Oxygen modulation of pulmonary arterial prostacyclin synthesis is developmentally regulated

To better understand the role of prostacyclin [prostaglandin (PG) I₂] in oxygen mediation of vasomotor tone in the developing lung, we determined the ontogeny of the direct effects of acute changes in oxygen on in vitro PGI₂ synthesis and adenosine 3',5'-cyclic monophosphate (cAMP) production in intrapulmonary arteries from fetal and newborn lambs. In the absence of varying oxygen, PGI₂ synthesis increased 6.9-fold from early to late in the third trimester, and it rose an additional 3.2-fold from late gestation to 1 wk of age, and another 2.1-fold from 1 to 4 wk. PGE₂ synthesis similarly rose 4.9-fold during the third trimester, but it then fell 69% from late gestation to 1 wk of age and remained unchanged postnatally. Paralleling the developmental increase in PGI₂ synthesis, basal cAMP production rose 6.2- fold from the early third trimester to 4 wk of age. In contrast, PGI₂- stimulated cAMP production was similar in all age groups. With an acute decline in PO₂ in vitro from 680 to 40 mmHg, PGI₂ and PGE₂ synthesis in fetal arteries fell 33-46 and 39-55%, respectively. In contrast, they were increased by 9-145% and 44-130%, respectively, at lower PO₂ in arteries from newborn lambs. Basal cAMP production was altered by decreased oxygen in a similar manner, falling by 35-39% in fetal arteries yet increasing by 21-47% in the newborn. PGI₂-stimulated cAMP production, however, was not affected by oxygen at all ages except in the early third trimester. Thus there is a dramatic developmental increase in pulmonary arterial PGI₂ synthesis that causes a marked maturational rise in cAMP production. In addition, decreased oxygen acutely attenuates PGI₂ and PGE₂ synthesis and cAMP production in fetal pulmonary arteries, whereas it enhances those processes in the newborn.