Prostaglandin biosynthetic activities of isolated fetal lamb ductus arteriosus, other blood vessels, and lung tissue.
Experimental evidence from many laboratories implicates products of arachidonic acid metabolism in perinatal homeostasis of the circulation of the ductus arteriosus. Studies were conducted to define the potential prostaglandin and prostanoid biosynthetic capabilities of the isolated fetal lamb ductus arteriosus, other fetal blood vessels, and isolated fetal and neonatal lung tissue as possible humoral sources of vasoactive products. Because the biosynthetic pathway is a sequential cascade of enzyme reactions, both radiolabeled synthetic endoperoxide (PGH2) and arachidonic acid were used as substrates. Prostacyclin (PGI2) synthase was the primary enzymatic pathway for metabolism of exogenous PGH2 by the isolated ductus arteriosus; no conclusive evidence was found for enzymatic formation of PGE2 or thromboxane A2 (TXA2). The PGI2 synthase activity of the ductus arteriosus was intermediate between arterial tissues (high) and veins (low). A relatively high cyclooxygenase activity was apparent in isolated lung tissue exhibited enzymatic activity for the formation of PGI2, PGE2, and TXA2 from synthetic PGH2. Lung thromboxane synthase activity was markedly elevated late in term due to an apparent increase in Vmax without change in Km, indicative of increased enzyme concentration. Although exogenous PGE2 has been shown to be a more potent relaxant of the ductus arteriosus than PGI2, our study could not positively identify an enzymatic pathway for the total intramural biosynthesis of PGE2. Similarly, no evidence was found for a locally generated constrictor prostanoid, e.g., TXA2. Our results suggest that humoral sources of vasodilator (PGE2 and PGI2) and vasoconstrictor (TXA2) products may be more important than local production in control of the ductus arteriosus and point to the importance of the fetal and neonatal lung in cardiovascular adaptations and homeostasis.
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D001808:Blood Vessels / Q000196:embryology* / Q000378:metabolism; D015232:Dinoprostone; D004373:Ductus Arteriosus / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000378:metabolism*; D008168:Lung / Q000196:embryology* / Q000378:metabolism; D011247:Pregnancy; D011450:Prostaglandin Endoperoxides, Synthetic / Q000096:biosynthesis; D044262:Prostaglandin H2; D011453:Prostaglandins / Q000096:biosynthesis*; D011458:Prostaglandins E / Q000096:biosynthesis; D011463:Prostaglandins H / Q000096:biosynthesis; D012756:Sheep
D011450:Prostaglandin Endoperoxides, Synthetic; D011453:Prostaglandins; D011458:Prostaglandins E; D011463:Prostaglandins H; D044262:Prostaglandin H2; D015121:6-Ketoprostaglandin F1 alpha; D015232:Dinoprostone