Nitric oxide modulates gut ischemia-reperfusion-induced P-selectin expression in murine liver.

Abstract

Reperfusion of ischemic intestine is associated with P-selectin-dependent adhesion of leukocytes in the liver microcirculation. The objective of this study was to define the contribution of nitric oxide (NO) to the enhanced P-selectin expression and increased leukocyte rolling elicited by gut ischemia-reperfusion (I/R). Leukocyte rolling (monitored by intravital microscopy) in the terminal hepatic venules (THV) and P-selectin expression (measured using the dual-radiolabeled monoclonal antibody technique) were determined in mice after 15 min of superior mesenteric artery occlusion and 30 min of reperfusion. After 30 min of reperfusion, P-selectin expression was significantly increased in the liver, intestine, and lung, with a corresponding increase in the number of rolling leukocytes (in THV). The NO synthase inhibitor NG-monomethyl-L-arginine exaggerated the gut I/R-induced increases in both rolling leukocytes and P-selectin expression (in liver and intestine), responses that were not detected with coadministration of L-arginine or in P-selectin-deficient mice. The NO donor diethylenetriamine/NO and L-arginine were both effective in attenuating the gut I/R-induced increases in rolling leukocytes (in THV) and P-selectin expression (in liver, intestine, and lung). These findings indicate that NO modulates gut I/R-induced recruitment of rolling leukocytes in THV via an action on P-selectin expression.