Superoxide and hydrogen peroxide counterregulate myogenic contractions in renal afferent arterioles from a mouse model of chronic kidney disease

Li, Lingli; Lai, En Yin; Luo, Zhiwei; Solis, Glenn; Griendling, Kathy K.; Taylor, W. Robert; José, Pedro A.; Wellsten, Anton; Welch, William J.; Wilcox, Christopher S.

doi:10.1016/j.kint.2017.02.009

Cited by 23 publications

(35 citation statements)

References 31 publications

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“…The possible mediators are increased contractile protein expression [ 40 ] or decreased potassium channels protein [ 6 , 41 ]. We confirmed that metabolism of H 2 O 2 with PEG-catalase did not affect contractions of arterioles from normal mice [ 7 ], However, PEG-catalase markedly reduced the responsiveness to ET-1 in arterioles from diabetic mice. Increased H 2 O 2 was related to diabetes rather than ET-1 since it was found in diabetic arterioles under basal condition and was not increased even by 10 −7 mol·l −1 of ET-1.…”

Section: Discussionsupporting

confidence: 76%

“…Both O 2 .− and H 2 O 2 have been implicated in modulating myogenic contraction. O 2 .− promotes normal myogenic contractions [ 5 , 6 ] whereas H 2 O 2 has opposite effects [ 6 , 7 ]. Diabetic animals have increased ROS in renal afferent arterioles [ 1 ] and increased responses to ET-1 in microvessels from pancreatic islet [ 8 ] and the optic fundus capillary [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

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Enhanced Renal Afferent Arteriolar Reactive Oxygen Species and Contractility to Endothelin-1 Are Associated with Canonical Wnt Signaling in Diabetic Mice

Zhang

Huang

Wang

et al. 2018

Kidney Blood Press Res

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Background/Aims: Canonical Wnt signaling is involved in oxidative stress, vasculopathy and diabetes mellitus but its role in diabetic renal microvascular dysfunction is unclear. We tested the hypothesis that enhanced canonical Wnt signaling in renal afferent arterioles from diabetic mice increases reactive oxygen species (ROS) and contractions to endothelin-1 (ET-1). Methods: Streptozotocin-induced diabetes or control C57Bl/6 mice received vehicle or sulindac (40 mg·kg^-1·day^-1) to block Wnt signaling for 4 weeks. ET-1 contractions were measured by changes of afferent arteriolar diameter. Arteriolar H₂O₂, O₂ ^-, protein expression and enzymatic activity were assessed using sensitive fluorescence probes, immunoblotting and colorimetric assay separately. Results: Compared to control, diabetic mouse afferent arteriole had increased O₂^- (+ 84%) and H₂O₂ (+ 91%) and enhanced responses to ET-1 at 10^-8 mol·l^-1 (-72±4% of versus -43±4%, P< 0.05) accompanied by reduced protein expressions and activities for catalase and superoxide dismutase 2 (SOD2). Arteriolar O₂ ^- was increased further by ET-1 and contractions to ET-1 reduced by PEG-SOD in both groups whereas H₂O₂ unchanged by ET-1 and contractions were reduced by PEG-catalase selectively in diabetic mice. The Wnt signaling protein β-catenin was upregulated (3.3-fold decrease in p-β-catenin/β-catenin) while the glycogen synthase kinase-3β (GSK-3β) was downregulated (2.6-fold increase in p-GSK-3β/ GSK-3β) in preglomerular vessels of diabetic mice. Sulindac normalized the Wnt signaling proteins, arteriolar O₂ ^-, H₂O₂ and ET-1 contractions while doubling microvascular catalase and SOD2 expression in diabetic mice. Conclusion: Increased ROS, notably H₂O₂ contributes to enhanced afferent arteriolar responses to ET-1 in diabetes, which is closely associated with Wnt signaling. Antioxidant pharmacological strategies targeting Wnt signaling may improve vascular function in diabetic nephropathy.

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Section: Discussionsupporting

confidence: 76%

Section: Introductionmentioning

confidence: 99%

Enhanced Renal Afferent Arteriolar Reactive Oxygen Species and Contractility to Endothelin-1 Are Associated with Canonical Wnt Signaling in Diabetic Mice

Zhang

Huang

Wang

et al. 2018

Kidney Blood Press Res

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“…The different vascular actions mediated by Nox2 activation in renal arteries, i.e vasodilation versus vasoconstriction/VSM hypertrophy, might therefore be ascribed to differential cell-dependent activation of Nox2 in the endothelium or VSM, respectively, as proposed for human coronary arterioles [9] . However, the ability to induce vasoconstriction or vasodilatation has also been ascribed to the type of Nox isoenzyme, since Nox2-derived O 2 .- and Nox4-derived H 2 O 2 were recently shown to contract and relax, respectively, renal arterioles thus counterregulating afferent arteriole myogenic response [51] . H 2 O 2 is released upon endothelial stimulation in renal arteries and participates in the EDH relaxation of renal VSM [22] .…”

Section: Discussionmentioning

confidence: 99%

Hydrogen peroxide derived from NADPH oxidase 4- and 2 contributes to the endothelium-dependent vasodilatation of intrarenal arteries

et al. 2018

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The role of NADPH oxidase (Nox)-derived reactive oxygen species in kidney vascular function has extensively been investigated in the harmful context of oxidative stress in diabetes and obesity-associated kidney disease. Since hydrogen peroxide (H2O2) has recently been involved in the non-nitric oxide (NO) non-prostanoid relaxations of intrarenal arteries, the present study was sought to investigate whether NADPH oxidases may be functional sources of vasodilator H2O2 in the kidney and to assess their role in the endothelium-dependent relaxations of human and rat intrarenal arteries. Renal interlobar arteries isolated from the kidney of renal tumor patients who underwent nephrectomy, and from the kidney of Wistar rats, were mounted in microvascular myographs to assess function. Superoxide (O2.-) and H2O2 production was measured by chemiluminescence and Amplex Red fluorescence, and Nox2 and Nox4 enzymes were detected by Western blotting and by double inmunolabeling along with eNOS. Nox2 and Nox4 proteins were expressed in the endothelium of renal arterioles and glomeruli co-localized with eNOS, levels of expression of both enzymes being higher in the cortex than in isolated arteries. Pharmacological inhibition of Nox with apocynin and of CYP 2C epoxygenases with sulfaphenazol, but not of the NO synthase (NOS), reduced renal NADPH-stimulated O2.- and H2O2 production. Under conditions of cyclooxygenase and NOS blockade, acetylcholine induced endothelium-dependent relaxations that were blunted by the non-selective Nox inhibitor apocynin and by the Nox2 or the Nox1/4 inhibitors gp91ds-tat and GKT136901, respectively. Acetylcholine stimulated H2O2 production that was reduced by gp91ds-tat and by GKT136901. These results suggest the specific involvement of Nox4 and Nox2 subunits as physiologically relevant endothelial sources of H2O2 generation that contribute to the endothelium-dependent vasodilatation of renal arteries and therefore have a protective role in kidney vasculature.

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“…Impairment of renal autoregulation, which is determined by the tubuloglomerular feedback response and myogenic contraction of the VSMC of the afferent arteriole in response to an increase in perfusion pressure, has been related to CKD progression, as impaired autoregulation augments the pressure in the glomerular capillaries and causes renal parenchymal damage with accelerated loss of kidney function. ROS, as shown by experimental studies, might mediate the impaired myogenic responses of afferent arterioles from the kidneys in CKD models [101,102,103,104,105]. Both Nox2 and Nox4 are expressed in renal resistance arteries, and accumulating data in the literature has shed light on the role of Nox2-derived ROS in the regulation of afferent arteriolar tone and renal hemodynamics [101,102].…”

Section: Oxidative Stress Microvascular Dysfunction and Chronic mentioning

confidence: 99%

Oxidative Stress in the Pathogenesis and Evolution of Chronic Kidney Disease: Untangling Ariadne’s Thread

Duni

Liakopoulos

Roumeliotis

et al. 2019

IJMS

237

177

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Amplification of oxidative stress is present since the early stages of chronic kidney disease (CKD), holding a key position in the pathogenesis of renal failure. Induction of renal pro-oxidant enzymes with excess generation of reactive oxygen species (ROS) and accumulation of dityrosine-containing protein products produced during oxidative stress (advanced oxidation protein products—AOPPs) have been directly linked to podocyte damage, proteinuria, and the development of focal segmental glomerulosclerosis (FSGS) as well as tubulointerstitial fibrosis. Vascular oxidative stress is considered to play a critical role in CKD progression, and ROS are potential mediators of the impaired myogenic responses of afferent renal arterioles in CKD and impaired renal autoregulation. Both oxidative stress and inflammation are CKD hallmarks. Oxidative stress promotes inflammation via formation of proinflammatory oxidized lipids or AOPPs, whereas activation of nuclear factor κB transcription factor in the pro-oxidant milieu promotes the expression of proinflammatory cytokines and recruitment of proinflammatory cells. Accumulating evidence implicates oxidative stress in various clinical models of CKD, including diabetic nephropathy, IgA nephropathy, polycystic kidney disease as well as the cardiorenal syndrome. The scope of this review is to tackle the issue of oxidative stress in CKD in a holistic manner so as to provide a future framework for potential interventions.

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Superoxide and hydrogen peroxide counterregulate myogenic contractions in renal afferent arterioles from a mouse model of chronic kidney disease

Cited by 23 publications

References 31 publications

Enhanced Renal Afferent Arteriolar Reactive Oxygen Species and Contractility to Endothelin-1 Are Associated with Canonical Wnt Signaling in Diabetic Mice

Enhanced Renal Afferent Arteriolar Reactive Oxygen Species and Contractility to Endothelin-1 Are Associated with Canonical Wnt Signaling in Diabetic Mice

Hydrogen peroxide derived from NADPH oxidase 4- and 2 contributes to the endothelium-dependent vasodilatation of intrarenal arteries

Oxidative Stress in the Pathogenesis and Evolution of Chronic Kidney Disease: Untangling Ariadne’s Thread

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