Maturational Changes in Ovine Pulmonary Metabolism of Platelet-Activating Factor: Implications for Postnatal Adaptation

Abstract

We recently reported that PAF acetylhydrolase (PAF-Ah) mRNA level and PAF-Ah activity in lamb lungs are up-regulated in the immediate newborn period, thereby facilitating the fall in postnatal PAF levels as well as a fall in pulmonary vascular resistance (B. O. Ibe, F. C. Sardar, and J. U. Raj, Mol Genet Metab 69:46–55, 2000). We have studied hypoxia effects on PAF synthesis and PAF-Ah activity in fetal lamb pulmonary arterial smooth muscle cells (FPASMC) and endothelial cells (FPAEC). We also studied PAF synthesis by platelets, and PAF-Ah activity in plasma of perinatal lambs at different ages. PAF synthesis (means ± SEM, pmol/106 cells) by SMC in baseline was 168 ± 27 and increased 3-fold on stimulation with A23187. Hypoxia augmented A23187-stimulated PAF synthesis by 30%. In FPAEC, baseline synthesis was 0.54 ± 0.062 and increased 3-fold to 1.72 ± .34. Hypoxia had no effect on PAF synthesis by EC. FPASMC produced over 300-fold more PAF than FPAEC. PAF synthesis by platelets was 47.02 ± 7.1, 63.4 ± 6.6, 71.5 ± 9.9, and 62.2 ± 5.2 for fetal, and newborn lambs <2 h, <1 day, and 6–12 days, old, respectively. PAF synthesis by platelets of <1 day-old lambs was different from that of fetal lambs. PAF-Ah activity (nmol lyso-PAF/min/mg protein) by FPASMC in normoxia was 3.41 ± 0.38 which was 50% higher than the rate in hypoxia. Activity in FPAEC was 1.75 ± 0.37 which was not different from hypoxia. PAF-Ah activity in fetal lamb plasma was 47.83 ± 6.87 which was different from 155.32 ± 12.10, the activity in plasma of newborn <1 day old. Activity in the other perinatal lambs did not differ from fetal or newborn <1 d. Our data suggest that lower pulmonary vascular PAF synthesis in normoxia together with higher PAF-Ah activity during immediate postnatal period is necessary to ensure rapid catabolism of PAF in vivo so as to facilitate postnatal adaptation of the pulmonary and systemic circulations.