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1. Chronic renal failure (CRF) is associated with the abnormal regulation of nitric oxide (NO) synthesis at the systemic level. The transport ofl-arginine, upregulated in blood cells from uraemic patients, modulates NO synthesis in this pathological condition. The model of partial nephrectomy in rats is widely accepted as a valid model of uraemia. Because there are no reports ofl-arginine transport in blood cells from uraemic rats, the aim of the present study was to investigatel-arginine transport in red blood cells (RBCs) from these rats. 2. The kinetics ofl-arginine transport in RBC and plasma and the amino acid profiles of RBC were investigated in control, sham-operated and subtotally nephrectomized rats. 3. l-Arginine transport was mediated via the cationic amino acid transport system y+ and a transport system with kinetics resembling the human system y+L. In control RBC, the apparent Ki forl-leucine inhibition ofl-arginine transport via system y+L was 0.16 ± 0.02 and 4.8 ± 2 mmol/L in the presence of Li+ and Na+, respectively. 4. The Vmax values forl-arginine transport via system y+L and system y+ were similar in RBC from control sham-operated and uraemic rats. Moreover,l-arginine concentrations in plasma and RBC were not affected by uraemia. 5. The findings of the present study provide the first evidence thatl-arginine transport in rat erythrocytes is mediated by two distinct cationic transport systems with characteristics of systems y+ and y+L, which accept neutral amino acids only in the presence of Li+. In contrast with previous studies in uraemic patients, plasma levels and maximal transport rates ofl-arginine were not altered in this rat model of CRF. [ABSTRACT FROM AUTHOR]

1. Nitric oxide (NO) produced by human platelets plays an important role in all stages of platelet activation.l-Arginine, the precursor for NO synthesis, modulates NO production by platelets. Thel-arginine analogues asymmetric dimethylarginine (ADMA) andNG-monomethyl-l-arginine (l-NMMA) are endogenous inhibitors of nitric oxide synthase (NOS), involved in the physiopathology of arterial hypertension. The aim of the present study was to investigate the inhibitory effects of endogenous and exogenousl-arginine analogues onl-arginine influx in platelets from healthy controls and hypertensive patients.2. Twelve patients with uncomplicated essential hypertension (stage I) and 15 age-matched normotensive controls participated in the present study. Platelets were isolated and incubated withl-[3H]-arginine and increasing concentrations ofl-arginine analogues (5–2000 µmol/L).3. The influx ofl-arginine was inhibited in a concentration-dependent manner byl-NMMA in platelets from controls (Ki = 42 ± 6 µmol/L) and this inhibitory effect was markedly higher in hypertensive platelets (Ki = 23 ± 4 µmol/L).4. Similarly, the Ki for ADMA inhibition ofl-arginine transport was significantly more pronounced in platelets from hypertensive patients (Ki = 16 ± 1 µmol/L) compared with controls (Ki = 27 ± 2 µmol/L).5. In contrast,NG-nitro-l-arginine methyl ester (l-NAME) was found to be a weak inhibitor ofl-arginine influx in platelets from controls (Ki = 1917 ± 319 µmol/L) and hypertensive patients (Ki = 2279 ± 578 µmol/L). Aminoguanidine, a selective inhibitor of inducible NOS, failed to inhibitl-arginine transport.6. Our findings provide the first evidence that ADMA andl-NMMA markedly inhibitl-arginine transport in human platelets, an effect that is more pronounced in hypertensive patients. It is possible that endogenousl-arginine analogues, by inhibiting NO synthesis, are involved in the platelet activation present in hypertension. [ABSTRACT FROM AUTHOR]