[Regulation of liver metabolism and hemodynamics by the hepatic nerves]

Abstract

The liver is innervated by sympathetic and parasympathetic nerves. The effects and mechanisms of actions of hepatic nerves were studied in the isolated rat, guinea pig and Tupaia liver perfused in a non-recirculating manner either via the portal vein or via both the hepatic artery and the portal vein. The arterial plexus was stimulated at the common hepatic artery, the portal plexus at the mesenteric vein or both plexus jointly at the artery and the portal vein in the liver hilus (1-20 Hz, 2 ms, 20 V, 0.5-5 min). Upon nerve stimulation sympathetic effects clearly predominated; parasympathetic actions could only be demonstrated in the presence of alpha- and beta-antagonists. Sympathetic stimulation increased glucose output, shifted lactate uptake to output, decreased ketone body, urea and glutamine formation as well as ammonia uptake, lowered oxygen uptake, reduced perfusion flow combined with an intrahepatic redistribution and perfusate mobilization, and caused an overflow of noradrenaline into the hepatic vein. All effects were mediated predominantly via alpha-receptors; they were dependent on extracellular calcium. Some effects were modulated by hormones: the glucagon-mediated increase of glucose output was further enhanced but that of lactate uptake was decreased by nerve stimulation; in the presence of insulin glucose output was increased only slightly. Parasympathetic stimulation had no effect on basal metabolism or hemodynamics. Yet, it antagonized the glucagon-stimulated glucose release and enhanced the slight, insulin-dependent increase of glucose utilization. The sympathetic nerves may act directly at the parenchymal cells or indirectly via an overflow of neurotransmitter from the vasculature or via hemodynamic changes. Experiments with the vessel relaxant sodium nitroprusside and with retrograde perfusion indicate that neither hemodynamic alterations nor noradrenaline overflow from the vasculature play a major role in the sympathetic alterations in glucose and lactate metabolism; rather the nerves appear to act directly within the parenchyma. Comparative studies with rat, guinea pig and tupaia livers corroborate the view that the sympathetic nerves act in the rat via contacts to only a few periportal hepatocytes with signal propagation through gap junctions, while they act in the guinea pig and tupaia via contacts to almost all parenchymal cells. Sympathetic nerve stimulation caused an increase in the activity of glycogen phosphorylase and a decrease of glycogen synthase; it left the activity of pyruvate kinase and the levels of fructose 2.6-bisphosphate and cyclic AMP unaltered.(ABSTRACT TRUNCATED AT 400 WORDS)