Acute neurogenic airway plasma exudation and edema induced by inhaled wood smoke in guinea pigs: Role of tachykinins and hydroxyl radical

You Shuei Lin, Yu Ru Kou

研究成果: 雜誌貢獻文章同行評審

20 引文 斯高帕斯(Scopus)

摘要

We studied the mechanisms underlying the wood smoke-induced acute airway injury in 120 anaesthetized guinea pigs. Five minutes after airway exposure, various doses of wood smoke produced a dose-dependent increase in Evans blue dye contents at all airway levels measured. Additionally, inhaled wood smoke produced submucosal edema of the trachea and bronchus, and peribronchial edema. These acute airway responses were nearly abolished by pretreatment with CP-96,345 alone [a tachykinin NK1 receptor antagonist; (2S,3S)-cis-2-(diphenylmethyl)-N-((2-methoxyphenyl)-methyl)-1-azabicyclo(2.2.2.)-octan-3-amine] or with a combination of CP-96,345 and dimethylthiourea (a hydroxyl radical scavenger), and were attenuated by pretreatment with dimethylthiourea alone, yet were not affected by pretreatment with SR-48,968 [a tachykinin NK2 receptor antagonist; (S)-N-methyl-N(4-(4-acetylamino-4-phenylpiperidino)-2-(3,4-dichlorophenyl)-butyl)benzamide], with a combination of CP-96,344 and SR-48,965 (inactive enantiomers), with MK-886 [a leukotriene biosynthesis inhibitor; L-663,536(3-(1-(4-chlorobenzyl)-3-t-butyl-thio-5-isopropylindol-2-yl)-2,2-dimethylpropanoic acid], with indomethacin (a cyclooxygenase inhibitor), or with N(G)-nitro-L-arginine methyl ester (a nitric oxide (NO) synthase inhibitor). The activity of airway neutral endopeptidase (an enzyme for tachykinin degradation) was not influenced by wood smoke at 5-min post-exposure. We conclude that both endogenous tachykinins and hydroxyl radical play an important role in producing smoke-induced acute airway plasma exudation and airway edema in guinea pigs. The contribution of tachykinins to these neurogenic responses is mediated via the activation of tachykinin NK1 receptors and partly via a hydroxyl radical mechanism, and is not associated with inactivation of neutral endopeptidase. Copyright (C) 2000 Elsevier Science B.V.

原文英語
頁(從 - 到)139-148
頁數10
期刊European Journal of Pharmacology
394
發行號1
DOIs
出版狀態已發佈 - 四月 7 2000

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

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