Endothelin-1 contributes to antigen-induced airway hyperresponsiveness

K. Noguchi, K. Ishikawa, M. Yano, A. Ahmed, A. Cortes, W. M. Abraham

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Endothelin A (ET(A))-receptors mediate ET-1 contractions of ovine airway smooth muscle. Therefore, the ET(A)-receptor antagonist, BQ-123, was used to test the hypothesis that ET-1 contributes to antigen-induced airway responses in sheep allergic to Ascaris suum. We first established the protective effect of BQ-123 by demonstrating that BQ-123 given as an aerosol (0.3 or 1.0 mg/kg in 3 ml buffer) orby continuous intravenous infusion (100 μg · kg-1 · min-1) significantly blocked the bronchoconstriction to aerosolized ET-1 (0.2-200 μg/ml). To determine whether ET-1 contributed to antigen-induced airway responses, BQ-123 was given either as an intravenous infusion (100 μg · kg-1 · min-1) beginning 30 min before and continuing for 8 h after antigen challenge or as an aerosol (1 mg/kg in 3 ml buffer) 30 min before and 4, 8, and 24 h after antigen challenge. Neither treatment with intravenous infusion nor aerosolized BQ-123 blocked the immediate antigen-induced bronchoconstriction, but both treatments significantly reduced the late response (~50%). The treatments with aerosolized BQ-123 also blocked the antigen-induced airway hyperresponsiveness to inhaled carbachol seen 24 h after challenge. Subsequently, we found that sheep developed airway hyperresponsiveness to inhaled carbachol at 4 and 24 h after ET-1 challenge, an effect that was blocked by aerosolized BQ-123. We conclude that in allergic sheep 1) aerosolized ET-1 causes bronchoconstriction, in part, by stimulation of ET(A)-receptors, 2) ET-1 is released in the airways after antigen challenge, and 3) this peptide contributes to the severity of the allergic responses, probably by increasing airway smooth muscle responsiveness.

Original languageEnglish
Pages (from-to)700-705
Number of pages6
JournalJournal of Applied Physiology
Volume79
Issue number3
StatePublished - Jan 1 1995
Externally publishedYes

Fingerprint

Endothelin-1
Antigens
Bronchoconstriction
Sheep
Intravenous Infusions
Carbachol
Aerosols
Smooth Muscle
Buffers
Ascaris suum
Endothelins
cyclo(Trp-Asp-Pro-Val-Leu)
Therapeutics
Peptides

Keywords

  • animal model of asthma
  • bronchoconstriction
  • endothelin receptors

ASJC Scopus subject areas

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

Cite this

Noguchi, K., Ishikawa, K., Yano, M., Ahmed, A., Cortes, A., & Abraham, W. M. (1995). Endothelin-1 contributes to antigen-induced airway hyperresponsiveness. Journal of Applied Physiology, 79(3), 700-705.

Endothelin-1 contributes to antigen-induced airway hyperresponsiveness. / Noguchi, K.; Ishikawa, K.; Yano, M.; Ahmed, A.; Cortes, A.; Abraham, W. M.

In: Journal of Applied Physiology, Vol. 79, No. 3, 01.01.1995, p. 700-705.

Research output: Contribution to journalArticle

Noguchi, K, Ishikawa, K, Yano, M, Ahmed, A, Cortes, A & Abraham, WM 1995, 'Endothelin-1 contributes to antigen-induced airway hyperresponsiveness', Journal of Applied Physiology, vol. 79, no. 3, pp. 700-705.
Noguchi K, Ishikawa K, Yano M, Ahmed A, Cortes A, Abraham WM. Endothelin-1 contributes to antigen-induced airway hyperresponsiveness. Journal of Applied Physiology. 1995 Jan 1;79(3):700-705.
Noguchi, K. ; Ishikawa, K. ; Yano, M. ; Ahmed, A. ; Cortes, A. ; Abraham, W. M. / Endothelin-1 contributes to antigen-induced airway hyperresponsiveness. In: Journal of Applied Physiology. 1995 ; Vol. 79, No. 3. pp. 700-705.
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