Mechanism underlying ozone-induced in vitro hyperresponsiveness in canine bronchi.
The effects of ozone inhalation on the contractility of canine bronchi and the mechanisms underlying any changes observed were investigated. Ozone inhalation caused acetylcholine airway hyperresponsiveness in vivo. Isolated segments of bronchi (3rd to 5th order) from dogs previously exposed to ozone (or normal air) were mounted in organ baths. Contractile responses to electrical field stimulation (FS) in all tissues decreased in magnitude over time (measured at 10, 120, 210, and 300 min after mounting tissues in the organ baths); responses to 150 mM KCl did not show such a progressive decrease. Ozone inhalation produced a dramatic enhancement of FS responses, a smaller enhancement of responses to carbachol (10(-8)-10(-4) M), and no change in responses to KCl (150 mM). In the presence of 10(-5) M indomethacin, all responses were enhanced and tended to increase in magnitude over time; indomethacin also abolished the differences in responsiveness between the control and ozone-exposed tissues. In the presence of the thromboxane receptor antagonist L-670,596 (10(-8) M), the magnitudes of all FS responses showed a progressive decrease over time while KCl responses did not; again, the differences in FS responses between control and ozone-exposed tissues were decreased or made insignificant. In conclusion, ozone produced airway hyperresponsiveness in vivo and hyperresponsiveness in canine bronchi in vitro via decreased prejunctional and postjunctional inhibition (likely mediated by prostaglandin E2) and increased prejunctional excitation mediated by thromboxane A2. However, direct measurements of mediator release should be carried out to reach a firm conclusion.
Janssen
L J
LJ
Department of Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
O'Byrne
P M
PM
Daniel
E E
EE
D000280:Administration, Inhalation; D000818:Animals; D001980:Bronchi / Q000294:innervation / Q000473:pathology; D001982:Bronchial Diseases / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D016084:Bronchoconstriction / Q000187:drug effects; D004285:Dogs; D004558:Electric Stimulation; D007213:Indomethacin / Q000494:pharmacology; D009130:Muscle, Smooth / Q000294:innervation / Q000473:pathology; D009469:Neuromuscular Junction / Q000503:physiopathology; D009929:Organ Size; D010126:Ozone / Q000494:pharmacology; D012130:Respiratory Hypersensitivity / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors
D013928:Thromboxane A2; D010126:Ozone; D007213:Indomethacin