Time course of airway hyperresponsiveness and remodeling induced by
hyperoxia in rats.
Szarek, John L., Heather L. Ramsay, Anastasia Andringa, Marian L.
Miller.
Marshall University School of Medicine, Department of Pharmacology,
Huntington WV 25704-9388 and University of Cincinnati Medical Center,
Department of Environmental Health, Cincinnati OH 45267-0056
APStracts 2:0054L, 1995.
The purpose of this study was to answer two questions concerning
hyperoxia-induced airway hyperresponsiveness: 1) What is the time
course of the development of airway hyperresponsiveness? and, 2) What
is the relationship between the increase in responsiveness and smooth
muscle area?. Segments of intrapulmonary bronchi were isolated from
male Sprague-Dawley rats that had been exposed to 80-85% oxygen for a
period of 1, 3, 5, or 7 days and from aged-matched control animals
that breathed room air. Hyperoxia increased the sensitivity (log
concentration or frequency that elicited a half-maximal response) and
reactivity (maximum tension developed) of the airways to electrical
field stimulation (EFS) after 3, 5, and 7 days; sensitivity to
acetylcholine was not affected, but reactivity was increased after 7
days. Hyperoxia increased smooth muscle area beginning 5 days after
commencing the exposure. After normalizing tension responses to
smooth muscle area, reactivity of the airways to the stimuli was not
different between the two groups, but sensitivity to EFS was still
increased. The increase in reactivity observed after 5 and 7 days of
exposure can be explained by an increase in smooth muscle area that
occurred at these time points. The fact that the sensitivity of the
airways to EFS remained increased after normalization together with
the fact that the increase in airway responsiveness after 3 days of
exposure occurred at a time when smooth muscle area was not different
from control, suggest that mechanisms other than increased smooth
muscle area contribute to the development of hyperoxia-induced airway
hyperresponsiveness.
Received 14 November 1994; accepted in final form 4 April 1995.
APS Manuscript Number L328-4.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 25 April 1995.