INCREASED DUCTAL RESPONSIVENESS TO PGE(2) AFTER MATERNAL TREATMENT WITH ASPIRIN AND IBUPROFEN

This work was conducted to determine whether aspirin and ibuprofen, wh en administered prenatally may potentiate a reopening of the neonatal ductus arteriosus (DA) induced by PGE(2) after postnatal closure. In t he first experiment, a subcutaneous injection of PGE(2) (4 mu g) was a dministered to newborn rats 3 hr after a Cesarean delivery from pregna nt females which had been orally given 100 or 300 mg/kg/day of aspirin and 10 or 30 mg/kg/day of ibuprofen on days 18, 19 and 20 of gestatio n. The ratio of the DA to the pulmonary artery (PA) was determined at intervals after the injection. The DA/PA ratio was significantly highe r in newborn rats from mothers who were transplacentally administered these agents than the control. We also examined the hypothesis that ma ternal treatment with nonsteroidal anti-inflammatory drugs (NSAID), su ch as aspirin and ibuprofen, inhibits the catabolism of PGE(2) and tha t the increased reopening of the DA was partly due to this inhibition. 15-hydroxy prostaglandin dehydrogenase (15-PGDH) in neonatal lungs, t he key enzyme involved in catalyzing PGE(2) to convert it to its inact ive metabolite 15-keto-PGE(2) was not affected by maternal treatment w ith aspirin and ibuprofen. These results suggest that the increased du ctal responsiveness to PGE(2) in newborn rats was a common response af ter maternal NSAID treatment, but the catabolism of PGE(2) in the lung s did not always contribute to this response.