EFFECTS OF NO SYNTHASE INHIBITORS, ARGININE-DEFICIENT DIET, AND AMILORIDE IN PREGNANT RATS

This study tests the hypothesis that nitric oxide synthase (NOS) inhib ition is linked to N-G-nitro-L-arginine methyl ester (L-NAME)-mediated intrauterine growth retardation (IUGR) and fetal limb reduction defic its (LRD) in pregnant darns. Administration of L-NAME (1 mg/ml) or ami noguanidine (AG, 500 mu g/ml) in the drinking water or intraperitoneal administration of L-N-5-(1-iminoethyl)ornithine (L-NIO, 10 mg.kg(-1). day-(1)) on gestational days 13-20 decreased nitrite and nitrate plus nitrate (RNI) levels in the urine and plasma and decreased RNI in incu bates of aorta and fetal limbs compared with pregnant rats given amilo ride (50 mu g/ml) or water (control). Although all drugs caused fetal IUGR, only L-NAME and amiloride caused fetal deaths and LRD. Urine and tissue levels of RNI were unchanged in rats fed an arginine-free diet (AFD) on gestational days 13-20, and yet fetal IUGR, deaths, and LRD were prevalent. L-NAME and L-NIO inhibited tissue RNI in these rats, b ut only L-NAME potentiated the fetal abnormalities and resorptions. Pl asma arginine concentrations decreased with AFD >> L-NAME > L-NIO. Pla sma ornithine, a precursor for polyamine synthesis, decreased with AFD and increased with L-NAME. Thus inhibition of NOS is not linked to LR D. The ability of L-NAME and amiloride to produce fetal IUGR and LRD m ay result from L-NAME-mediated modulation of amino acid delivery to th e fetus and amiloride-mediated inhibition of protein synthesis. Finall y, IUGR appears unrelated to LRD.