15849232

pubmed:Citation

4

In cultured endothelial cells, 70-95% of extracellular l-arginine uptake has been attributed to the cationic amino acid transporter-1 protein (CAT-1). We tested the hypothesis that extracellular l-arginine entry into endothelial cells via CAT-1 plays a crucial role in endothelial nitric oxide (NO) production during in vivo conditions. Using l-lysine, the preferred amino acid transported by CAT-1, we competitively inhibited extracellular l-arginine transport into endothelial cells during conditions of NaCl hyperosmolarity, low oxygen, and flow increase. Our prior studies indicate that each of these perturbations causes NO-dependent vasodilation. The perivascular NO concentration ([NO]) and blood flow were determined in the in vivo rat intestinal microvasculature. Suppression of extracellular l-arginine transport significantly and strongly inhibited increases in vascular [NO] and intestinal blood flow during NaCl hyperosmolarity, lowered oxygen tension, and increased flow. These results suggest that l-arginine from the extracellular space is accumulated by CAT-1. When CAT-1-mediated transport of extracellular l-arginine into endothelial cells was suppressed, the endothelial cell NO response to a wide range of physiological stimuli was strongly depressed.

eng

IM

MEDLINE

0363-6135

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H1381-90

pubmed-meshheading:15849232-Animals, pubmed-meshheading:15849232-Anti-Arrhythmia Agents, pubmed-meshheading:15849232-Arginine, pubmed-meshheading:15849232-Cationic Amino Acid Transporter 1, pubmed-meshheading:15849232-Cations, pubmed-meshheading:15849232-Endothelium, Vascular, pubmed-meshheading:15849232-Enzyme Inhibitors, pubmed-meshheading:15849232-Extracellular Space, pubmed-meshheading:15849232-Jejunum, pubmed-meshheading:15849232-Lysine, pubmed-meshheading:15849232-Male, pubmed-meshheading:15849232-Microcirculation, pubmed-meshheading:15849232-NG-Nitroarginine Methyl Ester, pubmed-meshheading:15849232-Nitric Oxide, pubmed-meshheading:15849232-Osmolar Concentration, pubmed-meshheading:15849232-Oxygen, pubmed-meshheading:15849232-Perfusion, pubmed-meshheading:15849232-Rats, pubmed-meshheading:15849232-Rats, Sprague-Dawley, pubmed-meshheading:15849232-Regional Blood Flow, pubmed-meshheading:15849232-Sodium Chloride, pubmed-meshheading:15849232-Thiourea

Transport of extracellular l-arginine via cationic amino acid transporter is required during in vivo endothelial nitric oxide production.

Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, N.I.H., Extramural