Hypoxia attenuates metabolism of platelet activating factor by fetal and newborn lamb lungs

Abstract

The metabolism of platelet activating factor (PAF) by lungs of near-term fetal and 5- to 9-day-old lambs was studied during normoxia and hypoxia at 37 degrees C in 30 mM Tris buffer. PAF synthesis was studied in lung cytosol and membrane using 250 microM [3H]acetyl CoA, 40 microM lyso-PAF, and 50 micrograms protein. PAF catabolism was studied in lung homogenate (LH) using 50 microM [3H]alkyl-PAF. PAF was extracted and assayed by thin-layer chromatography (TLC) and liquid scintillation spectrometry. Levels of PAF synthesized (nmol/min per mg protein) by fetal lung membrane versus cytosol were 1.35 +/- 0.07 versus 0.61 +/- 0.08, which were greater than those by newborn which were 0.33 +/- 0.07 versus 0.17 +/- 0.03. Hypoxia did not alter PAF synthesis by the lungs. PAF catabolism (nmol lyso-PAF/min per mg protein) by fetal LH was 0.07 +/- 0.01, which increased to 0.24 +/- 0.02 during normoxia. In newborn LH, the rate was 0.24 +/- 0.04 and increased to 0.33 +/- 0.01 during normoxia. PAF catabolism was higher in newborn than in fetal LH. An increase in pO2 augmented PAF catabolism, more in fetal than in newborn LH. Thus rate of PAF synthesis decreases from fetus to newborn, but PAF catabolism increases from fetus to newborn. The higher rate of PAF synthesis coupled with a low rate of PAF catabolism in the hypoxic environment of fetal lungs may predispose the fetus to a high PAF level, which may contribute to the high basal vasomotor tone in fetal lungs. A fall in PAF level with oxygenation, due to increased PAF catabolism, may facilitate the normal fall in pulmonary vascular resistance at birth.