Mechanisms of metabisulfite-induced bronchoconstriction: evidence for bradykinin B2-receptor stimulation.
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 micrograms; 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 less than 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 less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Mansour
E
E
Division of Pulmonary Diseases, University of Miami, Mount Sinai Medical Center, Miami Beach, Florida 33140.
Ahmed
A
A
Cortes
A
A
Caplan
J
J
Burch
R M
RM
Abraham
W M
WM
D000818:Animals; D001249:Asthma / Q000503:physiopathology; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology; D016084:Bronchoconstriction / Q000187:drug effects* / Q000502:physiology; D005520:Food Preservatives / Q000633:toxicity; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000502:physiology; D012756:Sheep; D013447:Sulfites / Q000633:toxicity*; D015244:Thiorphan / Q000494:pharmacology
D005520:Food Preservatives; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; D013447:Sulfites; C005200:sodium metabisulfite; D015244:Thiorphan; C053010:NPC 567; D001920:Bradykinin