scholarly journals Uptake of nitric oxide synthase inhibitors by macrophage RAW 264.7 cells

1994 ◽  
Vol 301 (2) ◽  
pp. 313-316 ◽  
Author(s):  
K Schmidt ◽  
P Klatt ◽  
B Mayer

Uptake of the nitric oxide synthase inhibitors NG-methyl-L-arginine (L-NMA) and NG-nitro-L-arginine (L-NNA) by macrophages is mediated by two different mechanisms. Activation of the cells with cytokines resulted in an up-regulation of L-NMA uptake but did not affect L-NNA transport. Characterization of the transport sites revealed that uptake of L-NMA is mediated by a cationic amino acid transporter (system y+) whereas a neutral amino acid transporter (system L) accounts for the uptake of L-NNA.

2001 ◽  
Vol 280 (2) ◽  
pp. H859-H867 ◽  
Author(s):  
Peter B. Stathopulos ◽  
Xiangru Lu ◽  
Ji Shen ◽  
Jeremy A. Scott ◽  
James R. Hammond ◽  
...  

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-α 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 ofl-arginine on NO production was blocked byl-lysine, a basic amino acid that shares the same system y+ transporter withl-arginine, and by the NOS inhibitor N G-nitro-l-arginine methyl ester (l-NAME). Treatment with l-lysine andl-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 andl-arginine uptake and suggest that l-arginine transport plays an important role in enhanced NO production in heart failure.


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