TY - JOUR
T1 - Cationic amino acid transport in the renal medulla and blood pressure regulation
AU - Kakoki, Masao
AU - Wang, Weili
AU - Mattson, David L.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2002
Y1 - 2002
N2 - Previous studies have indicated that NO synthesis in isolated inner medullary collecting duct cells is reduced by cationic amino acids that compete with L-arginine for cellular uptake. In the present study, we investigated the effects of chronic renal medullary infusion of cationic amino acids on renal NO concentration and mean arterial pressure (MAP) in Sprague-Dawley rats. Renal medullary infusion of L-ornithine (50 μg/kg per min) or L-lysine (50 μg/kg per min) markedly decreased NO in the medulla (vehicle, 124±11 nmol/L; L-ornithine, 45±4 nmol/L; L-lysine, 42±6 nmol/L) and increased MAP (vehicle, 111±7 mm Hg; L-ornithine, 143±6 mm Hg; L-lysine, 148±3 mm Hg) after 5 days of infusion. In contrast, intravenous infusion of the same dose of L-ornithine or L-lysine for 5 days increased plasma concentration to levels similar to those observed with intramedullary infusion but did not change NO in the medulla or alter MAP. Furthermore, the NO-suppressing and hypertensive effects of medullary interstitial infusion of L-ornithine (50 μg/kg per min) were attenuated by simultaneous infusion of L-arginine (500 μg/kg per min; NO, 97±10 nmol/L; MAP, 124±3 mm Hg). A 5-day infusion of an antisense oligonucleotide against CAT-1 (18-mer, 8.3 nmol/h) significantly decreased CAT-1 protein in the medulla, decreased NO in the medulla (scrambled oligo, 124±10 nmol/L; antisense oligo, 67±11 nmol/L), and increased MAP (scrambled oligo, 113±2 mm Hg; antisense oligo, 130±2 mm Hg). These results suggest that uptake of L-arginine by cationic amino acid transport systems in the renal medulla plays an important role in the regulation of medullary NO and MAP in rats.
AB - Previous studies have indicated that NO synthesis in isolated inner medullary collecting duct cells is reduced by cationic amino acids that compete with L-arginine for cellular uptake. In the present study, we investigated the effects of chronic renal medullary infusion of cationic amino acids on renal NO concentration and mean arterial pressure (MAP) in Sprague-Dawley rats. Renal medullary infusion of L-ornithine (50 μg/kg per min) or L-lysine (50 μg/kg per min) markedly decreased NO in the medulla (vehicle, 124±11 nmol/L; L-ornithine, 45±4 nmol/L; L-lysine, 42±6 nmol/L) and increased MAP (vehicle, 111±7 mm Hg; L-ornithine, 143±6 mm Hg; L-lysine, 148±3 mm Hg) after 5 days of infusion. In contrast, intravenous infusion of the same dose of L-ornithine or L-lysine for 5 days increased plasma concentration to levels similar to those observed with intramedullary infusion but did not change NO in the medulla or alter MAP. Furthermore, the NO-suppressing and hypertensive effects of medullary interstitial infusion of L-ornithine (50 μg/kg per min) were attenuated by simultaneous infusion of L-arginine (500 μg/kg per min; NO, 97±10 nmol/L; MAP, 124±3 mm Hg). A 5-day infusion of an antisense oligonucleotide against CAT-1 (18-mer, 8.3 nmol/h) significantly decreased CAT-1 protein in the medulla, decreased NO in the medulla (scrambled oligo, 124±10 nmol/L; antisense oligo, 67±11 nmol/L), and increased MAP (scrambled oligo, 113±2 mm Hg; antisense oligo, 130±2 mm Hg). These results suggest that uptake of L-arginine by cationic amino acid transport systems in the renal medulla plays an important role in the regulation of medullary NO and MAP in rats.
KW - Amino acid
KW - Arterial pressure
KW - Kidney
KW - Nitric oxide
KW - Renal blood flow
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U2 - 10.1161/hy0202.102700
DO - 10.1161/hy0202.102700
M3 - Article
C2 - 11847199
AN - SCOPUS:0036178037
VL - 39
SP - 287
EP - 292
JO - Hypertension
JF - Hypertension
SN - 0194-911X
IS - 2 I
ER -