title: Ventilatory responses to ozone are reduced in immature rats.
abstract: During ozone (O(3)) exposure, adult rats decrease their minute ventilation (VE). To determine whether such changes are also observed in immature animals, Sprague-Dawley rats, aged 2, 4, 6, 8, or 12 wk, were exposed to O(3) (2 ppm) in nose-only-exposure plethysmographs. Baseline VE normalized for body weight decreased with age from 2.1 +/- 0.1 ml. min(-1). g(-1) in 2-wk-old rats to 0. 72 +/- 0.03 ml. min(-1). g(-1) in 12-wk-old rats, consistent with the higher metabolic rates of younger animals. In adult (8- and 12-wk-old) rats, O(3) caused 40-50% decreases in VE that occurred primarily as the result of a decrease in tidal volume. In 6-wk-old rats, O(3)-induced changes in VE were significantly less, and in 2- and 4-wk-old rats, no significant changes in VE were observed during O(3) exposure. The increased baseline VE and the smaller decrements in VE induced by O(3) in the immature rats imply that their delivered dose of O(3) is much higher than in adult rats. To determine whether these differences in O(3) dose influence the extent of injury, we measured bronchoalveolar lavage protein concentrations. The magnitude of the changes in bronchoalveolar lavage induced by O(3) was significantly greater in 2- than in 8-wk-old rats (267 +/- 47 vs. 165 +/- 22%, respectively, P < 0.05). O(3) exposure also caused a significant increase in PGE(2) in 2-wk-old but not in adult rats. The results indicate that the ventilatory response to O(3) is absent in 2-wk-old rats and that lack of this response, in conjunction with a greater specific ventilation, leads to greater lung injury.
authors.affiliation: Physiology Program, Harvard School of Public Health, Boston, MA 02115, USA. sshore@hsph.harvard.edu
authors.forename: S A
authors.initials: SA
authors.lastname: Shore
authors.forename: J H
authors.initials: JH
authors.lastname: Abraham
authors.forename: I N
authors.initials: IN
authors.lastname: Schwartzman
authors.forename: G G
authors.initials: GG
authors.lastname: Murthy
authors.forename: J D
authors.initials: JD
authors.lastname: Laporte
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000502:physiology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002452:Cell Count; D015232:Dinoprostone / Q000032:analysis; D005260:Female; D007958:Leukocyte Count; D008297:Male; D009504:Neutrophils / Q000166:cytology; D010126:Ozone / Q000494:pharmacology*; D011506:Proteins / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration / Q000187:drug effects*
chemical_list: D011506:Proteins; D010126:Ozone; D015232:Dinoprostone