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.
Department of Anatomy II, Azabu University School of Veterinary Medicine, Kanagawa, Japan.
H
H
Togashi
T
T
Takizawa
M
M
Kawahata
M
M
Yamamoto
K
K
Arishima
T
T
Masaoka
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