title: Restrictive lung disease in rats exposed chronically to an urban profile of ozone.
abstract: The potential for irreversible lung impairment resulting from life-long ozone (O3) exposure remains uncertain. To address this question, young adult rats (male, F-344) were exposed to a simulated urban profile of O3 for 1, 3, 13, 52, or 78 wk, after which pulmonary function tests were performed. To assess reversibility of effects, cohorts from the 13-, 52-, and 78-wk groups were evaluated, respectively, after an additional 6, 27, and 17 wk of clean air. Static and dynamic lung properties were based on measurements of lung volume apportionment, respiratory system compliance (Crs), DLCO, multibreath N2 washout, and maximum expiratory flow-volume relationships. Electrocardiography was also performed in unanesthetized, restrained rats after 52 and 78 wk, as were determinations of wet and dry lung weights, lung collagen, and associated connective tissue crosslinks. Small (< 10%) but significant reductions in TLC and RV were noted after 13, 52, and 78 wk of O3 exposure. At 13 and 52 wk, N2 washout was enhanced, though at 78 wk it was similar to control. None of these changes appeared progressive with continued O3 exposure. Post exposure to clean air did not completely reverse the reduction in TLC. Additionally, Crs, though not affected during O3 exposure, decreased during the air recovery. No O3-related changes in collagen were apparent, however. Thus, near life-long exposure of F-344 rats to a worse-case, urban profile of O3 appears to have led to a functionally restrictive, i.e. "stiffened," lung without overt fibrosis. Furthermore, certain aspects of the O3-induced effect were not fully reversible.
authors.affiliation: Health Effects Research Laboratory, United States Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Costa
authors.forename: J S
authors.initials: JS
authors.lastname: Tepper
authors.forename: M A
authors.initials: MA
authors.lastname: Stevens
authors.forename: W P
authors.initials: WP
authors.lastname: Watkinson
authors.forename: D L
authors.initials: DL
authors.lastname: Doerfler
authors.forename: T R
authors.initials: TR
authors.lastname: Gelzleichter
authors.forename: J A
authors.initials: JA
authors.lastname: Last
mesh_terms: D000393:Air Pollutants / Q000009:adverse effects*; D000818:Animals; D003094:Collagen / Q000032:analysis; D004562:Electrocardiography; D006909:Hydroxyproline / Q000032:analysis; D008168:Lung / Q000737:chemistry / Q000503:physiopathology*; D008170:Lung Compliance; D008173:Lung Diseases, Obstructive / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D010126:Ozone / Q000009:adverse effects*; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors; D014109:Total Lung Capacity
chemical_list: D000393:Air Pollutants; D010126:Ozone; D003094:Collagen; D006909:Hydroxyproline