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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/28684629/genetic-deletion-of-nadph-oxidase-1-rescues-microvascular-function-in-mice-with-metabolic-disease
#2
Jennifer A Thompson, Sebastian Larion, James D Mintz, Eric J Belin de Chantemele, David J Fulton, David W Stepp
Rationale: Early vascular changes in metabolic disease that precipitate the development of cardiovascular complications are largely driven by reactive oxygen species (ROS) accumulation, yet the extent to which excess ROS derive from specific Nox isoforms remains ill-defined. Objective: Identify the role of Nox1 in the development of microvascular dysfunction in metabolic disease. Methods and Results: Four genotypes were generated by breeding Nox1 knock-out (KO) mice with db/db mice: lean (HdbWnox1); lean Nox1 KO (HdbKnox1); obese (KdbWnox1); obese KK (KdbKnox1)...
July 6, 2017: Circulation Research
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
#3
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
#4
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
#5
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
#6
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/28655717/deletion-of-ucp1-enhances-ex-vivo-aortic-vasomotor-function-in-female-but-not-male-mice-despite-similar-susceptibility-to-metabolic-dysfunction
#7
Nathan C Winn, Zachary I Grunewald, Michelle L Gastecki, Makenzie L Woodford, Rebecca J Welly, Stephanie L Clookey, James R Ball, T'Keaya L Gaines, Natalia G Karasseva, Jill A Kanaley, Harold S Sacks, Victoria J Vieira-Potter, Jaume Padilla
Females are typically more insulin sensitive than males which may be partly attributed to greater brown adipose tissue (BAT) activity and uncoupling protein 1 (UCP1) content. Accordingly, we tested the hypothesis that UCP1 deletion would abolish sex differences in insulin sensitivity and that whitening of thoracic periaortic BAT caused by UCP1 loss would be accompanied with impaired thoracic aortic function. Furthermore, because UCP1 exerts antioxidant effects, we examined whether UCP1 deficiency-induced metabolic dysfunction was mediated by oxidative stress...
June 27, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28633109/endothelial-nlrp3-inflammasome-activation-and-arterial-neointima-formation-associated-with-acid-sphingomyelinase-during-hypercholesterolemia
#8
Saisudha Koka, Min Xia, Yang Chen, Owais M Bhat, Xinxu Yuan, Krishna M Boini, Pin-Lan Li
The NLRP3 inflammasome has been reported to be activated by atherogenic factors, whereby endothelial injury and consequent atherosclerotic lesions are triggered in the arterial wall. However, the mechanisms activating and regulating NLRP3 inflammasomes remain poorly understood. The present study tested whether acid sphingomyelinase (ASM) and ceramide associated membrane raft (MR) signaling platforms contribute to the activation of NLRP3 inflammasomes and atherosclerotic lesions during hypercholesterolemia. We found that 7-ketocholesterol (7-Keto) or cholesterol crystal (ChC) markedly increased the formation and activation of NLRP3 inflammasomes in mouse carotid arterial endothelial cells (CAECs), as shown by increased colocalization of NLRP3 with ASC or caspase-1, enhanced caspase-1 activity and elevated IL-1β levels, which were markedly attenuated by mouse Asm siRNA, ASM inhibitor- amitriptyline, and deletion of mouse Asm gene...
June 15, 2017: Redox Biology
https://www.readbyqxmd.com/read/28630313/targeting-reactive-nitrogen-species-suppresses-hereditary-pancreatic-cancer
#9
Mo Li, Qian Chen, Teng Ma, Xiaochun Yu
Germline mutation of BRCA2 induces hereditary pancreatic cancer. However, how BRCA2 mutation specifically induces pancreatic tumorigenesis remains elusive. Here, we have examined a mouse model of Brca2-deficiency-induced pancreatic tumors and found that excessive reactive nitrogen species (RNS), such as nitrite, are generated in precancerous pancreases, which induce massive DNA damage, including DNA double-strand breaks. RNS-induced DNA lesions cause genomic instability in the absence of Brca2. Moreover, with the treatment of antioxidant tempol to suppress RNS, not only are DNA lesions significantly reduced, but also the onset of pancreatic cancer is delayed...
July 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28626074/a-type-potassium-channels-contribute-to-prorenin-increase-of-firing-activity-in-hypothalamic-vasopressin-neurosecretory-neurons
#10
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
#11
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
#12
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/28598474/anisotropic-longitudinal-electronic-relaxation-affects-dnp-at-cryogenic-temperatures
#13
E M M Weber, H Vezin, J G Kempf, G Bodenhausen, D Abergél, D Kurzbach
We report the observation of anisotropic longitudinal electronic relaxation in nitroxide radicals under typical dynamic nuclear polarization conditions. This anisotropy affects the efficiency of dynamic nuclear polarization at cryogenic temperatures of 4 K and high magnetic fields of 6.7 T. Under our experimental conditions, the electron paramagnetic resonance spectrum of nitroxides such as TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl) is only partly averaged by electronic spectral diffusion, so that the relaxation times T1e(ω) vary across the spectrum...
June 21, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28589150/tempol-a-superoxide-dismutase-mimetic-agent-inhibits-superoxide-anion-induced-inflammatory-pain-in-mice
#14
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/28584168/palmitate-and-oleate-exert-differential-effects-on-insulin-signalling-and-glucose-uptake-in-human-skeletal-muscle-cells
#15
Selina Mäkinen, Yen H Nguyen, Paulina Skrobuk, Heikki A Koistinen
Saturated fatty acids are implicated in the development of insulin resistance, whereas unsaturated fatty acids may have a protective effect on metabolism. We tested in primary human myotubes if insulin resistance induced by saturated fatty acid palmitate can be ameliorated by concomitant exposure to unsaturated fatty acid oleate. Primary human myotubes were pretreated with palmitate, oleate or their combination for 12 h. Glucose uptake was determined by intracellular accumulation of [(3)H]-2-deoxy-d-glucose, insulin signalling and activation of endoplasmic reticulum (ER) stress by Western blotting, and mitochondrial reactive oxygen species (ROS) production by fluorescent dye MitoSOX...
July 2017: Endocrine Connections
https://www.readbyqxmd.com/read/28575410/enhanced-endothelin-1-rho-kinase-signaling-and-coronary-microvascular-dysfunction-in-hypertensive-myocardial-hypertrophy
#16
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
#17
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/28562691/chronic-treatment-with-paeonol-improves-endothelial-function-in-mice-through-inhibition-of-endoplasmic-reticulum-stress-mediated-oxidative-stress
#18
Ker Woon Choy, Yeh Siang Lau, Dharmani Murugan, Mohd Rais Mustafa
Endoplasmic reticulum (ER) stress leads to endothelial dysfunction which is commonly associated in the pathogenesis of several cardiovascular diseases. We explored the vascular protective effects of chronic treatment with paeonol (2'-hydroxy-4'-methoxyacetophenone), the major compound from the root bark of Paeonia suffruticosa on ER stress-induced endothelial dysfunction in mice. Male C57BL/6J mice were injected intraperitoneally with ER stress inducer, tunicamycin (1 mg/kg/week) for 2 weeks to induce ER stress...
2017: PloS One
https://www.readbyqxmd.com/read/28556994/hyperglycemia-in-pregnant-rats-causes-gender-related-vascular-dysfunction-in-adult-offspring-role-of-cyclooxygenase-2
#19
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
#20
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
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