The Role of Mediators in the Response of the Canine Peripheral Lung to 1 ppm Ozone

Publisher Website
Google Scholar
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 (Rcs) of 220.7 .+-. 13.8% immediately after exposure. Four 5-min exposure of ozone to the same segments over a 3-h period yielded reproducible Rcs 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 concentration of TxB2 was not significantly greater in ozone-exposured 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 Rcs 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 characteristic 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 selectie metabolites of arachidonic acid.