PERINATAL NITRIC-OXIDE SYNTHASE INHIBITION RETARDS NEONATAL GROWTH BYINDUCING HYPERTROPHIC PYLORIC-STENOSIS IN RATS

Administration of the nitric oxide synthase (NOS) inhibitor, N-G-nitro -L-arginine methyl ester (L-NAME) during pregnancy has been shown to c ompromise fetal growth. This study was designed to determine whether a minoguanidine, a predominate inhibitor of inducible NOS, affects fetal outcome. In addition, we extended the prenatal administration of L-NA ME into the postnatal period (14 d) to determine whether neonatal grow th 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 w as given directly (intraperitoneally) (39.7 +/- 1.1 versus 24.1 +/- 1. 0 g) or indirectly (35.6 +/- 0.5 versus 22.2 +/- 1.2 g) via maternal b reast milk. Neonatal growth retardation was asymmetric, with brain spa ring, suggesting a nutritional origin. L-NAME administration resulted in growth retardation that extended into adulthood, without evidence o f catch-up growth. Treated neonates displayed the hallmarks of hypertr ophic pyloric stenosis. Significant increases in stomach weight/pup we ight (9.9 +/- 0.3 versus 8.2 +/- 0.4 x 10(3)) and stomach volume/pup w eight (12.0 +/- 0.6 versus 9.4 +/- 0.6 mL/100 g) with a concomitant de crease 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). M uscularis hypertrophy at the pyloric sphincter in the L-NAME-treated p ups was noted by histology. Blood pressure was elevated in the L-NAME- treated pups (93 +/- 6 versus 60 +/- 5 mmHg in control pups, p < 0.05) . These findings are consistent with inhibition of neuronal and endoth elial NOS activity. We conclude that NO, formed via the constitutive i soforms of NOS, is a critical determinant of fetal and neonatal growth and maturation.