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Evidence for altered central noradrenergic function in experimental acute liver failure in the rat
Author(s) -
Michalak Adrianna,
Rose Christopher,
Buu Paul N.,
Butterworth Roger F.
Publication year - 1998
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510270208
Subject(s) - hepatic encephalopathy , medicine , endocrinology , norepinephrine , microdialysis , encephalopathy , serotonergic , monoamine neurotransmitter , coma (optics) , central nervous system , serotonin , dopamine , receptor , cirrhosis , physics , optics
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, [ 3 H]‐prazosin (α 1 sites), [ 3 H]‐RX821002 (α 2 sites), and [ 125 ]I‐iodopindolol (β 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 α 1 and β 1 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 α 1 /β 1 receptor–mediated noradrenergic mechanisms may play a role in the pathogenesis of brain edema and encephalopathy in this condition.