The role of mediators in the response of the canine peripheral lung to 1 ppm ozone

S. R. Kleeberger, J. Kolbe, N. F. Adkinson, S. P. Peters, E. Spannhake Wm.

Research output: Contribution to journalArticlepeer-review

Abstract

We tested the hypothesis that the in vivo response of the canine peripheral lung to 1 ppm ozone is mediated, in part, by histamine and cyclooxygenase and lipoxygenase products of arachidonic acid metabolism. Ozone was delivered for 5 min to lobar segments through a wedged bronchoscope and resulted in a mean (± 1 SE) increase in collateral system resistance (R(cs)) of 220.7 ± 13.8% immediately after exposure. Four 5-min exposures of ozone to the same segments over a 3-h period yielded reproducible R(cs) responses, i.e., tolerance to the exposure regimen was not exhibited. Analyses of bronchoalveolar lavage fluid obtained from the isolated segment 1 min after a single exposure to ozone indicated significant increases, compared with control, in mean concentrations of PGD2 (135.3 ± 33.3 pg/ml versus 47.8 ± 16.0; p < 0.025) and histamine (1.43 ± 0.19 ng/ml versus 1.18 ± 0.17; p < 0.05). Additionally, a molecule that exhibited high reactivity with LTB4 antibody was found in greater concentrations in ozone-exposed segments compared to controls (821.5 ± 206.7 pg/ml versus 437.5 ± 78.8; p < 0.05). In contrast, the concentrations of TXB2 was not significantly greater in ozone-exposed segments compared to controls (37.2 ± 6.6 pg/ml versus 33.7 ± 10.3; p < 0.05). Cyclooxygenase inhibition (indomethacin, 5 mg/kg, IV) significantly inhibited the R(cs) response by 32% (p < 0.05) and histamine H1-receptor blockade (chlorpheniramine maleate, 5 mg/kg, IV) reduced the response by 30% (p < 0.05). However, blockade of thromboxane synthetase (UK-37,248, 3 mg/kg, IV) had no significant effect on the ozone-induced response. These data indicate that the airways of the canine peripheral lung do not exhibit characteristics of tolerance to repeated 5-min exposures of 1 ppm ozone. The data also suggest that the bronchoconstrictive response to a single ozone exposure is mediated, in part, by histamine and selective metabolites of arachidonic acid.

Original languageEnglish (US)
Pages (from-to)321-325
Number of pages5
JournalAmerican Review of Respiratory Disease
Volume137
Issue number2
DOIs
StatePublished - 1988

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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