Hepatic ischemia is associated with an increase in liver parenchyma nitric oxide that is in part enzyme-independent.
BACKGROUND
Nitric oxide (NO) might be involved in liver response to local ischemia-reperfusion injury.


METHODS
A specific NO-sensitive electrode was inserted into liver parenchyma of anesthetized rabbits. After a 45-min period of stable NO signal, the vascular pedicle of the caudal lobe of the liver was clamped for 45 min, then the clamp was removed. Perfusion of the right upper lobe was left unchanged. The same procedure was applied in other animals after administration of a long-acting nonspecific NO synthase inhibitor NAPNA.


RESULTS
Occlusion of the caudal pedicle was associated with a mean threefold increase in NO signal measured in the caudal lobe. After unclamping, this signal returned within 8 min to baseline value and remained stable for the next 6 h. In the right upper lobe, NO signal was unaffected by caudal lobe ischemia. By the end of the 6-h reperfusion period, administration of the NO inhibitor l-NAME led to a suppression of the NO signal, thus demonstrating the specificity of the measurement. Plasma nitrate and nitrite concentrations remained almost unchanged during the study period in all groups. In animals whose NO synthases had been previously inhibited by NAPNA, clamping the caudal pedicle for 45 min was still associated with a significant increase in caudal lobe NO signal.


CONCLUSIONS
Nitric oxide is present in liver parenchyma, and its generation is dramatically affected by an ischemia injury. The increased NO generation during local ischemia is, at least in part, independent of NO synthases.
Lhuillier
Franck
F
Department of Anesthesiology and Intensive Care, Hôpital E Herriot, Lyon, France.
Parmantier
Pierre
P
Goudable
Joelle
J
Crova
Philippe
P
Delafosse
Bertrand
B
Annat
Guy
G
Cespuglio
Raymond
R
Viale
Jean Paul
JP
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007511:Ischemia / Q000201:enzymology / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000098:blood supply* / Q000201:enzymology / Q000378:metabolism*; D008102:Liver Circulation / Q000187:drug effects / Q000502:physiology*; D008111:Liver Function Tests; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D011817:Rabbits; D015427:Reperfusion Injury / Q000201:enzymology / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase