PMID- 11158987 OWN - NLM STAT- MEDLINE DCOM- 20010322 LR - 20200930 IS - 0363-6135 (Print) IS - 0363-6135 (Linking) VI - 280 IP - 2 DP - 2001 Feb TI - Increased L-arginine uptake and inducible nitric oxide synthase activity in aortas of rats with heart failure. PG - H859-67 AB - 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. FAU - Stathopulos, P B AU - Stathopulos PB AD - Cardiology Research Laboratory, Departments of Medicine, Pharmacology, and Toxicology, London Health Sciences Centre, University of Western Ontario, London, Ontario, Canada N6A 4G5. FAU - Lu, X AU - Lu X FAU - Shen, J AU - Shen J FAU - Scott, J A AU - Scott JA FAU - Hammond, J R AU - Hammond JR FAU - McCormack, D G AU - McCormack DG FAU - Arnold, J M AU - Arnold JM FAU - Feng, Q AU - Feng Q LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Am J Physiol Heart Circ Physiol JT - American journal of physiology. Heart and circulatory physiology JID - 100901228 RN - 0 (DNA Primers) RN - 0 (Enzyme Inhibitors) RN - 0 (Tumor Necrosis Factor-alpha) RN - 10028-17-8 (Tritium) RN - 94ZLA3W45F (Arginine) RN - EC 1.14.13.39 (Nitric Oxide Synthase) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type II) RN - EC 1.14.13.39 (Nos2 protein, rat) RN - V55S2QJN2X (NG-Nitroarginine Methyl Ester) SB - IM MH - Animals MH - Aorta/*enzymology MH - Arginine/*pharmacokinetics MH - Blood Pressure/physiology MH - DNA Primers MH - Disease Models, Animal MH - Dose-Response Relationship, Drug MH - Endothelium, Vascular/drug effects/metabolism MH - Enzyme Inhibitors/pharmacology MH - Gene Expression Regulation, Enzymologic MH - Heart Failure/*metabolism MH - Heart Rate/physiology MH - Male MH - NG-Nitroarginine Methyl Ester/pharmacology MH - Nitric Oxide Synthase/*genetics/*metabolism MH - Nitric Oxide Synthase Type II MH - Rats MH - Rats, Sprague-Dawley MH - Tritium MH - Tumor Necrosis Factor-alpha/genetics MH - Ventricular Pressure/physiology EDAT- 2001/02/13 11:00 MHDA- 2001/03/27 10:01 CRDT- 2001/02/13 11:00 PHST- 2001/02/13 11:00 [pubmed] PHST- 2001/03/27 10:01 [medline] PHST- 2001/02/13 11:00 [entrez] AID - 10.1152/ajpheart.2001.280.2.H859 [doi] PST - ppublish SO - Am J Physiol Heart Circ Physiol. 2001 Feb;280(2):H859-67. doi: 10.1152/ajpheart.2001.280.2.H859.