Airway effects of inhaled bradykinin, substance P, and neurokinin A in sheep

W. M. Abraham, A. Ahmed, A. Cortes, M. Soler, S. G. Farmer, L. E. Baugh, S. L. Harbeson

Research output: Contribution to journalArticlepeer-review

34 Scopus citations


The effects of inhaled bradykinin (BK), substance P (SP), and neurokinin A (NKA) on pulmonary resistance and airway responsiveness to carbachol were studied in conscious allergic sheep. Inhaled BK (20 breaths, 0.1 to 5.0 mg · ml-1) caused dose-dependent increases in pulmonary resistance. Neither inhaled SP nor NKA (20 breaths, 0.1 to 1.0 mg · ml-1) produced significant bronchoconstriction in allergic sheep. However, the response to SP could be enhanced (p < 0.05) by pretreatment with the neutral endopeptidase inhibitor, thiorphan (40 breaths, 1 mg · ml-1). Sheep that were allergic to Ascaris suum antigen were 5.9 times (p < 0.05) more sensitive to the constrictor effects of BK than nonallergic sheep. BK-induced bronchoconstriction was blocked in a dose-dependent fashion by the BK β2-receptor antagonist, NPC 567 (D-arginine{hydroxyproline3,D-phenylalanine7}BK). Atropine (0.2 mg · kg-1, intravenously) and nedocromil sodium (1 mg · kg-1 in 3 ml of saline, aerosolized) significantly inhibited the BK-induced bronchoconstriction by 97% and 43%, respectively. Chlorpheniramine (2 mg · kg-1, intravenously) had no effect. NKA caused a transient increase in airway responsiveness in allergic sheep, producing a mean 1.9-fold leftward shift in dose-response curves to aerosolized carbachol (p < 0.05). This hyperresponsiveness was not evident 24 hours after NKA challenge. Neither SP nor BK changed airway responsiveness. Thus, in allergic sheep, inhaled BK caused a more pronounced bronchoconstriction than that observed in nonallergic sheep. The bronchoconstriction was blocked by a BK-receptor antagonist and appeared to be partially mediated via cholinergic reflexes. The sensory neuropeptides, unlike BK, were not potent bronchoconstrictors when they were administered by inhalation, but NKA may play a role in modulating airway responsiveness.

Original languageEnglish (US)
Pages (from-to)557-564
Number of pages8
JournalThe Journal of Allergy and Clinical Immunology
Issue number2
StatePublished - Feb 1991
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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