Microcirculatory dysfunction during intestinal ischemia-reperfusion.
Oxido-reductive stress is a crucial factor of the tissue response during ischemia-reoxygenation injuries. Reperfusion affects primarily the microvasculature in a manner consistent with an acute inflammatory reaction. In this respect, the salient data suggest an important connection between endothelial cell-derived humoral mediators and the perivascular mast cell system. Increased endothelin-1 and decreased nitric oxide formation, mast cell degranulation and leukocyte accumulation coexist in gastrointestinal ischemia-reperfusion syndromes too. Constitutively produced nitric oxide inhibits, while increasingly formed endothelin-1 significantly enhances the degranulation of the intestinal mast cells. The endothelin-A receptor-dependent mast cell degranulation per se plays a secondary role in reperfusion-induced structural injury, but contributes significantly to leukocyte recruitment into the reperfused intestinal mucosa. It is conceivable therefore, that the nitric oxide--endothelin-1--mast cell cycle is involved in the mechanism of ischemia-reperfusion-induced endothelial cell-leukocyte interactions, where mast cells act to amplify the process of leukocyte sequestration. The alteration in the balance between endothelial cell-derived proadhesive vasoconstrictor and antiadhesive vasodilator factors exerts a significant influence on the mucosal integrity, and the antagonism of endothelin-A receptor activation in this setting tips the equilibrium toward tissue salvage.
Boros
M
M
Institute of Surgical Research, University of Szeged, Szeged, Hungary. boros@expsur.szote.u-szeged.hu
D000818:Animals; D006801:Humans; D007413:Intestinal Mucosa / Q000098:blood supply* / Q000378:metabolism / Q000503:physiopathology*; D008833:Microcirculation / Q000502:physiology; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology*