Published online before print September 22, 2003, doi: 10.1161/01.HYP.0000094557.36656.D0
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(Hypertension. 2003;42:1014.)
© 2003 American Heart Association, Inc.
Scientific Contributions |
L-Arginine Reverses p47phox and gp91phox Expression Induced by High Salt in Dahl Rats
From the Department of Cardiovascular Physiology, Kagawa Medical University, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
Correspondence to Hiroaki Kosaka, Department of Cardiovascular Physiology, Kagawa Medical University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan. E-mail hkosaka{at}kms.ac.jp
Derangements in the production and degradation of reactive oxygen species (ROS) as well as nitric oxide (NO) have been implicated in cardiovascular diseases. We explored how supplementation with L-arginine, an NO synthase substrate, restores such derangements of ROS/NO systems in Dahl salt-sensitive, hypertensive (DS) rats. We detected an increase of NADPH oxidase activity, a key enzyme that produces superoxide, in the membrane fraction of the renal cortex derived from DS rats loaded with high salt for 4 weeks; high salt loading also remarkably increased urinary H2O2, 8-isoprostane, and thromboxane B2 excretion and decreased plasma NO end products. These changes from high salt loading were counteracted by oral L-arginine supplementation. We further examined expression patterns of NADPH oxidase subunits in renal cortex derived from these animals. High salt loading increased gp91phox and p47phox but not p22phox or Rac1 or mRNA abundance, which were counteracted with L-arginine supplementation. Western blot analyses after subcellular fractionation revealed that L-arginine supplementation distinctly decreases membrane localization of p47phox protein, as it decreases total expression of Rac1 protein in DS rats with high salt loading. These results disclose that high salt loading causes a deficiency in available L-arginine amounts for NO synthases and induces NADPH oxidase activation in the renal cortex of DS rats, which L-arginine supplementation markedly restores. Since superoxide rapidly eliminates NO, which inhibits sodium reabsorption in the cortical collecting duct, superoxide production caused by upregulated NADPH oxidase activity in the renal cortex of high salt–loaded DS rats may accelerate sodium reabsorption and hypertension.
Key Words: rats, Dahl • arginine • hypertension, sodium-dependent • nitric oxide • cardiovascular diseases
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