Role of nitric oxide in regulating the ductus arteriosus caliber in fetal rats.
The role of nitric oxide (NO) on the ductus arteriosus (DA) patency was examined in fetal rats at various stages of gestation. N(G)-nitro-L-arginine methyl ester (L-NAME, 50 mg/kg, i.p.), an NO synthase (NOS) inhibitor, or indomethacin (3 mg/kg, p.o.), a cyclooxygenase inhibitor, was administered at 3 hr before cesarean section to pregnant rats ranging from day 17 to day 21 of gestation. Dams were decapitated and the fetuses were obtained by cesarean section. The fetuses were rapidly frozen in an acetone-dry ice mixture. Using rapid-freezing and shaving methods, the calibers of the DA and pulmonary artery were measured. The constrictive effect of L-NAME on the fetal DA caliber was stronger than that of indomethacin in 19-day-old and immature fetuses. In near-term fetuses, the constrictive effects of L-NAME were reduced, while indomethacin caused marked DA constriction. We conclude that endogenous NO may play a major role in regulating the patency of the DA in earlier fetal stages, while dilator prostaglandins may play a greater role in regulating the ductal patency in the near-term fetus.
Takizawa
T
T
Department of Developmental Biotechnology, Azabu University School of Veterinary Medicine, Kanagawa, Japan.
Kihara
T
T
Kamata
A
A
Yamamoto
M
M
Arishima
K
K
D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004373:Ductus Arteriosus / Q000187:drug effects / Q000196:embryology*; D005314:Embryonic and Fetal Development; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005865:Gestational Age; D007213:Indomethacin / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000196:embryology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011247:Pregnancy; D011651:Pulmonary Artery / Q000187:drug effects / Q000196:embryology; D051381:Rats; D017208:Rats, Wistar
D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin