Cyclooxygenase inhibitors increase canine tracheal muscle response to parasympathetic stimuli in situ.
Cyclooxygenase inhibitors increase canine tracheal muscle response to parasympathetic stimuli in situ.
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环氧合酶抑制剂可增加犬气管肌肉对副交感神经原位刺激的反应。
DOI：
10.1152/jappl.1990.68.6.2597
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
McClure,CL
中科院分区：
文献类型：
--
作者：
Bethel,RA;McClure,CL
为了确定环氧合酶抑制剂是否改变副交感神经对气道平滑肌的原位控制，我们用静脉注射吲哚美辛、甲氨蝶呤或生理盐水对麻醉犬进行预处理，并测量电刺激迷走神经时气管肌肉的等长收缩。吲哚美辛和甲氰氨酯增加气道平滑肌对副交感神经刺激的反应。在随后确定环氧合酶抑制剂作用部位的实验中，我们发现吲哚美辛不会改变气管肌肉对动脉内乙酰胆碱（一种毒蕈碱激动剂）的反应，但会增加对动脉内碘化二甲基哌嗪（一种烟碱激动剂）的反应。此外，在用吲哚美辛和BW 755 C（组合的环氧合酶-脂氧合酶抑制剂）的组合预处理后对副交感神经刺激的反应与单独使用吲哚美辛或甲氨蝶呤后的反应没有显著差异。我们的结论是，环氧合酶抑制剂增加的敏感性，气管平滑肌的收缩反应，副交感神经刺激，他们发挥其作用的节后副交感神经元，他们的效果是prejunctional。该效应似乎继发于环氧合酶产物的减少，而不是脂氧合酶产物的增加。这些结果表明，内源性环氧合酶产物可能调节副交感神经控制的气道平滑肌在体内。它们可能与气道高反应性的基础机制有关，炎症介质通过这些机制调节气道反应性，非甾体抗炎药通过这些机制在某些哮喘患者中诱导严重的支气管收缩反应。
To determine whether cyclooxygenase inhibitors alter parasympathetic control of airway smooth muscle in situ, we pretreated anesthetized dogs with intravenous indomethacin, meclofenamate, or normal saline and measured the isometric contraction of tracheal muscle in response to electrical stimulation of the vagus nerves. Indomethacin and meclofenamate increase the response of airway smooth muscle to parasympathetic stimulation. In subsequent experiments to determine the site of action of cyclooxygenase inhibitors, we found that indomethacin does not alter the response of tracheal muscle to intra-arterial acetylcholine (a muscarinic agonist) but does augment the response to intra-arterial dimethylpiperaziniumiodide (a nicotinic agonist). Moreover, the response to parasympathetic stimulation after pretreatment with a combination of indomethacin and BW755C (a combined cyclooxygenase-lipoxygenase inhibitor) does not differ significantly from the response after indomethacin or meclofenamate alone. We conclude that cyclooxygenase inhibitors increase the sensitivity of the contractile response of tracheal smooth muscle to parasympathetic stimulation, that they exert their effect on the postganglionic parasympathetic neuron, and that their effect is prejunctional. The effect appears secondary to a decrease in cyclooxygenase products rather than to an increase in lipoxygenase products. These findings suggest that endogenous cyclooxygenase products may modulate parasympathetic control of airway smooth muscle in vivo. They may relate to the mechanisms that underlie airway hyperresponsiveness, by which mediators of inflammation modulate airway responsiveness and by which nonsteroidal anti-inflammatory drugs induce severe bronchoconstrictor responses in some persons who have asthma.