Metabolism of endogenous arachidonic acid by isolated lungs of neonatal and adult rabbits stimulated with calcium ionophore: effect of hypoxia.

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 (pO2 greater than 100 torr) or hypoxia (pO2 less than 40 torr) and arachidonic acid metabolism stimulated by the addition of A23187 (5 microM) 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. LTC4 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.