Age-dependent sensitivity of the lamb ductus arteriosus to indomethacin and prostaglandins

Abstract

Endogenous prostaglandins inhibit the ability of the ductus arteriosus to contract in response to oxygen. We studied the effects of endogenous prostaglandins and indomethacin (an inhibitor of endogenous prostaglandin production) on isometric contraction of isolated rings of lamb ductus arteriosus from animals of different gestational ages (98 to 103 days and 136 to 147 days; term is 150 days). Rings from animals at about 100 days' gestation have a significantly larger indomethacin-induced contraction than rings from animals near term. The lamb ductus arteriosus forms two prostaglandins that relax the vessel: postaglandin E2 and prostacyclin. PGI2 was three orders of magnitude less potent than PGE2. Rings from the younger animals were significantly more sensitive to the relaxing action of PGE2 and PGI2 than were rings from animals near term. This increased sensitivity of immature animals to endogenous prostaglandins is consistent with the more potent effect of indomethacin on rings from immature animals. These observations are also consistent with the findings that preterm infants have an increased incidence of patent ductus arteriosus and that indomethacin can constrict the ductus arteriosus in preterm infants.