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1 Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC, USA
2 Cell and Molecular Physiology, University of North Carolina, Chapel Hill, NC, USA
3 Physiology, Medical College of Wisconsin, Milwaukee, WI, USA
* To whom correspondence should be addressed. E-mail: dmattson{at}mcw.edu.
Experiments were performed to determine if 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/min each, n=6-8/group). In contrast, intramedullary infusion of L-arginine increased NO concentration and medullary blood flow. Flow cytometry experiments with DAF-FM, a fluorophore reactive to intracellular NO, demonstrated that L-ornithine, L-lysine, and L-homoarginine decreased NO by 54-57% of control while L-arginine increased NO by 21% in freshly isolated inner medullary cells (1 mmol/L each, n>1000 cells/experiment). The mRNA for the cationic amino acid transporter 1 (CAT1) was predominantly expressed in the inner medulla, and CAT1 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.
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