This Article Full Text Full Text (PDF) All Versions of this Article: 42/5/1014    most recent 01.HYP.0000094557.36656.D0v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fujii, S. Articles by Kosaka, H. Search for Related Content PubMed PubMed Citation Articles by Fujii, S. Articles by Kosaka, H. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB (L)-ARGININE NITRIC OXIDE PROSTAGLANDIN F2ALPHA SODIUM CHLORIDE Medline Plus Health Information High Blood Pressure Related Collections Hypertension - basic studies

(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

This article has been cited by other articles:

				H. Matsui, K. Ando, H. Kawarazaki, A. Nagae, M. Fujita, T. Shimosawa, M. Nagase, and T. Fujita Salt Excess Causes Left Ventricular Diastolic Dysfunction in Rats With Metabolic Disorder Hypertension, August 1, 2008; 52(2): 287 - 294. [Abstract] [Full Text] [PDF]

				E. Grossman Does Increased Oxidative Stress Cause Hypertension? Diabetes Care, February 1, 2008; 31(Supplement_2): S185 - S189. [Abstract] [Full Text] [PDF]

				C.-C. Yang, M.-C. Ma, C.-T. Chien, M.-S. Wu, W.-K. Sun, and C.-F. Chen Hypoxic preconditioning attenuates lipopolysaccharide-induced oxidative stress in rat kidneys J. Physiol., July 1, 2007; 582(1): 407 - 419. [Abstract] [Full Text] [PDF]

				R. Liu, J. L. Garvin, Y. Ren, P. J. Pagano, and O. A. Carretero Depolarization of the macula densa induces superoxide production via NAD(P)H oxidase Am J Physiol Renal Physiol, June 1, 2007; 292(6): F1867 - F1872. [Abstract] [Full Text] [PDF]

				A. K. Khanna and G. M. Pieper NADPH oxidase subunits (NOX-1, p22phox, Rac-1) and tacrolimus-induced nephrotoxicity in a rat renal transplant model Nephrol. Dial. Transplant., February 1, 2007; 22(2): 376 - 385. [Abstract] [Full Text] [PDF]

				S. Wesseling, J. A. Joles, H. van Goor, H. A. Bluyssen, P. Kemmeren, F. C. Holstege, H. A. Koomans, and B. Braam Transcriptome-based identification of pro- and antioxidative gene expression in kidney cortex of nitric oxide-depleted rats Physiol Genomics, January 17, 2007; 28(2): 158 - 167. [Abstract] [Full Text] [PDF]

				K. Bedard and K.-H. Krause The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology Physiol Rev, January 1, 2007; 87(1): 245 - 313. [Abstract] [Full Text] [PDF]

				H. Matsui, T. Shimosawa, Y. Uetake, H. Wang, S. Ogura, T. Kaneko, J. Liu, K. Ando, and T. Fujita Protective Effect of Potassium Against the Hypertensive Cardiac Dysfunction: Association With Reactive Oxygen Species Reduction Hypertension, August 1, 2006; 48(2): 225 - 231. [Abstract] [Full Text] [PDF]

				N. E. Taylor, P. Glocka, M. Liang, and A. W. Cowley Jr NADPH Oxidase in the Renal Medulla Causes Oxidative Stress and Contributes to Salt-Sensitive Hypertension in Dahl S Rats Hypertension, April 1, 2006; 47(4): 692 - 698. [Abstract] [Full Text] [PDF]

				H. Zhou, A. Kato, T. Miyaji, H. Yasuda, Y. Fujigaki, T. Yamamoto, K. Yonemura, S. Takebayashi, H. Mineta, and A. Hishida Urinary marker for oxidative stress in kidneys in cisplatin-induced acute renal failure in rats Nephrol. Dial. Transplant., March 1, 2006; 21(3): 616 - 623. [Abstract] [Full Text] [PDF]

				N. E. Taylor and A. W. Cowley Jr. Effect of renal medullary H2O2 on salt-induced hypertension and renal injury Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2005; 289(6): R1573 - R1579. [Abstract] [Full Text] [PDF]

				S. Wesseling, D. A. Ishola Jr., J. A. Joles, H. A. Bluyssen, H. A. Koomans, and B. Braam Resistance to oxidative stress by chronic infusion of angiotensin II in mouse kidney is not mediated by the AT2 receptor Am J Physiol Renal Physiol, June 1, 2005; 288(6): F1191 - F1200. [Abstract] [Full Text] [PDF]

				M. Herrera and J. L. Garvin Recent Advances in the Regulation of Nitric Oxide in the Kidney Hypertension, June 1, 2005; 45(6): 1062 - 1067. [Abstract] [Full Text] [PDF]

				G. Cherla and E. A. Jaimes Role of L-Arginine in the Pathogenesis and Treatment of Renal Disease J. Nutr., October 1, 2004; 134(10): 2801S - 2806S. [Abstract] [Full Text] [PDF]

				R. M. Touyz Reactive Oxygen Species, Vascular Oxidative Stress, and Redox Signaling in Hypertension: What Is the Clinical Significance? Hypertension, September 1, 2004; 44(3): 248 - 252. [Abstract] [Full Text] [PDF]

				M.-S. Zhou, E. A. Jaimes, and L. Raij Atorvastatin Prevents End-Organ Injury in Salt-Sensitive Hypertension: Role of eNOS and Oxidant Stress Hypertension, August 1, 2004; 44(2): 186 - 190. [Abstract] [Full Text] [PDF]

				D. W. Jones Dietary Sodium and Blood Pressure Hypertension, May 1, 2004; 43(5): 932 - 935. [Full Text] [PDF]