1. Transport of L-arginine was investigated under zero-trans condition
s in human erythrocytes from healthy donors and patients with heart fa
ilure. 2. Saturable influx of L-arginine was mediated by the classical
cationic amino acid transport systems y(+) and y(+)L. 3. The V-max fo
r L-arginine transport via system y(+) increased from 292 to 490 mu mo
l 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-arg
inine via system y(+)L was unaffected in erythrocytes from patients wi
th 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 (1
25 mu mol/l). Plasma from patients with heart failure also contained t
he 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 elevat
ed in erythrocytes from patients with heart failure compared with cont
rols, consistent with an increased transport capacity for L-arginine a
nd N-G-monomethyl-L-arginine. 8. The present study provides the first
evidence that system y(+) mediates the increased transport of L-argini
ne in human erythrocytes from patients with chronic heart failure. The
se findings are similar to our previous results obtained in patients w
ith chronic renal failure. Since both pathologies seem to present with
an increased synthesis of nitric oxide, studies of L-arginine transpo
rt in erythrocytes may provide a valuable paradigm to study abnormalit
ies of the L-arginine-nitric oxide signalling pathway.