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.

• Authors: D Payne, P Kubes
• Journal: The American journal of physiology (Am J Physiol) Vol. 265 Issue 1 Pt 1 Pg. G189-95 (Jul 1993) ISSN: 0002-9513 [Print] United States
• PMID: 8393297 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Sydnones
• 3-(cis-2,6-dimethylpiperidino)sydnonimine
• Nitroprusside
• Nitric Oxide
• linsidomine
• Molsidomine
• Cyclic GMP

Topics

• Animals
• Cats
• Cyclic GMP (physiology)
• Intestinal Mucosa (metabolism)
• Intestines (blood supply)
• Ischemia (metabolism)
• Molsidomine (analogs & derivatives, pharmacology)
• Nitric Oxide (pharmacology)
• Nitroprusside (pharmacology)
• Permeability (drug effects)
• Regional Blood Flow (physiology)
• Reperfusion Injury (metabolism, prevention & control)
• Sydnones (pharmacology)