Oleic acid induces pulmonary injury independent of eicosanoids in the isolated, perfused rabbit lung.
Intravenous injection of oleic acid (OA) induces acute, edematous lung injury resembling some of the features of adult respiratory distress syndrome. One class of inflammatory agents speculated to be mediators of acute lung injury are eicosanoids. We tested the hypothesis that 5-lipoxygenase and cyclooxygenase metabolites of arachidonic acid mediate the pulmonary injury induced by OA. OA (0.1 ml), injected as a bolus into the pulmonary artery (PA) of isolated, Krebs-perfused rabbit lungs, resulted in significant (P less than .05) increases in lung weight (an index of pulmonary edema), maximum airway pressure, perfusate immunoreactive (i) 6-keto PGF1a, and a significant, though minimal, increase in perfusate i-thromboxane B2. No measurable increases were recorded in PA pressure or perfusate i-leukotriene (LT) C4/D4. Neither pretreatment with the LTD4/E4 antagonist, LY171883 (10 microM), nor the 5-lipoxygenase/cyclooxygenase inhibitor, BW755C (100 microM), attenuated the pulmonary edema. However, BW755C abrogated the increase in i6-keto PGF1a. Additionally, administration of exogenous LTD4 (100 nM) into the perfusate produced only a minimal increase in lung weight in the isolated rabbit lungs (n = 4). These results demonstrate that 5-lipoxygenase and cyclooxygenase metabolites do not appear to mediate OA-induced injury in the isolated, Krebs-perfused rabbit lung.
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D066298:In Vitro Techniques; D008170:Lung Compliance / Q000187:drug effects; D008171:Lung Diseases / Q000139:chemically induced* / Q000378:metabolism; D008297:Male; D009829:Oleic Acids / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D011720:Pyrazoles / Q000494:pharmacology; D011817:Rabbits; D013189:SRS-A / Q000378:metabolism / Q000494:pharmacology; D013777:Tetrazoles / Q000494:pharmacology
D000098:Acetophenones; D001095:Arachidonic Acids; D005231:Fatty Acids, Unsaturated; D009829:Oleic Acids; D011720:Pyrazoles; D013189:SRS-A; D013777:Tetrazoles; D016718:Arachidonic Acid; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; C044660:LY 171883