AJP - Gastrointestinal and Liver Physiology, Vol 267, Issue 4 562-G568, Copyright © 1994 by American Physiological Society
Nitric oxide attenuates leukocyte-endothelial interaction via P-selectin in splanchnic ischemia-reperfusion
T. W. Gauthier, K. L. Davenpeck and A. M. Lefer
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
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.
