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

Masao Kakoki, Hyung Suk Kim, William J. Arendshorst, David L. Mattson

Research output: Contribution to journalArticlepeer-review

60 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)R1478-R1485
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number6 56-6
StatePublished - Dec 2004
Externally publishedYes


  • Cytometry
  • Kidney
  • Laser Doppler flowmetry
  • Microdialysis

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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