ENHANCEMENT OF NEONATAL RAT DUCTAL RESPONSIVENESS TO PROSTAGLANDIN E-2 AFTER MATERNAL TREATMENT WITH ENALAPRIL OR CAPTOPRIL

This work was conducted to determine whether the angiotensin-convertin g enzyme inhibitors (ACEIs) (enalapril and captopril) administered to mother rats prenatally can potentiate a re-opening of the neonatal duc tus arteriosus (DA) induced by prostaglandin E-2 (PGE(2)) after postna tal closure. A subcutaneous injection of PGE(2) (4 mu g) was administe red to newborn rats 3 hr after a Cesarean delivery from females which had been orally given 0.1, 1 or 10 mg/kg/day of enalapril or 15 or 150 mg/kg/day of captopril from day 14 to day 20 of gestation. The ratio of the DA to the pulmonary artery (PA) was determined at intervals aft er the injection. The DA/PA ratio was significantly higher in the newb orn rats of mothers who were transplacentally administered these agent s compared to the controls, except at the low dose (0.1 mg/kg) group o f enalapril. We found that the level in the neonatal lungs of 15-hydro xy prostaglandin dehydrogenase, a key enzyme that catalyzes PGE(2) to convert it to its inactive metabolite 15-keto-PGE(2), was not affected after maternal treatment with enalapril or captopril. These results i ndicate that the increased ductal responsiveness to PGE(2) in newborn rats was a common response after maternal ACEI treatment, but the cata bolism of PGE(2) in the lungs did not contribute to this response.