NITRIC-OXIDE INHIBITION CAUSES INTRAUTERINE GROWTH-RETARDATION AND HINDLIMB DISRUPTIONS IN RATS

OBJECTIVE: Our purpose was to determine the effects of nitric oxide sy nthase inhibition on maternal and fetal health in the last third of pr egnancy. 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-nitr o-D-arginine methyl ester or no treatment. Maternal blood pressure, bl ood chemistry studies, and placenta and pup size were determined. A se parate group of rats received nitroprusside sodium in conjunction with N-G-nitro-L-arginine methyl ester. RESULTS: N-G-nitro-L-arginine meth yl ester caused a dose-dependent reduction in placenta and pup size. A mniotic fluid levels of cyclic guanosine monophosphate were significan tly 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-arg inine methyl ester and was prevented by coadministration of nitropruss ide sodium. Maternal blood pressure and blood and urine chemistry stud ies were unaffected by N-G-nitro-L-arginine methyl ester. CONCLUSION: Chronic reductions of nitric oxide production in the last third of pre gnancy result in significant intrauterine growth retardation and hemor rhagic disruptions of hind limbs. Maternal complications were minimal and did not mimic preeclampsia.