Ito K, Sakamoto T, Hayashi Y, Morishita M, Shibata E, Sakai K, Takeuchi Y, Torii S
Department of Pediatrics, Nagoya University School of Medicine, Japan.
Eur J Pharmacol. 1996 Jul 4;307(3):291-8. doi: 10.1016/0014-2999(96)00285-3.
We have investigated the effects of CP-99,994 [(+)-(2s,3s)-3-(2-methoxybenzylamino)-2-phenylpiperidine], a tachykinin NK1 receptor antagonist, HOE 140 (D-Arg[Hyp3,Thi5,D-Tic7,Oic8]bradykinin), a bradykinin B2 receptor antagonist, and ketotifen (4-(1-methyl-4-piperidylidene)4 H-benzo[4,5]cycloheptal[1,2-b]thiophen-10(9H)-one hydrogen fumarate), a histamine H1 receptor antagonist with mast cell-stabilizing properties, on microvascular leakage induced by gaseous formaldehyde. Extravasation of Evans blue dye into airway tissues was used as an index of airway microvascular leakage. Leakage of dye in the trachea and main bronchi increased significantly in a concentration-dependent fashion after 10 min inhalation of formaldehyde (5-45 parts per million (ppm)). The airway response induced by 10 min inhalation of 15 ppm formaldehyde (trachea: 119.5 +/- 13.9 ng/mg, n = 7; main bronchi: 139.6 +/- 7.9 ng/mg, n = 7) was abolished by the administration of CP-99,994 (3 and 6 mg/kg i.v.), but not by the administration of HOE 140 (0.65 mg/kg i.v.) nor ketotifen (1 mg/kg i.v.). The increase in vascular permeability induced by formaldehyde in the rat airway was mediated predominantly by NK1 receptor stimulation. Activation of bradykinin receptors and mast cells did not appear to play an important role in this airway response.
我们研究了速激肽NK1受体拮抗剂CP-99,994 [（+）-（2s，3s）-3-（2-甲氧基苄基氨基）-2-苯基哌啶]、缓激肽B2受体拮抗剂HOE 140 [D-Arg（Hyp3，Thi5，D-Tic7，Oic8）缓激肽]和具有肥大细胞稳定特性的组胺H1受体拮抗剂酮替芬（4-（1-甲基-4-哌啶叉基）-4H-苯并[4,5]环庚并[1,2-b]噻吩-10（9H）-酮富马酸氢盐）对气态甲醛诱导的微血管渗漏的影响。伊文思蓝染料向气道组织的外渗被用作气道微血管渗漏的指标。吸入甲醛（5-45百万分之一（ppm））10分钟后，气管和主支气管中的染料渗漏以浓度依赖性方式显著增加。吸入15 ppm甲醛10分钟所诱导的气道反应（气管：119.5±13.9 ng/mg，n = 7；主支气管：139.6±7.9 ng/mg，n = 7）被静脉注射CP-99,994（3和6 mg/kg）消除，但未被静脉注射HOE 140（0.65 mg/kg）或酮替芬（1 mg/kg）消除。甲醛在大鼠气道中诱导的血管通透性增加主要由NK1受体刺激介导。缓激肽受体和肥大细胞的激活在这种气道反应中似乎未起重要作用。
