Prostaglandins: a possible regulator of muscle tone in the ductus arteriosus.

We have shown that E-type prostaglandins are potent relaxant of the lamb ductus arteriosus at low, but not high, oxygen tensions, and that their effect is possibly controlled by the rate of endogenous PG synthesis. These findings, together with the demonstration of the contractile effect of PG synthesis blockers on the hypoxic ductus in vitro and in vivo and of the relaxant effect of GSH in vitro, strongly suggest that E-type prostaglandins are responsible for maintaining ductus patency during fetal life. The endoperoxide intermediates may act in concert with PGEs. While our findings argue against the idea that PGF2alpha mediates the oxygen-induced constriction, they suggest that suppression of PGE activity in a high oxygen environment might be important to the initiation of ductus closure at birth. An extension of this concept is that continued patency of the ductus after birth results from either the excessive formation of PGEs or from the persistence of a "fetal-like" response of ductal muscle to endogenous or bloodborne PGEs, or both. The present scheme of PGE action is amenable to practical applications. Our work and that of Elliott et al. (15) prove that PGEs can be used to reopen a constricted ductus in children with cyanotic congenital heart disease, thus improving their change of survival during subsequent corrective surgery. Conversely, treatment with blockers of PG synthesis is envisaged as an alternative to surgery for closing a persistent ductus.