Uptake of Amino Acids by Brain Micro vessels Isolated from Rats with Experimental Chronic Renal Failure

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Abstract
The neurological disorders seen in patients with chronic renal failure and liver cirrhosis are analogous. Previous in vivo studies have shown that the impaired blood- brain amino acid transport seen in rats with chronic renal failure is similar to that of rats with portocaval anastomosis. To elucidate whether a comparable underlying pathogenic mechanism plays a role in both pathological conditions, blood and brain amino acid levels together with amino acid transport by isolated brain microvessels have been studied in rats with chronic failure and in sham-operated rats. Brain microvessels isolated from rats with experimental chronic renal failure showed that the uptake of labeled large neutral amino acid, i.e., leucine or phenylalanine, but not of lysine or .alpha.-methylaminoisobutyric acid, was significantly increased with respect to sham-operated rats; conversely, the uptake of glutamic acid in rats with chronic renal failure was significantly lower compared with values in controls. Kinetic analysis indicated that this was mainly due to increased exchange transport activity (Vmax) of the L-system, rather than to changes in the affinity (Km) of the carrier system for the relative substrate. These data, together with the significant rise of brain glutamine levels and an increased brain-to-plasma ratio of the sum of large neutral amino acids, are analogous to what was previously observed in rats with portocaval anastomosis. Because increased brain influx of large neutral amino acids, especially the neurotransmitter precursor amino acids, is thought to be responsible for the altered brain neurotransmission observed in chronic liver failure, these data support the hypothesis that the neurological disorders seen in chronic renal failure may result from functional modifications to the L-system''s transport activity at the blood-brain barrier, similar to those observed in chronic liver failure.