title: Effect of ozone treatment on airway reactivity and epithelium-derived relaxing factor in guinea pigs.
abstract: Ozone (O(3)) 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 O(3) (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, O(3) caused 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. O(3) 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 O(3)-induced hyperreactivity to MCh.
authors.affiliation: Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA. jsf2@cdc.gov
authors.forename: J S
authors.initials: JS
authors.lastname: Fedan
authors.forename: L L
authors.initials: LL
authors.lastname: Millecchia
authors.forename: R A
authors.initials: RA
authors.lastname: Johnston
authors.forename: A
authors.initials: A
authors.lastname: Rengasamy
authors.forename: A
authors.initials: A
authors.lastname: Hubbs
authors.forename: R D
authors.initials: RD
authors.lastname: Dey
authors.forename: L X
authors.initials: LX
authors.lastname: Yuan
authors.forename: D
authors.initials: D
authors.lastname: Watson
authors.forename: W T
authors.initials: WT
authors.lastname: Goldsmith
authors.forename: J S
authors.initials: JS
authors.lastname: Reynolds
authors.forename: L
authors.initials: L
authors.lastname: Orsini
authors.forename: J
authors.initials: J
authors.lastname: Dortch-Carnes
authors.forename: D
authors.initials: D
authors.lastname: Cutler
authors.forename: D G
authors.initials: DG
authors.lastname: Frazer
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000502:physiology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D010126:Ozone / Q000633:toxicity*; D010477:Perfusion; D014132:Trachea / Q000187:drug effects* / Q000473:pathology / Q000502:physiology
chemical_list: D016210:Methacholine Chloride; D009569:Nitric Oxide; D010126:Ozone