Impairment of metabolic hepatic nerve action by chronic but not acute ethanol intoxication studied in isolated perfused rat liver

Background/Aims: Liver carbohydrate metabolism and blood flow are regulated by hepatic nerves and hormones such as glucagon, insulin or catecholamines. Acute and chronic application of alcohol are known to depress the function of central and peripheral nerves. The extent of inhibition of the autonomic nervous system is not well characterized; thus, the possible impairment of hepatic nerve function by acute and chronic application of ethanol was investigated. Methods: Rat livers were perfused simultaneously via both the portal vein and hepatic artery. Hepatic nerves were stimulated electrically for 2 min (20 Hz, 20 V, 2 ms). As a control, noradrenaline (1 μM) was infused into the portal vein for 2 minutes. Results: During acute application of ethanol in portal concentrations of 50, 150 and 300 mM, which elevated basal glucose release, stimulation of hepatic nerves as well as portal noradrenaline infusion caused the same increase in glucose output and decrease in portal and arterial flow as in controls. Following chronic application of ethanol by feeding rats the Lieber-DeCarli liquid diet containing 5% (v/v) ethanol for 4 and 6 weeks, only nerve stimulation caused a significantly reduced enhancement of glucose output (50%, p<0.025), whereas portal noradrenaline was as effective as in controls. Noradrenaline overflow was significantly reduced following nerve stimulation. Conclusion: The decrease in nerve stimulation-dependent glucose output and noradrenaline overflow in chronically ethanol fed rats indicates an impaired function of hepatic nerves.