Abstract
ABSTRACT: Administration of the nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) during pregnancy has been shown to compromise fetal growth. This study was designed to determine whether aminoguanidine, a predominate inhibitor of inducible NOS, affects fetal outcome. In addition, we extended the prenatal administration of L-NAME into the postnatal period (14 d) to determine whether neonatal growth and maturation were also affected. L-NAME, but not aminoguanidine, compromises fetal and placental growth. When compared with control 14-d-old pups, postnatal L-NAME compromised neonatal growth, whether it was given directly (intraperitoneally) (39.7 ± 1.1 versus 24.1 ± 1.0 g) or indirectly (38.6 ± 0.5 versus 22.2 ± 1.2 g) via maternal breast milk. Neonatal growth retardation was asymmetric, with brain sparing, suggesting a nutritional origin. L-NAME administration resulted in growth retardation that extended into adulthood, without evidence of catch-up growth. Treated neonates displayed the hallmarks of hypertrophic pyloric stenosis. Significant increases in stomach weight/pup weight (9.9 ± 0.3 versus 8.2 ± 0.4 X 103) and stomach volume/pup weight (12.0 ± 0.6 versus 9.4 ± 0.6 mL/100 g) with a concomitant decrease in small intestine weight/length (2.10 ± 0.08 versus 3.18 ± 0.13 g/100 cm) was noted in treated versus control pups (p < 0.05). Muscularis hypertrophy at the pyloric sphincter in the L-NAME-treated pups was noted by histology. Blood pressure was elevated in the L-NAME-treated pups (93 ± 6 versus 60 ± 5 mm Hg in control pups, p < 0.05). These findings are consistent with inhibition of neuronal and endothelial NOS activity. We conclude that NO, formed via the constitutive isoforms of NOS, is a critical determinant of fetal and neonatal growth and maturation.
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Voelker, C., Miller, M., Zhang, XJ. et al. Perinatal Nitric Oxide Synthase Inhibition Retards Neonatal Growth by Inducing Hypertrophic Pyloric Stenosis in Rats. Pediatr Res 38, 768–774 (1995). https://doi.org/10.1203/00006450-199511000-00022
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DOI: https://doi.org/10.1203/00006450-199511000-00022
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