Lipid mediators in the control of the ductus arteriosus

The ductus arteriosus (DA) is kept open during fetal development by the continuous relaxant effects of prostaglandins (PG), primarily E2. Although this PGE2 is probably intramurally produced. a subsidiary role for blood-borne PGE2 and PGI2 is not excluded. PGE2 synthetic activity develops early in the developing ductus and is greater in immature than in mature tissues. Ductus sensitivity to PGE2 is greatly diminished after exposure to oxygen. Arachidonic acid (the precursor of PGE2) may inactivates cytochrome P-450, completely reverses the contractile tension of the DA at both low (4 to 12 torr) and high (511 to 712 torr) oxygen tension and is equally effective in the presence and absence of indomethacin. Carbon monoxide-induced relaxation occurs with a PCO/PO2 ratio of 0.27 and is reversed by white light and by monochromatic light with maximal reversal seen at 450 nm wavelength. Both these findings favor involvement of a cytochrome P-450. Metyrapone and phenylimidazole, chemical inhibitors of cytochrome P-450, also relax the ductus. These findings suggest that ductus tone is controlled through the opposing activities of cyclooxygenase and monooxygenase products of AA. The former predominate in the fetus, and the latter at birth when they induce closure/