Production and Actions of Superoxide in the Renal Medulla

Zou, Ai-Ping; Li, Ningjun; Cowley, Allen W.

doi:10.1161/01.hyp.37.2.547

Cited by 274 publications

(315 citation statements)

References 41 publications

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“…NAD(P)H oxidase has been assigned a major role in ROS generation in vascular and cardiac tissue with contributions from other sources such as xanthine oxidase and mitochondrial respiration (8). In the kidney, NAD(P)H oxidase mediates production of O 2 ·Ϫ in mesangial cells (27), thick ascending limb cells (16), and rat renal medullary homogenates (15). Thus, this oxidase may play a critical role in producing ROS in the kidney.…”

Section: Discussionmentioning

confidence: 99%

“…O 2 ·Ϫ is produced in activated phagocytes by the enzyme NADPH oxidase (2,11). NAD(P)H oxidase has also been implicated in O 2 ·Ϫ signaling in the vasculature (12) and in the kidney cortex (13,14) and medulla (15). Activation of NAD(P)H oxidase mediates generation of O 2 ·Ϫ induced by Ang II (12,16) and is implicated in the pathogenesis of several models of hypertension (2,14).…”

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confidence: 99%

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Salt Intake, Oxidative Stress, and Renal Expression of NADPH Oxidase and Superoxide Dismutase

Kitiyakara

Chabrashvili²,

Chen³

et al. 2003

Journal of the American Society of Nephrology

281

236

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Abstract. The hypothesis that a high salt (HS) intake increases oxidative stress was investigated and was related to renal cortical expression of NAD(P)H oxidase and superoxide dismutase (SOD). 8-Isoprostane PGF 2␣ and malonyldialdehyde were measured in groups (n ϭ 6 to 8) of conscious rats during low-salt, normal-salt, or HS diets. NADPH-and NADH-stimulated superoxide anion (O 2 ·Ϫ ) generation was assessed by chemiluminescence, and expression of NAD(P)H oxidase and SOD were assessed with real-time PCR. Excretion of 8-isoprostane and malonyldialdehyde increased incrementally twoto threefold with salt intake (P Ͻ 0.001), whereas prostaglandin E 2 was unchanged. Renal cortical NADH-and NADPHstimulable O 2 ·Ϫ generation increased (P Ͻ 0.05) 30 to 40% with salt intake. Compared with low-salt diet, HS significantly (P Ͻ 0.005) increased renal cortical mRNA expression of gp91 phox and p47 phox and decreased expression of intracellular CuZn (IC)-SOD and mitochondrial (Mn)-SOD. Despite suppression of the renin-angiotensin system, salt loading enhances oxidative stress. This is accompanied by increased renal cortical NADH and NADPH oxidase activity and increased expression of gp91 phox and p47 phox and decreased IC-and Mn-SOD. Thus, salt intake enhances generation of O 2 ·Ϫ accompanied by enhanced renal expression and activity of NAD(P)H oxidase with diminished renal expression of IC-and Mn-SOD.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Salt Intake, Oxidative Stress, and Renal Expression of NADPH Oxidase and Superoxide Dismutase

Kitiyakara

Chabrashvili²,

Chen³

et al. 2003

Journal of the American Society of Nephrology

281

236

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“…Activity of NADPH was measured by using fluorescence spectrometry of DHE in tissue homogenates of CG from sham rats and DOCA rats (5,51). In a microtiter plate, freshly prepared CG homogenates were incubated with DHE (10 mol/l), salmon testes DNA (0.5 mg/ml, Stratagene, La Jolla, CA), and the substrates for NADPH oxidase ␤-NADH (0.1 mmol/l, Sigma) or ␤-NADPH (0.1 mmol/l, Sigma) for 30 min at 37°C in a dark chamber.…”

Section: Methodsmentioning

confidence: 99%

Superoxide anion is elevated in sympathetic neurons in DOCA-salt hypertension via activation of NADPH oxidase

Dai

Chen²,

Kreulen³

2006

American Journal of Physiology-Heart and Circulatory Physiology

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Ϫ ⅐) production is elevated in sympathetic ganglion neurons and in the vasculature of hypertensive animals; however, it is not known what enzymatic pathway(s) are responsible for O 2 Ϫ ⅐ production. To determine the pathway(s) of O 2 Ϫ ⅐ production in sympathetic neurons, we examined the presence of mRNA of NADPH oxidase subunits in sympathetic ganglionic neurons and differentiated PC-12 cells. The mRNAs for NADPH oxidase subunits p47 phox , p22 phox , gp91 phox , and NOX1 were present in sympathetic neurons and PC-12 cells, whereas the NOX4 homologue was present in sympathetic neurons but not PC-12 cells. Freshly dissociated celiac ganglion neurons from normal rats and PC-12 cells produced O 2 Ϫ ⅐ when treated with the PKC activator PMA; O 2 Ϫ ⅐ production increased by 317% and 254%, respectively. The PMA-evoked increases were reduced by pretreatment with the NADPH oxidase inhibitor apocynin. These findings indicate that NADPH oxidase is the primary source of O 2 Ϫ ⅐ in sympathetic ganglion neurons. When celiac ganglia from hypertensive rats were incubated with apocynin, O 2 Ϫ ⅐ levels were reduced to the same levels as normotensive animals, indicating that NADPH oxidase activity accounted for the elevated O 2 Ϫ ⅐ levels in hypertensive animals. To test this latter finding, we compared NADPH oxidase activity in extracts of prevertebral sympathetic ganglia of DOCA-salt hypertensive rats and shamoperated rats. NADPH oxidase activities were 49.9% and 78.6% higher in sympathetic ganglia of DOCA rats compared with normotensive controls when using ␤-NADH and ␤-NADPH as substrates, respectively. Thus elevated O 2 Ϫ ⅐ levels in hypertension may be a result of the increased activity of NADPH oxidase in postganglionic sympathetic neurons. sympathetic ganglia; phorbol ester; reduced nicotinamide adenine dinucleotide phosphate oxidase; hypertension; deoxycorticosterone acetate VASCULAR ENDOTHELIAL CELLS, smooth muscle cells, and fibroblasts generate reactive oxygen species (ROS), such as O 2 Ϫ ⅐ and H 2 O 2 . ROS play critical roles in both normal and pathophysiological states of vascular cells, including the modulation of redox-sensitive signaling pathways and gene expression, or in the pathophysiology of hypertension and atherosclerosis (16,22,26,36). Several models of hypertension are associated with an increase in vascular O 2 Ϫ ⅐ (41, 42), and this increased O 2 Ϫ ⅐ may quench the endogenous vasodilator nitric oxide (NO) to cause a loss of NO bioactivity in the vessel wall and impair the endothelium-dependent vasorelaxation, resulting in hypertension (26). ROS-mediated endothelial dysfunction in ANG II-infused rats (24) and in DOCA-salt hypertensive rats (42) can be reversed by antioxidant enzyme, endothelial NO synthase (34), or superoxide dismutase (26). ROS can also induce the expression of cardiovascular-related genes, such as those for adhesion molecules and vasoactive substances. For example, the cytokine interleukin 1 activates VCAM-1 gene expression through a mechanism that is repressed ϳ90% by the antioxidant...

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“…Hyperglycemia induces mitochondrial electron-transport chain enzymes in cultured human mesangial cells to increase ROS production, leading to NF-B activation and COX-2 protein expression (162). The renal outer medulla is considered to be the major site for mitochondrial respiratory chain enzyme-mediated ROS production and, together with nicotinamide adenine nucleotide (NADH) oxidase (not NADPH oxidase), has been implicated in regulation of medullary blood flow (MBF) and sodium excretion (387). DETC (a SOD inhibitor) decreased MBF and increased sodium retention and hypertension, whereas the SOD mimetic, tempol, had the opposite effects, demonstrating that O 2 иϪ is vasconstrictive and antinatriuretic.…”

Section: Role Of Renal Oxidative Stress In Hypertension 2053mentioning

confidence: 99%

“…The Nox4 isoform of NAD(P)H oxidase is unique in that it also can use NADH as the substrate for generating O 2 иϪ (173). This may be relevant to the kidneys, as the cortex and outer medulla preferentially use NADH as a substrate and express Nox4 at high levels in these regions (387).…”

Section: Nistala Et Al 2062mentioning

confidence: 99%