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Superoxide AND Tempol

Brandi Wynne, Trinity Kronk, Otor Al-Khalili, Benjamin Ko, Franziska Theilig, Douglas Eaton, Robert Hoover
OBJECTIVE: Hypertension is characterized by increased sodium reabsorption along the aldosterone-sensitive distal nephron (ASDN) and systemic inflammation. Interleukin-6 (IL-6) is a possible mediator, signaling via the transmembrane IL-6 receptor alpha (IL-6Rα); however, whether IL-6Rα is present in the distal convoluted tubule (DCT) is unknown. Increased sodium reabsorption is not always correlated with increased aldosterone (Aldo). Thus, understanding how Aldo-independent sodium reabsorption occurs is critical...
September 2016: Journal of Hypertension
Priscila de Souza, Karla Lorena Guarido, Karin Scheschowitsch, Luísa Mota da Silva, Maria Fernanda Werner, Jamil Assreuy, José Eduardo da Silva-Santos
We investigated long-lasting changes in endothelial and vascular function in adult rat survivors of severe sepsis induced by cecal ligation and puncture (CLP) model. For this, male Wistar rats (200-350g) had their cecum punctured once (non-transfixing hole) with a 14-gauge needle. Performed in this way, a mortality rate around 30% was achieved in the first 72h. The survivors, together with age-matched control rats (not subjected to CLP), were maintained in our holding room for 60 days (S60 group) and had the descending thoracic aorta processed for functional, histological, biochemical or molecular analyses...
September 30, 2016: Redox Biology
Julia Dolinina, Kristinn Sverrisson, Anna Rippe, Carl M Öberg, Bengt Rippe
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, while 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...
September 28, 2016: American Journal of Physiology. Renal Physiology
Brandi Wynne, Trinity Kronk, Otor Al-Khalili, Benjamin Ko, Franziska Theilig, Douglas Eaton, Robert Hoover
OBJECTIVE: Hypertension is characterized by increased sodium reabsorption along the aldosterone-sensitive distal nephron (ASDN) and systemic inflammation. Interleukin-6 (IL-6) is a possible mediator, signaling via the transmembrane IL-6 receptor alpha (IL-6Rα); however, whether IL-6Rα is present in the distal convoluted tubule (DCT) is unknown. Increased sodium reabsorption is not always correlated with increased aldosterone (Aldo). Thus, understanding how Aldo-independent sodium reabsorption occurs is critical...
September 2016: Journal of Hypertension
Katharina Krueger, Jianlin Shen, Alexandra Maier, Martin Tepel, Alexandra Scholze
Mitochondrial superoxide dismutase 2 (SOD2) converts superoxide anions to hydrogen peroxide and oxygen. Human data on SOD2 protein content in chronic kidney disease (CKD) are sparse and mortality data are lacking. We investigated SOD2 protein content in monocytes from patients with hemodialysis therapy (n = 81), CKD stage 1-5 (n = 120), and healthy controls (n = 13) using in-cell Western assays. SOD2 protein decreased from CKD stage 1 until stage 4 whereas it increased again in stage 5 with and without hemodialysis...
2016: Oxidative Medicine and Cellular Longevity
Hila Roshanravan, Eun Y Kim, Stuart E Dryer
The arachidonic acid metabolite 20-hydroxyeicosatetraenoic acid (20-HETE) regulates renal function, including changes in glomerular function evoked during tubuloglomerular feedback (TGF). This study describes the cellular actions of 20-HETE on cultured podocytes, assessed by whole-cell recordings from cultured podocytes combined with pharmacological and cell-biological manipulations of cells. Bath superfusion of 20-HETE activates cationic currents that are blocked by the pan-TRP blocker SKF-96365 and by 50 μM La(3+), and which are attenuated after siRNA knockdown of TRPC6 subunits...
2016: Frontiers in Physiology
Kathleen M Lukaszewicz, Mahesh P Paudyal, John R Falck, Julian H Lombard
OBJECTIVE: The potential contribution of CYP4A enzymes to endothelial dysfunction in Dahl salt-sensitive (SS) rats was determined by comparison to SS-5(BN) consomic rats having chromosome 5 carrying CYP4A alleles from the Brown Norway (BN) rat introgressed into the SS genetic background. METHODS: The following experiments were performed in cerebral arteries from HS-fed SS and SS-5(BN) rats ± the SOD inhibitor DETC and/or the superoxide scavenger Tempol: 1) endothelial function was determined via video microscopy ± acute addition of the CYP4A inhibitor DDMS or Tempol; 2) vascular oxidative stress was assessed with DHE fluorescence ± acute addition of DDMS, L-NAME, or PEG-SOD; and 3) CYP4A protein levels were compared by Western blotting...
August 18, 2016: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
Alejandra Z Vielma, Luisa León, Ignacio C Fernández, Daniel R González, Mauricio P Boric
S-nitrosylation of several Ca2+ regulating proteins in response to β-adrenergic stimulation was recently described in the heart; however the specific nitric oxide synthase (NOS) isoform and signaling pathways responsible for this modification have not been elucidated. NOS-1 activity increases inotropism, therefore, we tested whether β-adrenergic stimulation induces NOS-1-dependent S-nitrosylation of total proteins, the ryanodine receptor (RyR2), SERCA2 and the L-Type Ca2+ channel (LTCC). In the isolated rat heart, isoproterenol (10 nM, 3-min) increased S-nitrosylation of total cardiac proteins (+46±14%) and RyR2 (+146±77%), without affecting S-nitrosylation of SERCA2 and LTCC...
2016: PloS One
Qixiong Zhang, Hui Tao, Yongyao Lin, Ying Hu, Huijie An, Dinglin Zhang, Shibin Feng, Houyuan Hu, Ruibing Wang, Xiaohui Li, Jianxiang Zhang
Oxidative stress, resulting from excessive generation of reactive oxygen species (ROS), plays a pivotal role in the initiation and progression of inflammatory bowel disease (IBD). To develop an efficacious and safe nanotherapy against IBD, we designed and developed a superoxide dismutase/catalase mimetic nanomedicine comprising a hydrogen peroxide-eliminating nanomatrix and a free radical scavenger Tempol (Tpl). To this end, an oxidation-responsive β-cyclodextrin material (OxbCD) was synthesized, and a Tpl-loaded OxbCD nanoparticle (Tpl/OxbCD NP) was produced...
October 2016: Biomaterials
S Novella, X Vidal-Gómez, A Mompeón, D Pérez-Cremades, G Segarra, P Medina, C Hermenegildo
OBJECTIVE: The role of ageing in the development of vascular disease is currently associated with a rise in oxidative stress. Thromboxane A2 (TXA2) is an inflammatory and oxidant endogenous vasoconstrictor which action increases with ageing and lack of estrogens, both conditions found in menopause. Our aim was to determine superoxide anion (O2-) levels in response to TXA2 in aortic vascular tissue from senescent and ovariectomized mice and the role of cyclooxygenase as source of O2-. DESIGN AND METHOD: Senescence accelerated mice (SAM) were used in this study...
September 2016: Journal of Hypertension
Akram Ranjbar, Hassan Ghasemi, Mahdi Hatami, Farahanaz Dadras, Tavakol Heidary Shayesteh, Farhad Khoshjou
INTRODUCTION: Diabetic nephropathy (DN) is the most common cause of the chronic kidney disease in the world. Oxidative stress on the other hand has a major and well known role in its pathophysiology. OBJECTIVES: The aim of the study is to figure out if tempol, a synthetic antioxidant agent, modifies DN and to determine its relevance to changes of serum oxidative biomarkers. MATERIALS AND METHODS: Twenty-seven male rats were equally divided in to 4 groups (7 rats for each group)...
2016: Journal of Renal Injury Prevention
Vienna E Brunt, Taylor M Eymann, Michael A Francisco, Matthew J Howard, Christopher T Minson
Passive heat therapy (repeated hot tub or sauna use) reduces cardiovascular risk, but its effects on the mechanisms underlying improvements in microvascular function have yet to be studied. We investigated the effects of heat therapy on microvascular function and whether improvements were related to changes in nitric oxide (NO) bioavailability using cutaneous microdialysis. Eighteen young, sedentary, otherwise healthy subjects participated in 8 wk of heat therapy (hot water immersion to maintain rectal temperature ≥38...
September 1, 2016: Journal of Applied Physiology
Eun Young Jang, Chae Ha Yang, David M Hedges, Soo Phil Kim, Jun Yeon Lee, Tyler G Ekins, Brandon T Garcia, Hee Young Kim, Ashley C Nelson, Nam Jun Kim, Scott C Steffensen
Methamphetamine (METH) markedly increases dopamine (DA) release in the mesolimbic DA system, which plays an important role in mediating the reinforcing effects of METH. METH-induced DA release results in the formation of reactive oxygen species (ROS), leading to oxidative damage. We have recently reported that ROS are implicated in behavior changes and DA release in the nucleus accumbens (NAc) following cocaine administration. The aim of this study was to evaluate the involvement of ROS in METH-induced locomotor activity, self-administration and enhancement of DA release in the NAc...
July 14, 2016: Addiction Biology
Yilin Ren, Branislava Janic, Kristopher Kutskill, Edward L Peterson, Oscar A Carretero
Connecting tubule glomerular feedback (CTGF) is a mechanism where an increase in sodium (Na) concentration in the connecting tubule (CNT) causes the afferent arteriole (Af-Art) to dilate. We recently reported that aldosterone within the CNT lumen enhances CTGF via a nongenomic effect involving GPR30 receptors and sodium/hydrogen exchanger (NHE), but the signaling pathways of this mechanism are unknown. We hypothesize that aldosterone enhances CTGF via cAMP/protein kinase A (PKA) pathway that activates protein kinase C (PKC) and stimulates superoxide (O-2) production...
July 13, 2016: American Journal of Physiology. Renal Physiology
Peng Jin, Tao Li, Xueqi Li, Xinghua Shen, Yanru Zhao
Myocardial infarction is a major contributor to morbidity and mortality in diabetes, which is characterized by inadequate angiogenesis and consequent poor blood reperfusion in the diabetic ischemic heart. The aim of the present study was to investigate the effect that oxidative stress in endothelial progenitor cells (EPCs) has on cardiac angiogenesis in diabetic mice. EPCs derived from diabetic mice revealed reductions in superoxide dismutase (SOD) expression levels and activity compared with those from normal mice...
June 2016: Experimental and Therapeutic Medicine
Jingyun Shao, Peng Wang, An Liu, Xusheng Du, Jie Bai, Mingwei Chen
Punicalagin (PG), a major bioactive ingredient in pomegranate juice, has been proven to have anti-oxidative stress properties and to exert protective effects on acute lung injuries induced by lipopolysaccharides. This study aimed to investigate the effects of PG treatment on hypoxic pulmonary hypertension (HPH) and the underlying mechanisms responsible for the effects. Rats were exposed to 10% oxygen for 2 wk (8 h/day) to induce the HPH model. PG (5, 15, 45[Formula: see text]mg/kg) was orally administered 10[Formula: see text]min before hypoxia each day...
2016: American Journal of Chinese Medicine
Chris Nevitt, Grant McKenzie, Katelyn Christian, Jeff Austin, Sarah Hencke, James Hoying, Amanda LeBlanc
Aging and cardiovascular disease are associated with the loss of nitric oxide (NO) signaling and a decline in the ability to increase coronary blood flow reserve (CFR). Thrombospondin-1 (Thbs-1), through binding of CD47, has been shown to limit NO-dependent vasodilation in peripheral vascular beds via formation of superoxide (O2 (-)). The present study tests the hypothesis that, similar to the peripheral vasculature, blocking CD47 will improve NO-mediated vasoreactivity in coronary arterioles from aged individuals, resulting in improved CFR...
June 1, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Aisah A Aubdool, Xenia Kodji, Nayaab Abdul-Kader, Richard Heads, Elizabeth S Fernandes, Stuart Bevan, Susan D Brain
BACKGROUND AND PURPOSE: Transient receptor potential ankyrin-1 (TRPA1) activation is known to mediate neurogenic vasodilatation. We investigated the mechanisms involved in TRPA1-mediated peripheral vasodilatation in vivo using the TRPA1 agonist cinnamaldehyde. EXPERIMENTAL APPROACH: Changes in vascular ear blood flow were measured in anaesthetized mice using laser Doppler flowmetry. KEY RESULTS: Topical application of cinnamaldehyde to the mouse ear caused a significant increase in blood flow in the skin of anaesthetized wild-type (WT) mice but not in TRPA1 knockout (KO) mice...
August 2016: British Journal of Pharmacology
Yusi Wang, Paramita Pati, Yiming Xu, Feng Chen, David W Stepp, Yuqing Huo, R Daniel Rudic, David J R Fulton
The circadian clock is a transcriptional network that functions to regulate the expression of genes important in the anticipation of changes in cellular and organ function. Recent studies have revealed that the recognition of pathogens and subsequent initiation of inflammatory responses are strongly regulated by a macrophage-intrinsic circadian clock. We hypothesized that the circadian pattern of gene expression might be influenced by inflammatory stimuli and that loss of circadian function in immune cells can promote pro-inflammatory behavior...
2016: PloS One
Petra Haberzettl, Timothy E O'Toole, Aruni Bhatnagar, Daniel J Conklin
BACKGROUND: Epidemiological evidence suggests that exposure to ambient air fine particular matter (PM2.5) increases the risk of developing type 2 diabetes and cardiovascular disease. However, the mechanisms underlying these effects of PM2.5 remain unclear. OBJECTIVES: We tested the hypothesis that PM2.5 exposure decreases vascular insulin sensitivity by inducing pulmonary oxidative stress. METHODS: Mice fed control (10-13% kcal fat) and high-fat (60% kcal fat, HFD) diet, treated with 4-hydroxy-2,2,6,6-tetramethylpiperidine1-oxyl (TEMPOL) or mice overexpressing lung-specific extracellular superoxide dismutase (ecSOD) were exposed to HEPA-filtered air or concentrated PM2...
April 29, 2016: Environmental Health Perspectives
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