Enhancement of neonatal rat ductal responsiveness to prostaglandin E2 after maternal treatment with enalapril or captopril.
This work was conducted to determine whether the angiotensin-converting enzyme inhibitors (ACEIs) (enalapril and captopril) administered to mother rats prenatally can potentiate a re-opening of the neonatal ductus arteriosus (DA) induced by prostaglandin E2 (PGE2) after postnatal closure. A subcutaneous injection of PGE2 (4 micrograms) was administered 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 after the injection. The DA/PA ratio was significantly higher in the newborn rats of mothers who were transplacentally administered these agents compared to the controls, except at the low dose (0.1 mg/kg) group of enalapril. We found that the level in the neonatal lungs of 15-hydroxy prostaglandin dehydrogenase, a key enzyme that catalyzes PGE2 to convert it to its inactive metabolite 15-keto-PGE2, was not affected after maternal treatment with enalapril or captopril. These results indicate that the increased ductal responsiveness to PGE2 in newborn rats was a common response after maternal ACEI treatment, but the catabolism of PGE2 in the lungs did not contribute to this response.
Togashi
H
H
Department of Anatomy II, Azabu University School of Veterinary Medicine, Kanagawa, Japan.
Takizawa
T
T
Kawahata
M
M
Yamamoto
M
M
Arishima
K
K
Masaoka
T
T
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002216:Captopril / Q000494:pharmacology*; D015232:Dinoprostone / Q000494:pharmacology*; D004373:Ductus Arteriosus / Q000187:drug effects* / Q000502:physiology; D004656:Enalapril / Q000494:pharmacology*; D005260:Female; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011651:Pulmonary Artery / Q000187:drug effects* / Q000254:growth & development; D051381:Rats; D017208:Rats, Wistar
D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; D002216:Captopril; D015232:Dinoprostone