Xanthine oxidase decreases production of gut wall nitric oxide.
Multiorgan failure is often the lethal outcome of intratracheal aspiration of acidic gastric juice. The pathogenesis of multiorgan failure may involve a systemic imbalance between pro-inflammatory and anti-inflammatory factors. In an anesthetized rat model, intratracheal instillation of HCl elicited intestinal inflammation which was exaggerated by xanthine oxidase (XO) and attenuated by nitric oxide (NO). We hypothesized that XO may mediate injury in part by suppression of NO formation. Therefore, we measured intestinal tissue concentrations of the stable NO oxidative metabolites (NO2- and NO3-) following intratracheal (IT) instillation of NaCl or HCl alone or in combination with interventions aimed at increasing or decreasing XO activity. Compared with IT NaCl (control treatment) jejunal tissue NO2- and NO2- + NO3- concentrations were increased by allopurinol pretreatment, which inhibits XO, and were decreased by systemically administered XO, as well as by IT HCl. The decreased NO2- and NO2- + NO3- concentrations found following IT HCl were completely reversed by either allopurinol or by systemically administered L-arginine (the precursor of NO). We conclude that manipulation of the pro-inflammatory XO system has a reciprocal effect on the intestinal anti-inflammatory NO system in either the undamaged or the endobronchially acidified lung model.
Terada
L S
LS
Department of Medicine, School of Medicine, University of Colorado Health Sciences Center, Denver 80262, USA.
Radisavljevic
Z
Z
Mahr
N N
NN
Jacobson
E D
ED
D000818:Animals; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D007442:Intubation, Intratracheal; D007583:Jejunum / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000502:physiology; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D014969:Xanthine Oxidase / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology
D009569:Nitric Oxide; D014969:Xanthine Oxidase