NITRIC-OXIDE INHIBITION CAUSES INTRAUTERINE GROWTH-RETARDATION AND HINDLIMB 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. STUDY DESIGN: Pregnant rats were treated from gestational day 13 to day 19 or 20 with the nitric oxide synthase inhibitor N-G-nitro-L-arginine methyl ester, which was administered in the drinking water ad libitum. Control animals received the inactive enantiomer N-G-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 N-G-nitro-L-arginine methyl ester. RESULTS: N-G-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 N-G-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 N-G-nitro-L-arginine methyl ester. CONCLUSION: 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.