Metabolites of arachidonic acid in experimental lung vascular injury.
Several metabolites of arachidonic acid have potent effects on lung vascular and airway function. Some of these substances are released from the lungs when the lungs are diffusely injured. For example, after infusion of Escherichia coli endotoxin into unanesthetized sheep, high concentrations of both cyclooxygenase and lipoxygenase products appear in lung lymph. These products appear in sequential waves: thromboxane B2 peaks early, coincident with peak pulmonary artery pressure and maximum changes in lung mechanics; a prostacyclin metabolite peaks slightly later as pulmonary artery pressure begins to fall; both 5- and 12-lipoxygenation products peak even later, as lung vascular permeability begins to increase. Cyclooxygenase inhibitors attenuate the early changes in lung mechanics and pulmonary artery pressure caused by endotoxemia in sheep but do not prevent the later increase in lung vascular permeability. High doses of corticosteroids attenuate both the late phase increase in lung lymph lipoxygenation products and the increase in vascular permeability. These unequivocal associations between lung injury and endogenous generation of biologically active arachidonate metabolites suggest but do not prove that these substances mediate the pathophysiology.
D000818:Animals; D001095:Arachidonic Acids / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D004731:Endotoxins / Q000633:toxicity; D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008168:Lung / Q000098:blood supply / Q000503:physiopathology; D055370:Lung Injury; D008196:Lymph / Q000378:metabolism / Q000503:physiopathology; D008469:Meclofenamic Acid / Q000494:pharmacology; D008775:Methylprednisolone / Q000494:pharmacology; D012756:Sheep
D001095:Arachidonic Acids; D004731:Endotoxins; D007093:Imidazoles; D008469:Meclofenamic Acid; C029899:imidazole; D007052:Ibuprofen; D008775:Methylprednisolone; D007213:Indomethacin