Does oxygen regulate prostaglandin-induced relaxation in the lamb ductus arteriosus?

It has been speculated that hypoxia might cause vasodilation of the ductus arteriosus by enhancing the relaxing action of endogenous prostaglandins. Using isolated rings of lamb ductus arteriosus, we measured immunoreactive PGE₂ released into the bath solution. We found that after a period of stabilization following suspension of the rings in low PO₂, only a negligible amount of PGE₂ was released by the rings (1.15 ± 0.52 pg PGE₂/mg wet weight per 45 min, n14, ±SEM). When rings were exposed to a high PO₂, significant amounts of PGE₂ were released (32.3 ± 12.6 pg PGE₂/mg wet weight per 45 min). These observations were supported by our findings that indomethacin had a negligible contractile effect (0.11 ± 0.09 g/mm², n=11) on rings equilibrated in a low PO₂, but caused a significant contraction (0.55 ± 0.12 g/mm², n=11) in rings incubated in a high PO₂. These findings do not support the hypothesis that low PO₂ increases PGE₂ production by the lamb ductus arteriosus. They are consistent with the hypothesis that endogenous PGE₂ inhibits the ability of the vessel to contract in response to oxygen. In addition (if these in vitro results can be extrapolated to the in vivo situation), the demonstration that the ductus arteriosus needs an oxygen tension greater than that present in utero to produce effective amounts of PGE₂, strengthens the hypothesis that circulating levels of PGE₂ may be important in the prenatal maintenance of ductal patency.