AJP - Lung Cellular and Molecular Physiology, Vol 269, Issue 2 227-L233, Copyright © 1995 by American Physiological Society
Time course of airway hyperresponsiveness and remodeling induced by hyperoxia in rats
J. L. Szarek, H. L. Ramsay, A. Andringa and M. L. Miller
Department of Pharmacology, Marshall University School of Medicine, Huntington, West Virginia 25704-9388, USA.
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? 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% O2 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, suggests that mechanisms
other than increased smooth muscle area contribute to the development of
hyperoxia-induced airway hyperresponsiveness.
