Nitric oxide attenuates and xanthine oxidase exaggerates lung
damage induced gut injury.
Brooks, Eric C., Nancy N. Mahr, Zivotije Radisavljevic, Eugene D.
Jacobson, and Lance S. Terada.
Department of Medicine and Webb Waring Institute for Biomedical
Research, University of Colorado Health Sciences Center, Denver,
Colorado 80262
APStracts 3:0263G, 1996.
Aspirated gastric contents can evoke multiorgan failure. We
hypothesized that secondary intestinal epithelial dysfunction
following lung damage would be mediated by xanthine oxidase (XO) and
antagonized by endogenous gut nitric oxide (NO). Isosmotic saline or
hydrochloric acid (HCl) solutions were instilled intratracheally in
anesthetized rats, and intestinal injury was assessed 190 minutes
later by measuring the blood to lumen clearance of 51Cr-labelled
ethylenediaminetetraacetate (51Cr-EDTA clearance) and gut wall
neutrophil population density. Intratracheal HCl increased 51Cr-EDTA
clearance and this transepithelial leak was attenuated by either
systemic L-arginine or intraluminal NO, and by chronic dietary
pretreatment with allopurinol or sodium tungstate. Conversely, lung
damage induced gut leak was exaggerated by NO synthase inhibition or
intravenous XO administration. Intratracheal HCl also increased
intestinal wall neutrophil density and myeloperoxide activity. We
conclude that two enzymatic systems involved in remote gut barrier
dysfunction following endobronchial acidification are XO as mediator
and NO synthase as antagonist.
Received 6 May 1996; accepted in final form 28 October 1996.
APS Manuscript Number G182-6.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996