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Perinatal nitric oxide synthase inhibition retards neonatal growth by inducing hypertrophic pyloric stenosis in rats.

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 10(3)) 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.
AuthorsC A Voelker, M J Miller, X J Zhang, S Eloby-Childress, D A Clark, M R Pierce
JournalPediatric research (Pediatr Res) Vol. 38 Issue 5 Pg. 768-74 (Nov 1995) ISSN: 0031-3998 [Print] United States
PMID8552447 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Guanidines
  • Nitric Oxide
  • Arginine
  • Nitric Oxide Synthase
  • pimagedine
  • NG-Nitroarginine Methyl Ester
Topics
  • Animals
  • Animals, Newborn
  • Arginine (analogs & derivatives, pharmacology)
  • Body Weight
  • Disease Models, Animal
  • Embryonic and Fetal Development (drug effects, physiology)
  • Female
  • Growth
  • Guanidines (pharmacology)
  • Hypertrophy (chemically induced, physiopathology)
  • NG-Nitroarginine Methyl Ester
  • Nitric Oxide (physiology)
  • Nitric Oxide Synthase (antagonists & inhibitors)
  • Pregnancy
  • Pyloric Stenosis (chemically induced, physiopathology)
  • Rats

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