Neurogenic plasma leakage in mouse airways

Peter Baluk, Gavin Thurston, Thomas J. Murphy, Nigel W. Bunnett, Donald M. Mcdonald

Research output: Contribution to journalArticle

Abstract

1. This study sought to determine whether neurogenic inflammation occurs in the airways by examining the effects of capsaicin or substance P on microvascular plasma leakage in the trachea and lungs of male pathogen-free C57BL/6 mice. 2. Single bolus intravenous injections of capsaicin (0.5 and 1 μmol kg-1, i.v.) or substance P (1, 10 and 37 nmol kg-1, i.v.) failed to induce significant leakage in the trachea, assessed as extravasation of Evans blue dye, but did induce leakage in the urinary bladder and skin. 3. Pretreatment with captopril (2.5 mg kg-1, i.v.), a selective inhibitor of angiotensin converting enzyme (ACE), either alone or in combination with phosphoramidon (2.5 mg kg-1, i.v.), a selective inhibitor of neutral endopeptidase (NEP), increased baseline leakage of Evans blue in the absence of any exogenous inflammatory mediator. The increase was reversed by the bradykinin B2 receptor antagonist Hoe 140 (0.1 mg kg-1, i.v.). 4. After pretreatment with phosphoramidon and captopril, capsaicin increased the Evans blue leakage above the baseline in the trachea, but not in the lung. This increase was reversed by the tachykinin (NK1) receptor antagonist SR 140333 (0.7 mg kg-1, i.v.), but not by the NK2 receptor antagonist SR 48968 (1 mg kg-1, i.v.). 5. Experiments using Monastral blue pigment as a tracer localized the leakage to postcapillary venules in the trachea and intrapulmonary bronchi, although the labelled vessels were less numerous in mice than in comparably treated rats. Blood vessels of the pulmonary circulation were not labelled. 6. We conclude that neurogenic inflammation can occur in airways of pathogen-free mice, but only after the inhibition of enzymes that normally degrade inflammatory peptides. Neurogenic inflammation does not involve the pulmonary microvasculature.

Original languageEnglish (US)
Pages (from-to)522-528
Number of pages7
JournalBritish Journal of Pharmacology
Volume126
Issue number2
DOIs
StatePublished - 1999

Keywords

  • Capsaicin
  • Captopril
  • Endothelial cells
  • Hoe 140
  • Phosphoramidon
  • Plasma leakage
  • SR 140333
  • SR 48968
  • Substance P
  • Vascular permeability

ASJC Scopus subject areas

  • Pharmacology

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  • Cite this

    Baluk, P., Thurston, G., Murphy, T. J., Bunnett, N. W., & Mcdonald, D. M. (1999). Neurogenic plasma leakage in mouse airways. British Journal of Pharmacology, 126(2), 522-528. https://doi.org/10.1038/sj.bjp.0702323