Mechanisms of metabisulfite-induced bronchoconstriction: Evidence for bradykinin B2-receptor stimulation

E. Mansour, A. Ahmed, A. Cortes, J. Caplan, R. M. Burch, W. M. Abraham

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26 Scopus citations

Abstract

Sodium metabisulfite (MBS) is a food preservative that can trigger bronchoconstriction in asthmatic subjects. Previous studies designed to identify the mechanisms involved in this response have yielded conflicting results. We noted certain similarities between the pharmacology of MBS- induced airway responses and those elicited by bradykinin (BK), another provocating agent in asthmatic subjects. Therefore we used allergic sheep to determine whether MBS-induced bronchoconstriction 1) had a pharmacology similar to that previously seen with BK in this model, including protection by a BK B2-receptor antagonist, NPC-567, and 2) was associated with increased concentrations of immunoreactive kinins in bronchoalveolar lavage. We measured specific lung resistance before and immediately after inhaled buffer and increasing concentrations of MBS (30 breaths of 25, 50, and 100 mg/ml) and calculated the concentration producing 100% increase in specific lung resistance over baseline (PC100). In seven sheep, geometric mean control PC100 was 33.1 mg/ml. Pretreatment with either the anticholinergic agent ipratropium bromide (180 μg; PC100 87.1 mg/ml) or the antiasthma drug nedocromil sodium (1 mg/kg aerosol; PC100 97.7 mg/ml) blocked the MBS-induced bronchoconstriction (P < 0.05), whereas the histamine H1- receptor antagonist chlorpheniramine (2 mg/kg iv) was ineffective. Furthermore the MBS-induced bronchoconstriction was not affected by the neutral endopeptidase inhibitor thiorphan (40 breaths of a 1 mg/ml solution) or the angiotensin-converting enzyme inhibitor enalaprilat (2.5 mg aerosol). In six sheep the MBS-induced bronchoconstriction was completely blocked by NPC-567 (20 breaths, 5 mg/ml aerosol): after treatment with NPC-567 mean PC100 was 100 mg/ml compared with 57.5 mg/ml in the control trial (P < 0.05). Accordingly, the MBS-induced bronchial response was associated with a ninefold increase in bronchoalveolar lavage immunoreactive-kinins. Thus, in allergic sheep, inhaled MBS causes bronchoconstriction that does not involve histamine release but, rather, appears to involve stimulation of BK B2- receptors with subsequent activation of cholinergic mechanisms.

Original languageEnglish (US)
Pages (from-to)1831-1837
Number of pages7
JournalJournal of applied physiology
Volume72
Issue number5
StatePublished - Jan 1 1992

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Keywords

  • angiotensin-converting enzyme inhibitor
  • asthma
  • bradykinin
  • bradykinin antagonist
  • neutral endopeptidase inhibitor
  • sheep

ASJC Scopus subject areas

  • Endocrinology
  • Physiology
  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation

Cite this

Mansour, E., Ahmed, A., Cortes, A., Caplan, J., Burch, R. M., & Abraham, W. M. (1992). Mechanisms of metabisulfite-induced bronchoconstriction: Evidence for bradykinin B2-receptor stimulation. Journal of applied physiology, 72(5), 1831-1837.