Limitations of exogenous L-arginine in exerting a cytoprotective effect onhepatic ischemia/reperfusion injury

To test whether or not the L-arginine/nitric oxide (NO) pathway induces a p rotective effect, we investigated the effect of exogenous L-arginine on hep atic ischemia/ reperfusion (I/R) injury, using ex vivo perfusion of the iso lated rat liver. The rat liver was removed and preserved in cold saline for 60 min, followed by 120 min of reperfusion with oxygenated perfusate at 37 degrees C. Either 600 mg/kg of L-arginine (groups 1 and 4), D-arginine (gr oup 2), N-G-nitro-L-arginine methyl ester (L-NAME) (group 3), or saline (gr oup 5) were administered through the portal vein starting from 5 min before reperfusion to 5 min after reperfusion. In group 4, 600 mg/ kg of L-NAME w as preadministered at 10 min prior to the administration of L-arginine. The intrahepatic nitric oxide (NO) levels showed only a temporal elevation (22 7% +/- 70% of the pre-reperfusion levels at 5 min) after reperfusion in gro up 1. Pretreatment with L-NAME suppressed the elevation of the NO levels im mediately after reperfusion in group 4. The lactate dehydrogenase release t o the effluent perfusate significantly decreased and the histological findi ngs showed that the sinusoidal damage observed after reperfusion was mitiga ted in group 1 more than in the other groups. These results thus suggest th at exogenous L-arginine produced a relatively small amount of NO and theref ore resulted in a slight decrease of hepatic I/R injury.