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 journalArticle

34 Citations (Scopus)

Abstract

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
Pages (from-to)557-564
Number of pages8
JournalJournal of Allergy and Clinical Immunology
Volume87
Issue number2
StatePublished - Dec 1 1991
Externally publishedYes

Fingerprint

Neurokinin A
Bradykinin
Substance P
Sheep
Bronchoconstriction
Carbachol
Thiorphan
Nedocromil
Bronchoconstrictor Agents
Chlorpheniramine
Ascaris suum
Neprilysin
Lung
Airway Resistance
Protease Inhibitors
Neuropeptides
Atropine
Cholinergic Agents
Inhalation
Reflex

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Abraham, W. M., Ahmed, A., Cortes, A., Soler, M., Farmer, S. G., Baugh, L. E., & Harbeson, S. L. (1991). Airway effects of inhaled bradykinin, substance P, and neurokinin A in sheep. Journal of Allergy and Clinical Immunology, 87(2), 557-564.

Airway effects of inhaled bradykinin, substance P, and neurokinin A in sheep. / Abraham, W. M.; Ahmed, A.; Cortes, A.; Soler, M.; Farmer, S. G.; Baugh, L. E.; Harbeson, S. L.

In: Journal of Allergy and Clinical Immunology, Vol. 87, No. 2, 01.12.1991, p. 557-564.

Research output: Contribution to journalArticle

Abraham, WM, Ahmed, A, Cortes, A, Soler, M, Farmer, SG, Baugh, LE & Harbeson, SL 1991, 'Airway effects of inhaled bradykinin, substance P, and neurokinin A in sheep', Journal of Allergy and Clinical Immunology, vol. 87, no. 2, pp. 557-564.
Abraham WM, Ahmed A, Cortes A, Soler M, Farmer SG, Baugh LE et al. Airway effects of inhaled bradykinin, substance P, and neurokinin A in sheep. Journal of Allergy and Clinical Immunology. 1991 Dec 1;87(2):557-564.
Abraham, W. M. ; Ahmed, A. ; Cortes, A. ; Soler, M. ; Farmer, S. G. ; Baugh, L. E. ; Harbeson, S. L. / Airway effects of inhaled bradykinin, substance P, and neurokinin A in sheep. In: Journal of Allergy and Clinical Immunology. 1991 ; Vol. 87, No. 2. pp. 557-564.
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