Role of nitric oxide in gut ischemia-reperfusion-induced hepatic microvascular dysfunction.
The overall objective of this study was to assess the contribution of an altered bioavailability of nitric oxide (NO) to the leukocyte adhesion and hypoxic stress elicited in the liver by gut ischemia-reperfusion (I/R). The accumulation of leukocytes, number of nonperfused sinusoids (NPS), and NADH autofluorescence were monitored (by intravital microscopy) in mouse liver after 15 min of superior mesenteric artery occlusion and 60 min of reperfusion. Leukostasis, NPS, and NADH autofluorescence (indicating hypoxia) were all increased in the liver at 60 min after gut I/R. The NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) exaggerated the liver leukostasis elicited by gut I/R, responses that were prevented by coadministration of L-arginine. The NO donor diethylenetriamine-NO (DETA-NO) and L-arginine were both effective in attenuating the gut I/R-induced leukostasis and increased NADH autofluorescence, whereas neither DETA nor D-arginine exerted a protective action. These findings indicate that NO is an important determinant of the liver leukostasis, impaired sinusoidal perfusion, and tissue hypoxia elicited by gut I/R.
Horie
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Department of Molecular and Cellular Physiology, Louisiana State University Medical Center, Shreveport 71130, USA.
Wolf
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R
Granger
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DN
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001682:Biological Availability; D007422:Intestines / Q000098:blood supply*; D007511:Ischemia / Q000503:physiopathology*; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology; D008102:Liver Circulation / Q000187:drug effects / Q000502:physiology*; D008638:Mesenteric Arteries / Q000502:physiology; D008641:Mesenteric Vascular Occlusion; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology*; D009243:NAD / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D014226:Triazenes / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
C105351:1-hydroxy-2-oxo-3,3-bis(2-aminoethyl)-1-triazene; D014226:Triazenes; D009243:NAD; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000410:Alanine Transaminase