Biphasic response of the ductus arteriosus to combined administration of indomethacin and L-NAME in fetal rats.
We studied the combined effects of indomethacin, a cyclooxygenase inhibitor, and N(G)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide (NO) synthase inhibitor, on the patency of the ductus arteriosus (DA) in fetal rats. Pregnant rats were administered indomethacin (3 mg/kg) orally 3 h before cesarean section, and then L-NAME (5 and 50 mg/kg), D-NAME, an enantiomer of L-NAME (50 mg/kg), or methylene blue, a soluble guanylate cyclase inhibitor (100 mg/kg), was injected intraperitoneally at various times before the cesarean section. Using rapid freezing and shaving methods, the calibers of the DA were measured. Compared with the indomethacin alone group, L-NAME caused a rapid and marked increase in the DA caliber 0.5 h after injection in fetal rats in which the DA was constricted by treatment with indomethacin. Subsequently, the transient ductal dilatation was completely reversed by 3 h after the L-NAME injection. Methylene blue also caused a biphasic response, but D-NAME did not affect the DA caliber. We conclude that the inhibition of both cyclooxygenase (indomethacin) and NO synthase (L-NAME) or NO action (methylene blue) causes a biphasic effect on the DA caliber in fetal rats.
Takizawa
T
T
Department of Developmental Biotechnology, Azabu University School of Veterinary Medicine, Sagamihara, Japan. takizawa@azabu-u.ac.jp
Horikoshi
E
E
Kamata
A
A
D000818:Animals; D016861:Cyclooxygenase Inhibitors; D004373:Ductus Arteriosus / Q000187:drug effects* / Q000196:embryology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology*; D008751:Methylene Blue / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism
D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D008751:Methylene Blue; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin