Significance of thromboxane generation in ozone-induced airway hyperresponsiveness in dogs

Research output: Contribution to journalArticle

  • Authors:
  • H. Aizawa
  • K. F. Chung
  • G. D. Leikauf
  • I. Ueki
  • R. A. Bethel
  • And 3 others
  • External authors:
  • P. M. O'Byrne
  • T. Hirose
  • J. A. Nadel


To determine whether thromboxane A2 may be involved in ozone (O3)-induced airway hyperresponsiveness, we studied the effect of a thromboxane synthase inhibitor (OKY-046, 100 μg·kg-1·min-1 iv) in five dogs exposed to O3. Airway responsiveness was assessed by determining the provocative concentration of acetylcholine aerosol that increased total pulmonary resistance by 5 cmH2O·l-1·s. O3 (3 ppm) increased airway responsiveness as demonstrated by a decrease in acetylcholine provocative concentration from 2.42 (geometric SEM=1.64) to 0.14 mg/ml (geometric SEM=1.30). OKY-046 significantly inhibited this effect without altering pre-O3 responsiveness or the O3-induced increase in neutrophils and airway epithelial cells in bronchoalveolar lavage fluid. To further examine the role of thromboxane A2, we studied the effect of a thromboxane A2 mimetic, U-46619, on airway responsiveness in five additional dogs. U-46619 in subthreshold doses (i.e., sufficient to increase base-line pulmonary resistance) caused a fourfold increase in airway responsiveness to acetylcholine. Subthreshold doses of histamine had no effect. These results suggest that thromboxane A2 may be an important mediator of O3-induced airway hyperresponsiveness.

Bibliographical metadata

Original languageEnglish
Pages (from-to)1918-1923
Number of pages6
JournalJournal of Applied Physiology
Issue number6
Publication statusPublished - 1 Dec 1985