Document Detail

Alleviation of wood smoke-induced lung injury by tachykinin receptor antagonist and hydroxyl radical scavenger in guinea pigs.
MedLine Citation:
PMID:  11502280     Owner:  NLM     Status:  MEDLINE    
We recently reported that wood smoke inhalation initially (within 5 min) causes airway injury and subsequently produces both airway and parenchymal injury after a delay (within 2 h). In this study, we investigated the mediator mechanisms of this delayed smoke-induced lung injury in 126 anesthetized and artificially ventilated guinea pigs who received challenges of either air or 40 tidal breaths of wood smoke. Two hours after inhalation, wood smoke produced various injurious responses, including increases in alveolar-capillary permeability, microvascular permeabilities, and histological injury scores, in airway and parenchymal tissues. Pre-treatment given before smoke challenge with CP-96,345 [a tachykinin NK1 receptor antagonist; (2S,3S)-cis-2-(diphenylmethyl)-N-((2-methoxyphenyl)-methyl)-1-aza bicyclo(2.2.2.)-octan-3-amine], dimethylthiourea (a hydroxyl radical scavenger), or a combination of these two drugs largely alleviated both the airway and parenchymal responses, whereas pre-treatment with SR-48,968 [a tachykinin NK2 receptor antagonist; (S)-N-methyl-N(4-(4-acetylamino-4-phenylpiperidino)-2-(3,4-dichlorophenyl)-butyl)benzamide] or a combination of CP-96,344 and SR-48,965 (inactive enantiomers) failed to do so. Post-treatment given at 5 min after smoke challenge with CP-96,345 or dimethylthiourea significantly alleviated the parenchymal responses, while having no effect on the airway responses. Pre-treatment with dimethylthiourea prevented the smoke-induced reduction in airway neutral endopeptidase activity (an enzyme for tachykinin degradation). We concluded that (1) tachykinins and hydroxyl radical play important roles in producing smoke-induced delayed lung injury in guinea pigs, and both may be involved in the spread of injury from the airways to the pulmonary parenchyma, and (2) the contribution of tachykinins is mediated via the activation of tachykinin NK1 receptors, and is associated with the hydroxyl radical-induced inactivation of airway neutral endopeptidase.
Y S Lin; C Y Ho; G J Tang; Y R Kou
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of pharmacology     Volume:  425     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2001 Aug 
Date Detail:
Created Date:  2001-08-14     Completed Date:  2001-09-20     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  141-8     Citation Subset:  IM    
Institute of Physiology, School of Medicine and Life Science, National Yang-Ming University, Taipei, Taiwan.
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MeSH Terms
Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
Biphenyl Compounds / therapeutic use*
Disease Models, Animal
Free Radical Scavengers / therapeutic use*
Guinea Pigs
Hydroxyl Radical / metabolism
Neprilysin / antagonists & inhibitors,  metabolism
Receptors, Tachykinin / antagonists & inhibitors,  metabolism*
Respiratory Distress Syndrome, Adult / chemically induced,  drug therapy*,  enzymology,  metabolism
Tachykinins / metabolism*
Thiourea / analogs & derivatives,  therapeutic use
Reg. No./Substance:
0/Anti-Inflammatory Agents, Non-Steroidal; 0/Biphenyl Compounds; 0/Free Radical Scavengers; 0/Receptors, Tachykinin; 0/Tachykinins; 132746-60-2/CP 96345; 3352-57-6/Hydroxyl Radical; 61805-96-7/1,3-dimethylthiourea; 62-56-6/Thiourea; EC

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