Effect of nitric oxide on the hypoglycaemic phase of endotoxaemia

Depletion of liver glycogen stores and subsequent hypoglycaemia is one of the unresolved features in endotoxaemia. The aim of this study was to elucidate the effect of L-arginine treatment on the glucose requirement and impending liver damage during the hypoglycaemic period of endotoxaemia.

Sixty-three of 98 male Wistar rats were assigned equally to one of three groups and received saline as control, L-arginine as selective nitric oxide donor or N(G)-nitro-L-arginine methyl ester for non-selective inhibition of nitric oxide production 1 h before endotoxin injection. At 2, 4 and 6 h following endotoxin, blood and liver samples were collected. Plasma nitrite plus nitrate, glucose, insulin and glucagon concentrations and total liver-reduced glutathione were measured. Hepatocellular glycogen content and liver damage were assessed simultaneously by histological quantification. An additional seven rats were allocated to each group and subjected to i.v. glucose tolerance test during the hypoglycaemic period.

Increased levels of endogenousglutathione (P = 0.003) and excess nitric oxide (P = 0.002) apparently protected the liver from endotoxin-induced injury by preserving the optimum glucose consumption rate, insulin/glucagon ratio and liver glycogen in L-arginine-plus-endotoxin-treated group. Furthermore, expected hypoglycaemic period was not observed in these animals.

Exogenous L-arginine prevented the excessive liver glycogen release without inhibiting glucose consumption while decreasing hepatic injury during the expected hypoglycaemic phase of endotoxaemia.