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.
Kakoki
Masao
M
Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, USA.
Kim
Hyung-Suk
HS
Arendshorst
William J
WJ
Mattson
David L
DL
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