（而非格列本脲）增加了基线压力并增强了峰值缺氧反应。两种 K+ 通道阻滞剂（但 EDRF 抑制剂除外）也通过降低自发血管舒张率来延长缺氧反应。 TEA（而非格列本脲）抑制组胺血管舒张。这些结果表明 EDRF 和 EDHF 在控制大鼠肺血管反应性中的作用。 EDRF 显然与常氧肺的低血管张力无关，并且不介导组胺的血管舒张，但它确实调节缺氧升压反应。 EDHF 的确切作用尚不确定，但它也可能调节缺氧血管收缩并介导至少部分组胺血管舒张。
Recent studies indicate that the endothelium of isolated rat pulmonary arteries releases two different factors, endothelium-derived relaxing factor (EDRF) and hyperpolarizing factor (EDHF), which participate in histamine- and acetylcholine-induced relaxation. There is evidence for EDRF vasoreactivity in perfused lungs, but a role for EDHF, which hyperpolarizes vascular smooth muscle by activating membrane K+ channels, has not been reported. We used the inhibitors of EDRF, 20 microM hemoglobin, 200 microM NG-mono-methyl-L-arginine, and 2 mM L-canavanine, the nonselective blocker of K+ channels, 10 mM tetraethylammonium (TEA), and the inhibitor of ATP-sensitive K+ channels, 20 microM glibenclamide, to compare the roles of EDRF and EDHF in the vasoregulation of meclofenamate-treated, salt solution-perfused rat lungs. The three EDRF inhibitors had little or no effect on baseline perfusion pressure, but each potentiated the peak pressor response to airway hypoxia. Neither of them inhibited the pulmonary vasodilation to 5 microM histamine. TEA, but not glibenclamide, increased baseline pressure and potentiated the peak hypoxic response. Both K+ channel blockers, but not the EDRF inhibitors, also prolonged the hypoxic response by reducing the rate of spontaneous vasodilation. TEA, but not glibenclamide, inhibited histamine vasodilation. These results suggest roles for both EDRF and EDHF in the control of rat pulmonary vascular reactivity. EDRF is apparently not responsible for the low vascular tone of the normoxic lung and does not mediate the vasodilation to histamine, but it does modulate the hypoxic pressor response. The exact role of EDHF is uncertain, but it may also modulate hypoxic vasoconstriction and mediate at least part of the histamine vasodilation.