Renal Oxidative Stress in Medullary Thick Ascending Limbs Produced by Elevated NaCl and Glucose

Mori, Takefumi; Cowley, Allen W.

doi:10.1161/01.hyp.0000113295.31481.36

Cited by 72 publications

(79 citation statements)

References 41 publications

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“…Increased salt may induce oxidative stress, independent of a change in blood pressure, because a salt load increased NADPH oxidase O 2 ⅐Ϫ production in tissue strips of medullary thick ascending limb. 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.…”

Section: Taylor Et Al Renal Medullary Nadph Oxidase and Hypertensionmentioning

confidence: 98%

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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Section: Taylor Et Al Renal Medullary Nadph Oxidase and Hypertensionmentioning

confidence: 98%

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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“…62 When the juxtamedullary glomeruli are injured by hypertension, the impairment of oxygen delivery downstream from the vasa recta vessels would be expected to result in tubulointerstitial injuries in the outer medulla. Superimposed on these factors, a number of other elements, including neurohormonal factors, 56 inflammatory pathways, 53 oxidative stress 63,64 and tubular transport, 65,66 are involved in the pathogenesis of the injuries, among which tubulovascular crosstalk is of particular interest. 63,64,67,68 We have recently shown that an increase in tubular transport at the mTAL enhances superoxide production and reduces nitric oxide synthesis.…”

Section: Albuminuria and Endothelial Dysfunctionmentioning

confidence: 99%

Strain vessel hypothesis: a viewpoint for linkage of albuminuria and cerebro-cardiovascular risk

et al. 2009

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Albuminuria is closely associated with stroke and cardiovascular diseases (CVDs) as well as the salt sensitivity of blood pressure (BP). Although albuminuria may reflect generalized endothelial dysfunction, there may be more specific hemodynamic mechanisms underlying these associations. Cerebral hemorrhage and infarction occur most frequently in the area of small perforating arteries that are exposed to high pressure and that have to maintain strong vascular tone in order to provide large pressure gradients from the parent vessels to the capillaries. Analogous to the perforating arteries are the glomerular afferent arterioles of the juxtamedullary nephrons. Hypertensive vascular damage occurs first and more severely in the juxtamedullary glomeruli. Therefore, albuminuria may be an early sign of vascular damages imposed on 'strain vessels' such as perforating arteries and juxtamedullary afferent arterioles. Coronary circulation also occurs under unique hemodynamic conditions, in which the entire epicardial segments are exposed to very high pressure with little flow during systolic phases. From the evolutionary point of view, we speculate that such circulatory systems in the vital organs are mandatory for survival under the danger of hypoperfusion due to difficult access to salt and water as well as high risks of wound injuries. In addition, albuminuria would indicate an impairment of renal medullary circulation, downstream from the juxtamedullary glomeruli, and therefore an impaired pressure natriuresis, which would lead to salt sensitivity of BP. Our 'strain vessel hypothesis' may explain why hypertension and diabetes, unforeseen in the concept of evolution, preferentially affect vital organs such as the brain, heart and kidney.

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“…In contrast, exposure of isolated PTCs to fatty acid-conjugated albumin induced mitochondrial ROS production that was reversed with rotenone and not by NAD(P)H oxidase or XO inhibitors (139). Further to elucidate the importance of redox mechanisms in the kidney, pericytes of intact vasa recta (VR) were compared with pericytes of VR with disrupted endothelium for Ang II-mediated superoxide production (221). Interestingly, Ang II did not increase superoxide production in either scenario; however, addition of an NO scavenger led to increased superoxide production in endothelium-denuded vessels, suggesting crosstalk between different cell types, which is inhibited by antioxidants (NO).…”

Section: B Ros and The Glomerular Basement Membrane (Gbm)mentioning

confidence: 99%

Redox Control of Renal Function and Hypertension

Nistala

Whaley‐Connell

Sowers

2008

Antioxidants & Redox Signaling

139

123

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Renal Oxidative Stress in Medullary Thick Ascending Limbs Produced by Elevated NaCl and Glucose

Cited by 72 publications

References 41 publications

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

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

Strain vessel hypothesis: a viewpoint for linkage of albuminuria and cerebro-cardiovascular risk

Redox Control of Renal Function and Hypertension

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