Indomethacin inhibits the airway hyperresponsiveness but not the neutrophil influx induced by ozone in dogs

Journal Article · Wed Aug 01 04:00:00 EDT 1984 · Am. Rev. Respir. Dis.; (United States)

OSTI ID:6546336

O'Byrne, P M; Walters, E H; Aizawa, H; Fabbri, L M; Holtzman, M J; Nadel, J A

To determine whether oxygenation products of arachidonic acid may be involved in the airway hyperresponsiveness induced by ozone exposure, we studied whether ozone-induced hyperresponsiveness could be inhibited by the prostaglandin synthetase inhibitor, indomethacin, in dogs. Airway responsiveness was assessed with dose-response curves of acetylcholine aerosol versus pulmonary resistance in 2 sets of experiments: in one set, 5 dogs were given no indomethacin treatment and were studied both before and after ozone exposure (3.0 ppm, 2 h); in another set, the same dogs were studied before indomethacin treatment or ozone exposure and then during treatment (1 mg/kg every 12 h for 4 days) both before and after ozone exposure. On each occasion, we also determined the number of neutrophils in biopsies of the airway epithelium. When the dogs were not treated with indomethacin, ozone caused a marked increase in responsiveness to acetylcholine and a marked increase in the number of neutrophils in the airway epithelium. When the dogs were given indomethacin, responsiveness was no different during treatment than before treatment, but more importantly, responsiveness did not increase significantly after they were exposed to ozone. Interestingly, indomethacin treatment did not affect either the baseline number of epithelial neutrophils before ozone exposure or the increase in the number of neutrophils after exposure. The results suggest that oxygenation products of arachidonic acid that are sensitive to inhibition by indomethacin play a role in ozone-induced hyperresponsiveness without affecting the influx of neutrophils.

• Research Organization: Department of Medicine, University of California, San Francisco
• OSTI ID: 6546336
• Journal Information: Am. Rev. Respir. Dis.; (United States), Journal Name: Am. Rev. Respir. Dis.; (United States) Vol. 130:2; ISSN ARRDA
• Country of Publication: United States
• Language: English

Related Subjects

560305* -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
ANTIPYRETICS
BIOLOGICAL EFFECTS
BIOLOGICAL FUNCTIONS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
DOGS
DRUGS
FUNCTIONS
INHIBITION
LEUKOCYTES
MAMMALS
MATERIALS
NEUTROPHILS
OZONE
PROSTAGLANDINS
RESPONSE MODIFYING FACTORS
VERTEBRATES