The Superoxide Scavenger And Antioxidant, L-Propionyl-carnitine, Is Metabolically Enhanced Following Exercise In Hypoxia

During hypertension kidney fails to maintain Na balance, leading to increased blood volume and blood pressure. It has been suggested that humoral defects and in the last decade in Na transport disorders have been described in different tubular segments. Our aim was to investigate the interaction between antidiuretic hormone (ADH) and angiotensin II (Ang II) in oxygen consumption (QO2, as a marker of Na transport ) in the loop of Henle , in normotensive and hypertensive animals. To do that we used suspensions of thick ascending limbs of the loop of Henle and and measured QO2, cAMP and superoxide production. We found that In normotensive animals, the basal QO2 was 112 ± 5 nmol O2/min/mg protein. ADH (1 nM) increased QO2 227% compared to baseline values. In the presence of ADH and Ang II (1 nM) initially decreased QO2 with a subsequent recovery (279 ± 17 nmol O2/min/mg protein). ADH increased cAMP levels, whereas Ang II decreased it. In contratst, ADH caused no effect in superoxide levels in thick ascending limbs of normotensive and increased after 3.3 minutes incubation. In hypertensive rats, the QO2 was stimulated by 98% after ADH. In these rats, and Ang II + ADH produced an initial decrease QO2 and a subsequent over-stimulation by ADH (184 % increase , p <0.05 vs normotensive animals) . Unlike what was observed in normotensive animals, Ang II increased early superoxide levels before at 1.7 minutes incubation and reached significant values compared to basal. In addition Losartan blocked the Ang II -induced effects. The superoxide scavenger tempol blocked the increase in Ang II -induced QO2 in both animal models. Taken together these results indicate that in hypertensive animals there is an additive effect between ADH and Ang II in the thick ascending limb of the loop of Henle. Therefore, the abnormal mechanism observed in hypertensive animals could explain the Na positive balance in this model of arterial hypertension.

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Abstract 199: Hydrogen Peroxide Mediates the pH Conditioned Chloride Conductance in Nodose Ganglia Neurons

Hypertension ◽

10.1161/hyp.60.suppl_1.a199 ◽

2012 ◽

Vol 60 (suppl_1) ◽

Author(s):

Runping Wang ◽

Yongjun Lu ◽

Carol A Whiteis ◽

Christopher J Benson ◽

Mark W Chapleau ◽

...

Keyword(s):

Conditioned Response ◽

Vagal Afferents ◽

Induced Responses ◽

Oxygen Species ◽

Patch Clamp Technique ◽

Whole Cell Patch Clamp ◽

Nodose Ganglia ◽

Rate Of Increase ◽

Induced Currents ◽

Superoxide Scavenger

pH sensitivity has been rarely studied in vagal afferents of nodose ganglia (NG) neurons. Using whole-cell patch-clamp technique in isolated NG neurons, we recently identified a pH-conditioned Cl - current (pH-I) that was evoked following 2 or 3 brief (10s) exposures to low extracellular pH (7.0-6.0) in 16 of 22 (70%) cells (FASEB J, 2012). The current is large (904.3±159.9pA) and prolonged, lasting 10∼15 minutes, and causes significant depolarization (Δ35.2±4.4mV). In the present study, we tested the hypothesis that reactive oxygen species (ROS) mediates this pH-conditioned Cl - conductance. We found that the rate of increase in fluorescence [(F-F 0 )/F 0 ] of NG neurons loaded with dihydroethidine (ROS dye) rose dramatically following the brief exposures to pH 6.0 from a control of 0.04±0.01 to 0.12±0.02 units/min over 10∼15 minutes (n=31 neurons, p<0.01). Moreover superfusion of neurons with H 2 O 2 induced currents that mimicked the pH conditioned currents. Because of similarities between the pH-conditioned Cl - conductance and the previously described “swell-activated” Cl - current induced with hypoosmotic solutions, we superfused the NG neurons with the H 2 O 2 scavenger PEG-catalase (1000 units/ml). PEG-catalase blocked significantly (p<0.01) the “swell” response to 210 mOsm from 23.3±6.3pA/pF to 0.57±0.39 pA/pF (n=4) as well as the pH-conditioned response from 25.7±6.5pA/pF (n=6) to 6.9±1.4 pA/pF (n=12). The superoxide scavenger PEG-SOD did not affect the current. These results indicate that both pH-conditioned and swell-induced responses are mediated by H 2 O 2 . Opening of these outward Cl - conductances that cause sustained depolarization of vagal afferents may induce a beneficial reflex sympathoinhibition during myocardial ischemia/acidosis or initiate a gastro-intestinal post-prandial satiety reflex.

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Abstract 38: Reactive Oxygen Species Contribute To Aneurysmal Rupture in Mice

Stroke ◽

10.1161/str.44.suppl_1.a38 ◽

2013 ◽

Vol 44 (suppl_1) ◽

Author(s):

Kenji Shimada ◽

Yoshiteru Tada ◽

Kosuke Wada ◽

Mari Kudo ◽

Shoko Murakami ◽

...

Keyword(s):

Nadph Oxidase ◽

Xanthine Oxidase ◽

Intracranial Aneurysms ◽

Oxidase Inhibitor ◽

Oxygen Species ◽

Gelatinase Activity ◽

Xanthine Oxidase Inhibitor ◽

Aneurysmal Rupture ◽

Nadph Oxidase Inhibitor ◽

Superoxide Scavenger

Background and Purpose: Inflammation and apoptosis are recognized as key factors for aneurysmal rupture. Reactive oxygen species (ROS) mediates both inflammation and apoptosis in vascular walls. Therefore, we hypothesized that ROS produced by xanthine oxidase and NADPH oxidase contributes to aneurysmal rupture. Recently we have demonstrated the feasibility of using a mouse model of intracranial aneurysms to test pharmacological therapies for the prevention of aneurysmal rupture. We tested the hypothesis by using this newly established mouse model. Methods: Intracranial aneurysms were induced in male mice using a combination of a single injection of elastase into the cerebrospinal fluid and the deoxycorticosterone acetate (DOCA) salt hypertension. Six days after aneurysm induction, we started 2-week treatment with vehicle (n=27), a superoxide scavenger (tempol; n=13), a xanthine oxidase inhibitor (oxypurinol; n=15), and a NADPH oxidase inhibitor (apocynin; n=16). Aneurysmal rupture was detected by neurological symptoms and confirmed by the presence of intracranial aneurysms with subarachnoid hemorrhage. Dihydroethidium staining and in situ zymography were performed to detect superoxide production and gelatinase activity, respectively. Results: A superoxide scavenger (tempol) significantly reduced rupture rate (vehicle vs. tempol: 74% vs. 27%, P < 0.05) (Figure1). It reduced superoxide production and gelatinase activity in aneurysmal walls (Figure2). Furthermore, the xanthine oxidase inhibitor (oxypurinol), and the NADPH oxidase inhibitor (apocynin) reduced the rupture rate (vehicle vs. oxypurinol: 74% vs. 30%, P< 0.05, vehicle vs. apocynin: 74% vs. 33%, P < 0.05). Conclusion: Our results indicate that superoxide produced by xanthine oxidase and NADPH oxidase contributes to aneurysmal rupture, by activating matrix metalloproteinases.

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Pivotal participation of nitrogen dioxide in l-arginine induced acute necrotizing pancreatitis: protective role of superoxide scavenger 4-OH-TEMPO

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2004.11.032 ◽

2005 ◽

Vol 326 (2) ◽

pp. 313-320 ◽

Cited By ~ 28

Author(s):

Aleksandra Dąbrowska ◽

Dagmara Jacewicz ◽

Agnieszka Łapińska ◽

Bogdan Banecki ◽

Adam Figarski ◽

...

Keyword(s):

Nitrogen Dioxide ◽

Necrotizing Pancreatitis ◽

Protective Role ◽

Acute Necrotizing Pancreatitis ◽

Acute Necrotizing ◽

Superoxide Scavenger

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O2-induced ENaC expression is associated with NF-κB activation and blocked by superoxide scavenger

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1998.275.4.l764 ◽

1998 ◽

Vol 275 (4) ◽

pp. L764-L770 ◽

Cited By ~ 25

Author(s):

Bijan Rafii ◽

A. Keith Tanswell ◽

Gail Otulakowski ◽

Olli Pitkänen ◽

Rose Belcastro-Taylor ◽

...

Keyword(s):

Short Circuit ◽

Short Circuit Current ◽

Nuclear Factor Κb ◽

Lung Epithelial Cells ◽

Mrna Levels ◽

Nuclear Factor ◽

Lung Epithelial ◽

Distal Lung ◽

Superoxide Scavenger ◽

Transcription Factor Nuclear Factor

Cultured rat fetal distal lung epithelial cells (FDLEs), when switched from fetal (3%) to postnatal (21%) O2 concentrations, have increased epithelial Na+ channel (ENaC) mRNA levels and amiloride-sensitive Na+transport [O. Pitkänen, A. K. Tanswell, G. Downey, and H. O’Brodovich. Am. J. Physiol. 270 ( Lung Cell. Mol. Physiol. 14): L1060–L1066, 1996]. The mechanisms by which O2 mediates these effects are unknown. After isolation, FDLEs were kept at 3% O2 overnight, then switched to 21% O2 (3–21% O2 group) or maintained at 3% O2 (3–3% O2 group) for 48 h. The amiloride-sensitive short-circuit current ( I sc) in the 3–21% O2 group was double that in the 3–3% O2 group. Amiloride-sensitive I sc could not be induced by medium conditioned by 21% O2-exposed FDLEs but was reversed by returning the cells to 3% O2. Neither the cyclooxygenase inhibitor ibuprofen, liposome-encapsulated catalase, nor hydroperoxide scavengers (U-74389G or Trolox) blocked the O2-induced amiloride-sensitive I sc. In contrast, the cell-permeable superoxide scavenger tetramethylpiperidine- N-oxyl (TEMPO) eliminated the O2-induced increases in amiloride-sensitive I sc and ENaC mRNA levels. The switch from 3 to 21% O2 induced the transcription factor nuclear factor-κB, which could also be blocked by TEMPO. We conclude that 1) the O2-induced increase in amiloride-sensitive I sc is reversible and 2) the O2-induced increase in amiloride-sensitive I sc and ENaC mRNA levels is associated with activation of nuclear factor-κB and may be mediated, at least in part, by superoxide.

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Effects of free radical generation on mouse pial arterioles: probable role of hydroxyl radicals

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1983.245.1.h139 ◽

1983 ◽

Vol 245 (1) ◽

pp. H139-H142 ◽

Cited By ~ 6

Author(s):

W. I. Rosenblum

Keyword(s):

Free Radical ◽

Xanthine Oxidase ◽

Hydroxyl Radicals ◽

Free Radical Scavengers ◽

Radical Scavengers ◽

Pial Arterioles ◽

Probable Role ◽

Radical Generation ◽

Superoxide Scavenger

Mouse pial arterioles were exposed to the free radical-generating reactants acetaldehyde and xanthine oxidase. Concentrations of 0.5 mM acetaldehyde and 0.1 U/ml xanthine oxidase caused reversible dilations, whereas higher concentrations produced initial constrictions followed by reversible dilations. The following free radical scavengers inhibited the dilation when added to the lower concentrations of reactants: superoxide dismutase, a superoxide scavenger; catalase, an H2O2 scavenger; and mannitol, a hydroxyl scavenger. In addition, pretreatment of the animal with dimethyl sulfoxide, a hydroxyl scavenger, also inhibited the response. The scavengers were also tested against either the dilation produced by increased inspired CO2 or against the dilation produced by local application of 10(-3) M papaverine. No significant effect was observed. The data support the hypothesis that hydroxyl radicals can dilate pial arterioles, since all the scavengers can ultimately reduce levels of hydroxyl generated by acetaldehyde plus xanthine oxidase.

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