Effects of Renal Perfusion Pressure on Renal Medullary Hydrogen Peroxide and Nitric Oxide Production

Jin, Chunhua; Hu, Chunyan; Polichnowski, Aaron J.; Mori, Takefumi; Skelton, M. M.; Ito, Sadayoshi; Cowley, Allen W.

doi:10.1161/hypertensionaha.109.128827

Cited by 46 publications

(47 citation statements)

References 36 publications

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“…As pressures were increased in ϳ30-mmHg steps between 80 and 150 mmHg, significant increases in medullary interstitial H 2 O 2 concentrations were observed along with parallel increases in urinary excretion of H 2 O 2 ( Fig. 3A) (84). Since increases in medullary H 2 O 2 reduce Na ϩ excretion, these observations indicate that H 2 O 2 plays a modulatory role in reducing the steepness of the pressure-natriuresis relationship, serving to dampen the pressure-natriuresis response.…”

Section: ·ϫmentioning

confidence: 95%

Reactive oxygen species as important determinants of medullary flow, sodium excretion, and hypertension

Cowley

Abe

Mori

et al. 2015

American Journal of Physiology-Renal Physiology

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logical evidence linking the production of superoxide, hydrogen peroxide, and nitric oxide in the renal medullary thick ascending limb of Henle (mTAL) to regulation of medullary blood flow, sodium homeostasis, and long-term control of blood pressure is summarized in this review. Data obtained largely from rats indicate that experimentally induced elevations of either superoxide or hydrogen peroxide in the renal medulla result in reduction of medullary blood flow, enhanced Na ϩ reabsorption, and hypertension. A shift in the redox balance between nitric oxide and reactive oxygen species (ROS) is found to occur naturally in the Dahl salt-sensitive (SS) rat model, where selective reduction of ROS production in the renal medulla reduces salt-induced hypertension. Excess medullary production of ROS in SS rats emanates from the medullary thick ascending limbs of Henle [from both the mitochondria and membrane NAD(P)H oxidases] in response to increased delivery and reabsorption of excess sodium and water. There is evidence that ROS and perhaps other mediators such as ATP diffuse from the mTAL to surrounding vasa recta capillaries, resulting in medullary ischemia, which thereby contributes to hypertension.superoxide (O 2 ·Ϫ ); hydrogen peroxide (H2O2); nitric oxide (NO); NAD(P)H oxidase; mTAL; medullary blood flow; kidney; Dahl SS rats REACTIVE OXYGEN SPECIES (ROS) are chemically reactive molecules derived from oxygen, whose role as mediators of intracellular signaling cascades is well recognized. The following is a brief review of physiological data linking superoxide (O 2 ·Ϫ ), hydrogen peroxide (H 2 O 2 ), and nitric oxide (NO) production in the medullary thick ascending limbs of Henle (mTAL) to sodium (Na ϩ ) homeostasis, the regulation of medullary blood flow (MBF), and the long-term regulation of arterial blood pressure. MBF to the renal medulla can be importantly controlled by the constriction and dilation of the descending vasa recta (VR) capillaries, which branch from the efferent arterioles of the juxtamedullary glomeruli (49, 147, 149) and whose tone is controlled by the smooth muscle-like pericytes (49, 90, 146 -149). The role of NO cross talk from mTAL to surrounding VR in the renal medulla has been reviewed in detail elsewhere (19, 33) and will be discussed here largely with regard to its ROS-related counterregulatory functions. The present review will first summarize data showing that either the excess endogenous production or reduced scavenging of O 2 ·Ϫ or H 2 O 2 within the renal medulla results in a decrease in MBF and Na ϩ excretion, leading to hypertension and renal injury. Second, evidence will be summarized supporting the hypothesis that a high dietary salt intake results in increased luminal flow and delivery of NaCl to the mTAL, thereby signaling via both mechanical forces (stretch and shear) and increased Na ϩ transport, an increased mitochondrial and membrane NA-D(P)H oxidase production of O 2 ·Ϫ and H 2 O 2 . Third, studies will be reviewed showing that reduction of MBF leads to hypertension a...

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Section: ·ϫmentioning

confidence: 95%

Reactive oxygen species as important determinants of medullary flow, sodium excretion, and hypertension

Cowley

Abe

Mori

et al. 2015

American Journal of Physiology-Renal Physiology

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“…An elevation of renal perfusion pressure during hypertension may directly increase ROS production in the renal medulla, MBF and NaCl delivery to, and reabsorption by, the TAL (125). Jin et al (125) reported that a short-term increase of renal perfusion pressure enhanced the production of both NO and H 2 O 2 in the outer medulla of rats. The increased NO was attributed to the pressure-induced increase in MBF that enhanced vascular shear stress and to the increased H 2 O 2 with higher flow rates through the mTAL.…”

Section: Intrarenal Distribution Of Blood Flowmentioning

confidence: 99%

Oxidative Stress in Hypertension: Role of the Kidney

Araújo

Wilcox

2014

Antioxidants & Redox Signaling

158

131

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Significance: Renal oxidative stress can be a cause, a consequence, or more often a potentiating factor for hypertension. Increased reactive oxygen species (ROS) in the kidney have been reported in multiple models of hypertension and related to renal vasoconstriction and alterations of renal function. Nicotinamide adenine dinucleotide phosphate oxidase is the central source of ROS in the hypertensive kidney, but a defective antioxidant system also can contribute. Recent Advances: Superoxide has been identified as the principal ROS implicated for vascular and tubular dysfunction, but hydrogen peroxide (H 2 O 2 ) has been implicated in diminishing preglomerular vascular reactivity, and promoting medullary blood flow and pressure natriuresis in hypertensive animals. Critical Issues and Future Directions: Increased renal ROS have been implicated in renal vasoconstriction, renin release, activation of renal afferent nerves, augmented contraction, and myogenic responses of afferent arterioles, enhanced tubuloglomerular feedback, dysfunction of glomerular cells, and proteinuria. Inhibition of ROS with antioxidants, superoxide dismutase mimetics, or blockers of the reninangiotensin-aldosterone system or genetic deletion of one of the components of the signaling cascade often attenuates or delays the onset of hypertension and preserves the renal structure and function. Novel approaches are required to dampen the renal oxidative stress pathways to reduced O 2 -rather than H 2 O 2 selectivity and/or to enhance the endogenous antioxidant pathways to susceptible subjects to prevent the development and renaldamaging effects of hypertension. Antioxid. Redox Signal. 20, 74-101.

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“…Urine and blood samples were collected during infusion experiments and Na + , K + , and creatinine levels were analyzed as previously described. 60,61 Figure 8. Chronic intravenous infusion of EGF prevents development of hypertension and kidney damage in SS rats fed a HS diet.…”

Section: Elisa Assay and Biochemical Analyses Of Electrolytesmentioning

confidence: 99%

Deficiency of Renal Cortical EGF Increases ENaC Activity and Contributes to Salt-Sensitive Hypertension

Pavlov¹,

Levchenko²,

O’Connor³

et al. 2013

Journal of the American Society of Nephrology

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Various stimuli, including hormones and growth factors, modulate epithelial sodium channels (ENaCs), which fine-tune Na + absorption in the kidney. Members of the EGF family are important for maintaining transepithelial Na + transport, but whether EGF influences ENaC, perhaps mediating salt-sensitive hypertension, is not well understood. Here, the ENaC inhibitor benzamil attenuated the development of hypertension in Dahl salt-sensitive rats. Feeding these salt-sensitive rats a high-salt diet led to lower levels of EGF in the kidney cortex and enhanced the expression and activity of ENaC compared with feeding a lowsalt diet. To directly evaluate the role of EGF in the development of hypertension and its effect on ENaC activity, we infused EGF intravenously while continuously monitoring BP of the salt-sensitive rats. Infusion of EGF decreased ENaC activity, prevented the development of hypertension, and attenuated glomerular and renal tubular damage. Taken together, these findings indicate that cortical EGF levels decrease with a high-salt diet in salt-sensitive rats, promoting ENaC-mediated Na + reabsorption in the collecting duct and the development of hypertension. More than 76 million American adults have high BP 1 and the likelihood of developing hypertension significantly increases with age. Nearly 40% of African Americans aged .20 years exhibit hypertension and nearly 70% of these individuals have a form of hypertension that is highly sensitive to salt intake. A reduced ability to maintain sodium homeostasis and normal levels of arterial pressure is a hallmark of all forms of hypertension. 2 In the kidney, discretionary Na + reabsorption in response to endocrine input to the aldosterone-sensitive distal nephron (ASDN) is a determinant of the pressurenatriuresis relationship, which is of fundamental importance in the long-term control of arterial pressure. 2,3 Although sodium transport in ASDN accounts for a small proportion of renal sodium transport (,10%), ENaC activity is the rate-limiting step for this discretionary Na + reabsorption. 4 The Dahl salt-sensitive (SS) rat strain used in this study is a genetic animal model of hypertension and kidney disease that reveals disease traits similar to those observed in humans. This inbred strain exhibits a low-renin, sodium-sensitive form of hypertension that is associated with severe and progressive proteinuria, glomerulosclerosis, and renal interstitial fibrosis. [5][6][7] The EGF and related hormones are multipotent agents [8][9][10][11] involved in regulation of various renal

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Effects of Renal Perfusion Pressure on Renal Medullary Hydrogen Peroxide and Nitric Oxide Production

Cited by 46 publications

References 36 publications

Reactive oxygen species as important determinants of medullary flow, sodium excretion, and hypertension

Reactive oxygen species as important determinants of medullary flow, sodium excretion, and hypertension

Oxidative Stress in Hypertension: Role of the Kidney

Deficiency of Renal Cortical EGF Increases ENaC Activity and Contributes to Salt-Sensitive Hypertension

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