Effect of prostaglandins and some methyl derivatives on the ductus arteriosus.

In vitro studies showed that PGF2a constricted the ductus arteriosus of newborn animals, whereas PGEs produced dilatation. The finding that constriction could also be produced by c-GMP and dilatation by c-AMP raised the possibility that the PGs might produce their effects by altering the relative proportions of cyclic nucleotides in the ductus wall. Results of experiments with inhibitors of PG synthesis and with drugs which are known to interfere with the degradation of c-GMP and c-AMP accorded with this hypothesis. Angiographic studies in neonatal piglets showed that PGEs and PGAs were potent dilators of the ductus. Prostaglandin action was confirmed in infants with congenital heart disease who were dependent on ductus patency for survival. In those patients, PGs proved to be an extremely useful tool. Experimental studies are in progress in the hope of finding a PGE analog, active by the oral route, which may be suitable for the long-term treatment of patients.