Metabolism of Endogenous Arachidonic Acid by Isolated Lungs of Neonatal and Adult Rabbits Stimulated with Calcium Ionophore: Effect of Hypoxia

Abstract

We have determined the effect of hypoxia on arachidonic acid metabolism by rabbit lungs stimulated with calcium ionophore A23187. Isolated lungs of neonatal and adult rabbits were perfused during normoxia (p O₂ > 100 torr) or hypoxia (p O₂ < 40 torr) and arachidonic acid metabolism stimulated by the addition of A23187 (5 μM) to the perfusate. Cyclooxygenase metabolites PGE₂, TxA₂, and PGI₂ were measured by radioimmunoassay and lipoxygenase metabolites LTB₄, LTC₄, LTD₄, and LTE₄ by HPLC. During normoxia, neonatal lungs synthesized the three cyclooxygenase metabolites that we measured in similar amounts. LTC₄ constituted 56% of the leukotrienes produced. Hypoxia caused a 100% increase in the amount of PGI₂ synthesized by neonatal lungs; however, total TxB₂ and PGE₂ production was not altered significantly. LTC₄ production decreased significantly during hypoxia, whereas LTE₄ production increased. Adult lungs synthesized significantly lower amounts of both cyclooxygenase and 5-lipoxygenase products than neonatal lungs. During normoxia, PGE₂ was measured in highest amount in adult lungs. Similar to the neonatal lungs, LTC₄ was the predominant leukotriene (56%) measured. During hypoxia, there was a 100% increase in PGI₂ production by adult lungs, as was observed in neonatal lungs. There was also a small but significant increase in PGE₂ production, with no change in TxA₂ production. ETC₄ production also decreased, but there was a marked increase in synthesis of LTB₄ by adult lungs. Our data demonstrate that hypoxia alters the profile of arachidonic acid metabolites produced by rabbit lungs stimulated with A23187. Also, the age of the rabbit significantly affects both the amount and profile of metabolites synthesized by stimulated lungs during normoxia and hypoxia.