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            -Arginine Reverses p47phox and gp91phox Expression Induced by High Salt in Dahl Rats

Fujii, Shigemoto; Zhang, Ling; Igarashi, Jun–ichi; Kosaka, Hiroaki

doi:10.1161/01.hyp.0000094557.36656.d0

Cited by 69 publications

(60 citation statements)

References 67 publications

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“…8 Thus, eNOS uncoupling seems to be a common mechanism of endothelial dysfunction, leading to reduced NO production and increased ROS production in the blood vessel wall. In DS rats, high salt intake induced the activation of NADPH oxidase , 24 and in another study, such activation increased ROS production, with subsequent endothelial dysfunction. 25 The production of ROS by NADPH oxidase oxidized BH4 to BH2 and caused eNOS uncoupling.…”

Section: Discussionmentioning

confidence: 78%

Telmisartan improves endothelial dysfunction and renal autoregulation in Dahl salt-sensitive rats

et al. 2009

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Hypertensive vascular disorders are characterized by endothelial dysfunction. Loss of renal autoregulation causes glomerular hypertension. However, the relationship between the autoregulatory response and glomerular damage has not been well examined. We examined the contributions of uncoupled endothelial nitric oxide synthase (eNOS) in hypertensive renal disease, and the relationship between the degree of autoregulation impairment and glomerular injury. We also investigated the effects of telmisartan on eNOS coupling and renal autoregulation. Male Dahl salt-sensitive hypertensive (DS) rats (14-week old) fed an 8% salt diet were used to examine endothelial dysfunction and impaired renal autoregulation caused by glomerular hypertension. Some DS rats were treated with telmisartan (3.0 mg kg À1 day À1 ), an angiotensin receptor blocker, for 2 weeks. Increased superoxide production and decreased nitric oxide production, as detected by fluorescent indicator perfusion methods, were observed in the glomeruli and arterioles of hypertensive DS rats. Telmisartan improved the imbalance of superoxide and nitric oxide in the glomeruli and arterioles. Decreased serum tetrahydrobiopterin levels and coupled eNOS seen in the DS rat kidney were improved with telmisartan treatment. The endothelial relaxation reaction was impaired in DS rat aortic arteries. Autoregulatory capacity in response to step changes in perfusion pressure was also impaired in DS rat kidney. Treatment with telmisartan improved these abnormalities. Endothelial dysfunction in the glomeruli and impaired renal autoregulation, which may cause glomerular sclerosis, were observed in DS rat kidney. Telmisartan treatment improves these dysfunctions in hypertensive renal disease.

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Section: Discussionmentioning

confidence: 78%

Telmisartan improves endothelial dysfunction and renal autoregulation in Dahl salt-sensitive rats

et al. 2009

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“…37 In vivo, Sprague Dawley rats fed a high-salt diet did not develop hypertension but exhibited increased urinary 8-isoprostane excretion and renal cortical gp91 phox and p47 phox subunit mRNA expression. 38 Although it has been shown that NADPH oxidase subunits are upregulated in SS rats fed a high-salt diet, 15 no study has previously shown an elevation in renal medullary NADPH oxidase in SS rats on a normal salt diet. Interestingly, in the present study, the subunit gp91 phox was not upregulated in the SS rat, whereas the p22 phox and p47 phox subunits were.…”

Section: Taylor Et Al Renal Medullary Nadph Oxidase and Hypertensionmentioning

confidence: 99%

“…[11][12][13] However, the source of the oxidative stress specifically in the renal medulla of SS rats and the contribution of O 2 ⅐Ϫ to salt-induced hypertension in this region is unclear. Several enzymes have been implicated as possible sources of elevated ROS in hypertension, including NADPH oxidase, 14,15 xanthine oxidase, 16 NO synthase (NOS), 17 cyclooxygenase, 18 and mitochondrial electron transport leakage. 19 It has been suggested that reductions of enzymes that scavenge ROS, such as superoxide dismutases (SOD), 20 catalase, and glutathione peroxidase (GPx), may also play a role.…”

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confidence: 99%

NADPH Oxidase in the Renal Medulla Causes Oxidative Stress and Contributes to Salt-Sensitive Hypertension in Dahl S Rats

et al. 2006

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Abstract-Dahl salt-sensitive (SS) rats exhibit increased renal medullary oxidative stress and blood pressure salt-sensitivity compared with consomic, salt-resistant SS-13 BN rats, despite highly similar genetic backgrounds. The present study examined potential sources of renal medullary superoxide in prehypertensive SS rats fed a 0.4% NaCl diet by assessing activity and protein levels of superoxide producing and scavenging enzymes. Superoxide production was nearly doubled in SS rats compared with SS-13 BN rats as determined by urinary 8-isoprostane excretion and renal medullary oxy-ethidium microdialysate levels. Medullary superoxide production in tissue homogenates was greater in SS rats, and the NADPH oxidase inhibitor diphenylene iodonium preferentially reduced SS levels to those found in SS-13 BN rats. Dinitrophenol, a mitochondrial uncoupler, eliminated the remaining superoxide production in both strains, whereas inhibition of xanthine oxidase, NO synthase, and cycloxygenase had no effect. L-arginine, NO synthase, superoxide dismutase, catalase, and glutathione peroxidase activities between SS and SS-13 BN rats did not differ. Chronic blood pressure responses to a 4% NaCl diet were then determined in the presence or absence of the NADPH oxidase inhibitor apocynin (3.5 g/kg per minute), chronically delivered directly into the renal medulla. Apocynin infusion reduced renal medullary interstitial superoxide from 1059Ϯ130 to 422Ϯ80 (oxyethidium fluorescence units) and mean arterial pressure from 175Ϯ4 to 157Ϯ6 mm Hg in SS rats, whereas no effects on either were observed in the SS-13 BN . We conclude that excess renal medullary superoxide production in SS rats contributes to salt-induced hypertension, and NADPH oxidase is the major source of the excess superoxide.

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“…A decrease in the ratio of reduced tetrahydrobiopterin to oxidized dihydrobiopterin in the renal medulla has been shown to blunt NO production, and has been proposed to contribute to saltsensitive hypertension. 37 Oral L-arginine supplementation reverses p47 phox and gp91 phox expression induced by high salt in the renal cortex of Dahl rats, 38 suggesting that substrate supplementation can restore the imbalance between NO and reactive oxygen species, presumably by increasing NOSderived NO. In addition, L-arginine transport has been shown to affect NOS activity and NO production in the renal medulla.…”

Section: Regulation Of Nos Activitymentioning

confidence: 99%

Recent Advances in the Regulation of Nitric Oxide in the Kidney

Herrera

Garvin

2005

Hypertension

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Abstract-Nitric oxide (NO) plays important roles in the regulation of renal function and the long-term control of blood pressure. New roles of NO have been proposed recently in diabetes, nephrotoxicity, and pregnancy. NO derived from all 3 NOS isoforms contributes to the overall regulation of kidney function, and recent advances in our understanding of their regulation have been made lately. In this regard, substrate and cofactor availability play important roles in regulating nitric oxide synthase (NOS) activity not only by limiting enzyme activity but also by influencing the coupling of NOS with its cofactors, tetrahydrobiopterin and NADPH. Protein-protein interactions are now recognized to be important negative and positive regulators of NOS. Phosphorylation is another component of the mechanism whereby NOS is activated or deactivated. Increased NOS expression can also influence enzyme activity; however, the degree of expression does not always correlate with enzyme activity because increased NO levels can result in inhibition of NOS. Finally, other potential regulators of NOS such as endogenous L-arginine analogs may also be important. In this article, we summarize recent advances in the regulation of activity and expression of the NOS isoforms within the kidney. renal function and long-term regulation of blood pressure. [1][2][3][4] This is best evidenced by the fact that inhibiting intrarenal NO production increased blood pressure. 5 In addition, reduced NO has been identified as a common denominator of many hypertensive models. 6 -9 The effects of NO on blood pressure via actions in the kidney occur through multiple mechanisms. These include increasing renal blood flow caused by vasodilatation, 10 increasing glomerular filtration, 11 inhibiting sodium transport along the nephron, 12-14 and regulating release of renin. 15 NO produced by each of the 3 nitric oxide synthases (NOS), NOS 1, NOS 2, and NOS 3, reportedly contributes to the regulation of renal function. Inhibition of NOS activity within the kidney is known to lead to sodium retention and hypertension. This review addresses recent advances in our understanding of the role played by renal NO in various physiological and pathophysiological conditions, as well as how NO production is regulated. Roles for Renal NOHistorically, NO produced by the kidney has been thought of primarily as a factor that regulates urinary volume and sodium excretion. The physiological effects of NO can be mediated via changes in renal hemodynamics and/or salt and water absorption by the nephron. NO reduces renal vascular tone in part by dilating the afferent arteriole. 16 It also increases glomerular filtration rate. 11 NO modulates renin secretion by the juxtaglomerular apparatus 15 and tubuloglomerular feedback. 3 Finally, NO regulates transport in various nephron segments as reviewed recently by Ortiz and Garvin. 12 More recently it has been recognized that in a number of pathophysiological conditions, the actions of NO on renal hemodynamics and/or nephron transport are ...

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l -Arginine Reverses p47phox and gp91phox Expression Induced by High Salt in Dahl Rats

Cited by 69 publications

References 67 publications

Telmisartan improves endothelial dysfunction and renal autoregulation in Dahl salt-sensitive rats

Telmisartan improves endothelial dysfunction and renal autoregulation in Dahl salt-sensitive rats

NADPH Oxidase in the Renal Medulla Causes Oxidative Stress and Contributes to Salt-Sensitive Hypertension in Dahl S Rats

Recent Advances in the Regulation of Nitric Oxide in the Kidney

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