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.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pediatrics, University of Texas Southwestern Medical Center at Dallas 75235-9063.
P W
PW
Shaul
M A
MA
Farrar
R R
RR
Magness
D000375:Aging / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D000242:Cyclic AMP / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis; D011464:Epoprostenol / Q000096:biosynthesis*; D005333:Fetus / Q000378:metabolism*; D010100:Oxygen / Q000494:pharmacology*; D011453:Prostaglandins / Q000096:biosynthesis; D011651:Pulmonary Artery / Q000378:metabolism*; D012756:Sheep
D011453:Prostaglandins; D011464:Epoprostenol; D000242:Cyclic AMP; D015232:Dinoprostone; D010100:Oxygen