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.
Gauthier
T W
TW
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Davenpeck
K L
KL
Lefer
A M
AM
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006439:Hemodynamics; D007150:Immunohistochemistry; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology*; D007962:Leukocytes / Q000502:physiology*; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology*; D019007:P-Selectin; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion; D026423:S-Nitroso-N-Acetylpenicillamine; D013152:Splanchnic Circulation; D014665:Vasodilator Agents / Q000494:pharmacology
D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D014665:Vasodilator Agents; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D010396:Penicillamine