Nitric oxide attenuates leukocyte-endothelial interaction via P-selectin in splanchnic ischemia-reperfusion

We studied the effects of exogenous nitric oxide (NO) on leukocyte-endothelial interaction after 60 min of splanchnic artery ischemia and 120 min of reperfusion (SAO/R) in pentobarbital sodium-anesthetized rats via intravital microscopy. Treatment with the NO donor S-nitroso-N-acetylpenicillamine (SNAP, 20 micrograms/kg bolus followed by infusion at 20 micrograms.kg-1.h-1), beginning 10 min before reperfusion, resulted in significantly decreased leukocyte-endothelial interaction. This was manifested by a significant decrease in leukocyte rolling and adherence in the postcapillary venules. Tissue protection was demonstrated by a significantly lower plasma free amino-nitrogen concentration in the SNAP-treated SAO/R rats compared with those receiving NO-depleted SNAP (P < 0.05). Immunohistochemical localization of P-selectin showed significantly decreased P-selectin expression on the venular endothelium after SAO/R in rats given SNAP 10 min before reperfusion (23.0 +/- 3.2% vs. 54.9 +/- 12.1% positive staining, respectively, P < 0.01). From these data, we conclude that the effects of exogenous NO on leukocyte-endothelial interaction after ischemia-reperfusion appear to be at least partially mediated through the endothelial adhesion molecule P-selectin.