Nitric oxide inhibition causes intrauterine growth retardation and hind-limb disruptions in rats.
OBJECTIVE
Our purpose was to determine the effects of nitric oxide synthase inhibition on maternal and fetal health in the last third of pregnancy.


METHODS
Pregnant rats were treated from gestational day 13 to day 19 or 20 with the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester, which was administered in the drinking water ad libitum. Control animals received the inactive enantiomer NG-nitro-D-arginine methyl ester or no treatment. Maternal blood pressure, blood chemistry studies, and placenta and pup size were determined. A separate group of rats received nitroprusside sodium in conjunction with NG-nitro-L-arginine methyl ester.


RESULTS
NG-nitro-L-arginine methyl ester caused a dose-dependent reduction in placenta and pup size. Amniotic fluid levels of cyclic guanosine monophosphate were significantly reduced at 0.1 mg/ml but not at higher doses. Hemorrhagic necrosis of fetal hind limbs occurred only with treatment with NG-nitro-L-arginine methyl ester and was prevented by coadministration of nitroprusside sodium. Maternal blood pressure and blood and urine chemistry studies were unaffected by NG-nitro-L-arginine methyl ester.


CONCLUSIONS
Chronic reductions of nitric oxide production in the last third of pregnancy result in significant intrauterine growth retardation and hemorrhagic disruptions of hind limbs. Maternal complications were minimal and did not mimic preeclampsia.
Department of Pediatrics, Louisiana State University Medical Center, New Orleans 70112-2822.
A L
AL
Diket
M R
MR
Pierce
U K
UK
Munshi
C A
CA
Voelker
S
S
Eloby-Childress
S S
SS
Greenberg
X J
XJ
Zhang
D A
DA
Clark
M J
MJ
Miller
D000653:Amniotic Fluid / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005315:Fetal Diseases / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control; D005317:Fetal Growth Retardation / Q000139:chemically induced* / Q000378:metabolism; D005333:Fetus / Q000187:drug effects; D006470:Hemorrhage / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control; D006614:Hindlimb / Q000098:blood supply; D019331:NG-Nitroarginine Methyl Ester; D009336:Necrosis; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D009599:Nitroprusside / Q000494:pharmacology; D010920:Placenta / Q000187:drug effects; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D009599:Nitroprusside; D009569:Nitric Oxide; D001120:Arginine; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester