Nitric oxide attenuates and xanthine oxidase exaggerates lung damage-induced gut injury.
Aspirated gastric contents can evoke multiorgan failure. We hypothesized that secondary intestinal epithelial dysfunction after lung damage would be mediated by xanthine oxidase (XO) and antagonized by endogenous gut nitric oxide (NO). Isosmotic saline or HCl solutions were instilled intratracheally in anesthetized rats, and intestinal injury was assessed 190 min later by measuring the blood-to-lumen clearance of 51Cr-labeled EDTA (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 after endobronchial acidification are XO as mediator and NO synthase as antagonist.
Brooks
E C
EC
Department of Medicine, University of Colorado Health Sciences Center, Denver 80262, USA.
Mahr
N N
NN
Radisavljevic
Z
Z
Jacobson
E D
ED
Terada
L S
LS
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002199:Capillary Permeability / Q000187:drug effects; D004492:Edetic Acid / Q000493:pharmacokinetics; D004791:Enzyme Inhibitors; D006851:Hydrochloric Acid / Q000008:administration & dosage / Q000494:pharmacology; D007410:Intestinal Diseases / Q000209:etiology*; D008168:Lung / Q000378:metabolism; D008171:Lung Diseases / Q000150:complications*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology*; D011652:Pulmonary Circulation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014132:Trachea; D014969:Xanthine Oxidase / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D001120:Arginine; D004492:Edetic Acid; D014969:Xanthine Oxidase; D006851:Hydrochloric Acid; D019331:NG-Nitroarginine Methyl Ester