Osmotic regulation of airway reactivity by epithelium.
Osmotic regulation of airway reactivity by epithelium.
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发表时间：
1999-05
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通讯作者：
J. Fedan;Long-Xing Yuan;V. Chang;J. Viola;D. Cutler;Loreen L. Pettit
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作者：
J. Fedan;Long-Xing Yuan;V. Chang;J. Viola;D. Cutler;Loreen L. Pettit
吸入非等渗溶液可引起哮喘气道的肺阻塞。我们评估了呼吸道上皮参与气道对非等渗溶液反应的假设，使用豚鼠分离的、灌注的气管制剂来限制施用于气道粘膜（腔内）或浆膜（腔外）表面的药物。在甲基苯甲胺收缩的气管中，腔内等量施用NaCl或KCl可引起松弛，这种松弛不受环加氧酶抑制剂吲哚美辛的影响，但通过去除上皮和Na+和Cl-通道阻滞剂可以减弱。Na+-K+- 2cl -共转运体和一氧化氮合酶阻滞剂对松弛产生轻微抑制，而Na+，K+泵抑制产生小的增强。腔内高渗透性KCl和NaCl抑制腔内或腔外应用甲胆碱引起的收缩，以及电场刺激（+/-吲哚美辛）引起的神经源性胆碱能收缩。外施NaCl和KCl引起上皮依赖性松弛（KCl随后是收缩）。与高渗透压的作用相反，腔内低渗透压引起罂粟碱抑制性收缩（+/-上皮）。这些结果表明，上皮是一种渗透传感器，通过释放上皮源性松弛因子，通过调节平滑肌反应性和兴奋性神经传递来调节气道直径。
Inhalation of nonisotonic solutions can elicit pulmonary obstruction in asthmatic airways. We evaluated the hypothesis that the respiratory epithelium is involved in responses of the airways to nonisotonic solutions using the guinea pig isolated, perfused trachea preparation to restrict applied agents to the mucosal (intraluminal) or serosal (extraluminal) surface of the airway. In methacholine-contracted tracheae, intraluminally applied NaCl or KCl equipotently caused relaxation that was unaffected by the cyclo-oxygenase inhibitor, indomethacin, but was attenuated by removal of the epithelium and Na+ and Cl- channel blockers. Na+-K+-2Cl- cotransporter and nitric oxide synthase blockers caused a slight inhibition of relaxation, whereas Na+,K+-pump inhibition produced a small potentiation. Intraluminal hyperosmolar KCl and NaCl inhibited contractions in response to intra- or extraluminally applied methacholine, as well as neurogenic cholinergic contractions elicited with electric field stimulation (+/- indomethacin). Extraluminally applied NaCl and KCl elicited epithelium-dependent relaxation (which for KCl was followed by contraction). In contrast to the effects of hyperosmolarity, intraluminal hypo-osmolarity caused papaverine-inhibitable contractions (+/- epithelium). These findings suggest that the epithelium is an osmotic sensor which, through the release of epithelium-derived relaxing factor, can regulate airway diameter by modulating smooth muscle responsiveness and excitatory neurotransmission.