The role of mediators in the response of the canine peripheral lung to 1 ppm ozone.
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 exposures 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 less than 0.025) and histamine (1.43 +/- 0.19 ng/ml versus 1.18 +/- 0.17; p less than 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 less than 0.05). In contrast, the concentration 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 less than 0.05). Cyclooxygenase inhibition (indomethacin, 5 mg/kg, IV) significantly inhibited the Rcs response by 32% (p less than 0.05) and histamine H1-receptor blockade (chlorpheniramine maleate, 5 mg/kg, IV) reduced the response by 30% (p less than 0.05). However, blockade of thromboxane synthetase (UK-37,248, 3 mg/kg, IV) had no significant effect on the ozone-induced response.(ABSTRACT TRUNCATED AT 250 WORDS)
Kleeberger
S R
SR
Department of Environmental Health Sciences and Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205.
Kolbe
J
J
Adkinson
N F
NF
Peters
S P
SP
Spannhake
E W
EW
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001980:Bronchi / Q000187:drug effects / Q000502:physiology; D001992:Bronchoalveolar Lavage Fluid / Q000032:analysis; D016861:Cyclooxygenase Inhibitors; D004285:Dogs; D006632:Histamine / Q000502:physiology*; D007975:Leukotriene B4 / Q000032:analysis; D008084:Lipoxygenase / Q000502:physiology*; D008168:Lung / Q000187:drug effects* / Q000502:physiology; D008297:Male; D010126:Ozone / Q000633:toxicity*; D015230:Prostaglandin D2; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D011457:Prostaglandins D / Q000032:analysis; D013929:Thromboxane B2 / Q000032:analysis; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D011457:Prostaglandins D; D007975:Leukotriene B4; D016718:Arachidonic Acid; D013929:Thromboxane B2; D010126:Ozone; D006632:Histamine; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D013930:Thromboxane-A Synthase; D015230:Prostaglandin D2