Mechanism of Action of Sympathetic Hepatic Nerves on Carbohydrate Metabolism in Perfused Rat Liver

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Abstract
In the perfused rat liver stimulation of the hepatic nerves around the portal vein and the hepatic artery was previously shown to increase glucose output, to shift lactate uptake to output, to decrease and re-distribute intrahepatic perfusion flow and to cause an overflow of noradrenaline into the hepatic vein. The metabolic effects could be caused directly via nerve hepatocyte contacts or indirectly (i) by the hemodynamic changes and/or (ii) by noradrenaline overflow from the afferent vasculature into the sinusoids. Evidence against the indirect modes of nerve action is presented. 1) Reduction of perfusion flow by lowering the perfusion pressure from 2 to 1 ml .times. min-1 .times. g-1.sbd.as after nerve stimulation.sbd.or to 0.35 ml .times. min-1 .times. g-1.sbd.far beyond the nerve stimulation-dependent effect.sbd.did not change glucose output and lowered lactate uptake only slightly. Only re-increase of flow to 2 ml .times. min-1 .times. g-1 enhanced glucose and lactate release transiently due to washout of glucose and lactate accumulated in parenchymal areas not perfused during low perfusion flow. 2) In chemically sympathetctomized livers nerve stimulation decreased perfusion flow almost normally but without changing the intrahepatic microcirculation; yet it enhanced glucose and lactate output only insignificantly and caused noradrenaline overflow of less than 10% of normal. Conversely, in the presence of nitroprussiate (III) nerve stimulation reduced overall flow only slightly without intrahepatic redistribution but still increased glucose and lactate output strongly and caused normal noradrenaline overflow. 3) During retrograde perfusion from the hepatic to the portal vein, when noradrenaline overflow from the afferent vasculature cannot reach the sinusoids, nerve stimulation caused an increase of glucose and lactate output, an overflow of noradrenaline and a reduction of perfusion flow similar to that observed during orthograde perfusion from the portal to the hepatic vein. The observation that flow reduction, due to different reasons, does not increase glucose and lactate output to an extent and with a time course comparable to that caused by nerve action and conversely, the finding that the metabolic nerve effects were preserved when flow changes were inhibited by nitroprussiate suggest that the hemodynamic alterations cannot be major mechanisms for the increase of glucose and lactate output after sympathetic nerve stimulation. The similarity of the metabolic nerve effects during ortho- and retrograde perfusion preclude noradrenaline overflow from the afferent vasculature into the sinusoids as a major mechanism. Thus, in rat liver a direct action via nerve-hepatocyte contacts is indicated.