Nitric oxide modulates gut ischemia-reperfusion-induced P-selectin expression in murine liver.
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.
Department of Molecular and Cellular Physiology, Center of Excellence in Arthritis and Rheumatology, Louisiana State University Medical Center, Shreveport, Louisiana 71130, USA.
Y
Y
Horie
R
R
Wolf
D C
DC
Anderson
D N
DN
Granger
D000818:Animals; D000911:Antibodies, Monoclonal; D001120:Arginine / Q000494:pharmacology; D003433:Crosses, Genetic; D003671:DEET / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000098:blood supply*; D007511:Ischemia / Q000503:physiopathology*; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology; D008099:Liver / Q000098:blood supply / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D017538:Mesenteric Artery, Superior; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000502:physiology*; D019007:P-Selectin / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D051381:Rats; D015424:Reperfusion; D013152:Splanchnic Circulation / Q000502:physiology*; D019323:omega-N-Methylarginine / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D019007:P-Selectin; D003671:DEET; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine