The role of endogenous endothelin (receptor) in injured lung.

结果表明：白细胞毒素（Lx）可使离体大鼠肺组织和肺灌流液中内皮素1（ET 1）含量增加，肺湿重（WLW）和肺灌流液中LDH活性增加。ET_A受体拮抗剂BQ 123可抑制ET_1、WLW和灌流液LDH活性的升高。ET 1和Lx在其本身不增加WLW的浓度下的组合显著增加WLW以及灌流液LDH活性。BQ 123预处理可抑制ET_1和ET_B受体激动剂LX. IRL 1620联合作用引起的肺水肿，在离体大鼠肺动脉环中，Lx引起内皮素依赖性血管舒张，而BQ 123或TAK 044的存在显著抑制了Lx引起的血管舒张ET_（B）受体拮抗剂BQ 788或ET_（B）受体拮抗剂RES 7011对ET非特异性受体拮抗剂bnt的抑制作用。在体外培养的人肺内皮细胞中，Lx可促进细胞内O_2 ~-的产生，而ET_1和ET_3则无此作用，由此我们认为，Lx是一种肺损伤物质，低剂量时可引起血管舒张，高剂量时可引起血管舒张，而低剂量时则无此作用。Lx通过激活ET_A受体引起肺水肿性损伤，我们进一步推测Lx本身并不刺激ET_A受体，一种受体或刺激ET产生的信使。

The Summary of our reasearh results are :In isolated perfused rat lungs leukotoxin (Lx) increased content of endothelin 1 (ET1) in lung tissue and in the perfusate in association with comparable increase in wet lung weight (WLW) and perfusate LDH activity. BQ123, an ET_A receptor antagonist, suppressed such increase of ET1, WLW and perfusate LDH activity. The combinetion of ET1 and Lx, at concentrations that by themselves did not increase WLW,significantly increased WLW as well as the perfusate LDH activity. Pretreatment with BQ123 suppressed the edematous lung injury generated by the combination of ET1 and Lx.IRL1620, an ET_B receptor agonist, exerted rapid increase in perfusion pressure and edematous lung injury.In isolated rat pulmonary arterial rings Lx caused endothelin-dependent vasodilation which was significantly suppressed in the presenceof BQ123 or TAK044 (ET nonspecific receptor antagonist) bnt not in the presence of BQ788 (ET_B receptor antagonist) or RES7011 (ET_B receptor antagonist). In human cultured pulmonary endothelial cells Lx enhanced intracellular O_2^- production but either ET1 or ET3 did not show such an effect.From these experimental results we concluded that Lx, a lung injury producing substance with low dose caused vasodilation and with its higher dose, caused edematous lung injury via activation of ET_A receptor.We further speculate the possibitity that Lx itselt stimulate ET_A receptor or stimulate the production of ET which act as a messenger.