Human and rat airway smooth muscle responsiveness after ozone exposure in vitro.
We previously reported that NO2 and acrolein administered ex vivo to the lung altered the subsequent responsiveness of airway smooth muscle. The aim of this study was to determine the dose-response relationship for O3 in both human isolated bronchi and rat tracheae and to investigate the mechanisms underlying O3-induced airway responsiveness. Exposure to 1 ppm O3 for 15 min significantly increased the maximal response to carbachol of rat tracheal rings to 149.6 +/- 5.4% of the reference response to acetylcholine (ACh) compared with that of unexposed rings (131.3 +/- 2.4%, n = 6, P < 0.05). The change in maximal airway responsiveness to carbachol, when plotted against the product of exposure concentration and exposure time to O3, a surrogate for the dose, formed a bell-shaped curve. The peak of this dose-response curve was shifted to the right for human bronchi (50 ppm x min, n = 5) compared with that of rat tracheae (15 ppm x min, n = 6). In the rat trachea, responses to KCl were not altered by O3, whereas those to 5-hydroxytryptamine hydrochloride (5-HT) were significantly increased. Finally, in the absence of external Ca2+, O3 exposure still potentiated the maximal response to carbachol from 73.6 +/- 13.9 to 137.0 +/- 6.0% and that to 5-HT from 21.5 +/- 5.5 to 38.7 +/- 2.2% of the reference ACh response. These results indicate that O3 alters the subsequent in vitro airway responsiveness depending on 1) the dose, 2) the nature of the agonist, and 3) the species investigated. Because in vitro exposure to O3 increases responses to agonists that release intracellular Ca2+ and since this effect is maintained in Ca(2+)-free solution, the mechanism of O3-induced increase in airway smooth muscle responsiveness is likely to involve an enhancement in intracellular Ca2+ release.
Roux
E
E
Laboratoire de Physiologie Cellulaire Respiratoire, Université Bordeaux 2, France.
Guibert
C
C
Crevel
H
H
Savineau
J P
JP
Marthan
R
R
D000403:Airway Resistance / Q000187:drug effects*; D000818:Animals; D002118:Calcium / Q000502:physiology; D002217:Carbachol; D006801:Humans; D066298:In Vitro Techniques; D009130:Muscle, Smooth; D010126:Ozone / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D014132:Trachea / Q000187:drug effects / Q000502:physiology
D010126:Ozone; D002217:Carbachol; D002118:Calcium