Studies were conducted to investigate the metabolism of monoamines, in particular that of norepinephrine (NE), in the brain of rats with hepatic failure. Hepatic failure was induced in rats by either acute ischemic hepatic failure (AIHF) or portacaval anastomosis (PCS). Brain levels of NE and its metabolites including 3-methoxy-4-hydroxyphenylglycol (MHPG), the final metabolite of NE in the central nervous system, were determined by HPLC-voltammetry.
The following results were obtained:
1) AIHF rats showed significantly higher total-MHPG and lower NE levels in the brain as compared with controls.
2) In AIHF rats, a significant negative correlation between NE and either phenylalanine (Phe) or tyrosine (Tyr), as well as a significant positive correlation between MHPG and Phe or Tyr were demonstrated in the brain.
3) Altered NE and MHPG levels in the brain of AIHF rats were found to restore toward normal following the treatment with Fischer's solution.
4) PCS rats showed significantly higher total-MHPG levels in the brain as compared with controls, while no significant change was observed in NE level.
In conclution, the reduction of NE level in the brain of AIHF model appears to be caused, at least in part, by the enhanced catabolism of NE due to increased brain contents of Tyr and Phe. This finding seems to support the Fischer's hypothesis of "false neurotransmitter" in hepatic encephalopathy.