The role of nitric oxide (NO) on the ductus arteriosus (DA) patency was exa
mined in fetal rats at various stages of gestation. NO-nitro-L-arginine met
hyl ester (L-NAME, 50 mg/kg, ip), an NO synthase (NOS) inhibitor, or indome
thacin (3 mg/kg, po), a cyclooxygenase inhibitor, was administered at 3 hr
before cesarean section to pregnant rats ranging from day 17 to day 21 of g
estation. Dams were decapitated and the fetuses were obtained by cesarean s
ection. The fetuses were rapidly frozen in an acetone-dry ice mixture. Usin
g 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 cal
iber was stronger than that of indomethacin in 19-day-old and immature fetu
ses. In near-term fetuses, the constrictive effects of L-NAME were reduced,
while indomethacin caused marked DA constriction. We conclude that endogen
ous 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 regu
lating the ductal patency in the near-term fetus.