Endogenous arachidonic acid metabolism by calcium ionophore stimulated ferret lungs. Effect of age, hypoxia.

We have studied the metabolism of endogenous arachidonic acid by isolated perfused lungs of ferrets when stimulated with calcium ionophore A23187 at two ages, neonatal (2- to 3-week-old) and adult (greater than 6 months). We have also determined the effect of hypoxia on lung metabolism of arachidonic acid in the two age groups. Lungs were perfused with Kreb's bicarbonate buffer in a recirculating system and eicosanoid production was stimulated by addition of A23187 (5 microM). Eicosanoids produced were measured in perfusate and lung homogenate supernatant. Cyclooxygenase metabolites; PGE2, TxB2 and 6-keto-PGF1 alpha were measured by radioimmunoassay and 5-lipoxygenase metabolites, leukotrienes; LTB4, LTC4, LTD4 and LTE4 by high performance liquid chromatography. During normoxia, leukotriene production, LTC4 and LTB4, was 10- to 20-fold higher in neonatal than in adult lungs, but total amount of cyclooxygenase products measured was similar. Compared with adult lungs, neonatal lungs produced more 6-keto-PGF1 alpha, but produced less PGE2. There was no difference in TxB2 production by neonatal and adult lungs. Hypoxia increased the production of 5-lipoxygenase metabolites in adult lungs, with production of cyclooxygenase metabolites remaining unchanged, whereas hypoxia decreased all eicosanoid production in neonatal lungs. In summary, there are age-related differences in endogenous arachidonic acid metabolism by isolated ferret lungs when stimulated with calcium ionophore A23187 as well as age related differences in the effect of hypoxia on endogenous arachidonic acid metabolism in ferret lungs.