RT Journal Article
SR Electronic
T1 Effect of Ozone Treatment on Airway Reactivity and Epithelium-Derived Relaxing Factor in Guinea Pigs
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 724
OP 734
VO 293
IS 3
A1 Jeffrey S. Fedan
A1 Lyndell L. Millecchia
A1 Richard A. Johnston
A1 Appavoo Rengasamy
A1 Ann Hubbs
A1 Richard D. Dey
A1 Long-Xing Yuan
A1 David Watson
A1 W. Travis Goldsmith
A1 Jeffrey S. Reynolds
A1 Larry Orsini
A1 Juanita Dortch-Carnes
A1 Deborah Cutler
A1 David G. Frazer
YR 2000
UL http://jpet.aspetjournals.org/content/293/3/724.abstract
AB Ozone (O3) is toxic to respiratory epithelium and causes airway inflammation and hyperreactivity. To evaluate the role of the epithelium in the development of hyperreactivity, we examined in guinea pigs the effects of inhaled O3 (3 ppm for 1 h; 0–24 h after exposure) on 1) reactivity to inhaled methacholine (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 and relaxation responses, 5) transepithelial potential difference, and 6) microscopic analysis of nitrotyrosine immunofluorescence, substance P fiber density, and tracheal morphology. At 0 h, O3caused hyperreactivity to inhaled MCh and mucosally but not serosally applied MCh in IPT (only in the presence of the epithelium) and a decrease in transepithelial potential difference. Inhibition of EpDRF-induced relaxation responses occurred at 2 h. All of these changes returned to control by 12 to 18 h. O3 had no effect on neurogenic responses. Nitrotyrosine immunofluorescence appeared in the trachea at 0 h in detached epithelial cell ghosts and in intrapulmonary airways by 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 extrapulmonary 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 increase in epithelial permeability and a decrease in EpDRF production may contribute to O3-induced hyperreactivity to MCh. U.S. Government