EVIDENCE FOR ALTERED CENTRAL NORADRENERGIC FUNCTION IN EXPERIMENTAL ACUTE LIVER-FAILURE IN THE RAT

These is increasing evidence to suggest that central noradrenergic mec hanisms may contribute to the central nervous system manifestations of acute liver failure. To further elucidate this possibility, extracell ular brain concentrations of the monoamines, noradrenaline (NA), dopam ine (DA), and serotonin, were measured by high-performance liquid chro matography with electrochemical detection in microdialysates from the extracellular compartment of frontal cortex in rats with acute (ischem ic) liver failure at various times during the progression of encephalo pathy and brain edema, as well as in obligate control groups of animal s. In addition, binding sites for the noradrenergic receptor subtype l igands, [H-3]-prazosin (alpha(1) sites), [H-3]-RX821002 (alpha(2) site s), and [I-125]-iodopindolol (beta sites), were assessed using quantit ative receptor autoradiography in regions of the brains of rats at com a stage of acute liver failure and of control groups of animals. Coma stages of encephalopathy in acute liver failure were associated with s electively increased noradrenaline concentrations (P < .05) and a conc omitant selective loss of alpha(1) and beta(1) sites in frontal cortex and thalamus. These findings add to a growing body of evidence that c entral noradrenergic function is modified in acute liver failure and s uggest that alpha(1)/beta(1) receptor-mediated noradrenergic mechanism s may play a role in the pathogenesis of brain edema and encephalopath y in this condition.