Nitric oxide donors reduce the rise in reperfusion-induced intestinal mucosal permeability

Abstract

Recent data have demonstrated that inhibition of nitric oxide synthesis exacerbated the mucosal injury associated with reperfusion of the postischemic intestine. In this study, using a feline 1-h intestinal ischemia followed by reperfusion model, we tested the possibility that exogenous sources of nitric oxide may prevent the reperfusion-induced mucosal barrier disruption and examined the mechanisms involved. Mucosal barrier integrity was assessed by determining 51Cr-EDTA clearance from blood to lumen. Intestinal blood flow and resistance were also determined. Reperfusion after 1 h of ischemia significantly increased 51Cr-EDTA clearance (0.05 +/- 0.01 to 0.35 +/- 0.07 ml.min-1.100 g-1) and decreased intestinal blood flow by 50%. Exogenous sources of nitric oxide including SIN-1, CAS-754, and nitroprusside as well as exogenous L-arginine all reduced reperfusion-induced mucosal barrier dysfunction without improving intestinal blood flow. Inhibition of endogenous nitric oxide with NG-nitro-L-arginine methyl ester between 1 and 2 h of reperfusion further augmented the rise in mucosal permeability associated with ischemia-reperfusion. Addition of the permeable analogue of guanosine 3',5'-cyclic monophosphate, 8-bromoguanosine 3',5'-cyclic monophosphate, improved reperfusion-induced intestinal blood flow significantly but did not provide protection against mucosal barrier disruption associated with the first hour of ischemia-reperfusion. Exogenous sources of nitric oxide can reduce reperfusion-induced mucosal barrier dysfunction independent of alterations in intestinal blood flow.

Óxido nítrico: revisão

“…Embora pequenas quantidades sejam necessárias para a homeostasia, grandes quantidades, como aquelas produzidas na ativação da iNOS são citotóxicas. Porém, a produção de grandes quantidades de NO pode ser importante na defesa contra invasores celulares, tumores celulares e ainda em lesões vasculares com perda endotelial 13,[37][38][39] . A expressão da iNOS é o resultado de uma resposta inflamatória localizada ou difusa resultante de uma infecção ou dano tecidual.…”

Interactive role of nitric oxide and superoxide anion in neutrophil-mediated endothelial cell injury

“…NO has also been viewed as an important molecule in preventing vascular thrombosis [7], inflammatory cell-mediated injury [8], and reperfusion injury [9,10]. Despite extensive evidence that excess production of NO in the presence of O 2 Ϫ leads to cytotoxic events [11,12], NO has also been implicated in limiting injury to target cells or tissues during events associated with excess production of ROI [9,10,13]. However, the mechanism by which NO prevents the ROI-mediated injury is not well defined and thus needs further evaluation.…”

Probiotics and Oxidative Stress

“…The principal metabiotics are short-chain fatty acids but also other substances like polyamines (putrescine, spermidine, spermine) have an impact (Larqué et al, 2007). It has been demonstrated, that NO produced by LAB protects mucosa for damages and excessive permeability (Payne et al, 1993;Korhonen et al, 2001). …”