Journal of Applied Physiology, Vol 69, Issue 3 880-884, Copyright © 1990 by American Physiological Society
Effect of thromboxane antagonists on ozone-induced airway responses in dogs
G. L. Jones, C. G. Lane and P. M. O'Byrne
Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Airway hyperresponsiveness after inhaled ozone in dogs may occur as a
result of thromboxane release in the airway. In this study, two thromboxane
receptor antagonists, L-655,240 and L-670,596, were used in doses that
inhibit the response to an inhaled thromboxane mimetic, U-46619, to
determine further the role of thromboxane in ozone-induced airway
hyperresponsiveness. Dogs were studied on 2 days separated by 1 wk. On each
day, the dogs inhaled ozone (3 ppm) for 30 min. On one randomly assigned
day, 10 dogs received an infusion of L-655,240 (5 mg.kg-1.h-1) and 5 dogs
received an infusion of L-670,596 (1 mg.kg-1.h-1); on the other day dogs
received a control infusion. Airway responses to doubling doses of
acetylcholine were measured before and after inhalation of ozone and were
expressed as the concentration of acetylcholine giving a rise in resistance
of 5 cmH2O.l-1.s from baseline (acetylcholine provocation concentration).
The development of airway hyperresponsiveness after ozone was not inhibited
by the thromboxane antagonists. The mean log difference in the
acetylcholine provocative concentration before and after ozone on the
L-655,240 treatment day was 0.62 +/- 0.12 (SE) and on the control day was
0.71 +/- 0.12 (P = 0.48); on the L-670,596 treatment day the mean log
difference was 0.68 +/- 0.15 (SE) and on the control day it was 0.75 +/-
0.19 (P = 0.45). These results do not support an important role for
thromboxane in causing ozone-induced airway hyperresponsiveness.
