Increased L-arginine uptake and inducible nitric oxide synthase activity in aortas of rats with heart failure.
L-Arginine crosses the cell membrane primarily through the system y(+) transporter. The aim of this study was to investigate the role of L-arginine transport in nitric oxide (NO) production in aortas of rats with heart failure induced by myocardial infarction. Tumor necrosis factor-alpha levels in aortas 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 aortas of rats with heart failure compared with sham rats (P < 0.05). Aortic strips 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 production 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-arginine methyl ester (L-NAME). Treatment with L-lysine and L-NAME in vivo decreased plasma nitrate and nitrite levels in rats with heart failure (P < 0.05). Our data demonstrate that NO production is dependent on iNOS activity and L-arginine uptake and suggest that L-arginine transport plays an important role in enhanced NO production in heart failure.
Stathopulos
P B
PB
Cardiology Research Laboratory, Departments of Medicine, Pharmacology, and Toxicology, London Health Sciences Centre, University of Western Ontario, London, Ontario, Canada N6A 4G5.
Lu
X
X
Shen
J
J
Scott
J A
JA
Hammond
J R
JR
McCormack
D G
DG
Arnold
J M
JM
Feng
Q
Q
D000818:Animals; D001011:Aorta / Q000201:enzymology*; D001120:Arginine / Q000493:pharmacokinetics*; D001794:Blood Pressure / Q000502:physiology; D017931:DNA Primers; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D006333:Heart Failure / Q000378:metabolism*; D006339:Heart Rate / Q000502:physiology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000235:genetics* / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017207:Rats, Sprague-Dawley; D014316:Tritium; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D017725:Ventricular Pressure / Q000502:physiology
D017931:DNA Primers; D004791:Enzyme Inhibitors; D014409:Tumor Necrosis Factor-alpha; D014316:Tritium; D001120:Arginine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D019331:NG-Nitroarginine Methyl Ester