Human and rat airway smooth muscle responsiveness after ozone
exposure in vitro.
Roux, Etienne, Christelle Guibert, Huguette Crevel, Jean-Pierre
Savineau, and Roger Marthan.
LABORATOIRE DE PHYSIOLOGIE CELLULAIRE RESPIRATOIRE -
UNIVERSIT[acute]e BORDEAUX 2, 33076 BORDEAUX CEDEX - FRANCE
APStracts 3:0100L, 1996.
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 to 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 (C) and
exposure time (T) 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 to 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 5HT 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 5HT 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. Since in vitro exposure to O3 increases responses to
agonists that release intracellular Ca2+ and since this effect is
maintained in Ca2+-free solution, the mechanism of O3-induced
increase in airway smooth muscle responsiveness in likely to involve
an enhancement in intracellular Ca2+ release.
Received 21 February 1996; accepted in final form 5 June 1996.
APS Manuscript Number L56-6.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 28 June 96