Effect of thromboxane antagonists on ozone-induced airway responses in dogs
- McMaster Univ., 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.
- OSTI ID:
- 6065522
- Journal Information:
- Journal of Applied Physiology (1985); (USA), Vol. 69:3; ISSN 8750-7587
- Country of Publication:
- United States
- Language:
- English
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ACETYLCHOLINE
BIOCHEMICAL REACTION KINETICS
OZONE
TOXICITY
PROSTAGLANDINS
BIOLOGICAL FUNCTIONS
DOGS
ENZYME INHIBITORS
INHALATION
RECEPTORS
RESPIRATORY SYSTEM DISEASES
AMINES
AMMONIUM COMPOUNDS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
DISEASES
DRUGS
ESTERS
FUNCTIONS
INTAKE
KINETICS
MAMMALS
MEMBRANE PROTEINS
NEUROREGULATORS
ORGANIC COMPOUNDS
PARASYMPATHOMIMETICS
PROTEINS
QUATERNARY COMPOUNDS
REACTION KINETICS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology