Effect of thromboxane antagonists on ozone-induced airway responses in dogs.
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.
Jones
G L
GL
Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Lane
C G
CG
O'Byrne
P M
PM
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000109:Acetylcholine / Q000494:pharmacology; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D002227:Carbazoles / Q000008:administration & dosage / Q000494:pharmacology; D004285:Dogs; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology; D007262:Infusions, Intravenous; D010126:Ozone / Q000633:toxicity*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000008:administration & dosage / Q000494:pharmacology; D012130:Respiratory Hypersensitivity / Q000139:chemically induced* / Q000503:physiopathology; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors*
D002227:Carbazoles; D007211:Indoles; D011450:Prostaglandin Endoperoxides, Synthetic; C052517:L 655240; C061299:L 670596; D013928:Thromboxane A2; D010126:Ozone; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000109:Acetylcholine