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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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