Evidence for altered central noradrenergic function in experimental acute liver failure in the rat

Hepatology. 1998 Feb;27(2):362-8. doi: 10.1002/hep.510270208.


These is increasing evidence to suggest that central noradrenergic mechanisms may contribute to the central nervous system manifestations of acute liver failure. To further elucidate this possibility, extracellular brain concentrations of the monoamines, noradrenaline (NA), dopamine (DA), and serotonin, were measured by high-performance liquid chromatography with electrochemical detection in microdialysates from the extracellular compartment of frontal cortex in rats with acute (ischemic) liver failure at various times during the progression of encephalopathy and brain edema, as well as in obligate control groups of animals. In addition, binding sites for the noradrenergic receptor subtype ligands, [3H]-prazosin (alpha1 sites), [3H]-RX821002 (alpha2 sites), and [125]I-iodopindolol (beta sites), were assessed using quantitative receptor autoradiography in regions of the brains of rats at coma stage of acute liver failure and of control groups of animals. Coma stages of encephalopathy in acute liver failure were associated with selectively increased noradrenaline concentrations (P < .05) and a concomitant selective loss of alpha1 and beta1 sites in frontal cortex and thalamus. These findings add to a growing body of evidence that central noradrenergic function is modified in acute liver failure and suggest that alpha1/beta1 receptor-mediated noradrenergic mechanisms may play a role in the pathogenesis of brain edema and encephalopathy in this condition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-Antagonists / metabolism
  • Adrenergic alpha-Antagonists / pharmacology
  • Adrenergic beta-Antagonists / metabolism
  • Adrenergic beta-Antagonists / pharmacology
  • Animals
  • Autoradiography
  • Cerebral Cortex / metabolism*
  • Chromatography, High Pressure Liquid
  • Coma / metabolism
  • Dopamine / metabolism
  • Frontal Lobe / metabolism*
  • Hippocampus / chemistry
  • Hypothalamus / chemistry
  • Idazoxan / analogs & derivatives
  • Idazoxan / metabolism
  • Liver Failure, Acute / metabolism*
  • Microdialysis
  • Norepinephrine / metabolism*
  • Pindolol / analogs & derivatives
  • Pindolol / metabolism
  • Prazosin / metabolism
  • Propanolamines / pharmacology
  • Putamen / chemistry
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Adrenergic / analysis
  • Serotonin / metabolism
  • Thalamus / chemistry


  • Adrenergic alpha-Antagonists
  • Adrenergic beta-Antagonists
  • Propanolamines
  • Receptors, Adrenergic
  • Serotonin
  • ICI 118551
  • Pindolol
  • ICI 89406
  • 2-methoxyidazoxan
  • Dopamine
  • Norepinephrine
  • Prazosin
  • Idazoxan