L-Arginine uptake affects nitric oxide production and blood flow in the renal medulla.
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 micromol.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.
Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, USA.
Masao
M
Kakoki
Hyung-Suk
HS
Kim
William J
WJ
Arendshorst
David L
DL
Mattson
D000818:Animals; D001120:Arginine / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D001692:Biological Transport; D007679:Kidney Medulla / Q000187:drug effects / Q000502:physiology*; D017078:Laser-Doppler Flowmetry; D008239:Lysine / Q000097:blood; D008297:Male; D017551:Microdialysis; D009569:Nitric Oxide / Q000378:metabolism*; D009952:Ornithine / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology*; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*
D009569:Nitric Oxide; D001120:Arginine; D009952:Ornithine; D008239:Lysine