Increased L-arginine transport in human erythrocytes in chronic heart failure

1. Transport of L-arginine was investigated under zero-trans conditions in human erythrocytes from healthy donors and patients with heart failure. 2. Saturable influx of L-arginine was mediated by the classical cationic amino acid transport systems y(+) and y(+)L. 3. The V-max for L-arginine transport via system y(+) increased from 292 to 490 mu mol h(-1)1(-1) of cells in heart failure. 4. With system y(+) inhibited by N-ethylmaleimide (0.2 mmol/l), the V-max for the transport of L-arginine via system y(+)L was unaffected in erythrocytes from patients with heart failure. 5. The inhibition of L-arginine and L-leucine influx by N-G-monomethyl-L-arginine was similar in erythrocytes from control and heart failure patients. 6. Plasma L-arginine levels were reduced in patients with heart failure (59 mu mol/l) compared with controls (125 mu mol/l). Plasma from patients with heart failure also contained the endogenous L-arginine analogue N-G-monomethyl-L-arginine, which was undetectable in plasma from controls. 7. Intracellular concentrations of L-arginine and N-G-monomethyl-L-arginine were significantly elevated in erythrocytes from patients with heart failure compared with controls, consistent with an increased transport capacity for L-arginine and N-G-monomethyl-L-arginine. 8. The present study provides the first evidence that system y(+) mediates the increased transport of L-arginine in human erythrocytes from patients with chronic heart failure. These findings are similar to our previous results obtained in patients with chronic renal failure. Since both pathologies seem to present with an increased synthesis of nitric oxide, studies of L-arginine transport in erythrocytes may provide a valuable paradigm to study abnormalities of the L-arginine-nitric oxide signalling pathway.