Increased constriction of the ductus arteriosus with combined administration of indomethacin and L-NAME in fetal rats.
We studied age-related changes and the caliber of the ductus arteriosus (DA) after two-pathway inhibition of prostaglandin E(2) and nitric oxide (NO) by the combined administration of indomethacin, a cyclooxygenase inhibitor, and N(G)-nitro-L-arginine methyl ester (L-NAME), an NO synthase inhibitor, in fetal rats. Pregnant rats from day 18 to 21 of gestation were used. They were administered indomethacin orally (3 mg/kg) 3 h before cesarean section, and then L-NAME (50 mg/kg) was injected intraperitoneally 3 h before the rats were killed. Using rapid-freezing and shaving methods, the caliber of the DA in fetal rats was measured. Compared with the indomethacin alone group, indomethacin plus L-NAME further constricted the DA after indomethacin and L-NAME were simultaneously administered 3 h before the rats were sacrificed. The extent of the final DA constriction was almost equal to the addition of each effect of indomethacin and L-NAME. We concluded that the magnitude of DA constriction following indomethacin plus L-NAME was due to the additive effects of these agents, suggesting a possible method to treat patent DA in premature infants.
Takizawa
T
T
Department of Developmental Biotechnology, Azabu University School of Veterinary Medicine, Sagamihara, Japan. takizawa@azabu-u.ac.jp
Kihara
T
T
Kamata
A
A
D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D015232:Dinoprostone / Q000037:antagonists & inhibitors; D004373:Ductus Arteriosus / Q000187:drug effects*; D004374:Ductus Arteriosus, Patent / Q000188:drug therapy; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D005260:Female; D007213:Indomethacin / Q000008:administration & dosage* / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage* / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects
D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D019001:Nitric Oxide Synthase; D015232:Dinoprostone; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin