Gastroschisis increases small bowel nitric oxide synthase activity.
In gastroschisis, the eviscerated fetal bowel frequently is damaged and this results in hypoperistalsis and malabsorption. The mechanistic link that ties gastroschisis-induced intestinal damage to dysfunction may be nitric oxide (NO) and the enzyme responsible for producing it, NO synthase. Using a fetal rabbit model, the authors investigated the hypothesis that the hypoperistalsis and malabsorption associated with gastroschisis may be attributable to abnormal small bowel NO synthase activity. Using the 3H-arginine-to-3H-citrulline conversion assay, they measured NO synthase activity in the small bowel of full-term fetal rabbits with and without gastroschisis. The mean total small bowel NO synthase activity of fetal rabbits with gastroschisis was 2.5 times greater than that of control littermates without gastroschisis (n = 6; 5,726 +/- 834 v 2,208 +/- 537 mean pmol/mg protein/min; P = .004). This increased NO synthase activity also was studied by measuring the individual isoforms of NO synthase, and the site of increased NO synthase activity was localized to the small bowel epithelium and neurons. After detecting and localizing the gastroschisis-induced increase in NO synthase activity, the authors explored the mechanism of this increase using NADPH-diaphorase staining. With this histological staining technique, no quantitative increase was found in the small bowel NO synthase of the rabbits with gastroschisis. This suggests that the increased NO synthase activity found in these rabbits is the result of accelerated enzyme kinetics. These findings suggest that the increased NO synthase activity caused by gastroschisis may contribute to the common clinical sequelae of malabsorption and intestinal dysmotility.
Bealer
J F
JF
Fetal Treatment Center, University of California, San Francisco 94143-0570, USA.
Graf
J
J
Bruch
S W
SW
Adzick
N S
NS
Harrison
M R
MR
D000818:Animals; D004195:Disease Models, Animal; D005333:Fetus / Q000201:enzymology; D005769:Gastrointestinal Motility; D006555:Hernia, Ventral / Q000150:complications / Q000151:congenital* / Q000201:enzymology* / Q000503:physiopathology; D006801:Humans; D007421:Intestine, Small / Q000737:chemistry / Q000201:enzymology*; D008286:Malabsorption Syndromes / Q000209:etiology; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000502:physiology*; D011817:Rabbits
D019001:Nitric Oxide Synthase