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

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)139-148
Number of pages10
JournalEuropean Journal of Pharmacology
Volume394
Issue number1
DOIs
Publication statusPublished - Apr 7 2000

Keywords

  • CP-96,345
  • Tachykinin NK receptor
  • Tachykinin NK receptor
  • Wood smoke

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

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