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

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Abstract
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−1each; 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.