GASTROSCHISIS INCREASES SMALL-BOWEL NITRIC-OXIDE SYNTHASE ACTIVITY

In gastroschisis, the eviscerated fetal bowel frequently is damaged an d this results in hypoperistalsis and malabsorption. The mechanistic l ink that ties gastroschlsis-induced intestinal damage to dysfunction m ay be nitric oxide (NO) and the enzyme responsible for producing it: N O synthase. Using a fetal rabbit model, the authors investigated the h ypothesis that the hypoperistalsis and malabsorption associated with g astroschisis may be attributable to abnormal small bowel NO synthase a ctivity. Using the H-3-arginine-to-3H-citrulline conversion assay, the y 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 gr eater 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 indiv idual isoforms of NO synthase, and the site of increased NO synthase a ctivity was localized to the small bowel epithelium and neurons. After detecting and localizing the gastroschisis-induced increase in NO syn thase activity, the authors explored the mechanism of this increase us ing NADPH-diaphorase staining. With this histological staining techniq ue, 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 synthas e activity caused by gastroschisis may contribute to the common clinic al sequelae of malabsorption and intestinal dysmotility. Copyright (C) 1996 by W.B. Saunders Company