Js. Fedan et al., Effect of ozone treatment on airway reactivity and epithelium-derived relaxing factor in guinea pigs, J PHARM EXP, 293(3), 2000, pp. 724-734
Citations number
54
Categorie Soggetti
Pharmacology & Toxicology
Journal title
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Ozone (O-3) is toxic to respiratory epithelium and causes airway inflammati
on and hyperreactivity. To evaluate the role of the epithelium in the devel
opment of hyperreactivity, we examined in guinea pigs the effects of inhale
d O-3 (3 ppm for 1 h; 0-24 h after exposure) on 1) reactivity to inhaled me
thacholine (MCh), 2) reactivity of the isolated, perfused trachea (IPT) to
MCh, 3) epithelium-derived relaxing factor (EpDRF)-mediated relaxations of
IPT induced by mucosal hyperosmolar solutions, 4) neurogenic contraction an
d relaxation responses, 5) transepithelial potential difference, and 6) mic
roscopic analysis of nitrotyrosine immunofluorescence, substance P fiber de
nsity, and tracheal morphology. At 0 h, O-3 caused hyperreactivity to inhal
ed MCh and mucosally but not serosally applied MCh in IPT (only in the pres
ence of the epithelium) and a decrease in transepithelial potential differe
nce. Inhibition of EpDRF-induced relaxation responses occurred at 2 h. All
of these changes returned to control by 12 to 18 h. O-3 had no effect on ne
urogenic responses. Nitrotyrosine immunofluorescence appeared in the trache
a at 0 h in detached epithelial cell ghosts and in intrapulmonary airways b
y 6 h. Substance P fiber density was elevated in smooth muscle at 0 and 18
h but not in epithelium or lamina propria of intrapulmonary and extrapulmon
ary bronchi. Loss of cilia and mucosubstances in the mucosa occurred at 0 h
; the epithelium became markedly attenuated over 12 to 24 h. A reversible i
ncrease in epithelial permeability and a decrease in EpDRF production may c
ontribute to O-3-induced hyperreactivity to MCh.