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This Article Full Text Full Text (PDF) All Versions of this Article: 287/6/R1478    most recent 00386.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (8) Citing Articles via Google Scholar Google Scholar Articles by Kakoki, M. Articles by Mattson, D. L. Search for Related Content PubMed PubMed Citation Articles by Kakoki, M. Articles by Mattson, D. L.

RENAL HEMODYNAMICS AND CARDIORENAL INTEGRATION

L-Arginine uptake affects nitric oxide production and blood flow in the renal medulla

¹Department of Pathology and Laboratory Medicine and ²Department of Cell and Molecular Physiology, University of North Carolina, Chapel Hill, North Carolina; and ³Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin

Submitted 8 June 2004 ; accepted in final form 13 August 2004

Experiments were performed to determine whether L-arginine transport regulates nitric oxide (NO) production and hemodynamics in the renal medulla. The effects of renal medullary interstitial infusion of cationic amino acids, which compete with L-arginine for cellular uptake, on NO levels and blood flow in the medulla were examined in anesthetized rats. NO concentration in the renal inner medulla, measured with a microdialysis-oxyhemoglobin trapping technique, was significantly decreased by 26–44% and renal medullary blood flow, measured by laser Doppler flowmetry, was significantly reduced by 20–24% during the acute renal medullary interstitial infusion of L-ornithine, L-lysine, and L-homoarginine (1 µmol·kg^–1·min^–1 each; n = 6–8/group). In contrast, intramedullary infusion of L-arginine increased NO concentration and medullary blood flow. Flow cytometry experiments with 4-amino-5-methylamino-2',7'-difluorescein diacetate, a fluorophore reactive to intracellular NO, demonstrated that L-ornithine, L-lysine, and L-homoarginine decreased NO by 54–57% of control, whereas L-arginine increased NO by 21% in freshly isolated inner medullary cells (1 mmol/l each, n > 1,000 cells/experiment). The mRNA for the cationic amino acid transporter-1 was predominantly expressed in the inner medulla, and cationic amino acid transporter-1 protein was localized by immunohistochemistry to the collecting ducts and vasa recta in the inner medulla. These results suggest that L-arginine transport by cationic amino acid transport mechanisms is important in the production of NO and maintenance of blood flow in the renal medulla.

kidney; microdialysis; laser Doppler flowmetry; cytometry

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