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Am J Physiol Heart Circ Physiol (April 22, 2005). doi:10.1152/ajpheart.01231.2004
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Submitted on December 7, 2004
Accepted on April 8, 2005

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

Brett G Zani1 and H. Glenn Bohlen1*

1 Cellular and Integrative Physiology, Indiana University Medical School, Indianapolis, Indiana, USA

* To whom correspondence should be addressed. E-mail: gbohlen{at}iupui.edu.

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 each of these perturbations cause 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 to 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.




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