Epithelium Derived Rclaxing Factor-Its Role in Airway Hyperreactivity-

推测气道上皮细胞通过释放上皮源性松弛因子(EPDRF)来调节气道张力。为了研究这种可能性，我们试图回答以下问题1。EPDRF真的存在吗？：通过应用Ilhan和Sahin开发的同轴生物测定系统，我们证实了豚鼠呼吸道上皮细胞释放了平滑肌松弛因子。有人批评说，在这个系统中看到的松弛是由于气管管腔狭窄导致的组织缺氧造成的。我们改进了同轴生物测定系统，通过在内插入钢圈来消除气管内径的减小。利用该系统，我们观察了乙酰胆碱刺激上皮完整的气管时，兔主动脉条的松弛。根据这些结果，我们得出结论，在这个系统中看到的松弛不是由于组织的缺氧，而是由于松弛因子从气管上皮释放。此外，我们还检测了阿托品、哌仑西平和4-DAMP对乙酰胆碱…的影响。NE诱导更多的EPDRF释放。阿托品和4-DAMP对松弛的抑制作用约为哌仑西平的50倍。根据这些结果，我们得出结论，上皮性M受体的刺激可能在诱导EPDRF2的释放中起作用。什么是EPDRF？：我们研究了一氧化氮是豚鼠呼吸道EPDRF的可能性。我们首先研究了一氧化氮能否松弛离体气管条，然后研究了血管系统中已知的内皮依赖性松弛抑制剂--血红蛋白亚甲蓝和N^G-单甲基-L-精氨酸(L-NMMA)对高渗刺激诱导的气管条上皮依赖松弛的影响。全气管与血红蛋白预先孵育可显著抑制渗透压诱导的EPDR，但亚甲蓝和L-NMMA预先孵育不能抑制该作用。高渗刺激诱导EPDR后，Hb进入上皮侧可逆转松弛，但亚甲蓝和L-NMMA不能逆转松弛。这些结果表明，尽管EPDR和血管EDR有一定的药理相似之处，一氧化氮可以松弛气道平滑肌，但一氧化氮不参与渗透诱导的EPDR。较少

It is speculated that airway epithelium regulate airway tone by releasing epithelium derived relaxing factor (EpDRF). To examine this possibility, we tried to answer the following questions.1. Does EpDRF really exist? : By applying co-axial bioassay system developed by Ilhan and Sahin, we confirmed that guinea-pig airway epithelium releases smooth muscle relaxant factor. There was a criticism that the relaxation seen in this system is caused by tissue hypoxia due to the narrowing of tracheal lumen. We modified co-axial bioassay system to eliminate reduction of tracheal diameter by inserting steel coil inside. With this system, we observed relaxation of rabbit aortic strip when the epithelium intact trachea was stimulated with acetylcholine. From these results we concluded that relaxation seen in this system is not due to tissue hypoxia but due to the release of relaxing factor from tracheal epithelium. In addition, we examined effects of atropine, pirenzepine, and 4-DAMP on acetylcholi … More ne induced EpDRF release. Atropine and 4-DAMP were about 50 times more potent in suppressing relaxation than pirenzepine. From these results, we concluded that epithelial muscarinic-M3 receptor stimulation may be responsiblc in inducing the release of EpDRF.2. What is EpDRF? : We examined the possibility that nitric oxide is one of EpDRF in guinea-pig airways. We studied first, whether nitric oxide could relax isolated tracheal strips, and then examined the effects of known inhibitors of endothelium-dependent relaxation (EDR) in the vascular system, hemoglobin methylene blue, and N^G-monomethyl-L-arginine (L-NMMA), on epithelium-dependent relaxation (EpDR) induced by hyperosmotic stimuli in perfused whole tracheal preparations, Nitric oxide produced concentration-dependent and complete relaxation of epithelium-denuded tracheal strips. Preincubation of the whole trachea with hemoglobin significantly inhibited osmotic-induced EpDR, but preincubation with methylene blue and L-NMMA did not. Hemoglobin introduced into the epithelial side after EpDR induced by hyperosmotic stimuli reversed relaxation, but methylene blue and L-NMMA did not. These results suggest that although EpDR and vascular EDR have some pharmacological similarities and nitric oxide can relax airway smooth muscle, nitric oxide is not responsible for osmotic-induced EpDR. Less