Increased ductal responsiveness to PGE2 after maternal treatment with aspirin and ibuprofen.
This work was conducted to determine whether aspirin and ibuprofen, when administered prenatally may potentiate a reopening of the neonatal ductus arteriosus (DA) induced by PGE2 after postnatal closure. In the first experiment, a subcutaneous injection of PGE2 (4 microgram(s)) was administered to newborn rats 3 hr after a Cesarean delivery from pregnant 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 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 newborn rats from mothers who were transplacentally administered these agents than the control. We also examined the hypothesis that maternal treatment with nonsteroidal anti-inflammatory drugs (NSAID), such as aspirin and ibuprofen, inhibits the catabolism of PGE2 and that the increased reopening of the DA was partly due to this inhibition. 15-hydroxy prostaglandin dehydrogenase (15-PGDH) in neonatal lungs, the key enzyme involved in catalyzing PGE2 to convert it to its inactive metabolite 15-keto-PGE2, was not affected by maternal treatment with aspirin and ibuprofen. These results suggest that the increased ductal responsiveness to PGE2 in newborn rats was a common response after maternal NSAID treatment, but the catabolism of PGE2 in the lungs did not always contribute to this response.
Takizawa
T
T
Department of Developmental and Reproductive Biotechnology, Azabu University School of Veterinary Medicine, Kanagawa, Japan.
Ikeda
Y
Y
Kawahata
M
M
Togashi
H
H
Yamamoto
M
M
Arishima
K
K
Masaoka
T
T
D000284:Administration, Oral; D000818:Animals; D000831:Animals, Newborn; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D002585:Cesarean Section; D015232:Dinoprostone / Q000494:pharmacology*; D004373:Ductus Arteriosus / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005865:Gestational Age; D006911:Hydroxyprostaglandin Dehydrogenases / Q000378:metabolism; D007052:Ibuprofen / Q000008:administration & dosage / Q000494:pharmacology*; D008168:Lung / Q000201:enzymology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011651:Pulmonary Artery / Q000187:drug effects* / Q000196:embryology / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase; D015232:Dinoprostone; D001241:Aspirin; D007052:Ibuprofen