Activation of L-arginine transport in peripheral blood mononuclear cells in chronic renal failure

Abstract.

Transport of LL-arginine, the precursor for nitric oxide (NO) synthesis, has been investigated in human peripheral blood mononuclear cells (PBMCs) obtained from healthy volunteers and chronic renal failure patients. Chronic renal failure patients were either on treatment by haemodialysis or continuous ambulatory peritoneal dialysis (CAPD). Saturable influx of L-arginine in PBMCs was mediated by the cationic amino acid transport systems y⁺ and y⁺L. Initial rates of L-arginine transport (2 µM) via system y⁺ were significantly increased in chronic renal failure patients, whereas transport via system y⁺L was unaffected. The increase in L-arginine transport via system y⁺ was: 1.7-fold in uraemic patients on CAPD, 4.3-fold in uraemic patients pre-haemodialysis and 2.6-fold post-haemodialysis. When the intracellular PBMCs amino acid profile was analysed in chronic renal failure patients and control subjects, L-lysine and L-arginine concentrations were significantly increased in pre-haemodialysis uraemic patients and restored to normal values by haemodialysis and CAPD. The present study provides the first evidence that system y⁺ mediates the increased transport of L-arginine in PBMCs from patients with chronic renal failure. The increased activity of system y⁺ may provide the necessary supply of L-arginine to sustain NO synthesis in PBMCs exposed to increased levels of circulating cytokines in chronic renal failure.