scholarly journals Nitric oxide synthase inhibition causes acute increases in glomerular permeability in vivo, dependent upon reactive oxygen species

2016 ◽  
Vol 311 (5) ◽  
pp. F984-F990 ◽  
Author(s):  
Julia Dolinina ◽  
Kristinn Sverrisson ◽  
Anna Rippe ◽  
Carl M. Öberg ◽  
Bengt Rippe
Keyword(s):  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
High Performance ◽  
Reactive Oxygen ◽  
Size Exclusion ◽  
Oxygen Species ◽  
Glomerular Permeability ◽  
No Donor ◽  
Filtration Barrier

There is increasing evidence that the permeability of the glomerular filtration barrier (GFB) is partly regulated by a balance between the bioavailability of nitric oxide (NO) and that of reactive oxygen species (ROS). It has been postulated that normal or moderately elevated NO levels protect the GFB from permeability increases, whereas ROS, through reducing the bioavailability of NO, have the opposite effect. We tested the tentative antagonism between NO and ROS on glomerular permeability in anaesthetized Wistar rats, in which the left ureter was cannulated for urine collection while simultaneously blood access was achieved. Rats were systemically infused with either l-NAME or l-NAME together with the superoxide scavenger Tempol, or together with l-arginine or the NO-donor DEA-NONOate, or the cGMP agonist 8-bromo-cGMP. To measure glomerular sieving coefficients (theta, θ) to Ficoll, rats were infused with FITC-Ficoll 70/400 (mol/radius 10–80 Å). Plasma and urine samples were analyzed by high-performance size-exclusion chromatography (HPSEC) for determination of θ for Ficoll repeatedly during up to 2 h. l-NAME increased θ for Ficoll70Å from 2.27 ± 1.30 × 10−5 to 8.46 ± 2.06 × 10−5 ( n = 6, P < 0.001) in 15 min. Tempol abrogated these increases in glomerular permeability and an inhibition was also observed with l-arginine and with 8-bromo-cGMP. In conclusion, acute NO synthase inhibition in vivo by l-NAME caused rapid increases in glomerular permeability, which could be reversed by either an ROS antagonist or by activating the guanylyl cyclase-cGMP pathway. The data strongly suggest a protective effect of NO in maintaining normal glomerular permeability in vivo.

scholarly journals Acute reactive oxygen species (ROS)-dependent effects of IL-1β, TNF-α, and IL-6 on the glomerular filtration barrier (GFB) in vivo

2015 ◽  
Vol 309 (9) ◽  
pp. F800-F806 ◽  
Author(s):  
Kristinn Sverrisson ◽  
Josefin Axelsson ◽  
Anna Rippe ◽  
Daniel Asgeirsson ◽  
Bengt Rippe
Keyword(s):  
Reactive Oxygen Species ◽  
Glomerular Filtration ◽  
Reactive Oxygen ◽  
Size Exclusion ◽  
Oxygen Species ◽  
Glomerular Filtration Barrier ◽  
Glomerular Permeability ◽  
Filtration Barrier ◽  
Tnf Α ◽  
Superoxide Scavenger

This study was performed to investigate the immediate actions of the proinflammatory cytokines IL-1β, TNF-α, and IL-6 on the permeability of the glomerular filtration barrier (GFB) in rats and to test whether these actions are dependent upon the release of reactive oxygen species (ROS). In anesthetized rats, blood access was achieved and the left ureter was cannulated for urine collection. Rats were continuously infused intravenously with either IL-1β (0.4 and 2 μg·kg−1·h−1), TNF-α (0.4 and 2 μg·kg−1·h−1), or IL-6 (4 and 8 μg·kg−1·h−1), together with polydisperse FITC-Ficoll-70/400 and inulin for 1 h. Plasma and urine samples were analyzed by high performance size exclusion chromatography (HPSEC) for determination of glomerular sieving coefficients (θ). The glomerular filtration rate (GFR) was also assessed (51Cr-EDTA). In separate experiments, the superoxide scavenger tempol (30 mg·kg−1·h−1) was given before and during cytokine infusions. IL-1β and TNF-α caused rapid, partly reversible increases in glomerular permeability to large molecules (Ficoll50–80Å), peaking at 5–30 min, while IL-6 caused a more gradual increase in permeability, leveling off at 60 min. Tempol almost completely abrogated the glomerular permeability effects of the cytokines infused. In conclusion IL-1β, TNF-α, and IL-6, when infused systemically, caused immediate and partly reversible increases in glomerular permeability, which could be inhibited by the superoxide scavenger tempol, suggesting an important role of ROS in acute cytokine-induced permeability changes in the GFB.

Scavengers of reactive oxygen species, paracalcitol, RhoA, and Rac-1 inhibitors and tacrolimus inhibit angiotensin II-induced actions on glomerular permeability

2013 ◽  
Vol 305 (3) ◽  
pp. F237-F243 ◽  
Author(s):  
Josefin Axelsson ◽  
Anna Rippe ◽  
Kristinn Sverrisson ◽  
Bengt Rippe
Keyword(s):  
Reactive Oxygen Species ◽  
Kinase Inhibitor ◽  
Reactive Oxygen ◽  
Small Gtpases ◽  
Size Exclusion ◽  
Ros Generation ◽  
Oxygen Species ◽  
Ang Ii ◽  
Glomerular Permeability ◽  
Filtration Barrier

Systemic infusions of ANG II rapidly induce large, dynamic increases in the permeability of the glomerular filtration barrier (GFB) in rats. After binding to its receptor(s), ANG II generates reactive oxygen species (ROS) and produces Ca2+ influx into cells, leading to activation of a plethora of signaling cascades, including, e.g., calcineurin and small GTPases, such as Rac-1 and RhoA. In the present study we sought to interact with some of these cascades to test potential novel antiproteinuric agents. In anesthetized Wistar rats, the left urether was cannulated for urine collection, and blood access was achieved. Rats were infused with ANG II (16 ng·kg−1·min−1) alone, or together with the ROS scavengers tempol or dimethylthiourea (DMTU) or the D-vitamin analog paracalcitol, the RhoA-kinase inhibitor Y-27632, the Rac-1 inhibitor NSC-23766, or the calcineurin inhibitor tacrolimus. FITC-Ficoll-70/400 (mol.radius 10–80 Å) and 51Cr-EDTA were infused throughout the experiment. Plasma and urine samples were taken during baseline and at 5 and 15 min after the start of the infusions and analyzed by high-performance size-exclusion chromatography for determination of glomerular sieving coefficients (θ) for Ficoll10–80Å. ANG II infusion into rats caused marked increases in glomerular permeability to large Ficoll molecules (Ficoll50–80Å), which were abrogated by the ROS scavenger tempol and partly by DMTU. Paracalcitol, RhoA, and Rac-1 inhibition, and, to some extent tacrolimus, but not prostacyclin, could also inhibit the glomerular permeability actions of ANG II. Our data suggest that cellular ROS generation and active Ca2+ signaling are involved in ANG II-induced increases in glomerular permeability.

scholarly journals Reactive oxygen species and nitric oxide imbalances lead to in vivo and in vitro arrhythmogenic phenotype in acute phase of experimental Chagas disease

2020 ◽  
Vol 16 (3) ◽  
pp. e1008379 ◽  
Author(s):  
Artur Santos-Miranda ◽  
Julliane Vasconcelos Joviano-Santos ◽  
Grazielle Alves Ribeiro ◽  
Ana Flávia M. Botelho ◽  
Peter Rocha ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Chagas Disease ◽  
Acute Phase ◽  
Reactive Oxygen ◽  
Oxygen Species

Imaging of Reactive Oxygen Species and Nitric Oxide In Vivo in Plant Tissues

2008 ◽  
pp. 397-409 ◽  
Author(s):  
Luisa M. Sandalio ◽  
María Rodríguez‐Serrano ◽  
María C. Romero‐Puertas ◽  
Luis A. del Río
Keyword(s):  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Plant Tissues ◽  
Oxygen Species

scholarly journals Correction: Reactive oxygen species and nitric oxide imbalances lead to in vivo and in vitro arrhythmogenic phenotype in acute phase of experimental Chagas disease

2020 ◽  
Vol 16 (10) ◽  
pp. e1009049
Author(s):  
Artur Santos-Miranda ◽  
Julliane Vasconcelos Joviano-Santos ◽  
Grazielle Alves Ribeiro ◽  
Ana Flávia M. Botelho ◽  
Peter Rocha ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Chagas Disease ◽  
Acute Phase ◽  
Reactive Oxygen ◽  
Oxygen Species

scholarly journals The H2S Donor GYY4137 Stimulates Reactive Oxygen Species Generation in BV2 Cells While Suppressing the Secretion of TNF and Nitric Oxide

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2966 ◽  
Author(s):  
Milica Lazarević ◽  
Emanuela Mazzon ◽  
Miljana Momčilović ◽  
Maria Basile ◽  
Giuseppe Colletti ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Microglial Cells ◽  
Oxygen Species ◽  
Bv2 Cells ◽  
The Central Nervous System

GYY4137 is a hydrogen sulfide (H2S) donor that has been shown to act in an anti-inflammatory manner in vitro and in vivo. Microglial cells are among the major players in immunoinflammatory, degenerative, and neoplastic disorders of the central nervous system, including multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, and glioblastoma multiforme. So far, the effects of GYY4137 on microglial cells have not been thoroughly investigated. In this study, BV2 microglial cells were stimulated with interferon-gamma and lipopolysaccharide and treated with GYY4137. The agent did not influence the viability of BV2 cells in concentrations up to 200 μM. It inhibited tumor necrosis factor but not interleukin-6 production. Expression of CD40 and CD86 were reduced under the influence of the donor. The phagocytic ability of BV2 cells and nitric oxide production were also affected by the agent. Surprisingly, GYY4137 upregulated generation of reactive oxygen species (ROS) by BV2 cells. The effect was mimicked by another H2S donor, Na2S, and it was not reproduced in macrophages. Our results demonstrate that GYY4137 downregulates inflammatory properties of BV2 cells but increases their ability to generate ROS. Further investigation of this unexpected phenomenon is warranted.

Noradrenaline Protects In Vivo Rat Heart Against Infarction and Ventricular Arrhythmias Via Nitric Oxide and Reactive Oxygen Species

2011 ◽  
Vol 169 (1) ◽  
pp. 9-15 ◽  
Author(s):  
Alireza Imani ◽  
Mahdieh Faghihi ◽  
Sayyed Shahabeddin Sadr ◽  
Somayeh Sadeghi Niaraki ◽  
Ali Mohammad Alizadeh
Keyword(s):  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Rat Heart ◽  
Ventricular Arrhythmias ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
In Vivo Rat Heart

scholarly journals Galectin-1-deficient mice are protected against Trypanosoma cruzi infection through altered neutrophil migration and production of reactive oxygen species and nitric oxide

2020 ◽  
Author(s):  
Thalita Bachelli Riul ◽  
Helioswilton Sales de Campos ◽  
Djalma de Souza Lima-Junior ◽  
Ana Elisa Caleiro Seixas Azzolini ◽  
Cristina Ribeiro de Barros Cardoso ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Trypanosoma Cruzi ◽  
Neutrophil Migration ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Infection Site ◽  
Neutrophil Accumulation

SUMMARYTrypanosoma cruzi is an intracellular parasite that causes Chagas disease that affects millions of people worldwide. Many cellular and molecular aspects of this neglected disease are not fully understood. Prior studies have shown that galectin-1 (Gal-1), a β-galactoside-binding protein that regulates leukocyte recruitment to the inflammatory site, and promotes T. cruzi infection, but the mechanism is unclear. Here, we report that C57BL/6 mice lacking Gal-1 (Lgals1−/−) exhibited lower parasitemia and higher survival rates than their wildtype (WT) counterparts when infected with T. cruzi Y strain. Two weeks after infection, Lgals1−/− mice displayed greater neutrophil accumulation in infection site and heart tissue than WT mice. In T. cruzi-infected Lgals1−/− mice, infiltrated neutrophils produced increased levels of reactive oxygen species (ROS), while macrophages and neutrophils produced increased levels of nitric oxide (NO), which reduced replication and viability of parasites in vitro and downregulated IL-1β production. Pharmacological inhibition of NADPH oxidase and NO synthase during early in vivo infection reversed the protective effect of Gal-1 deficiency in Lgals1−/− mice. Together, our findings demonstrate that lacking Gal-1 favors neutrophil migration to the infection site and increases production of ROS and NO, thereby controlling the early steps of T. cruzi infection by reducing parasitemia and prolonging survival of infected mice.

scholarly journals High salt intake shifts the mechanisms of flow-induced dilation in the middle cerebral arteries of Sprague-Dawley rats

2018 ◽  
Vol 315 (3) ◽  
pp. H718-H730 ◽  
Author(s):  
Anita Matic ◽  
Ivana Jukic ◽  
Ana Stupin ◽  
Lidija Baric ◽  
Zrinka Mihaljevic ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Cerebral Arteries ◽  
Hypoxia Inducible Factor ◽  
Reactive Oxygen ◽  
High Salt ◽  
Oxygen Species ◽  
Hypoxia Inducible Factor 1Α ◽  
Middle Cerebral Arteries

The goal of the present study was to examine the effect of 1 wk of high salt (HS) intake and the role of oxidative stress in changing the mechanisms of flow-induced dilation (FID) in isolated pressurized middle cerebral arteries of male Sprague-Dawley rats ( n = 15–16 rats/group). Reduced FID in the HS group was restored by intake of the superoxide scavenger tempol (HS + tempol in vivo group). The nitric oxide (NO) synthase inhibitor Nω-nitro-l-arginine methyl ester, cyclooxygenase inhibitor indomethacin, and selective inhibitor of microsomal cytochrome P-450 epoxidase activity N-(methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide significantly reduced FID in the low salt diet-fed group, whereas FID in the HS group was mediated by NO only. Cyclooxygenase-2 mRNA (but not protein) expression was decreased in the HS and HS + tempol in vivo groups. Hypoxia-inducible factor-1α and VEGF protein levels were increased in the HS group but decreased in the HS + tempol in vivo group. Assessment by direct fluorescence of middle cerebral arteries under flow revealed significantly reduced vascular NO levels and increased superoxide/reactive oxygen species levels in the HS group. These results suggest that HS intake impairs FID and changes FID mechanisms to entirely NO dependent, in contrast to the low-salt diet-fed group, where FID is NO, prostanoid, and epoxyeicosatrienoic acid dependent. These changes were accompanied by increased lipid peroxidation products in the plasma of HS diet-fed rats, increased vascular superoxide/reactive oxygen species levels, and decreased NO levels, together with increased expression of hypoxia-inducible factor-1α and VEGF. NEW & NOTEWORTHY High-salt (HS) diet changes the mechanisms of flow-induced dilation in rat middle cerebral arteries from a combination of nitric oxide-, prostanoid-, and epoxyeicosatrienoic acid-dependent mechanisms to, albeit reduced, a solely nitric oxide-dependent dilation. In vivo reactive oxygen species scavenging restores flow-induced dilation in HS diet-fed rats and ameliorates HS-induced increases in the transcription factor hypoxia-inducible factor-1α and expression of its downstream target genes.

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