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Superoxide AND Tempol

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https://www.readbyqxmd.com/read/28712765/losartan-reverses-cox-2-dependent-vascular-dysfunction-in-offspring-of-hyperglycaemic-rats
#1
Diego Barbosa de Queiroz, Fernanda Elizabethe Ramos-Alves, Juliana Santos-Rocha, Gloria Pinto Duarte, Fabiano Elias Xavier
AIMS: This study examined whether chronic treatment with losartan, an angiotensin II type 1 receptor (AT1R) antagonist, might reverse COX-2-mediated vascular dysfunction in mesenteric resistance arteries (MRA) from offspring of hyperglycaemic rats. MATERIALS AND METHODS: Male 12-month-old offspring of hyperglycaemic (O-DR) and normoglycaemic (O-CR) rats were treated with losartan (15mg·kg·day(-1)) during 2months. Third order MRA of untreated and losartan-treated O-DR and O-CR were mounted in wire myograph for isometric tension measurements...
July 13, 2017: Life Sciences
https://www.readbyqxmd.com/read/28674038/genetic-interference-with-endothelial-peroxisome-proliferator-activated-receptor-%C3%AE-augments-effects-of-angiotensin-ii-while-impairing-responses-to-angiotensin-1-7
#2
T Michael De Silva, Chunyan Hu, Dale A Kinzenbaw, Mary L Modrick, Curt D Sigmund, Frank M Faraci
Pharmacological activation of peroxisome proliferator-activated receptor-γ (PPAR-γ) protects the vasculature. Much less is known on the cell-specific impact of PPAR-γ when driven by endogenous ligands. Recently, we found that endothelial PPAR-γ protects against angiotensin II-induced endothelial dysfunction. Here, we explored that concept further examining whether effects were sex dependent along with underlying mechanisms. We studied mice expressing a human dominant-negative mutation in PPAR-γ driven by the endothelial-specific vascular cadherin promoter (E-V290M), using nontransgenic littermates as controls...
July 3, 2017: Hypertension
https://www.readbyqxmd.com/read/28673614/ros-dependent-activation-of-rhoa-rho-kinase-in-pulmonary-artery-role-of-src-family-kinases-and-arhgef1
#3
Charles E MacKay, Yasin Shaifta, Vladimir V Snetkov, Asvi A Francois, Jeremy P T Ward, Greg A Knock
The role of reactive oxygen species (ROS) in smooth muscle contraction is poorly understood. We hypothesised that G-protein coupled receptor (GPCR) activation and hypoxia induce Rho-kinase activity and contraction in rat intra-pulmonary artery (IPA) via stimulation of ROS production and subsequent Src-family kinase (SrcFK) activation. The T-type prostanoid receptor agonist U46619 induced ROS production in pulmonary artery smooth muscle cells (PASMC). U46619 also induced c-Src cysteine oxidation, SrcFK auto-phosphorylation, MYPT-1 and MLC20 phosphorylation and contraction in IPA, and all these responses were inhibited by antioxidants (ebselen, Tempol)...
July 1, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28666030/contribution-of-reactive-oxygen-species-to-the-pathogenesis-of-pulmonary-arterial-hypertension
#4
Nikki L Jernigan, Jay S Naik, Laura Weise-Cross, Neil D Detweiler, Lindsay M Herbert, Tracylyn R Yellowhair, Thomas C Resta
Pulmonary arterial hypertension is associated with a decreased antioxidant capacity. However, neither the contribution of reactive oxygen species to pulmonary vasoconstrictor sensitivity, nor the therapeutic efficacy of antioxidant strategies in this setting are known. We hypothesized that reactive oxygen species play a central role in mediating both vasoconstrictor and arterial remodeling components of severe pulmonary arterial hypertension. We examined the effect of the chemical antioxidant, TEMPOL, on right ventricular systolic pressure, vascular remodeling, and enhanced vasoconstrictor reactivity in both chronic hypoxia and hypoxia/SU5416 rat models of pulmonary hypertension...
2017: PloS One
https://www.readbyqxmd.com/read/28659507/pressor-response-to-angiotensin-ii-is-enhanced-in-aged-mice-and-associated-with-inflammation-vasoconstriction-and-oxidative-stress
#5
Quynh Nhu Dinh, Grant R Drummond, Barbara K Kemp-Harper, Henry Diep, T Michael De Silva, Hyun Ah Kim, Antony Vinh, Avril A B Robertson, Matthew A Cooper, Ashley Mansell, Sophocles Chrissobolis, Christopher G Sobey
Aging is commonly associated with chronic low-grade inflammation and hypertension but it is unknown whether a cause-effect relationship exists between them. We compared the sensitivity of young adult (8-12 w) and aged (23-31 mo) male C57Bl6J mice to develop hypertension in response to a slow-pressor dose of angiotensin II (Ang II; 0.28 mg/kg/d; 28 d). In young mice, the pressor response to Ang II was gradual and increased to 142±8 mmHg over 28 d. However, in aged mice, Ang II promptly increased SBP and reached 155±12 mmHg by 28 d...
June 28, 2017: Aging
https://www.readbyqxmd.com/read/28626074/a-type-potassium-channels-contribute-to-prorenin-increase-of-firing-activity-in-hypothalamic-vasopressin-neurosecretory-neurons
#6
Soledad Pitra, Javier E Stern
Recent studies support an important contribution of prorenin (PR) and its receptor (PRR) to the regulation of hypothalamic sympathetic and neurosecretory outflows to the cardiovascular system, including systemic release of vasopressin (VP), both under physiological and cardiovascular disease conditions. Still, the identification of precise cellular mechanisms and neuronal/molecular targets remain unknown. We recently showed that PRR is expressed in VP neurons, and that their activation increases neuronal activity...
June 16, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28603016/rapid-repeatable-in%C3%A2-vivo-detection-of-retinal-reactive-oxygen-species
#7
Ning Fan, Sean M Silverman, Yang Liu, Xizhen Wang, Byung-Jin Kim, Liping Tang, Abbot F Clark, Xuyang Liu, Iok-Hou Pang
Oxidative injuries, such as those related to reactive oxygen species (ROS), have been implicated in various retinal and optic nerve disorders. Many ROS detection methods have been developed. Although widely utilized, many of these methods are useful only in post mortem tissues, or require relatively expensive equipment, or involve intraocular injection. In the present study, we demonstrated and characterized a chemiluminescent probe L-012 as a noninvasive, in vivo ROS detection agent in the mouse retina. Using optic nerve crush (ONC) and retinal ischemia/reperfusion (I/R) as injury models, we show that L-012 produced intensive luminescent signals specifically in the injured eyes...
June 8, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28600985/nox2-contributes-to-hyperinsulinemia-induced-redox-imbalance-and-impaired-vascular-function
#8
Abeer M Mahmoud, Mohamed M Ali, Edwin R Miranda, Jacob T Mey, Brian K Blackburn, Jacob M Haus, Shane A Phillips
Insulin resistance promotes vascular endothelial dysfunction and subsequent development of cardiovascular disease. Previously we found that skeletal muscle arteriolar flow-induced dilation (FID) was reduced following a hyperinsulinemic clamp in healthy adults. Therefore, we hypothesized that hyperinsulinemia, a hallmark of insulin resistance, contributes to microvascular endothelial cell dysfunction via inducing oxidative stress that is mediated by NADPH oxidase (Nox) system. We examined the effect of insulin, at levels that are comparable with human hyperinsulinemia on 1) FID of isolated arterioles from human skeletal muscle tissue in the presence and absence of Nox inhibitors and 2) human adipose microvascular endothelial cell (HAMECs) expression of nitric oxide (NO), endothelial NO synthase (eNOS), and Nox-mediated oxidative stress...
June 3, 2017: Redox Biology
https://www.readbyqxmd.com/read/28589150/tempol-a-superoxide-dismutase-mimetic-agent-inhibits-superoxide-anion-induced-inflammatory-pain-in-mice
#9
Catia C F Bernardy, Ana C Zarpelon, Felipe A Pinho-Ribeiro, Cássia Calixto-Campos, Thacyana T Carvalho, Victor Fattori, Sergio M Borghi, Rubia Casagrande, Waldiceu A Verri
The present study evaluated the anti-inflammatory and analgesic effects of the superoxide dismutase mimetic agent tempol in superoxide anion-induced pain and inflammation. Mice were treated intraperitoneally with tempol (10-100 mg/kg) 40 min before the intraplantar injection of a superoxide anion donor, potassium superoxide (KO2, 30 μg). Mechanical hyperalgesia and thermal hyperalgesia, paw edema, and mRNA expression of peripheral and spinal cord mediators involved in inflammatory pain, TNFα, IL-1β, IL-10, COX-2, preproET-1, gp91(phox), Nrf2, GFAP, and Iba-1, were evaluated...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28575410/enhanced-endothelin-1-rho-kinase-signaling-and-coronary-microvascular-dysfunction-in-hypertensive-myocardial-hypertrophy
#10
Shu-Huai Tsai, Guangrong Lu, Xin Xu, Yi Ren, Travis W Hein, Lih Kuo
Aims: Hypertensive cardiac hypertrophy is associated with reduced coronary flow reserve, but its impact on coronary flow regulation and vasomotor function remains incompletely understood and requires further investigation. Methods and results: Left ventricular hypertrophy was induced in mice by transverse aortic coarctation (TAC) for 4 weeks. The left coronary artery blood velocity (LCABV) and myocardium lactate level were measured following the metabolic activation by isoproterenol...
May 29, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28574428/reduced-dietary-selenium-impairs-vascular-function-by-increasing-oxidative-stress-in-sprague-dawley-rat-aortas
#11
Ana Stupin, Anita Cosic, Sanja Novak, Monika Vesel, Ivana Jukic, Brigita Popovic, Krunoslav Karalic, Zdenko Loncaric, Ines Drenjancevic
This study aimed to determine whether low dietary Se content affects the function and mechanisms mediating the vascular relaxation of rat aortas, and to test the role of oxidative stress in observed differences. Male Sprague Dawley (SD) rats were maintained for 10 weeks on low Se (low-Se group; N = 20) or normal Se content (norm-Se group; N = 20) rat chow. Dose responses to acetylcholine (ACh; 10(-9)-10(-5)M) and the response to reduced pO₂ were tested in noradrenaline-precontracted aortic rings in the absence/presence of the nitric oxide synthase (NOS) inhibitor nitro-l-arginine methyl ester (l-NAME), the cyclooxygenase 1 and 2 (COX-1, 2) inhibitor Indomethacin, and the antioxidative agent Tempol in tissue bath...
June 2, 2017: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/28556994/hyperglycemia-in-pregnant-rats-causes-gender-related-vascular-dysfunction-in-adult-offspring-role-of-cyclooxygenase-2
#12
Francine Gomes de Sá, Diego Barbosa de Queiroz, Fernanda Elizabethe Ramos-Alves, Juliana Santos-Rocha, Odair Alves da Silva, Hicla Steffany Moreira, Geórgia Andrade Leal, Marcelo Aurélio da Rocha, Gloria Pinto Duarte, Fabiano Elias Xavier
Exposure to maternal hyperglycemia induces hypertension and vascular dysfunction in adult male offspring. Because female offspring from several fetal programming models are protected from the effects of fetal insult, in this study we analyzed possible differences relative to gender in blood pressure and vascular function in hyperglycemia-programmed offspring. Hyperglycemia was induced on gestation day 7 (streptozotocin, 50 mg.kg(-1) ). Blood pressure, acetylcholine and phenylephrine/noradrenaline responses were analyzed in aorta and mesenteric resistance arteries (MRA) of 3-, 6- and 12-month-old male and female offspring...
May 30, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28544543/acute-toll-like-receptor-4-activation-impairs-rat-renal-microvascular-autoregulatory-behaviour
#13
Justin P Van Beusecum, Shali Zhang, Anthony K Cook, Edward W Inscho
AIM: Little is known about how toll-like receptor 4 (TLR4) influences the renal microvasculature. We hypothesized that acute TLR4 stimulation with lipopolysaccharide (LPS) impairs afferent arteriole autoregulatory behaviour, partially through reactive oxygen species (ROS). METHODS: We assessed afferent arteriole autoregulatory behaviour after LPS treatment (1 mg kg(-1) ; i.p.) using the in vitro blood perfused juxtamedullary nephron preparation. Autoregulatory behaviour was assessed by measuring diameter responses to step-wise changes in renal perfusion pressure...
May 25, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28533261/the-superoxide-dismutase-mimetic-tempol-does-not-alleviate-glucocorticoid-mediated-rarefaction-of-rat-skeletal-muscle-capillaries
#14
Erin R Mandel, Emily C Dunford, Ghoncheh Abdifarkosh, Patrick C Turnbull, Christopher G R Perry, Michael C Riddell, Tara L Haas
Sustained elevations in circulating glucocorticoids elicit reductions in skeletal muscle microvascular content, but little is known of the underlying mechanisms. We hypothesized that glucocorticoid-induced oxidative stress contributes to this phenomenon. In rats that were implanted with corticosterone (CORT) or control pellets, CORT caused a significant decrease in muscle glutathione levels and a corresponding increase in protein carbonylation, an irreversible oxidative modification of proteins. Decreased endothelial nitric oxide synthase and increased endothelin-1 mRNA levels were detected after 9 days of CORT, and blood flow to glycolytic muscles was diminished...
May 2017: Physiological Reports
https://www.readbyqxmd.com/read/28532685/nitroxide-4-hydroxy-2-2-6-6-tetramethylpiperidine-1-oxyl-tempol-inhibits-the-reductase-activity-of-protein-disulfide-isomerase-via-covalent-binding-to-the-cys400-residue-on-cxxc-redox-motif-at-the-a-active-site
#15
Gérsika Bitencourt Santos, Lucia Gonzalez-Perilli, Mauricio Mastrogiovanni, Adrián Aicardo, Cláudio Daniel Cerdeira, Andrés Trostchansky, Maísa Ribeiro Pereira Lima Brigagão
BACKGROUND AND AIM: Oxidative stress arising from inflammatory processes is a serious cause of cell and tissue damage. Tempol is an efficient antioxidant with superoxide dismutase-like activity. The purpose of this paper is to address the inhibition of protein disulfide isomerase (PDI), an essential redox chaperone whose active sites contain the Cys-Gly-His-Cys (CXXC) motif, by the nitroxide Tempol. RESULTS: In the presence of Tempol (5-120 μM), the reductase activity of PDI was reversibly affected both in vitro and in activated mice neutrophils, with an IC50 of 22...
June 25, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28521553/glutaraldehyde-polymerized-hemoglobin-and-tempol-polyhb-tempol-has-superoxide-dismutase-activity-that-can-attenuate-oxidative-stress-on-endothelial-cells-induced-by-superoxide-anion
#16
Mengdi Wu, Kun Feng, Qiuhui Li, Huiya Ma, Hongli Zhu, Yudou Xie, Gaofei Yan, Chao Chen, Kunping Yan
A Tempol compound with an amine group (4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl, NH2-Tempol) was cross-linked to hemoglobin in a one-step polymerization reaction to produce a novel hemoglobin-based oxygen carrier (HBOC) designated PolyHb-Tempol. The reaction parameters, including the reaction time, pH, temperature, and ratio of reactants, were optimized, and the physiochemical properties of the resulting product were characterized. PolyHb-Tempol didn't show any toxicity towards endothelial cells. Furthermore, from observations of cell morphology and viability, PolyHb-Tempol showed a significant ability to inhibit or eliminate oxidative stress induced by superoxide free radicals...
May 18, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/28515175/role-for-reactive-oxygen-species-in-flow-stimulated-inner-medullary-collecting-duct-endothelin-1-production
#17
Will Wheatley, Donald E Kohan
Inner medullary collecting duct (IMCD)-derived endothelin-1 (ET-1) is stimulated by volume expansion, in part through augmented luminal flow, whereupon it can elicit natriuresis and diuresis. Since flow can alter nitric oxide (NO) and reactive oxygen species (ROS), both of which can affect collecting duct salt transport, we asked whether NO and/or ROS mediate flow-stimulated IMCD ET-1. Mouse IMCD3 cells were exposed to flow and ET-1/GAPDH mRNA assessed. A shear stress of 10 dyne/cm2 for 1 hr increased ET-1 mRNA by 4-fold compared to no flow (ET-1 flow response)...
May 17, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28456572/treatment-with-sodium-nitroprusside-improves-the-endothelial-function-in-aortic-rings-with-endothelial-dysfunction
#18
Tereza Cristina Buzinari, Jorge Camargo Oishi, Thiago Francisco De Moraes, Izabela Pereira Vatanabe, Heloisa Sobreiro Selistre-de-Araújo, Cezar Rangel Pestana, Gerson Jhonatan Rodrigues
PURPOSE: Verify if sodium nitroprusside (SNP) is able to improve endothelial function and if this effect is independent of nitric oxide (NO) release of the compound. METHODS: Normotensive (2K) and hypertensive (2K-1C) wistar rats were used. Intact endothelium aortas were placed in a myograph and incubated with SNP: 0.1nM; 1nM or 10nM during 30min. Cumulative concentration-effect curves for acetylcholine (Ach) were realized to measure the relaxing capacity. Intracellular NO were measured (by DAF-2DA probe) in HUVEC treated with SNP 0...
April 27, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28438648/the-superoxide-dismutase-mimetic-tempol-blunts-diabetes-induced-upregulation-of-nadph-oxidase-and-endoplasmic-reticulum-stress-in-a-rat-model-of-diabetic-nephropathy
#19
Miles J De Blasio, Anand Ramalingam, Anh H Cao, Darnel Prakoso, Ji-Ming Ye, Raelene Pickering, Anna M D Watson, Judy B de Haan, David M Kaye, Rebecca H Ritchie
Endoplasmic reticulum (ER) stress contributes to progression of diabetic nephropathy, which promotes end-stage renal failure in diabetic patients. This study was undertaken to investigate the actions of tempol and ramipril, pharmacological agents that target the consequences of NADPH oxidase, on diabetic nephropathy in a rat model of type 1 diabetes, with an emphasis on markers of ER stress. Male Sprague-Dawley rats were injected intravenously with a single bolus of streptozotocin (55mg/kg) to induce type 1 diabetes...
July 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28397867/oxidative-stress-causes-hypertension-and-activation-of-nuclear-factor-%C3%AE%C2%BAb-after-high-fructose-and-salt-treatments
#20
Waleska C Dornas, Leonardo M Cardoso, Maísa Silva, Natália L S Machado, Deoclécio A Chianca-Jr, Andréia C Alzamora, Wanderson G Lima, Vincent Lagente, Marcelo E Silva
There is evidence that diets rich in salt or simple sugars as fructose are associated with abnormalities in blood pressure regulation. However, the mechanisms underlying pathogenesis of salt- and fructose-induced kidney damage and/or consequent hypertension yet remain largely unexplored. Here, we tested the role of oxidative state as an essential factor along with high salt and fructose treatment in causing hypertension. Fischer male rats were supplemented with a high-fructose diet (20% in water) for 20 weeks and maintained on high-salt diet (8%) associate in the last 10 weeks...
April 11, 2017: Scientific Reports
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