Increased L-arginine uptake and inducible nitric oxide synthase activity in aortas of rats with heart failure

Arginine crosses the cell membrane primarily through the system y(+) transp orter. The aim of this study was to investigate the role of L-arginine tran sport in nitric oxide (NO) production in aortas of rats with heart failure induced by myocardial infarction. Tumor necrosis factor-alpha levels in aor tas of rats with heart failure were six times higher than in sham rats (P< 0.01). L-Arginine uptake was increased in aortas of rats with heart failure compared with sham rats (P< 0.01). Cationic amino acid transporter-2B and inducible (i) nitric oxide synthase (NOS) expression were increased in aort as of rats with heart failure compared with sham rats (P< 0.05). Aortic str ips from rats with heart failure treated with L-arginine but not D-arginine increased NO production (P< 0.05). The effect of L-arginine on NO producti on was blocked by L-lysine, a basic amino acid that shares the same system y(+) transporter with L-arginine, and by the NOS inhibitor N-G-nitro-L-argi nine methyl ester (L-NAME). Treatment with L-lysine and L-NAME in vivo decr eased plasma nitrate and nitrite levels in rats with heart failure (P< 0.05 ). Our data demonstrate that NO production is dependent on iNOS activity an d L-arginine uptake and suggest that L-arginine transport plays an importan t role in enhanced NO production in heart failure.