Adenosine preconditioning attenuates hepatic reperfusion injury in the rat by preventing the down-regulation of endothelial nitric oxide synthase.
BACKGROUND
Previous work has suggested that in the liver, adenosine preconditioning is mediated by nitric oxide. Whether the endothelial isoform of nitric oxide synthase plays a part in this mechanism has however not yet been investigated.


METHODS
Wistar rats were used (6 in each group)--Groups: (1) sham, (2) ischemia-reperfusion, (3) adenosine + ischemia-reperfusion, (4) endothelial isoform inhibitor + adenosine + ischemia-reperfusion.


RESULTS
Using immunohistochemistry, this study has revealed a decrease in the expression of endothelial nitric oxide synthase following hepatic ischemia-reperfusion. This was prevented by adenosine pre-treatment. When an inhibitor of endothelial nitric oxide synthase was administered prior to adenosine pre-treatment, pre-conditioning did not occur despite normal expression of endothelial nitric oxide synthase.


CONCLUSIONS
These findings suggest that adenosine attenuates hepatic injury by preventing the downregulation of endothelial nitric oxide synthase that occurs during ischemia-reperfusion.
Serracino-Inglott
Ferdinand
F
Division of Surgery, Anaesthetics & Intensive Care, Imperial College School of Medicine, Hammersmith Hospital, London W12 0NN, UK. fsinglott@hotmail.com
Virlos
Ioannis T
IT
Habib
Nagy A
NA
Williamson
Robin C N
RC
Mathie
Robert T
RT
D000241:Adenosine / Q000494:pharmacology / Q000627:therapeutic use*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D015536:Down-Regulation / Q000187:drug effects; D007511:Ischemia / Q000201:enzymology; D019194:Ischemic Preconditioning; D008099:Liver / Q000098:blood supply* / Q000201:enzymology / Q000473:pathology; D008107:Liver Diseases / Q000097:blood / Q000201:enzymology / Q000517:prevention & control*; D008297:Male; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000201:enzymology / Q000517:prevention & control*
D019001:Nitric Oxide Synthase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000241:Adenosine