Trans monounsaturated fatty acids and saturated fatty acids have similar effects on postprandial flow-mediated vasodilation

NARCIS (Netherlands)

Roos, de N.M.; Siebelink, E.; Bots, M.L.; Tol, van A.; Schouten, E.G.; Katan, M.B.

2002-01-01

Objective: Several studies suggest that a fatty meal impairs flow-mediated vasodilation (FMD), a measur9e of endothelial function. We tested whether the impairment was greater for trans fats than for saturated fats. We did this because we previously showed that replacement of saturated fats by trans

Ghrelin-related peptides do not modulate vasodilator nitric oxide production or superoxide levels in mouse systemic arteries.

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Ku, Jacqueline M; Sleeman, Mark W; Sobey, Christopher G; Andrews, Zane B; Miller, Alyson A

2016-04-01

The ghrelin gene is expressed in the stomach where it ultimately encodes up to three peptides, namely, acylated ghrelin, des-acylated ghrelin and obestatin, which all have neuroendocrine roles. Recently, the authors' reported that these peptides have important physiological roles in positively regulating vasodilator nitric oxide (NO) production in the cerebral circulation, and may normally suppress superoxide production by the pro-oxidant enzyme, Nox2-NADPH oxidase. To date, the majority of studies using exogenous peptides infer that they may have similar roles in the systemic circulation. Therefore, this study examined whether exogenous and endogenous ghrelin-related peptides modulate NO production and superoxide levels in mouse mesenteric arteries and/or thoracic aorta. Using wire myography, it was found that application of exogenous acylated ghrelin, des-acylated ghrelin or obestatin to mouse thoracic aorta or mesenteric arteries failed to elicit a vasorelaxation response, whereas all three peptides elicited vasorelaxation responses of rat thoracic aorta. Also, none of the peptides modulated mouse aortic superoxide levels as measured by L-012-enhanced chemiluminescence. Next, it was found that NO bioactivity and superoxide levels were unaffected in the thoracic aorta from ghrelin-deficient mice when compared with wild-type mice. Lastly, using novel GHSR-eGFP reporter mice in combination with double-labelled immunofluorescence, no evidence was found for the growth hormone secretagogue receptor (GHSR1a) in the throracic aorta, which is the only functional ghrelin receptor identified to date. Collectively these findings demonstrate that, in contrast to systemic vessels of other species (e.g. rat and human) and mouse cerebral vessels, ghrelin-related peptides do not modulate vasodilator NO production or superoxide levels in mouse systemic arteries. © 2016 John Wiley & Sons Australia, Ltd.

Exercise-mediated vasodilation in human obesity and metabolic syndrome: effect of acute ascorbic acid infusion.

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Limberg, Jacqueline K; Kellawan, J Mikhail; Harrell, John W; Johansson, Rebecca E; Eldridge, Marlowe W; Proctor, Lester T; Sebranek, Joshua J; Schrage, William G

2014-09-15

We tested the hypothesis that infusion of ascorbic acid (AA), a potent antioxidant, would alter vasodilator responses to exercise in human obesity and metabolic syndrome (MetSyn). Forearm blood flow (FBF, Doppler ultrasound) was measured in lean, obese, and MetSyn adults (n = 39, 32 ± 2 yr). A brachial artery catheter was inserted for blood pressure monitoring and local infusion of AA. FBF was measured during dynamic handgrip exercise (15% maximal effort) with and without AA infusion. To account for group differences in blood pressure and forearm size, and to assess vasodilation, forearm vascular conductance (FVC = FBF/mean arterial blood pressure/lean forearm mass) was calculated. We examined the time to achieve steady-state FVC (mean response time, MRT) and the rise in FVC from rest to steady-state exercise (Δ, exercise - rest) before and during acute AA infusion. The MRT (P = 0.26) and steady-state vasodilator responses to exercise (ΔFVC, P = 0.31) were not different between groups. Intra-arterial infusion of AA resulted in a significant increase in plasma total antioxidant capacity (174 ± 37%). AA infusion did not alter MRT or steady-state FVC in any group (P = 0.90 and P = 0.85, respectively). Interestingly, higher levels of C-reactive protein predicted longer MRT (r = 0.52, P exercise does not alter the time course or magnitude of exercise-mediated vasodilation in groups of young lean, obese, or MetSyn adults. However, systemic inflammation may limit the MRT to exercise, which can be improved with AA. Copyright © 2014 the American Physiological Society.

VIP/PACAP receptor mediation of cutaneous active vasodilation during heat stress in humans.

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Kellogg, Dean L; Zhao, Joan L; Wu, Yubo; Johnson, John M

2010-07-01

Vasoactive intestinal peptide (VIP) is implicated in cutaneous active vasodilation in humans. VIP and the closely related pituitary adenylate cyclase activating peptide (PACAP) act through several receptor types: VIP through VPAC1 and VPAC2 receptors and PACAP through VPAC1, VPAC2, and PAC1 receptors. We examined participation of VPAC2 and/or PAC1 receptors in cutaneous vasodilation during heat stress by testing the effects of their specific blockade with PACAP6-38. PACAP6-38 dissolved in Ringer's was administered by intradermal microdialysis at one forearm site while a control site received Ringer's solution. Skin blood flow was monitored by laser-Doppler flowmetry (LDF). Blood pressure was monitored noninvasively and cutaneous vascular conductance (CVC) calculated. A 5- to 10-min baseline period was followed by approximately 70 min of PACAP6-38 (100 microM) perfusion at one site in normothermia and a 3-min period of body cooling. Whole body heating was then performed to engage cutaneous active vasodilation and was maintained until CVC had plateaued at an elevated level at all sites for 5-10 min. Finally, 58 mM sodium nitroprusside was perfused through both microdialysis sites to effect maximal vasodilation. No CVC differences were found between control and PACAP6-38-treated sites during normothermia (19 +/- 3%max untreated vs. 20 +/- 3%max, PACAP6-38 treated; P > 0.05 between sites) or cold stress (11 +/- 2%max untreated vs. 10 +/- 2%max, PACAP6-38 treated, P > 0.05 between sites). PACAP6-38 attenuated the increase in CVC during whole body heating when compared with untreated sites (59 +/- 3%max untreated vs. 46 +/- 3%max, PACAP6-38 treated, P < 0.05). We conclude that VPAC2 and/or PAC1 receptor activation is involved in cutaneous active vasodilation in humans.

Modulatory Effect of 2-(4-Hydroxyphenylamino-1,4-naphthoquinone on Endothelial Vasodilation in Rat Aorta

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Javier Palacios

2016-01-01

Full Text Available The vascular endothelium plays an essential role in the control of the blood flow. Pharmacological agents like quinone (menadione at various doses modulate this process in a variety of ways. In this study, Q7, a 2-phenylamino-1,4-naphthoquinone derivative, significantly increased oxidative stress and induced vascular dysfunction at concentrations that were not cytotoxic to endothelial or vascular smooth muscle cells. Q7 reduced nitric oxide (NO levels and endothelial vasodilation to acetylcholine in rat aorta. It also blunted the calcium release from intracellular stores by increasing the phenylephrine-induced vasoconstriction when CaCl2 was added to a calcium-free medium but did not affect the influx of calcium from extracellular space. Q7 increased the vasoconstriction to BaCl2 (10−3 M, an inward rectifying K+ channels blocker, and blocked the vasodilation to KCl (10−2 M in aortic rings precontracted with BaCl2. This was recovered with sodium nitroprusside (10−8 M, a NO donor. In conclusion, Q7 induced vasoconstriction was through a modulation of cellular mechanisms involving calcium fluxes through K+ channels, and oxidative stress induced endothelium damage. These findings contribute to the characterization of new quinone derivatives with low cytotoxicity able to pharmacologically modulate vasodilation.

Role of local neurons in cerebrocortical vasodilation elicited from cerebellum

International Nuclear Information System (INIS)

Iadecola, C.; Arneric, S.P.; Baker, H.D.; Tucker, L.W.; Reis, D.J.

1987-01-01

The vasodilation elicited in cerebral cortex by stimulation of the cerebellar fastigial nucleus (FN) is mediated by input pathways coming from the basal forebrain. The authors studied whether these pathways mediate the cortical vasodilation via a direct action on local blood vessels or via interposed local neurons. Neurons were destroyed in the primary sensory cortex by local microinjection of the excitotoxin ibotenic acid (IBO). Five days later rats were anesthetized, paralyzed, and ventilated. Arterial pressure and blood gases were controlled, and FN was stimulated electrically. Local cerebral blood flow (LCBF) was measured using the [ 14 C]iodoantipyrine technique with autoradiography. Five days after IBO, neurons were destroyed in a restricted cortical area, and afferent fibers and terminals were preserved. The selectivity of the neuronal loss was established by histological and biochemical criteria and by transport of horseradish, peroxidase from or into the lesion. Within the lesion, resting LCBF was unaffected, but the increase in LCBF evoked from the FN was abolished. In contrast the vasodilation elicited by hypercapnia was preserved. In the rest of the brain the vasodilation elicited from FN was largely unaffected. The authors conclude that the vasodilation evoked from FN in cerebral cortex depends on the integrity of a restricted population of local neurons that interact with the local microvasculature

Direct sGC activation bypasses no scavenging reactions of intravascular free oxy-hemoglobin and limits vasoconstriction

NARCIS (Netherlands)

N.J.H. Raat (Nicolaas); D.M. Tabima (D. Marcela); P. Specht (Patricia); J. Tejero (Jesús); M.P. Champion (Michael); D.B. Kim-Shapiro (Daniel); J.G. Baust (John ); E.G. Mik (Egbert); M. Hildesheim (Mariana); J.-P. Stasch (Johannes-Peter); E.-M. Becker (Eva-Maria); H. Truebel (Hubert); M.T. Gladwin (Mark)

2013-01-01

textabstractAims: Hemoglobin-based oxygen carriers (HBOC) provide a potential alternative to red blood cell (RBC) transfusion. Their clinical application has been limited by adverse effects, in large part thought to be mediated by the intravascular scavenging of the vasodilator nitric oxide (NO) by

The Role of Vasodilator Receptors of Renin-angiotensin System on Nitric Oxide Formation and Kidney Circulation after Angiotensin II Infusion in Renal Ischemia/Reperfusion Rats.

Science.gov (United States)

Maleki, Maryam; Hasanshahi, Jalal; Moslemi, Fatemeh

2018-01-01

Nitric oxide (NO) as a vasodilator factor has renoprotective effect against renal ischemia. The balance between angiotensin II (Ang II) and NO can affect kidney homeostasis. The aim of this study was to determine NO alteration in response to renin-Ang system vasodilator receptors antagonists (PD123319; Ang II type 2 receptor antagonist and A779; Mas receptor antagonist) in renal ischemia/reperfusion injury (IRI) in rats. Sixty-three Wistar male and female rats were used. Animals from each gender were divided into four groups received saline, Ang II, PD123319 + Ang II, and A779 + Ang II after renal IRI. Renal IRI induced with an adjustable hook. Blood pressure and renal blood flow (RBF) measured continuously. The nitrite levels were measured in serum, kidney, and urine samples. In female rats, the serum and kidney nitrite levels increased significantly by Ang II ( P < 0.05) and decreased significantly ( P < 0.05) when PD123319 was accompanied with Ang II. Such observation was not seen in male. Ang II decreased RBF significantly in all groups ( P < 0.05), while PD + Ang II group showed significant decrease in RBF in comparison with the other groups in female rats ( P < 0.05). Males show more sensibility to Ang II infusion; in fact, it is suggested that there is gender dimorphism in the Ang II and NO production associated with vasodilator receptors.

Effect of subchronic exposure to mainstream cigarette smoke on endothelium-dependent vasodilation in rat arteries

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Helena Lenasi

2005-07-01

Full Text Available Background: Cigarette smoking is reported to impair endothelium-dependent vasodilation. The aim of the present study was to assess the effect of 30-day exposure to mainstream cigarette smoke on vascular reactivity of rat abdominal aorta, carotid, renal and mesenteric artery. Separately, the NO-mediated and the EDHF-mediated, endothelium-dependent vascular relaxations were determined.Methods: Two groups of »Whistar Kyoto« rats were exposed to mainstream cigarette smoke (2 hours/day, 5 days/week for 30 days and to fresh conditioned air, respectively. Rats were sacrificed on the second day after the last exposition to cigarette smoke. Vascular reactivity studies were performed on isolated, endothelium-intact, phenylephrine-preconstricted rat artery rings. Cumulative concentration-relaxation curves to acetylcholine (ACh were obtained in the absence and presence of the endothelial NO synthase (eNOS inhibitor N ω nitro L-arginine (L-NA and the cyclo-oxygenase (COX inhibitor diclofenac, respectively. After washing period of 1 hour, vessels were exposed either to the intracellular superoxide scavenger tiron, to the cytochrome P450 (CYP inhibitor miconazole or the Na-K-ATPase inhibitor ouabain before being preconstricted with phenylephrine and determining the concentration-response curve to ACh.Results: ACh induced concentration-dependent relaxations. In none of the vessels investigated did we observe a significant difference in the relaxations obtained in arteries from control rats and rats exposed to cigarettee smoke. Although smoking is known to cause an increase in oxidative stress, treatment of the vessels with tiron did not affect the NOmediated relaxations. To evaluate the contribution of EDHF to endothelium-dependent vasodilation rings were preincubated with L-NA. The EDHF-mediated relaxations were significantly attenuated compared to the NO-mediated relaxations in renal and mesenteric artery and almost completely abolished in aorta and

Modulatory Effect of 2-(4-Hydroxyphenyl)amino-1,4-naphthoquinone on Endothelial Vasodilation in Rat Aorta.

Science.gov (United States)

Palacios, Javier; Cifuentes, Fredi; Valderrama, Jaime A; Benites, Julio; Ríos, David; González, Constanza; Chiong, Mario; Cartes-Saavedra, Benjamín; Lafourcade, Carlos; Wyneken, Ursula; González, Pamela; Owen, Gareth I; Pardo, Fabián; Sobrevia, Luis; Buc Calderon, Pedro

The vascular endothelium plays an essential role in the control of the blood flow. Pharmacological agents like quinone (menadione) at various doses modulate this process in a variety of ways. In this study, Q7 , a 2-phenylamino-1,4-naphthoquinone derivative, significantly increased oxidative stress and induced vascular dysfunction at concentrations that were not cytotoxic to endothelial or vascular smooth muscle cells. Q7 reduced nitric oxide (NO) levels and endothelial vasodilation to acetylcholine in rat aorta. It also blunted the calcium release from intracellular stores by increasing the phenylephrine-induced vasoconstriction when CaCl 2 was added to a calcium-free medium but did not affect the influx of calcium from extracellular space. Q7 increased the vasoconstriction to BaCl 2 (10 -3  M), an inward rectifying K + channels blocker, and blocked the vasodilation to KCl (10 -2  M) in aortic rings precontracted with BaCl 2 . This was recovered with sodium nitroprusside (10 -8  M), a NO donor. In conclusion, Q7 induced vasoconstriction was through a modulation of cellular mechanisms involving calcium fluxes through K + channels, and oxidative stress induced endothelium damage. These findings contribute to the characterization of new quinone derivatives with low cytotoxicity able to pharmacologically modulate vasodilation.

Elevated blood pressure in cytochrome P4501A1 knockout mice is associated with reduced vasodilation to omega − 3 polyunsaturated fatty acids

Energy Technology Data Exchange (ETDEWEB)

Agbor, Larry N.; Walsh, Mary T.; Boberg, Jason R.; Walker, Mary K., E-mail: mwalker@salud.unm.edu

2012-11-01

In vitro cytochrome P4501A1 (CYP1A1) metabolizes omega − 3 polyunsaturated fatty acids (n − 3 PUFAs); eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), primarily to 17,18-epoxyeicosatetraenoic acid (17,18-EEQ) and 19,20-epoxydocosapentaenoic acid (19,20-EDP), respectively. These metabolites have been shown to mediate vasodilation via increases in nitric oxide (NO) and activation of potassium channels. We hypothesized that genetic deletion of CYP1A1 would reduce vasodilatory responses to n − 3 PUFAs, but not the metabolites, and increase blood pressure (BP) due to decreases in NO. We assessed BP by radiotelemetry in CYP1A1 wildtype (WT) and knockout (KO) mice ± NO synthase (NOS) inhibitor. We also assessed vasodilation to acetylcholine (ACh), EPA, DHA, 17,18-EEQ and 19,20-EDP in aorta and mesenteric arterioles. Further, we assessed vasodilation to an NO donor and to DHA ± inhibitors of potassium channels. CYP1A1 KO mice were hypertensive, compared to WT, (mean BP in mm Hg, WT 103 ± 1, KO 116 ± 1, n = 5/genotype, p < 0.05), and exhibited a reduced heart rate (beats per minute, WT 575 ± 5; KO 530 ± 7; p < 0.05). However, BP responses to NOS inhibition and vasorelaxation responses to ACh and an NO donor were normal in CYP1A1 KO mice, suggesting that NO bioavailability was not reduced. In contrast, CYP1A1 KO mice exhibited significantly attenuated vasorelaxation responses to EPA and DHA in both the aorta and mesenteric arterioles, but normal vasorelaxation responses to the CYP1A1 metabolites, 17,18-EEQ and 19,20-EDP, and normal responses to potassium channel inhibition. Taken together these data suggest that CYP1A1 metabolizes n − 3 PUFAs to vasodilators in vivo and the loss of these vasodilators may lead to increases in BP. -- Highlights: ► CYP1A1 KO mice are hypertensive. ► CYP1A1 KO mice exhibit reduced vasodilation responses to n-3 PUFAs. ► Constitutive CYP1A1 expression regulates blood pressure and vascular function.

Elevated blood pressure in cytochrome P4501A1 knockout mice is associated with reduced vasodilation to omega − 3 polyunsaturated fatty acids

International Nuclear Information System (INIS)

Agbor, Larry N.; Walsh, Mary T.; Boberg, Jason R.; Walker, Mary K.

2012-01-01

In vitro cytochrome P4501A1 (CYP1A1) metabolizes omega − 3 polyunsaturated fatty acids (n − 3 PUFAs); eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), primarily to 17,18-epoxyeicosatetraenoic acid (17,18-EEQ) and 19,20-epoxydocosapentaenoic acid (19,20-EDP), respectively. These metabolites have been shown to mediate vasodilation via increases in nitric oxide (NO) and activation of potassium channels. We hypothesized that genetic deletion of CYP1A1 would reduce vasodilatory responses to n − 3 PUFAs, but not the metabolites, and increase blood pressure (BP) due to decreases in NO. We assessed BP by radiotelemetry in CYP1A1 wildtype (WT) and knockout (KO) mice ± NO synthase (NOS) inhibitor. We also assessed vasodilation to acetylcholine (ACh), EPA, DHA, 17,18-EEQ and 19,20-EDP in aorta and mesenteric arterioles. Further, we assessed vasodilation to an NO donor and to DHA ± inhibitors of potassium channels. CYP1A1 KO mice were hypertensive, compared to WT, (mean BP in mm Hg, WT 103 ± 1, KO 116 ± 1, n = 5/genotype, p < 0.05), and exhibited a reduced heart rate (beats per minute, WT 575 ± 5; KO 530 ± 7; p < 0.05). However, BP responses to NOS inhibition and vasorelaxation responses to ACh and an NO donor were normal in CYP1A1 KO mice, suggesting that NO bioavailability was not reduced. In contrast, CYP1A1 KO mice exhibited significantly attenuated vasorelaxation responses to EPA and DHA in both the aorta and mesenteric arterioles, but normal vasorelaxation responses to the CYP1A1 metabolites, 17,18-EEQ and 19,20-EDP, and normal responses to potassium channel inhibition. Taken together these data suggest that CYP1A1 metabolizes n − 3 PUFAs to vasodilators in vivo and the loss of these vasodilators may lead to increases in BP. -- Highlights: ► CYP1A1 KO mice are hypertensive. ► CYP1A1 KO mice exhibit reduced vasodilation responses to n-3 PUFAs. ► Constitutive CYP1A1 expression regulates blood pressure and vascular function.

A NO way to BOLD?

DEFF Research Database (Denmark)

Aamand, Rasmus; Dalsgaard, Thomas; Ho, Yi Ching Lynn

2013-01-01

Neurovascular coupling links neuronal activity to vasodilation. Nitric oxide (NO) is a potent vasodilator, and in neurovascular coupling NO production from NO synthases plays an important role. However, another pathway for NO production also exists, namely the nitrate-nitrite-NO pathway. On this ......Neurovascular coupling links neuronal activity to vasodilation. Nitric oxide (NO) is a potent vasodilator, and in neurovascular coupling NO production from NO synthases plays an important role. However, another pathway for NO production also exists, namely the nitrate-nitrite-NO pathway...... to stimuli. A faster and smaller BOLD response, with less variation across local cortex, is consistent with an enhanced hemodynamic coupling during elevated nitrate intake. These findings suggest that dietary patterns, via the nitrate-nitrite-NO pathway, may be a potential way to affect key properties....... On this basis, we hypothesized that dietary nitrate (NO3-) could influence the brain's hemodynamic response to neuronal stimulation. In the present study, 20 healthy male participants were given either sodium nitrate (NaNO3) or sodium chloride (NaCl) (saline placebo) in a crossover study and were shown visual...

Long-term estradiol treatment improves VIP-mediated vasodilation in atherosclerotic proximal coronary arteries

DEFF Research Database (Denmark)

Dalsgaard, T.; Mortensen, Alicja; Larsen, C. R.

2003-01-01

arteries. Female ovariectomized homozygous Watanabe heritable hyperlipidemic rabbits were randomized to 16 weeks treatment with 17beta-estradiol or placebo. The diet was semisynthetic, thereby avoiding the influence of phytoestrogens. Artery ring segments were mounted for isometric tension recordings...... in myographs. Following precontraction, the dose-response relationships for VIP and PACAP were evaluated. Treatment with 17beta-estradiol significantly improved the maximum VIP-mediated vasodilation (E-max, percentage of precontraction) in proximal coronary arteries (45.8 +/- 9.6% vs. 24.1 +/- 3.7%, p ....05). In the same artery segment, 17β-estradiol induced a significant decrease in the relative ratio between the repeated contractile response to potassium 30 and 120 mM (100 +/- 7% vs. 132 +/- 11%, p

Endothelin B receptor blockade attenuates pulmonary vasodilation in oxygen-ventilated fetal lambs.

Science.gov (United States)

Ivy, D Dunbar; Lee, Dong-Seok; Rairigh, Robyn L; Parker, Thomas A; Abman, Steven H

2004-01-01

Endothelin-1 (ET-1) contributes to the regulation of pulmonary vascular tone in the normal ovine fetus and in models of perinatal pulmonary hypertension. In the fetal lamb lung, the effects of ET-1 depend on the balance of at least two endothelin receptor subtypes: ETA and ETB. ETA receptors are located on smooth muscle cells and mediate vasoconstriction and smooth muscle proliferation. Stimulation of endothelial ETB receptors causes vasodilation through release of nitric oxide and also functions to remove ET-1 from the circulation. However, whether activation of ETB receptors contributes to the fall in pulmonary vascular tone at birth is unknown. To determine the role of acute ETB receptor blockade in pulmonary vasodilation in response to birth-related stimuli, we studied the hemodynamic effects of selective ETB receptor blockade with BQ-788 during mechanical ventilation with low (<10%) and high FiO2 (100%) in near-term fetal sheep. Intrapulmonary infusion of BQ-788 did not change left pulmonary artery (LPA) blood flow and pulmonary vascular resistance (PVR) at baseline. In comparison with controls, BQ-788 treatment attenuated the rise in LPA flow with low and high FiO2 ventilation (p <0.001 vs. control for each FiO2 concentration). PVR progressively decreased during mechanical ventilation with low and high FiO2 in both groups, but PVR remained higher after BQ-788 treatment throughout the study period (p <0.001). We conclude that selective ETB receptor blockade attenuates pulmonary vasodilation at birth. We speculate that ETB receptor stimulation contributes to pulmonary vasodilation at birth in the ovine fetus.

Ebselen does not improve oxidative stress and vascular function in patients with diabetes: a randomized, crossover trial.

Science.gov (United States)

Beckman, Joshua A; Goldfine, Allison B; Leopold, Jane A; Creager, Mark A

2016-12-01

Oxidative stress is a key driver of vascular dysfunction in diabetes mellitus. Ebselen is a glutathione peroxidase mimetic. A single-site, randomized, double-masked, placebo-controlled, crossover trial was carried out in 26 patients with type 1 or type 2 diabetes to evaluate effects of high-dose ebselen (150 mg po twice daily) administration on oxidative stress and endothelium-dependent vasodilation. Treatment periods were in random order of 4 wk duration, with a 4-wk washout between treatments. Measures of oxidative stress included nitrotyrosine, plasma 8-isoprostanes, and the ratio of reduced to oxidized glutathione. Vascular ultrasound of the brachial artery and plethysmographic measurement of blood flow were used to assess flow-mediated and methacholine-induced endothelium-dependent vasodilation of conduit and resistance vessels, respectively. Ebselen administration did not affect parameters of oxidative stress or conduit artery or forearm arteriolar vascular function compared with placebo treatment. There was no difference in outcome by diabetes type. Ebselen, at the dose and duration evaluated, does not improve the oxidative stress profile, nor does it affect endothelium-dependent vasodilation in patients with diabetes mellitus. Copyright © 2016 the American Physiological Society.

Role of nitric oxide in vasodilation in upstream muscle during intermittent pneumatic compression.

Science.gov (United States)

Chen, Long-En; Liu, Kang; Qi, Wen-Ning; Joneschild, Elizabeth; Tan, Xiangling; Seaber, Anthony V; Stamler, Jonathan S; Urbaniak, James R

2002-02-01

This study investigated the dosage effects of nitric oxide synthase (NOS) inhibitor N(G)-monomethyl-L-arginine (L-NMMA) on intermittent pneumatic compression (IPC)-induced vasodilation in uncompressed upstream muscle and the effects of IPC on endothelial NOS (eNOS) expression in upstream muscle. After L-NMMA infusion, mean arterial pressure increased by 5% from baseline (99.5 +/- 18.7 mmHg; P < 0.05). Heart rate and respiratory rate were not significantly affected. One-hour IPC application on legs induced a 10% dilation from baseline in 10- to 20-microm arterioles and a 10-20% dilation in 21- to 40 microm arterioles and 41- to 70-microm arteries in uncompressed cremaster muscle. IPC-induced vasodilation was dose dependently reduced, abolished, or even reversed by concurrently infused L-NMMA. Moreover, expression of eNOS mRNA in uncompressed cremaster muscle was upregulated to 2 and 2.5 times normal at the end of 1- and 5-h IPC on legs, respectively, and the expression of eNOS protein was upregulated to 1.8 times normal. These increases returned to baseline level after cessation of IPC. The results suggest that eNOS plays an important role in regulating the microcirculation in upstream muscle during IPC.

Dietary restriction but not angiotensin II type 1 receptor blockade improves DNA damage-related vasodilator dysfunction in rapidly aging Ercc1Δ/- mice.

Science.gov (United States)

Wu, Haiyan; van Thiel, Bibi S; Bautista-Niño, Paula K; Reiling, Erwin; Durik, Matej; Leijten, Frank P J; Ridwan, Yanto; Brandt, Renata M C; van Steeg, Harry; Dollé, Martijn E T; Vermeij, Wilbert P; Hoeijmakers, Jan H J; Essers, Jeroen; van der Pluijm, Ingrid; Danser, A H Jan; Roks, Anton J M

2017-08-01

DNA damage is an important contributor to endothelial dysfunction and age-related vascular disease. Recently, we demonstrated in a DNA repair-deficient, prematurely aging mouse model ( Ercc1 Δ/- mice) that dietary restriction (DR) strongly increases life- and health span, including ameliorating endothelial dysfunction, by preserving genomic integrity. In this mouse mutant displaying prominent accelerated, age-dependent endothelial dysfunction we investigated the signaling pathways involved in improved endothelium-mediated vasodilation by DR, and explore the potential role of the renin-angiotensin system (RAS). Ercc1 Δ/- mice showed increased blood pressure and decreased aortic relaxations to acetylcholine (ACh) in organ bath experiments. Nitric oxide (NO) signaling and phospho-Ser 1177 -eNOS were compromised in Ercc1 Δ / - DR improved relaxations by increasing prostaglandin-mediated responses. Increase of cyclo-oxygenase 2 and decrease of phosphodiesterase 4B were identified as potential mechanisms. DR also prevented loss of NO signaling in vascular smooth muscle cells and normalized angiotensin II (Ang II) vasoconstrictions, which were increased in Ercc1 Δ/- mice. Ercc1 Δ/ - mutants showed a loss of Ang II type 2 receptor-mediated counter-regulation of Ang II type 1 receptor-induced vasoconstrictions. Chronic losartan treatment effectively decreased blood pressure, but did not improve endothelium-dependent relaxations. This result might relate to the aging-associated loss of treatment efficacy of RAS blockade with respect to endothelial function improvement. In summary, DR effectively prevents endothelium-dependent vasodilator dysfunction by augmenting prostaglandin-mediated responses, whereas chronic Ang II type 1 receptor blockade is ineffective. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Novel approaches to improving endothelium-dependent nitric oxide-mediated vasodilatation

DEFF Research Database (Denmark)

Simonsen, Ulf; Rodriguez-Rodriguez, Rosalia; Dalsgaard, Thomas

2009-01-01

Endothelial dysfunction, which is defined by decreased endothelium-dependent vasodilatation, is associated with an increased number of cardiovascular events. Nitric oxide (NO) bioavailability is reduced by altered endothelial signal transduction or increased formation of radical oxygen species...... reacting with NO. Endothelial dysfunction is therapeutically reversible and physical exercise, calcium channel blockers, angiotensin converting enzyme inhibitors, and angiotensin receptor antagonists improve flow-evoked endothelium-dependent vasodilation in patients with hypertension and diabetes. We have...... the endothelial signal transduction pathways involved in vasorelaxation and NO release induced by an olive oil component, oleanolic acid, and (3) investigated the role of calcium-activated K channels in the release of NO induced by receptor activation. Tempol increases endothelium-dependent vasodilatation...

Efecto vasodilatador mediado por óxido nítrico del extracto hidroalcohólico de Zea mays L. (maíz morado en anillos aórticos de rata Vasodilator effect mediated by nitric oxide of the Zea mays L (andean purple corn hydroalcoholic extract in aortic rings of rat

Directory of Open Access Journals (Sweden)

Oscar Moreno-Loaiza

2010-12-01

Full Text Available Objetivo. Evaluar la respuesta vasodilatadora e inhibidora de la vasoconstricción del extracto hidroalcohólico de Zea mays L. (maíz morado y determinar si esta respuesta es mediada por óxido nítrico (NO. Materiales y métodos. Se obtuvo un extracto de las corontas de maíz morado maceradas durante ocho días en etanol al 70%, y posterior concentración del producto. Se trabajó con anillos aórticos de rata en cámara de órganos aislados, bañada con solución Krebs-Hensleit (K-H y se registró la actividad vasomotora con un transductor de tensión isométrica. Se produjo una contracción basal con KCl 120 mM sobre la cual determinó el efecto vasodilatador de tres dosis del extracto: 0,1; 0,5 y 1,0 mg/mL. Se utilizó L-NG-Nitroarginina metil ester (L-NAME para comprobar que la vasodilatación depende de la óxido nítrico sinteasa (NOs. Luego se comparó la inhibición de la contracción vascular tras la incubación durante 30 minutos, con extracto de maíz morado y captopril 10-5 M. Resultados. Se observó una reducción de la contracción máxima (100% a 85,25 ± 2,60%, 77,76 ± 3,23% y 73,3 ± 4,87%, para las dosis de 0,1; 0,5 y 1,0 mg/mL, respectivamente. La vasodilatación fue inhibida por la incubación previa con L-NAME. El extracto de maíz morado no inhibió la contracción vascular, a diferencia del captopril (reducción a 75,27 ± 8,61%. Conclusión. El extracto hidroalcohólico de Zea mays L produce vasodilatación dependiente de la síntesis de NO.Objective: To evaluate the vasodilator response of the hydroalcoholic extract of Zea mays L. (Andean purple corn and to determine if this response is mediated by nitric oxide (NO. Material and methods: We obtained an extract by maceration for eight days of Andean purple corn cobs in 70% ethanol and subsequent concentration of the product. Thoracic aortic rings were evaluated in an isolated organ chamber, bathed with Krebs-Hensleit solution (KH, and vasomotor activity was recorded

Nitric oxide-dependent vasodilation and Ca2+ signalling induced by erythrodiol in rat aorta

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Fidèle Ntchapda

2015-06-01

suggested by functional studies. Conclusions: The present results suggest that the mechanism of relaxation seems to be mainly mediated by the endothelial production of NO. Such a vasorelaxation was an endotheliumdependent effect, via the NO/soluble guanylate cyclase/cyclic guanosine monophosphate pathway. This result also suggests that erythrodiol causes a slow influx of extracellular Ca2+ release from the intracellular Ca2+ stores and an inhibition of Ca2+ extruding mechanism. It can be concluded that erythrodiol may have interesting therapeutic potential as a new vasodilator drug, for protecting the cardiovascular system.

Nitric oxide (NO) in normal and hypoxic vascular regulation of the spiny dogfish, Squalus acanthias.

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Swenson, Kai E; Eveland, Randy L; Gladwin, Mark T; Swenson, Erik R

2005-02-01

Nitric oxide (NO) is a potent vasodilator in terrestrial vertebrates, but whether vascular endothelial-derived NO plays a role in vascular regulation in fish remains controversial. To explore this issue, a study was made of spiny dogfish sharks (Squalus acanthias) in normoxia and acute hypoxia (60 min exposure to seawater equilibrated with 3% oxygen) with various agents known to alter NO metabolism or availability. In normoxia, nitroprusside (a NO donor) reduced blood pressure by 20%, establishing that vascular smooth muscle responds to NO. L-arginine, the substrate for NO synthase, had no hemodynamic effect. Acetylcholine, which stimulates endothelial NO and prostaglandin production in mammals, reduced blood pressure, but also caused marked bradycardia. L-NAME, an inhibitor of all NO synthases, caused a small 10% rise in blood pressure, but cell-free hemoglobin (a potent NO scavenger and hypertensive agent in mammals) had no effect. Acute hypoxia caused a 15% fall in blood pressure, which was blocked by L-NAME and cell-free hemoglobin. Serum nitrite, a marker of NO production, rose with hypoxia, but not with L-NAME. Results suggest that NO is not an endothelial-derived vasodilator in the normoxic elasmobranch. The hypertensive effect of L-NAME may represent inhibition of NO production in the CNS and nerves regulating blood pressure. In acute hypoxia, there is a rapid up-regulation of vascular NO production that appears to be responsible for hypoxic vasodilation.

Antioxidant and Vasodilator Activity of Ugni molinae Turcz. (Murtilla and Its Modulatory Mechanism in Hypotensive Response

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Ignacio Jofré

2016-01-01

Full Text Available Hypertension is a systemic condition with high morbidity and mortality rates worldwide, which poses an increased risk for cardiovascular diseases. In this study, we demonstrated the antioxidant and vasodilator activity of Ugni molinae Turcz. (Murtilla fruit, a berry native to Chile and proposed models to explain its modulatory mechanism in hypotensive response. Murtilla fruits were cultivated in a germplasm bank and submitted to chemical and biological analyses. The phenolic compounds gallic acid, Catechin, Quercetin-3-β-D-glucoside, Myricetin, Quercetin, and Kaempferol were identified. Murtilla extract did not generate toxic effects on human endothelial cells and had significant antioxidant activity against ROS production, lipid peroxidation, and superoxide anion production. Furthermore, it showed dose-dependent vasodilator activity in aortic rings in the presence of endothelium, whose hypotensive mechanism is partially mediated by nitric oxide synthase/guanylate cyclase and large-conductance calcium-dependent potassium channels. Murtilla fruits might potentially have beneficial effects on the management of cardiovascular diseases.

A Rare Case of Intermittent Claudication Associated with Impaired Arterial Vasodilation

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J. J. Posthuma

2017-01-01

Full Text Available Exercise-related intermittent claudication is marked by reduced blood flow to extremities caused by either stenosis or impaired vascular function. Although intermittent claudication is common in the elderly, it rarely occurs in the young and middle-aged individuals. Here, we report a case of exercise-related claudication in a 41-year-old woman, in the absence of overt vascular pathology. Using a series of imaging and functional tests, we established that her complaints were due to impaired arterial vasodilation, possibly due to a defect in nitrous oxide-mediated dilation. The symptoms were reversible upon administration of a calcium antagonist, showing reversibility of the vascular impairment. Identification of reversible vascular “stiffness” merits consideration in young and otherwise healthy subjects with claudication of unknown origin.

Vasodilator interactions in skeletal muscle blood flow regulation

DEFF Research Database (Denmark)

Hellsten, Ylva; Nyberg, Michael Permin; Jensen, Lasse Gliemann

2012-01-01

During exercise, oxygen delivery to skeletal muscle is elevated to meet the increased oxygen demand. The increase in blood flow to skeletal muscle is achieved by vasodilators formed locally in the muscle tissue, either on the intraluminal or the extraluminal side of the blood vessels. A number...... vasodilators are both stimulated by several compounds, eg. adenosine, ATP, acetylcholine, bradykinin, and are affected by mechanically induced signals, such as shear stress. NO and prostacyclin have also been shown to interact in a redundant manner where one system can take over when formation of the other...... is compromised. Although numerous studies have examined the role of single and multiple pharmacological inhibition of different vasodilator systems, and important vasodilators and interactions have been identified, a large part of the exercise hyperemic response remains unexplained. It is plausible...

Melatonin mediates vasodilation through both direct and indirect activation of BKCa channels.

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Zhao, T; Zhang, H; Jin, C; Qiu, F; Wu, Y; Shi, L

2017-10-01

Melatonin, synthesized primarily by the pineal gland, is a neuroendocrine hormone with high membrane permeability. The vascular effects of melatonin, including vasoconstriction and vasodilation, have been demonstrated in numerous studies. However, the mechanisms underlying these effects are not fully understood. Large-conductance Ca 2+ -activated K + (BK Ca ) channels are expressed broadly on smooth muscle cells and play an important role in vascular tone regulation. This study explored the mechanisms of myocyte BK Ca channels and endothelial factors underlying the action of melatonin on the mesenteric arteries (MAs). Vascular contractility and patch-clamp studies were performed on myocytes of MAs from Wistar rats. Melatonin induced significant vasodilation on MAs. In the presence of N ω -nitro-l-arginine methyl ester (l-NAME), a potent endothelial oxide synthase (eNOS) inhibitor, melatonin elicited concentration-dependent relaxation, with lowered pIC 50 The effect of melatonin was significantly attenuated in the presence of BK Ca channel blocker iberiotoxin or MT1/MT2 receptor antagonist luzindole in both (+) l-NAME and (-) l-NAME groups. In the (+) l-NAME group, iberiotoxin caused a parallel rightward shift of the melatonin concentration-relaxation curve, with pIC 50 lower than that of luzindole. Both inside-out and cell-attached patch-clamp recordings showed that melatonin significantly increased the open probability, mean open time and voltage sensitivity of BK Ca channels. In a cell-attached patch-clamp configuration, the melatonin-induced enhancement of BK Ca channel activity was significantly suppressed by luzindole. These findings indicate that in addition to the activation of eNOS, melatonin-induced vasorelaxation of MAs is partially attributable to its direct (passing through the cell membrane) and indirect (via MT1/MT2 receptors) activation of the BK Ca channels on mesenteric arterial myocytes. © 2017 Society for Endocrinology.

6-Gingerol alleviates exaggerated vasoconstriction in diabetic rat aorta through direct vasodilation and nitric oxide generation

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Ghareib SA

2015-11-01

-gingerol. Moreover, in vitro effects of 6-gingerol on NO release and the effect of 6-gingerol on AGE production were examined. Results showed that incubation of aortae with 6-gingerol (0.3–10 µM alleviated the exaggerated vasoconstriction of diabetic aortae to phenylephrine in a concentration-dependent manner with no significant effect on the impaired relaxatory response to acetylcholine. Similar results were seen in the aortae exposed to methylglyoxal. In addition, 6-gingerol induced a direct vasodilation effect that was significantly inhibited by Nω-nitro-L-arginine methyl ester hydrochloride and methylene blue. Furthermore, 6-gingerol stimulated aortic NO generation but had no effect on AGE formation. In conclusion, 6-gingerol ameliorates enhanced vascular contraction in diabetic aortae, which may be partially attributed to its ability to increase the production of NO and stimulation of cyclic guanosine monophosphate. Keywords: diabetes, 6-gingerol, vasorelaxant, nitric oxide, advanced glycation end products, vascular complications

Functional pulmonary atresia in newborn with normal intracardiac anatomy: Successful treatment with inhaled nitric oxide and pulmonary vasodilators

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Gürkan Altun

2013-01-01

Full Text Available Functional pulmonary atresia is characterized by a structurally normal pulmonary valve that does not open during right ventricular ejection. It is usually associated with Ebstein′s anomaly, Uhl′s anomaly, neonatal Marfan syndrome and tricuspid valve dysplasia. However, functional pulmonary atresia is rarely reported in newborn with anatomically normal heart. We report a newborn with functional pulmonary atresia who had normal intracardiac anatomy, who responded to treatment with nitric oxide and other vasodilator therapy successfully.

Effect of Dietary Docosahexaenoic Acid Supplementation on the Participation of Vasodilator Factors in Aorta from Orchidectomized Rats.

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Diva M Villalpando

Full Text Available Benefits of n-3 polyunsaturated fatty acids (PUFAs against cardiovascular diseases have been reported. Vascular tone regulation is largely mediated by endothelial factors whose release is modulated by sex hormones. Since the incidence of cardiovascular pathologies has been correlated with decreased levels of sex hormones, the aim of this study was to analyze whether a diet supplemented with the specific PUFA docosahexaenoic acid (DHA could prevent vascular changes induced by an impaired gonadal function. For this purpose, control and orchidectomized rats were fed with a standard diet supplemented with 5% (w/w sunflower oil or with 3% (w/w sunflower oil plus 2% (w/w DHA. The lipid profile, the blood pressure, the production of prostanoids and nitric oxide (NO, and the redox status of biological samples from control and orchidectomized rats, fed control or DHA-supplemented diet, were analyzed. The vasodilator response and the contribution of NO, prostanoids and hyperpolarizing mechanisms were also studied. The results showed that orchidectomy negatively affected the lipid profile, increased the production of prostanoids and reactive oxygen species (ROS, and decreased NO production and the antioxidant capacity, as well as the participation of hyperpolarizing mechanisms in the vasodilator responses. The DHA-supplemented diet of the orchidectomized rats decreased the release of prostanoids and ROS, while increasing NO production and the antioxidant capacity, and it also improved the lipid profile. Additionally, it restored the participation of hyperpolarizing mechanisms by activating potassium. Since the modifications induced by the DHA-supplemented diet were observed in the orchidectomized, but not in the healthy group, DHA seems to exert cardioprotective effects in physiopathological situations in which vascular dysfunction exists.

Systemic low-dose aspirin and clopidogrel independently attenuate reflex cutaneous vasodilation in middle-aged humans.

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Holowatz, Lacy A; Jennings, John D; Lang, James A; Kenney, W Larry

2010-06-01

Chronic systemic platelet cyclooxygenase (COX) inhibition with low-dose aspirin [acetylsalicylic acid (ASA)] significantly attenuates reflex cutaneous vasodilation in middle-aged humans, whereas acute, localized, nonisoform-specific inhibition of vascular COX with intradermal administration of ketorolac does not alter skin blood flow during hyperthermia. Taken together, these data suggest that platelets may be involved in reflex cutaneous vasodilation, and this response is inhibited with systemic pharmacological platelet inhibition. We hypothesized that, similar to ASA, specific platelet ADP receptor inhibition with clopidogrel would attenuate reflex vasodilation in middle-aged skin. In a double-blind crossover design, 10 subjects (53+/-2 yr) were instrumented with four microdialysis fibers for localized drug administration and heated to increase body core temperature [oral temperature (Tor)] 1 degrees C during no systemic drug (ND), and after 7 days of systemic ASA (81 mg) and clopidogrel (75 mg) treatment. Skin blood flow (SkBF) was measured using laser-Doppler flowmetry over each site assigned as 1) control, 2) nitric oxide synthase inhibited (NOS-I; 10 mM NG-nitro-L-arginine methyl ester), 3) COX inhibited (COX-I; 10 mM ketorolac), and 4) NOS-I+COX-I. Data were normalized and presented as a percentage of maximal cutaneous vascular conductance (%CVCmax; 28 mM sodium nitroprusside+local heating to 43 degrees C). During ND conditions, SkBF with change (Delta) in Tor=1.0 degrees C was 56+/-3% CVCmax. Systemic low-dose ASA and clopidogrel both attenuated reflex vasodilation (ASA: 43+/-3; clopidogrel: 32+/-3% CVCmax; both P0.05). NOS-I attenuated vasodilation in ND and ASA (ND: 28+/-6; ASA: 25+/-4% CVCmax; both P0.05). NOS-I+COX-I was not different compared with NOS-I alone in either systemic treatment condition. Both systemic ASA and clopidogrel reduced the time required to increase Tor 1 degrees C (ND: 58+/-3 vs. ASA: 45+/-2; clopidogrel: 39+/-2 min; both Preflex

Role of endothelium-derived hyperpolarization in the vasodilatation of rat intrarenal arteries

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Pinilla, Estéfano; Sánchez-Pina, Ana; Muñoz Picos, Mercedes

2016-01-01

Background and purpose: Endothelium-dependent vasodilation plays an important role in the regulation of vascular tone in different vascular beds. Besides the release of prostacyclin (PGI2) and nitric oxide (NO), the endothelium mediates vasodilation through endothelium-derived hyperpolarization (...

Inhibition by ketamine and amphetamine analogs of the neurogenic nitrergic vasodilations in porcine basilar arteries

International Nuclear Information System (INIS)

Chen, Mei-Fang; Lai, Su-Yu; Kung, Po-Cheng; Lin, Yo-Cheng; Yang, Hui-I; Chen, Po-Yi; Liu, Ingrid Y.; Lua, Ahai Chang; Lee, Tony Jer-Fu

2016-01-01

The abuse of ketamine and amphetamine analogs is associated with incidence of hypertension and strokes involving activation of sympathetic activities. Large cerebral arteries at the base of the brain from several species receive dense sympathetic innervation which upon activation causes parasympathetic-nitrergic vasodilation with increased regional blood flow via axo-axonal interaction mechanism, serving as a protective mechanism to meet O 2 demand in an acutely stressful situation. The present study was designed to examine effects of ketamine and amphetamine analogs on axo-axonal interaction-mediated neurogenic nitrergic vasodilation in porcine basilar arteries using techniques of blood-vessel myography, patch clamp and two-electrode voltage clamp, and calcium imaging. In U46619-contracted basilar arterial rings, nicotine (100 μM) and electrical depolarization of nitrergic nerves by transmural nerve stimulation (TNS, 8 Hz) elicited neurogenic nitrergic vasodilations. Ketamine and amphetamine analogs concentration-dependently inhibited nicotine-induced parasympathetic-nitrergic vasodilation without affecting that induced by TNS, nitroprusside or isoproterenol. Ketamine and amphetamine analogs also concentration-dependently blocked nicotine-induced inward currents in Xenopus oocytes expressing α3β2-nicotinic acetylcholine receptors (nAChRs), and nicotine-induced inward currents as well as calcium influxes in rat superior cervical ganglion neurons. The potency in inhibiting both inward-currents and calcium influxes is ketamine > methamphetamine > hydroxyamphetamine. These results indicate that ketamine and amphetamine analogs, by blocking nAChRs located on cerebral perivascular sympathetic nerves, reduce nicotine-induced, axo-axonal interaction mechanism-mediated neurogenic dilation of the basilar arteries. Chronic abuse of these drugs, therefore, may interfere with normal sympathetic-parasympathetic interaction mechanism resulting in diminished neurogenic

Inhibition by ketamine and amphetamine analogs of the neurogenic nitrergic vasodilations in porcine basilar arteries

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Chen, Mei-Fang [Department of Medical Research, Buddhist Tzu Chi General Hospital, Hualien, Taiwan (China); Tzu Chi Center for Vascular Medicine, Buddhist Tzu Chi General Hospital, Hualien, Taiwan (China); Tzu Chi University of Science and Technology, Hualien, Taiwan (China); Lai, Su-Yu; Kung, Po-Cheng; Lin, Yo-Cheng [Department of Pharmacology and Toxicology, College of Medicine, Tzu Chi University, Hualien, Taiwan (China); Yang, Hui-I [Department of Medical Research, Buddhist Tzu Chi General Hospital, Hualien, Taiwan (China); Chen, Po-Yi [Department of Medical Research, Buddhist Tzu Chi General Hospital, Hualien, Taiwan (China); Department of Pharmacology and Toxicology, College of Medicine, Tzu Chi University, Hualien, Taiwan (China); Liu, Ingrid Y. [Department of Molecular Biology and Human Genetics, Tzu Chi University, Hualien, Taiwan (China); Lua, Ahai Chang [Department of Laboratory Medicine and Biotechnology & Graduate Institute of Medical Biotechnology, Tzu Chi University, Hualien, Taiwan (China); Lee, Tony Jer-Fu, E-mail: tlee@mail.tcu.edu.tw [Department of Medical Research, Buddhist Tzu Chi General Hospital, Hualien, Taiwan (China); Tzu Chi Center for Vascular Medicine, Buddhist Tzu Chi General Hospital, Hualien, Taiwan (China); Department of Life Sciences, College of Life Sciences, Tzu Chi University, Hualien, Taiwan (China); Department of Pharmacology and Toxicology, College of Medicine, Tzu Chi University, Hualien, Taiwan (China); Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, IL (United States)

2016-08-15

The abuse of ketamine and amphetamine analogs is associated with incidence of hypertension and strokes involving activation of sympathetic activities. Large cerebral arteries at the base of the brain from several species receive dense sympathetic innervation which upon activation causes parasympathetic-nitrergic vasodilation with increased regional blood flow via axo-axonal interaction mechanism, serving as a protective mechanism to meet O{sub 2} demand in an acutely stressful situation. The present study was designed to examine effects of ketamine and amphetamine analogs on axo-axonal interaction-mediated neurogenic nitrergic vasodilation in porcine basilar arteries using techniques of blood-vessel myography, patch clamp and two-electrode voltage clamp, and calcium imaging. In U46619-contracted basilar arterial rings, nicotine (100 μM) and electrical depolarization of nitrergic nerves by transmural nerve stimulation (TNS, 8 Hz) elicited neurogenic nitrergic vasodilations. Ketamine and amphetamine analogs concentration-dependently inhibited nicotine-induced parasympathetic-nitrergic vasodilation without affecting that induced by TNS, nitroprusside or isoproterenol. Ketamine and amphetamine analogs also concentration-dependently blocked nicotine-induced inward currents in Xenopus oocytes expressing α3β2-nicotinic acetylcholine receptors (nAChRs), and nicotine-induced inward currents as well as calcium influxes in rat superior cervical ganglion neurons. The potency in inhibiting both inward-currents and calcium influxes is ketamine > methamphetamine > hydroxyamphetamine. These results indicate that ketamine and amphetamine analogs, by blocking nAChRs located on cerebral perivascular sympathetic nerves, reduce nicotine-induced, axo-axonal interaction mechanism-mediated neurogenic dilation of the basilar arteries. Chronic abuse of these drugs, therefore, may interfere with normal sympathetic-parasympathetic interaction mechanism resulting in diminished neurogenic

Anaerobic ammonium oxidation mediated by Mn-oxides: from sediment to strain level.

Science.gov (United States)

Javanaud, Cedric; Michotey, Valerie; Guasco, Sophie; Garcia, Nicole; Anschutz, Pierre; Canton, Mathieu; Bonin, Patricia

2011-11-01

Nitrite and (29)N(2) productions in slurry incubations of anaerobically sediment after (15)NO(3) or (15)NH(4) labelling in the presence of Mn-oxides suggested that anaerobic Mn-oxides mediated nitrification coupled with denitrification in muddy intertidal sediments of Arcachon Bay (SW Atlantic French coast). From this sediment, bacterial strains were isolated and physiologically characterized in terms of Mn-oxides and nitrate reduction as well as potential anaerobic nitrification. One of the isolated strain, identified as Marinobacter daepoensis strain M4AY14, was a denitrifier. Nitrous oxide production by this strain was demonstrated in the absence of nitrate and with Mn-oxides and NH(4) amendment, giving indirect proof of anaerobic nitrate or nitrite production. Anaerobic Mn-oxide-mediated nitrification was confirmed by (29)N(2) production in the presence of (15)NO(3) and (14)NH(4) under denitrifying conditions. Anaerobic nitrification by M4AY14 seemed to occur only in the absence of nitrate, or at nitrate levels lower than that of Mn-oxides. Most of the other isolates were affiliated with the Shewanella genus and were able to use both nitrate and Mn-oxides as electron acceptors. When both electron acceptors were present, whatever their concentrations, nitrate and Mn-oxide reduction co-occurred. These data indicate that bacterial Mn-oxide reduction could be an important process in marine sediments with low oxygen concentrations, and demonstrate for the first time the role of bacteria in anaerobic Mn-mediated nitrification. Copyright © 2011 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Voluntary wheel running selectively augments insulin-stimulated vasodilation in arterioles from white skeletal muscle of insulin-resistant rats.

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Mikus, Catherine R; Roseguini, Bruno T; Uptergrove, Grace M; Morris, E Matthew; Rector, Randy Scott; Libla, Jessica L; Oberlin, Douglas J; Borengasser, Sarah J; Taylor, Angelina M; Ibdah, Jamal A; Laughlin, Maurice Harold; Thyfault, John P

2012-11-01

Exercise (RUN) prevents declines in insulin-mediated vasodilation, an important component of insulin-mediated glucose disposal, in rats prone to obesity and insulin resistance. Determine whether RUN (1) improves insulin-stimulated vasodilation after insulin resistance has been established, and (2) differentially affects arterioles from red and white muscle. Insulin signaling and vasoreactivity to insulin (1-1000 μIU/mL) were assessed in 2A from the Gw and Gr of SED OLETF rats at 12 and 20 weeks of age (SED12, SED20) and those undergoing RUN (RUN20) or caloric restriction (CR20; to match body weight of RUN) from 12 to 20 weeks. Glucose and insulin responses to i.p. glucose were reduced in RUN20, elevated in SED20 (p RUN20 (p RUN selectively improved insulin-mediated vasodilation in Gw 2As, in part through attenuated ET-1 sensitivity/production, an adaptation that was independent of changes in adiposity and may contribute to enhanced insulin-stimulated glucose disposal. © 2012 John Wiley & Sons Ltd.

In Premature Newborns Intraventricular Hemorrhage Causes Cerebral Vasospasm and Associated Neurodisability via Heme-Induced Inflammasome-Mediated Interleukin-1 Production and Nitric Oxide Depletion

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Michael Eisenhut

2017-08-01

Full Text Available BackgroundIntraventricular hemorrhage (IVH occurs in 60–70% of neonates weighing 500–750 g and 10–20% of those weighing 1,000–1,500 g. All forms of IVH have been associated with neurocognitive deficits. Both subarachnoid and IVHs have been associated with delayed vasospasm leading to neurological deficits. Pathways linking hemoglobin release from blood clots to vasospasm include heme-induced activation of inflammasomes releasing interleukin-1 (IL-1 that can cause calcium dependent and independent vasospasm. Free hemoglobin is a potent scavenger of nitric oxide (NO. Depletion of NO, a potent endogenous vasodilator, has been associated with features of vasospasm.HypothesisIn premature newborns, IVH causes cerebral vasospasm and associated neurodisability via heme-induced increased inflammasome-mediated IL-1 production and NO depletion.Confirmation of hypothesis and implicationsThis hypothesis could be confirmed in the IVH animal model with visualization of any associated vasospasm by angiography and in newborns with IVH by transcranial Doppler ultrasonography and correlation with cerebrospinal fluid IL-1 and NO metabolite levels. Confirmation of the role of heme in activation of inflammasomes causing IL-1 production and NO binding could be achieved by measuring the effect of heme scavenging interventions on IL-1 levels and levels of NO metabolites. In addition to removal of the accumulated blood of an IVH by drainage, irrigation, and fibrinolytic therapy intrathecal application of vasodilators and heme scavenging agents like haptoglobin and haemopexin and systemic treatment with inhibitors of inflammasomes like telmisartan could be used to prevent and treat cerebral vasospasm, and thus reduce the risk of associated brain injury in premature neonates.

Correlative intravital imaging of cGMP signals and vasodilation in mice

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Martin eThunemann

2014-10-01

Full Text Available Cyclic guanosine monophosphate (cGMP is an important signaling molecule and drug target in the cardiovascular system. It is well known that stimulation of the vascular nitric oxide (NO-cGMP pathway results in vasodilation. However, the spatiotemporal dynamics of cGMP signals themselves and the cGMP concentrations within specific cardiovascular cell types in health, disease, and during pharmacotherapy with cGMP-elevating drugs are largely unknown. To facilitate the analysis of cGMP signaling in vivo, we have generated transgenic mice that express fluorescence resonance energy transfer (FRET-based cGMP sensor proteins. Here, we describe two models of intravital FRET/cGMP imaging in the vasculature of cGMP sensor mice: (1 epifluorescence-based ratio imaging in resistance-type vessels of the cremaster muscle and (2 ratio imaging by multiphoton microscopy within the walls of subcutaneous blood vessels accessed through a dorsal skinfold chamber. Both methods allow simultaneous monitoring of NO-induced cGMP transients and vasodilation in living mice. Detailed protocols of all steps necessary to perform and evaluate intravital imaging experiments of the vasculature of anesthetized mice including surgery, imaging, and data evaluation are provided. An image segmentation approach is described to estimate FRET/cGMP changes within moving structures such as the vessel wall during vasodilation. The methods presented herein should be useful to visualize cGMP or other biochemical signals that are detectable with FRET-based biosensors, such as cyclic adenosine monophosphate or Ca2+, and to correlate them with respective vascular responses. With further refinement and combination of transgenic mouse models and intravital imaging technologies, we envision an exciting future, in which we are able to ‘watch’ biochemistry, (patho physiology, and pharmacotherapy in the context of a living mammalian organism.

iNOS-dependent sweating and eNOS-dependent cutaneous vasodilation are evident in younger adults, but are diminished in older adults exercising in the heat.

Science.gov (United States)

Fujii, Naoto; Meade, Robert D; Alexander, Lacy M; Akbari, Pegah; Foudil-Bey, Imane; Louie, Jeffrey C; Boulay, Pierre; Kenny, Glen P

2016-02-01

Nitric oxide synthase (NOS) contributes to sweating and cutaneous vasodilation during exercise in younger adults. We hypothesized that endothelial NOS (eNOS) and neuronal NOS (nNOS) mediate NOS-dependent sweating, whereas eNOS induces NOS-dependent cutaneous vasodilation in younger adults exercising in the heat. Further, aging may upregulate inducible NOS (iNOS), which may attenuate sweating and cutaneous vasodilator responses. We hypothesized that iNOS inhibition would augment sweating and cutaneous vasodilation in exercising older adults. Physically active younger (n = 12, 23 ± 4 yr) and older (n = 12, 60 ± 6 yr) adults performed two 30-min bouts of cycling at a fixed rate of metabolic heat production (400 W) in the heat (35°C). Sweat rate and cutaneous vascular conductance (CVC) were evaluated at four intradermal microdialysis sites with: 1) lactated Ringer (control), 2) nNOS inhibitor (nNOS-I, NPLA), 3) iNOS inhibitor (iNOS-I, 1400W), or 4) eNOS inhibitor (eNOS-I, LNAA). In younger adults during both exercise bouts, all inhibitors decreased sweating relative to control, albeit a lower sweat rate was observed at iNOS-I compared with eNOS-I and nNOS-I sites (all P exercise protocol (all P exercise bouts (all P > 0.05). We show that iNOS and eNOS are the main contributors to NOS-dependent sweating and cutaneous vasodilation, respectively, in physically active younger adults exercising in the heat, and that iNOS inhibition does not alter sweating or cutaneous vasodilation in exercising physically active older adults. Copyright © 2016 the American Physiological Society.

Getting to NO Alzheimer’s Disease: Neuroprotection versus Neurotoxicity Mediated by Nitric Oxide

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Rachelle Balez

2016-01-01

Full Text Available Alzheimer’s disease (AD is a neurodegenerative disorder involving the loss of neurons in the brain which leads to progressive memory loss and behavioral changes. To date, there are only limited medications for AD and no known cure. Nitric oxide (NO has long been considered part of the neurotoxic insult caused by neuroinflammation in the Alzheimer’s brain. However, focusing on early developments, prior to the appearance of cognitive symptoms, is changing that perception. This has highlighted a compensatory, neuroprotective role for NO that protects synapses by increasing neuronal excitability. A potential mechanism for augmentation of excitability by NO is via modulation of voltage-gated potassium channel activity (Kv7 and Kv2. Identification of the ionic mechanisms and signaling pathways that mediate this protection is an important next step for the field. Harnessing the protective role of NO and related signaling pathways could provide a therapeutic avenue that prevents synapse loss early in disease.

Vasodilator effects of red wines in subcutaneous small resistance artery of patients with essential hypertension.

Science.gov (United States)

Porteri, Enzo; Rizzoni, Damiano; De Ciuceis, Carolina; Boari, Gianluca E M; Platto, Caterina; Pilu, Annamaria; Miclini, Marco; Agabiti Rosei, Claudia; Bulgari, Giuseppe; Agabiti Rosei, Enrico

2010-04-01

It has been suggested that in animal models, red wine may have a protective effect on the vascular endothelium. However, it is not known whether this effect is also present in human small vessels and whether it is specific for certain wines. The objective of this study is to compare the vasodilator effects in subcutaneous small resistance arteries of wines with different flavonoid content as well as of ethanol vs. wines in normotensive (NT) subjects and in patients with essential hypertension (EH). Twenty-six EH and 27 NT were included in the study. Subcutaneous small resistance arteries were dissected and mounted on a micromyograph. Then we evaluated vasodilator responses as concentration-response curves (20, 30, and 50 microl) to the following items: (i) a red wine produced in small oak barrels ("en barrique": EB) (Barolo Oberto 1994), (ii) a red wine produced in large wood barrels (LB) (Barolo Scarzello 1989), (iii) a red wine produced in steel tanks (Albarello Rosso del Salento 1997), and (iv) a white wine produced in steel tanks in the presence or absence of an inhibitor of the nitric oxide (NO) synthase (L-NMMA 100 micromol/l). A dose-dependent vasodilator effect of red wines (particularly EB and LB) was detected in both NT and HT. The observed response was not reduced after preincubation with L-NMMA. Our results suggest red wines are more potent vasodilator than ethanol alone, possibly depending on the content of polyphenols or tannic acid. HT show similar responses compared with NT, indicating that red wine is not harmful in this population.

Oxidant-NO dependent gene regulation in dogs with type I diabetes: impact on cardiac function and metabolism

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Ojaimi Caroline

2010-08-01

Full Text Available Abstract Background The mechanisms responsible for the cardiovascular mortality in type I diabetes (DM have not been defined completely. We have shown in conscious dogs with DM that: 1 baseline coronary blood flow (CBF was significantly decreased, 2 endothelium-dependent (ACh coronary vasodilation was impaired, and 3 reflex cholinergic NO-dependent coronary vasodilation was selectively depressed. The most likely mechanism responsible for the depressed reflex cholinergic NO-dependent coronary vasodilation was the decreased bioactivity of NO from the vascular endothelium. The goal of this study was to investigate changes in cardiac gene expression in a canine model of alloxan-induced type 1 diabetes. Methods Mongrel dogs were chronically instrumented and the dogs were divided into two groups: one normal and the other diabetic. In the diabetic group, the dogs were injected with alloxan monohydrate (40-60 mg/kg iv over 1 min. The global changes in cardiac gene expression in dogs with alloxan-induced diabetes were studied using Affymetrix Canine Array. Cardiac RNA was extracted from the control and DM (n = 4. Results The array data revealed that 797 genes were differentially expressed (P 2+ cycling genes (ryanodine receptor; SERCA2 Calcium ATPase, structural proteins (actin alpha. Of particular interests are genes involved in glutathione metabolism (glutathione peroxidase 1, glutathione reductase and glutathione S-transferase, which were markedly down regulated. Conclusion our findings suggest that type I diabetes might have a direct effect on the heart by impairing NO bioavailability through oxidative stress and perhaps lipid peroxidases.

Nitroglycerin-mediated, but not flow-mediated vasodilation, is associated with blunted nocturnal blood pressure fall in patients with resistant hypertension.

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Fontes-Guerra, Priscila C A; Cardoso, Claudia R L; Muxfeldt, Elizabeth S; Salles, Gil F

2015-08-01

Endothelial function by flow-mediated (FMD) and nitroglycerin-mediated vasodilations (NMD) was scarcely investigated in resistant hypertension. We aimed to assess the independent correlates of FMD and NMD in resistant hypertensive patients, particularly their associations with ambulatory blood pressures (BP) and nocturnal BP fall patterns. In a cross-sectional study, 280 resistant hypertensive patients performed 24-h ambulatory BP monitoring, carotid-femoral pulse wave velocity, polysomnography, and brachial artery FMD and NMD by high-resolution ultrasonography. Independent correlates of FMD, NMD, and brachial artery diameter (BAD) were assessed by multiple linear and logistic regressions. Median (interquartile range) FMD was 0.75% (-0.6 to +4.4%) and NMD was 11.8% (7.1-18.4%). Baseline BAD and diabetes were independently associated with both FMD and NMD. Older age and prior cardiovascular diseases were associated with altered FMD, whereas higher night-time SBP and lower nocturnal SBP fall were associated with impaired NMD. Moreover, there was a significant gradient of impaired NMD according to blunted nocturnal BP decline patterns. BAD was independently associated with age, sex, BMI, albuminuria, and nocturnal SBP fall. Further adjustments to blood flow velocity, aortic stiffness, plasma aldosterone concentration, and sleep apnea did not change these relationships. NMD, but not FMD, is independently associated with unfavorable night-time BP levels and nondipping patterns, and may be a better cardiovascular risk marker in patients with resistant hypertension. BAD also may provide additional prognostic information.

Lipid Emulsion Inhibits Vasodilation Induced by a Toxic Dose of Bupivacaine via Attenuated Dephosphorylation of Myosin Phosphatase Target Subunit 1 in Isolated Rat Aorta

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Ok, Seong-Ho; Byon, Hyo-Jin; Kwon, Seong-Chun; Park, Jungchul; Lee, Youngju; Hwang, Yeran; Baik, Jiseok; Choi, Mun-Jeoung; Sohn, Ju-Tae

2015-01-01

Lipid emulsions are widely used for the treatment of systemic toxicity that arises from local anesthetics. The goal of this in vitro study was to examine the cellular mechanism associated with the lipid emulsion-mediated attenuation of vasodilation induced by a toxic dose of bupivacaine in isolated endothelium-denuded rat aorta. The effects of lipid emulsion on vasodilation induced by bupivacaine, mepivacaine, and verapamil were assessed in isolated aorta precontracted with phenylephrine, the Rho kinase stimulant NaF, and the protein kinase C activator phorbol 12,13-dibutyrate (PDBu). The effects of Rho kinase inhibitor Y-27632 on contraction induced by phenylephrine or NaF were assessed. The effects of bupivacaine on intracellular calcium concentrations ([Ca2+]i) and tension induced by NaF were simultaneously measured. The effects of bupivacaine alone and lipid emulsion plus bupivacaine on myosin phosphatase target subunit 1 (MYPT1) phosphorylation induced by NaF were examined in rat aortic vascular smooth muscle cells. In precontracted aorta, the lipid emulsion attenuated bupivacaine-induced vasodilation but had no effect on mepivacaine-induced vasodilation. Y-27632 attenuated contraction induced by either phenylephrine or NaF. The lipid emulsion attenuated verapamil-induced vasodilation. Compared with phenylephrine-induced precontracted aorta, bupivacaine-induced vasodilation was slightly attenuated in NaF-induced precontracted aorta. The magnitude of the bupivacaine-induced vasodilation was higher than that of a bupivacaine-induced decrease in [Ca2+]i. Bupivacaine attenuated NaF-induced MYPT1 phosphorylation, whereas lipid emulsion pretreatment attenuated the bupivacaine-induced inhibition of MYPT1 phosphorylation induced by NaF. Taken together, these results suggest that lipid emulsions attenuate bupivacaine-induced vasodilation via the attenuation of inhibition of MYPT1 phosphorylation evoked by NaF. PMID:26664257

Organic nitrates: update on mechanisms underlying vasodilation, tolerance and endothelial dysfunction.

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Münzel, Thomas; Steven, Sebastian; Daiber, Andreas

2014-12-01

Given acutely, organic nitrates, such as nitroglycerin (GTN), isosorbide mono- and dinitrates (ISMN, ISDN), and pentaerythrityl tetranitrate (PETN), have potent vasodilator and anti-ischemic effects in patients with acute coronary syndromes, acute and chronic congestive heart failure and arterial hypertension. During long-term treatment, however, side effects such as nitrate tolerance and endothelial dysfunction occur, and therapeutic efficacy of these drugs rapidly vanishes. Recent experimental and clinical studies have revealed that organic nitrates per se are not just nitric oxide (NO) donors, but rather a quite heterogeneous group of drugs considerably differing for mechanisms underlying vasodilation and the development of endothelial dysfunction and tolerance. Based on this, we propose that the term nitrate tolerance should be avoided and more specifically the terms of GTN, ISMN and ISDN tolerance should be used. The present review summarizes preclinical and clinical data concerning organic nitrates. Here we also emphasize the consequences of chronic nitrate therapy on the supersensitivity of the vasculature to vasoconstriction and on the increased autocrine expression of endothelin. We believe that these so far rather neglected and underestimated side effects of chronic therapy with at least GTN and ISMN are clinically important. Copyright © 2014 Elsevier Inc. All rights reserved.

Mediator oxidation systems in organic electrosynthesis

International Nuclear Information System (INIS)

Ogibin, Yurii N; Elinson, Michail N; Nikishin, Gennady I

2009-01-01

The data on the use of mediator oxidation systems activated by electric current (anodic or parallel anodic and cathodic) in organic electrosynthesis are considered and generalised. Electrochemical activation of these systems permits successful application of catalytic versions and easy scaling of mediator-promoted processes. Chemical and environmental advantages of electrochemical processes catalysed by mediator oxidation systems are demonstrated. Examples of the application of organic and inorganic mediators for the oxidation of various classes of organic compounds under conditions of electrolysis are given.

Regulation and control of nitric oxide (NO) in macrophages

DEFF Research Database (Denmark)

Kovacevic, Zaklina; Sahni, Sumit; Lok, K.H.

2017-01-01

We recently demonstrated that a novel storage and transport mechanism for nitric oxide (NO) mediated by glutathione-S-transferase P1 (GSTP1) and multidrug resistance protein 1 (MRP1/ABCC1), protects M1-macrophage (M1-MØ) models from large quantities of endogenous NO. This system stores and transp......We recently demonstrated that a novel storage and transport mechanism for nitric oxide (NO) mediated by glutathione-S-transferase P1 (GSTP1) and multidrug resistance protein 1 (MRP1/ABCC1), protects M1-macrophage (M1-MØ) models from large quantities of endogenous NO. This system stores...... be responsible for delivering cytotoxic NO as DNICs via MRP1 from M1-MØs, to tumor cell targets....

Data on a single oral dose of camu camu (Myrciaria dubia pericarp extract on flow-mediated vasodilation and blood pressure in young adult humans

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Tadayoshi Miyashita

2018-02-01

Full Text Available This data article describes the flow-mediated vasodilation (FMD responses, represented by changes in arterial diameter, and blood pressure changes in young adults after a single oral dose of camu camu (Myrciaria dubia pericarp extract or placebo (cross-over design. Ten healthy men and 10 healthy women participated in this study. Ultrasonic diagnostic equipment was used to monitor arterial diameter changes, indicative of FMD, for 110 s after the administration of the camu camu extract or placebo. In addition, the systolic and diastolic blood pressure values were recorded.

Data on a single oral dose of camu camu (Myrciaria dubia) pericarp extract on flow-mediated vasodilation and blood pressure in young adult humans.

Science.gov (United States)

Miyashita, Tadayoshi; Koizumi, Ryosuke; Myoda, Takao; Sagane, Yoshimasa; Niwa, Koichi; Watanabe, Toshihiro; Minami, Kazuhiro

2018-02-01

This data article describes the flow-mediated vasodilation (FMD) responses, represented by changes in arterial diameter, and blood pressure changes in young adults after a single oral dose of camu camu ( Myrciaria dubia ) pericarp extract or placebo (cross-over design). Ten healthy men and 10 healthy women participated in this study. Ultrasonic diagnostic equipment was used to monitor arterial diameter changes, indicative of FMD, for 110 s after the administration of the camu camu extract or placebo. In addition, the systolic and diastolic blood pressure values were recorded.

Impaired endothelial nitric oxide bioavailability: a common link between aging, hypertension, and atherogenesis?

LENUS (Irish Health Repository)

Walsh, Thomas

2012-01-31

Endothelial-derived nitric oxide (NO) is responsible for maintaining continuous vasodilator tone and for regulating local perfusion and systemic blood pressure. It also has significant antiproliferative effects on vascular smooth muscle and platelet anti-aggregatory effects. Impaired endothelial-dependent (NO mediated) vasorelaxation is observed in most animal and human models of healthy aging. It also occurs in age-associated conditions such as atherosclerosis and hypertension. Such "endotheliopathy" increases vascular risk in older adults. Studies have indicated that pharmacotherapeutic intervention with angiotensin-converting enzyme inhibitors and 3-hydroxy-3-methyl-glutaryl coenzyme-A reductase inhibitors may improve NO-mediated vasomotor function. This review, evaluates the association between impaired endothelial NO bioavailability, accelerated vascular aging, and the age-associated conditions hypertension and atherogenesis. This is important, because pharmacotherapy aimed at improving endothelial NO bioavailability could modify age-related vascular disease and transform age into a potentially modifiable vascular risk factor, at least in a subpopulation of older adults.

Acetylcholine-induced vasodilation in the uterine vascular bed of pregnant rats with adriamycin-induced nephrosis.

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Yousif, Mariam H; Adeagbo, Ayotunde S; Kadavil, Elizabeth A; Chandrasekhar, Bindu; Oriowo, Mabayoje A

2002-01-01

This project was designed to study endothelium-dependent vasodilation in the uterine vascular bed during experimentally induced preeclampsia in rats. Uterine vascular beds were isolated from non-pregnant and pregnant rats with or without treatment with adriamycin (ADR) and perfused with physiological solution. Thereafter, vasodilator responses to acetylcholine were recorded. RECORDS: Pregnant ADR-treated rats displayed symptoms of preeclampsia including hypertension and proteinuria. Blood pressure was 110.0 +/- 4.7 mm Hg (n = 5) in control pregnant rats and 136.0 +/- 5.3 mm Hg (n = 5) in ADR-treated pregnant rats, and urinary protein concentrations were 0.35 mg/ml (n = 5) and 13.2 +/- 3.6 mg/ml (n = 9), respectively. Both blood pressure and proteinuria values were significantly (p acetylcholine-induced dose-dependent vasodilator responses in the vascular beds were not significantly different between the pregnant and nonpregnant rats. Although acetylcholine-induced vasodilation was significantly reduced by N omega-nitro-L-arginine methyl ester hydrochloride (L-NAME) in both groups, the residual response to acetylcholine was not affected by indomethacin, suggesting that prostanoids were not involved in this response. The L-NAME-resistant component, endothelium-derived hyperpolarizing factor (EDHF), was greater in ADR-treated uterine beds than in those of the controls, indicating a significant contribution from EDHF in these vessels. In the presence of an elevated external potassium ion concentration, acetylcholine produced similar vasodilator responses, indicating that the release of nitric oxide was not impaired. These results indicate that endothelium-dependent vasodilation was not impaired in this model of preeclampsia.

Autonomic Blockade Reverses Endothelial Dysfunction in Obesity-Associated Hypertension.

Science.gov (United States)

Gamboa, Alfredo; Figueroa, Rocío; Paranjape, Sachin Y; Farley, Ginnie; Diedrich, Andre; Biaggioni, Italo

2016-10-01

Impaired nitric oxide (NO) vasodilation (endothelial dysfunction) is associated with obesity and thought to be a factor in the development of hypertension. We previously found that NO synthesis inhibition had similar pressor effects in obese hypertensives compared with healthy control during autonomic blockade, suggesting that impaired NO vasodilation is secondary to sympathetic activation. We tested this hypothesis by determining the effect of autonomic blockade (trimethaphan 4 mg/min IV) on NO-mediated vasodilation (increase in forearm blood flow to intrabrachial acetylcholine) compared with endothelial-independent vasodilation (intrabrachial sodium nitroprusside) in obese hypertensive subjects (30blood flow (from 3.9±0.7 to 5.2±1.2 mL/100 mL per minute, P=0.078). As expected, NO-mediated vasodilation was blunted on the intact day compared with NO-independent vasodilation; forearm blood flow increased from 3.6±0.6 to 10.1±1.1 with the highest dose of nitroprusside, but only from 3.7±0.4 to 7.2±0.8 mL/100 mL per minute with the highest dose of acetylcholine, Pblood flow responses to acetylcholine were restored by autonomic blockade and were no longer different to nitroprusside (from 6.2±1.1 to 11.4±1.6 mL/100 mL per minute and from 5.2±0.9 to 12.5±0.9, respectively, P=0.58). Our results support the concept that sympathetic activation contributes to the impairment in NO-mediated vasodilation seen in obesity-associated hypertension and provides further rationale to explore it as a therapeutic target. © 2016 American Heart Association, Inc.

Cigarette smoking impairs nitric oxide-mediated cerebral blood flow increase: Implications for Alzheimer's disease

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Noboru Toda

2016-08-01

Full Text Available Cerebral blood flow is mainly regulated by nitrergic (parasympathetic, postganglionic nerves and nitric oxide (NO liberated from endothelial cells in response to shear stress and stretch of vasculature, whereas sympathetic vasoconstrictor control is quite weak. On the other hand, peripheral vascular resistance and blood flow are mainly controlled by adrenergic vasoconstrictor nerves; endothelium-derived NO and nitrergic nerves play some roles as vasodilator factors. Cigarette smoking impairs NO synthesis in cerebral vascular endothelial cells and nitrergic nerves leading to interference with cerebral blood flow and glucose metabolism in the brain. Smoking-induced cerebral hypoperfusion is induced by impairment of synthesis and actions of NO via endothelial nitric oxide synthase (eNOS/neuronal NOS (nNOS inhibition and by increased production of oxygen radicals, resulting in decreased actions of NO on vascular smooth muscle. Nicotine acutely and chronically impairs the action of endothelial NO and also inhibits nitrergic nerve function in chronic use. Impaired cerebral blood supply promotes the synthesis of amyloid β that accelerates blood flow decrease. This vicious cycle is thought to be one of the important factors involving in Alzheimer's disease (AD. Quitting smoking is undoubtedly one of the important ways to prevent and delay the genesis or slow the progress of impaired cognitive function and AD.

Characteristics of MOX dissolution with silver mediated electrolytic oxidation method

Energy Technology Data Exchange (ETDEWEB)

Umeda, Miki; Nakazaki, Masato; Kida, Takashi; Sato, Kenji; Kato, Tadahito; Kihara, Takehiro; Sugikawa, Susumu [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

2003-03-01

MOX dissolution with silver mediated electrolytic oxidation method is to be applied to the preparation of plutonium nitrate solution to be used for criticality safety experiments at Nuclear Fuel Cycle Safety Engineering Research Facility (NUCEF). Silver mediated electrolytic oxidation method uses the strong oxidisation ability of Ag(II) ion. This method is though to be effective for the dissolution of MOX, which is difficult to be dissolved with nitric acid. In this paper, the results of experiments on dissolution with 100 g of MOX are described. It was confirmed from the results that the MOX powder to be used at NUCEF was completely dissolved by silver mediated electrolytic oxidation method and that Pu(VI) ion in the obtained solution was reduced to tetravalent by means of NO{sub 2} purging. (author)

Hydralazine-induced vasodilation involves opening of high conductance Ca2+-activated K+ channels

DEFF Research Database (Denmark)

Bang, Lone; Nielsen-Kudsk, J E; Gruhn, N

1998-01-01

The purpose of this study was to investigate whether high conductance Ca2+-activated K+ channels (BK(Ca)) are mediating the vasodilator action of hydralazine. In isolated porcine coronary arteries, hydralazine (1-300 microM), like the K+ channel opener levcromakalim, preferentially relaxed......M) suppressed this response by 82% (P opening of BK(Ca) takes part in the mechanism whereby...

Metabolic control of muscle blood flow during exercise in humans

DEFF Research Database (Denmark)

Boushel, Robert Christopher

2003-01-01

that combined blockade of NOS and PGI2, and NOS and cytochrome P450, both attenuate exercise-induced hyperemia in humans. Combined vasodilator blockade studies offer the potential to uncover important interactions and compensatory vasodilator responses. The signaling pathways that link metabolic events evoked...... to exert control of muscle vasodilation. Adenosine, nitric oxide (NO), prostacyclin (PGI2), and endothelial-derived hyperpolarization factor (EDHF) are possible mediators of muscle vasodilation during exercise. In humans, adenosine has been shown to contribute to functional hyperemia as blood flow...... by muscle contraction to vasodilatory signals in the local vascular bed remains an important area of study....

Nitric oxide mediates insect cellular immunity via phospholipase A2 activation

Science.gov (United States)

After infection or invasion is recognized, biochemical mediators act in signaling insect immune functions. These include biogenic amines, insect cytokines, eicosanoids and nitric oxide (NO). Treating insects or isolated hemocyte populations with different mediators often leads to similar results. Se...

Myeloperoxidase potentiates nitric oxide-mediated nitrosation.

Science.gov (United States)

Lakshmi, Vijaya M; Nauseef, William M; Zenser, Terry V

2005-01-21

Nitrosation is an important reaction elicited by nitric oxide (NO). To better understand how nitrosation occurs in biological systems, we assessed the effect of myeloperoxidase (MPO), a mediator of inflammation, on nitrosation observed during NO autoxidation. Nitrosation of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ; 10 mum) to 2-nitrosoamino-3-methylimidazo[4,5-f]quinoline (N-NO-IQ) was monitored by HPLC. Using the NO donor spermine NONOate at pH 7.4, MPO potentiated N-NO-IQ formation. The minimum effective quantity of necessary components was 8.5 nm MPO, 0.25 mum H(2)O(2)/min, and 0.024 mum NO/min. Autoxidation was only detected at >/=1.2 mum NO/min. MPO potentiation was not affected by a 40-fold excess flux of H(2)O(2) over NO or less than a 2.4-fold excess flux of NO over H(2)O(2). Potentiation was due to an 8.8-fold increased affinity of MPO-derived nitrosating species for IQ. Autoxidation was inhibited by azide, suggesting involvement of the nitrosonium ion, NO(+). MPO potentiation was inhibited by NADH, but not azide, suggesting oxidative nitrosylation with NO(2)(.) or an NO(2)(.)-like species. MPO nonnitrosative oxidation of IQ with 0.3 mm NO(2)(-) at pH 5.5 was inhibited by azide, but not NADH, demonstrating differences between MPO oxidation of IQ with NO compared with NO(2)(-). Using phorbol ester-stimulated human neutrophils, N-NO-IQ formation was increased with superoxide dismutase and inhibited by catalase and NADH, but not NaN(3). This is consistent with nitrosation potentiation by MPO, not peroxynitrite. Increased N-NO-IQ formation was not detected with polymorphonuclear neutrophils from two unrelated MPO-deficient patients. Results suggest that the highly diffusible stable gas NO could initiate nitrosation at sites of neutrophil infiltration.

Brain natriuretic peptide is a potent vasodilator in aged human microcirculation and shows a blunted response in heart failure patients

DEFF Research Database (Denmark)

Edvinsson, Marie-Louise; Uddman, Erik; Edvinsson, Lars

2014-01-01

in the forearm was measured by laser Doppler Flowmetry. Local heating (+44°C, 10 min) was used to evoke a maximum local dilator response. RESULTS: Non-invasive iontophoretic administration of either BNP or acetylcholine (ACh), a known endothelium-dependent dilator, elicited an increase in local flow. The nitric......, the vasodilator responses to ACh and to local heating were only somewhat attenuated in CHF patients. Thus, dilator capacity and nitric oxide signalling were not affected to the same extent as BNP-mediated dilation, indicating a specific downregulation of the latter response. CONCLUSIONS: The findings show...... for the first time that microvascular responses to BNP are markedly reduced in CHF patients. This is consistent with the hypothesis of BNP receptor function is downregulated in CHF....

Reaction mechanisms of ruthenium tetroxide mediated oxidations of organic compounds

Energy Technology Data Exchange (ETDEWEB)

Froehaug, Astrid Elisabeth

1995-12-31

This thesis reports a study of the mechanism of ruthenium tetroxide mediated oxidations of saturated hydrocarbons, ethers, alkenes and alcohols. Several methods were used. The RuO{sub 4}-mediated oxidations of adamantane and cis-decalin were studied in CCl{sub 4}-CH{sub 3}CN-H{sub 2}O and in acetone-water. The rate of reaction was found to be moderately influenced by the polarity of the solvent. Solvent properties other than the polarity were also found to influence the reaction rates. From the oxidations of adamantane and adamantane-1,3,5,7-d{sub 4} two primary kinetic deuterium isotope effects were found. These were comparable with the deuterium isotope effects found for the analogous oxidations of cis-decalin and cis-decalin-d{sub 18}. The results seem to exclude both a one step hydride abstraction reaction mechanism and a one step concerted mechanism, as well as a scheme where two such mechanisms compete. The observations may be explained by a two step reaction mechanism consisting of a pre-equilibrium with formation of a substrate-RuO{sub 4} complex followed by a concerted rate determining reaction. The RuO{sub 4}-mediated oxidation of ethers was of kinetic second order with a small enthalpy of activation and a large negative entropy of activation. Oxidation of cyclopropylmethyl methyl ether gave methyl cyclopropanecarboxylate, no rearranged products were observed. On RuO{sub 4} oxidations in CCl{sub 4} with NaIO{sub 4} as stoichiometric oxidant, no chlorinated products were observed. Several observations not in agreement with a hydride or a hydrogen abstraction mechanism may be explained by assuming that the reaction proceeds by either a concerted reaction or by a reversible oxidative addition of the ether to RuO{sub 4} followed by a slow concerted step. 228 refs., 9 figs., 27 tabs.

Effects of supplementation with the fat-soluble vitamins E and D on fasting flow-mediated vasodilation in adults: a meta-analysis of randomized controlled trials.

Science.gov (United States)

Joris, Peter J; Mensink, Ronald P

2015-03-10

The effects of fat-soluble vitamin supplementation on cardiovascular disease (CVD) risk are not clear. Therefore, we performed a meta-analysis to quantify effects of fat-soluble vitamin supplements on fasting flow-mediated vasodilation (FMD) of the brachial artery, a validated marker to assess CVD risk. Randomized placebo-controlled trials (RCTs) were identified by a systematic search till July 2014. Seven RCTs studying the effects of vitamin E supplements (range: 300 to 1800 IU per day) and nine RCTs examining the effects of vitamin D supplements, that involved, respectively, 303 and 658 adults, were included. No studies with carotenoid or vitamin K supplements were found. Vitamin E supplementation increased FMD vs. control by 2.42% (95% CI: 0.46% to 4.37%; p = 0.015). No effects of vitamin D supplementation were found (0.15%; 95% CI: -0.21% to 0.51%; p = 0.41). These effects did not depend on subject characteristics, treatment characteristics or technical aspects of the FMD measurement. However, no dose-response relationship was evident for vitamin E, statistical significance depended on one study, while the levels of supplement were far above recommended intakes. The current meta-analysis, therefore, does not provide unambiguous evidence to support the use of fat-soluble vitamin supplements to improve fasting FMD in adults.

Vasodilator Therapy: Nitrates and Nicorandil.

Science.gov (United States)

Tarkin, Jason M; Kaski, Juan Carlos

2016-08-01

Nitrates have been used to treat symptoms of chronic stable angina for over 135 years. These drugs are known to activate nitric oxide (NO)-cyclic guanosine-3',-5'-monophasphate (cGMP) signaling pathways underlying vascular smooth muscle cell relaxation, albeit many questions relating to how nitrates work at the cellular level remain unanswered. Physiologically, the anti-angina effects of nitrates are mostly due to peripheral venous dilatation leading to reduction in preload and therefore left ventricular wall stress, and, to a lesser extent, epicardial coronary artery dilatation and lowering of systemic blood pressure. By counteracting ischemic mechanisms, short-acting nitrates offer rapid relief following an angina attack. Long-acting nitrates, used commonly for angina prophylaxis are recommended second-line, after beta-blockers and calcium channel antagonists. Nicorandil is a balanced vasodilator that acts as both NO donor and arterial K(+) ATP channel opener. Nicorandil might also exhibit cardioprotective properties via mitochondrial ischemic preconditioning. While nitrates and nicorandil are effective pharmacological agents for prevention of angina symptoms, when prescribing these drugs it is important to consider that unwanted and poorly tolerated hemodynamic side-effects such as headache and orthostatic hypotension can often occur owing to systemic vasodilatation. It is also necessary to ensure that a dosing regime is followed that avoids nitrate tolerance, which not only results in loss of drug efficacy, but might also cause endothelial dysfunction and increase long-term cardiovascular risk. Here we provide an update on the pharmacological management of chronic stable angina using nitrates and nicorandil.

Hormonal therapy with estradiol and drospirenone improves endothelium-dependent vasodilation in the coronary bed of ovariectomized spontaneously hypertensive rats

International Nuclear Information System (INIS)

Borgo, M.V.; Claudio, E.R.G.; Silva, F.B.; Romero, W.G.; Gouvea, S.A.; Moysés, M.R.; Santos, R.L.; Almeida, S.A.; Podratz, P.L.; Graceli, J.B.; Abreu, G.R.

2015-01-01

Drospirenone (DRSP) is a progestin with anti-aldosterone properties and it reduces blood pressure in hypertensive women. However, the effects of DRSP on endothelium-dependent coronary vasodilation have not been evaluated. This study investigated the effects of combined therapy with estrogen (E2) and DRSP on endothelium-dependent vasodilation of the coronary bed of ovariectomized (OVX) spontaneously hypertensive rats. Female spontaneously hypertensive rats (n=87) at 12 weeks of age were randomly divided into sham operated (Sham), OVX, OVX treated with E2 (E2), and OVX treated with E2 and DRSP (E2+DRSP) groups. Hemodynamic parameters were directly evaluated by catheter insertion into the femoral artery. Endothelium-dependent vasodilation in response to bradykinin in the coronary arterial bed was assessed using isolated hearts according to a modified Langendorff method. Coronary protein expression of endothelial nitric oxide synthase and estrogen receptor alpha (ER-α) was assessed by Western blotting. Histological slices of coronary arteries were stained with hematoxylin and eosin, and morphometric parameters were analyzed. Oxidative stress was assessed in situ by dihydroethidium fluorescence. Ovariectomy increased systolic blood pressure, which was only prevented by E2+DRSP treatment. Estrogen deficiency caused endothelial dysfunction, which was prevented by both treatments. However, the vasodilator response in the E2+DRSP group was significantly higher at the three highest concentrations compared with the OVX group. Reduced ER-α expression in OVX rats was restored by both treatments. Morphometric parameters and oxidative stress were augmented by OVX and reduced by E2 and E2+DRSP treatments. Hormonal therapy with E2 and DRSP may be an important therapeutic option in the prevention of coronary heart disease in hypertensive post-menopausal women

Hormonal therapy with estradiol and drospirenone improves endothelium-dependent vasodilation in the coronary bed of ovariectomized spontaneously hypertensive rats

Directory of Open Access Journals (Sweden)

M.V. Borgo

2016-01-01

Full Text Available Drospirenone (DRSP is a progestin with anti-aldosterone properties and it reduces blood pressure in hypertensive women. However, the effects of DRSP on endothelium-dependent coronary vasodilation have not been evaluated. This study investigated the effects of combined therapy with estrogen (E2 and DRSP on endothelium-dependent vasodilation of the coronary bed of ovariectomized (OVX spontaneously hypertensive rats. Female spontaneously hypertensive rats (n=87 at 12 weeks of age were randomly divided into sham operated (Sham, OVX, OVX treated with E2 (E2, and OVX treated with E2 and DRSP (E2+DRSP groups. Hemodynamic parameters were directly evaluated by catheter insertion into the femoral artery. Endothelium-dependent vasodilation in response to bradykinin in the coronary arterial bed was assessed using isolated hearts according to a modified Langendorff method. Coronary protein expression of endothelial nitric oxide synthase and estrogen receptor alpha (ER-α was assessed by Western blotting. Histological slices of coronary arteries were stained with hematoxylin and eosin, and morphometric parameters were analyzed. Oxidative stress was assessed in situ by dihydroethidium fluorescence. Ovariectomy increased systolic blood pressure, which was only prevented by E2+DRSP treatment. Estrogen deficiency caused endothelial dysfunction, which was prevented by both treatments. However, the vasodilator response in the E2+DRSP group was significantly higher at the three highest concentrations compared with the OVX group. Reduced ER-α expression in OVX rats was restored by both treatments. Morphometric parameters and oxidative stress were augmented by OVX and reduced by E2 and E2+DRSP treatments. Hormonal therapy with E2 and DRSP may be an important therapeutic option in the prevention of coronary heart disease in hypertensive post-menopausal women.

Hormonal therapy with estradiol and drospirenone improves endothelium-dependent vasodilation in the coronary bed of ovariectomized spontaneously hypertensive rats

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Borgo, M.V.; Claudio, E.R.G.; Silva, F.B.; Romero, W.G.; Gouvea, S.A.; Moysés, M.R.; Santos, R.L.; Almeida, S.A. [Departamento de Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal de Espírito Santo, Vitória, ES (Brazil); Podratz, P.L.; Graceli, J.B. [Departamento de Morfologia, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Abreu, G.R. [Departamento de Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal de Espírito Santo, Vitória, ES (Brazil)

2015-11-17

Drospirenone (DRSP) is a progestin with anti-aldosterone properties and it reduces blood pressure in hypertensive women. However, the effects of DRSP on endothelium-dependent coronary vasodilation have not been evaluated. This study investigated the effects of combined therapy with estrogen (E2) and DRSP on endothelium-dependent vasodilation of the coronary bed of ovariectomized (OVX) spontaneously hypertensive rats. Female spontaneously hypertensive rats (n=87) at 12 weeks of age were randomly divided into sham operated (Sham), OVX, OVX treated with E2 (E2), and OVX treated with E2 and DRSP (E2+DRSP) groups. Hemodynamic parameters were directly evaluated by catheter insertion into the femoral artery. Endothelium-dependent vasodilation in response to bradykinin in the coronary arterial bed was assessed using isolated hearts according to a modified Langendorff method. Coronary protein expression of endothelial nitric oxide synthase and estrogen receptor alpha (ER-α) was assessed by Western blotting. Histological slices of coronary arteries were stained with hematoxylin and eosin, and morphometric parameters were analyzed. Oxidative stress was assessed in situ by dihydroethidium fluorescence. Ovariectomy increased systolic blood pressure, which was only prevented by E2+DRSP treatment. Estrogen deficiency caused endothelial dysfunction, which was prevented by both treatments. However, the vasodilator response in the E2+DRSP group was significantly higher at the three highest concentrations compared with the OVX group. Reduced ER-α expression in OVX rats was restored by both treatments. Morphometric parameters and oxidative stress were augmented by OVX and reduced by E2 and E2+DRSP treatments. Hormonal therapy with E2 and DRSP may be an important therapeutic option in the prevention of coronary heart disease in hypertensive post-menopausal women.

Dietary nitrate restores compensatory vasodilation and exercise capacity in response to a compromise in oxygen delivery in the noncompensator phenotype.

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Bentley, Robert F; Walsh, Jeremy J; Drouin, Patrick J; Velickovic, Aleksandra; Kitner, Sarah J; Fenuta, Alyssa M; Tschakovsky, Michael E

2017-09-01

Recently, dietary nitrate supplementation has been shown to improve exercise capacity in healthy individuals through a potential nitrate-nitrite-nitric oxide pathway. Nitric oxide has been shown to play an important role in compensatory vasodilation during exercise under hypoperfusion. Previously, we established that certain individuals lack a vasodilation response when perfusion pressure reductions compromise exercising muscle blood flow. Whether this lack of compensatory vasodilation in healthy, young individuals can be restored with dietary nitrate supplementation is unknown. Six healthy (21 ± 2 yr), recreationally active men completed a rhythmic forearm exercise. During steady-state exercise, the exercising arm was rapidly transitioned from an uncompromised (below heart) to a compromised (above heart) position, resulting in a reduction in local pressure of -31 ± 1 mmHg. Exercise was completed following 5 days of nitrate-rich (70 ml, 0.4 g nitrate) and nitrate-depleted (70 ml, ~0 g nitrate) beetroot juice consumption. Forearm blood flow (in milliliters per minute; brachial artery Doppler and echo ultrasound), mean arterial blood pressure (in millimeters of mercury; finger photoplethysmography), exercising forearm venous effluent (ante-cubital vein catheter), and plasma nitrite concentrations (chemiluminescence) revealed two distinct vasodilatory responses: nitrate supplementation increased (plasma nitrite) compared with placebo (245 ± 60 vs. 39 ± 9 nmol/l; P nitrate supplementation (568 ± 117 vs. 714 ± 139 ml ⋅ min -1 ⋅ 100 mmHg -1 ; P = 0.005) but not in placebo (687 ± 166 vs. 697 ± 171 min -1 ⋅ 100 mmHg -1 ; P = 0.42). As such, peak exercise capacity was reduced to a lesser degree (-4 ± 39 vs. -39 ± 27 N; P = 0.01). In conclusion, dietary nitrate supplementation during a perfusion pressure challenge is an effective means of restoring exercise capacity and enabling compensatory vasodilation. NEW & NOTEWORTHY Previously, we

Crosstalk between nitrite, myoglobin and reactive oxygen species to regulate vasodilation under hypoxia.

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Matthias Totzeck

Full Text Available The systemic response to decreasing oxygen levels is hypoxic vasodilation. While this mechanism has been known for more than a century, the underlying cellular events have remained incompletely understood. Nitrite signaling is critically involved in vessel relaxation under hypoxia. This can be attributed to the presence of myoglobin in the vessel wall together with other potential nitrite reductases, which generate nitric oxide, one of the most potent vasodilatory signaling molecules. Questions remain relating to the precise concentration of nitrite and the exact dose-response relations between nitrite and myoglobin under hypoxia. It is furthermore unclear whether regulatory mechanisms exist which balance this interaction. Nitrite tissue levels were similar across all species investigated. We then investigated the exact fractional myoglobin desaturation in an ex vivo approach when gassing with 1% oxygen. Within a short time frame myoglobin desaturated to 58±12%. Given that myoglobin significantly contributes to nitrite reduction under hypoxia, dose-response experiments using physiological to pharmacological nitrite concentrations were conducted. Along all concentrations, abrogation of myoglobin in mice impaired vasodilation. As reactive oxygen species may counteract the vasodilatory response, we used superoxide dismutase and its mimic tempol as well as catalase and ebselen to reduce the levels of reactive oxygen species during hypoxic vasodilation. Incubation of tempol in conjunction with catalase alone and catalase/ebselen increased the vasodilatory response to nitrite. Our study shows that modest hypoxia leads to a significant nitrite-dependent vessel relaxation. This requires the presence of vascular myoglobin for both physiological and pharmacological nitrite levels. Reactive oxygen species, in turn, modulate this vasodilation response.

Candesartan restores pressure-induced vasodilation and prevents skin pressure ulcer formation in diabetic mice.

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Danigo, Aurore; Nasser, Mohamad; Bessaguet, Flavien; Javellaud, James; Oudart, Nicole; Achard, Jean-Michel; Demiot, Claire

2015-02-18

Angiotensin II type 1 receptor (AT1R) blockers have beneficial effects on neurovascular complications in diabetes and in organ's protection against ischemic episodes. The present study examines whether the AT1R blocker candesartan (1) has a beneficial effect on diabetes-induced alteration of pressure-induced vasodilation (PIV, a cutaneous physiological neurovascular mechanism which could delay the occurrence of tissue ischemia), and (2) could be protective against skin pressure ulcer formation. Male Swiss mice aged 5-6 weeks were randomly assigned to four experimental groups. In two groups, diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ, 200 mg.kg(-1)). After 6 weeks, control and STZ mice received either no treatment or candesartan (1 mg/kg-daily in drinking water) during 2 weeks. At the end of treatment (8 weeks of diabetes duration), C-fiber mediated nociception threshold, endothelium-dependent vasodilation and PIV were assessed. Pressure ulcers (PUs) were then induced by pinching the dorsal skin between two magnetic plates for three hours. Skin ulcer area development was assessed during three days, and histological examination of the depth of the skin lesion was performed at day three. After 8 weeks of diabetes, the skin neurovascular functions (C-fiber nociception, endothelium-dependent vasodilation and PIV) were markedly altered in STZ-treated mice, but were fully restored by treatment with candesartan. Whereas in diabetes mice exposure of the skin to pressure induced wide and deep necrotic lesions, treatment with candersartan restored their ability to resist to pressure-induced ulceration as efficiently as the control mice. Candesartan decreases the vulnerability to pressure-induced ulceration and restores skin neurovascular functions in mice with STZ-induced established diabetes.

Nitric Oxide-Mediated Posttranslational Modifications: Impacts at the Synapse

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Sophie A. Bradley

2016-01-01

Full Text Available Nitric oxide (NO is an important gasotransmitter molecule that is involved in numerous physiological processes throughout the nervous system. In addition to its involvement in physiological plasticity processes (long-term potentiation, LTP; long-term depression, LTD which can include NMDAR-mediated calcium-dependent activation of neuronal nitric oxide synthase (nNOS, new insights into physiological and pathological consequences of nitrergic signalling have recently emerged. In addition to the canonical cGMP-mediated signalling, NO is also implicated in numerous pathways involving posttranslational modifications. In this review we discuss the multiple effects of S-nitrosylation and 3-nitrotyrosination on proteins with potential modulation of function but limit the analyses to signalling involved in synaptic transmission and vesicular release. Here, crucial proteins which mediate synaptic transmission can undergo posttranslational modifications with either pre- or postsynaptic origin. During normal brain function, both pathways serve as important cellular signalling cascades that modulate a diverse array of physiological processes, including synaptic plasticity, transcriptional activity, and neuronal survival. In contrast, evidence suggests that aging and disease can induce nitrosative stress via excessive NO production. Consequently, uncontrolled S-nitrosylation/3-nitrotyrosination can occur and represent pathological features that contribute to the onset and progression of various neurodegenerative diseases, including Parkinson’s, Alzheimer’s, and Huntington’s.

Skeletal muscle contraction-induced vasodilation in the microcirculation.

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Hong, Kwang-Seok; Kim, Kijeong

2017-10-01

Maximal whole body exercise leads skeletal muscle blood flow to markedly increase to match metabolic demands, a phenomenon termed exercise hyperaemia that is accomplished by increasing vasodilation. However, local vasodilatory mechanisms in response to skeletal muscle contraction remain uncertain. This review highlights metabolic vasodilators released from contracting skeletal muscle, endothelium, or blood cells. As a considerable skeletal muscle vasodilation potentially results in hypotension, sympathetic nerve activity needs to be augmented to elevate cardiac output and blood pressure during dynamic exercise. However, since the enhanced sympathetic vasoconstriction restrains skeletal muscle blood flow, intramuscular arteries have an indispensable ability to blunt sympathetic activity for exercise hyperaemia. In addition, we discuss that mechanical compression of the intramuscular vasculature contributes to causing the initial phase of increasing vasodilation following a single muscle contraction. We have also chosen to focus on conducted (or ascending) electrical signals that evoke vasodilation of proximal feed arteries to elevate blood flow in the microcirculation of skeletal muscle. Endothelial hyperpolarization originating within distal arterioles ascends into the proximal feed arteries, thereby increasing total blood flow in contracting skeletal muscle. This brief review summarizes molecular mechanisms underlying the regulation of skeletal muscle blood flow to a single or sustained muscle contraction.

Relaxing Responses to Hydrogen Peroxide and Nitric Oxide in Human Pericardial Resistance Arteries Stimulated with Endothelin-1

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Leurgans, Thomas M; Bloksgaard, Maria; Irmukhamedov, Akhmadjon

2018-01-01

In human pericardial resistance arteries, effects of the endothelium-dependent vasodilator bradykinin are mediated by NO during contraction induced by K(+) or the TxA2 analogue U46619 and by H2 O2 during contraction by endothelin-1 (ET-1), respectively. We tested the hypotheses that ET-1 reduces...... also acts as an endothelium-dependent vasodilator. This article is protected by copyright. All rights reserved....

Involvement of inositol biosynthesis and nitric oxide in the mediation of UV-B induced oxidative stress

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Dmytro I Lytvyn

2016-04-01

Full Text Available The involvement of NO-signaling in ultraviolet B (UV-B induced oxidative stress in plants is an open question. Inositol biosynthesis contributes to numerous cellular functions, including the regulation of plants tolerance to stress. This work reveals the involvement of inositol-3-phosphate synthase 1 (IPS1, a key enzyme for biosynthesis of myo-inositol and its derivatives, in the response to NO-dependent oxidative stress in Arabidopsis. Homozygous mutants deficient for IPS1 (atips1 and wild-type plants were transformed with a reduction-oxidation-sensitive green fluorescent protein 2 (grx1-rogfp2 and used for the dynamic measurement of UV-B-induced and SNP (sodium nitroprusside-mediated oxidative stresses by confocal microscopy. atips1 mutants displayed greater tissue-specific resistance to the action of UV-B than the wild type. SNP can act both as an oxidant or repairer depending on the applied concentration, but mutant plants were more tolerant than the wild type to nitrosative effects of high concentration of SNP. Additionally, pretreatment with low concentrations of SNP (10, 100 μM before UV-B irradiation resulted in a tissue-specific protective effect that was enhanced in atips1. We conclude that the interplay between nitric oxide and inositol signaling can be involved in the mediation of UV-B-initiated oxidative stress in the plant cell.

Cold induced peripheral vasodilation at high altitudes- a field study

NARCIS (Netherlands)

Daanen, H.A.M.; Ruiten, H.J.A. van

2000-01-01

A significant reduction in cold-induced vasodilation (CIVD) is observed at high altitudes. No agreement is found in the literature about acclimatization effects on CIVD. Two studies were performed to investigate the effect of altitude acclimatization on CIVD. In the first study 13 male subjects

Thallium-201 myocardial imaging during coronary vasodilation induced by oral dipyridamole

International Nuclear Information System (INIS)

Gould, K.L.; Sorenson, S.G.; Albro, P.; Caldwell, J.H.; Chaudhuri, T.; Hamilton, G.W.

1986-01-01

Myocardial perfusion imaging of 201 TI injected during maximum exercise has been an important diagnostic tool for coronary artery disease. Pharmacologic coronary vasodilation by i.v. infusion of dipyridamole may be used in lieu of exercise stress for purposes of diagnostic perfusion imaging. However, i.v. dipyridamole is not currently available from commercial sources for widespread routine use. Accordingly, this study was carried out in order to determine whether high dose, oral dipyridamole would be useful as a coronary vasodilator for purposes of diagnostic perfusion imaging. Fifty-eight patients undergoing diagnostic coronary arteriography also had myocardial perfusion imaging with 201TI under conditions of rest, maximum exercise stress, and high dose oral dipyridamole. Of those patients who had a defect on exercise thallium images, 75% also had a perfusion defect on thallium images after high dose oral dipyridamole. These results indicate that oral dipyridamole causes sufficient coronary arteriolar vasodilation and increase of coronary flow in nonstenotic arteries to identify perfusion defects comparable to those seen on maximum exercise stress in at least 75% of cases. In 25% of patients with exercise defects, no perfusion defect was seen after oral dipyridamole. Thus, oral dipyridamole is a potent coronary vasodilator, comparable to exercise stress in most cases, but in a minority of patients may not be comparable to exercise stress

Circulating microparticles from patients with valvular heart disease and cardiac surgery inhibit endothelium-dependent vasodilation.

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Fu, Li; Hu, Xiao-Xia; Lin, Ze-Bang; Chang, Feng-Jun; Ou, Zhi-Jun; Wang, Zhi-Ping; Ou, Jing-Song

2015-09-01

Vascular function is very important for maintaining circulation after cardiac surgery. Circulating microparticles (MPs) generated in various diseases play important roles in causing inflammation, coagulation, and vascular injury. However, the impact of MPs generated from patients who have valvular heart disease (VHD), before and after cardiac surgery, on vascular function remains unknown. This study is designed to investigate the impact of such MPs on vasodilation. Microparticles were isolated from age-matched healthy subjects and patients who had VHD, before cardiac surgery, and at 12 hours and 72 hours afterward. The number of MPs was measured and compared. Effects evaluated were of the impact of MPs on: vasodilation of mice aorta; the phosphorylation and expression of Akt, endothelial nitric oxide synthase (eNOS), protein kinase C-βII (PKC-βII), and p70 ribosomal protein S6 kinase (p70S6K); expression of caveolin-1; the association of eNOS with heat shock protein 90 (HSP90); and generation of nitric oxide and superoxide anion of human umbilical vein endothelial cells. Compared with the healthy subjects, VHD patients had significantly higher levels of circulating MPs and those MPs before cardiac surgery can: impair endothelium-dependent vasodilation; inhibit phosphorylation of Akt and eNOS; increase activation of PKC-βII and p70S6K; enhance expression of caveolin-1; reduce the association of HSP90 with eNOS; decrease nitric oxide production, and increase superoxide anion generation. These deleterious effects were even stronger in postoperative MPs. Our data demonstrate that MPs generated from VHD patients before and after cardiac surgery contributed to endothelial dysfunction, by uncoupling and inhibiting eNOS. Circulating MPs are potential therapeutic targets for the maintenance of vascular function postoperatively. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Data describing the flow-mediated vasodilation responses and blood pressure in young adult humans after a single dose of oral edible emu oil

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Tadayoshi Miyashita

2018-04-01

Full Text Available The data provided herein include flow-mediated vasodilation responses, represented by changes in arterial diameter, and blood pressure in young adults after a single oral dose of edible emu oil or placebo (cross-over design. Ten healthy men and 10 healthy women participated. Increased blood flow in the antebrachial region was induced by inflating a pressure cuff and subsequently releasing the pressure by deflating the cuff. After the release, the arterial diameter was continuously monitored for 110 sec using ultrasonic diagnostic equipment. The changes in the arterial diameter from 20 to 110 sec post-cuff deflation are described in line graphs and tables. In addition, systolic and diastolic blood pressure data are provided in a table.

O2-mediated oxidation of ferrous nitrosylated human serum heme-albumin is limited by nitrogen monoxide dissociation

International Nuclear Information System (INIS)

Ascenzi, Paolo; Gullotta, Francesca; Gioia, Magda; Coletta, Massimo; Fasano, Mauro

2011-01-01

Research highlights: → Human serum heme-albumin displays globin-like properties. → O 2 -mediated oxidation of ferrous nitrosylated human serum heme-albumin. → Allosteric modulation of human serum heme-albumin reactivity. → Rifampicin is an allosteric effector of human serum heme-albumin. → Human serum heme-albumin is a ROS and NOS scavenger. -- Abstract: Human serum heme-albumin (HSA-heme-Fe) displays globin-like properties. Here, kinetics of O 2 -mediated oxidation of ferrous nitrosylated HSA-heme-Fe (HSA-heme-Fe(II)-NO) is reported. Values of the first-order rate constants for O 2 -mediated oxidation of HSA-heme-Fe(II)-NO (i.e., for ferric HSA-heme-Fe formation) and for NO dissociation from HSA-heme-Fe(II)-NO (i.e., for NO replacement by CO) are k = 9.8 x 10 -5 and 8.3 x 10 -4 s -1 , and h = 1.3 x 10 -4 and 8.5 x 10 -4 s -1 , in the absence and presence of rifampicin, respectively, at pH = 7.0 and T = 20.0 o C. The coincidence of values of k and h indicates that NO dissociation represents the rate limiting step of O 2 -mediated oxidation of HSA-heme-Fe(II)-NO. Mixing HSA-heme-Fe(II)-NO with O 2 does not lead to the formation of the transient adduct(s), but leads to the final ferric HSA-heme-Fe derivative. These results reflect the fast O 2 -mediated oxidation of ferrous HSA-heme-Fe and highlight the role of drugs in modulating allosterically the heme-Fe-atom reactivity.

Renal and femoral venous blood flows are regulated by different mechanisms dependent on α-adrenergic receptor subtypes and nitric oxide in anesthetized rats.

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Fioretti, Alexandre C; Ogihara, Cristiana A; Cafarchio, Eduardo M; Venancio, Daniel P; de Almeida, Roberto Lopes; Antonio, Bruno B; Sato, Monica A

2017-12-01

Venous and arterial walls are responsive to sympathetic system and circulating substances, nevertheless, very few is known about the venous blood flow regulation simultaneously to arterial vascular beds. In this study, we compared the venous and arterial blood flow regulation in visceral and muscular beds upon injection of different doses of vasoactive drugs which act in arterial vascular beds. Anesthetized adult male Wistar rats underwent to right femoral artery and vein cannulation for hemodynamic recordings and infusion of drugs. Doppler flow probes were placed around the left renal artery and vein, and left femoral artery and vein to evaluate the changes in flood flow. Phenylephrine (PHE) injection (α 1 -adrenergic receptor agonist) elicited vasoconstriction in all arteries and veins. Intravenous prazosin (PZS) (1mg/kg, α 1 -adrenergic receptor blocker) caused renal artery vasodilation, but not in the other beds. Vasoconstrictor effect of PHE was abolished by PZS in all vascular beds, except in femoral vein. Phentolamine (PTL) injection (1mg/kg, α 1 /α 2 -adrenergic receptor blocker) produced renal artery vasodilation with no change in other beds. After PTL, the vasoconstriction evoked by PHE was abolished in all vascular beds. Sodium Nitroprusside (SNP), a nitric oxide donor, elicited vasodilation in all beds, and after PTL but not post PZS injection, SNP enhanced the vasodilatory effect in femoral vein. Our findings suggest that the vasoconstriction in renal and femoral veins is mediated by different subtypes of α-adrenoceptors. The nitric oxide-dependent vasodilation in femoral vein enhances when α 2 -adrenoceptors are not under stimulation, but not in the other vascular beds investigated. Copyright © 2017 Elsevier Inc. All rights reserved.

Treatment of spontaneously hypertensive rats with rosiglitazone and/or enalapril restores balance between vasodilator and vasoconstrictor actions of insulin with simultaneous improvement in hypertension and insulin resistance.

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Potenza, Maria A; Marasciulo, Flora L; Tarquinio, Mariela; Quon, Michael J; Montagnani, Monica

2006-12-01

Spontaneously hypertensive rats (SHRs) exhibit endothelial dysfunction and insulin resistance. Reciprocal relationships between endothelial dysfunction and insulin resistance may contribute to hypertension by causing imbalanced regulation of endothelial-derived vasodilators (e.g., nitric oxide) and vasoconstrictors (e.g., endothelin-1 [ET-1]). Treatment of SHRs with rosiglitazone (insulin sensitizer) and/or enalapril (ACE inhibitor) may simultaneously improve hypertension, insulin resistance, and endothelial dysfunction by rebalancing insulin-stimulated production of vasoactive mediators. When compared with WKY control rats, 12-week-old vehicle-treated SHRs were hypertensive, overweight, and insulin resistant, with elevated fasting levels of insulin and ET-1 and reduced serum adiponectin levels. In mesenteric vascular beds (MVBs) isolated from vehicle-treated SHRs and preconstricted with norepinephrine (NE) ex vivo, vasodilator responses to insulin were significantly impaired, whereas the ability of insulin to oppose vasoconstrictor actions of NE was absent (versus WKY controls). Three-week treatment of SHRs with rosiglitazone and/or enalapril significantly reduced blood pressure, insulin resistance, fasting insulin, and ET-1 levels and increased adiponectin levels to values comparable with those observed in vehicle-treated WKY controls. By restoring phosphatidylinositol 3-kinase-dependent effects, rosiglitazone and/or enalapril therapy of SHRs also significantly improved vasodilator responses to insulin in MVB preconstricted with NE ex vivo. Taken together, our data provide strong support for the existence of reciprocal relationships between endothelial dysfunction and insulin resistance that may be relevant for developing novel therapeutic strategies for the metabolic syndrome.

Purple grape juice improves endothelial function and reduces the susceptibility of LDL cholesterol to oxidation in patients with coronary artery disease.

Science.gov (United States)

Stein, J H; Keevil, J G; Wiebe, D A; Aeschlimann, S; Folts, J D

1999-09-07

In vitro, the flavonoid components of red wine and purple grape juice are powerful antioxidants that induce endothelium-dependent vasodilation of vascular rings derived from rat aortas and human coronary arteries. Although improved endothelial function and inhibition of LDL oxidation may be potential mechanisms by which red wine and flavonoids reduce cardiovascular risk, the in vivo effects of grape products on endothelial function and LDL oxidation have not been investigated. This study assessed the effects of ingesting purple grape juice on endothelial function and LDL susceptibility to oxidation in patients with coronary artery disease (CAD). Fifteen adults with angiographically documented CAD ingested 7.7+/-1.2 mL. kg(-1). d(-1) of purple grape juice for 14 days. Flow-mediated vasodilation (FMD) was measured using high-resolution brachial artery ultrasonography. Susceptibility of LDL particles to oxidation was determined from the rate of conjugated diene formation after exposure to copper chloride. At baseline, FMD was impaired (2.2+/-2. 9%). After ingestion of grape juice, FMD increased to 6.4+/-4.7% (P=0.003). In a linear regression model that included age, artery diameter, lipid values, and use of lipid-lowering and antioxidant therapies, the effect of grape juice on FMD remained significant (mean change 4.2+/-4.4%, PFMD and reduces LDL susceptibility to oxidation in CAD patients. Improved endothelium-dependent vasodilation and prevention of LDL oxidation are potential mechanisms by which flavonoids in purple grape products may prevent cardiovascular events, independent of alcohol content.

Decreased active vasodilator sensitivity in aged skin.

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Kenney, W L; Morgan, A L; Farquhar, W B; Brooks, E M; Pierzga, J M; Derr, J A

1997-04-01

Older men and women respond to local and reflex-mediated heat stress with an attenuated increase in cutaneous vascular conductance (CVC). This study was performed to test the hypothesis that an augmented or sustained noradrenergic vasoconstriction (VC) may play a role in this age-related difference. Fifteen young (22 +/- 1 yr) and 15 older (66 +/- 1 yr) men exercised at 50% peak oxygen uptake in a 36 degrees C environment. Skin perfusion was monitored at two sites on the right forearm by laser-Doppler flowmetry: one site pretreated with bretylium tosylate (BT) to block the local release of norepinephrine and thus VC and an adjacent control site. Blockade of reflex VC was verified during whole body cooling using a water-perfused suit. CVC (perfusion divided by mean arterial pressure) at each site was reported as a percentage of the maximal CVC (%CVCmax) induced at the end of each experiment by prolonged local heating at 42 degrees C. Neither age nor BT affected the %CVCmax (75-86%) attained at high core temperatures. During the early rise phase of CVC, the %CVCmax-change in esophageal temperature (delta T(es)) curve was shifted to the right in the older men (effective delta T(es) associated with 50% CVC response for young, 0.22 +/- 0.04 and 0.39 +/- 0.04 degrees C and for older, 0.73 +/- 0.04 and 0.85 +/- 0.04 degrees C at control and BT sites, respectively). BT had no interactive effect on this age difference, suggesting a lack of involvement of the VC system in the attenuated CVC response of individuals over the age of 60 yr. Additionally, increases in skin vascular conductance were quantitatively compared by measuring increases in total forearm vascular conductance (FVC, restricted to the forearm skin under these conditions). After the initial approximately 0.2 degrees C increase in T(es), FVC was 40-50% lower in the older men (P < 0.01) for the remainder of the exercise. Decreased active vasodilator sensitivity to increasing core temperature, coupled with

Vasodilator Activity of the Essential Oil from Aerial Parts of Pectis brevipedunculata and Its Main Constituent Citral in Rat Aorta

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Gisele Zapata-Sudo

2013-03-01

Full Text Available The essential oil of Pectis brevipedunculata (EOPB, a Brazilian ornamental aromatic grass, is characterized by its high content of citral (81.9%: neral 32.7% and geranial 49.2%, limonene (4.7% and α-pinene (3.4%. Vasodilation induced by EOPB and isolated citral was investigated in pre-contracted vascular smooth muscle, using thoracic aorta from Wistar Kyoto (WKY rats which was prepared for isometric tension recording. EOPB promoted intense relaxation of endothelium-intact and denuded aortic rings with the concentration to induce 50% of the maximal relaxation (IC50 of 0.044% ± 0.006% and 0.093% ± 0.015% (p 0.05. In endothelium-intact aorta, EOPB-induced vasorelaxation was significantly reduced by L-NAME, a nitric oxide synthase inhibitor. The vasodilator activity of citral was increased in the KCl-contracted aorta and citral attenuated the contracture elicited by Ca2+ in depolarized aorta. EOPB and citral elicited vasorelaxation on thoracic aorta by affecting the NO/cyclic GMP pathway and the calcium influx through voltage-dependent L-type Ca2+ channels, respectively.

Vasodilator activity of the essential oil from aerial parts of Pectis brevipedunculata and its main constituent citral in rat aorta.

Science.gov (United States)

Pereira, Sharlene Lopes; Marques, André Mesquita; Sudo, Roberto Takashi; Kaplan, Maria Auxiliadora Coelho; Zapata-Sudo, Gisele

2013-03-07

The essential oil of Pectis brevipedunculata (EOPB), a Brazilian ornamental aromatic grass, is characterized by its high content of citral (81.9%: neral 32.7% and geranial 49.2%), limonene (4.7%) and α-pinene (3.4%). Vasodilation induced by EOPB and isolated citral was investigated in pre-contracted vascular smooth muscle, using thoracic aorta from Wistar Kyoto (WKY) rats which was prepared for isometric tension recording. EOPB promoted intense relaxation of endothelium-intact and denuded aortic rings with the concentration to induce 50% of the maximal relaxation (IC50) of 0.044% ± 0.006% and 0.093% ± 0.015% (p 0.05). In endothelium-intact aorta, EOPB-induced vasorelaxation was significantly reduced by L-NAME, a nitric oxide synthase inhibitor. The vasodilator activity of citral was increased in the KCl-contracted aorta and citral attenuated the contracture elicited by Ca2+ in depolarized aorta. EOPB and citral elicited vasorelaxation on thoracic aorta by affecting the NO/cyclic GMP pathway and the calcium influx through voltage-dependent L-type Ca2+ channels, respectively.

Pregnancy Augments VEGF-Stimulated In Vitro Angiogenesis and Vasodilator (NO and H2S) Production in Human Uterine Artery Endothelial Cells.

Science.gov (United States)

Zhang, Hong-Hai; Chen, Jennifer C; Sheibani, Lili; Lechuga, Thomas J; Chen, Dong-Bao

2017-07-01

Augmented uterine artery (UA) production of vasodilators, including nitric oxide (NO) and hydrogen sulfide (H2S), has been implicated in pregnancy-associated and agonist-stimulated rise in uterine blood flow that is rate-limiting to pregnancy health. Developing a human UA endothelial cell (hUAEC) culture model from main UAs of nonpregnant (NP) and pregnant (P) women for testing a hypothesis that pregnancy augments endothelial NO and H2S production and endothelial reactivity to vascular endothelial growth factor (VEGF). Main UAs from NP and P women were used for developing hUAEC culture models. Comparisons were made between NP- and P-hUAECs in in vitro angiogenesis, activation of cell signaling, expression of endothelial NO synthase (eNOS) and H2S-producing enzymes cystathionine β-synthase (CBS) and cystathionine γ-lyase, and NO/H2S production upon VEGF stimulation. NP- and P-hUAECs displayed a typical cobblestone-like shape in culture and acetylated low-density lipoprotein uptake, stained positively for endothelial and negatively for smooth muscle markers, maintained key signaling proteins during passage, and had statistically significant greater eNOS and CBS proteins in P- vs NP-hUAECs. Treatment with VEGF stimulated in vitro angiogenesis and eNOS protein and NO production only in P-hUEACs and more robust cell signaling in P- vs NP-hUAECs. VEGF stimulated CBS protein expression, accounting for VEGF-stimulated H2S production in hUAECs. Comparisons between NP- and P-hUAECs reveal that pregnancy augments VEGF-stimulated in vitro angiogenesis and NO/H2S production in hUAECs, showing that the newly established hUAEC model provides a critical in vitro tool for understanding human uterine hemodynamics. Copyright © 2017 Endocrine Society

Safety and Efficacy of Intracoronary Vasodilators in the Treatment of No-Reflow after Primary Percutaneous Intervention in Patients with Acute ST-Elevation Myocardial Infarction: A Literature Review

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Mostafa Dastani

2016-04-01

Full Text Available Introduction: The investigation of no-reflow phenomenon after Percutaneous Coronary Intervention (PCI in patients with acute ST-segment Elevation Myocardial Infarction (STEMI has therapeutic implications. Several vasodilators were administered through intracoronary injection to treat this phenomenon. We aimed to elucidate the risk factors, predictors, and long-term effects of no-reflow phenomenon, and to compare the effects of various vasodilators on re-opening the obstructed vessels. Materials and Methods: All the reviewed articles were retrieved from MEDLINE and Science Direct (up to October 2014. All no-reflow cases were determined through Thrombolysis in Myocardial Infarction grading (TIMI system. Results: Four articles were included, two of which mainly focused on risk factors, predictors, and long-term prognosis of no-reflow phenomenon, and its association with patient mortality and morbidity. The other two articles evaluated therapeutic interventions and compared their efficacy in treating no-reflow. Conclusion: Development of no-reflow in patients with STEMI after primary PCI is associated with low myocardial salvage by primary PCI, large scintigraphic infarct size, deteriorated left ventricle ejection fraction at six months, and increased risk of first-year mortality. During primary PCI, intracoronary infusion of diltiazem and verapamil can reverse no-reflow more effectively than nitroglycerin.

NO-independent mechanism mediates tempol-induced renal vasodilation in SHR

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de Richelieu, Louise Tilma; Sørensen, Charlotte Mehlin; Salomonsson, Max

2005-01-01

whether the effects of tempol were due to a restored NO system, we used the NOS inhibitor N(w)-nitro-L-arginine methyl ester (L-NAME). Renal blood flow (RBF) and mean arterial pressure (MAP) were measured in vivo by electromagnetic flowmetry and arterial catheterization in 10- to 12-wk-old anesthetized......We investigated whether tempol, a superoxide dismutase mimetic, affected renal hemodynamics and arterial pressure in spontaneously hypertensive rats (SHR) and Sprague-Dawley (SD) rats. We also examined whether tempol affected exaggerated renal vasoconstrictor responses to ANG II in SHR. To test...... used as controls. ANG II (1-4 ng) was administered as a bolus via a renal artery catheter. L-NAME was administered intravenously for 15-20 min. Renal vascular resistance (RVR) was elevated in SHR-C compared with SD-C. In SHR-T, baseline RVR was not different from SD-C and SD-T rats. Tempol had...

Nitric oxide in the stress axis.

Science.gov (United States)

López-Figueroa, M O; Day, H E; Akil, H; Watson, S J

1998-10-01

In recent years nitric oxide (NO) has emerged as a unique biological messenger. NO is a highly diffusible gas, synthesized from L-arginine by the enzyme nitric oxide synthase (NOS). Three unique subtypes of NOS have been described, each with a specific distribution profile in the brain and periphery. NOS subtype I is present, among other areas, in the hippocampus, hypothalamus, pituitary and adrenal gland. Together these structures form the limbic-hypothalamic-pituitary-adrenal (LHPA) or stress axis, activation of which is one of the defining features of a stress response. Evidence suggests that NO may modulate the release of the stress hormones ACTH and corticosterone, and NOS activity and transcription is increased in the LHPA axis following various stressful stimuli. Furthermore, following activation of the stress axis, glucocorticoids are thought to down-regulate the transcription and activity of NOS via a feedback mechanism. Taken together, current data indicate a role for NO in the regulation of the LHPA axis, although at present this role is not well defined. It has been suggested that NO may act as a cellular communicator in plasticity and development, to facilitate the activation or the release of other neurotransmitters, to mediate immune responses, and/or as a vasodilator in the regulation of blood flow. In the following review we summarize some of the latest insights into the function of NO, with special attention to its relationship with the LHPA axis.

Preserved microvascular endothelial function in young, obese adults with functional loss of nitric oxide signaling

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John eHarrell

2015-12-01

Full Text Available Data indicate endothelium-dependent dilation (EDD may be preserved in the skeletal muscle microcirculation of young, obese adults. Preserved EDD might be mediated by compensatory mechanisms, impeding insight into preclinical vascular dysfunction. We aimed to determine the functional roles of nitric oxide synthase (NOS and cyclooxygenase (COX toward EDD in younger obese adults. We first hypothesized EDD would be preserved in young, obese adults. Further, we hypothesized a reduced contribution of NOS in young, obese adults would be replaced by increased COX signaling. Microvascular EDD was assessed with Doppler ultrasound and brachial artery infusion of acetylcholine (ACh in younger (27±1 yr obese (n=29 and lean (n=46 humans. Individual and combined contributions of NOS and COX were examined with intra-arterial infusions of L-NMMA and ketorolac, respectively. Vasodilation was quantified as an increase in forearm vascular conductance (ΔFVC. Arterial endothelial cell biopsies were analyzed for protein expression of endothelial nitric oxide synthase (eNOS. ΔFVC to ACh was similar between groups. After L-NMMA, ΔFVC to ACh was greater in obese adults (p<0.05. There were no group differences in ΔFVC to ACh with ketorolac. With combined NOS-COX inhibition, ΔFVC was greater in obese adults at the intermediate dose of ACh. Surprisingly, arterial endothelial cell eNOS and phosphorylated eNOS were similar between groups. Younger obese adults exhibit preserved EDD and eNOS expression despite functional dissociation of NOS-mediated vasodilation and similar COX signaling. Compensatory NOS- and COX-independent vasodilatory mechanisms conceal reduced NOS contributions in otherwise healthy obese adults early in life, which may contribute to vascular dysfunction.

Organic mononitrites of 1,2-propanediol act as an effective NO-releasing vasodilator in pulmonary hypertension and exhibit no cross-tolerance with nitroglycerin in anesthetized pigs

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Nilsson KF

2018-03-01

pressures and resistances, but only PDNO reduced the ratio between pulmonary and systemic vascular resistances significantly. After the 5 h GTN infusion, the hemodynamic response to GTN infusions (n=6 was significantly suppressed, whereas PDNO (n=6 produced similar hemodynamic effects to those observed before the GTN infusion.Conclusion: PDNO is a vasodilator with selectivity for pulmonary circulation exhibiting no cross-tolerance to GTN, but GTN causes non selective vasodilatation with substantial tolerance development in the pulmonary and systemic circulations. Inorganic nitrite has no vasodilatory properties at relevant doses. Keywords: nitrites, nitrates, nitric oxide donors, tachyphylaxis, PDNO

Vascular function in health, hypertension, and diabetes

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Nyberg, Michael Permin; Gliemann, Lasse; Hellsten, Ylva

2015-01-01

muscle, which can affect muscle function. Central aspects in the vascular impairments are alterations in the formation of prostacyclin, the bioavailability of NO and an increased formation of vasoconstrictors and reactive oxygen species (ROS). Regular physical activity effectively improves vascular......, the increase in muscle blood flow required for oxygen supply during exercise is achieved through a substantial increase in vasodilators locally formed in the active muscle tissue that overcome the vasoconstrictor signals. Most of the vasodilator signals are mediated via endothelial cells, which lead...... to the formation of vasodilators such as nitric oxide (NO) and prostacyclin. In essential hypertension and type II diabetes, the endothelial function and regulation of vascular tone is impaired with consequent increases in peripheral vascular resistance and inadequate regulation of oxygen supply to the skeletal...

Differences in finger skin contact cooling response between an arterial occlusion and a vasodilated condition.

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Jay, Ollie; Havenith, George

2006-05-01

To assess the presence and magnitude of the effect of skin blood flow on finger skin cooling on contact with cold objects against the background of circulatory disorder risks in occupational exposures, this study investigates the effect of zero vs. close-to-maximal hand blood flow on short-term (cooling response at a contact pressure that allows capillary perfusion of the distal pulp of the fingertip. Six male volunteers touched a block of aluminium with a finger contact force of 0.5 N at a temperature of -2 degrees C under a vasodilated and an occluded condition. Before both conditions, participants were required to exercise in a hot room for > or = 30 min for cutaneous vasodilation to occur (increase in rectal temperature of 1 degrees C). Under the vasodilated condition, forearm blood flow rate rose as high as 16.8 ml.100 ml(-1).min(-1). Under the occluded condition, the arm was exsanguinated, after which a blood pressure cuff was secured on the wrist inducing arterial occlusion. Contact temperature of the finger pad during the subsequent cold contact exposure was measured. No significant difference was found between the starting skin temperatures for the two blood flow conditions, but a distinct difference in shape of the contact cooling curve was apparent between the two blood flow conditions, with Newtonian cooling observed under the occluded condition, whereas a rewarming of the finger skin toward the end of the exposure occurred for the vasodilated condition. Blood flow was found to significantly increase contact temperature from 40 s onward (P cooling during a vasodilated state.

Activation of endothelial nitric oxide synthase by dietary isoflavones: role of NO in Nrf2-mediated antioxidant gene expression.

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Mann, Giovanni E; Rowlands, David J; Li, Francois Y L; de Winter, Patricia; Siow, Richard C M

2007-07-15

The endothelium plays a key role in the maintenance of vascular homeostasis, and increased oxidative stress in vascular disease leads to reduced nitric oxide bioavailability and impaired endothelium-dependent relaxation of resistance vessels. Although epidemiological evidence suggests that diets containing high amounts of natural antioxidants afford protection against coronary heart disease (CHD), antioxidant supplementation trials have largely reported only marginal health benefits. There is controversy concerning the cardiovascular benefits of prolonged estrogen/progestin or soy isoflavone therapy for postmenopausal women and patients with an increased risk of CHD. Research on the potential health benefits of soy isoflavones and other polyphenols contained in red wine, green and black tea and dark chocolate developed rapidly during the 1990's, and recent clinical trials and studies in animal models and cultured endothelial cells provide important and novel insights into the mechanisms by which dietary polyphenols afford protection against oxidative stress. In this review, we highlight that NO and reactive oxygen radicals may mediate dietary polyphenol induced activation of Nrf2, which in turn triggers antioxidant response element (ARE) driven transcription of phase II detoxifying and antioxidant defense enzymes in vascular cells.

Nitric oxide synthase inhibition and cerebrovascular regulation

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Iadecola, C; Pelligrino, D A; Moskowitz, M A

1994-01-01

tone and may play an important role in selected vasodilator responses of the cerebral circulation. Furthermore, evidence has been presented suggesting that NO participates in the mechanisms of cerebral ischemic damage. Despite the widespread attention that NO has captured in recent years and the large......There is increasing evidence that nitric oxide (NO) is an important molecular messenger involved in a wide variety of biological processes. Recent data suggest that NO is also involved in the regulation of the cerebral circulation. Thus, NO participants in the maintenance of resting cerebrovascular...

Vasomotor Regulation of Coronary Microcirculation by Oxidative Stress: Role of Arginase

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Lih eKuo

2013-08-01

Full Text Available Overproduction of reactive oxygen species, i.e., oxidative stress, is associated with the activation of redox signaling pathways linking to inflammatory insults and cardiovascular diseases by impairing endothelial function and consequently blood flow dysregulation due to microvascular dysfunction. This review focuses on the regulation of vasomotor function in the coronary microcirculation by endothelial nitric oxide (NO during oxidative stress and inflammation related to the activation of L-arginine consuming enzyme arginase. Superoxide produced in the vascular wall compromises vasomotor function by not only scavenging endothelium-derived NO but also inhibiting prostacyclin synthesis due to formation of peroxynitrite. The upregulation of arginase contributes to the deficiency of endothelial NO and microvascular dysfunction in various vascular diseases by initiating or following oxidative stress and inflammation. Hydrogen peroxide, a diffusible and stable oxidizing agent, exerts vasodilator function and plays important roles in the physiological regulation of coronary blood flow. In occlusive coronary ischemia, the release of hydrogen peroxide from the microvasculature helps to restore vasomotor function of coronary collateral microvessels with exercise training. However, excessive production and prolonged exposure of microvessels to hydrogen peroxide impairs NO-mediated endothelial function by reducing L-arginine availability through hydroxyl radical-dependent upregulation of arginase. The redox signaling can be a double-edged sword in the microcirculation, which helps tissue survival in one way by improving vasomotor regulation and elicits oxidative stress and tissue injury in the other way by causing vascular dysfunction. The impact of vascular arginase on the development of vasomotor dysfunction associated with angiotensin II receptor activation, hypertension, ischemia-reperfusion, hypercholesterolemia and inflammatory insults is discussed.

Vasodilator stress impairs the left ventricular function obtained with gated single-photon emission computed tomography in patients with known or suspected coronary artery disease

International Nuclear Information System (INIS)

Odagiri, Keiichi; Uehara, Akihiko; Kurata, Chinori

2010-01-01

Transient ischemic dilatation (TID) and post-stress dysfunction of the left ventricle (LV) are important markers of severe coronary artery disease (CAD). To clarify the effects of stressor type on TID and post-stress LV dysfunction, changes in LV measurements were compared between patients with exercise- or vasodilator-induced stress. The 689 patients referred for technetium-99m tetrofosmin myocardial perfusion imaging were included. Patients were stressed with either a vasodilator (n=236) or exercise (n=453). LV measurements were obtained with electrocardiogram (ECG)-gated single photon emission computed tomography (SPECT). LV end-diastolic and end-systolic volume indexes (LVEDVI, LVESVI) increased and LV ejection fraction (LVEF) decreased after stress in the vasodilator-stress group. Vasodilator-stress and the summed difference score (SDS) were independent variables that decreased LVEF after stress. Even in patients without reversible defects, vasodilator-stress impaired LV function. There were no differences in the stress-to-rest ratios of LVEDVI (rEDV) and LVESVI (rESV) among patients with normal myocardial perfusion, fixed defects and reversible defects in the vasodilator-stress group, whereas in the exercise-stress group, rESV was significantly higher in the patients with reversible defects than in those without reversible defects. Within the vasodilator-stress group, neither rEDV nor rESV correlated with the SDS. Vasodilator-stress by itself decreases LVEF after stress. TID should be carefully interpreted when vasodilator-stress is used to detect severe CAD. (author)

Bradykinin or acetylcholine as vasodilators to test endothelial venous function in healthy subjects

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Eneida R. Rabelo

2008-01-01

Full Text Available INTRODUCTION: The evaluation of endothelial function has been performed in the arterial bed, but recently evaluation within the venous system has also been explored. Endothelial function studies employ different drugs that act as endothelium-dependent vasodilatory response inductors. OBJECTIVES: The aim of this study is to compare the endothelium-dependent venous vasodilator response mediated by either acetylcholine or bradykinin in healthy volunteers. METHODS AND RESULTS: Changes in vein diameter after phenylephrine-induced venoconstriction were measured to compare venodilation induced by acetylcholine or bradykinin (linear variable differential transformer dorsal hand vein technique. We studied 23 healthy volunteers; 31% were male, and the subject had a mean age of 33 ± 8 years and a mean body mass index of 23 ± 2 kg/m². The maximum endothelium-dependent venodilation was similar for both drugs (p = 0.13, as well as the mean responses for each dose of both drugs (r = 0.96. The maximum responses to acetylcholine and bradykinin also had good agreement. CONCLUSION: There were no differences between acetylcholine and bradykinin as venodilators in this endothelial venous function investigation.

Combination of nitric oxide therapy, anti-oxidative therapy, low level laser therapy, plasma rich platelet therapy and stem cell therapy as a novel therapeutic application to manage the pain and treat many clinical conditions

Science.gov (United States)

Halasa, Salaheldin; Dickinson, Eva

2014-02-01

From hypertension to diabetes, cancer to HIV, stroke to memory loss and learning disorders to septic shock, male impotence to tuberculosis, there is probably no pathological condition where nitric oxide does not play an important role. Nitric oxide is an analgesic, immune-modulator, vasodilator, anti-apoptotic, growth modulator, angiogenetic, anti-thrombotic, anti-inflammatory and neuro-modulator. Because of the above actions of nitric oxide, many clinical conditions associated with abnormal Nitric oxide (NO) production and bioavailability. Our novel therapeutic approach is to restore the homeostasis of nitric oxide and replace the lost cells by combining nitric oxide therapy, anti-oxidative therapy, low level laser therapy, plasma rich platelet therapy and stem cell therapy.

Chronic hindlimb ischemia impairs functional vasodilation and vascular reactivity in mouse feed arteries

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Trevor R Cardinal

2011-12-01

Full Text Available Vasodilation of lower leg arterioles is impaired in animal models of chronic peripheral ischemia. In addition to arterioles, feed arteries are a critical component of the vascular resistance network, accounting for as much as 50% of the pressure drop across the arterial circulation. Despite the critical importance of feed arteries in blood flow control, the impact of ischemia on feed artery vascular reactivity is unknown. At 14 days following unilateral resection of the femoral-saphenous artery-vein pair, functional vasodilation of the profunda femoris artery was severely impaired, 11 ± 9% versus 152 ± 22%. Although endothelial and smooth muscle-dependent vasodilation were both impaired in ischemic arteries compared to control arteries (Ach: 40 ± 14% vs 81 ± 11%, SNP: 43 ± 12% vs and 85 ± 11%, the responses to acetylcholine and sodium nitroprusside were similar, implicating impaired smooth muscle-dependent vasodilation. Conversely, vasoconstriction responses to norepinephrine were not different between ischemic and control arteries, -68 ± 3% versus -66 ± 3%, indicating that smooth muscle cells were functional following the ischemic insult. Finally, maximal dilation responses to acetylcholine, in vitro, were significantly impaired in the ischemic artery compared to control, 71 ± 9% versus 97 ± 2%, despite a similar generation of myogenic tone to the same intravascular pressure (80 mmHg. These data indicate that ischemia impairs feed artery vasodilation by impairing the vascular wall’s responsiveness to vasodilating stimuli. Future studies to examine the mechanistic basis for these observations or treatment strategies to improve feed artery vasodilation following ischemia could provide the foundation for an alternative therapeutic paradigm for peripheral arterial occlusive disease.

Arginase strongly impairs neuronal nitric oxide-mediated airway smooth muscle relaxation in allergic asthma

NARCIS (Netherlands)

Maarsingh, H; Leusink, J; Bos, I Sophie T; Zaagsma, J; Meurs, H

2006-01-01

Background: Using guinea pig tracheal preparations, we have recently shown that endogenous arginase activity attenuates inhibitory nonadrenergic noncholinergic (iNANC) nerve-mediated airway smooth muscle relaxation by reducing nitric oxide (NO) production - due to competition with neuronal

Endothelial CaMKII as a regulator of eNOS activity and NO-mediated vasoreactivity.

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Shubha Murthy

Full Text Available The multifunctional Ca2+/calmodulin-dependent protein kinase II (CaMKII is a serine/threonine kinase important in transducing intracellular Ca2+ signals. While in vitro data regarding the role of CaMKII in the regulation of endothelial nitric oxide synthase (eNOS are contradictory, its role in endothelial function in vivo remains unknown. Using two novel transgenic models to express CaMKII inhibitor peptides selectively in endothelium, we examined the effect of CaMKII on eNOS activation, NO production, vasomotor tone and blood pressure. Under baseline conditions, CaMKII activation was low in the aortic wall. Consistently, systolic and diastolic blood pressure, heart rate and plasma NO levels were unaltered by endothelial CaMKII inhibition. Moreover, endothelial CaMKII inhibition had no significant effect on NO-dependent vasodilation. These results were confirmed in studies of aortic rings transduced with adenovirus expressing a CaMKII inhibitor peptide. In cultured endothelial cells, bradykinin treatment produced the anticipated rapid influx of Ca2+ and transient CaMKII and eNOS activation, whereas CaMKII inhibition blocked eNOS phosphorylation on Ser-1179 and dephosphorylation at Thr-497. Ca2+/CaM binding to eNOS and resultant NO production in vitro were decreased under CaMKII inhibition. Our results demonstrate that CaMKII plays an important role in transient bradykinin-driven eNOS activation in vitro, but does not regulate NO production, vasorelaxation or blood pressure in vivo under baseline conditions.

Involvement of the nitric oxide in melatonin-mediated protection against injury.

Science.gov (United States)

Fan, Wenguo; He, Yifan; Guan, Xiaoyan; Gu, Wenzhen; Wu, Zhi; Zhu, Xiao; Huang, Fang; He, Hongwen

2018-05-01

Melatonin is a hormone mainly synthesized by the pineal gland in vertebrates and known well as an endogenous regulator of circadian and seasonal rhythms. It has been demonstrated that melatonin is involved in many physiological and pathophysiological processes showing antioxidant, anti-apoptotic and anti-inflammatory properties. Nitric oxide (NO) is a free radical gas in the biological system, which is produced by nitric oxide synthase (NOS) family. NO acts as a biological mediator and plays important roles in different systems in humans. The NO/NOS system exerts a broad spectrum of signaling functions. Accumulating evidence has clearly revealed that melatonin regulates NO/NOS system through multiple mechanisms that may influence physiological and pathophysiological processes. This article reviews the latest evidence for the effects of melatonin on NO/NOS regulation in different organs and disease conditions, the potential cellular mechanisms by which melatonin is involved in organ protection are discussed. Copyright © 2018 Elsevier Inc. All rights reserved.

Ferroxidase-Mediated Iron Oxide Biomineralization

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Zeth, Kornelius; Hoiczyk, Egbert; Okuda, Mitsuhiro

2016-01-01

Iron oxide biomineralization occurs in all living organisms and typically involves protein compartments ranging from 5 to 100nm in size. The smallest iron-oxo particles are formed inside dodecameric Dps protein cages, while the structurally related ferritin compartments consist of twice as many......, translocation, oxidation, nucleation, and storage, that are mediated by ferroxidase centers. Thus, compartmentalized iron oxide biomineralization yields uniform nanoparticles strictly determined by the sizes of the compartments, allowing customization for highly diverse nanotechnological applications....... identical protein subunits. The largest known compartments are encapsulins, icosahedra made of up to 180 protein subunits that harbor additional ferritin-like proteins in their interior. The formation of iron-oxo particles in all these compartments requires a series of steps including recruitment of iron...

Efferent pathways in sodium overload-induced renal vasodilation in rats.

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Nathalia O Amaral

Full Text Available Hypernatremia stimulates the secretion of oxytocin (OT, but the physiological role of OT remains unclear. The present study sought to determine the involvement of OT and renal nerves in the renal responses to an intravenous infusion of hypertonic saline. Male Wistar rats (280-350 g were anesthetized with sodium thiopental (40 mg. kg(-1, i.v.. A bladder cannula was implanted for collection of urine. Animals were also instrumented for measurement of mean arterial pressure (MAP and renal blood flow (RBF. Renal vascular conductance (RVC was calculated as the ratio of RBF by MAP. In anesthetized rats (n = 6, OT infusion (0.03 µg • kg(-1, i.v. induced renal vasodilation. Consistent with this result, ex vivo experiments demonstrated that OT caused renal artery relaxation. Blockade of OT receptors (OXTR reduced these responses to OT, indicating a direct effect of this peptide on OXTR on this artery. Hypertonic saline (3 M NaCl, 1.8 ml • kg(-1 b.wt., i.v. was infused over 60 s. In sham rats (n = 6, hypertonic saline induced renal vasodilation. The OXTR antagonist (AT; atosiban, 40 µg • kg(-1 • h(-1, i.v.; n = 7 and renal denervation (RX reduced the renal vasodilation induced by hypernatremia. The combination of atosiban and renal denervation (RX+AT; n = 7 completely abolished the renal vasodilation induced by sodium overload. Intact rats excreted 51% of the injected sodium within 90 min. Natriuresis was slightly blunted by atosiban and renal denervation (42% and 39% of load, respectively, whereas atosiban with renal denervation reduced sodium excretion to 16% of the load. These results suggest that OT and renal nerves are involved in renal vasodilation and natriuresis induced by acute plasma hypernatremia.

Protease activated receptors (PARS) mediation in gyroxin biological activity

International Nuclear Information System (INIS)

Silva, Jose Alberto Alves da

2009-01-01

Gyroxin is a serine protease enzyme from the South American rattlesnake (Crotalus durissus terrificus) venom; it is only partially characterized and has multiple activities. Gyroxin induces blood coagulation, blood pressure decrease and a neurotoxic behavior named barrel rotation. The mechanisms involved in this neurotoxic activity are not known. Whereas gyroxin is a member of enzymes with high potential to become a new drug with clinical applications such as thrombin, batroxobin, ancrod, tripsyn and kalicrein, it is important to find out how gyroxin works. The analysis on agarose gel electrophoresis and circular dichroism confirmed the molecules' integrity and purity. The gyroxin intravenous administration in mice proved its neurotoxicity (barrel rotation). In vivo studies employing intravital microscopy proved that gyroxin induces vasodilation with the participation of protease activated receptors (PARs), nitric oxide and Na+K+ATPase. The leukocytes' adherence and rolling counting indicated that gyroxin has no pro inflammatory activity. Gyroxin induced platelet aggregation, which was blocked by inhibitors of PAR1 and PAR4 receptors (SCH 79797 and tcY-NH 2 , respectively). Finally, it was proved that the gyroxin temporarily alter the permeability of the blood brain barrier (BBB). Our study has shown that both the protease-activated receptors and nitric oxide are mediators involved in the biological activities of gyroxin. (author)

EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of a health claim related to cocoa flavanols and maintenance of normal endothelium-dependent vasodilation pursuant to Article 13(5) of Regulation (EC) No 1924/2006

DEFF Research Database (Denmark)

Tetens, Inge

Following an application from Barry Callebaut Belgium nv, submitted pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Belgium, the Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scientific substantiation...... of a health claim related to cocoa flavanols and maintenance of normal endothelium-dependent vasodilation. Cocoa flavanols are sufficiently characterised. The claimed effect is “help maintain endothelium-dependent vasodilation which contributes to healthy blood flow”. The target population proposed...... by the applicant is the general healthy adult population. The Panel considers that maintenance of normal endothelium-dependent vasodilation is a beneficial physiological effect. In weighing the evidence, the Panel took into account that cocoa flavanols consumed for 12 weeks have been shown to increase fasting ED...

Beneficial Effects of Apelin on Vascular Function in Patients With Central Obesity.

Science.gov (United States)

Schinzari, Francesca; Veneziani, Augusto; Mores, Nadia; Barini, Angela; Di Daniele, Nicola; Cardillo, Carmine; Tesauro, Manfredi

2017-05-01

Patients with central obesity have impaired insulin-stimulated vasodilation and increased ET-1 (endothelin 1) vasoconstriction, which may contribute to insulin resistance and vascular damage. Apelin enhances insulin sensitivity and glucose disposal but also acts as a nitric oxide (NO)-dependent vasodilator and a counter-regulator of AT 1 (angiotensin [Ang] II type 1) receptor-induced vasoconstriction. We, therefore, examined the effects of exogenous (Pyr 1 )apelin on NO-mediated vasodilation and Ang II- or ET-1-dependent vasoconstrictor tone in obese patients. In the absence of hyperinsulinemia, forearm blood flow responses to graded doses of acetylcholine and sodium nitroprusside were not different during saline or apelin administration (both P >0.05). During intra-arterial infusion of regular insulin, however, apelin enhanced the vasodilation induced by both acetylcholine and nitroprusside (both P 0.05). In conclusion, in patients with central obesity, apelin has favorable effects not only to improve insulin-stimulated endothelium-dependent and endothelium-independent vasodilator responses but also to blunt Ang II- and ET-1-dependent vasoconstriction by a mechanism not involving NO. Taken together, our results suggest that targeting the apelin system might favorably impact some hemodynamic abnormalities of insulin-resistant states like obesity. © 2017 American Heart Association, Inc.

Effect of skin temperature on cutaneous vasodilator response to the β-adrenergic agonist isoproterenol.

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Hodges, Gary J; Kellogg, Dean L; Johnson, John M

2015-04-01

The vascular response to local skin cooling is dependent in part on a cold-induced translocation of α2C-receptors and an increased α-adrenoreceptor function. To discover whether β-adrenergic function might contribute, we examined whether β-receptor sensitivity to the β-agonist isoproterenol was affected by local skin temperature. In seven healthy volunteers, skin blood flow was measured from the forearm by laser-Doppler flowmetry and blood pressure was measured by finger photoplethysmography. Data were expressed as cutaneous vascular conductance (CVC; laser-Doppler flux/mean arterial blood pressure). Pharmacological agents were administered via intradermal microdialysis. We prepared four skin sites: one site was maintained at a thermoneutral temperature of 34°C (32 ± 10%CVCmax) one site was heated to 39°C (38 ± 11%CVCmax); and two sites were cooled, one to 29°C (22 ± 7%CVCmax) and the other 24°C (16 ± 4%CVCmax). After 20 min at these temperatures to allow stabilization of skin blood flow, isoproterenol was perfused in concentrations of 10, 30, 100, and 300 μM. Each concentration was perfused for 15 min. Relative to the CVC responses to isoproterenol at the thermoneutral skin temperature (34°C) (+21 ± 10%max), low skin temperatures reduced (at 29°C) (+17 ± 6%max) or abolished (at 24°C) (+1 ± 5%max) the vasodilator response, and warm (39°C) skin temperatures enhanced the vasodilator response (+40 ± 9%max) to isoproterenol. These data indicate that β-adrenergic function was influenced by local skin temperature. This finding raises the possibility that a part of the vasoconstrictor response to direct skin cooling could include reduced background β-receptor mediated vasodilation. Copyright © 2015 the American Physiological Society.

Effects of long-term vasodilator therapy in patients with carotid sinus hypersensitivity.

Science.gov (United States)

Brignole, M; Menozzi, C; Gaggioli, G; Musso, G; Foglia-Manzillo, G; Mascioli, G; Fradella, G; Bottoni, N; Mureddu, R

1998-08-01

In patients affected by carotid sinus hypersensitivity, long-term vasodilator therapy might increase the risk of syncopal episodes by reducing systolic blood pressure and venous return to the heart. Thirty-two patients (mean age 73 +/- 9 years; 20 men) who met all the following criteria were included: (1) one or more episodes of syncope occurring during long-term (>6 months) treatment with angiotensin-converting enzyme inhibitors, long-acting nitrates, calcium antagonists, or a combination of these; (2) a positive response to carotid sinus massage, defined as the reproduction of spontaneous syncope in the presence of ventricular asystole > or =3 seconds or a fall in systolic blood pressure > or =50 mm Hg; (3) negative workup for other causes of syncope. The patients were randomly assigned to continue or to discontinue use of vasodilators; carotid sinus massage was repeated 2 weeks after randomization. By the end of the study period, the baseline values of systolic blood pressure were significantly different between the 2 groups of patients both in supine (P=.01) and upright (P=.03) positions. Syncope had been induced by carotid sinus massage in 81% of patients in the "on-vasodilator" group and in 62% of patients in the "off-vasodilator" group (P=.21). The cardioinhibitory reflex was of similar magnitude in the 2 groups, being found in 50% of the patients in each group, with a maximum ventricular pause of 7.1 +/- 2.7 and 6.7 +/- 1.8 seconds, respectively. The percentage decrease of blood pressure did not differ between the 2 groups, even if, in absolute values, the baseline difference of blood pressure roughly persisted for the duration of the test. In consequence of that, the rise of blood pressure to similar values was delayed approximately 30 seconds in the "on-vasodilator" group and took more than 2 minutes to return to baseline values. In patients affected by carotid sinus hypersensitivity, chronic vasodilator therapy does not have a direct effect on carotid

Relative rates of albumin equilibration in the skin interstitium and lymph during vasodilation

International Nuclear Information System (INIS)

Powers, M.R.; Wallace, J.R.; Bell, D.R.

1986-01-01

The initial equilibration of 125 I-labeled albumin between the vascular and extravascular compartments was studied in hindpaw skin of 6 anesthetized rabbits. Papavarine (200 ug/min) was infused into a small branch of the femoral artery of one limb with the contralateral limb as a control. There was a 1.2-fold increase in lymph flow (p 131 I-labeled albumin injected 10 min before ending the experiment. Endogenous albumin was measured in plasma, lymph, and tissue samples using rocket electroimmunoassay. After 3 hrs of tracer infusion, lymph specific activity relative to plasma was significantly greater in the vasodilated hindlimb (0.30 +/- 0.07 vs 0.13 +/- 0.05; mean +/- SE; p < 0.01). Extravascular specific activity relative to plasma was greater in the vasodilated limb (0.13 +/- 0.02 vs 0.09 +/- 0.02; p < 0.05). Thus, vasodilation increased the rates at which lymph and tissue equilibrate with plasma. Also, the difference between lymph and tissue equilibration was greater in the vasodilated hindlimb

Dihydralazine induces marked cerebral vasodilation in man

DEFF Research Database (Denmark)

Schroeder, T; Sillesen, H

1987-01-01

of dihydralazine was of the same order of magnitude as the effect of 5% CO2 inhalation. These results in normal subjects should be extrapolated to diseased persons only with extreme caution. Still, the very marked and long lasting vasodilation observed suggests that dihydralazine, from a theoretical point of view.......v. xenon-133 technique in seven young, normotensive volunteers before and 15, 60 and 180 min after 6.25 mg i.v. dihydralazine, corresponding approximately to 0.1 mg kg-1 body weight. For comparison the CBF reactivity to inhalation of 5% CO2 in air was investigated. Dihydralazine increased CBF throughout...... the period of study, in median 16, 27 and 23% at the three periods of measurements, respectively. The arterial blood pressure remained unchanged, whereas heart rate increased significantly. During CO2 inhalation, CBF increased on average 29%. Thus, the cerebral vasodilation exerted by a small i.v. dose...

Nutritionally Mediated Oxidative Stress and Inflammation

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Alexandra Muñoz

2013-01-01

Full Text Available There are many sources of nutritionally mediated oxidative stress that trigger inflammatory cascades along short and long time frames. These events are primarily mediated via NFκB. On the short-term scale postprandial inflammation is characterized by an increase in circulating levels of IL-6 and TNF-α and is mirrored on the long-term by proinflammatory gene expression changes in the adipocytes and peripheral blood mononuclear cells (PBMCs of obese individuals. Specifically the upregulation of CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β, CXCL2/MIP-2α, and CXCL3/MIP-2β is noted because these changes have been observed in both adipocytes and PBMC of obese humans. In comparing numerous human intervention studies it is clear that pro-inflammatory and anti-inflammatory consumption choices mediate gene expression in humans adipocytes and peripheral blood mononuclear cells. Arachidonic acid and saturated fatty acids (SFAs both demonstrate an ability to increase pro-inflammatory IL-8 along with numerous other inflammatory factors including IL-6, TNFα, IL-1β, and CXCL1 for arachidonic acid and IGB2 and CTSS for SFA. Antioxidant rich foods including olive oil, fruits, and vegetables all demonstrate an ability to lower levels of IL-6 in PBMCs. Thus, dietary choices play a complex role in the mediation of unavoidable oxidative stress and can serve to exacerbate or dampen the level of inflammation.

Arginase up-regulation and eNOS uncoupling contribute to impaired endothelium-dependent vasodilation in a rat model of intrauterine growth restriction.

Science.gov (United States)

Grandvuillemin, Isabelle; Buffat, Christophe; Boubred, Farid; Lamy, Edouard; Fromonot, Julien; Charpiot, Philippe; Simoncini, Stephanie; Sabatier, Florence; Dignat-George, Françoise; Peyter, Anne-Christine; Simeoni, Umberto; Yzydorczyk, Catherine

2018-05-09

Individuals born after intrauterine growth restriction (IUGR) are at increased risk of developing cardiovascular diseases in adulthood, notably hypertension (HTN). Alterations in the vascular system, particularly impaired endothelium-dependent vasodilation, may play an important role in long-term effects of IUGR. Whether such vascular dysfunction precedes HTN has not been fully established in individuals born after IUGR. Moreover, the intimate mechanisms of altered endothelium-dependent vasodilation remain incompletely elucidated. We therefore investigated, using a rat model of IUGR, whether impaired endothelium-dependent relaxation precedes the development of HTN and whether key components of the L-Arginine-nitric oxide (NO) pathway are involved in its pathogenesis. Pregnant rats were fed with a control (CTRL, 23% casein) or low-protein diet (LP, 9% casein) to induce IUGR. Systolic blood pressure (SBP) was measured by tail-cuff plethysmography in 5- and 8-week-old male offspring. Aortic rings were isolated to investigate relaxation to acetylcholine, NO production, eNOS protein content, arginase activity, and superoxide anion production. SBP was not different at 5 weeks, but significantly increased in 8-week-old LP vs. CRTL offspring. In 5-week-old LP vs. CRTL males, endothelium-dependent vasorelaxation was significantly impaired, but restored by pre-incubation with L-Arginine or the arginase inhibitor BEC; NO production was significantly reduced, but restored by L-Arginine pretreatment; total eNOS protein, dimer/monomer ratio, and arginase activity were significantly increased; superoxide anion production was significantly enhanced, but normalized by pretreatment with the NOS inhibitor L-NNA. In this model, IUGR leads to early-impaired endothelium-dependent vasorelaxation, resulting from arginase up-regulation and eNOS uncoupling, which precedes the development of HTN.

Placental oxidative stress and maternal endothelial function in pregnant women with normotensive fetal growth restriction.

Science.gov (United States)

Yoshida, Atsumi; Watanabe, Kazushi; Iwasaki, Ai; Kimura, Chiharu; Matsushita, Hiroshi; Wakatsuki, Akihiko

2018-04-01

The purpose of this study was to investigate the relationship between placental oxidative stress and maternal endothelial function in pregnant women with normotensive fetal growth restriction (FGR). We examined serum concentrations of oxygen free radicals (d-ROMs), maternal angiogenic factor (PlGF), and sFlt-1, placental oxidative DNA damage, and maternal endothelial function in 17 women with early-onset preeclampsia (PE), 18 with late-onset PE, 14 with normotensive FGR, and 21 controls. Flow-mediated vasodilation (FMD) was assessed as a marker of maternal endothelial function. Immunohistochemical analysis was performed to measure the proportion of placental trophoblast cell nuclei staining positive for 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage. Maternal serum d-ROM, sFlt-1 concentrations, and FMD did not significantly differ between the control and normotensive FGR groups. The proportion of nuclei staining positive for 8-OHdG was significantly higher in the normotensive FGR group relative to the control group. Our findings demonstrate that, despite the presence of placental oxidative DNA damage as observed in PE patients, pregnant women with normotensive FGR show no increase in the concentrations of sFlt-1 and d-ROMs, or a decrease in FMD.

Nanocarriers for Nitric Oxide Delivery

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Juliana Saraiva

2011-01-01

Full Text Available Nitric oxide (NO is a promising pharmaceutical agent that has vasodilative, antibacterial, and tumoricidal effects. To study the complex and wide-ranging roles of NO and to facilitate its therapeutic use, a great number of synthetic compounds (e.g., nitrosothiols, nitrosohydroxyamines, N-diazeniumdiolates, and nitrosyl metal complexes have been developed to chemically stabilize and release NO in a controlled manner. Although NO is currently being exploited in many biomedical applications, its use is limited by several factors, including a short half-life, instability during storage, and potential toxicity. Additionally, efficient methods of both localized and systemic in vivo delivery and dose control are needed. One strategy for addressing these limitations and thus increasing the utility of NO donors is based on nanotechnology.

Syncytiotrophoblast extracellular vesicles impair rat uterine vascular function via the lectin-like oxidized LDL receptor-1.

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Floor Spaans

LOX-1 and reduced nitric oxide mediated vasodilation. Moreover, we postulate that the LOX-1 pathway could be a potential therapeutic target in pathologies associated with vascular dysfunction during pregnancy.

Nonspecific microvascular vasodilation during iontophoresis is attenuated by application of hyperosmolar saline.

Science.gov (United States)

Asberg, A; Holm, T; Vassbotn, T; Andreassen, A K; Hartmann, A

1999-07-01

Iontophoretic administration of acetylcholine chloride (ACh) and sodium nitroprusside (SNP) combined with laser Doppler skin blood perfusion measurements are used for determination of endothelial-dependent and -independent vasodilation. However, the method is biased by nonspecific vasodilation. The primary aim of this study was to investigate if iontophoresis-induced nonspecific vasodilation may be attenuated by addition of high molar concentrations of NaCl to the iontophoresis solutions. Secondary we investigated the applicability of 5 mol/liter NaCl solution as vehicle for ACh and SNP in this method. Skin perfusion changes were determined for iontophoresis of pure vehicles, deionized water and 5 mol/liter NaCl solution, in 12 healthy volunteers. Responses in skin perfusion to iontophoresis of ACh and SNP dissolved in both vehicles were also investigated. Addition of 5 mol/liter NaCl to deionized water significantly attenuated the nonspecific vasodilation and lowered the potential applied over the skin. The inter- and intraindividual coefficients of variation to ACh and SNP responses became, however, higher using hyperosmolar vehicle. During iontophoresis of SNP (in deionized water) we were unable to distinguish between SNP and vehicle effects. This study shows that the nonspecific vasodilation induced by iontophoresis can be attenuated by addition of 5 mol/liter NaCl, possibly due to lower electrical potential over the skin. However, the variability of the method was not improved. When deionized water was used as vehicle the effect of SNP could not be differentiated from that of the vehicle. This was not the case for ACh. Copyright 1999 Academic Press.

Exogenous nitric oxide (NO) generated by NO-plasma treatment modulates osteoprogenitor cells early differentiation

International Nuclear Information System (INIS)

Elsaadany, Mostafa; Subramanian, Gayathri; Ayan, Halim; Yildirim-Ayan, Eda

2015-01-01

In this study, we investigated whether nitric oxide (NO) generated using a non-thermal plasma system can mediate osteoblastic differentiation of osteoprogenitor cells without creating toxicity. Our objective was to create an NO delivery mechanism using NO-dielectric barrier discharge (DBD) plasma that can generate and transport NO with controlled concentration to the area of interest to regulate osteoprogenitor cell activity. We built a non-thermal atmospheric pressure DBD plasma nozzle system based on our previously published design and similar designs in the literature. The electrical and spectral analyses demonstrated that N 2 dissociated into NO under typical DBD voltage–current characteristics. We treated osteoprogenitor cells (MC3T3-E1) using NO-plasma treatment system. Our results demonstrated that we could control NO concentration within cell culture media and could introduce NO into the intracellular space using NO-plasma treatment with various treatment times. We confirmed that NO-plasma treatment maintained cell viability and did not create any toxicity even with prolonged treatment durations. Finally, we demonstrated that NO-plasma treatment induced early osteogenic differentiation in the absence of pro-osteogenic growth factors/proteins. These findings suggest that through the NO-plasma treatment system we are able to generate and transport tissue-specific amounts of NO to an area of interest to mediate osteoprogenitor cell activity without subsequent toxicity. This opens up the possibility to develop DBD plasma-assisted tissue-specific NO delivery strategies for therapeutic intervention in the prevention and treatment of bone diseases. (paper)

Adenosine/nitric oxide crosstalk in the branchial circulation of Squalus acanthias and Anguilla anguilla.

Science.gov (United States)

Pellegrino, D; Tota, B; Randall, D J

2005-10-01

The potent vasomodulator adenosine (AD), thanks to the interaction with by A(1) and A(2) receptors, dilates systemic, coronary and cerebral vasculatures but exert a constrictor action in several vessels of respiratory organs. Recent investigations suggest that nitric oxide (NO) contributes to AD effects. In fish, both NO and AD induce atypical effects compared to mammals. Since there is very little information on the role of NO and its involvement in mediating the actions of AD in fish, we have analysed this question in the branchial vasculature of the elasmobranch Squalus acanthias and the teleost Anguilla anguilla using an isolated perfused head and a branchial basket preparation, respectively. In both dogfish and eel, AD dose-response curves showed a biphasic effect: vasoconstriction (pico to nanomolar range) and vasodilation (micromolar range). Both effects were abolished by the classic xanthine inhibitor theophylline (Theo) and also by specific antagonists of A(1) and A(2) receptor subtypes. To analyse the involvement of the NO/cGMP system in the AD responses, we tested a NOS inhibitor, l-NIO, and a specific soluble guanylate cyclase (sGC) blocker, ODQ. In both dogfish and eel preparations l-NIO abrogated all vasomotor effects of AD, whereas ODQ blocked the AD-mediated vasoconstriction without affecting the vasorelaxant response. This indicates that only AD-induced vasoconstriction is mediated by a NO-cGMP-dependent mechanism. By using the NO donor SIN-1, we showed a dose-dependent vasoconstrictory effect which was completely blocked by ODQ. These results provide compelling evidence that the vasoactive role of AD in the branchial circulation of S. acanthias and A. anguilla involves a NO signalling.

Oxygen mediates vascular smooth muscle relaxation in hypoxia.

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Jessica Dada

Full Text Available The activation of soluble guanylate cyclase (sGC by nitric oxide (NO and other ligands has been extensively investigated for many years. In the present study we considered the effect of molecular oxygen (O2 on sGC both as a direct ligand and its affect on other ligands by measuring cyclic guanosine monophosphate (cGMP production, as an index of activity, as well as investigating smooth muscle relaxation under hypoxic conditions. Our isolated enzyme studies confirm the function of sGC is impaired under hypoxic conditions and produces cGMP in the presence of O2, importantly in the absence of NO. We also show that while O2 could partially affect the magnitude of sGC stimulation by NO when the latter was present in excess, activation by the NO independent, haem-dependent sGC stimulator 3-(5'-hydroxymethyl-2'-furyl-1-benzylindazole (YC-1 was unaffected. Our in vitro investigation of smooth muscle relaxation confirmed that O2 alone in the form of a buffer bolus (equilibrated at 95% O2/5% CO2 had the ability to dilate vessels under hypoxic conditions and that this was dependent upon sGC and independent of eNOS. Our studies confirm that O2 can be a direct and important mediator of vasodilation through an increase in cGMP production. In the wider context, these observations are key to understanding the relative roles of O2 versus NO-induced sGC activation.

Cerium oxide and platinum nanoparticles protect cells from oxidant-mediated apoptosis

International Nuclear Information System (INIS)

Clark, Andrea; Zhu Aiping; Sun Kai; Petty, Howard R.

2011-01-01

Catalytic nanoparticles represent a potential clinical approach to replace or correct aberrant enzymatic activities in patients. Several diseases, including many blinding eye diseases, are promoted by excessive oxidant stress due to reactive oxygen species (ROS). Cerium oxide and platinum nanoparticles represent two potentially therapeutic nanoparticles that de-toxify ROS. In the present study, we directly compare these two classes of catalytic nanoparticles. Cerium oxide and platinum nanoparticles were found to be 16 ± 2.4 and 1.9 ± 0.2 nm in diameter, respectively. Using surface plasmon-enhanced microscopy, we find that these nanoparticles associate with cells. Furthermore, cerium oxide and platinum nanoparticles demonstrated superoxide dismutase catalytic activity, but did not promote hemolytic or cytolytic pathways in living cells. Importantly, both cerium oxide and platinum nanoparticles reduce oxidant-mediated apoptosis in target cells as judged by the activation of caspase 3. The ability to diminish apoptosis may contribute to maintaining healthy tissues.

Nitric oxide-mediated bystander signal transduction induced by heavy-ion microbeam irradiation

Science.gov (United States)

Tomita, Masanori; Matsumoto, Hideki; Funayama, Tomoo; Yokota, Yuichiro; Otsuka, Kensuke; Maeda, Munetoshi; Kobayashi, Yasuhiko

2015-07-01

In general, a radiation-induced bystander response is known to be a cellular response induced in non-irradiated cells after receiving bystander signaling factors released from directly irradiated cells within a cell population. Bystander responses induced by high-linear energy transfer (LET) heavy ions at low fluence are an important health problem for astronauts in space. Bystander responses are mediated via physical cell-cell contact, such as gap-junction intercellular communication (GJIC) and/or diffusive factors released into the medium in cell culture conditions. Nitric oxide (NO) is a well-known major initiator/mediator of intercellular signaling within culture medium during bystander responses. In this study, we investigated the NO-mediated bystander signal transduction induced by high-LET argon (Ar)-ion microbeam irradiation of normal human fibroblasts. Foci formation by DNA double-strand break repair proteins was induced in non-irradiated cells, which were co-cultured with those irradiated by high-LET Ar-ion microbeams in the same culture plate. Foci formation was suppressed significantly by pretreatment with an NO scavenger. Furthermore, NO-mediated reproductive cell death was also induced in bystander cells. Phosphorylation of NF-κB and Akt were induced during NO-mediated bystander signaling in the irradiated and bystander cells. However, the activation of these proteins depended on the incubation time after irradiation. The accumulation of cyclooxygenase-2 (COX-2), a downstream target of NO and NF-κB, was observed in the bystander cells 6 h after irradiation but not in the directly irradiated cells. Our findings suggest that Akt- and NF-κB-dependent signaling pathways involving COX-2 play important roles in NO-mediated high-LET heavy-ion-induced bystander responses. In addition, COX-2 may be used as a molecular marker of high-LET heavy-ion-induced bystander cells to distinguish them from directly irradiated cells, although this may depend on the time

Effects of sapropterin on endothelium-dependent vasodilation in patients with CADASIL: a randomized controlled trial.

Science.gov (United States)

De Maria, Renata; Campolo, Jonica; Frontali, Marina; Taroni, Franco; Federico, Antonio; Inzitari, Domenico; Tavani, Alessandra; Romano, Silvia; Puca, Emanuele; Orzi, Francesco; Francia, Ada; Mariotti, Caterina; Tomasello, Chiara; Dotti, Maria Teresa; Stromillo, Maria Laura; Pantoni, Leonardo; Pescini, Francesca; Valenti, Raffaella; Pelucchi, Claudio; Parolini, Marina; Parodi, Oberdan

2014-10-01

Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a rare autosomal dominant disorder caused by NOTCH3 mutations, is characterized by vascular smooth muscle and endothelial cells abnormalities, altered vasoreactivity, and recurrent lacunar infarcts. Vasomotor function may represent a key factor for disease progression. Tetrahydrobiopterin, essential cofactor for nitric oxide synthesis in endothelial cells, ameliorates endothelial function. We assessed whether supplementation with sapropterin, a synthetic tetrahydrobiopterin analog, improves endothelium-dependent vasodilation in CADASIL patients. In a 24-month, multicenter randomized, double-blind, placebo-controlled trial, CADASIL patients aged 30 to 65 years were randomly assigned to receive placebo or sapropterin 200 to 400 mg BID. The primary end point was change in the reactive hyperemia index by peripheral arterial tonometry at 24 months. We also assessed the safety and tolerability of sapropterin. Analysis was done by intention-to-treat. The intention-to-treat population included 61 patients. We found no significant difference between sapropterin (n=32) and placebo (n=29) in the primary end point (mean difference in reactive hyperemia index by peripheral arterial tonometry changes 0.19 [95% confidence interval, -0.18, 0.56]). Reactive hyperemia index by peripheral arterial tonometry increased after 24 months in 37% of patients on sapropterin and in 28% on placebo; however, after adjustment for age, sex, and clinical characteristics, improvement was not associated with treatment arm. The proportion of patients with adverse events was similar on sapropterin and on placebo (50% versus 48.3%); serious adverse events occurred in 6.3% versus 13.8%, respectively. Sapropterin was safe and well-tolerated at the average dose of 5 mg/kg/day, but did not affect endothelium-dependent vasodilation in CADASIL patients. https://www.clinicaltrialsregister.eu. Unique

Calcium-mediated signaling and calmodulin-dependent kinase regulate hepatocyte-inducible nitric oxide synthase expression.

Science.gov (United States)

Zhang, Baochun; Crankshaw, Will; Nesemeier, Ryan; Patel, Jay; Nweze, Ikenna; Lakshmanan, Jaganathan; Harbrecht, Brian G

2015-02-01

Induced nitric oxide synthase (iNOS) is induced in hepatocytes by shock and inflammatory stimuli. Excessive NO from iNOS mediates shock-induced hepatic injury and death, so understanding the regulation of iNOS will help elucidate the pathophysiology of septic shock. In vitro, cytokines induce iNOS expression through activation of signaling pathways including mitogen-activated protein kinases and nuclear factor κB. Cytokines also induce calcium (Ca(2+)) mobilization and activate calcium-mediated intracellular signaling pathways, typically through activation of calmodulin-dependent kinases (CaMK). Calcium regulates NO production in macrophages but the role of calcium and calcium-mediated signaling in hepatocyte iNOS expression has not been defined. Primary rat hepatocytes were isolated, cultured, and induced to produce NO with proinflammatory cytokines. Calcium mobilization and Ca(2+)-mediated signaling were altered with ionophore, Ca(2+) channel blockers, and inhibitors of CaMK. The Ca(2+) ionophore A23187 suppressed cytokine-stimulated NO production, whereas Ethylene glycol tetraacetic acid and nifedipine increased NO production, iNOS messenger RNA, and iNOS protein expression. Inhibition of CaMK with KN93 and CBD increased NO production but the calcineurin inhibitor FK 506 decreased iNOS expression. These data demonstrate that calcium-mediated signaling regulates hepatocyte iNOS expression and does so through a mechanism independent of calcineurin. Changes in intracellular calcium levels may regulate iNOS expression during hepatic inflammation induced by proinflammatory cytokines. Copyright © 2015 Elsevier Inc. All rights reserved.

Epoetin beta pegol ameliorates flow-mediated dilation with improving endothelial nitric oxide synthase coupling state in nonobese diabetic rats.

Science.gov (United States)

Serizawa, Kenichi; Yogo, Kenji; Tashiro, Yoshihito; Kawasaki, Ryohei; Endo, Koichi; Shimonaka, Yasushi; Hirata, Michinori

2017-04-01

Patients with diabetic nephropathy have a high cardiovascular mortality. Epoetin beta pegol (continuous erythropoietin receptor activator, C.E.R.A.) is a drug for the treatment of renal anemia. In this study, we investigated the effect of C.E.R.A. on vascular endothelial function as evaluated by flow-mediated dilation (FMD) and the relationship between hematopoiesis and FMD in diabetic nephropathy rats. Male Spontaneously Diabetic Torii rats (SDT, 22 weeks old) were used. C.E.R.A. (0.6, 1.2 μg/kg) was administered subcutaneously once every 2 weeks for 8 weeks. At 1 week after last administration (31 weeks old), we assessed FMD in the femoral arteries of anesthetized rats using a high-resolution ultrasound system. FMD was also measured 1 week after single C.E.R.A. treatment (5.0 μg/kg) to examine the influence of hematopoiesis. Flow-mediated dilation was significantly decreased in SDT rats before the start of C.E.R.A. treatment (22 weeks old). Repeated administration of C.E.R.A. dose-dependently improved FMD in SDT rats (31 weeks old) without changing blood glucose, nitroglycerin-induced vasodilation, or kidney function. Long-term administration of C.E.R.A. improved the state of endothelial nitric oxide synthase uncoupling in the femoral arteries of SDT rats, which showed a positive correlation with FMD. On the other hand, there was no correlation between FMD and Hb or Hct in SDT rats. Furthermore, at 1 week after single administration of C.E.R.A., FMD was not significantly improved although hemoglobin levels were comparable with levels following long-term C.E.R.A. Long-term treatment with C.E.R.A. improved FMD in SDT rats even after onset of endothelial dysfunction. © 2017 The Authors. Cardiovascular Therapeutics Published by John Wiley & Sons Ltd.

Peroxometal-mediated oxidation of bromine leading to ...

Indian Academy of Sciences (India)

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Peroxometal-mediated oxidation of bromine leading to environmentally favourable protocol for selective bromination of organic substrates: Implications for vanadium bromo peroxidase (VBrPO). SIDDHARTHA D DHAR and MIHIR K CHAUDHURI. Department of Chemistry, Indian Institute of Technology,. Guwahati 781 001 ...

Cleavage of olefinic double bonds by mediated anodic oxidation

International Nuclear Information System (INIS)

Baeumer, U.-St.; Schaefer, H.J.

2003-01-01

Seven alkenes, e.g. 1-decene, methyl oleate, cyclododecene, norbornene, are cleaved by indirect anodic oxidation with IO 4 - /RuCl 3 as mediator to carboxylic acids. The best performance was achieved with two alternative ex cell-methods. Periodate is regenerated from iodate in a divided cell at a PbO 2 /Ti-anode. In the chemical reactor alkene and the produced carboxylic acid are immobilized in a chromatography column on Chromosorb W and oxidized with IO 4 - /RuO 4 in CH 3 CN/water. In the alternative version the alkene is oxidized in an emulsion generated by sonication and the organic phase is retained in the reactor by a separator. Acids and diacids are obtained in 61-91% chemical yield and good current yields. The amount of consumed periodate can be reduced to less than 5% of the amount needed for the chemical oxidation. The mediated anodic cleavage of alkenes is altogether an interesting alternative to ozonolysis

Skeletal muscle beta-receptors and isoproterenol-stimulated vasodilation in canine heart failure

International Nuclear Information System (INIS)

Frey, M.J.; Lanoce, V.; Molinoff, P.B.; Wilson, J.R.

1989-01-01

To investigate whether heart failure alters beta-adrenergic receptors on skeletal muscle and its associated vasculature, the density of beta-adrenergic receptors, isoproterenol-stimulated adenylate cyclase activity, and coupling of the guanine nucleotide-binding regulatory protein were compared in 18 control dogs and 16 dogs with heart failure induced by 5-8 wk of ventricular pacing at 260 beats/min. Hindlimb vascular responses to isoproterenol were compared in eight controls and eight of the dogs with heart failure. In dogs with heart failure, the density of beta-receptors on skeletal muscle was reduced in both gastrocnemius (control: 50 +/- 5; heart failure: 33 +/- 8 fmol/mg of protein) and semitendinosus muscle (control: 43 +/- 9; heart failure: 27 +/- 9 fmol/mg of protein, both P less than 0.05). Receptor coupling to the ternary complex, as determined by isoproterenol competition curves with and without guanosine 5'-triphosphate (GTP), was unchanged. Isoproterenol-stimulated adenylate cyclase activity was significantly decreased in semitendinosus muscle (control: 52.4 +/- 4.6; heart failure: 36.5 +/- 9.5 pmol.mg-1.min-1; P less than 0.05) and tended to be decreased in gastrocnemius muscle (control: 40.1 +/- 8.5; heart failure: 33.5 +/- 4.5 pmol.mg-1.min-1; P = NS). Isoproterenol-induced hindlimb vasodilation was not significantly different in controls and in dogs with heart failure. These findings suggest that heart failure causes downregulation of skeletal muscle beta-adrenergic receptors, probably due to receptor exposure to elevated catecholamine levels, but does not reduce beta-receptor-mediated vasodilation in muscle

The Deletion of Endothelial Sodium Channel α (αENaC Impairs Endothelium-Dependent Vasodilation and Endothelial Barrier Integrity in Endotoxemia in Vivo

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Magdalena Sternak

2018-04-01

Full Text Available The role of epithelial sodium channel (ENaC activity in the regulation of endothelial function is not clear. Here, we analyze the role of ENaC in the regulation of endothelium-dependent vasodilation and endothelial permeability in vivo in mice with conditional αENaC subunit gene inactivation in the endothelium (endo-αENaCKO mice using unique MRI-based analysis of acetylcholine-, flow-mediated dilation and vascular permeability. Mice were challenged or not with lipopolysaccharide (LPS, from Salmonella typhosa, 10 mg/kg, i.p.. In addition, changes in vascular permeability in ex vivo organs were analyzed by Evans Blue assay, while changes in vascular permeability in perfused mesenteric artery were determined by a FITC-dextran-based assay. In basal conditions, Ach-induced response was completely lost, flow-induced vasodilation was inhibited approximately by half but endothelial permeability was not changed in endo-αENaCKO vs. control mice. In LPS-treated mice, both Ach- and flow-induced vasodilation was more severely impaired in endo-αENaCKO vs. control mice. There was also a dramatic increase in permeability in lungs, brain and isolated vessels as evidenced by in vivo and ex vivo analysis in endotoxemic endo-αENaCKO vs. control mice. The impaired endothelial function in endotoxemia in endo-αENaCKO was associated with a decrease of lectin and CD31 endothelial staining in the lung as compared with control mice. In conclusion, the activity of endothelial ENaC in vivo contributes to endothelial-dependent vasodilation in the physiological conditions and the preservation of endothelial barrier integrity in endotoxemia.

The mechanism of mediated oxidation of carboxylates with ferrocene as redox catalyst in absence of grafting effects. An experimental and theoretical approach

International Nuclear Information System (INIS)

Hernández-Muñoz, Lindsay S.; Galano, Annia; Astudillo-Sánchez, Pablo D.; Abu-Omar, Mahdi M.; González, Felipe J.

2014-01-01

Graphical abstract: - Highlights: • The mechanism of mediated oxidation of carboxylates. • Thermodynamics of the mediated Kolbe and Non-Kolbe mechanisms. • The oxidation of acetate and diphenylacetate ions by using ferrocene as redox catalyst. • Simulation and DFT calculations of the mediated oxidation of carboxylates. • Radical and carbocationic pathways in the carboxylate oxidation in acetonitrile. - Abstract: The oxidation of tetrabutylammonium carboxylates by using ferrocene derivatives as redox mediators has been recently used to perform the covalent grafting of carbon surfaces with organic and organometallic groups. Due to the intervention of this surface process, a partial description of the reaction mechanism has only been stated. Therefore, this article concerns about two features of the oxidation of carboxylates mediated by ferrocene. In the first part, it is discussed that in the oxidation of acetate ions by using ferrocene as redox catalyst, the gap between both oxidation potentials is very high, which means that the homogeneous electron transfer between the acetate ion and the electrochemically generated ferrocenium ion is energetically unfavorable. However, by using density functional theory calculations, it has been shown that the whole set of coupled chemical reactions involved either in a Kolbe or Non-Kolbe pathway drive the overall mechanisms towards a thermodynamically favorable situation. In order to avoid the strong covalent grafting process that occurs during the mediated oxidation of acetate ions, the second part of this work deals with the oxidation of tetrabutylammonium diphenylacetate by using ferrocene as a redox mediator in acetonitrile on glassy carbon electrodes. With this carboxylate, no electrode inhibition process occurs and, therefore cyclic voltammetry simulation was done to propose the electrochemical and chemical steps that are present when a carboxylate oxidation is performed in the presence of ferrocene derivatives

Benzyl Alcohol-Mediated Versatile Method to Fabricate Nonstoichiometric Metal Oxide Nanostructures.

Science.gov (United States)

Qamar, Mohammad; Adam, Alaaldin; Azad, Abdul-Majeed; Kim, Yong-Wah

2017-11-22

Nanostructured metal oxides with cationic or anionic deficiency find applications in a wide range of technological areas including the energy sector and environment. However, a facile route to prepare such materials in bulk with acceptable reproducibility is still lacking; many synthesis techniques are still only bench-top and cannot be easily scaled-up. Here, we report that the benzyl alcohol (BA)-mediated method is capable of producing a host of nanostructured metal oxides (MO x , where M = Ti, Zn, Ce, Sn, In, Ga, or Fe) with inherent nonstoichiometry. It employs multifunctional BA as a solvent, a reducing agent, and a structure-directing agent. Depending on the oxidation states of metal, elemental or nonstoichiometric oxide forms are obtained. Augmented photoelectrochemical oxidation of water under visible light by some of these nonstoichiometric oxides highlights the versatility of the BA-mediated synthesis protocol.

Wearing graduated compression stockings augments cutaneous vasodilation but not sweating during exercise in the heat.

Science.gov (United States)

Fujii, Naoto; Nikawa, Toshiya; Tsuji, Bun; Kenny, Glen P; Kondo, Narihiko; Nishiyasu, Takeshi

2017-05-01

The activation of cutaneous vasodilation and sweating are essential to the regulation of core temperature during exercise in the heat. We assessed the effect of graduated compression induced by wearing stockings on cutaneous vasodilation and sweating during exercise in the heat (30°C). On two separate occasions, nine young males exercised for 45 min or until core temperature reached ~1.5°C above baseline resting while wearing either (1) stockings causing graduated compression (graduate compression stockings, GCS), or (2) loose-fitting stockings without compression (Control). Forearm vascular conductance was evaluated by forearm blood flow (venous occlusion plethysmography) divided by mean arterial pressure to estimate cutaneous vasodilation. Sweat rate was estimated using the ventilated capsule technique. Core and skin temperatures were measured continuously. Exercise duration was similar between conditions (Control: 42.2 ± 3.6 min vs. GCS: 42.2 ± 3.6 min, P  = 1.00). Relative to Control, GCS increased forearm vascular conductance during the late stages (≥30 min) of exercise (e.g., at 40 min, 15.6 ± 5.6 vs. 18.0 ± 6.0 units, P  = 0.01). This was paralleled by a greater sensitivity (23.1 ± 9.1 vs. 32.1 ± 15.0 units°C -1 , P  = 0.043) and peak level (14.1 ± 5.1 vs. 16.3 ± 5.7 units, P  = 0.048) of cutaneous vasodilation as evaluated from the relationship between forearm vascular conductance with core temperature. However, the core temperature threshold at which an increase in forearm vascular conductance occurred did not differ between conditions (Control: 36.9 ± 0.2 vs. GCS: 37.0 ± 0.3°C, P  = 0.13). In contrast, no effect of GCS on sweating was measured (all P  > 0.05). We show that the use of GCS during exercise in the heat enhances cutaneous vasodilation and not sweating. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American

Induced vasodilation as treatment for Raynaud's disease.

Science.gov (United States)

Jobe, J B; Sampson, J B; Roberts, D E; Beetham, W P

1982-11-01

We examined the efficacy of induced vasodilation as a treatment of idiopathic Raynaud's disease. Eight persons with Raynaud's disease and seven normal persons each received 27 simultaneous pairings of hand immersion in warm water (43 degrees C) for 10 minutes with exposure of the whole body to cold (0 degrees C). A second group of seven normal persons and nine persons with Raynaud's disease received no treatments. All subjects had cold test exposures (0 degrees C) at the start and end of the study. Subjects with Raynaud's disease who received treatments showed significant increases in digital temperatures (2.2 degrees C) during the cold test compared with the values of untreated subjects with Raynaud's disease (p less than 0.05); normal subjects who had received treatments showed no difference from those who had not. Digital temperatures of subjects with Raynaud's disease after treatment increased to levels approaching those of normal subjects, although they showed lower digital temperatures during initial exposure to cold (p less than 0.01). This therapy offers a practical alternative to traditional treatments.

Cooperative electrocatalytic alcohol oxidation with electron-proton-transfer mediators

Science.gov (United States)

Badalyan, Artavazd; Stahl, Shannon S.

2016-07-01

The electrochemical oxidation of alcohols is a major focus of energy and chemical conversion efforts, with potential applications ranging from fuel cells to biomass utilization and fine-chemical synthesis. Small-molecule electrocatalysts for processes of this type are promising targets for further development, as demonstrated by recent advances in nickel catalysts for electrochemical production and oxidation of hydrogen. Complexes with tethered amines that resemble the active site of hydrogenases have been shown both to catalyse hydrogen production (from protons and electrons) with rates far exceeding those of such enzymes and to mediate reversible electrocatalytic hydrogen production and oxidation with enzyme-like performance. Progress in electrocatalytic alcohol oxidation has been more modest. Nickel complexes similar to those used for hydrogen oxidation have been shown to mediate efficient electrochemical oxidation of benzyl alcohol, with a turnover frequency of 2.1 per second. These compounds exhibit poor reactivity with ethanol and methanol, however. Organic nitroxyls, such as TEMPO (2,2,6,6-tetramethyl-1-piperidine N-oxyl), are the most widely studied electrocatalysts for alcohol oxidation. These catalysts exhibit good activity (1-2 turnovers per second) with a wide range of alcohols and have great promise for electro-organic synthesis. Their use in energy-conversion applications, however, is limited by the high electrode potentials required to generate the reactive oxoammonium species. Here we report (2,2‧-bipyridine)Cu/nitroxyl co-catalyst systems for electrochemical alcohol oxidation that proceed with much faster rates, while operating at an electrode potential a half-volt lower than that used for the TEMPO-only process. The (2,2‧-bipyridine)Cu(II) and TEMPO redox partners exhibit cooperative reactivity and exploit the low-potential, proton-coupled TEMPO/TEMPOH redox process rather than the high-potential TEMPO/TEMPO+ process. The results show how

Neuronal nitric oxide synthase mediates insulin- and oxidative stress-induced glucose uptake in skeletal muscle myotubes.

Science.gov (United States)

Kellogg, Dean L; McCammon, Karen M; Hinchee-Rodriguez, Kathryn S; Adamo, Martin L; Roman, Linda J

2017-09-01

Previously published studies strongly suggested that insulin- and exercise-induced skeletal muscle glucose uptake require nitric oxide (NO) production. However, the signal transduction mechanisms by which insulin and contraction regulated NO production and subsequent glucose transport are not known. In the present study, we utilized the myotube cell lines treated with insulin or hydrogen peroxide, the latter to mimic contraction-induced oxidative stress, to characterize these mechanisms. We found that insulin stimulation of neuronal nitric oxide synthase (nNOS) phosphorylation, NO production, and GLUT4 translocation were all significantly reduced by inhibition of either nNOS or Akt2. Hydrogen peroxide (H 2 O 2 ) induced phosphorylation of nNOS at the same residue as did insulin, and also stimulated NO production and GLUT4 translocation. nNOS inhibition prevented H 2 O 2 -induced GLUT4 translocation. AMP activated protein kinase (AMPK) inhibition prevented H 2 O 2 activation and phosphorylation of nNOS, leading to reduced NO production and significantly attenuated GLUT4 translocation. We conclude that nNOS phosphorylation and subsequently increased NO production are required for both insulin- and H 2 O 2 -stimulated glucose transport. Although the two stimuli result in phosphorylation of the same residue on nNOS, they do so through distinct protein kinases. Thus, insulin and H 2 O 2 -activated signaling pathways converge on nNOS, which is a common mediator of glucose uptake in both pathways. However, the fact that different kinases are utilized provides a basis for the use of exercise to activate glucose transport in the face of insulin resistance. Copyright © 2017. Published by Elsevier Inc.

Nitric oxide agents impair insulin-mediated signal transduction in rat skeletal muscle

Directory of Open Access Journals (Sweden)

Ragoobirsingh Dalip

2006-05-01

Full Text Available Abstract Background Evidence demonstrates that exogenously administered nitric oxide (NO can induce insulin resistance in skeletal muscle. We have investigated the modulatory effects of two NO donors, S-nitroso-N-acetyl-D, L-penicillamine (SNAP and S-nitrosoglutathione (GSNO on the early events in insulin signaling in rat skeletal myocytes. Results Skeletal muscle cells from 6–8 week old Sprague-Dawley rats were treated with SNAP or GSNO (25 ng/ml in the presence or absence of glucose (25 mM and insulin (100 nM. Cellular insulin receptor-β levels and tyrosine phosphorylation in IRS-1 were significantly reduced, while serine phosphorylation in IRS-1 was significantly increased in these cells, when compared to the insulin-stimulated control. Reversal to near normal levels was achieved using the NO scavenger, 2-(4-carboxyphenyl-4, 4, 5, 5-tetramethylimidazoline-1-oxyl 3-oxide (carboxy-PTIO. Conclusion These data suggest that NO is a potent modulator of insulin-mediated signal transduction and may play a significant role in the pathogenesis of type 2 diabetes mellitus.

A marine microbial consortium apparently mediating anaerobic oxidation of methane

DEFF Research Database (Denmark)

Boetius, A.; Ravenschlag, K.; Schubert, CJ

2000-01-01

microorganisms mediating this reaction have not yet been isolated, and the pathway of anaerobic oxidation of methane is insufficiently understood. Recent data suggest that certain archaea reverse the process of methanogenesis by interaction with sulphate-reducing bacteria(5-7). Here we provide microscopic...... cells and are surrounded by sulphate-reducing bacteria. These aggregates were abundant in gas-hydrate-rich sediments with extremely high rates of methane-based sulphate reduction, and apparently mediate anaerobic oxidation of methane.......A large fraction of globally produced methane is converted to CO2 by anaerobic oxidation in marine sediments(1). Strong geochemical evidence for net methane consumption in anoxic sediments is based on methane profiles(2), radiotracer experiments(3) and stable carbon isotope data(4). But the elusive...

Reactive oxygen species mediate nitric oxide production through ERK/JNK MAPK signaling in HAPI microglia after PFOS exposure

Energy Technology Data Exchange (ETDEWEB)

Wang, Cheng; Nie, Xiaoke; Zhang, Yan [Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China); Li, Ting; Mao, Jiamin [Department of Labor and Environmental Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China); Liu, Xinhang [Department of Occupational Medicine and Environmental Toxicology, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China); Gu, Yiyang; Shi, Jiyun [Department of Labor and Environmental Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China); Xiao, Jing [Department of Occupational Medicine and Environmental Toxicology, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China); Wan, Chunhua [Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China); Wu, Qiyun, E-mail: wqy@ntu.edu.cn [Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China)

2015-10-15

Perfluorooctane sulfonate (PFOS), an emerging persistent contaminant that is commonly encountered during daily life, has been shown to exert toxic effects on the central nervous system (CNS). However, the molecular mechanisms underlying the neurotoxicity of PFOS remain largely unknown. It has been widely acknowledged that the inflammatory mediators released by hyper-activated microglia play vital roles in the pathogenesis of various neurological diseases. In the present study, we examined the impact of PFOS exposure on microglial activation and the release of proinflammatory mediators, including nitric oxide (NO) and reactive oxidative species (ROS). We found that PFOS exposure led to concentration-dependent NO and ROS production by rat HAPI microglia. We also discovered that there was rapid activation of the ERK/JNK MAPK signaling pathway in the HAPI microglia following PFOS treatment. Moreover, the PFOS-induced iNOS expression and NO production were attenuated after the inhibition of ERK or JNK MAPK by their corresponding inhibitors, PD98059 and SP600125. Interestingly, NAC, a ROS inhibitor, blocked iNOS expression, NO production, and activation of ERK and JNK MAPKs, which suggested that PFOS-mediated microglial NO production occurs via a ROS/ERK/JNK MAPK signaling pathway. Finally, by exposing SH-SY5Y cells to PFOS-treated microglia-conditioned medium, we demonstrated that NO was responsible for PFOS-mediated neuronal apoptosis. - Highlights: • PFOS exposure induced expression of iNOS and production of NO in HAPI microglia. • PFOS induced the production of ROS in HAPI microglia. • ERK/JNK MAPK pathways were activated following PFOS exposure in HAPI microglia. • NO released by HAPI microglia participated in the apoptosis of SH-SY5Y cells.

Reactive oxygen species mediate nitric oxide production through ERK/JNK MAPK signaling in HAPI microglia after PFOS exposure

International Nuclear Information System (INIS)

Wang, Cheng; Nie, Xiaoke; Zhang, Yan; Li, Ting; Mao, Jiamin; Liu, Xinhang; Gu, Yiyang; Shi, Jiyun; Xiao, Jing; Wan, Chunhua; Wu, Qiyun

2015-01-01

Perfluorooctane sulfonate (PFOS), an emerging persistent contaminant that is commonly encountered during daily life, has been shown to exert toxic effects on the central nervous system (CNS). However, the molecular mechanisms underlying the neurotoxicity of PFOS remain largely unknown. It has been widely acknowledged that the inflammatory mediators released by hyper-activated microglia play vital roles in the pathogenesis of various neurological diseases. In the present study, we examined the impact of PFOS exposure on microglial activation and the release of proinflammatory mediators, including nitric oxide (NO) and reactive oxidative species (ROS). We found that PFOS exposure led to concentration-dependent NO and ROS production by rat HAPI microglia. We also discovered that there was rapid activation of the ERK/JNK MAPK signaling pathway in the HAPI microglia following PFOS treatment. Moreover, the PFOS-induced iNOS expression and NO production were attenuated after the inhibition of ERK or JNK MAPK by their corresponding inhibitors, PD98059 and SP600125. Interestingly, NAC, a ROS inhibitor, blocked iNOS expression, NO production, and activation of ERK and JNK MAPKs, which suggested that PFOS-mediated microglial NO production occurs via a ROS/ERK/JNK MAPK signaling pathway. Finally, by exposing SH-SY5Y cells to PFOS-treated microglia-conditioned medium, we demonstrated that NO was responsible for PFOS-mediated neuronal apoptosis. - Highlights: • PFOS exposure induced expression of iNOS and production of NO in HAPI microglia. • PFOS induced the production of ROS in HAPI microglia. • ERK/JNK MAPK pathways were activated following PFOS exposure in HAPI microglia. • NO released by HAPI microglia participated in the apoptosis of SH-SY5Y cells.

Antioxidant systems are regulated by nitric oxide-mediated post-translational modifications (NO-PTMs

Directory of Open Access Journals (Sweden)

Juan Carlos Begara-Morales

2016-02-01

Full Text Available Nitric oxide (NO is a biological messenger that orchestrates a plethora of plant functions, mainly through post-translational modifications (PTMs such as S-nitrosylation or tyrosine nitration. In plants, hundreds of proteins have been identified as potential targets of these NO-PTMs under physiological and stress conditions indicating the relevance of NO in plant-signaling mechanisms. Among these NO protein targets, there are different antioxidant enzymes involved in the control of reactive oxygen species (ROS, such as H2O2, which is also a signal molecule. This highlights the close relationship between ROS/NO signaling pathways. The major plant antioxidant enzymes, including catalase, superoxide dismutases (SODs peroxiredoxins (Prx and all the enzymatic components of the ascorbate-glutathione (Asa-GSH cycle, have been shown to be modulated to different degrees by NO-PTMs. This mini-review will update the recent knowledge concerning the interaction of NO with these antioxidant enzymes, with a special focus on the components of the Asa-GSH cycle and their physiological relevance.

Increasing Muscle Mass Improves Vascular Function in Obese (db/db) Mice

Science.gov (United States)

Qiu, Shuiqing; Mintz, James D.; Salet, Christina D.; Han, Weihong; Giannis, Athanassios; Chen, Feng; Yu, Yanfang; Su, Yunchao; Fulton, David J.; Stepp, David W.

2014-01-01

Background A sedentary lifestyle is an independent risk factor for cardiovascular disease and exercise has been shown to ameliorate this risk. Inactivity is associated with a loss of muscle mass, which is also reversed with isometric exercise training. The relationship between muscle mass and vascular function is poorly defined. The aims of the current study were to determine whether increasing muscle mass by genetic deletion of myostatin, a negative regulator of muscle growth, can influence vascular function in mesenteric arteries from obese db/db mice. Methods and Results Myostatin expression was elevated in skeletal muscle of obese mice and associated with reduced muscle mass (30% to 50%). Myostatin deletion increased muscle mass in lean (40% to 60%) and obese (80% to 115%) mice through increased muscle fiber size (PMyostatin deletion decreased adipose tissue in lean mice, but not obese mice. Markers of insulin resistance and glucose tolerance were improved in obese myostatin knockout mice. Obese mice demonstrated an impaired endothelial vasodilation, compared to lean mice. This impairment was improved by superoxide dismutase mimic Tempol. Deletion of myostatin improved endothelial vasodilation in mesenteric arteries in obese, but not in lean, mice. This improvement was blunted by nitric oxide (NO) synthase inhibitor l‐NG‐nitroarginine methyl ester (l‐NAME). Prostacyclin (PGI2)‐ and endothelium‐derived hyperpolarizing factor (EDHF)‐mediated vasodilation were preserved in obese mice and unaffected by myostatin deletion. Reactive oxygen species) was elevated in the mesenteric endothelium of obese mice and down‐regulated by deletion of myostatin in obese mice. Impaired vasodilation in obese mice was improved by NADPH oxidase inhibitor (GKT136901). Treatment with sepiapterin, which increases levels of tetrahydrobiopterin, improved vasodilation in obese mice, an improvement blocked by l‐NAME. Conclusions Increasing muscle mass by genetic deletion of

Hyperglycemia and Oxidative Stress Strengthen the Association Between Myeloperoxidase and Blood Pressure

NARCIS (Netherlands)

van der Zwan, L.P.; Scheffer, P.G.; Dekker, J.M.; Stehouwer, C.D.A.; Heine, R.J.; Teerlink, T.

2010-01-01

Scavenging of the vasodilator nitric oxide by myeloperoxidase activity in the vasculature may contribute to hypertension. Because hydrogen peroxide is a cosubstrate of myeloperoxidase, hyperglycemia-induced oxidative stress may strengthen the relationship between myeloperoxidase and blood pressure.

Opening the microcirculation: can vasodilators be useful in sepsis?

NARCIS (Netherlands)

Buwalda, Mattijn; Ince, Can

2002-01-01

Objective: A prominent feature of sepsis is dysfunction of the microcirculation, with impaired perfusion and regional tissue oxygenation causing a deficit in oxygen extraction. If shunting of oxygen transport past closed hypoxic microcirculatory beds is responsible for this, vasodilator therapy,

Wearing graduated compression stockings augments cutaneous vasodilation in heat-stressed resting humans.

Science.gov (United States)

Fujii, Naoto; Nikawa, Toshiya; Tsuji, Bun; Kondo, Narihiko; Kenny, Glen P; Nishiyasu, Takeshi

2017-05-01

We investigated whether graduated compression induced by stockings enhances cutaneous vasodilation in passively heated resting humans. Nine habitually active young men were heated at rest using water-perfusable suits, resulting in a 1.0 °C increase in body core temperature. Heating was repeated twice on separate occasions while wearing either (1) stockings that cause graduated compression (pressures of 26.4 ± 5.3, 17.5 ± 4.4, and 6.1 ± 2.0 mmHg at the ankle, calf, and thigh, respectively), or (2) loose-fitting stockings without causing compression (Control). Forearm vascular conductance during heating was evaluated by forearm blood flow (venous occlusion plethysmography) divided by mean arterial pressure to estimate heat-induced cutaneous vasodilation. Body core (esophageal), skin, and mean body temperatures were measured continuously. Compared to the Control, forearm vascular conductance during heating was higher with graduated compression stockings (e.g., 23.2 ± 5.5 vs. 28.6 ± 5.8 units at 45 min into heating, P = 0.001). In line with this, graduated compression stockings resulted in a greater sensitivity (27.5 ± 8.3 vs. 34.0 ± 9.4 units °C -1 , P = 0.02) and peak level (25.5 ± 5.8 vs. 29.7 ± 5.8 units, P = 0.004) of cutaneous vasodilation as evaluated from the relationship between forearm vascular conductance with mean body temperature. In contrast, the mean body temperature threshold for increases in forearm vascular conductance did not differ between the Control and graduated compression stockings (36.5 ± 0.1 vs. 36.5 ± 0.2 °C, P = 0.85). Our results show that graduated compression associated with the use of stockings augments cutaneous vasodilation by modulating sensitivity and peak level of cutaneous vasodilation in relation to mean body temperature. However, the effect of these changes on whole-body heat loss remains unclear.

Flavonoids from artichoke (Cynara scolymus L.) up-regulate endothelial-type nitric-oxide synthase gene expression in human endothelial cells.

Science.gov (United States)

Li, Huige; Xia, Ning; Brausch, Isolde; Yao, Ying; Förstermann, Ulrich

2004-09-01

Nitric oxide (NO) produced by endothelial nitric-oxide synthase (eNOS) represents an antithrombotic and anti-atherosclerotic principle in the vasculature. Hence, an enhanced expression of eNOS in response to pharmacological interventions could provide protection against cardiovascular diseases. In EA.hy 926 cells, a cell line derived from human umbilical vein endothelial cells (HUVECs), an artichoke leaf extract (ALE) increased the activity of the human eNOS promoter (determined by luciferase reporter gene assay). An organic subfraction from ALE was more potent in this respect than the crude extract, whereas an aqueous subfraction of ALE was without effect. ALE and the organic subfraction thereof also increased eNOS mRNA expression (measured by an RNase protection assay) and eNOS protein expression (determined by Western blot) both in EA.hy 926 cells and in native HUVECs. NO production (measured by NO-ozone chemiluminescence) was increased by both extracts. In organ chamber experiments, ex vivo incubation (18 h) of rat aortic rings with the organic subfraction of ALE enhanced the NO-mediated vasodilator response to acetylcholine, indicating that the up-regulated eNOS remained functional. Caffeoylquinic acids and flavonoids are two major groups of constituents of ALE. Interestingly, the flavonoids luteolin and cynaroside increased eNOS promoter activity and eNOS mRNA expression, whereas the caffeoylquinic acids cynarin and chlorogenic acid were without effect. Thus, in addition to the lipid-lowering and antioxidant properties of artichoke, an increase in eNOS gene transcription may also contribute to its beneficial cardiovascular profile. Artichoke flavonoids are likely to represent the active ingredients mediating eNOS up-regulation.

Inducible nitric-oxide synthase plays a minimal role in lymphocytic choriomeningitis virus-induced, T cell-mediated protective immunity and immunopathology

DEFF Research Database (Denmark)

Bartholdy, C; Nansen, A; Christensen, Jeanette Erbo

1999-01-01

-mediated immune response was found to be unaltered in iNOS-deficient mice compared with wild-type C57BL/6 mice, and LCMV- induced general immunosuppression was equally pronounced in both strains. In vivo analysis revealed identical kinetics of virus clearance, as well as unaltered clinical severity of systemic......By using mice with a targetted disruption in the gene encoding inducible nitric-oxide synthase (iNOS), we have studied the role of nitric oxide (NO) in lymphocytic choriomeningitis virus (LCMV)-induced, T cell-mediated protective immunity and immunopathology. The afferent phase of the T cell...... LCMV infection in both strains. Concerning the outcome of intracerebral infection, no significant differences were found between iNOS-deficient and wild-type mice in the number or composition of mononuclear cells found in the cerebrospinal fluid on day 6 post-infection. Likewise, NO did not influence...

Normalization of hemoglobin-based oxygen carrier-201 induced vasoconstriction: targeting nitric oxide and endothelin.

Science.gov (United States)

Taverne, Yannick J; de Wijs-Meijler, Daphne; Te Lintel Hekkert, Maaike; Moon-Massat, Paula F; Dubé, Gregory P; Duncker, Dirk J; Merkus, Daphne

2017-05-01

pressures. HBOC-201-induced vasoconstriction is mediated by scavenging nitric oxide (NO) and by upregulating endothelin (ET) production. Pressor effects can be prevented by adjuvant treatment with NO donors or direct vasodilators, such as nitroglycerin or adenosine, but dosages must be carefully monitored to avoid hypotension. However, hemodynamic normalization is more easily achieved via administration of an ET receptor blocker.

An update on oxidative stress-mediated organ pathophysiology.

Science.gov (United States)

Rashid, Kahkashan; Sinha, Krishnendu; Sil, Parames C

2013-12-01

Exposure to environmental pollutants and drugs can result in pathophysiological situations in the body. Research in this area is essential as the knowledge on cellular survival and death would help in designing effective therapeutic strategies that are needed for the maintenance of the normal physiological functions of the body. In this regard, naturally occurring bio-molecules can be considered as potential therapeutic targets as they are normally available in commonly consumed foodstuffs and are thought to have minimum side effects. This review article describes the detailed mechanisms of oxidative stress-mediated organ pathophysiology and the ultimate fate of the cells either to survive or to undergo necrotic or apoptotic death. The mechanisms underlying the beneficial role of a number of naturally occurring bioactive molecules in oxidative stress-mediated organ pathophysiology have also been included in the review. The review provides useful information about the recent progress in understanding the mechanism(s) of various types of organ pathophysiology, the complex cross-talk between these pathways, as well as their modulation in stressed conditions. Additionally, it suggests possible therapeutic applications of a number of naturally occurring bioactive molecules in conditions involving oxidative stress. Copyright © 2013 Elsevier Ltd. All rights reserved.

Biochemistry and pathology of radical-mediated protein oxidation

DEFF Research Database (Denmark)

Dean, R T; Fu, S; Stocker, R

1997-01-01

Radical-mediated damage to proteins may be initiated by electron leakage, metal-ion-dependent reactions and autoxidation of lipids and sugars. The consequent protein oxidation is O2-dependent, and involves several propagating radicals, notably alkoxyl radicals. Its products include several catego...

High-intensity interval training prevents oxidant-mediated diaphragm muscle weakness in hypertensive mice.

Science.gov (United States)

Bowen, T Scott; Eisenkolb, Sophia; Drobner, Juliane; Fischer, Tina; Werner, Sarah; Linke, Axel; Mangner, Norman; Schuler, Gerhard; Adams, Volker

2017-01-01

Hypertension is a key risk factor for heart failure, with the latter characterized by diaphragm muscle weakness that is mediated in part by increased oxidative stress. In the present study, we used a deoxycorticosterone acetate (DOCA)-salt mouse model to determine whether hypertension could independently induce diaphragm dysfunction and further investigated the effects of high-intensity interval training (HIIT). Sham-treated (n = 11), DOCA-salt-treated (n = 11), and DOCA-salt+HIIT-treated (n = 15) mice were studied over 4 wk. Diaphragm contractile function, protein expression, enzyme activity, and fiber cross-sectional area and type were subsequently determined. Elevated blood pressure confirmed hypertension in DOCA-salt mice independent of HIIT (P HIIT. Myosin heavy chain (MyHC) protein expression tended to decrease (∼30%; P = 0.06) in DOCA-salt vs. sham- and DOCA-salt+HIIT mice, whereas oxidative stress increased (P HIIT further prevented direct oxidant-mediated diaphragm contractile dysfunction (P hypertension induces diaphragm contractile dysfunction via an oxidant-mediated mechanism that is prevented by HIIT.-Bowen, T. S., Eisenkolb, S., Drobner, J., Fischer, T., Werner, S., Linke, A., Mangner, N., Schuler, G., Adams, V. High-intensity interval training prevents oxidant-mediated diaphragm muscle weakness in hypertensive mice. © FASEB.

Stress response to cadmium and manganese in Paracentrotus lividus developing embryos is mediated by nitric oxide

International Nuclear Information System (INIS)

Migliaccio, Oriana; Castellano, Immacolata; Romano, Giovanna; Palumbo, Anna

2014-01-01

Highlights: • NO is produced in sea urchin embryos in response to cadmium and manganese. • Cadmium and manganese affect the expression of specific genes. • NO levels regulate directly or indirectly the expression of some metal-induced genes. • NO is proposed as a sensor of different stress agents in sea urchin embryos. - Abstract: Increasing concentrations of contaminants, often resulting from anthropogenic activities, have been reported to occur in the marine environment and affect marine organisms. Among these, the metal ions cadmium and manganese have been shown to induce developmental delay and abnormalities, mainly reflecting skeleton elongation perturbation, in the sea urchin Paracentrotus lividus, an established model for toxicological studies. Here, we provide evidence that the physiological messenger nitric oxide (NO), formed by L-arginine oxidation by NO synthase (NOS), mediates the stress response induced by cadmium and manganese in sea urchins. When NO levels were lowered by inhibiting NOS, the proportion of abnormal plutei increased. Quantitative expression of a panel of 19 genes involved in stress response, skeletogenesis, detoxification and multidrug efflux processes was followed at different developmental stages and under different conditions: metals alone, metals in the presence of NOS inhibitor, NO donor and NOS inhibitor alone. These data allowed the identification of different classes of genes whose metal-induced transcriptional expression was directly or indirectly mediated by NO. These results open new perspectives on the role of NO as a sensor of different stress agents in sea urchin developing embryos

Stress response to cadmium and manganese in Paracentrotus lividus developing embryos is mediated by nitric oxide

Energy Technology Data Exchange (ETDEWEB)

Migliaccio, Oriana; Castellano, Immacolata [Laboratory of Cellular and Developmental Biology, Stazione Zoologica Anton Dohrn, Villa Comunale, 80121 Naples (Italy); Romano, Giovanna [Laboratory of Functional and Evolutionary Ecology, Stazione Zoologica Anton Dohrn, Villa Comunale, 80121 Naples (Italy); Palumbo, Anna, E-mail: anna.palumbo@szn.it [Laboratory of Cellular and Developmental Biology, Stazione Zoologica Anton Dohrn, Villa Comunale, 80121 Naples (Italy)

2014-11-15

Highlights: • NO is produced in sea urchin embryos in response to cadmium and manganese. • Cadmium and manganese affect the expression of specific genes. • NO levels regulate directly or indirectly the expression of some metal-induced genes. • NO is proposed as a sensor of different stress agents in sea urchin embryos. - Abstract: Increasing concentrations of contaminants, often resulting from anthropogenic activities, have been reported to occur in the marine environment and affect marine organisms. Among these, the metal ions cadmium and manganese have been shown to induce developmental delay and abnormalities, mainly reflecting skeleton elongation perturbation, in the sea urchin Paracentrotus lividus, an established model for toxicological studies. Here, we provide evidence that the physiological messenger nitric oxide (NO), formed by L-arginine oxidation by NO synthase (NOS), mediates the stress response induced by cadmium and manganese in sea urchins. When NO levels were lowered by inhibiting NOS, the proportion of abnormal plutei increased. Quantitative expression of a panel of 19 genes involved in stress response, skeletogenesis, detoxification and multidrug efflux processes was followed at different developmental stages and under different conditions: metals alone, metals in the presence of NOS inhibitor, NO donor and NOS inhibitor alone. These data allowed the identification of different classes of genes whose metal-induced transcriptional expression was directly or indirectly mediated by NO. These results open new perspectives on the role of NO as a sensor of different stress agents in sea urchin developing embryos.

Identification of a salivary vasodilator in the primary North American vector of bluetongue viruses, Culicoides variipennis.

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Perez de Leon, A A; Ribeiro, J M; Tabachnick, W J; Valenzuela, J G

1997-09-01

Several species of Culicoides biting midges are important pests and vectors of pathogens affecting humans and other animals. Bluetongue is the most economically important arthropod-borne animal disease in the United States. Culicoides variipennis is the primary North American vector of the bluetongue viruses. A reddish halo surrounding a petechial hemorrhage was noticed at the site of C. variipennis blood feeding in previously unexposed sheep and rabbits. Salivary gland extracts of nonblood-fed C. variipennis injected intradermally into sheep and rabbits induced cutaneous vasodilation in the form of erythema. A local, dose-dependent erythema, without edema or pruritus, was noted 30 min after injection. Erythema was inapparent with salivary gland extracts obtained after blood feeding. This observation suggested that the vasodilatory activity was inoculated into the host skin at the feeding site. The vasodilatory activity was insoluble in ethanol and destroyed by trypsin or chymotrypsin, which indicated that vasodilation was due to a protein. The association of cutaneous vasodilation with a salivary protein was corroborated by reversed-phase, high-performance liquid chromatography (HPLC). Fractionation of salivary gland extracts by molecular sieving HPLC resulted in maximal vasodilatory activity that coeluted with a protein having a relative molecular weight (MWr) of 22.45 kD. The C. variipennis vasodilator appears to be biologically active at the nanogram level. This vasodilator likely assists C. variipennis during feeding by increasing blood flow from host superficial blood vessels surrounding the bite site. The identification of a salivary vasodilator in C. variipennis may have implications for the transmission of Culicoides-borne pathogens and in the development of dermatitis resulting from the sensitization of humans and animals to Culicoides salivary antigens.

Black tea and maintenance of normal endotheliumdependent vasodilation: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006

DEFF Research Database (Denmark)

Sjödin, Anders Mikael

2018-01-01

on the scientific substantiation of a health claim related to black tea and maintenance of normal endotheliumdependent vasodilation. The scope of the application was proposed to fall under a health claim based on newly developed scientific evidence. The food proposed by the applicant as the subject of the health...... claim is black tea beverages, either freshly prepared or reconstituted from water extract powders of black tea, characterised by the content of flavanols (expressed as catechins plus theaflavins) of at least 30 mg per 200 mL serving. The Panel considers that black tea characterised by the content....... Of the five human intervention studies provided on the chronic effect of black tea consumption on endothelium-dependent vasodilation, two investigated the effect after regular consumption of black tea for a sufficiently long time period (i.e. at least 4 weeks). These two studies did not allow an effect...

Role of calcium-activated potassium channels with small conductance in bradykinin-induced vasodilation of porcine retinal arterioles

DEFF Research Database (Denmark)

Dalsgaard, Thomas; Kroigaard, Christel; Bek, Toke

2009-01-01

PURPOSE: Endothelial dysfunction and impaired vasodilation may be involved in the pathogenesis of retinal vascular diseases. In the present study, the mechanisms underlying bradykinin vasodilation were examined and whether calcium-activated potassium channels of small (SK(Ca)) and intermediate (IK...

Waste treatment in NUCEF facility with silver mediated electrochemical oxidation technique

International Nuclear Information System (INIS)

Umeda, M.; Sugikawa, S.

2000-01-01

Silver mediated electrochemical oxidation technique has been considered one of promising candidates for alpha-bearing waste treatment. Destruction tests of organic compounds, such as insoluble tannin, TBP and dodecane, were carried out by this technique and the experimental data such as destruction rates, current efficiencies and intermediates were obtained. These compounds could be completely mineralized without the formation of reactive organic nitrate associated to safety hazards. On the basis of these results, the applicability of silver mediated electrochemical oxidation technique to waste treatment in NUCEF was evaluated. (authors)

Hypervalent iodine/TEMPO-mediated oxidation in flow systems: a fast and efficient protocol for alcohol oxidation

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Nida Ambreen

2013-07-01

Full Text Available Hypervalent iodine(III/TEMPO-mediated oxidation of various aliphatic, aromatic and allylic alcohols to their corresponding carbonyl compounds was successfully achieved by using microreactor technology. This method can be used as an alternative for the oxidation of various alcohols achieving excellent yields and selectivities in significantly shortened reaction times.

Differential Changes of Aorta and Carotid Vasodilation in Type 2 Diabetic GK and OLETF Rats: Paradoxical Roles of Hyperglycemia and Insulin

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Mei-Fang Zhong

2012-01-01

Full Text Available We investigated large vessel function in lean Goto-Kakizaki diabetic rats (GK and Otsuka Long-Evans Tokushima Fatty diabetic rats (OLETF with possible roles of hyperglycemia/hyperosmolarity and insulin. Both young and old GK showed marked hyperglycemia with normal insulin level and well-preserved endothelium-dependent and endothelium-independent vasodilation in aorta and carotid artery. There were significant elevations in endothelial/inducible nitric oxide synthase (eNOS/iNOS and inducible/constitutive heme oxygenase (HO-1/HO-2 in GK. The endothelium-dependent vasodilation in GK was inhibited partly by NOS blockade and completely by simultaneous blocking of HO and NOS. In contrast, OLETF showed hyperinsulinemia and mild hyperglycemia but significant endothelium dysfunction beginning at early ages with concomitantly reduced eNOS. Insulin injection corrected hyperglycemia in GK but induced endothelium dysfunction and intima hyperplasia. Hyperglycemia/hyperosmolarity in vitro enhanced vessel eNOS/HO. We suggest that hyperinsulinemia plays a role in endothelium dysfunction in obese diabetic OLETF, while hyperglycemia/hyperosmolarity-induced eNOS/HO upregulation participates in the adaptation of endothelium function in lean diabetic GK.

Ruthenium Complexes as NO Donors for Vascular Relaxation Induction

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Renata Galvão de Lima

2014-07-01

Full Text Available Nitric oxide (NO donors are substances that can release NO. Vascular relaxation induction is among the several functions of NO, and the administration of NO donors is a pharmacological alternative to treat hypertension. This review will focus on the physicochemical description of ruthenium-derived NO donor complexes that release NO via reduction and light stimulation. In particular, we will discuss the complexes synthesized by our research group over the last ten years, and we will focus on the vasodilation and arterial pressure control elicited by these complexes. Soluble guanylyl cyclase (sGC and potassium channels are the main targets of the NO species released from the inorganic compounds. We will consider the importance of the chemical structure of the ruthenium complexes and their vascular effects.

Carboxyhemoglobin formation secondary to nitric oxide therapy in the setting of interstitial lung disease and pulmonary hypertension.

Science.gov (United States)

Ruisi, Phillip; Ruisi, Michael

2011-01-01

Carbon monoxide (CO) has been widely recognized as an exogenous poison, although endogenous mechanisms for its formation involve heme-oxygenase (HO) isoforms, more specifically HO-1, in the setting of oxidative stress such as acute respiratory distress syndrome, sepsis, trauma, and nitric oxide use have been studied. In patients with refractory hypoxemia, inhaled nitric oxide (iNO) therapy is used to selectively vasodilate the pulmonary vasculature and improve ventilation-perfusion match. Inhaled nitric oxide is rapidly inactivated on binding to hemoglobin in the formation of nitrosyl- and methemoglobin in the pulmonary vasculature. Hence, inhaled nitric oxide has minimal systemic dissemination. Several experimental design studies involving lab rats have demonstrated increased levels of carboxyhemoglobin and exhaled CO as a result of nitric oxide HO-1 induction.

Detection of human collateral circulation by vasodilation-thallium-201 tomography

International Nuclear Information System (INIS)

Nienaber, C.A.; Salge, D.; Spielmann, R.P.; Montz, R.; Bleifeld, W.

1990-01-01

Coronary arteriolar vasodilation may provoke redistribution of flow to collateral-dependent jeopardized myocardium. To assess the physiologic significance of collaterals, 80 consecutive post-infarction patients (age 58 +/- 8 years) underwent vasodilation-redistribution thallium-201 tomographic imaging after administration of 0.56 mg of intravenous dipyridamole/kg body weight. Circumferential profile analysis of thallium-201 uptake and redistribution in representative left ventricular tomograms provided quantitative assessment of transient and fixed defects and separation between periinfarctional and distant inducible hypoperfusion. Tomographic perfusion data were correlated to wall motion and collateral circulation between distinct anatomic perfusion territories. Patients were grouped according to presence (59%) or absence (41%) of angiographically visible collateral channels to jeopardized myocardium. In the presence of collaterals, distant reversible defects were larger than in absence of collaterals (p less than 0.05); the extent of combined periinfarctional and distant redistribution was also larger in collateralized patients (p less than 0.025), whereas the size of the persistent perfusion defect was similar in both groups. By prospective analysis the tomographic perfusion pattern of combined periinfarctional and distant redistribution revealed a sensitivity of 85% and a specificity of 78% for the detection of significant collateral circulation in this group of patients. Thus, using the exhausted flow reserve as a diagnostic tool, vasodilation-thallium-201 tomography has the potential to identify and quantitate collateralized myocardium in post-infarction patients and may guide diagnostic and therapeutic decision-making

Vasodilator-Stimulated Phosphoprotein Activity Is Required for Coxiella burnetii Growth in Human Macrophages.

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Punsiri M Colonne

2016-10-01

Full Text Available Coxiella burnetii is an intracellular bacterial pathogen that causes human Q fever, an acute flu-like illness that can progress to chronic endocarditis and liver and bone infections. Humans are typically infected by aerosol-mediated transmission, and C. burnetii initially targets alveolar macrophages wherein the pathogen replicates in a phagolysosome-like niche known as the parasitophorous vacuole (PV. C. burnetii manipulates host cAMP-dependent protein kinase (PKA signaling to promote PV formation, cell survival, and bacterial replication. In this study, we identified the actin regulatory protein vasodilator-stimulated phosphoprotein (VASP as a PKA substrate that is increasingly phosphorylated at S157 and S239 during C. burnetii infection. Avirulent and virulent C. burnetii triggered increased levels of phosphorylated VASP in macrophage-like THP-1 cells and primary human alveolar macrophages, and this event required the Cα subunit of PKA. VASP phosphorylation also required bacterial protein synthesis and secretion of effector proteins via a type IV secretion system, indicating the pathogen actively triggers prolonged VASP phosphorylation. Optimal PV formation and intracellular bacterial replication required VASP activity, as siRNA-mediated depletion of VASP reduced PV size and bacterial growth. Interestingly, ectopic expression of a phospho-mimetic VASP (S239E mutant protein prevented optimal PV formation, whereas VASP (S157E mutant expression had no effect. VASP (S239E expression also prevented trafficking of bead-containing phagosomes to the PV, indicating proper VASP activity is critical for heterotypic fusion events that control PV expansion in macrophages. Finally, expression of dominant negative VASP (S157A in C. burnetii-infected cells impaired PV formation, confirming importance of the protein for proper infection. This study provides the first evidence of VASP manipulation by an intravacuolar bacterial pathogen via activation of PKA

Nitric oxide bioavailability dysfunction involves in atherosclerosis.

Science.gov (United States)

Chen, Jing-Yi; Ye, Zi-Xin; Wang, Xiu-Fen; Chang, Jian; Yang, Mei-Wen; Zhong, Hua-Hua; Hong, Fen-Fang; Yang, Shu-Long

2018-01-01

The pathological characteristics of atherosclerosis (AS) include lipid accumulation, fibrosis formation and atherosclerotic plaque produced in artery intima, which leads to vascular sclerosis, lumen stenosis and irritates the ischemic changes of corresponding organs. Endothelial dysfunction was closely associated with AS. Nitric oxide (NO) is a multifunctional signaling molecule involved in the maintenance of metabolic and cardiovascular homeostasis. NO is also a potent endogenous vasodilator and enters for the key processes that suppresses the formation vascular lesion even AS. NO bioavailability indicates the production and utilization of endothelial NO in organisms, its decrease is related to oxidative stress, lipid infiltration, the expressions of some inflammatory factors and the alteration of vascular tone, which plays an important role in endothelial dysfunction. The enhancement of arginase activity and the increase in asymmetric dimethylarginine and hyperhomocysteinemia levels all contribute to AS by intervening NO bioavailability in human beings. Diabetes mellitus, obesity, chronic kidney disease and smoking, etc., also participate in AS by influencing NO bioavailability and NO level. Here, we reviewed the relationship between NO bioavailability and AS according the newest literatures. Copyright © 2017. Published by Elsevier Masson SAS.

Mediated electrochemical oxidation of organic wastes using a Co(III) mediator in a neutral electrolyte

International Nuclear Information System (INIS)

Balazs, G.B.; Lewis, P.R.

1999-01-01

An electrochemical cell with a Co(III) mediator and neutral pH anolyte provides efficient destruction of organic and mixed wastes. The organic waste is concentrated in the anolyte reservoir, where the cobalt mediator oxidizes the organics and insoluble radioactive species and is regenerated at the anode until all organics are converted to carbon dioxide and destroyed. The neutral electrolyte is non-corrosive, and thus extends the lifetime of the cell and its components. 2 figs

Nitric oxide is a mediator of methamphetamine (METH)-induced neurotoxicity. In vitro evidence from primary cultures of mesencephalic cells.

Science.gov (United States)

Sheng, P; Cerruti, C; Ali, S; Cadet, J L

1996-10-31

METH is a monoaminergic toxic that destroys dopamine terminals in vivo. Oxidative mechanisms associated with DA metabolism are thought to play an important role in its toxic effects. These ideas were supported by the demonstration that CuZn-superoxide dismutase (CuZnSOD) transgenic mice were protected against the toxic effects of the drug. In the present study, we sought to determine if nitric oxide (NO) production was also involved in METH-induced neurotoxicity using primary cultures obtained from fetal rat mesencephalon. METH caused dose- and time-dependent cell death in vitro. Blockade of nitric oxide (NO) formation with several nitric oxide (NO) synthase blockers attenuated METH-mediated toxicity. Moreover, inhibition of ADP-ribosylation with nicotinamide and benzamide also provided protection against the toxicity of the drug. These results, together with our previous results in transgenic mice, support a role for free radicals in METH-induced toxic effects.

Nitric oxide heme interactions in nitrophorin from Cimex lectularius

Energy Technology Data Exchange (ETDEWEB)

Christmann, R.; Auerbach, H., E-mail: auerbach@physik.uni-kl.de [University of Kaiserslautern, Department of Physics (Germany); Berry, R. E.; Walker, F. A. [The University of Arizona, Department of Chemistry and Biochemistry (United States); Schünemann, V. [University of Kaiserslautern, Department of Physics (Germany)

2016-12-15

The nitrophorin from the bedbug Cimex lectularius (cNP) is a nitric oxide (NO) carrying protein. Like the nitrophorins (rNPs) from the kissing bug Rhodnius prolixus, cNP forms a stable heme Fe(III)-NO complex, where the NO can be stored reversibly for a long period of time. In both cases, the NPs are found in the salivary glands of blood-sucking bugs. The insects use the nitrophorins to transport the NO to the victim’s tissues, resulting in vasodilation and reduced blood coagulation. However, the structure of cNP is significantly different to those of the rNPs from Rhodnius prolixus. Furthermore, the cNP can bind a second NO molecule to the proximal heme cysteine when present at higher concentrations. High field Mössbauer spectroscopy on {sup 57}Fe enriched cNP complexed with NO shows reduction of the heme iron and formation of a ferrous nitric oxide (Fe(II)-NO) complex. Density functional theory calculations reproduce the experimental Mössbauer parameters and confirm this observation.

Plant cells oxidize hydroxylamines to NO

Science.gov (United States)

Rümer, Stefan; Gupta, Kapuganti Jagadis; Kaiser, Werner M.

2009-01-01

Plants are known to produce NO via the reduction of nitrite. Oxidative NO production in plants has been considered only with respect to a nitric oxide synthase (NOS). Here it is shown that tobacco cell suspensions emitted NO when hydroxylamine (HA) or salicylhydroxamate (SHAM), a frequently used AOX inhibitor, was added. NG-hydroxy-L-arginine, a putative intermediate in the NOS-reaction, gave no NO emission. Only a minor fraction (≤1%) of the added HA or SHAM was emitted as NO. Production of NO was decreased by anoxia or by the addition of catalase, but was increased by conditions inducing reactive oxygen (ROS) or by the addition of hydrogen peroxide. Cell-free enzyme solutions generating superoxide or hydrogen peroxide also led to the formation of NO from HA or (with lower rates) from SHAM, and nitrite was also an oxidation product. Unexpectedly, the addition of superoxide dismutase (SOD) to cell suspensions stimulated NO formation from hydroxylamines, and SOD alone (without cells) also catalysed the production of NO from HA or SHAM. NO production by SOD plus HA was higher in nitrogen than in air, but from SOD plus SHAM it was lower in nitrogen. Thus, SOD-catalysed NO formation from SHAM and from HA may involve different mechanisms. While our data open a new possibility for oxidative NO formation in plants, the existence and role of these reactions under physiological conditions is not yet clear. PMID:19357430

Regular aerobic exercise reduces endothelin-1-mediated vasoconstrictor tone in overweight and obese adults.

Science.gov (United States)

Dow, Caitlin A; Stauffer, Brian L; Brunjes, Danielle L; Greiner, Jared J; DeSouza, Christopher A

2017-09-01

What is the central question of this study? Does aerobic exercise training reduce endothelin-1 (ET-1)-mediated vasoconstrictor tone in overweight/obese adults? And, if so, does lower ET-1 vasoconstriction underlie the exercise-related enhancement in endothelium-dependent vasodilatation in overweight/obese adults? What is the main finding and its importance? Regular aerobic exercise reduces ET-1-mediated vasoconstrictor tone in previously sedentary overweight/obese adults, independent of weight loss. Decreased ET-1 vasoconstriction is an important mechanism underlying the aerobic exercise-induced improvement in endothelium-dependent vasodilator function in overweight/obese adults. Endothelin-1 (ET-1)-mediated vasoconstrictor tone is elevated in overweight and obese adults, contributing to vasomotor dysfunction and increased cardiovascular disease risk. Although the effects of habitual aerobic exercise on endothelium-dependent vasodilatation in overweight/obese adults have been studied, little is known regarding ET-1-mediated vasoconstriction. Accordingly, the aims of the present study were to determine the following: (i) whether regular aerobic exercise training reduces ET-1-mediated vasoconstrictor tone in overweight and obese adults; and, if so, (ii) whether the reduction in ET-1-mediated vasoconstriction contributes to exercise-induced improvement in endothelium-dependent vasodilatation in this population. Forearm blood flow (FBF) in response to intra-arterial infusion of selective ET A receptor blockade (BQ-123, 100 nmol min -1 for 60 min), acetylcholine [4.0, 8.0 and 16.0 μg (100 ml tissue) -1  min -1 ] in the absence and presence of ET A receptor blockade and sodium nitroprusside [1.0, 2.0 and 4.0 μg (100 ml tissue) -1  min -1 ] were determined before and after a 3 month aerobic exercise training intervention in 25 (16 men and nine women) overweight/obese (body mass index 30.1 ± 0.5 kg m -2 ) adults. The vasodilator response to BQ-123 was

Water-mediated interactions between trimethylamine-N-oxide and urea.

Science.gov (United States)

Hunger, Johannes; Ottosson, Niklas; Mazur, Kamila; Bonn, Mischa; Bakker, Huib J

2015-01-07

The amphiphilic osmolyte trimethylamine-N-oxide (TMAO) is commonly found in natural organisms, where it counteracts biochemical stress associated with urea in aqueous environments. Despite the important role of TMAO as osmoprotectant, the mechanism behind TMAO's action has remained elusive. Here, we study the interaction between urea, TMAO, and water in solution using broadband (100 MHz-1.6 THz) dielectric spectroscopy. We find that the previously reported tight hydrogen bonds between 3 water molecules and the hydrophilic amine oxide group of TMAO, remain intact at all investigated concentrations of urea, showing that no significant hydrogen bonding occurs between the two co-solutes. Despite the absence of direct TMAO-urea interactions, the solute reorientation times of urea and TMAO show an anomalous nonlinear increase with concentration, for ternary mixtures containing equal amounts of TMAO and urea. The nonlinear increase of the reorientation correlates with changes in the viscosity, showing that the combination of TMAO and urea cooperatively enhances the hydrogen-bond structure of the ternary solutions. This nonlinear increase is indicative of water mediated interaction between the two solutes and is not observed if urea is combined with other amphiphilic solutes.

Evidence for shear stress-mediated dilation of the internal carotid artery in humans

DEFF Research Database (Denmark)

Carter, Howard Henry; Atkinson, Ceri L; Heinonen, Ilkka H A

2016-01-01

-mediated dilation of larger conduit arteries in humans. There was a strong association between change in shear and diameter of the internal carotid (r=0.68; Ptime in humans, that shear stress is an important stimulus for hypercapnic vasodilation of the internal carotid...... increases carotid shear stress, a known stimulus to vasodilation in other conduit arteries. To explore the hypothesis that shear stress contributes to hypercapnic internal carotid dilation in humans, temporal changes in internal and common carotid shear rate and diameter, along with changes in middle.......01) carotids. Diameter also increased (Ptime course is associated with shear...

Constraints on superoxide mediated formation of manganese oxides

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Deric R. Learman

2013-09-01

Full Text Available Manganese (Mn oxides are among the most reactive sorbents and oxidants within the environment, where they play a central role in the cycling of nutrients, metals, and carbon. Recent discoveries have identified superoxide (O2- (both of biogenic and abiogenic origin as an effective oxidant of Mn(II leading to the formation of Mn oxides. Here we examined the conditions under which abiotically produced superoxide led to oxidative precipitation of Mn and the solid-phases produced. Oxidized Mn, as both aqueous Mn(III and Mn(III/IV oxides, was only observed in the presence of active catalase, indicating that hydrogen peroxide, a product of the reaction of O2- with Mn(II, inhibits the oxidation process presumably through the reduction of Mn(III. Citrate and pyrophosphate increased the yield of oxidized Mn but decreased the amount of Mn oxide produced via formation of Mn(III-ligand complexes. While complexing ligands played a role in stabilizing Mn(III, they did not eliminate the inhibition of net Mn(III formation by H2O2. The Mn oxides precipitated were highly disordered colloidal hexagonal birnessite, similar to those produced by biotically generated superoxide. Yet, in contrast to the large particulate Mn oxides formed by biogenic superoxide, abiotic Mn oxides did not ripen to larger, more crystalline phases. This suggests that the deposition of crystalline Mn oxides within the environment requires a biological, or at least organic, influence. This work provides the first direct evidence that, under conditions relevant to natural waters, oxidation of Mn(II by superoxide can occur and lead to formation of Mn oxides. For organisms that oxidize Mn(II by producing superoxide, these findings may also point to other microbially mediated processes, in particular enzymatic hydrogen peroxide degradation and/or production of organic ligand metabolites, that allow for Mn oxide formation.

Differential effect of amylin on endothelial-dependent vasodilation in mesenteric arteries from control and insulin resistant rats.

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Mariam El Assar

Full Text Available Insulin resistance (IR is frequently associated with endothelial dysfunction and has been proposed to play a major role in cardiovascular disease (CVD. On the other hand, amylin has long been related to IR. However the role of amylin in the vascular dysfunction associated to IR is not well addressed. Therefore, the aim of the study was to assess the effect of acute treatment with amylin on endothelium-dependent vasodilation of isolated mesenteric arteries from control (CR and insulin resistant (IRR rats and to evaluate the possible mechanisms involved. Five week-old male Wistar rats received 20% D-fructose dissolved in drinking water for 8 weeks and were compared with age-matched CR. Plasmatic levels of glucose, insulin and amylin were measured. Mesenteric microvessels were dissected and mounted in wire myographs to evaluate endothelium-dependent vasodilation to acetylcholine. IRR displayed a significant increase in plasmatic levels of glucose, insulin and amylin and reduced endothelium-dependent relaxation when compared to CR. Acute treatment of mesenteric arteries with r-amylin (40 pM deteriorated endothelium-dependent responses in CR. Amylin-induced reduction of endothelial responses was unaffected by the H2O2 scavenger, catalase, but was prevented by the extracellular superoxide scavenger, superoxide dismutase (SOD or the NADPH oxidase inhibitor (VAS2870. By opposite, amylin failed to further inhibit the impaired relaxation in mesenteric arteries of IRR. SOD, or VAS2870, but not catalase, ameliorated the impairment of endothelium-dependent relaxation in IRR. At concentrations present in insulin resistance conditions, amylin impairs endothelium-dependent vasodilation in mircrovessels from rats with preserved vascular function and low levels of endogenous amylin. In IRR with established endothelial dysfunction and elevated levels of amylin, additional exposure to this peptide has no effect on endothelial vasodilation. Increased superoxide

alpha-adrenergic Blockade Unmasks a Greater Compensatory Vasodilation in Hypoperfused Contracting Muscle

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Darren P. Casey

2012-07-01

Full Text Available We previously demonstrated that acute hypoperfusion in exercising human muscle causes an immediate increase in vascular resistance that is followed by a partial restoration (less than 100% recovery of flow. In the current study we examined the contribution of alpha-adrenergic vasoconstriction in the initial changes in vascular resistance at the onset of hypoperfusion as well as in the recovery of flow over time. Nine healthy male subjects (29 ± 2 performed rhythmic forearm exercise (20% of maximum during hypoperfusion evoked by intra-arterial balloon inflation. Each trial included; baseline, exercise prior to inflation, exercise with inflation, and exercise after deflation (3 min each. Forearm blood flow (FBF; ultrasound, local (brachial artery, and systemic arterial pressure (MAP; Finometer were measured. The trial was repeated during phentolamine infusion (alpha-adrenergic receptor blockade. Forearm vascular conductance (FVC; ml min-1 100 mmHg-1 and resistance (mmHg ml min-1 was calculated from BF (ml min-1 and local MAP (mmHg. Recovery of FBF and FVC (steady state inflation plus exercise value – nadir/ [steady state exercise (control value-nadir] with phentolamine was enhanced compared with the respective control (no drug trial (FBF = 97 ± 5% vs. 81 ± 6%, P < 0.05; FVC = 126 ± 9% vs. 91 ± 5%, P < 0.01. However, the absolute (0.05 ± 0.01 vs. 0.06 ± 0.01 mmHg ml min-1; P = 0.17 and relative (35 ± 5% vs. 31 ± 2%; P = 0.41 increase in vascular resistance at the onset of balloon inflation was not different between the alpha-adrenergic receptor inhibition and control (no drug trials. Therefore, our data indicate that alpha-adrenergic mediated vasoconstriction restricts compensatory vasodilation during forearm exercise with hypoperfusion, but is not responsible for the initial increase in vascular resistance at the onset of hypoperfusion.

Efeito oxidativo do óxido nítrico e infertilidade no macho Oxidative effect of nitric oxide and male infertility

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Onofre Ferreira de Carvalho

2002-01-01

Full Text Available A capacidade de fertilização dos espermatozóides é dependente, entre outros fatores, da sua motilidade e da integridade de sua membrana. As substâncias oxidativas, quando produzidas em excesso no organismo, em particular no líquido seminal, comprometem a motilidade do espermatozóide e a sua viabilidade em promover a fertilização. Um dos agentes oxidantes capazes de promover estes efeitos é o óxido nítrico (ON, responsável pela mediação em vários processos fisiológicos. O uso de terapias antioxidantes no tratamento de alguns tipos de infertilidade deve ser feito com cautela, pois uma inibição muito severa poderá comprometer as taxas de ON e, conseqüentemente, irá influenciar outros mecanismos fisiológicos dependentes de sua concentração.The capacity of fertilization of the sperm is dependent, among other factors, of the mobility and integrity of its membrane. The oxidative substances when produced in excess in the organism, in matter in the seminal liquid, they commit the mobility and viability of the sperm in their capacity of fertilization. One of the oxidative substance capable to promote these effects is the nitric oxide (NO, responsible for the mediation in several physiologic processes. The use of antioxidant therapies in the treatment of some infertility types should be made with caution because it can commit the nitric oxide's levels and consequently, it will influence other physiologic mechanisms dependents of its concentration.

Cyclooxygenase inhibition improves endothelial vasomotor dysfunction of visceral adipose arterioles in human obesity

Science.gov (United States)

Farb, Melissa G.; Tiwari, Stephanie; Karki, Shakun; Ngo, Doan TM; Carmine, Brian; Hess, Donald T.; Zuriaga, Maria A.; Walsh, Kenneth; Fetterman, Jessica L.; Hamburg, Naomi M.; Vita, Joseph A.; Apovian, Caroline M.; Gokce, Noyan

2013-01-01

Objective The purpose of this study was to determine whether cyclooxygenase inhibition improves vascular dysfunction of adipose microvessels from obese humans. Design and Methods In 20 obese subjects (age 37±12 yrs, BMI 47±8 kg/m2) we collected subcutaneous and visceral fat during bariatric surgery and characterized adipose depot-specific gene expression, endothelial cell phenotype, and microvascular function. Vasomotor function was assessed in response to endothelium-dependent agonists using videomicroscopy of small arterioles from fat. Results Arterioles from visceral fat exhibited impaired endothelium-dependent, acetylcholine-mediated vasodilation, compared to the subcutaneous depot (p<0.001). Expression of mRNA transcripts relevant to the cyclooxygenase pathway were upregulated in visceral compared to subcutaneous fat. Pharmacological inhibition of cyclooxygenase with indomethacin improved endothelium-dependent vasodilator function of arterioles from visceral fat by 2-fold (p=0.01), whereas indomethacin had no effect in the subcutaneous depot. Indomethacin increased activation via serine-1177 phosphorylation of endothelial nitric oxide synthase in response to acetylcholine in endothelial cells from visceral fat. Inhibition of endothelial nitric oxide synthase with Nω-nitro-L-arginine methyl ester abrogated the effects of cyclooxygenase-inhibition suggesting that vascular actions of indomethacin were related to increased nitric oxide bioavailability. Conclusions Our findings suggest that cyclooxygenase-mediated vasoconstrictor prostanoids partly contribute to endothelial dysfunction of visceral adipose arterioles in human obesity. PMID:23640904

Comparison of the vasodilator responses of isolated human and rat middle meningeal arteries to migraine related compounds

DEFF Research Database (Denmark)

Grände, Gustaf; Labruijere, Sieneke; Haanes, Kristian Agmund

2014-01-01

, telcagepant) were applied to the isolated arteries, and both induced a significant decrease of the effect of exogenously administrated CGRP. In experiments on rat middle meningeal arteries, pre-contracted with PGF2α, similar tendencies were seen. When the pre-contraction was switched to K+ in a separate...... series of experiments, CGRP and sildenafil significantly relaxed the arteries. CONCLUSIONS: Still no definite answer can be given as to why pain is experienced during an attack of migraine. No clear correlation was found between the efficacy of a substance as a meningeal artery vasodilator in human...

Voltammetric determination of nitric oxide using a glassy carbon electrode modified with a nanohybrid consisting of myoglobin, gold nanorods, and reduced graphene oxide

International Nuclear Information System (INIS)

Marlinda, Ab Rahman; Jayabal, Subramaniam; Yusoff, Norazriena; Huang, Nay Ming; Pandikumar, Alagarsamy; Suriani, Abu Bakar

2016-01-01

Myoglobin-modified gold nanorods incorporating reduced graphene oxide (rGO) were fabricated and deposited on a glassy carbon electrode (GCE) to obtain a sensor for nitric oxide (NO). The Mb-AuNR/rGO nanohybrid showed a transverse localized surface plasmon resonance (LSPR) band with a peak at 508 nm, and a longitudinal LSPR band at 724 nm. The AuNRs have an average length of 38 ± 3 nm and a width of 11 ± 1 nm. The GCE modified with the nanohybrid is shown to be a viable sensor for the determination of NO by linear sweep voltammetry. Its electrocatalytic response toward the oxidation of NO is distinctly enhanced compared to other electrodes. The sensor, best operated at a working voltage of 0.85 V (vs. SCE), showed two linear response ranges (from 10 to 100 μM, and from 100 to 1000 μM), with a detection limit of 5.5 μM. Furthermore, it exhibits excellent selectivity for NO over common interferents such as NaNO 3 , and also over electroactive species such as ascorbate, dopamine, glucose, and uric acid. These properties make it a promising tool for the detection of NO in situations such as capillary and pulmonary hypertension and embolism, and during vasodilation. (author)

Fiber type-specific nitric oxide protects oxidative myofibers against cachectic stimuli.

Directory of Open Access Journals (Sweden)

Zengli Yu

2008-05-01

Full Text Available Oxidative skeletal muscles are more resistant than glycolytic muscles to cachexia caused by chronic heart failure and other chronic diseases. The molecular mechanism for the protection associated with oxidative phenotype remains elusive. We hypothesized that differences in reactive oxygen species (ROS and nitric oxide (NO determine the fiber type susceptibility. Here, we show that intraperitoneal injection of endotoxin (lipopolysaccharide, LPS in mice resulted in higher level of ROS and greater expression of muscle-specific E3 ubiqitin ligases, muscle atrophy F-box (MAFbx/atrogin-1 and muscle RING finger-1 (MuRF1, in glycolytic white vastus lateralis muscle than in oxidative soleus muscle. By contrast, NO production, inducible NO synthase (iNos and antioxidant gene expression were greatly enhanced in oxidative, but not in glycolytic muscles, suggesting that NO mediates protection against muscle wasting. NO donors enhanced iNos and antioxidant gene expression and blocked cytokine/endotoxin-induced MAFbx/atrogin-1 expression in cultured myoblasts and in skeletal muscle in vivo. Our studies reveal a novel protective mechanism in oxidative myofibers mediated by enhanced iNos and antioxidant gene expression and suggest a significant value of enhanced NO signaling as a new therapeutic strategy for cachexia.

Temporal evolution of vasospasm and clinical outcome after intra-arterial vasodilator therapy in patients with aneurysmal subarachnoid hemorrhage.

Directory of Open Access Journals (Sweden)

Laleh Daftari Besheli

Full Text Available Intra-arterial (IA vasodilator therapy is one of the recommended treatments to minimize the impact of aneurysmal subarachnoid hemorrhage-induced cerebral vasospasm refractory to standard management. However, its usefulness and efficacy is not well established. We evaluated the effect IA vasodilator therapy on middle cerebral artery blood flow and on discharge outcome. We reviewed records for 115 adults admitted to Neurointensive Care Unit to test whether there was a difference in clinical outcome (discharge mRS in those who received IA infusions. In a subset of 19 patients (33 vessels treated using IA therapy, we tested whether therapy was effective in reversing the trends in blood flow. All measures of MCA blood flow increased from day -2 to -1 before infusion (maximum Peak Systolic Velocity (PSV 232.2±9.4 to 262.4±12.5 cm/s [p = 0.02]; average PSV 202.1±8.5 to 229.9±10.9 [p = 0.02]; highest Mean Flow Velocity (MFV 154.3±8.3 to 172.9±10.5 [p = 0.10]; average MFV 125.5±6.3 to 147.8±9.5 cm/s, [p = 0.02] but not post-infusion (maximum PSV 261.2±14.6 cm/s [p = .89]; average PSV 223.4±11.4 [p = 0.56]; highest MFV 182.9±12.4 cm/s [p = 0.38]; average MFV 153.0±10.2 cm/s [p = 0.54]. After IA therapy, flow velocities were consistently reduced (day X infusion interaction p<0.01 for all measures. However, discharge mRS was higher in IA infusion group, even after adjusting for sex, age, and admission grades. Thus, while IA vasodilator therapy was effective in reversing the vasospasm-mediated deterioration in blood flow, clinical outcomes in the treated group were worse than the untreated group. There is need for a prospective randomized controlled trial to avoid potential confounding effect of selection bias.

Peripheral arterial vasodilation hypothesis: a proposal for the initiation of renal sodium and water retention in cirrhosis

DEFF Research Database (Denmark)

Schrier, R W; Arroyo, V; Bernardi, M

1988-01-01

Renal sodium and water retention and plasma volume expansion have been shown to precede ascites formation in experimental cirrhosis. The classical "underfilling" theory, in which ascites formation causes hypovolemia and initiates secondary renal sodium and water retention, thus seems unlikely...... with cirrhosis. Arterial vasodilators and arteriovenous fistula are other examples in which renal sodium and water retention occur secondary to a decreased filling of the arterial vascular tree. An increase in cardiac output and hormonal stimulation are common features of cirrhosis, arteriovenous fistula...... and drug-induced peripheral arterial vasodilation. However, a predilection for the retained sodium and water to transudate into the abdominal cavity occurs with cirrhosis because of the presence of portal hypertension. The Peripheral Arterial Vasodilation Hypothesis also explains the continuum from...

Apixaban Enhances Vasodilatation Mediated by Protease-Activated Receptor 2 in Isolated Rat Arteries

Directory of Open Access Journals (Sweden)

Ambra Villari

2017-07-01

Full Text Available Apixaban (APX is a direct inhibitor of factor X (FXa approved for prophylaxis and treatment of deep venous thrombosis and atrial fibrillation. Because FXa activates protease-activated receptor 2 (PAR-2 in endothelium and vascular smooth muscle, inhibition of FXa by APX may affect vasomotor function. The effect of APX was assessed in vitro, by wire myography, in rat mesenteric resistance arteries (MRAs and basilar arteries challenged with vasoconstrictors [phenylephrine (PE; 5-hydroxytryptamine (5-HT], vasodilators [acetylcholine (ACh; sodium nitroprusside (SNP] or with the PAR-2 peptide agonist SLIGRL. APX (10 μM reduced the vasoconstriction to PE and 5-HT while did not change the vasodilatation to ACh or SNP. SLIGRL induced concentration-dependent vasodilation in pre-constricted arteries, that was reduced by incubation with the NO inhibitor NG-nitro-L-arginine (L-NNA and abolished by endothelium removal. APX enhanced vasodilation to SLIGRL either in the presence or in the absence of L-NNA, but was ineffective in endothelium-denuded vessels. In preparations from heparin-treated rats (to inhibit FXa APX did not change the vasodilation to SLIGRL. FXa enzymatic activity, detected in mesentery homogenates from controls, was inhibited by APX, whereas APX-sensitive enzymatic activity was undetectable in homogenates from heparin-treated rats. Immunoblot analysis showed that incubation of MRA or aorta with APX increased the abundance of PAR-2, an effect not seen in MRA from heparin-treated rats or in endothelium-denuded aortas. In conclusion, inhibition of FXa by APX increases vasodilatation mediated by PAR-2. APX may act by inhibiting PAR-2 desensitization induced by endogenous FXa. This effect could be useful in the context of endothelial dysfunction associated to cardiovascular diseases.

Mid-Ir Cavity Ring-Down Spectrometer for Biological Trace Nitric Oxide Detection

Science.gov (United States)

Kan, Vincent; Ragab, Ahemd; Stsiapura, Vitali; Lehmann, Kevin K.; Gaston, Benjamin M.

2011-06-01

S-nitrosothiols have received much attention in biochemistry and medicine as donors of nitrosonium ion (NO^+) and nitric oxide (NO) - physiologically active molecules involved in vasodilation and signal transduction. Determination of S-nitrosothiols content in cells and tissues is of great importance for fundamental research and medical applications. We will report on our ongoing development of a instrument to measure trace levels of nitric oxide gas (NO), released from S-nitrosothiols after exposure to UV light (340 nm) or reaction with L-Cysteine+CuCl mixture. The instrument uses the method of cavity ring-down spectroscopy, probing rotationally resolved lines in the vibrational fundamental transition near 5.2 μm. The laser source is a continuous-wave, room temperature external cavity quantum cascade laser. An acousto-optic modulator is used to abruptly turn off the optical power incident on the cavity when the laser and cavity pass through resonance.

Absorption and oxidation of no in ionic liquids

DEFF Research Database (Denmark)

2013-01-01

The present invention concerns the absorption and in situ oxidation of nitric oxide (NO) in the presence of water and oxygen in ionic liquid compositions at ambient temperature.......The present invention concerns the absorption and in situ oxidation of nitric oxide (NO) in the presence of water and oxygen in ionic liquid compositions at ambient temperature....

Nitric Oxide Mediates Biofilm Formation and Symbiosis in Silicibacter sp. Strain TrichCH4B.

Science.gov (United States)

Rao, Minxi; Smith, Brian C; Marletta, Michael A

2015-05-05

Nitric oxide (NO) plays an important signaling role in all domains of life. Many bacteria contain a heme-nitric oxide/oxygen binding (H-NOX) protein that selectively binds NO. These H-NOX proteins often act as sensors that regulate histidine kinase (HK) activity, forming part of a bacterial two-component signaling system that also involves one or more response regulators. In several organisms, NO binding to the H-NOX protein governs bacterial biofilm formation; however, the source of NO exposure for these bacteria is unknown. In mammals, NO is generated by the enzyme nitric oxide synthase (NOS) and signals through binding the H-NOX domain of soluble guanylate cyclase. Recently, several bacterial NOS proteins have also been reported, but the corresponding bacteria do not also encode an H-NOX protein. Here, we report the first characterization of a bacterium that encodes both a NOS and H-NOX, thus resembling the mammalian system capable of both synthesizing and sensing NO. We characterized the NO signaling pathway of the marine alphaproteobacterium Silicibacter sp. strain TrichCH4B, determining that the NOS is activated by an algal symbiont, Trichodesmium erythraeum. NO signaling through a histidine kinase-response regulator two-component signaling pathway results in increased concentrations of cyclic diguanosine monophosphate, a key bacterial second messenger molecule that controls cellular adhesion and biofilm formation. Silicibacter sp. TrichCH4B biofilm formation, activated by T. erythraeum, may be an important mechanism for symbiosis between the two organisms, revealing that NO plays a previously unknown key role in bacterial communication and symbiosis. Bacterial nitric oxide (NO) signaling via heme-nitric oxide/oxygen binding (H-NOX) proteins regulates biofilm formation, playing an important role in protecting bacteria from oxidative stress and other environmental stresses. Biofilms are also an important part of symbiosis, allowing the organism to remain in a

IBX-mediated oxidation of unactivated cyclic amines: application in highly diastereoselective oxidative Ugi-type and aza-Friedel-Crafts reactions.

Science.gov (United States)

de Graaff, C; Bensch, L; van Lint, Matthijs J; Ruijter, E; Orru, R V A

2015-10-28

The first o-iodoxybenzoic acid (IBX) mediated oxidation of unactivated amines to imines is described. A range of meso-pyrrolidines were shown to be suitable substrates. The chemical space was further explored with one-pot oxidative Ugi-type and aza-Friedel-Crafts reactions, which proved to be highly diastereoselective.

Protease activated receptors (PARS) mediation in gyroxin biological activity; Mediacao dos receptores ativados por proteases (PARs) em atividades biologicas da giroxina

Energy Technology Data Exchange (ETDEWEB)

Silva, Jose Alberto Alves da

2009-07-01

Gyroxin is a serine protease enzyme from the South American rattlesnake (Crotalus durissus terrificus) venom; it is only partially characterized and has multiple activities. Gyroxin induces blood coagulation, blood pressure decrease and a neurotoxic behavior named barrel rotation. The mechanisms involved in this neurotoxic activity are not known. Whereas gyroxin is a member of enzymes with high potential to become a new drug with clinical applications such as thrombin, batroxobin, ancrod, tripsyn and kalicrein, it is important to find out how gyroxin works. The analysis on agarose gel electrophoresis and circular dichroism confirmed the molecules' integrity and purity. The gyroxin intravenous administration in mice proved its neurotoxicity (barrel rotation). In vivo studies employing intravital microscopy proved that gyroxin induces vasodilation with the participation of protease activated receptors (PARs), nitric oxide and Na+K+ATPase. The leukocytes' adherence and rolling counting indicated that gyroxin has no pro inflammatory activity. Gyroxin induced platelet aggregation, which was blocked by inhibitors of PAR1 and PAR4 receptors (SCH 79797 and tcY-NH{sub 2}, respectively). Finally, it was proved that the gyroxin temporarily alter the permeability of the blood brain barrier (BBB). Our study has shown that both the protease-activated receptors and nitric oxide are mediators involved in the biological activities of gyroxin. (author)

mediated oxidation of vic-dioxime to furoxan

Indian Academy of Sciences (India)

membered heterocycles and exhibit nitric oxide (NO) ... copper complexes (via chelation through nitrogen atoms of ... ammonium nitrate, this oxidation process was observed to take ... failed to produce the blue intermediate species at low ...

Human urotensin-II is an endothelium-dependent vasodilator in rat small arteries

Science.gov (United States)

Bottrill, Fiona E; Douglas, Stephen A; Hiley, C Robin; White, Richard

2000-01-01

The possible role of the endothelium in modulating responses to human urotensin-II (U-II) was investigated using isolated segments of rat thoracic aorta, small mesenteric artery, left anterior descending coronary artery and basilar artery.Human U-II was a potent vasoconstrictor of endothelium-intact isolated rat thoracic aorta (EC50=3.5±1.1 nM, Rmax=103±10% of control contraction induced by 60 mM KCl and 1 μM noradrenaline). However the contractile response was not significantly altered by removal of the endothelium or inhibition of nitric oxide synthesis with L-NAME (100 μM). Human U-II did not cause relaxation of noradrenaline-precontracted, endothelium-intact rat aortae.Human U-II contracted endothelium-intact rat isolated left anterior descending coronary arteries (EC50=1.3±0.8 nM, Rmax=20.1±4.9% of control contraction induced by 10 μM 5-HT). The contractile response was significantly enhanced by removal of the endothelium (Rmax=55.4±16.1%). Moreover, human U-II caused concentration-dependent relaxation of 5-HT-precontracted arteries, which was abolished by L-NAME or removal of the endothelium.No contractile effects of human U-II were found in rat small mesenteric arteries. However the peptide caused potent, concentration- and endothelium-dependent relaxations of methoxamine-precontracted vessels. The relaxant responses were potentiated by L-NAME (300 μM) but abolished in the additional presence of 25 mM KCl (which inhibits the actions of endothelium-derived hyperpolarizing factor).The present study is the first to show that human U-II is a potent endothelium-dependent vasodilator in some rat resistance vessels, and acts through release of EDHF as well as nitric oxide. Our findings have also highlighted clear anatomical differences in the responses of different vascular beds to human U-II which are likely to be important in determining the overall cardiovascular activity of this peptide. PMID:10952676

Comparison of vasodilator drug prazosin with digoxin in aortic regurgitation.

Science.gov (United States)

Hockings, B E; Cope, G D; Clarke, G M; Taylor, R R

1980-01-01

Intravenous administration of the vasodilator sodium nitroprusside has beneficial haemodynamic effects in subjects with severe aortic regurgitation while acute digitalisation can produce unwanted effects associated with an increase in systemic vascular resistance. This study compares the haemodynamic effects of the vasodilator prazosin and digoxin in eight patients with isolated severe aortic regurgitation. Prazosin 5 mg orally resulted in a 12 +/- 3 (SE) per cent increase in cardiac index (thermodilution), maintained over four to six hours, while digoxin 0.75 mg intravenously did not change the cardiac index. Prazosin reduced mean arterial pressure by 9 +/- 3 mmHg and systemic vascular resistance by 18 +/- 4 per cent while digoxin resulted in a 6 +/- 2 per cent increase in the latter. Mean pulmonary capillary wedge pressure fell 3 mmHg with prazosin. In this group of patients with severe aortic regurgitation but without severe cardiac failure, the changes with either drug, studied in doses conventionally used, were small but those with prazosin were directionally more desirable than those resulting from digoxin. PMID:7378215

Effect of the Menstrual Cycle on Maximum Oxygen Consumption and Endothelium-Dependent Vasodilation

National Research Council Canada - National Science Library

Andrews, Thomas

1997-01-01

.... We studied endothelium-dependent vasodilation of the brachial artery during three phases of the menstrual cycle in 20 eumenorrheic subjects to determine the effect of endogenous estradiol and progesterone...

Calcium and Superoxide-Mediated Pathways Converge to Induce Nitric Oxide-Dependent Apoptosis in Mycobacterium fortuitum-Infected Fish Macrophages.

Science.gov (United States)

Datta, Debika; Khatri, Preeti; Banerjee, Chaitali; Singh, Ambika; Meena, Ramavatar; Saha, Dhira Rani; Raman, Rajagopal; Rajamani, Paulraj; Mitra, Abhijit; Mazumder, Shibnath

2016-01-01

Mycobacterium fortuitum causes 'mycobacteriosis' in wide range of hosts although the mechanisms remain largely unknown. Here we demonstrate the role of calcium (Ca+2)-signalling cascade on M. fortuitum-induced apoptosis in headkidney macrophages (HKM) of Clarias sp. M. fortuitum could trigger intracellular-Ca+2 influx leading to the activation of calmodulin (CaM), protein kinase C alpha (PKCα) and Calmodulin kinase II gamma (CaMKIIg). Gene silencing and inhibitor studies established the role of CaM in M. fortuitum pathogenesis. We noted that CaMKIIg activation is regulated by CaM as well as PKCα-dependent superoxide anions. This is altogether first report of oxidised CaMKIIg in mycobacterial infections. Our studies with targeted-siRNA and pharmacological inhibitors implicate CaMKIIg to be pro-apoptotic and critical for the activation of extra-cellular signal regulated kinase 1/2 (ERK1/2). Inhibiting the ERK1/2 pathway attenuated nitric oxide synthase 2 (NOS2)-induced nitric oxide (NO) production. Conversely, inhibiting the NOS2-NO axis by specific-siRNA and inhibitors down-regulated ERK1/2 activation suggesting the crosstalk between ERK1/2 and NO is essential for pathogenesis induced by the bacterium. Silencing the NOS2-NO axis enhanced intracellular bacterial survival and attenuated caspase-8 mediated activation of caspase-3 in the infected HKM. Our findings unveil hitherto unknown mechanism of M. fortuitum pathogenesis. We propose that M. fortuitum triggers intracellular Ca+2 elevations resulting in CaM activation and PKCα-mediated superoxide generation. The cascade converges in common pathway mediated by CaMKIIg resulting in the activation of ERK1/2-NOS2 axis. The crosstalk between ERK1/2 and NO shifts the balance in favour of caspase dependent apoptosis of M. fortuitum-infected HKM.

Fabrication and characterization of an inorganic gold and silica nanoparticle mediated drug delivery system for nitric oxide

Energy Technology Data Exchange (ETDEWEB)

Das, Amitava; Singla, Sumit K; Shah, Vijay H [Gastroenterology Research Unit, Department of Internal Medicine, Mayo Clinic College of Medicine, 200 First Street S.W., Rochester, MN 55905 (United States); Mukherjee, Priyabrata; Mukhopadhyay, Debabrata; Patra, Chitta Ranjan [Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, 200 First Street S.W., Rochester, MN 55905 (United States); Guturu, Praveen [Department of Internal Medicine, UTMB, Galveston, TX 77555 (United States); Frost, Megan C, E-mail: patra.chittaranjan@mayo.edu, E-mail: patra.chitta@gmail.com [Department of Biomedical Engineering, Michigan Technological University, Houghton, MI 49931 (United States)

2010-07-30

Nitric oxide (NO) plays an important role in inhibiting the development of hepatic fibrosis and its ensuing complication of portal hypertension by inhibiting human hepatic stellate cell (HSC) activation. Here we have developed a gold nanoparticle and silica nanoparticle mediated drug delivery system containing NO donors, which could be used for potential therapeutic application in chronic liver disease. The gold nanoconjugates were characterized using several physico-chemical techniques such as UV-visible spectroscopy and transmission electron microscopy. Silica nanoconjugates were synthesized and characterized as reported previously. NO released from gold and silica nanoconjugates was quantified under physiological conditions (pH = 7.4 at 37 deg. C) for a substantial period of time. HSC proliferation and the vascular tube formation ability, manifestations of their activation, were significantly attenuated by the NO released from these nanoconjugates. This study indicates that gold and silica nanoparticle mediated drug delivery systems for introducing NO could be used as a strategy for the treatment of hepatic fibrosis or chronic liver diseases, by limiting HSC activation.

Fabrication and characterization of an inorganic gold and silica nanoparticle mediated drug delivery system for nitric oxide

International Nuclear Information System (INIS)

Das, Amitava; Singla, Sumit K; Shah, Vijay H; Mukherjee, Priyabrata; Mukhopadhyay, Debabrata; Patra, Chitta Ranjan; Guturu, Praveen; Frost, Megan C

2010-01-01

Nitric oxide (NO) plays an important role in inhibiting the development of hepatic fibrosis and its ensuing complication of portal hypertension by inhibiting human hepatic stellate cell (HSC) activation. Here we have developed a gold nanoparticle and silica nanoparticle mediated drug delivery system containing NO donors, which could be used for potential therapeutic application in chronic liver disease. The gold nanoconjugates were characterized using several physico-chemical techniques such as UV-visible spectroscopy and transmission electron microscopy. Silica nanoconjugates were synthesized and characterized as reported previously. NO released from gold and silica nanoconjugates was quantified under physiological conditions (pH = 7.4 at 37 deg. C) for a substantial period of time. HSC proliferation and the vascular tube formation ability, manifestations of their activation, were significantly attenuated by the NO released from these nanoconjugates. This study indicates that gold and silica nanoparticle mediated drug delivery systems for introducing NO could be used as a strategy for the treatment of hepatic fibrosis or chronic liver diseases, by limiting HSC activation.

Control of the neurovascular coupling by nitric oxide-dependent regulation of astrocytic Ca2+ signaling

Directory of Open Access Journals (Sweden)

Manuel Francisco Muñoz

2015-03-01

Full Text Available Neuronal activity must be tightly coordinated with blood flow to keep proper brain function, which is achieved by a mechanism known as neurovascular coupling. Then, an increase in synaptic activity leads to a dilation of local parenchymal arterioles that matches the enhanced metabolic demand. Neurovascular coupling is orchestrated by astrocytes. These glial cells are located between neurons and the microvasculature, with the astrocytic endfeet ensheathing the vessels, which allows fine intercellular communication. The neurotransmitters released during neuronal activity reach astrocytic receptors and trigger a Ca2+ signaling that propagates to the endfeet, activating the release of vasoactive factors and arteriolar dilation. The astrocyte Ca2+ signaling is coordinated by gap junction channels and hemichannels formed by connexins (Cx43 and Cx30 and channels formed by pannexins (Panx-1. The neuronal activity-initiated Ca2+ waves are propagated among neighboring astrocytes directly via gap junctions or through ATP release via connexin hemichannels or pannexin channels. In addition, Ca2+ entry via connexin hemichannels or pannexin channels may participate in the regulation of the astrocyte signaling-mediated neurovascular coupling. Interestingly, nitric oxide (NO can activate connexin hemichannel by S-nitrosylation and the Ca2+-dependent NO-synthesizing enzymes endothelial NO synthase (eNOS and neuronal NOS (nNOS are expressed in astrocytes. Therefore, the astrocytic Ca2+ signaling triggered in neurovascular coupling may activate NO production, which, in turn, may lead to Ca2+ influx through hemichannel activation. Furthermore, NO release from the hemichannels located at astrocytic endfeet may contribute to the vasodilation of parenchymal arterioles. In this review, we discuss the mechanisms involved in the regulation of the astrocytic Ca2+ signaling that mediates neurovascular coupling, with a special emphasis in the possible participation of NO in

[Vasodilative effects of indole alkaloids obtained from domestic plants, Uncaria rhynchophylla Miq. and Amsonia elliptica Roem. et Schult].

Science.gov (United States)

Ozaki, Y

1990-02-01

Vasodilative effects of hirsutine (HS) and hirsuteine (HST) which were isolated from the domestic plant Uncaria rhynchophylla Miq. and beta-yohimbine (beta-Y) which was isolated from the domestic plant Amsonia elliptica Roem. et Schult. were carried out. In the hind-limb artery of anesthetized dogs, intra-arterial administration of HS, HST and beta-Y caused a vasodilatation. The vasodilative potency of HS was somewhat stronger than that of HST, and the potency of both alkaloids was approximately equal to that of papaverine. The vasodilative effect of beta-Y was similar to that of yohimbine, which is considered to be derived from its alpha-adrenoceptor blocking effect, and the potency of both alkaloids was approximately the same, while the effect of beta-Y was stronger than that of papaverine. In the coronary artery, HS showed a vasodilatation and its potency was weaker than that of papaverine. Also, HS showed the same effect in the cerebral artery, and the potency of HS was approximately the same as that of papaverine. These results suggest that the mode of the vasodilative effect induced by HS may partly differ from that of papaverine.

Comparative effects of enzogenol and vitamin C supplementation versus vitamin C alone on endothelial function and biochemical markers of oxidative stress and inflammation in chronic smokers.

Science.gov (United States)

Young, Joanna M; Shand, Brett I; McGregor, Patrice M; Scott, Russell S; Frampton, Christopher M

2006-01-01

Chronic smoking is associated with endothelial dysfunction and inflammation, with oxidative stress contributing to both these processes. In this study, we investigated the effect of combined antioxidant treatment with Enzogenol, a flavonoid extract from the bark of Pinus radiata and vitamin C, over and above vitamin C alone, on endothelial function, plasma markers of inflammation and oxidative stress, blood pressure (BP) and anthropometrics. Forty-four chronic smokers without established cardiovascular disease were assigned randomly to receive either 480 mg Enzogenol and 60 mg vitamin C, or 60 mg vitamin C alone daily for 12 weeks. Endothelial function in the brachial artery was assessed by flow-mediated vasodilation (FMD). FMD improved in both treatment groups (p effect on macrovascular endothelial function over and above that seen in the vitamin C alone group. However, Enzogenol did demonstrate additional favourable effects on protein oxidative damage and fibrinogen levels.

Electrochemical Water Oxidation and Stereoselective Oxygen Atom Transfer Mediated by a Copper Complex.

Science.gov (United States)

Kafentzi, Maria-Chrysanthi; Papadakis, Raffaello; Gennarini, Federica; Kochem, Amélie; Iranzo, Olga; Le Mest, Yves; Le Poul, Nicolas; Tron, Thierry; Faure, Bruno; Simaan, A Jalila; Réglier, Marius

2018-04-06

Water oxidation by copper-based complexes to form dioxygen has attracted attention in recent years, with the aim of developing efficient and cheap catalysts for chemical energy storage. In addition, high-valent metal-oxo species produced by the oxidation of metal complexes in the presence of water can be used to achieve substrate oxygenation with the use of H 2 O as an oxygen source. To date, this strategy has not been reported for copper complexes. Herein, a copper(II) complex, [(RPY2)Cu(OTf) 2 ] (RPY2=N-substituted bis[2-pyridyl(ethylamine)] ligands; R=indane; OTf=triflate), is used. This complex, which contains an oxidizable substrate moiety (indane), is used as a tool to monitor an intramolecular oxygen atom transfer reaction. Electrochemical properties were investigated and, upon electrolysis at 1.30 V versus a normal hydrogen electrode (NHE), both dioxygen production and oxygenation of the indane moiety were observed. The ligand was oxidized in a highly diastereoselective manner, which indicated that the observed reactivity was mediated by metal-centered reactive species. The pH dependence of the reactivity was monitored and correlated with speciation deduced from different techniques, ranging from potentiometric titrations to spectroscopic studies and DFT calculations. Water oxidation for dioxygen production occurs at neutral pH and is probably mediated by the oxidation of a mononuclear copper(II) precursor. It is achieved with a rather low overpotential (280 mV at pH 7), although with limited efficiency. On the other hand, oxygenation is maximum at pH 8-8.5 and is probably mediated by the electrochemical oxidation of an antiferromagnetically coupled dinuclear bis(μ-hydroxo) copper(II) precursor. This constitutes the first example of copper-centered oxidative water activation for a selective oxygenation reaction. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Inhaled therapy for the management of perioperative pulmonary hypertension

Directory of Open Access Journals (Sweden)

C A Thunberg

2015-01-01

Full Text Available Patients with pulmonary hypertension (PH are at high risk for complications in the perioperative setting and often receive vasodilators to control elevated pulmonary artery pressure (PAP. Administration of vasodilators via inhalation is an effective strategy for reducing PAP while avoiding systemic side effects, chiefly hypotension. The prototypical inhaled pulmonary-specific vasodilator, nitric oxide (NO, has a proven track record but is expensive and cumbersome to implement. Alternatives to NO, including prostanoids (such as epoprostenol, iloprost, and treprostinil, NO-donating drugs (sodium nitroprusside, nitroglycerin, and nitrite, and phosphodiesterase inhibitors (milrinone, sildenafil may be given via inhalation for the purpose of treating elevated PAP. This review will focus on the perioperative therapy of PH using inhaled vasodilators.

Graphene oxide-mediated rapid dechlorination of carbon tetrachloride by green rust

DEFF Research Database (Denmark)

Huang, Li-Zhi; Hansen, Hans Christian B.; Daasbjerg, Kim

2017-01-01

Graphene-based nanomaterials can mediate environmentally relevant abiotic redox reactions of chlorinated aliphatic hydrocarbons. In this study as low amounts as ∼0.007 % of graphene oxide (GO) was found to catalyze the reduction of carbon tetrachloride by layered Fe(II)-Fe(III) hydroxide (Green R....... This study indicates that traces of graphene oxide can affect reaction pathways as well as kinetics for dechlorination processes in anoxic sediments by facilitating a partial dechlorination....

ATP induced vasodilatation and purinergic receptors in the human leg: roles of nitric oxide, prostaglandins and adenosine

DEFF Research Database (Denmark)

Mortensen, Stefan P; Gonzalez-Alonso, Jose; Bune, Laurids

2009-01-01

.05) and was associated with a parallel lowering in leg vascular conductance and cardiac output and a compensatory increase in leg O2 extraction. Infusion of theophylline did not alter the ATP induced leg hyperemia or systemic variables. Real time PCR analysis of the mRNA content from the vastus lateralus muscle of 8...... subjects showed the highest expression of P2Y2 receptors of the 10 investigated P2 receptor subtypes. Immunohistochemistry showed that P2Y2 receptors were located in the endothelium of microvessels and smooth muscle cells, whereas P2X1 receptors were located in the endothelium and the sacrolemma....... Collectively, these results indicate that NO and prostaglandins, but not adenosine, play a role in ATP induced vasodilation in human skeletal muscle. The localization of the P2Y2 and P2X1 receptors suggest that these receptors may mediate ATP induced vasodilation in skeletal muscle. Key words: Skeletal Muscle...

Iron-mediated lipid oxidation in 70% fish oil-in-ater emulsions

DEFF Research Database (Denmark)

Horn, Anna Frisenfeldt; Nielsen, Nina Skall; Jacobsen, Charlotte

2012-01-01

The objective of this study was to investigate the protective effect of five different emulsifiers on iron‐mediated lipid oxidation in 70% fish oil‐in‐water emulsions. The emulsifiers were either based on protein (whey protein isolate and sodium caseinate) or based on phospholipid (soy lecithin...... and two milk phospholipids with different phospholipid contents, MPL20 and MPL75). Lipid oxidation was studied at pH 4.5 and 7.0, and results were compared to lipid oxidation in neat fish oil. Results showed that all emulsions oxidised more than neat oil. Furthermore, emulsions prepared with proteins...

In vivo comparative study of ocular vasodilation, a relative indicator of hyperemia, in guinea pigs following treatment with bimatoprost ophthalmic solutions 0.01% and 0.03%

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Abayomi B Ogundele

2010-06-01

Full Text Available Abayomi B Ogundele, David Earnest, Marsha A McLaughlinAlcon Research, Limited, Fort Worth, TX, USAObjective: The objective of this in vivo study was to compare the incidence of vasodilation in guinea pigs following topical administration of bimatoprost ophthalmic solutions 0.01% and 0.03%.Methods: The study comprised 20 guinea pigs assigned to 2 treatment groups (10 per treatment group to receive either bimatoprost 0.01% or bimatoprost 0.03%. Animals were hand-held under 2.75 × magnification to score ocular vasodilation (a measure of hyperemia, using a scoring system developed at Alcon Research, Ltd. Following baseline ocular scoring, each animal received a 30 μL dose to the left eye of either bimatoprost 0.01% (3 μg or bimatoprost 0.03% (9 μg. Vasodilation was again scored at 1, 2, 3, 4, 5 and 6 hours after dosing. Incidence of vasodilation was calculated as the percent of total eyes in each 2-hour time interval with scores ≥2.Results: The incidence of vasodilation was higher in the bimatoprost 0.01% treatment group (range, 45.0% to 60.0% than the bimatoprost 0.03% treatment group (range, 30.0% to 52.2% at all post-dosing time points.Conclusion: The 2 bimatoprost formulations elicited ocular vasodilation of long duration (>6 hours in the guinea pig model, with the bimatoprost 0.01% treatment group showing a higher incidence of ocular vasodilation than the bimatoprost 0.03% treatment group. Further clinical studies would be needed to determine whether the higher incidence of vasodilation may also be attributed to the increased BAK concentration in the bimatoprost 0.01% formulation.Keywords: bitamoprost, ocular vasodilation, hyperemia

Extremely radioresistant microbe Deinococcus radiodurans does not survive tellurite-mediated oxidative stress: revelation of molecular basis

International Nuclear Information System (INIS)

Apte, Shree Kumar; Narasimha, Anaganti; Basu, Bhakti

2014-01-01

Deinococcus radiodurans exhibits extraordinary resistance to gamma radiation as well as oxidative stress. Comparison of tellurite stress with gamma irradiation, both of which impart severe oxidative stress, revealed that tellurite induced less ROS and caused less oxidative damage to proteins, but was much more lethal to D. radiodurans than gamma irradiation. The proteomic changes induced by tellurite exposure were mapped by two dimensional protein electrophoresis followed by mass spectrometry. Seventy proteins belonging to major functional categories of oxidative stress alleviation, protein translation/folding and metabolism were identified. Tellurite responsive proteome dynamics displayed (i) up-regulation of proteins involved in tellurite stress resistance and oxidative stress alleviation, dehydrogenases involved in generation of reducing potential, and chaperones (such DnaK), and (ii) down regulation of key glycolysis and TCA cycle enzymes, proteins involved in protein translation/folding and energy production. Tellurite stress also resulted in nearly 50% loss in the cellular reducing potential within 1h of exposure while gamma irradiation had no such effect. The findings provide a better insight into the mechanism of tellurite toxicity, beyond metal mediated oxidative stress, in this extremophile. (author)

Iron-mediated anaerobic oxidation of methane in brackish coastal sediments.

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Egger, Matthias; Rasigraf, Olivia; Sapart, Célia J; Jilbert, Tom; Jetten, Mike S M; Röckmann, Thomas; van der Veen, Carina; Bândă, Narcisa; Kartal, Boran; Ettwig, Katharina F; Slomp, Caroline P

2015-01-06

Methane is a powerful greenhouse gas and its biological conversion in marine sediments, largely controlled by anaerobic oxidation of methane (AOM), is a crucial part of the global carbon cycle. However, little is known about the role of iron oxides as an oxidant for AOM. Here we provide the first field evidence for iron-dependent AOM in brackish coastal surface sediments and show that methane produced in Bothnian Sea sediments is oxidized in distinct zones of iron- and sulfate-dependent AOM. At our study site, anthropogenic eutrophication over recent decades has led to an upward migration of the sulfate/methane transition zone in the sediment. Abundant iron oxides and high dissolved ferrous iron indicate iron reduction in the methanogenic sediments below the newly established sulfate/methane transition. Laboratory incubation studies of these sediments strongly suggest that the in situ microbial community is capable of linking methane oxidation to iron oxide reduction. Eutrophication of coastal environments may therefore create geochemical conditions favorable for iron-mediated AOM and thus increase the relevance of iron-dependent methane oxidation in the future. Besides its role in mitigating methane emissions, iron-dependent AOM strongly impacts sedimentary iron cycling and related biogeochemical processes through the reduction of large quantities of iron oxides.

Enteric Glia Mediate Neuron Death in Colitis Through Purinergic Pathways That Require Connexin-43 and Nitric OxideSummary

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Isola A.M. Brown

2016-01-01

Full Text Available Background & Aims: The concept of enteric glia as regulators of intestinal homeostasis is slowly gaining acceptance as a central concept in neurogastroenterology. Yet how glia contribute to intestinal disease is still poorly understood. Purines generated during inflammation drive enteric neuron death by activating neuronal P2X7 purine receptors (P2X7R; triggering adenosine triphosphate (ATP release via neuronal pannexin-1 channels that subsequently recruits intracellular calcium ([Ca2+]i in surrounding enteric glia. We tested the hypothesis that the activation of enteric glia contributes to neuron death during inflammation. Methods: We studied neuroinflammation in vivo using the 2,4-dinitrobenzene sulfonic acid model of colitis and in situ using whole-mount preparations of human and mouse intestine. Transgenic mice with a targeted deletion of glial connexin-43 (Cx43 [GFAP::CreERT2+/−/Cx43f/f] were used to specifically disrupt glial signaling pathways. Mice deficient in inducible nitric oxide (NO synthase (iNOS−/− were used to study NO production. Protein expression and oxidative stress were measured using immunohistochemistry and in situ Ca2+ and NO imaging were used to monitor glial [Ca2+]i and [NO]i. Results: Purinergic activation of enteric glia drove [Ca2+]i responses and enteric neuron death through a Cx43-dependent mechanism. Neurotoxic Cx43 activity, driven by NO production from glial iNOS, was required for neuron death. Glial Cx43 opening liberated ATP and Cx43-dependent ATP release was potentiated by NO. Conclusions: Our results show that the activation of glial cells in the context of neuroinflammation kills enteric neurons. Mediators of inflammation that include ATP and NO activate neurotoxic pathways that converge on glial Cx43 hemichannels. The glial response to inflammatory mediators might contribute to the development of motility disorders. Keywords: Enteric Nervous System, Hemichannels

Diet-induced obesity impairs endothelium-derived hyperpolarization via altered potassium channel signaling mechanisms.

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Rebecca E Haddock

Full Text Available BACKGROUND: The vascular endothelium plays a critical role in the control of blood flow. Altered endothelium-mediated vasodilator and vasoconstrictor mechanisms underlie key aspects of cardiovascular disease, including those in obesity. Whilst the mechanism of nitric oxide (NO-mediated vasodilation has been extensively studied in obesity, little is known about the impact of obesity on vasodilation to the endothelium-derived hyperpolarization (EDH mechanism; which predominates in smaller resistance vessels and is characterized in this study. METHODOLOGY/PRINCIPAL FINDINGS: Membrane potential, vessel diameter and luminal pressure were recorded in 4(th order mesenteric arteries with pressure-induced myogenic tone, in control and diet-induced obese rats. Obesity, reflecting that of human dietary etiology, was induced with a cafeteria-style diet (∼30 kJ, fat over 16-20 weeks. Age and sexed matched controls received standard chow (∼12 kJ, fat. Channel protein distribution, expression and vessel morphology were determined using immunohistochemistry, Western blotting and ultrastructural techniques. In control and obese rat vessels, acetylcholine-mediated EDH was abolished by small and intermediate conductance calcium-activated potassium channel (SK(Ca/IK(Ca inhibition; with such activity being impaired in obesity. SK(Ca-IK(Ca activation with cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl-6-methyl-pyrimidin-4-yl]-amine (CyPPA and 1-ethyl-2-benzimidazolinone (1-EBIO, respectively, hyperpolarized and relaxed vessels from control and obese rats. IK(Ca-mediated EDH contribution was increased in obesity, and associated with altered IK(Ca distribution and elevated expression. In contrast, the SK(Ca-dependent-EDH component was reduced in obesity. Inward-rectifying potassium channel (K(ir and Na(+/K(+-ATPase inhibition by barium/ouabain, respectively, attenuated and abolished EDH in arteries from control and obese rats, respectively; reflecting differential K

Susceptibility of Iα- and Iβ-Dominated Cellulose to TEMPO-Mediated Oxidation.

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Carlsson, Daniel O; Lindh, Jonas; Strømme, Maria; Mihranyan, Albert

2015-05-11

The susceptibility of Iα- and Iβ-dominated cellulose to TEMPO-mediated oxidation was studied in this work since the cellulose Iα-allomorph is generally considered to be thermodynamically less stable and therefore more reactive than the cellulose Iβ-allomorph. Highly crystalline Cladophora nanocellulose, which is dominated by the Iα-allomorph, was oxidized to various degrees with TEMPO oxidant via bulk electrolysis in the absence of co-oxidants. Further, the Cladophora nanocellulose was thermally annealed in glycerol to produce its Iβ-dominated form and then oxidized. The produced materials were subsequently studied using FTIR, CP/MAS (13)C NMR, XRD, and SEM. The solid-state analyses confirmed that the annealed Cladophora cellulose was successfully transformed from an Iα- to an Iβ-dominated form. The results of the analyses of pristine and annealed TEMPO-oxidized samples suggest that Iα- and Iβ-dominated cellulose do not differ in susceptibility to TEMPO-oxidation. This work hence suggests that cellulose from different sources are not expected to differ in susceptibility to the oxidation due to differences in allomorph composition.

Adenoviral transfer of the heme oxygenase-1 gene protects striatal astrocytes from heme-mediated oxidative injury.

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Teng, Zhi-Ping; Chen, Jing; Chau, Lee-Young; Galunic, Nicholas; Regan, Raymond F

2004-11-01

Heme oxygenase-1 (HO-1) is induced in the CNS after hemorrhage, and may have an effect on injury to surrounding tissue. Hemin, the preferred substrate of HO, is a neurotoxin that is present in intracranial hematomas. In a prior study, we observed that HO inhibitors increased the vulnerability of cultured cortical astrocytes to heme-mediated oxidative injury. To investigate the effect of HO more specifically, we used an adenoviral vector encoding the human HO-1 gene to specifically increase HO-1 expression. Incubation with 100 MOI of the HO-1 adenovirus (Adv-HHO-1) for 24 h increased both HO-1 protein and HO activity; a control adenovirus lacking the HO-1 gene had no effect. Using a DNA probe that was specific for human HO-1, 80.5 +/- 7.2% of astrocytes were observed to be infected by in situ hybridization. The cell death produced by 30-60 microM hemin was significantly reduced by pretreatment with 100 MOI Adv-HHO-1, as assessed by LDH release, propidium iodide exclusion, and MTT reduction assay. The threefold increase in cell protein oxidation produced by hemin was also attenuated in cultures pretreated with Adv-HHO-1. These results support the hypothesis that HO-1 protects astrocytes from heme-mediated oxidative injury. Specifically increasing astrocytic HO-1 by gene transfer may have a beneficial effect on hemorrhagic CNS injury.

Pulsed ultrasound enhances the delivery of nitric oxide from bubble liposomes to ex vivo porcine carotid tissue

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Sutton JT

2014-10-01

Full Text Available JT Sutton,1 JL Raymond,1 MC Verleye,2 GJ Pyne-Geithman,3 CK Holland4 1University of Cincinnati, Biomedical Engineering Program, Cincinnati, OH, 2University of Notre Dame Department of Chemical Engineering, Notre Dame, IN, 3University of Cincinnati, College of Medicine, Department of Neurosurgery and the University of Cincinnati Neuroscience Institute, and Mayfield Clinic, Cincinnati, OH, 4University of Cincinnati, College of Medicine, Internal Medicine, Division of Cardiovascular Diseases, Cincinnati, OH, USA Abstract: Ultrasound-mediated drug delivery is a novel technique for enhancing the penetration of drugs into diseased tissue beds noninvasively. By encapsulating drugs into microsized and nanosized liposomes, the therapeutic can be shielded from degradation within the vasculature until delivery to a target site by ultrasound exposure. Traditional in vitro or ex vivo techniques to quantify this delivery profile include optical approaches, cell culture, and electrophysiology. Here, we demonstrate an approach to characterize the degree of nitric oxide (NO delivery to porcine carotid tissue by direct measurement of ex vivo vascular tone. An ex vivo perfusion model was adapted to assess ultrasound-mediated delivery of NO. This potent vasodilator was coencapsulated with inert octafluoropropane gas to produce acoustically active bubble liposomes. Porcine carotid arteries were excised post mortem and mounted in a physiologic buffer solution. Vascular tone was assessed in real time by coupling the artery to an isometric force transducer. NO-loaded bubble liposomes were infused into the lumen of the artery, which was exposed to 1 MHz pulsed ultrasound at a peak-to-peak acoustic pressure amplitude of 0.34 MPa. Acoustic cavitation emissions were monitored passively. Changes in vascular tone were measured and compared with control and sham NO bubble liposome exposures. Our results demonstrate that ultrasound-triggered NO release from bubble liposomes

Affinin (Spilanthol, Isolated from Heliopsis longipes, Induces Vasodilation via Activation of Gasotransmitters and Prostacyclin Signaling Pathways

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Jesús Eduardo Castro-Ruiz

2017-01-01

Full Text Available Heliopsis longipes roots have been widely used in Mexican traditional medicine to relieve pain, mainly, toothaches. Previous studies have shown that affinin, the major alkamide of these roots, induces potent antinociceptive and anti-inflammatory activities. However, the effect of H. longipes root extracts and affinin on the cardiovascular system have not been investigated so far. In the present study, we demonstrated that the dichloromethane and ethanolic extracts of H. longipes roots, and affinin, isolated from these roots, produce a concentration-dependent vasodilation of rat aorta. Affinin-induced vasorelaxation was partly dependent on the presence of endothelium and was significantly blocked in the presence of inhibitors of NO, H2S, and CO synthesis (NG-nitro-l-arginine methyl ester (l-NAME, dl-propargylglycine (PAG, and chromium mesoporphyrin (CrMP, respectively; K+ channel blockers (glibenclamide (Gli and tetraethyl ammonium (TEA, and guanylate cyclase and cyclooxygenase inhibitors (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ and indomethacin (INDO, respectively. Our results demonstrate, for the first time, that affinin induces vasodilation by mechanisms that involve gasotransmitters, and prostacyclin signaling pathways. These findings indicate that this natural alkamide has therapeutic potential in the treatment of cardiovascular diseases.

Nanotoxicity: oxidative stress mediated toxicity of metal and metal oxide nanoparticles.

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Sarkar, Abhijit; Ghosh, Manoranjan; Sil, Parames Chandra

2014-01-01

Metal and metal oxide nanoparticles are often used as industrial catalysts or to improve product's functional properties. Recent advanced nanotechnology have been expected to be used in various fields, ranging from sensors, environmental remediation to biomedicine, medical biology and imaging, etc. However, the growing use of nanoparticles has led to their release into environment and increased levels of these particles at nearby sites or the surroundings of their manufacturing factories become obvious. The toxicity of metal and metal oxide nanoparticles on humans, animals, and certainly to the environment has become a major concern to our community. However, controversies still remain with respect to the toxic effects and the mechanisms of these nanoparticles. The scientific community now feels that an understanding of the toxic effects is necessary to handle these nanoparticles and their use. A new discipline, named nanotoxicology, has therefore been developed that basically refers to the study of the interactions of nanoparticles with biological systems and also measures the toxicity level related to human health. Nanoparticles usually generate reactive oxygen species to a greater extent than micro-sized particles resulting in increased pro-inflammatory reactions and oxidative stress via intracellular signaling pathways. In this review, we mainly focus on the routes of exposure of some metal and metal oxide nanoparticles and how these nanoparticles affect us or broadly the cells of our organs. We would also like to discuss the responsible mechanism(s) of the nanoparticle-induced reactive oxygen species mediated organ pathophysiology. A brief introduction of the characterization and application of these nanoparticles has also been included in the article.

Interferon-γ and NF-κB mediate nitric oxide production by mesenchymal stromal cells

International Nuclear Information System (INIS)

Oh, I.; Ozaki, K.; Sato, K.; Meguro, A.; Tatara, R.; Hatanaka, K.; Nagai, T.; Muroi, K.; Ozawa, K.

2007-01-01

Mesenchymal stromal cells (MSCs) have been shown to have an immunosuppressive effect. Previously, we demonstrated that nitric oxide (NO) is one of the immunomodulatory mediators of MSCs. We herein show that primary mouse bone marrow MSCs and three cell lines that mimic MSCs suppress both differentiation and proliferation in Th1 condition, whereas the suppression in Th2 condition is mild. NO production is inversely correlated with T cell proliferation in Th1 and Th2 conditions. NO is highly induced in Th1 and minimally induced in Th2. Moreover, an inhibitor of NO synthase restores both proliferation and interferon-γ (IFN-γ) production in Th1 condition. Furthermore, an anti-IFN-γ antibody strongly inhibits NO production and an inhibitor of NF-κB reduces the level of induction of inducible NO synthase (iNOS) in MSCs. Taken together, our results suggest that NO plays a significant role in the modification of Th1 and Th2 differentiation by MSCs, and that both IFN-γ and NF-κB are critical for NO production by MSCs

Vasodilator effects and putative guanylyl cyclase stimulation by 2-nitro-1-phenylethanone and 2-nitro-2-phenyl-propane-1,3-diol on rat aorta.

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Vasconcelos, Thiago Brasileiro de; Ribeiro-Filho, Helder Veras; Lahlou, Saad; Pereira, José Geraldo de Carvalho; Oliveira, Paulo Sérgio Lopes de; Magalhães, Pedro Jorge Caldas

2018-07-05

Compounds containing a nitro group may reveal vasodilator properties. Several nitro compounds have a NO 2 group in a short aliphatic chain connected to an aromatic group. In this study, we evaluated in rat aorta the effects of two nitro compounds, with emphasis on a putative recruitment of the soluble guanylate cyclase (sGC) pathway to induce vasodilation. Isolated aortic rings were obtained from male Wistar rats to compare the effects induced by 2-nitro-1-phenylethanone (NPeth) or 2-nitro-2-phenyl-propane-1,3-diol (NPprop). In aortic preparations contracted with phenylephrine or KCl, NPeth and NPprop induced vasorelaxant effects that did not depend on the integrity of vascular endothelium. NPeth had a lesser vasorelaxant efficacy than NPprop and only the NPprop effects were inhibited by pretreatment with the sGC inhibitors, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) or methylene blue. In an ODQ-preventable manner, NPprop inhibited the contractile component of the phenylephrine-induced response mediated by intracellular Ca 2+ release or by extracellular Ca 2+ recruitment through receptor- or voltage-operated Ca 2+ channels. In contrast, NPprop was inert against the transient contraction induced by caffeine in Ca 2+ -free medium. In an ODQ-dependent manner, NPprop inhibited the contraction induced by the protein kinase C activator phorbol 12,13-dibutyrate or by the tyrosine phosphatase inhibitor sodium orthovanadate. In silico docking analysis of a sGC homologous protein revealed preferential site for NPprop. In conclusion, the nitro compounds NPeth and NPprop induced vasorelaxation in rat aortic rings. Aliphatic chain substituents selectively interfered in the ability of these compounds to induce vasorelaxant effects, and only NPprop relaxed aortic rings via a sGC pathway. Copyright © 2018 Elsevier B.V. All rights reserved.

Augmentation of limb perfusion and reversal of tissue ischemia produced by ultrasound-mediated microbubble cavitation.

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Belcik, J Todd; Mott, Brian H; Xie, Aris; Zhao, Yan; Kim, Sajeevani; Lindner, Nathan J; Ammi, Azzdine; Linden, Joel M; Lindner, Jonathan R

2015-04-01

Ultrasound can increase tissue blood flow, in part, through the intravascular shear produced by oscillatory pressure fluctuations. We hypothesized that ultrasound-mediated increases in perfusion can be augmented by microbubble contrast agents that undergo ultrasound-mediated cavitation and sought to characterize the biological mediators. Contrast ultrasound perfusion imaging of hindlimb skeletal muscle and femoral artery diameter measurement were performed in nonischemic mice after unilateral 10-minute exposure to intermittent ultrasound alone (mechanical index, 0.6 or 1.3) or ultrasound with lipid microbubbles (2×10(8) IV). Studies were also performed after inhibiting shear- or pressure-dependent vasodilator pathways, and in mice with hindlimb ischemia. Ultrasound alone produced a 2-fold increase (Pultrasound power. Ultrasound-mediated augmentation in flow was greater with microbubbles (3- and 10-fold higher than control for mechanical index 0.6 and 1.3, respectively; Pultrasound and microbubbles by 70% (Pultrasound and ultrasound with microbubbles. In mice with unilateral hindlimb ischemia (40%-50% reduction in flow), ultrasound (mechanical index, 1.3) with microbubbles increased perfusion by 2-fold to a degree that was greater than the control nonischemic limb. Increases in muscle blood flow during high-power ultrasound are markedly amplified by the intravascular presence of microbubbles and can reverse tissue ischemia. These effects are most likely mediated by cavitation-related increases in shear and activation of endothelial nitric oxide synthase. © 2015 American Heart Association, Inc.

Producing nitric oxide by pulsed electrical discharge in air for portable inhalation therapy.

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Yu, Binglan; Muenster, Stefan; Blaesi, Aron H; Bloch, Donald B; Zapol, Warren M

2015-07-01

Inhalation of nitric oxide (NO) produces selective pulmonary vasodilation and is an effective therapy for treating pulmonary hypertension in adults and children. In the United States, the average cost of 5 days of inhaled NO for persistent pulmonary hypertension of the newborn is about $14,000. NO therapy involves gas cylinders and distribution, a complex delivery device, gas monitoring and calibration equipment, and a trained respiratory therapy staff. The objective of this study was to develop a lightweight, portable device to serve as a simple and economical method of producing pure NO from air for bedside or portable use. Two NO generators were designed and tested: an offline NO generator and an inline NO generator placed directly within the inspiratory line. Both generators use pulsed electrical discharges to produce therapeutic range NO (5 to 80 parts per million) at gas flow rates of 0.5 to 5 liters/min. NO was produced from air, as well as gas mixtures containing up to 90% O2 and 10% N2. Potentially toxic gases produced in the plasma, including nitrogen dioxide (NO2) and ozone (O3), were removed using a calcium hydroxide scavenger. An iridium spark electrode produced the lowest ratio of NO2/NO. In lambs with acute pulmonary hypertension, breathing electrically generated NO produced pulmonary vasodilation and reduced pulmonary arterial pressure and pulmonary vascular resistance index. In conclusion, electrical plasma NO generation produces therapeutic levels of NO from air. After scavenging to remove NO2 and O3 and filtration to remove particles, electrically produced NO can provide safe and effective treatment of pulmonary hypertension. Copyright © 2015, American Association for the Advancement of Science.

Microbially-mediated method for synthesis of non-oxide semiconductor nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Phelps, Tommy J.; Lauf, Robert J.; Moon, Ji-Won; Rondinone, Adam Justin; Love, Lonnie J.; Duty, Chad Edward; Madden, Andrew Stephen; Li, Yiliang; Ivanov, Ilia N.; Rawn, Claudia Jeanette

2017-09-19

The invention is directed to a method for producing non-oxide semiconductor nanoparticles, the method comprising: (a) subjecting a combination of reaction components to conditions conducive to microbially-mediated formation of non-oxide semiconductor nanoparticles, wherein said combination of reaction components comprises i) anaerobic microbes, ii) a culture medium suitable for sustaining said anaerobic microbes, iii) a metal component comprising at least one type of metal ion, iv) a non-metal component comprising at least one non-metal selected from the group consisting of S, Se, Te, and As, and v) one or more electron donors that provide donatable electrons to said anaerobic microbes during consumption of the electron donor by said anaerobic microbes; and (b) isolating said non-oxide semiconductor nanoparticles, which contain at least one of said metal ions and at least one of said non-metals. The invention is also directed to non-oxide semiconductor nanoparticle compositions produced as above and having distinctive properties.

Microbially-mediated method for synthesis of non-oxide semiconductor nanoparticles

Science.gov (United States)

Phelps, Tommy J.; Lauf, Robert J.; Moon, Ji Won; Rondinone, Adam J.; Love, Lonnie J.; Duty, Chad Edward; Madden, Andrew Stephen; Li, Yiliang; Ivanov, Ilia N.; Rawn, Claudia Jeanette

2014-06-24

The invention is directed to a method for producing non-oxide semiconductor nanoparticles, the method comprising: (a) subjecting a combination of reaction components to conditions conducive to microbially-mediated formation of non-oxide semiconductor nanoparticles, wherein said combination of reaction components comprises i) anaerobic microbes, ii) a culture medium suitable for sustaining said anaerobic microbes, iii) a metal component comprising at least one type of metal ion, iv) a non-metal component containing at least one non-metal selected from the group consisting of S, Se, Te, and As, and v) one or more electron donors that provide donatable electrons to said anaerobic microbes during consumption of the electron donor by said anaerobic microbes; and (b) isolating said non-oxide semiconductor nanoparticles, which contain at least one of said metal ions and at least one of said non-metals. The invention is also directed to non-oxide semiconductor nanoparticle compositions produced as above and having distinctive properties.

Redox functionality mediated by adsorbed oxygen on a Pd oxide film over a Pd(100) thin structure: a first-principles study

International Nuclear Information System (INIS)

Kusakabe, K; Ikuno, Y k; Nagara, H; Harada, K

2009-01-01

Stable oxygen sites on a PdO film over a Pd(100) thin structure with a (√5x√5)R27 o surface unit cell are determined using the first-principles electronic structure calculations with the generalized gradient approximation. The adsorbed monatomic oxygen goes to a site bridging two twofold-coordinated Pd atoms or to a site bridging a twofold-coordinated Pd atom and a fourfold-coordinated Pd atom. Estimated reaction energies of CO oxidation by reduction of the oxidized PdO film and N 2 O reduction mediated by oxidation of the PdO film are both exothermic. Motion of the adsorbed oxygen atom between the two stable sites is evaluated using the nudged elastic band method, where an energy barrier for a translational motion of the adsorbed oxygen may become ∼0.45 eV, which is low enough to allow fluxionality of the surface oxygen at high temperatures. The oxygen fluxionality is allowed by the existence of twofold-coordinated Pd atoms on the PdO film, whose local structure has a similarity to that of Pd catalysts for the Suzuki-Miyaura cross-coupling. Although NO x (including NO 2 and NO) reduction is not always catalyzed by the PdO film only, we conclude that continual redox reactions may happen mediated by oxygen-adsorbed PdO films over a Pd surface structure, when the influx of NO x and CO continues, and when the reaction cycle is kept on a well-designed oxygen surface.

Kinetic Study of Hydroxyl and Sulfate Radical-Mediated Oxidation of Pharmaceuticals in Wastewater Effluents.

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Lian, Lushi; Yao, Bo; Hou, Shaodong; Fang, Jingyun; Yan, Shuwen; Song, Weihua

2017-03-07

Advanced oxidation processes (AOPs), such as hydroxyl radical (HO • )- and sulfate radical (SO 4 •- )-mediated oxidation, are alternatives for the attenuation of pharmaceuticals and personal care products (PPCPs) in wastewater effluents. However, the kinetics of these reactions needs to be investigated. In this study, kinetic models for 15 PPCPs were built to predict the degradation of PPCPs in both HO • - and SO 4 •- -mediated oxidation. In the UV/H 2 O 2 process, a simplified kinetic model involving only steady state concentrations of HO • and its biomolecular reaction rate constants is suitable for predicting the removal of PPCPs, indicating the dominant role of HO • in the removal of PPCPs. In the UV/K 2 S 2 O 8 process, the calculated steady state concentrations of CO 3 •- and bromine radicals (Br • , Br 2 •- and BrCl •- ) were 600-fold and 1-2 orders of magnitude higher than the concentrations of SO 4 •- , respectively. The kinetic model, involving both SO 4 •- and CO 3 •- as reactive species, was more accurate for predicting the removal of the 9 PPCPs, except for salbutamol and nitroimidazoles. The steric and ionic effects of organic matter toward SO 4 •- could lead to overestimations of the removal efficiencies of the SO 4 •- -mediated oxidation of nitroimidazoles in wastewater effluents.

Loss of Female Sex Hormones Exacerbates Cerebrovascular and Cognitive Dysfunction in Aortic Banded Miniswine Through a Neuropeptide Y-Ca2+-Activated Potassium Channel-Nitric Oxide Mediated Mechanism.

Science.gov (United States)

Olver, T Dylan; Hiemstra, Jessica A; Edwards, Jenna C; Schachtman, Todd R; Heesch, Cheryl M; Fadel, Paul J; Laughlin, M Harold; Emter, Craig A

2017-10-31

Postmenopausal women represent the largest cohort of patients with heart failure with preserved ejection fraction, and vascular dementia represents the most common form of dementia in patients with heart failure with preserved ejection fraction. Therefore, we tested the hypotheses that the combination of cardiac pressure overload (aortic banding [AB]) and the loss of female sex hormones (ovariectomy [OVX]) impairs cerebrovascular control and spatial memory. Female Yucatan miniswine were separated into 4 groups (n=7 per group): (1) control, (2) AB, (3) OVX, and (4) AB-OVX. Pigs underwent OVX and AB at 7 and 8 months of age, respectively. At 14 months, cerebral blood flow velocity and spatial memory (spatial hole-board task) were lower in the OVX groups ( P <0.05), with significant impairments in the AB-OVX group ( P <0.05). Resting carotid artery β stiffness and vascular resistance during central hypovolemia were increased in the AB-OVX group ( P <0.05), and blood flow recovery after central hypovolemia was reduced in both OVX groups ( P <0.05). Isolated pial artery (pressure myography) vasoconstriction to neuropeptide Y was greatest in the AB-OVX group ( P <0.05), and vasodilation to the Ca 2+ -activated potassium channel α-subunit agonist NS-1619 was impaired in both AB groups ( P <0.05). The ratio of phosphorylated endothelial nitric oxide synthase:total endothelial nitric oxide synthase was depressed and Ca 2+ -activated potassium channel α-subunit protein was increased in AB groups ( P <0.05). Mechanistically, impaired cerebral blood flow control in experimental heart failure may be the result of heightened neuropeptide Y-induced vasoconstriction along with reduced vasodilation associated with decreased Ca 2+ -activated potassium channel function and impaired nitric oxide signaling, the effects of which are exacerbated in the absence of female sex hormones. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Caveolin-1 and CDC42 mediated endocytosis of silica-coated iron oxide nanoparticles in HeLa cells

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Nils Bohmer

2015-01-01

Full Text Available Nanomedicine is a rapidly growing field in nanotechnology, which has great potential in the development of new therapies for numerous diseases. For example iron oxide nanoparticles are in clinical use already in the thermotherapy of brain cancer. Although it has been shown, that tumor cells take up these particles in vitro, little is known about the internalization routes. Understanding of the underlying uptake mechanisms would be very useful for faster and precise development of nanoparticles for clinical applications. This study aims at the identification of key proteins, which are crucial for the active uptake of iron oxide nanoparticles by HeLa cells (human cervical cancer as a model cell line. Cells were transfected with specific siRNAs against Caveolin-1, Dynamin 2, Flotillin-1, Clathrin, PIP5Kα and CDC42. Knockdown of Caveolin-1 reduces endocytosis of superparamagnetic iron oxide nanoparticles (SPIONs and silica-coated iron oxide nanoparticles (SCIONs between 23 and 41%, depending on the surface characteristics of the nanoparticles and the experimental design. Knockdown of CDC42 showed a 46% decrease of the internalization of PEGylated SPIONs within 24 h incubation time. Knockdown of Dynamin 2, Flotillin-1, Clathrin and PIP5Kα caused no or only minor effects. Hence endocytosis in HeLa cells of iron oxide nanoparticles, used in this study, is mainly mediated by Caveolin-1 and CDC42. It is shown here for the first time, which proteins of the endocytotic pathway mediate the endocytosis of silica-coated iron oxide nanoparticles in HeLa cells in vitro. In future studies more experiments should be carried out with different cell lines and other well-defined nanoparticle species to elucidate possible general principles.

Catalytic oxidation of NO to NO2 on activated carbon

International Nuclear Information System (INIS)

Zhancheng Guo; Yusheng Xie

2001-01-01

Catalytic oxidation of NO to NO 2 over activated carbons PAN-ACF, pitch-ACF and coconut-AC at room temperature (30 o C) were studied to develop a method based on oxidative removal of NO from flue gases. For a dry gas, under the conditions of a gas space flow rate 1500 h -1 in the presence of oxygen of 2-20% in volume concentration, the activated coconut carbon with a surface area 1200 m 2 /g converted about 81-94% of NO with increasing oxygen concentration, the pitch based activated carbon fiber with a surface area 1000 m 2 /g about 44-75%, and the polyacrylonitrile-based activated carbon fiber with a surface area 1810 m 2 /g about 25-68%. The order of activity of the activated carbons was PAN-ACF c P NO P O2 β (F/W), where β is 0.042, 0.16, 0.31 for the coconut-AC, the pitch-ACF and the PAN-ACF respectively, and k c is 0.94 at 30 o C. (author)

Silver-mediated oxidative C-H difluoromethylation of phenanthridines and 1,10-phenanthrolines.

Science.gov (United States)

Zhu, Sheng-Qing; Xu, Xiu-Hua; Qing, Feng-Ling

2017-10-17

A silver-mediated oxidative difluoromethylation of phenanthridines and 1,10-phenanthrolines with TMSCF 2 H is disclosed. This C-H difluoromethylation of N-containing polycyclic aromatics constitutes an efficient method for the regioselective synthesis of difluoromethylated N-heterocycles.

Tapping but not massage enhances vasodilation and improves venous palpation of cutaneous veins.

Science.gov (United States)

Ichimura, Mika; Sasaki, Shinsuke; Mori, Masaharu; Ogino, Tetsuya

2015-01-01

This paper investigated whether tapping on the median cubital vein or massaging the forearm was more effective in obtaining better venous palpation for venipuncture. Forty healthy volunteers in their twenties were subjected to tapping (10 times in 5 sec) or massage (10 strokes in 20 sec from the wrist to the cubital fossa) under tourniquet inflation on the upper arm. Venous palpation was assessed using the venous palpation score (0-6, with 0 being impalpable). Three venous factors-venous depth, cross-sectional area, and elevation-were also measured using ultrasonography. The venous palpation score increased significantly by tapping but not by massage. Moreover, all 3 venous measurements changed significantly by tapping, while only the depth decreased significantly by massage. The three venous measurements correlated significantly with the venous palpation score, indicating that they are useful objective indicators for evaluating vasodilation. We suggest that tapping is an effective vasodilation technique.

Nitric oxide signaling and the cross talk with prostanoids pathways in vascular system.

Science.gov (United States)

Silva, Bruno R; Paula, Tiago D; Paulo, Michele; Bendhack, Lusiane M

2016-12-28

This review provides an overview of the cellular signaling of nitric oxide (NO) and prostanoids in vascular cells and the possible cross talk between their pathways, mainly in hypertension, since the imbalance of these two systems has been attributed to development of some cardiovascular diseases. It also deals with the modulation of vasodilation induced by NO donors. NO is a well-known second messenger involved in many cellular functions. In the vascular system, the NO produced by endothelial NO-synthase (eNOS) or released by NO donors acts in vascular smooth muscle cells, the binding of NO to Fe2+-heme of soluble guanylyl-cyclase (sGC) activates sGC and the production of cyclic guanosine-3-5-monophosphate (cGMP). The second messenger (cGMP) activates protein kinase G and the signaling cascade, including K+ channels. Activation of K+ channels leads to cell membrane hyperpolarization and Ca2+ channels blockade, which induce vascular relaxation. Moreover, the enzyme cyclooxygenase (COX) is also an important regulator of the vascular function by prostanoids production such as thromboxane A2 (TXA2) and prostacyclin (PGI2), which classically induce contraction and relaxation, respectively. Additionaly, studies indicate that the activity of both enzymes can be modulated by their products and reactive oxygen species (ROS) in cardiovascular diseases such as hypertension. The interaction of NO with cellular molecules, particularly the reaction of NO with ROS, determines the biological mechanisms of action and short half-life of NO. We have been working on the vascular effects of ruthenium-derived complexes that release NO. Our research group has published works on the vasodilating effects of ruthenium-derived NO donors and the mechanisms of vascular cells involved in the relaxation of the vascular smooth muscle in health and hypertensive rats. In our previous studies, we have compared the new NO donors synthesized by our group to SNP. It shows the cellular signaling of NO

Stathmin Mediates Hepatocyte Resistance to Death from Oxidative Stress by down Regulating JNK

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Zhao, Enpeng; Amir, Muhammad; Lin, Yu; Czaja, Mark J.

2014-01-01

Stathmin 1 performs a critical function in cell proliferation by regulating microtubule polymerization. This proliferative function is thought to explain the frequent overexpression of stathmin in human cancer and its correlation with a bad prognosis. Whether stathmin also functions in cell death pathways is unclear. Stathmin regulates microtubules in part by binding free tubulin, a process inhibited by stathmin phosphorylation from kinases including c-Jun N-terminal kinase (JNK). The involvement of JNK activation both in stathmin phosphorylation, and in hepatocellular resistance to oxidative stress, led to an examination of the role of stathmin/JNK crosstalk in oxidant-induced hepatocyte death. Oxidative stress from menadione-generated superoxide induced JNK-dependent stathmin phosphorylation at Ser-16, Ser-25 and Ser-38 in hepatocytes. A stathmin knockdown sensitized hepatocytes to both apoptotic and necrotic cell death from menadione without altering levels of oxidant generation. The absence of stathmin during oxidative stress led to JNK overactivation that was the mechanism of cell death as a concomitant knockdown of JNK1 or JNK2 blocked death. Hepatocyte death from JNK overactivation was mediated by the effects of JNK on mitochondria. Mitochondrial outer membrane permeabilization occurred in stathmin knockdown cells at low concentrations of menadione that triggered apoptosis, whereas mitochondrial β-oxidation and ATP homeostasis were compromised at higher, necrotic menadione concentrations. Stathmin therefore mediates hepatocyte resistance to death from oxidative stress by down regulating JNK and maintaining mitochondrial integrity. These findings demonstrate a new mechanism by which stathmin promotes cell survival and potentially tumor growth. PMID:25285524

Stathmin mediates hepatocyte resistance to death from oxidative stress by down regulating JNK.

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Enpeng Zhao

Full Text Available Stathmin 1 performs a critical function in cell proliferation by regulating microtubule polymerization. This proliferative function is thought to explain the frequent overexpression of stathmin in human cancer and its correlation with a bad prognosis. Whether stathmin also functions in cell death pathways is unclear. Stathmin regulates microtubules in part by binding free tubulin, a process inhibited by stathmin phosphorylation from kinases including c-Jun N-terminal kinase (JNK. The involvement of JNK activation both in stathmin phosphorylation, and in hepatocellular resistance to oxidative stress, led to an examination of the role of stathmin/JNK crosstalk in oxidant-induced hepatocyte death. Oxidative stress from menadione-generated superoxide induced JNK-dependent stathmin phosphorylation at Ser-16, Ser-25 and Ser-38 in hepatocytes. A stathmin knockdown sensitized hepatocytes to both apoptotic and necrotic cell death from menadione without altering levels of oxidant generation. The absence of stathmin during oxidative stress led to JNK overactivation that was the mechanism of cell death as a concomitant knockdown of JNK1 or JNK2 blocked death. Hepatocyte death from JNK overactivation was mediated by the effects of JNK on mitochondria. Mitochondrial outer membrane permeabilization occurred in stathmin knockdown cells at low concentrations of menadione that triggered apoptosis, whereas mitochondrial β-oxidation and ATP homeostasis were compromised at higher, necrotic menadione concentrations. Stathmin therefore mediates hepatocyte resistance to death from oxidative stress by down regulating JNK and maintaining mitochondrial integrity. These findings demonstrate a new mechanism by which stathmin promotes cell survival and potentially tumor growth.

The Traditional Herbal Medicine, Dangkwisoo-San, Prevents Cerebral Ischemic Injury through Nitric Oxide-Dependent Mechanisms

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Ji Hyun Kim

2011-01-01

Full Text Available Dangkwisoo-San (DS is an herbal extract that is widely used in traditional Korean medicine to treat traumatic ecchymosis and pain by promoting blood circulation and relieving blood stasis. However, the effect of DS in cerebrovascular disease has not been examined experimentally. The protective effects of DS on focal ischemic brain were investigated in a mouse model. DS stimulated nitric oxide (NO production in human brain microvascular endothelial cells (HBMECs. DS (10–300 μg/mL produced a concentration-dependent relaxation in mouse aorta, which was significantly attenuated by the nitric oxide synthase (NOS inhibitor L-NAME, suggesting that DS causes vasodilation via a NO-dependent mechanism. DS increased resting cerebral blood flow (CBF, although it caused mild hypotension. To investigate the effect of DS on the acute cerebral injury, C57/BL6J mice received 90 min of middle cerebral artery occlusion followed by 22.5 h of reperfusion. DS administered 3 days before arterial occlusion significantly reduced cerebral infarct size by 53.7% compared with vehicle treatment. However, DS did not reduce brain infarction in mice treated with the relatively specific endothelial NOS (eNOS inhibitor, N5-(1-iminoethyl-L-ornithine, suggesting that the neuroprotective effect of DS is primarily endothelium-dependent. This correlated with increased phosphorylation of eNOS in the brains of DS-treated mice. DS acutely improves CBF in eNOS-dependent vasodilation and reduces infarct size in focal cerebral ischemia. These data provide causal evidence that DS is cerebroprotective via the eNOS-dependent production of NO, which ameliorates blood circulation.

Synthesis of graphene oxide and reduced graphene oxide using volumetric method by a novel approach without NaNO2 or NaNO3

Science.gov (United States)

Gunda, Rajitha; Madireddy, Buchi Suresh; Dash, Raj Kishora

2018-02-01

In the present work, graphite was processed to graphene oxide (GO) using modified Hummer's method by volumetric titration approach, without attaining zero temperature and the addition of toxic chemicals (NaNO2/NaNO3). The complete oxidation of graphite to graphene oxide was obtained by controlled addition (volumetric titration) of KMnO4. The addition of higher KMnO4 resulted in partial oxidation and 2-3 mono-layers with less defects/disordered structure of reduced graphene oxide (RGO) sheets were achieved. Samples were analyzed by XRD, FT-IR, Raman analysis, and TEM analysis. X-ray diffraction displayed the oxidized peak of graphene oxide at 11.9° and reduced graphene oxide at 23.8°. The prolonged stability of the synthesized GO with lower mole ratios of oxidizing agent was confirmed from UV-visible spectroscopy. Based on the results, processed graphene oxide is found to be a candidate material for thermally stable capacitor application.

WNT5A-JNK regulation of vascular insulin resistance in human obesity.

Science.gov (United States)

Farb, Melissa G; Karki, Shakun; Park, Song-Young; Saggese, Samantha M; Carmine, Brian; Hess, Donald T; Apovian, Caroline; Fetterman, Jessica L; Bretón-Romero, Rosa; Hamburg, Naomi M; Fuster, José J; Zuriaga, María A; Walsh, Kenneth; Gokce, Noyan

2016-12-01

Obesity is associated with the development of vascular insulin resistance; however, pathophysiological mechanisms are poorly understood. We sought to investigate the role of WNT5A-JNK in the regulation of insulin-mediated vasodilator responses in human adipose tissue arterioles prone to endothelial dysfunction. In 43 severely obese (BMI 44±11 kg/m 2 ) and five metabolically normal non-obese (BMI 26±2 kg/m 2 ) subjects, we isolated arterioles from subcutaneous and visceral fat during planned surgeries. Using videomicroscopy, we examined insulin-mediated, endothelium-dependent vasodilator responses and characterized adipose tissue gene and protein expression using real-time polymerase chain reaction and Western blot analyses. Immunofluorescence was used to quantify endothelial nitric oxide synthase (eNOS) phosphorylation. Insulin-mediated vasodilation was markedly impaired in visceral compared to subcutaneous vessels from obese subjects (p<0.001), but preserved in non-obese individuals. Visceral adiposity was associated with increased JNK activation and elevated expression of WNT5A and its non-canonical receptors, which correlated negatively with insulin signaling. Pharmacological JNK antagonism with SP600125 markedly improved insulin-mediated vasodilation by sixfold (p<0.001), while endothelial cells exposed to recombinant WNT5A developed insulin resistance and impaired eNOS phosphorylation (p<0.05). We observed profound vascular insulin resistance in the visceral adipose tissue arterioles of obese subjects that was associated with up-regulated WNT5A-JNK signaling and impaired endothelial eNOS activation. Pharmacological JNK antagonism markedly improved vascular endothelial function, and may represent a potential therapeutic target in obesity-related vascular disease. © The Author(s) 2016.

Nitric oxide mediates the stress response induced by diatom aldehydes in the sea urchin Paracentrotus lividus.

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Giovanna Romano

Full Text Available Diatoms are ubiquitous and abundant primary producers that have been traditionally considered as a beneficial food source for grazers and for the transfer of carbon through marine food webs. However, many diatom species produce polyunsaturated aldehydes that disrupt development in the offspring of grazers that feed on these unicellular algae. Here we provide evidence that production of the physiological messenger nitric oxide increases after treatment with the polyunsaturated aldehyde decadienal in embryos of the sea urchin Paracentrotus lividus. At high decadienal concentrations, nitric oxide mediates initial apoptotic events leading to loss of mitochondrial functionality through the generation of peroxynitrite. At low decadienal concentrations, nitric oxide contributes to the activation of hsp70 gene expression thereby protecting embryos against the toxic effects of this aldehyde. When nitric oxide levels were lowered by inhibiting nitric oxide synthase activity, the expression of hsp70 in swimming blastula decreased and the proportion of abnormal plutei increased. However, in later pluteus stages nitric oxide was no longer able to exert this protective function: hsp70 and nitric oxide synthase expression decreased with a consequent increase in the expression of caspase-8. Our findings that nitric oxide production increases rapidly in response to a toxic exogenous stimulus opens new perspectives on the possible role of this gas as an important messenger to environmental stress in sea urchins and for understanding the cellular mechanisms underlying toxicity during diatom blooms.

Vascular endothelial dysfunction in β-thalassemia occurs despite increased eNOS expression and preserved vascular smooth muscle cell reactivity to NO.

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Ekatherina Stoyanova

Full Text Available The hereditary β-thalassemia major condition requires regular lifelong blood transfusions. Transfusion-related iron overloading has been associated with the onset of cardiovascular complications, including cardiac dysfunction and vascular anomalies. By using an untransfused murine model of β-thalassemia major, we tested the hypothesis that vascular endothelial dysfunction, alterations of arterial structure and of its mechanical properties would occur despite the absence of treatments.Vascular function and structure were evaluated ex vivo. Compared to the controls, endothelium-dependent vasodilation with acetylcholine was blunted in mesenteric resistance arteries of β-thalassemic mice while the endothelium-independent vasodilator (sodium nitroprusside produced comparable vessel dilation, indicating endothelial cell impairment with preserved smooth muscle cell reactivity to nitric oxide (NO. While these findings suggest a decrease in NO bioavailability, Western blotting showed heightened expression of aortic endothelial NO synthase (eNOS in β-thalassemia. Vascular remodeling of the common carotid arteries revealed increased medial elastin content. Under isobaric conditions, the carotid arteries of β-thalassemic mice exhibited decreased wall stress and softening due to structural changes of the vessel wall.A complex vasculopathy was identified in untransfused β-thalassemic mice characterized by altered carotid artery structure and endothelial dysfunction of resistance arterioles, likely attributable to reduced NO bioavailability despite enhanced vascular eNOS expression.

Defect-mediated magnetism of transition metal doped zinc oxide thin films

Science.gov (United States)

Roberts, Bradley Kirk

Magnetism in transition metal doped wide band-gap materials is of interest to further the fundamental science of materials and future spintronics applications. Large inter-dopant separations require mediation of ferromagnetism by some method; carrier-mediated mechanisms are typically applicable to dilute magnetic semiconductors with low Curie temperatures. Dilute magnetic oxides, commonly with poor conductivity and TC above room temperature, cannot be described within this theory. Recent experiment and theory developments suggest that ferromagnetic exchange in these materials can be mediated by defects. This research includes experimental results justifying and developing this approach. Thin films of Cr doped ZnO (band gap ˜3.3 eV) were deposited with several processing variations to enhance the effects of either 0-dimensional (vacancy, hydrogen-related defect) or two-dimensional defects (surface/interface) and thereby affect magnetism and conductivity. We observe surface magnetism in dielectric thin films of oxygen-saturated ZnO:Cr with spontaneous magnetic moment and conductance dropping approximately exponentially with increasing thickness. Uniform defect concentrations would not result in such magnetic ordering behavior indicating that magnetism is mediated either by surface defects or differing concentrations of point defects near the surface. Polarized neutron reflectivity profiling confirms a magnetically active region of ˜8 nm at the film surface. Hydrogen is notoriously present as a defect and carrier dopant in ZnO, and artificial introduction of hydrogen in dielectric ZnO:Cr films results in varying electronic and magnetic behavior. Free carriers introduced with hydrogen doping are not spin-polarized requiring an alternative explanation for ferromagnetism. We find from positron annihilation spectroscopy measurements that hydrogen doping increases the concentration of an altered VZn-related defect (a preliminary interpretation) throughout the film, which

Effects and mechanisms of action of sildenafil citrate in human chorionic arteries

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Lynch Tadhg

2009-04-01

Full Text Available Abstract Objectives Sildenafil citrate, a specific phosphodiesterase-5 inhibitor, is increasingly used for pulmonary hypertension in pregnancy. Sildenafil is also emerging as a potential candidate for the treatment of intra-uterine growth retardation and for premature labor. Its effects in the feto-placental circulation are not known. Our objectives were to determine whether phosphodiesterase-5 is present in the human feto-placental circulation, and to characterize the effects and mechanisms of action of sildenafil citrate in this circulation. Study Design Ex vivo human chorionic plate arterial rings were used in all experiments. The presence of phosphodiesterase-5 in the feto-placental circulation was determined by western blotting and immunohistochemical staining. In a subsequent series of pharmacologic studies, the effects of sildenafil citrate in pre-constricted chorionic plate arterial rings were determined. Additional studies examined the role of cGMP and nitric oxide in mediating the effects of sildenafil. Results Phosphodiesterase-5 mRNA and protein was demonstrated in human chorionic plate arteries. Immunohistochemistry demonstrated phosphodiesterase-5 within the arterial muscle layer. Sildenafil citrate produced dose dependent vasodilatation at concentrations at and greater than 10 nM. Both the direct cGMP inhibitor methylene blue and the cGMP-dependent protein kinase inhibitor Rp-8-Br-PET-cGMPS significantly attenuated the vasodilation produced by sildenafil citrate. Inhibition of NO production with L-NAME did not attenuate the vasodilator effects of sildenafil. In contrast, sildenafil citrate significantly enhanced the vasodilation produced by the NO donor sodium nitroprusside. Conclusion Phosphodiesterase-5 is present in the feto-placental circulation. Sildenafil citrate vasodilates the feto-placental circulation via a cGMP dependent mechanism involving increased responsiveness to NO.

Effects and mechanisms of action of sildenafil citrate in human chorionic arteries.

LENUS (Irish Health Repository)

Maharaj, Chrisen H

2009-01-01

OBJECTIVES: Sildenafil citrate, a specific phosphodiesterase-5 inhibitor, is increasingly used for pulmonary hypertension in pregnancy. Sildenafil is also emerging as a potential candidate for the treatment of intra-uterine growth retardation and for premature labor. Its effects in the feto-placental circulation are not known. Our objectives were to determine whether phosphodiesterase-5 is present in the human feto-placental circulation, and to characterize the effects and mechanisms of action of sildenafil citrate in this circulation. STUDY DESIGN: Ex vivo human chorionic plate arterial rings were used in all experiments. The presence of phosphodiesterase-5 in the feto-placental circulation was determined by western blotting and immunohistochemical staining. In a subsequent series of pharmacologic studies, the effects of sildenafil citrate in pre-constricted chorionic plate arterial rings were determined. Additional studies examined the role of cGMP and nitric oxide in mediating the effects of sildenafil. RESULTS: Phosphodiesterase-5 mRNA and protein was demonstrated in human chorionic plate arteries. Immunohistochemistry demonstrated phosphodiesterase-5 within the arterial muscle layer. Sildenafil citrate produced dose dependent vasodilatation at concentrations at and greater than 10 nM. Both the direct cGMP inhibitor methylene blue and the cGMP-dependent protein kinase inhibitor Rp-8-Br-PET-cGMPS significantly attenuated the vasodilation produced by sildenafil citrate. Inhibition of NO production with L-NAME did not attenuate the vasodilator effects of sildenafil. In contrast, sildenafil citrate significantly enhanced the vasodilation produced by the NO donor sodium nitroprusside. CONCLUSION: Phosphodiesterase-5 is present in the feto-placental circulation. Sildenafil citrate vasodilates the feto-placental circulation via a cGMP dependent mechanism involving increased responsiveness to NO.

Mediated electrochemical oxidation treatment for Rocky Flats combustible low-level mixed waste. Final report, FY 1993 and 1994

International Nuclear Information System (INIS)

Chiba, Z.; Lewis, P.R.; Murguia, L.C.

1994-09-01

Mediated Electrochemical Oxidation (MEO) is an aqueous process which destroys hazardous organics by oxidizing a mediator at the anode of an electrochemical cell; the mediator in turn oxidizes the organics within the bulk of the electrolyte. With this process organics can be nearly completely destroyed, that is, the carbon and hydrogen present in the hydrocarbon are almost entirely mineralized to carbon dioxide and water. The MEO process is also capable of dissolving radioactive materials, including difficult-to-dissolve compounds such as plutonium oxide. Hence, this process can treat mixed wastes, by destroying the hazardous organic components of the waste, and dissolving the radioactive components. The radioactive material can be recovered if desired, or disposed of as non-mixed radioactive waste. The process is inherently safe, since the hazardous and radioactive materials are completely contained in the aqueous phase, and the system operates at low temperatures (below 80 degree C) and at ambient pressures

Polyphenol fraction of extra virgin olive oil protects against endothelial dysfunction induced by high glucose and free fatty acids through modulation of nitric oxide and endothelin-1

OpenAIRE

Storniolo, Carolina Emilia; Roselló-Catafau, Joan; Pintó, Xavier; Mitjavila, María Teresa; Moreno, Juan José

2014-01-01

© 2014 The Authors. Epidemiological and clinical studies have reported that olive oil reduces the incidence of cardiovascular disease. However, the mechanisms involved in this beneficial effect have not been delineated. The endothelium plays an important role in blood pressure regulation through the release of potent vasodilator and vasoconstrictor agents such as nitric oxide (NO) and endothelin-1 (ET-1), respectively, events that are disrupted in type 2 diabetes. Extra virgin olive oil conta...

Roles of free radicals in NO oxidation by Fenton system and the enhancement on NO oxidation and H2O2 utilization efficiency.

Science.gov (United States)

Zhao, Haiqian; Dong, Ming; Wang, Zhonghua; Wang, Huaiyuan; Qi, Hanbing

2018-06-20

Low H 2 O 2 utilization efficiency is the main problem when Fenton system was used to oxidize NO in flue gas. To understand the behavior of the free radicals during NO oxidation process in Fenton system is crucial to solving this problem. The oxidation capacity of ·OH and HO 2 · on NO in Fenton system was compared and the useless consumption path of ·OH and HO 2 · that caused the low utilization efficiency of H 2 O 2 were studied. A method to enhance the oxidation ability and H 2 O 2 utilization efficiency by adding reducing additives in Fenton system was proposed. The results showed that both of ·OH and HO 2 · were active substances that oxidize NO. However, the oxidation ability of ·OH radicals was stronger. The vast majority of ·OH and HO 2 · was consumed by rapid reaction ·OH+HO 2 ·→H 2 O+O 2 , which was the primary reason for the low utilization efficiency of H 2 O 2 in Fenton system. Hydroxylamine hydrochloride and ascorbic acid could accelerate the conversion of Fe 3+ to Fe 2+ , thereby increase the generation rate of ·OH and decrease the generation rate of HO 2 ·. As a result, the oxidation ability and H 2 O 2 utilization efficiency were enhanced.

Functional Layer-by-Layer Thin Films of Inducible Nitric Oxide (NO) Synthase Oxygenase and Polyethylenimine: Modulation of Enzyme Loading and NO-Release Activity.

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Gunasekera, Bhagya; Abou Diwan, Charbel; Altawallbeh, Ghaith; Kalil, Haitham; Maher, Shaimaa; Xu, Song; Bayachou, Mekki

2018-03-07

Nitric oxide (NO) release counteracts platelet aggregation and prevents the thrombosis cascade in the inner walls of blood vessels. NO-release coatings also prevent thrombus formation on the surface of blood-contacting medical devices. Our previous work has shown that inducible nitric oxide synthase (iNOS) films release NO fluxes upon enzymatic conversion of the substrate l-arginine. In this work, we report on the modulation of enzyme loading in layer-by-layer (LbL) thin films of inducible nitric oxide synthase oxygenase (iNOSoxy) on polyethylenimine (PEI). The layer of iNOSoxy is electrostatically adsorbed onto the PEI layer. The pH of the iNOSoxy solution affects the amount of enzyme adsorbed. The overall negative surface charge of iNOSoxy in solution depends on the pH and hence determines the density of adsorbed protein on the positively charged PEI layer. We used buffered iNOSoxy solutions adjusted to pHs 8.6 and 7.0, while saline PEI solution was used at pH 7.0. Atomic force microscopy imaging of the outermost layer shows higher protein adsorption with iNOSoxy at pH 8.6 than with a solution of iNOSoxy at pH 7.0. Graphite electrodes with PEI/iNOSoxy films show higher catalytic currents for nitric oxide reduction mediated by iNOSoxy. The higher enzyme loading translates into higher NO flux when the enzyme-modified surface is exposed to a solution containing the substrate and a source of electrons. Spectrophotometric assays showed higher NO fluxes with iNOSoxy/PEI films built at pH 8.6 than with films built at pH 7.0. Fourier transform infrared analysis of iNOSoxy adsorbed on PEI at pH 8.6 and 7.0 shows structural differences of iNOSoxy in films, which explains the observed changes in enzymatic activity. Our findings show that pH provides a strategy to optimize the NOS loading and enzyme activity in NOS-based LbL thin films, which enables improved NO release with minimum layers of PEI/NOS.

Nitric oxide and cardiovascular risk factors

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Livio Dai Cas

2007-06-01

Full Text Available The endothelium is a dynamic organ with many properties that takes part in the regulation of the principal mechanisms of vascular physiology. Its principal functions include the control of blood-tissue exchange and permeability, the vascular tonus, and the modulation of inflammatory or coagulatory mechanisms. Many vasoactive molecules, produced by the endothelium, are involved in the control of these functions. The most important is nitric oxide (NO, a gaseous molecule electrically neutral with an odd number of electrons that gives the molecule chemically reactive radical properties. Already known in the twentieth century, NO, sometimes considered as a dangerous molecule, recently valued as an important endogenous vasodilator factor. Recently, it was discovered that it is involved in several physiological mechanisms of endothelial protection (Tab. I. In 1992, Science elected it as “molecule of the year”; 6 yrs later three American researchers (Louis Ignarro, Robert Furchgott and Fried Murad obtained a Nobel Prize for Medicine and Physiology “for their discoveries about NO as signal in the cardiovascular system”.

Intra-arterial vasodilators to prevent radial artery spasm: a systematic review and pooled analysis of clinical studies

Energy Technology Data Exchange (ETDEWEB)

Kwok, Chun Shing, E-mail: shingkwok@doctors.org.uk [Keele Cardiovascular Research Group, Keele University, Stoke-on-Trent (United Kingdom); Rashid, Muhammad [St. Helens & Knowsley Teaching Hospital (NHS) Trust, Whiston Hospital, Prescot (United Kingdom); Fraser, Doug [Manchester Heart Centre, Manchester Royal Infirmary (United Kingdom); Nolan, James [University Hospital of North Midlands, Stoke-on-Trent (United Kingdom); Mamas, Mamas [Keele Cardiovascular Research Group, Keele University, Stoke-on-Trent (United Kingdom); Farr Institute, Institute of Population Health, University of Manchester, Manchester (United Kingdom)

2015-12-15

Objectives: The aim of this study is to review the available literature on the efficacy and safety of agents used for prevention of RAS. Background: Different vasodilator agents have been used to prevent radial artery spasm (RAS) in patients undergoing transradial cardiac catheterization. Methods: We included studies that evaluated any intra-arterial drug administered in the setting cardiac catheterization that was undertaken through the transradial access site (TRA). We also compared studies for secondary outcomes of major bleeding, procedure time, and procedure failure rate in setting of RAS prevention, patent hemostasis and radial artery occlusion. Results: 22 clinical studies met the inclusion criteria. For placebo, RAS rate was 12% (4 studies, 638 participants), which was similar to 2.5 mg of verapamil 12% (3 studies, 768 participants) but greater than 5 mg of verapamil (4%, 2 studies, 497 participants). For nicorandil, there was a much higher RAS rate compared to placebo (16%, 3 studies, 447 participants). The lowest rates of RAS was found for nitroglycerin at both 100 μg (4%) and 200 μg (2%) doses, isosorbide mononitrate (4%) and nicardipine (3%). We found no information regarding the procedure failure rates, patent hemostasis, and radial artery occlusion in these studies. Conclusions: In this largest and up-to-date review on intra-arterial vasodilators use to reduce RAS, we have found that the verapamil at a dose of 5 mg or verapamil in combination with nitroglycerine are the best combinations to reduce RAS. - Highlights: • Radial artery spasm (RAS) causes procedural failure in transradial catheterization. • RAS may complicate 10–15% procedures undertaken through the radial approach. • We reviewed the efficacy of vasodilators that have been used to minimize RAS. • The pooled RAS rate was lowest with 5 mg of verapamil (4%) compared to placebo (12%). • The best combination of drugs to minimize RAS is nitroglycerine and verapamil.

Effect of biliary cirrhosis on nonadrenergic noncholinergic-mediated relaxation of rat corpus cavernosum: Role of nitric oxide pathway and endocannabinoid system

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Dehpour A.R.

2008-06-01

Full Text Available Background: Relaxation of the corpus cavernosum plays a major role in penile erection. Nitric oxide (NO is known to be the most important factor mediating relaxation of corpus cavernosum, which is mainly derived from nonadrenergic noncholinergic (NANC nerves. The aim of the present study was to investigate the effect of biliary cirrhosis on nonadrenergic noncholinergic (NANC-mediated relaxation of rat corpus cavernosum as well as the possible relevant roles of endocannabinoid and nitric oxide systems.Methods: Corporal strips from sham-operated and biliary cirrhotic rats were mounted under tension in a standard oxygenated organ bath with guanethidine sulfate (5 µM and atropine (1 µM to induce adrenergic and cholinergic blockade. The strips were precontracted with phenylephrine hydrochloride (7.5 µM and electrical field stimulation was applied at different frequencies (2, 5, 10, 15 Hz to obtain NANC-mediated relaxation. In separate precontracted strips of the sham and cirrhotic groups, the concentration-dependent relaxant responses to sodium nitroprusside (10 nM-1mM, as an NO donor, were assessed.  Results: The NANC-mediated relaxation was significantly enhanced in cirrhotic animals (P<0.01. Anandamide potentiated the relaxations in both groups (P<0.05. The cannabinoid CB1 receptor antagonist AM251 (10 µM and the vanilloid receptor antagonist capsazepine (10 µM each significantly prevented the enhanced relaxations in cirrhotic rats (P<0.01. The CB2 receptor antagonist AM630 had no effect on relaxations in the cirrhotic group. In a concentration-dependent manner, L-NAME (30-1000 nM inhibited relaxations in both the sham and cirrhotic groups, although cirrhotic groups were more resistant to the inhibitory effects of L-NAME. The degree of relaxation induced by sodium nitroprusside (10 nM-1 mM was similar in the two groups.Conclusions: Biliary cirrhosis enhances the neurogenic relaxation in rat corpus cavernosum probably via the NO pathway and

Destruction of hazardous and mixed wastes using mediated electrochemical oxidation in a Ag(II)HNO3 bench scale system

International Nuclear Information System (INIS)

Balazs, B.; Chiba, Z.; Hsu, P.; Lewis, P.; Murguia, L.; Adamson, M.

1997-01-01

Mediated Electrochemical Oxidation (MEO) is a promising technology for the destruction of organic containing wastes and the remediation of mixed wastes containing transuranic components. The combination of a powerful oxidant and an acid solution allows the conversion of nearly all organics, whether present in hazardous or in mixed waste, to carbon dioxide. Insoluble transuranics are dissolved in this process and may be recovered by separation and precipitation.The MEO technique offers several advantages which are inherent in the system. First, the oxidation/dissolution processes are accomplished at near ambient pressures and temperatures (30-70 degrees C). Second, all waste stream components and oxidation products (with the exception of evolved gases) are contained in an aqueous environment. This electrolyte acts as an accumulator for inorganics which were present in the original waste stream, and the large volume of electrolyte provides a thermal buffer for the energy released during oxidation of the organics. Third, the generation of secondary waste is minimal, as the process needs no additional reagents. Finally, the entire process can be shut down by simply turning off the power, affording a level of control unavailable in some other techniques.Numerous groups, both in the United States and Europe, have made substantial progress in the last decade towards understanding the mechanistic pathways, kinetics, and engineering aspects of the process. At Lawrence Livermore National Laboratory, substantial contributions have been made to this knowledge base in these areas and others. Conceptual design and engineering development have been completed for a pilot plant-scale MEO system, and numerous data have been gathered on the efficacy of the process for a wide variety of anticipated waste components. This presentation will review the data collected at LLNL for a bench scale system based primarily on the use of a Ag(II) mediator in a nitric acid electrolyte; results

Destruction of commercial pesticides by cerium redox couple mediated electrochemical oxidation process in continuous feed mode

International Nuclear Information System (INIS)

Balaji, Subramanian; Chung, Sang Joon; Ryu, Jae-Yong; Moon, Il Shik

2009-01-01

Mediated electrochemical oxidation was carried out for the destruction of commercial pesticide formulations using cerium(IV) in nitric acid as the mediator electrolyte solution in a bench scale set up. The mediator oxidant was regenerated in situ using an electrochemical cell. The real application of this sustainable process for toxic organic pollutant destruction lies in its ability for long term continuous operation with continuous organic feeding and oxidant regeneration with feed water removal. In this report we present the results of fully integrated MEO system. The task of operating the continuous feed MEO system for a long time was made possible by continuously removing the feed water using an evaporator set up. The rate of Ce(IV) regeneration in the electrochemical cell and the consumption for the pesticide destruction was matched based on carbon content of the pesticides. It was found that under the optimized experimental conditions for Ce(III) oxidation, organic addition and water removal destruction efficiency of ca. 99% was obtained for all pesticides studied. It was observed that the Ce(IV) concentration was maintained nearly the same throughout the experiment. The stable operation for 6 h proved that the process can be used for real applications and for possible scale up for the destruction of larger volumes of toxic organic wastes.

Resveratrol and Endothelial Nitric Oxide

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Ning Xia

2014-10-01

Full Text Available Nitric oxide (NO derived from the endothelial NO synthase (eNOS has antihypertensive, antithrombotic, anti-atherosclerotic and antiobesogenic properties. Resveratrol is a polyphenol phytoalexin with multiple cardiovascular and metabolic effects. Part of the beneficial effects of resveratrol are mediated by eNOS. Resveratrol stimulates NO production from eNOS by a number of mechanisms, including upregulation of eNOS expression, stimulation of eNOS enzymatic activity and reversal of eNOS uncoupling. In addition, by reducing oxidative stress, resveratrol prevents oxidative NO inactivation by superoxide thereby enhancing NO bioavailability. Molecular pathways underlying these effects of resveratrol involve SIRT1, AMPK, Nrf2 and estrogen receptors.

Three transcription regulators of the Nss family mediate the adaptive response induced by nitrate, nitric oxide or nitrous oxide in Wolinella succinogenes.

Science.gov (United States)

Kern, Melanie; Simon, Jörg

2016-09-01

Sensing potential nitrogen-containing respiratory substrates such as nitrate, nitrite, hydroxylamine, nitric oxide (NO) or nitrous oxide (N2 O) in the environment and subsequent upregulation of corresponding catabolic enzymes is essential for many microbial cells. The molecular mechanisms of such adaptive responses are, however, highly diverse in different species. Here, induction of periplasmic nitrate reductase (Nap), cytochrome c nitrite reductase (Nrf) and cytochrome c N2 O reductase (cNos) was investigated in cells of the Epsilonproteobacterium Wolinella succinogenes grown either by fumarate, nitrate or N2 O respiration. Furthermore, fumarate respiration in the presence of various nitrogen compounds or NO-releasing chemicals was examined. Upregulation of each of the Nap, Nrf and cNos enzyme systems was found in response to the presence of nitrate, NO-releasers or N2 O, and the cells were shown to employ three transcription regulators of the Crp-Fnr superfamily (homologues of Campylobacter jejuni NssR), designated NssA, NssB and NssC, to mediate the upregulation of Nap, Nrf and cNos. Analysis of single nss mutants revealed that NssA controls production of the Nap and Nrf systems in fumarate-grown cells, while NssB was required to induce the Nap, Nrf and cNos systems specifically in response to NO-generators. NssC was indispensable for cNos production under any tested condition. The data indicate dedicated signal transduction routes responsive to nitrate, NO and N2 O and imply the presence of an N2 O-sensing mechanism. © 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.

Nitric oxide mediates angiogenesis induced in vivo by platelet-activating factor and tumor necrosis factor-alpha.

Science.gov (United States)

Montrucchio, G.; Lupia, E.; de Martino, A.; Battaglia, E.; Arese, M.; Tizzani, A.; Bussolino, F.; Camussi, G.

1997-01-01

We evaluated the role of an endogenous production of nitric oxide (NO) in the in vitro migration of endothelial cells and in the in vivo angiogenic response elicited by platelet-activating factor (PAF), tumor necrosis factor-alpha (TNF), and basic fibroblast growth factor (bFGF). The NO synthase inhibitor, N omega-nitro-L-arginine-methyl ester (L-NAME), but not its enantiomer D-NAME, prevented chemotaxis of endothelial cells induced in vitro by PAF and by TNF. The motogenic activity of TNF was also inhibited by WEB 2170, a specific PAF-receptor antagonist. In contrast, chemotaxis induced by bFGF was not prevented by L-NAME or by WEB 2170. Angiogenesis was studied in vivo in a murine model in which Matrigel was used as a vehicle for the delivery of mediators. In this model, the angiogenesis induced by PAF and TNF was inhibited by WEB 2170 and L-NAME but not by D-NAME. In contrast, angiogenesis induced by bFGF was not affected by L-NAME or by WEB 2170. TNF, but not bFGF, induced PAF synthesis within Matrigel. These results suggest that NO mediates the angiogenesis induced by PAF as well as that induced by TNF, which is dependent on the production of PAF. In contrast, the angiogenic effect of bFGF appears to be both PAF and NO independent. Images Figure 3 Figure 4 PMID:9250168

Activation of Nrf2-mediated oxidative stress response in macrophages by hypochlorous acid

International Nuclear Information System (INIS)

Pi Jingbo; Zhang Qiang; Woods, Courtney G.; Wong, Victoria; Collins, Sheila; Andersen, Melvin E.

2008-01-01

Hypochlorous acid (HOCl), a potent oxidant generated when chlorine gas reacts with water, is important in the pathogenesis of many disorders. Transcription factor Nrf2-mediated antioxidant response represents a critical cellular defense mechanism that serves to maintain intracellular redox homeostasis and limit oxidative damage. In the present study, the effect of HOCl on Nrf2 activation was investigated in macrophages, one of the target cells of chlorine gas exposure. Exposure of RAW 264.7 macrophages to HOCl resulted in increased protein levels of Nrf2 in nuclear extractions, as well as a time- and dose-dependent increase in the expression of Nrf2 target genes, including heme oxygenase-1, NAD(P)H:quinone oxidoreductase 1 (NQO-1), glutamate cysteine ligase catalytic subunit (GCLC), and glutathione synthetase (GS). Additionally, intracellular glutathione (GSH), which is the prime scavenger for HOCl in cells, decreased within the first hour of HOCl exposure. The decline was followed by a GSH rebound that surpassed the initial basal levels by up to 4-fold. This reversal in GSH levels closely correlated with the gene expression profile of GCLC and GS. To study the mechanisms of Nrf2 activation in response to HOCl exposure, we examined the effects of several antioxidants on Nrf2-mediated response. Pretreatment with cell-permeable catalase, N-acetyl-L-cysteine or GSH-monoethyl ester markedly reduced expression of NQO-1 and GCLC under HOCl challenge conditions, suggesting intracellular ROS-scavenging capacity affects HOCl-induced Nrf2 activation. Importantly, pre-activation of Nrf2 with low concentrations of pro-oxidants protected the cells against HOCl-induced cell damage. Taken together, we provide direct evidence that HOCl activates Nrf2-mediated antioxidant response, which protects cells from oxidative damage

Nitric oxide-mediated modulation of iron regulatory proteins: implication for cellular iron homeostasis.

Science.gov (United States)

Kim, Sangwon; Ponka, Prem

2002-01-01

Iron regulatory proteins (IRP1 and IRP2) control the synthesis of transferrin receptors (TfR) and ferritin by binding to iron-responsive elements (IREs) that are located in the 3' untranslated region (UTR) and the 5' UTR of their respective mRNAs. Cellular iron levels affect binding of IRPs to IREs and consequently expression of TfR and ferritin. Moreover, NO(.), a redox species of nitric oxide that interacts primarily with iron, can activate IRP1 RNA-binding activity resulting in an increase in TfR mRNA levels and a decrease in ferritin synthesis. We have shown that treatment of RAW 264.7 cells (a murine macrophage cell line) with NO(+) (nitrosonium ion, which causes S-nitrosylation of thiol groups) resulted in a rapid decrease in RNA-binding of IRP2, followed by IRP2 degradation, and these changes were associated with a decrease in TfR mRNA levels and a dramatic increase in ferritin synthesis. Moreover, we demonstrated that stimulation of RAW 264.7 cells with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) increased IRP1 binding activity, whereas RNA-binding of IRP2 decreased and was followed by a degradation of this protein. Furthermore, the decrease of IRP2 binding/protein levels was associated with a decrease in TfR mRNA levels and an increase in ferritin synthesis in LPS/IFN-gamma-treated cells, and these changes were prevented by inhibitors of inducible nitric oxide synthase. These results suggest that NO(+)-mediated degradation of IRP2 plays a major role in iron metabolism during inflammation.

Ameliorating Effect of Piperine on NO-cGMP Pathway in Stress ...

African Journals Online (AJOL)

... dose of PP and SB-203580 enhanced effect of Piperine in stressed mice with no array on locomotor activity with direct influence on Nitric oxide. Piperine produced significant changes in Nitric oxide level which is pathophysiologic mediator(s) of depression, which validate the action of piperine on depression symptoms.

Optimization of NO oxidation by H2O2 thermal decomposition at moderate temperatures.

Science.gov (United States)

Zhao, Hai-Qian; Wang, Zhong-Hua; Gao, Xing-Cun; Liu, Cheng-Hao; Qi, Han-Bing

2018-01-01

H2O2 was adopted to oxidize NO in simulated flue gas at 100-500°C. The effects of the H2O2 evaporation conditions, gas temperature, initial NO concentration, H2O2 concentration, and H2O2:NO molar ratio on the oxidation efficiency of NO were investigated. The reason for the narrow NO oxidation temperature range near 500°C was determined. The NO oxidation products were analyzed. The removal of NOx using NaOH solution at a moderate oxidation ratio was studied. It was proven that rapid evaporation of the H2O2 solution was critical to increase the NO oxidation efficiency and broaden the oxidation temperature range. the NO oxidation efficiency was above 50% at 300-500°C by contacting the outlet of the syringe needle and the stainless-steel gas pipe together to spread H2O2 solution into a thin film on the surface of the stainless-steel gas pipe, which greatly accelerated the evaporation of H2O2. The NO oxidation efficiency and the NO oxidation rate increased with increasing initial NO concentration. This method was more effective for the oxidation of NO at high concentrations. H2O2 solution with a concentration higher than 15% was more efficient in oxidizing NO. High temperatures decreased the influence of the H2O2 concentration on the NO oxidation efficiency. The oxidation efficiency of NO increased with an increase in the H2O2:NO molar ratio, but the ratio of H2O2 to oxidized NO decreased. Over 80% of the NO oxidation product was NO2, which indicated that the oxidation ratio of NO did not need to be very high. An 86.7% NO removal efficiency was obtained at an oxidation ratio of only 53.8% when combined with alkali absorption.

Role of Inflammation and Oxidative Stress Mediators in Gliomas

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Alfredo Conti

2010-04-01

Full Text Available Gliomas are the most common primary brain tumors of the central nervous system. Despite relevant progress in conventional treatments, the prognosis of such tumors remains almost invariably dismal. The genesis of gliomas is a complex, multistep process that includes cellular neoplastic transformation, resistance to apoptosis, loss of control of the cell cycle, angiogenesis, and the acquisition of invasive properties. Among a number of different biomolecular events, the existence of molecular connections between inflammation and oxidative stress pathways and the development of this cancer has been demonstrated. In particular, the tumor microenvironment, which is largely orchestrated by inflammatory molecules, is an indispensable participant in the neoplastic process, promoting proliferation, survival and migration of such tumors. Proinflammatory cytokines, such as tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma, as well as chemokines and prostaglandins, are synthesized by resident brain cells and lymphocytes invading the affected brain tissue. Key mediators of cancer progression include nuclear factor-kappaB, reactive oxygen and nitrogen species, and specific microRNAs. The collective activity of these mediators is largely responsible for a pro-tumorigenic response through changes in cell proliferation, cell death, cellular senescence, DNA mutation rates, DNA methylation and angiogenesis. We provide a general overview of the connection between specific inflammation and oxidative stress pathway molecules and gliomas. The elucidation of specific effects and interactions of these factors may provide the opportunity for the identification of new target molecules leading to improved diagnosis and treatment.

Role of Inflammation and Oxidative Stress Mediators in Gliomas

Energy Technology Data Exchange (ETDEWEB)

Conti, Alfredo, E-mail: alfredo.conti@unime.it; Gulì, Carlo; La Torre, Domenico; Tomasello, Chiara; Angileri, Filippo F.; Aguennouz, M’Hammed [Department of Neuroscience and Department of Oncology, University of Messina, Policlinico Universitario, Via Consolare Valeria 1, 98125, Messina (Italy)

2010-04-26

Gliomas are the most common primary brain tumors of the central nervous system. Despite relevant progress in conventional treatments, the prognosis of such tumors remains almost invariably dismal. The genesis of gliomas is a complex, multistep process that includes cellular neoplastic transformation, resistance to apoptosis, loss of control of the cell cycle, angiogenesis, and the acquisition of invasive properties. Among a number of different biomolecular events, the existence of molecular connections between inflammation and oxidative stress pathways and the development of this cancer has been demonstrated. In particular, the tumor microenvironment, which is largely orchestrated by inflammatory molecules, is an indispensable participant in the neoplastic process, promoting proliferation, survival and migration of such tumors. Proinflammatory cytokines, such as tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma, as well as chemokines and prostaglandins, are synthesized by resident brain cells and lymphocytes invading the affected brain tissue. Key mediators of cancer progression include nuclear factor-kappaB, reactive oxygen and nitrogen species, and specific microRNAs. The collective activity of these mediators is largely responsible for a pro-tumorigenic response through changes in cell proliferation, cell death, cellular senescence, DNA mutation rates, DNA methylation and angiogenesis. We provide a general overview of the connection between specific inflammation and oxidative stress pathway molecules and gliomas. The elucidation of specific effects and interactions of these factors may provide the opportunity for the identification of new target molecules leading to improved diagnosis and treatment.

Role of Inflammation and Oxidative Stress Mediators in Gliomas

International Nuclear Information System (INIS)

Conti, Alfredo; Gulì, Carlo; La Torre, Domenico; Tomasello, Chiara; Angileri, Filippo F.; Aguennouz, M’Hammed

2010-01-01

Gliomas are the most common primary brain tumors of the central nervous system. Despite relevant progress in conventional treatments, the prognosis of such tumors remains almost invariably dismal. The genesis of gliomas is a complex, multistep process that includes cellular neoplastic transformation, resistance to apoptosis, loss of control of the cell cycle, angiogenesis, and the acquisition of invasive properties. Among a number of different biomolecular events, the existence of molecular connections between inflammation and oxidative stress pathways and the development of this cancer has been demonstrated. In particular, the tumor microenvironment, which is largely orchestrated by inflammatory molecules, is an indispensable participant in the neoplastic process, promoting proliferation, survival and migration of such tumors. Proinflammatory cytokines, such as tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma, as well as chemokines and prostaglandins, are synthesized by resident brain cells and lymphocytes invading the affected brain tissue. Key mediators of cancer progression include nuclear factor-kappaB, reactive oxygen and nitrogen species, and specific microRNAs. The collective activity of these mediators is largely responsible for a pro-tumorigenic response through changes in cell proliferation, cell death, cellular senescence, DNA mutation rates, DNA methylation and angiogenesis. We provide a general overview of the connection between specific inflammation and oxidative stress pathway molecules and gliomas. The elucidation of specific effects and interactions of these factors may provide the opportunity for the identification of new target molecules leading to improved diagnosis and treatment

Mediated electrochemical oxidation as an alternative to incineration for mixed wastes

International Nuclear Information System (INIS)

Chiba, Z.; Schumacher, B.; Lewis, P.; Murguia, L.

1995-02-01

Mediated Electrochemical Oxidation (MEO) is an aqueous process which oxidizes organics electrochemically at low temperatures and ambient pressures. The process can be used to treat mixed wastes containing hazardous organics by destroying the organic components of the wastes. The radioactive components of the wastes are dissolved in the electrolyte where they can be recovered if desired, or immobilized for disposal. The process of destroying organics is accomplished via a mediator, which is in the form of metallic ions in solution. At Lawrence Livermore National Laboratory (LLNL) we have worked with worked with several mediators, including silver, cobalt and cerium. We have tested mediators in nitric as well as sulfuric acids. We have recently completed extensive experimental studies on cobalt-sulfuric acid and silver-nitric acid systems for destroying the major organic components of Rocky Flats Plant combustible mixed wastes. Organics tested were: Trimsol (a cutting oil), cellulose (including paper and cloth), rubber (latex), plastics (Tyvek, polyethylene and polyvinyl chloride) and biomass (bacteria). The process was capable of destroying almost all of the organics tested, attaining high destruction efficiencies at reasonable coulombic efficiencies. The only exception was polyvinyl chloride, which was destroyed very slowly resulting in poor coulombic efficiencies. Besides the process development work mentioned above, we are working on the design of a pilot-plant scale integrated system to be installed in the Mixed Waste Management Facility (MWMF) at LLNL. The system will also be completely integrated with upstream and downstream processes (for example, feed preparation, off-gas and water treatment, and final forms encapsulation). The conceptual design for the NEO-MWMF system has been completed and preliminary design work has been initiated. Demonstration of the process with low-level mixed wastes is expected to commence in 1998

Haemoglobin modulates salicylate and jasmonate/ethylene-mediated resistance mechanisms against pathogens

DEFF Research Database (Denmark)

Mur, Luis A J; Sivakumaran, Anushen; Mandon, Julien

2012-01-01

Nitric oxide (NO) plays a role in defence against hemibiotrophic pathogens mediated by salicylate (SA) and also necrotrophic pathogens influenced by jasmonate/ethylene (JA/Et). This study examined how NO-oxidizing haemoglobins (Hb) encoded by GLB1, GLB2, and GLB3 in Arabidopsis could influence both...

Does PGE₁ vasodilator prevent orthopaedic implant-related infection in diabetes? Preliminary results in a mouse model.

Science.gov (United States)

Lovati, Arianna B; Romanò, Carlo L; Monti, Lorenzo; Vassena, Christian; Previdi, Sara; Drago, Lorenzo

2014-01-01

Implant-related infections are characterized by bacterial colonization and biofilm formation on the prosthesis. Diabetes represents one of the risk factors that increase the chances of prosthetic infections because of related severe peripheral vascular disease. Vasodilatation can be a therapeutic option to overcome diabetic vascular damages and increase the local blood supply. In this study, the effect of a PGE₁ vasodilator on the incidence of surgical infections in diabetic mice was investigated. A S. aureus implant-related infection was induced in femurs of diabetic mice, then differently treated with a third generation cephalosporin alone or associated with a PGE₁ vasodilator. Variations in mouse body weight were evaluated as index of animal welfare. The femurs were harvested after 28 days and underwent both qualitative and quantitative analysis as micro-CT, histological and microbiological analyses. The analysis performed in this study demonstrated the increased host response to implant-related infection in diabetic mice treated with the combination of a PGE₁ and antibiotic. In this group, restrained signs of infections were identified by micro-CT and histological analysis. On the other hand, the diabetic mice treated with the antibiotic alone showed a severe infection and inability to successfully respond to the standard antimicrobial treatment. The present study revealed interesting preliminary results in the use of a drug combination of antibiotic and vasodilator to prevent implant-related Staphylococcus aureus infections in a diabetic mouse model.

Effects of Electroacupuncture Stimulation at “Zusanli” Acupoint on Hepatic NO Release and Blood Perfusion in Mice

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Shu-you Wang

2015-01-01

Full Text Available The study is to observe the influence of electroacupuncture (EA stimulation at “Zusanli” (ST36 on the release of nitric oxide (NO and blood perfusion (BP in the liver and further explore whether the hepatic blood perfusion (HBP changes were regulated by EA ST36 induced NO in nitric oxide synthase inhibited mice. The HBP change of the mice was detected by laser speckle perfusion imaging (LSPI before and after being given interventions, and the NO in liver tissue was detected by nitric acid reductase in each group. The NO levels and HBP in the L-NAME group were significantly lower than those in the control group (P<0.01. The NO level and HBP increase in EA group were significantly higher than those in control group (P<0.05. The NO level in the L-NAME EA group was slightly higher than that in the L-NAME group. The HBP increase in the L-NAME EA group was not statistically significant. These results showed that EA could accelerate the synthesis of NO and thereby increase HBP via vasodilation in liver tissue.

Electron Transfer Mediator Effects in Water Oxidation Catalysis by Solution and Surface-Bound Ruthenium Bpy-Dicarboxylate Complexes

Energy Technology Data Exchange (ETDEWEB)

Sheridan, Matthew V.; Sherman, Benjamin D.; Marquard, Seth L.; Fang, Zhen; Ashford, Dennis L.; Wee, Kyung-Ryang; Gold, Alexander S.; Alibabaei, Leila; Rudd, Jennifer A.; Coggins, Michael K.; Meyer, Thomas J.

2015-11-12

Electrocatalytic water oxidation by the catalyst, ruthenium 2,2'-bipyridine-6,6'-dicarboxylate (bda) bis-isoquinoline (isoq), [Ru(bda)(isoq)₂], 1, was investigated at metal oxide electrodes surface-derivatized with electron transfer (ET) mediators. At indium-doped tin oxide (ITO) in pH 7.2 in H₂PO₄–/HPO₄²– buffers in 0.5 M NaClO₄ with added acetonitrile (MeCN), the catalytic activity of 1 is enhanced by the surface-bound redox mediators [Ru (4,4'-PO₃H₂-bpy)(4,4'-R-bpy)₂]²⁺ (RuPbpyR₂²⁺, R = Br, H, Me, or OMe, bpy = 2,2'-bipyridine). Rate-limiting ET between the Ru³⁺ form of the mediator and the Ru^IV(O) form in the [Ru^V/IV(O)]^+/0 couple of 1 is observed at relatively high concentrations of HPO₄^2– buffer base under conditions where O···O bond formation is facilitated by atom-proton transfer (APT). For the solution [Ru(bpy)₃]^3+/2+ mediator couple and 1 as the catalyst, catalytic currents vary systematically with the concentration of mediator and the HPO₄^2– buffer base concentration. Electron transfer mediation of water oxidation catalysis was also investigated on nanoparticle TiO₂ electrodes co-loaded with catalyst [Ru(bda)(py-4-O(CH₂)₃-PO₃H₂)₂], 2, (py = pyridine) and RuPbpyR₂²⁺ (R = H, Me, or OMe) with an interplay between rate-limiting catalyst oxidation and rate-limiting O···O bond formation by APT. Lastly, the co-loaded assembly RuPbpyR₂²⁺ + 2 has been investigated in a dye-sensitized photoelectrosynthesis cell for water splitting.

Vasodilation increases pulse pressure variation, mimicking hypovolemic status in rabbits

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Glauco A Westphal

2010-01-01

Full Text Available OBJECTIVE: To test the hypothesis that pulse pressure respiratory variation (PPV amplification, observed in hypovolemia, can also be observed during sodium nitroprusside (SNP-induced vasodilation. INTRODUCTION: PPV is largely used for early identification of cardiac responsiveness, especially when hypovolemia is suspected. PPV results from respiratory variation in transpulmonary blood flow and reflects the left ventricular preload variations during respiratory cycles. Any factor that decreases left ventricular preload can be associated with PPV amplification, as seen in hypovolemia. METHODS: Ten anesthetized and mechanically ventilated rabbits underwent progressive hypotension by either controlled hemorrhage (Group 1 or intravenous SNP infusion (Group 2. Animals in Group 1 (n = 5 had graded hemorrhage induced at 10% steps until 50% of the total volume was bled. Mean arterial pressure (MAP steps were registered and assumed as pressure targets to be reached in Group 2. Group 2 (n = 5 was subjected to a progressive SNP infusion to reach similar pressure targets as those defined in Group 1. Heart rate (HR, systolic pressure variation (SPV and PPV were measured at each MAP step, and the values were compared between the groups. RESULTS: SPV and PPV were similar between the experimental models in all steps (p > 0.16. SPV increased earlier in Group 2. CONCLUSION: Both pharmacologic vasodilation and graded hemorrhage induced PPV amplification similar to that observed in hypovolemia, reinforcing the idea that amplified arterial pressure variation does not necessarily represent hypovolemic status but rather potential cardiovascular responsiveness to fluid infusion.

Oscillatory dynamics of vasoconstriction and vasodilation identified by time-localized phase coherence

International Nuclear Information System (INIS)

Sheppard, L W; McClintock, P V E; Stefanovska, A; Vuksanovic, V

2011-01-01

We apply wavelet-based time-localized phase coherence to investigate the relationship between blood flow and skin temperature, and between blood flow and instantaneous heart rate (IHR), during vasoconstriction and vasodilation provoked by local cooling or heating of the skin. A temperature-controlled metal plate (∼10 cm 2 ) placed on the volar side of the left arm was used to provide the heating and cooling. Beneath the plate, the blood flow was measured by laser Doppler flowmetry and the adjacent skin temperature by a thermistor. Two 1 h datasets were collected from each of the ten subjects. In each case a 30 min basal recording was followed by a step change in plate temperature, to either 24 deg. C or 42 deg. C. The IHR was derived from simultaneously recorded ECG. We confirm the changes in the energy and frequency of blood flow oscillations during cooling and heating reported earlier. That is, during cooling, there was a significant decrease in the average frequency of myogenic blood flow oscillations (p < 0.05) and the myogenic spectral peak became more prominent. During heating, there was a significant (p < 0.05) general increase in spectral energy, associated with vasodilation, except in the myogenic interval. Weak phase coherence between temperature and blood flow was observed for unperturbed skin, but it increased in all frequency intervals as a result of heating. It was not significantly affected by cooling. We also show that significant (p < 0.05) phase coherence exists between blood flow and IHR in the respiratory and myogenic frequency intervals. Cooling did not affect this phase coherence in any of the frequency intervals, whereas heating enhanced the phase coherence in the respiratory and myogenic intervals. This can be explained by the reduction in vascular resistance produced by heating, a process where myogenic mechanisms play a key role. We conclude that the mechanisms of vasodilation and vasoconstriction, in response to temperature change, are

Enhancing hippocampal blood flow after cerebral ischemia and vasodilating basilar arteries: in vivo and in vitro neuroprotective effect of antihypertensive DDPH

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Li Sun

2015-01-01

Full Text Available 1-(2,6-Dimethylphenoxy-2-(3,4-dimethoxyphenylethylamino-propane hydrochloride (DDPH is a novel antihypertensive agent based on structural characteristics of mexiletine and verapamine. We investigated the effect of DDPH on vasodilatation and neuroprotection in a rat model of cerebral ischemia in vivo, and a rabbit model of isolated basilar arteries in vitro. Our results show that DDPH (10 mg/kg significantly increased hippocampal blood flow in vivo in cerebral ischemic rats, and exerted dose-dependent relaxation of isolated basilar arteries contracted by histamine or KCl in the in vitro rabbit model. DDPH (3 × 10 -5 M also inhibited histamine-stimulated extracellular calcium influx and intracellular calcium release. Our findings suggest that DDPH has a vasodilative effect both in vivo and in vitro, which mediates a neuroprotective effect on ischemic nerve tissue.

Nitric Oxide Synthesis Is Increased in Cybrid Cells with m.3243A>G Mutation

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Juliana Gamba

2012-12-01

Full Text Available Nitric oxide (NO is a free radical and a signaling molecule in several pathways, produced by nitric oxide synthase (NOS from the conversion of L-arginine to citrulline. Supplementation of L-arginine has been used to treat MELAS (mitochondrial encephalopathy with lactic acidosis and stroke like syndrome, a mitochondrial disease caused by the m.3243A>G mutation. Low levels of serum arginine and endothelium dysfunction have been reported in MELAS and this treatment may increase NO in endothelial cells and promote vasodilation, decreasing cerebral ischemia and strokes. Although clinical benefits have been reported, little is known about NO synthesis in MELAS. In this study we found that osteosarcoma derived cybrid cells with high levels of m.3243A>G had increased nitrite, an NO metabolite, and increased intracellular NO, demonstrated by an NO fluorescent probe (DAF-FM. Muscle vessels from patients with the same mutation had increased staining in NADPH diaphorase, suggestive of increased NOS. These results indicate increased production of NO in cells harboring the m.3243A>G, however no nitrated protein was detected by Western blotting. Further studies are necessary to clarify the exact mechanisms of L-arginine effect to determine the appropriate clinical use of this drug therapy.

TRPV4 activation mediates flow-induced nitric oxide production in the rat thick ascending limb

Science.gov (United States)

Garvin, Jeffrey L.

2014-01-01

Nitric oxide (NO) regulates renal function. Luminal flow stimulates NO production in the thick ascending limb (TAL). Transient receptor potential vanilloid 4 (TRPV4) is a mechano-sensitive channel activated by luminal flow in different types of cells. We hypothesized that TRPV4 mediates flow-induced NO production in the rat TAL. We measured NO production in isolated, perfused rat TALs using the fluorescent dye DAF FM. Increasing luminal flow from 0 to 20 nl/min stimulated NO from 8 ± 3 to 45 ± 12 arbitrary units (AU)/min (n = 5; P < 0.05). The TRPV4 antagonists, ruthenium red (15 μmol/l) and RN 1734 (10 μmol/l), blocked flow-induced NO production. Also, luminal flow did not increase NO production in the absence of extracellular calcium. We also studied the effect of luminal flow on NO production in TALs transduced with a TRPV4shRNA. In nontransduced TALs luminal flow increased NO production by 47 ± 17 AU/min (P < 0.05; n = 5). Similar to nontransduced TALs, luminal flow increased NO production by 39 ± 11 AU/min (P < 0.03; n = 5) in TALs transduced with a control negative sequence-shRNA while in TRPV4shRNA-transduced TALs, luminal flow did not increase NO production (Δ10 ± 15 AU/min; n = 5). We then tested the effect of two different TRPV4 agonists on NO production in the absence of luminal flow. 4α-Phorbol 12,13-didecanoate (1 μmol/l) enhanced NO production by 60 ± 11 AU/min (P < 0.002; n = 7) and GSK1016790A (10 ηmol/l) increased NO production by 52 ± 15 AU/min (P < 0.03; n = 5). GSK1016790A (10 ηmol/l) did not stimulate NO production in TRPV4shRNA-transduced TALs. We conclude that activation of TRPV4 channels mediates flow-induced NO production in the rat TAL. PMID:24966090

Gaseous Mediators Nitric Oxide and Hydrogen Sulfide in the Mechanism of Gastrointestinal Integrity, Protection and Ulcer Healing

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Marcin Magierowski

2015-05-01

Full Text Available Nitric oxide (NO and hydrogen sulfide (H2S are known as biological messengers; they play an important role in human organism and contribute to many physiological and pathophysiological processes. NO is produced from l-arginine by constitutive NO synthase (NOS and inducible NOS enzymatic pathways. This gaseous mediator inhibits platelet aggregation, leukocyte adhesion and contributes to the vessel homeostasis. NO is known as a vasodilatory molecule involved in control of the gastric blood flow (GBF and the maintenance of gastric mucosal barrier integrity in either healthy gastric mucosa or that damaged by strong irritants. Biosynthesis of H2S in mammals depends upon two enzymes cystathionine-β-synthase and cystathionine γ-lyase. This gaseous mediator, similarly to NO and carbon monoxide, is involved in neuromodulation, vascular contractility and anti-inflammatory activities. For decades, H2S has been known to inhibit cytochrome c oxidase and reduce cell energy production. Nowadays it is generally considered to act through vascular smooth muscle ATP-dependent K+ channels, interacting with intracellular transcription factors and promote sulfhydration of protein cysteine moieties within the cell, but the mechanism of potential gastroprotective and ulcer healing properties of H2S has not been fully explained. The aim of this review is to compare current results of the studies concerning the role of H2S and NO in gastric mucosa protection and outline areas that may pose new opportunities for further development of novel therapeutic targets.

From field to health: a simple way to increase the nutraceutical content of grape as shown by NO-dependent vascular relaxation.

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Fumagalli, Francesca; Rossoni, Mara; Iriti, Marcello; di Gennaro, Antonio; Faoro, Franco; Borroni, Emanuele; Borgo, Michele; Scienza, Attilio; Sala, Angelo; Folco, Giancarlo

2006-07-26

Polyphenolic grapevine components involved in plant resistance against pathogens possess various pharmacological properties that include nitric oxide (NO)-dependent vasodilation and anti-inflammatory and free radical scavenging activities, which may explain the protective effect of moderate red wine consumption against cardiovascular disease. The aim of this work was (a) to verify the possibility that preharvest treatments of grapevine with a plant activator, benzo-(1,2,3)-thiadiazole-7-carbothioic acid S-methyl ester (BTH), could lead to an enriched nutraceutical potential of wine and (b) to characterize the profile of metabolites responsible for pharmacological activity. Plant spraying at the end of veraison, with a water suspension of BTH (0.3 mM), led to increased whole anthocyanin content as confirmed by HPLC comparative analysis. Extracts from berry skins of BTH-treated grapevines caused NO-dependent vasorelaxation, with a concentration-response curve that was significantly shifted to the left of the control non-BTH-treated curve. Moreover, 1:1000 dilutions of berry extracts from BTH-treated plants significantly increased basal production of guanosine 3',5'-cyclic monophosphate (cGMP) in human vascular endothelial cells when compared to the corresponding extracts of untreated plants. These results show that BTH treatment increases anthocyanin content of grape extracts, as well as their ability to induce NO-mediated vasoprotection. No increase of anthocyanin content was observed in the wine extracts from BTH-treated vines. It is concluded that BTH treatment could be exploited to increase the nutraceutical potential of grapes.

Mediated Intercultural Communication Barrier in No Drama Zone! Group

OpenAIRE

Lizal, Valentino

2015-01-01

This research study aimed to describe the mediated intercultural communication barriers in the No Drama Zone! group. This study is a qualitative descriptive type of research, with case study method. By doing in depth interview and observation, researcher found two barriers that generates other barriers in the group's mediated intercultural communication. The two big barriers were: language and physical barriers. Language barriers in this group generated two barriers, emotional barrier and pe...

Synthesis of Monodispersed Tantalum(V) oxide Nanospheres by an Ethylene Glycol Mediated Route

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Tantalum(V) oxide (Ta2O5) nanospheres have been synthesized by a very simple ethylene glycol mediated route. The two-step process involves the formation of glycolate nanoparticles and their subsequent hydrolysis and calcination to generate the final Ta2O5 nanospheres. The synthes...

Assessment of inotropic and vasodilating effects of milrinone lactate in patients with dilated cardiomyopathy and severe heart failure

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Edson Antonio Bregagnollo

1999-02-01

Full Text Available OBJECTIVE: To assess the hemodynamic and vasodilating effects of milrinone lactate (ML in patients with dilated cardiomyopathy (DCM and New York Heart Association (NYHA class III and IV heart failure. METHODS: Twenty patients with DCM and NYHA class III and IV heart failure were studied. The hemodynamic and vasodilating effects of ML, administered intravenously, were evaluated. The following variables were compared before and during drug infusion: cardiac output (CO and cardiac index (CI; pulmonary capillary wedge pressure (PCWP; mean aortic pressure (MAP; mean pulmonary artery pressure (MPAP; mean right atrial pressure (MRAP; left ventricular systolic and end-diastolic pressures (LVSP and LVEDP, respectively; peak rate of left ventricular pressure rise (dP/dt; systemic vascular resistance (SVR; pulmonary vascular resistance (PVR; and heart rate (HR. RESULTS: All patients showed a significant improvement of the analysed parameters of cardiac performance with an increase of CO and CI; a significant improvement in myocardial contractility (dP/dt and reduction of the LVEDP; PCWP; PAP; MAP; MRAP; SVR; PVR. Were observed no significant increase in HR occurred. CONCLUSION: Milrinone lactate is an inotropic dilating drug that, when administered intravenously, has beneficial effects on cardiac performance and myocardial contractility. It also promotes reduction of SVR and PVR in patients with DCM and NYHA class III and IV of heart failure.

Vasodilators in the treatment of acute heart failure : what we know, what we don't

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Metra, Marco; Teerlink, John R.; Voors, Adriaan A.; Felker, G. Michael; Milo-Cotter, Olga; Weatherley, Beth; Dittrich, Howard; Cotter, Gad

2009-01-01

Although we have recently witnessed substantial progress in management and outcome of patients with chronic heart failure, acute heart failure (AHF) management and outcome have not changed over almost a generation. Vasodilators are one of the cornerstones of AHF management; however, to a large

The protective effect of dexanabinol (HU-211) on nitric oxide and cysteine protease-mediated neuronal death in focal cerebral ischemia.

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Durmaz, Ramazan; Ozden, Hilmi; Kanbak, Güngör; Aral, Erinç; Arslan, Okan Can; Kartkaya, Kazim; Uzuner, Kubilay

2008-09-01

We hypothesized that dexanabinol can prevent neuronal death by protecting neuronal lysosomes from nitric oxide (NO)-mediated toxicity, and in turn, by suppressing the release of cathepsins during cerebral ischemia. Focal cerebral ischemia was induced in two sets of animals by permanent middle cerebral artery occlusion. The first set was used to monitor NO concentration and cathepsin activity, while the second was used for histological examination with hematoxylin and eosin, and TUNEL staining. In post-ischemic brain tissue, NO content and cathepsin B and L activity increased (p 0.05). The number of eosinophilic and apoptotic neurons increased in the post-ischemic cerebral cortex (p agent for the treatment of stroke patients.

Determinants of the response of left ventricular ejection fraction to vasodilator stress in electrocardiographically gated {sup 82}rubidium myocardial perfusion PET

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Brown, Tracy L.Y.; Merrill, Jennifer; Bengel, Frank M. [Johns Hopkins University, Department of Radiology and Radiological Sciences, Division of Nuclear Medicine, Baltimore, MD (United States); Volokh, Lana [GE Healthcare, Haifa (Israel)

2008-02-15

Myocardial perfusion imaging with {sup 82}Rb PET allows for ECG-gated studies to be obtained early after radiotracer injection, capturing ventricular function close to peak pharmacologic action of dipyridamole. This is different from gated SPECT and may potentially provide additional diagnostic information. We sought to identify potential correlates of the PET-derived ejection fraction response to vasodilator stress. One hundred ten consecutive patients undergoing {sup 82}Rb PET myocardial perfusion imaging during evaluation for coronary artery disease were included. Using a GE Discovery STRx PET-CT scanner, ECG-gated images (eight bins) were obtained at rest and 4 min after dipyridamole infusion, 90 s after infusion of 1,480-2,220 MBq of {sup 82}Rb. Summed rest, stress, and difference scores (SRS, SSS, and SDS) were determined using a five-point scoring system and 20-segment model. Ejection fraction was calculated using automated QGS software. Significant reversibility (SDS {>=} 4) was found in 23 patients (21%). Mean LVEF in all patients was 47 {+-} 13% at rest and 53 {+-} 13% during dipyridamole. LVEF increased in 89 patients, and decreased in 17 patients during vasodilation. The change in LVEF was inversely correlated with SDS (r = -0.26; p = 0.007). Additionally, it was inversely correlated with resting LVEF (r = -0.20; p = 0.03) and SSS (r = -0.25; p = 0.009). No significant correlations were observed with SRS, heart rate, blood pressure, age, hypertension, hypercholesterolemia, or pretest likelihood of disease. At multivariate regression analysis, SDS was an independent predictor of the change in LVEF. Gated {sup 82}Rb PET during pharmacologic stress allows for assessment of the functional response to vasodilation. The magnitude of LVEF increase is determined by stress perfusion/reversible perfusion defects. Functional response to hyperemia may thus be incorporated in future evaluations of diagnostic and prognostic algorithms based on {sup 82}Rb PET. (orig.)

Does PGE₁ vasodilator prevent orthopaedic implant-related infection in diabetes? Preliminary results in a mouse model.

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Arianna B Lovati

Full Text Available BACKGROUND: Implant-related infections are characterized by bacterial colonization and biofilm formation on the prosthesis. Diabetes represents one of the risk factors that increase the chances of prosthetic infections because of related severe peripheral vascular disease. Vasodilatation can be a therapeutic option to overcome diabetic vascular damages and increase the local blood supply. In this study, the effect of a PGE₁ vasodilator on the incidence of surgical infections in diabetic mice was investigated. METHODOLOGY: A S. aureus implant-related infection was induced in femurs of diabetic mice, then differently treated with a third generation cephalosporin alone or associated with a PGE₁ vasodilator. Variations in mouse body weight were evaluated as index of animal welfare. The femurs were harvested after 28 days and underwent both qualitative and quantitative analysis as micro-CT, histological and microbiological analyses. RESULTS: The analysis performed in this study demonstrated the increased host response to implant-related infection in diabetic mice treated with the combination of a PGE₁ and antibiotic. In this group, restrained signs of infections were identified by micro-CT and histological analysis. On the other hand, the diabetic mice treated with the antibiotic alone showed a severe infection and inability to successfully respond to the standard antimicrobial treatment. CONCLUSIONS: The present study revealed interesting preliminary results in the use of a drug combination of antibiotic and vasodilator to prevent implant-related Staphylococcus aureus infections in a diabetic mouse model.

Anthocyanins protect against LPS-induced oxidative stress-mediated neuroinflammation and neurodegeneration in the adult mouse cortex.

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Khan, Muhammad Sohail; Ali, Tahir; Kim, Min Woo; Jo, Myeung Hoon; Jo, Min Gi; Badshah, Haroon; Kim, Myeong Ok

2016-11-01

Several studies provide evidence that reactive oxygen species (ROS) are key mediators of various neurological disorders. Anthocyanins are polyphenolic compounds and are well known for their anti-oxidant and neuroprotective effects. In this study, we investigated the neuroprotective effects of anthocyanins (extracted from black soybean) against lipopolysaccharide (LPS)-induced ROS-mediated neuroinflammation and neurodegeneration in the adult mouse cortex. Intraperitoneal injection of LPS (250 μg/kg) for 7 days triggers elevated ROS and oxidative stress, which induces neuroinflammation and neurodegeneration in the adult mouse cortex. Treatment with 24 mg/kg/day of anthocyanins for 14 days in LPS-injected mice (7 days before and 7 days co-treated with LPS) attenuated elevated ROS and oxidative stress compared to mice that received LPS-injection alone. The immunoblotting results showed that anthocyanins reduced the level of the oxidative stress kinase phospho-c-Jun N-terminal Kinase 1 (p-JNK). The immunoblotting and morphological results showed that anthocyanins treatment significantly reduced LPS-induced-ROS-mediated neuroinflammation through inhibition of various inflammatory mediators, such as IL-1β, TNF-α and the transcription factor NF- k B. Anthocyanins treatment also reduced activated astrocytes and microglia in the cortex of LPS-injected mice, as indicated by reductions in GFAP and Iba-1, respectively. Anthocyanins also prevent overexpression of various apoptotic markers, i.e., Bax, cytosolic cytochrome C, cleaved caspase-3 and PARP-1. Immunohistochemical fluoro-jade B (FJB) and Nissl staining indicated that anthocyanins prevent LPS-induced neurodegeneration in the mouse cortex. Our results suggest that dietary flavonoids, such as anthocyanins, have antioxidant and neuroprotective activities that could be beneficial to various neurological disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effect of NO2 and water on the catalytic oxidation of soot

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Christensen, Jakob Munkholt; Grunwaldt, Jan-Dierk; Jensen, Anker Degn

2017-01-01

The influence of adding NO2 to 10 vol% O2/N2 on non-catalytic soot oxidation and soot oxidation in intimate or loose contact with a catalyst has been investigated. In non-catalytic soot oxidation the oxidation rate is increased significantly at lower temperatures by NO2. For soot oxidation in tig...... exhibited a volcano-curve dependence on the heat of oxygen chemisorption, and among the tested pure metals and oxides Cr2O3 was the most active catalyst. Further improvements were achieved with a FeaCrbOx binary oxide catalyst....

Continuing versus discontinuing antiplatelet drugs, vasodilators, and/or cerebral ameliorators on perioperative total blood loss in total knee arthroplasty without pneumatic tourniquet

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Sachiyuki Tsukada, MD

2018-03-01

Full Text Available Background: Although studies have supported the utility of perioperative continuation of antiplatelet drugs, vasodilators, and cerebral ameliorators in most procedures, no study compared total volume of blood loss after total knee arthroplasty (TKA in patients continuing and discontinuing these drugs. Methods: We retrospectively reviewed 266 consecutive patients undergoing TKA, and included 67 patients (25.2% taking antiplatelet drugs, vasodilators, or cerebral ameliorators in this study. All TKAs were performed without a pneumatic tourniquet. The primary outcome was perioperative total blood loss calculated from blood volume and change in hemoglobin. As subgroup analysis, we compared perioperative total blood loss in patients taking antiplatelet drugs. Results: There was no significant difference between the continuing group (n = 38 and discontinuing group (n = 29 in terms of the perioperative total blood loss (1025 ± 364 vs 1151 ± 327 mL, respectively; mean difference 126 mL; 95% confidence interval −45 to 298 mL; P = .15. No major bleeding or thrombotic events occurred in either group until postoperative 3-month follow-up. In patients taking antiplatelet drugs (n = 51, no significant difference was observed in the total blood loss between the continuing group (n = 30 and discontinuing group (n = 21 (1056 ± 287 vs 1151 ± 305 mL, respectively; mean difference 95 mL; 95% confidence interval −75 to 264 mL; P = .27. Conclusions: No significant differences in terms of perioperative total blood loss were observed between patients continuing and discontinuing study drugs. Continuing these drugs may be preferable in the perioperative period of TKA. Keywords: Knee, Primary arthroplasty, Bleeding events, Thrombotic events, Noncardiac surgery

Optical properties of cerium oxide (CeO2) nanoparticles synthesized by hydroxide mediated method

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Ali, Mawlood Maajal; Mahdi, Hadeel Salih; Parveen, Azra; Azam, Ameer

2018-05-01

The nanoparticles of cerium oxide have been successfully synthesized by hydroxide mediated method, using cerium nitrate and sodium hydroxide as precursors. The microstructural properties were analyzed by X-ray diffraction technique (XRD). The X-ray diffraction results show that the cerium oxide nanoparticles were in cubic structure. The optical absorption spectra of cerium oxide were recorded by UV-VIS spectrophotometer in the range of 320 to 600 nm and photoluminescence spectra in the range of 400-540 nm and have been presented. The energy band gap was determined by Tauc relationship. The crystallite size was determined from Debye-Scherer equation and came out to be 6.4 nm.

TNF-Mediated Restriction of Arginase 1 Expression in Myeloid Cells Triggers Type 2 NO Synthase Activity at the Site of Infection

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Ulrike Schleicher

2016-05-01

Full Text Available Neutralization or deletion of tumor necrosis factor (TNF causes loss of control of intracellular pathogens in mice and humans, but the underlying mechanisms are incompletely understood. Here, we found that TNF antagonized alternative activation of macrophages and dendritic cells by IL-4. TNF inhibited IL-4-induced arginase 1 (Arg1 expression by decreasing histone acetylation, without affecting STAT6 phosphorylation and nuclear translocation. In Leishmania major-infected C57BL/6 wild-type mice, type 2 nitric oxide (NO synthase (NOS2 was detected in inflammatory dendritic cells or macrophages, some of which co-expressed Arg1. In TNF-deficient mice, Arg1 was hyperexpressed, causing an impaired production of NO in situ. A similar phenotype was seen in L. major-infected BALB/c mice. Arg1 deletion in hematopoietic cells protected these mice from an otherwise lethal disease, although their disease-mediating T cell response (Th2, Treg was maintained. Thus, deletion or TNF-mediated restriction of Arg1 unleashes the production of NO by NOS2, which is critical for pathogen control.

Organic Nitrate Therapy, Nitrate Tolerance, and Nitrate-Induced Endothelial Dysfunction: Emphasis on Redox Biology and Oxidative Stress.

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Daiber, Andreas; Münzel, Thomas

2015-10-10

Organic nitrates, such as nitroglycerin (GTN), isosorbide-5-mononitrate and isosorbide dinitrate, and pentaerithrityl tetranitrate (PETN), when given acutely, have potent vasodilator effects improving symptoms in patients with acute and chronic congestive heart failure, stable coronary artery disease, acute coronary syndromes, or arterial hypertension. The mechanisms underlying vasodilation include the release of •NO or a related compound in response to intracellular bioactivation (for GTN, the mitochondrial aldehyde dehydrogenase [ALDH-2]) and activation of the enzyme, soluble guanylyl cyclase. Increasing cyclic guanosine-3',-5'-monophosphate (cGMP) levels lead to an activation of the cGMP-dependent kinase I, thereby causing the relaxation of the vascular smooth muscle by decreasing intracellular calcium concentrations. The hemodynamic and anti-ischemic effects of organic nitrates are rapidly lost upon long-term (low-dose) administration due to the rapid development of tolerance and endothelial dysfunction, which is in most cases linked to increased intracellular oxidative stress. Enzymatic sources of reactive oxygen species under nitrate therapy include mitochondria, NADPH oxidases, and an uncoupled •NO synthase. Acute high-dose challenges with organic nitrates cause a similar loss of potency (tachyphylaxis), but with distinct pathomechanism. The differences among organic nitrates are highlighted regarding their potency to induce oxidative stress and subsequent tolerance and endothelial dysfunction. We also address pleiotropic effects of organic nitrates, for example, their capacity to stimulate antioxidant pathways like those demonstrated for PETN, all of which may prevent adverse effects in response to long-term therapy. Based on these considerations, we will discuss and present some preclinical data on how the nitrate of the future should be designed.

Organic Nitrate Therapy, Nitrate Tolerance, and Nitrate-Induced Endothelial Dysfunction: Emphasis on Redox Biology and Oxidative Stress

Science.gov (United States)

2015-01-01

Abstract Organic nitrates, such as nitroglycerin (GTN), isosorbide-5-mononitrate and isosorbide dinitrate, and pentaerithrityl tetranitrate (PETN), when given acutely, have potent vasodilator effects improving symptoms in patients with acute and chronic congestive heart failure, stable coronary artery disease, acute coronary syndromes, or arterial hypertension. The mechanisms underlying vasodilation include the release of •NO or a related compound in response to intracellular bioactivation (for GTN, the mitochondrial aldehyde dehydrogenase [ALDH-2]) and activation of the enzyme, soluble guanylyl cyclase. Increasing cyclic guanosine-3′,-5′-monophosphate (cGMP) levels lead to an activation of the cGMP-dependent kinase I, thereby causing the relaxation of the vascular smooth muscle by decreasing intracellular calcium concentrations. The hemodynamic and anti-ischemic effects of organic nitrates are rapidly lost upon long-term (low-dose) administration due to the rapid development of tolerance and endothelial dysfunction, which is in most cases linked to increased intracellular oxidative stress. Enzymatic sources of reactive oxygen species under nitrate therapy include mitochondria, NADPH oxidases, and an uncoupled •NO synthase. Acute high-dose challenges with organic nitrates cause a similar loss of potency (tachyphylaxis), but with distinct pathomechanism. The differences among organic nitrates are highlighted regarding their potency to induce oxidative stress and subsequent tolerance and endothelial dysfunction. We also address pleiotropic effects of organic nitrates, for example, their capacity to stimulate antioxidant pathways like those demonstrated for PETN, all of which may prevent adverse effects in response to long-term therapy. Based on these considerations, we will discuss and present some preclinical data on how the nitrate of the future should be designed. Antioxid. Redox Signal. 23, 899–942. PMID:26261901

Study on the effect of reactive oxygen species-mediated oxidative stress on the activation of mitochondrial apoptosis and the tenderness of yak meat.

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Wang, Lin-Lin; Yu, Qun-Li; Han, Ling; Ma, Xiu-Li; Song, Ren-De; Zhao, Suo-Nan; Zhang, Wen-Hua

2018-04-01

This study investigated the effect of reactive oxygen species-mediated oxidative stress on activation of mitochondrial apoptosis and tenderness of yak meat during postmortem ageing. Oxidative stress degree, Ca 2+ levels, membrane permeability transition pore opening, mitochondrial membrane potential, apoptotic factors and the shear force were examined. Results showed that the ROS generated by H 2 O 2 significantly increased mitochondrial oxidative stress by decreasing the activities of superoxide dismutase, catalase and glutathione peroxidase, and increasing lipid peroxidation. Furthermore, oxidative stress enhanced Ca 2+ production and cytochrome c release, changed the levels of Bcl-2 family proteins and activated caspase-9 and -3 activities. Ultimately, oxidative stress increased the apoptosis rate and tenderness of yak meat. These observations confirmed that ROS-mediated oxidative stress participates in the activation of the apoptotic cascade reaction involving Ca 2+ and Bcl-2 family proteins. The results further suggested that ROS-mediated oxidative stress plays a significant role in meat tenderization through the mitochondrial apoptotic pathway. Copyright © 2017. Published by Elsevier Ltd.

LDL oxidation by platelets propagates platelet activation via an oxidative stress-mediated mechanism.

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Carnevale, Roberto; Bartimoccia, Simona; Nocella, Cristina; Di Santo, Serena; Loffredo, Lorenzo; Illuminati, Giulio; Lombardi, Elisabetta; Boz, Valentina; Del Ben, Maria; De Marco, Luigi; Pignatelli, Pasquale; Violi, Francesco

2014-11-01

Platelets generate oxidized LDL (ox-LDL) via NOX2-derived oxidative stress. We investigated if once generated by activated platelets ox-LDL can propagate platelet activation. Experiments were performed in platelets from healthy subjects (HS), hyper-cholesterolemic patients and patients with NOX2 hereditary deficiency. Agonist-stimulated platelets from HS added with LDL were associated with a dose-dependent increase of reactive oxidant species and ox-LDL. Agonist-stimulated platelets from HS added with a fixed dose of LDL (57.14 μmol/L) or added with homogenized human atherosclerotic plaque showed enhanced ox-LDL formation (approximately +50% and +30% respectively), which was lowered by a NOX2 inhibitor (approximately -35% and -25% respectively). Compared to HS, ox-LDL production was more pronounced in agonist-stimulated platelet rich plasma (PRP) from hyper-cholesterolemic patients but was almost absent in PRP from NOX2-deficient patients. Platelet aggregation and 8-iso-PGF2α-ΙΙΙ formation increased in LDL-treated washed platelets (+42% and +53% respectively) and PRP (+31% and +53% respectively). Also, LDL enhanced platelet-dependent thrombosis at arterial shear rate (+33%) but did not affect platelet activation in NOX2-deficient patients. Platelet activation by LDL was significantly inhibited by CD36 or LOX1 blocking peptides, two ox-LDL receptor antagonists, or by a NOX2 inhibitor. LDL-added platelets showed increased p38MAPK (+59%) and PKC (+51%) phosphorylation, p47(phox) translocation to platelet membrane (+34%) and NOX2 activation (+30%), which were inhibited by ox-LDL receptor antagonists. Platelets oxidize LDL, which in turn amplify platelet activation via specific ox-LDL receptors; both effects are mediated by NOX2 activation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Oxidative stress augments toll-like receptor 8 mediated neutrophilic responses in healthy subjects

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Matsunaga Kazuto

2009-06-01

Full Text Available Abstract Background Excessive oxidative stress has been reported to be generated in inflamed tissues and contribute to the pathogenesis of inflammatory lung diseases, exacerbations of which induced by viral infections are associated with toll-like receptor (TLR activation. Among these receptors, TLR8 has been reported as a key receptor that recognizes single-strand RNA virus. However, it remains unknown whether TLR8 signaling is potentiated by oxidative stress. The aim of this study is to examine whether oxidative stress modulates TLR8 signaling in vitro. Methods Human peripheral blood neutrophils were obtained from healthy non-smokers and stimulated with TLR 7/8 agonist imidazoquinoline resiquimod (R848 in the presence or absence of hydrogen peroxide (H2O2. Neutrophilic responses including cytokine release, superoxide production and chemotaxis were examined, and the signal transduction was also analyzed. Results Activation of TLR8, but not TLR7, augmented IL-8 release. The R848-augmented IL-8 release was significantly potentiated by pretreatment with H2O2 (p L-cysteine reversed this potentiation. The combination of H2O2 and R848 significantly potentiated NF-kB phosphorylation and IkBα degradation. The H2O2-potentiated IL-8 release was suppressed by MG-132, a proteosome inhibitor, and by dexamethasone. The expressions of TLR8, myeloid differentiation primary response gene 88 (MyD88, and tumor necrosis factor receptor-associated factor 6 (TRAF6 were not affected by H2O2. Conclusion TLR8-mediated neutrophilic responses were markedly potentiated by oxidative stress, and the potentiation was mediated by enhanced NF-kB activation. These results suggest that oxidative stress might potentiate the neutrophilic inflammation during viral infection.

Nitric oxide as a mediator of gastrointestinal mucosal injury?—Say it ain't so

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Paul Kubes

1995-01-01

Full Text Available Nitric oxide has been suggested as a contributor to tissue injury in various experimental models of gastrointestinal inflammation. However, there is overwhelming evidence that nitric oxide is one of the most important mediators of mucosal defence, influencing such factors as mucus secretion, mucosal blood flow, ulcer repair and the activity of a variety of mucosal immunocytes. Nitric oxide has the capacity to down-regulate inflammatory responses in the gastrointestinal tract, to scavenge various free radical species and to protect the mucosa from injury induced by topical irritants. Moreover, questions can be raised regarding the evidence purported to support a role for nitric oxide in producing tissue injury. In this review, we provide an overview of the evidence supporting a role for nitric oxide in protecting the gastrointestinal tract from injury.

Inorganic nitrite and nitrate in cardiovascular therapy: A better alternative to organic nitrates as nitric oxide donors?

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Münzel, Thomas; Daiber, Andreas

2018-03-01

In 1867 the organic nitrite, amyl nitrite, was introduced as a therapeutic agent in the treatment of angina pectoris and was later substituted by the organic nitrate nitroglycerin (NTG). Despite having a highly potent vasodilator capacity in veins>coronary arteries>arterioles, the vasodilator effects NTG are rapidly attenuated by the development of nitrate tolerance. We and others established that NTG treatment stimulates the production of reactive oxygen species such as superoxide and peroxynitrite with subsequent marked attenuation of the NTG vasodilator potency. The nitrite anion (NO 2 - ) has more recently been characterized to possess novel pharmacotherapeutic actions such as modulation of vasodilation under hypoxic conditions, thereby providing protection in ischemia-reperfusion injury. Administration of NO 2 - /NO 3 - has also been shown to improve myocardial function in heart failure and to lower blood pressure. Despite these positive aspects there is still a great need to study inorganic nitrate and nitrite therapy in various cardiovascular diseases in prospective outcome directed studies. In case being successful, this kind of therapy would indeed represent a cheap, therefore affordable, effective cardiovascular therapy without major side effects as observed in response to therapy with organic nitrates. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Contribution of radiation-induced, nitric oxide-mediated bystander effect to radiation-induced adaptive response.

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Matsumoto, H.; Ohnishi, T.

There has been a recent upsurge of interest in radiation-induced adaptive response and bystander effect which are specific modes in stress response to low-dose low-dose rate radiation Recently we found that the accumulation of inducible nitric oxide NO synthase iNOS in wt p53 cells was induced by chronic irradiation with gamma rays followed by acute irradiation with X-rays but not by each one resulting in an increase in nitrite concentrations of medium It is suggested that the accumulation of iNOS may be due to the depression of acute irradiation-induced p53 functions by pre-chronic irradiation In addition we found that the radiosensitivity of wt p53 cells against acute irradiation with X-rays was reduced after chronic irradiation with gamma rays This reduction of radiosensitivity of wt p53 cells was nearly completely suppressed by the addition of NO scavenger carboxy-PTIO to the medium This reduction of radiosensitivity of wt p53 cells is just radiation-induced adaptive response suggesting that NO-mediated bystander effect may considerably contribute to adaptive response induced by radiation

Characterization and Catalytic Activity of Mn-Co/TiO2 Catalysts for NO Oxidation to NO2 at Low Temperature

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Lu Qiu

2016-01-01

Full Text Available A series of Mn-Co/TiO2 catalysts were prepared by wet impregnation method and evaluated for the oxidation of NO to NO2. The effects of Co amounts and calcination temperature on NO oxidation were investigated in detail. The catalytic oxidation ability in the temperature range of 403–473 K was obviously improved by doping cobalt into Mn/TiO2. These samples were characterized by nitrogen adsorption-desorption, X-ray diffraction (XRD, X-ray photoelectron spectroscopy (XPS, transmission electron microscope (TEM and hydrogen temperature programmed reduction (H2-TPR. The results indicated that the formation of dispersed Co3O4·CoMnO3 mixed oxides through synergistic interaction between Mn-O and Co-O was directly responsible for the enhanced activities towards NO oxidation at low temperatures. Doping of Co enhanced Mn4+ formation and increased chemical adsorbed oxygen amounts, which also accelerated NO oxidation.

Influence of the physico-chemical properties of CeO{sub 2}-ZrO{sub 2} mixed oxides on the catalytic oxidation of NO to NO{sub 2}

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Atribak, Idriss; Guillen-Hurtado, Noelia; Bueno-Lopez, Agustin [MCMA Group, Department of Inorganic Chemistry, Faculty of Sciences, University of Alicante, Carretera San Vicente del Raspeig s/n - 03690 San Vicente del Raspeig, Alicante (Spain); Garcia-Garcia, Avelina, E-mail: a.garcia@ua.es [MCMA Group, Department of Inorganic Chemistry, Faculty of Sciences, University of Alicante, Carretera San Vicente del Raspeig s/n - 03690 San Vicente del Raspeig, Alicante (Spain)

2010-10-01

Commercial and home-made Ce-Zr catalysts prepared by co-precipitation were characterised by XRD, Raman spectroscopy, N{sub 2} adsorption at -196 deg. C and XPS, and were tested for NO oxidation to NO{sub 2}. Among the different physico-chemical properties characterised, the surface composition seems to be the most relevant one in order to explain the NO oxidation capacity of these Ce-Zr catalysts. As a general trend, Ce-Zr catalysts with a cerium-rich surface, that is, high XPS-measured Ce/Zr atomic surface ratios, are more active than those with a Zr-enriched surface. The decrease in catalytic activity of the Ce-Zr mixed oxided upon calcinations at 800 deg. C with regard to 500 deg. C is mainly attributed to the decrease in Ce/Zr surface ratio, that is, to the surface segregation of Zr. The phase composition (cubic or t'' for Ce-rich compositions) seems not to be a direct effect on the catalytic activity for NO oxidation in the range of compositions tested. However, the formation of a proper solid solution prevents important surface segregation of Zr upon calcinations at high temperature. The effect of the BET surface area in the catalytic activity for NO oxidation of Ce-Zr mixed oxides is minor in comparison with the effect of the Ce/Zr surface ratio.

T-type Ca(2+) channels facilitate NO-formation, vasodilatation and NO-mediated modulation of blood pressure

DEFF Research Database (Denmark)

Svenningsen, Per; Andersen, Kenneth; Thuesen, Anne D

2014-01-01

nitric oxide synthase (eNOS) in arteries from wild type mice. Nitric oxide release measured as DAF fluorescence and cGMP levels were significantly lower in depolarized Cav3.1(-/-) compared to wild type arteries. In summary, the absence of T-type Cav3.1 channels attenuates NO-dependent dilatation...

Intermittent pneumatic compression regulates expression of nitric oxide synthases in skeletal muscles.

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Tan, Xiangling; Qi, Wen-Ning; Gu, Xiaosong; Urbaniak, James R; Chen, Long-En

2006-01-01

This study investigated the effects of intermittent pneumatic compression (IPC) on expression of nitric oxide synthase (NOS) isoforms in compressed (anterior tibialis, AT) and uncompressed (cremaster muscles, CM) skeletal muscles. Following IPC application of 0.5, 1, and 5h on both legs of rats, the endothelial NOS (eNOS) mRNA expression was significantly up-regulated to 1.2-, 1.8, and 2.7-fold from normal, respectively, in both AT and CM, and protein expression increased more than 1.5-fold of normal at each time point. Similarly, neuronal NOS expression was up-regulated, but to a lesser degree. In contrast, inducible NOS expression was significantly and time-dependently down-regulated in both muscles. After IPC cessation, eNOS levels returned to normal in both AT and CM. The results confirm our hypothesis that IPC-induced vasodilation is mediated by regulating expression of NOS isoforms, in particular eNOS, in both compressed and uncompressed skeletal muscles. The results also suggest the importance of precisely characterizing expression of each NOS isoform in tissue pathophysiology.

Nitric oxide (NO) is an endogenous anticonvulsant but not a mediator of the increase in cerebral blood flow accompanying bicuculline-induced seizures in rats

DEFF Research Database (Denmark)

Wang, Qian; Theard, M A; Pelligrino, D A

1994-01-01

) is NO an endogenous anticonvulsant or proconvulsant substance? and (2) is the cerebral blood flow (CBF) increase accompanying bicuculline (BC)-induced seizures mediated by NO? The experiments were performed in 300-400-g Wistar rats anesthetized with 0.6% halothane and 70% N2O/30% O2. CBF was measured using...

Plasma and catalyst for the oxidation of NOx

DEFF Research Database (Denmark)

Jõgi, Indrek; Erme, Kalev; Levoll, Erik

2018-01-01

. In the case of indirect oxidation, only ozone could reach the catalyst surface and improve the oxidation of NO2 to N2O5. The effect of catalyst at different experimental conditions was quantitatively described with the aid of simple global chemical kinetic models derived for the NO x oxidation either...... by plasma or ozone. The models allowed to compare the effect of different catalysts and to analyze the limitations for the efficiency improvement by catalyst....... to NO mediated by O radicals in plasma. Indirect NO oxidation by plasma produced ozone allows to circumvent the back-reaction and further oxidize NO2 to N2O5 but the slow reaction rate for the latter process limits the efficiency of this process. Present paper gives an overview of the role of metal...

Does PGE1 Vasodilator Prevent Orthopaedic Implant-Related Infection in Diabetes? Preliminary Results in a Mouse Model

Science.gov (United States)

Lovati, Arianna B.; Romanò, Carlo L.; Monti, Lorenzo; Vassena, Christian; Previdi, Sara; Drago, Lorenzo

2014-01-01

Background Implant-related infections are characterized by bacterial colonization and biofilm formation on the prosthesis. Diabetes represents one of the risk factors that increase the chances of prosthetic infections because of related severe peripheral vascular disease. Vasodilatation can be a therapeutic option to overcome diabetic vascular damages and increase the local blood supply. In this study, the effect of a PGE1 vasodilator on the incidence of surgical infections in diabetic mice was investigated. Methodology A S. aureus implant-related infection was induced in femurs of diabetic mice, then differently treated with a third generation cephalosporin alone or associated with a PGE1 vasodilator. Variations in mouse body weight were evaluated as index of animal welfare. The femurs were harvested after 28 days and underwent both qualitative and quantitative analysis as micro-CT, histological and microbiological analyses. Results The analysis performed in this study demonstrated the increased host response to implant-related infection in diabetic mice treated with the combination of a PGE1 and antibiotic. In this group, restrained signs of infections were identified by micro-CT and histological analysis. On the other hand, the diabetic mice treated with the antibiotic alone showed a severe infection and inability to successfully respond to the standard antimicrobial treatment. Conclusions The present study revealed interesting preliminary results in the use of a drug combination of antibiotic and vasodilator to prevent implant-related Staphylococcus aureus infections in a diabetic mouse model. PMID:24718359

Prognostic value of vasodilator response using rubidium-82 positron emission tomography myocardial perfusion imaging in patients with coronary artery disease

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Arasaratnam, Punitha; Sadreddini, Masoud; Yam, Yeung; Kansal, Vinay; Beanlands, Rob S. [University of Ottawa Heart Institute, Canada, Department of Medicine (Cardiology), Ottawa, ON (Canada); Dorbala, Sharmila; Di Carli, Marcelo F. [Brigham and Women' s Hospital, Division of Cardiovascular Medicine and Division of Nuclear Medicine, Boston, MA (United States); Merhige, Michael E. [Niagara Falls Memorial Medical Center, Departments of Cardiology, Internal Medicine, and Nuclear Medicine, Buffalo, NY (United States); Williams, Brent A. [Geisinger Medical Center, Department of Center for Health Research, Danville, PA (United States); Veledar, Emir; Shaw, Leslee J. [Emory University School of Medicine, Department of Medicine, Atlanta, GA (United States); Min, James K. [Weill Cornell Medical College, Department of Radiology and Department of Imaging, New York, NY (United States); Chen, Li [University of Ottawa Heart Institute, Cardiovascular Research Methods Centre, Ottawa, ON (Canada); Ruddy, Terrence D.; Chow, Benjamin J.W. [University of Ottawa Heart Institute, Canada, Department of Medicine (Cardiology), Ottawa, ON (Canada); University of Ottawa, Department of Radiology, Ottawa, ON (Canada); Germano, Guido; Berman, Daniel S. [Cedars-Sinai Medical Center, Department of Imaging, Los Angeles, CA (United States)

2018-04-15

Prognostic value of positron emission tomography (PET) myocardial perfusion imaging (MPI) is well established. There is paucity of data on how the prognostic value of PET relates to the hemodynamic response to vasodilator stress. We hypothesize that inadequate hemodynamic response will affect the prognostic value of PET MPI. Using a multicenter rubidium (Rb)-82 PET registry, 3406 patients who underwent a clinically indicated rest/stress PET MPI with a vasodilator agent were analyzed. Patients were categorized as, ''responders'' [increase in heart rate ≥ 10 beats per minute (bpm) and decrease in systolic blood pressure (SBP) ≥10 mmHg], ''partial responders'' (either a change in HR or SBP), and ''non-responders'' (no change in HR or SBP). Primary outcome was all-cause death (ACD), and secondary outcome was cardiac death (CD). Ischemic burden was measured using summed stress score (SSS) and % left ventricular (LV) ischemia. After a median follow-up of 1.68 years (interquartile range = 1.17- 2.55), there were 7.9% (n = 270) ACD and 2.6% (n = 54) CD. Responders with a normal PET MPI had an annualized event rate (AER) of 1.22% (SSS of 0-3) and 1.58% (% LV ischemia = 0). Partial and non-responders had higher AER with worsening levels of ischemic burden. In the presence of severe SSS ≥12 and LV ischemia of ≥10%, partial responders had an AER of 10.79% and 10.36%, compared to non-responders with an AER of 19.4% and 12.43%, respectively. Patient classification was improved when SSS was added to a model containing clinical variables (NRI: 42%, p < 0.001) and responder category was added (NRI: 61%, p < 0.001). The model including clinical variables, SSS and hemodynamic response has good discrimination ability (Harrell C statistics: 0.77 [0.74-0.80]). Hemodynamic response during a vasodilator Rb-82 PET MPI is predictive of ACD. Partial and non-responders may require additional risk stratification leading to

Development of a portable mini-generator to safely produce nitric oxide for the treatment of infants with pulmonary hypertension.

Science.gov (United States)

Yu, Binglan; Ferrari, Michele; Schleifer, Grigorij; Blaesi, Aron H; Wepler, Martin; Zapol, Warren M; Bloch, Donald B

2018-05-01

To test the safety of a novel miniaturized device that produces nitric oxide (NO) from air by pulsed electrical discharge, and to demonstrate that the generated NO can be used to vasodilate the pulmonary vasculature in rabbits with chemically-induced pulmonary hypertension. A miniature NO (mini-NO) generator was tested for its ability to produce therapeutic levels (20-80 parts per million (ppm)) of NO, while removing potentially toxic gases and metal particles. We studied healthy 6-month-old New Zealand rabbits weighing 3.4 ± 0.4 kg (mean ± SD, n = 8). Pulmonary hypertension was induced by chemically increasing right ventricular systolic pressure to 28-30 mmHg. The mini-NO generator was placed near the endotracheal tube. Production of NO was triggered by a pediatric airway flowmeter during the first 0.5 s of inspiration. In rabbits with acute pulmonary hypertension, the mini-NO generator produced sufficient NO to induce pulmonary vasodilation. Potentially toxic nitrogen dioxide (NO 2 ) and ozone (O 3 ) were removed by the Ca(OH) 2 scavenger. Metallic particles, released from the electrodes by the electric plasma, were removed by a 0.22 μm filter. While producing 40 ppm NO, the mini-NO generator was cooled by a flow of air (70 ml/min) and the external temperature of the housing did not exceed 31 °C. The mini-NO generator safely produced therapeutic levels of NO from air. The mini-NO generator is an effective and economical approach to producing NO for treating neonatal pulmonary hypertension and will increase the accessibility and therapeutic uses of life-saving NO therapy worldwide. Copyright © 2018 Elsevier Inc. All rights reserved.

Dermal application of nitric oxide releasing acidified nitrite-containing liniments significantly reduces blood pressure in humans.

Science.gov (United States)

Opländer, Christian; Volkmar, Christine M; Paunel-Görgülü, Adnana; Fritsch, Thomas; van Faassen, Ernst E; Mürtz, Manfred; Grieb, Gerrit; Bozkurt, Ahmet; Hemmrich, Karsten; Windolf, Joachim; Suschek, Christoph V

2012-02-15

Vascular ischemic diseases, hypertension, and other systemic hemodynamic and vascular disorders may be the result of impaired bioavailability of nitric oxide (NO). NO but also its active derivates like nitrite or nitroso compounds are important effector and signal molecules with vasodilating properties. Our previous findings point to a therapeutical potential of cutaneous administration of NO in the treatment of systemic hemodynamic disorders. Unfortunately, no reliable data are available on the mechanisms, kinetics and biological responses of dermal application of nitric oxide in humans in vivo. The aim of the study was to close this gap and to explore the therapeutical potential of dermal nitric oxide application. We characterized with human skin in vitro and in vivo the capacity of NO, applied in a NO-releasing acidified form of nitrite-containing liniments, to penetrate the epidermis and to influence local as well as systemic hemodynamic parameters. We found that dermal application of NO led to a very rapid and significant transepidermal translocation of NO into the underlying tissue. Depending on the size of treated skin area, this translocation manifests itself through a significant systemic increase of the NO derivates nitrite and nitroso compounds, respectively. In parallel, this translocation was accompanied by an increased systemic vasodilatation and blood flow as well as reduced blood pressure. We here give evidence that in humans dermal application of NO has a therapeutic potential for systemic hemodynamic disorders that might arise from local or systemic insufficient availability of NO or its bio-active NO derivates, respectively. Copyright © 2012 Elsevier Inc. All rights reserved.

The development and evaluation of a continuous flow process for the lipase-mediated oxidation of alkenes

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Charlotte Wiles

2009-06-01

Full Text Available We report the use of an immobilised form of Candida antarctica lipase B, Novozym® 435, in a preliminary investigation into the development of a continuous flow reactor capable of performing the chemo-enzymatic oxidation of alkenes in high yield and purity, utilising the commercially available oxidant hydrogen peroxide (100 volumes. Initial investigations focussed on the lipase-mediated oxidation of 1-methylcyclohexene, with the optimised reaction conditions subsequently employed for the epoxidation of an array of aromatic and aliphatic alkenes in 97.6 to 99.5% yield and quantitative purity.

Lanthanum-promoted copper-based hydrotalcites derived mixed oxides for NO{sub x} adsorption, soot combustion and simultaneous NO{sub x}-soot removal

Energy Technology Data Exchange (ETDEWEB)

Wang, Zhongpeng [School of Resources and Environment, University of Jinan, 106 Jiwei Road, Jinan 250022 (China); Inorganic Chemistry Laboratory, University of Oxford, South Parks Road, Oxford OX1 3QR (United Kingdom); Yan, Xiaotong; Bi, Xinlin; Wang, Liguo [School of Resources and Environment, University of Jinan, 106 Jiwei Road, Jinan 250022 (China); Zhang, Zhaoliang, E-mail: chm_zhangzl@ujn.edu.cn [School of Resources and Environment, University of Jinan, 106 Jiwei Road, Jinan 250022 (China); Jiang, Zheng; Xiao, Tiancun [Inorganic Chemistry Laboratory, University of Oxford, South Parks Road, Oxford OX1 3QR (United Kingdom); Umar, Ahmad [Department of Chemistry, College of Science and Arts, Najran University, P.O. Box 1988, Najran 11001 (Saudi Arabia); Promising Centre for Sensors and Electronic Devices (PCSED), Najran University, P.O. Box 1988, Najran 11001 (Saudi Arabia); Wang, Qiang, E-mail: qiang.wang.ox@gmail.com [College of Environmental Science and Engineering, Beijing Forestry University, 35 Tsinghua East Road, Beijing 100083 (China)

2014-03-01

Graphical abstract: - Highlights: • The addition of La in Cu-based oxides increased the types of active oxygen. • NO{sub x} adsorption, soot oxidation and simultaneous NO{sub x}-soot removal were enhanced. • The possible catalytic mechanism was studied via in situ FTIR analysis. • Soot oxidation was promoted by the NO{sub 2} intermediate. - Abstract: La-promoted Cu-based hydrotalcites derived mixed oxides were prepared and their catalytic activities for NO{sub x} adsorption, soot oxidation, and simultaneous NO{sub x}-soot removal were investigated. The catalysts were characterized by XRD, DTG, BET, FTIR, H2-TPR, TPD and TPO techniques. The oxides catalysts exhibited mesoporous properties with specific surface area of 45–160 m{sup 2}/g. The incorporation of La and Cu decreased the amount of basic sites due to the large decrease in surface areas. Under O{sub 2} atmosphere, La incorporation is dominant for soot oxidation activity, while Cu favors high selectivity to CO{sub 2} formation. A synergetic effect between La and Cu for catalyzed soot oxidation lies in the improved redox property and suitable basicity. The presence of NO in O{sub 2} significantly promoted soot oxidation on the catalysts with the ignition temperature decreased to about 300 °C. In O{sub 2}/NO atmosphere, NO{sub 2} acts as an intermediate which oxidizes soot to CO{sub 2} at a lower temperature with itself reduced to NO or N{sub 2}, contributing to the high catalytic performance in simultaneous removal of NO{sub x} and soot.

Alamandine acts via MrgD to induce AMPK/NO activation against Ang II hypertrophy in cardiomyocytes.

Science.gov (United States)

de Jesus, Itamar Couto Guedes; Scalzo, Sergio; Alves, Fabiana; Marques, Kariny; Rocha-Resende, Cibele; Bader, Michael; Santos, Robson A Souza; Guatimosim, Silvia

2018-02-14

The renin-angiotensin system (RAS) plays a pivotal role in the pathogenesis of cardiovascular diseases. New members of this system have been characterized and shown to have biologically relevant actions. Alamandine and its receptor MrgD are recently identified components of RAS. In the cardiovascular system alamandine actions included vasodilation, antihypertensive and anti-fibrosis effects. Currently, the actions of alamandine on cardiomyocytes are unknown. Here our goal was twofold: (1) to unravel the signaling molecules activated by the alamandine/MrgD axis in cardiomyocytes; (2) to evaluate the ability of this axis to prevent against Angiotensin II (Ang II)-induced hypertrophy. In cardiomyocytes from C57BL/6 mice, alamandine treatment induced an increase in nitric oxide (NO) production, which was blocked by D-Pro 7 -Ang-(1-7), a MrgD antagonist. This NO rise correlated with increased phosphorylation of AMPK. Alamandine induced NO production was preserved in Mas -/- myocytes, and lost in MrgD -/- cells. Binding of fluorescent-labeled alamandine was observed in wild-type cells, but it was dramatically reduced in MrgD -/- myocytes. We also assessed the consequences of prolonged alamandine exposure to cultured neonatal rat cardiomyocytes (NRCMs) treated with Ang II. Treatment of NRCMs with alamandine prevented Ang II-induced hypertrophy. Moreover, antihypertrophic actions of alamandine were mediated via MrgD and NO, since they could be prevented by D-Pro 7 -Ang-(1-7) or inhibitors of NO synthase or AMPK. β-alanine, a MrgD agonist, recapitulated alamandine's cardioprotective effects in cardiomyocytes. Our data show that alamandine via MrgD induces AMPK/NO signaling to counterregulate Ang II induced hypertrophy. These findings highlight the therapeutic potential of the alamandine/MrgD axis in the heart.

trans-2-Tritylcyclohexanol as a chiral auxiliary in permanganate-mediated oxidative cyclization of 2-methylenehept-5-enoates: application to the synthesis of trans-(+)-linalool oxide.

Science.gov (United States)

Al Hazmi, Ali M; Sheikh, Nadeem S; Bataille, Carole J R; Al-Hadedi, Azzam A M; Watkin, Sam V; Luker, Tim J; Camp, Nicholas P; Brown, Richard C D

2014-10-03

The permanganate-mediated oxidative cyclization of a series of 2-methylenehept-5-eneoates bearing different chiral auxiliaries was investigated, leading to the discovery of trans-2-tritylcyclohexanol (TTC) as a highly effective chiral controller for the formation of the 2,5-substituted THF diol product with high diastereoselectivity (dr ∼97:3). Chiral resolution of (±)-TTC, prepared in one step from cyclohexene oxide, afforded (-)-(1S,2R)-TTC (er >99:1), which was applied to the synthesis of (+)-trans-(2S,5S)-linalool oxide.

Laccase/Mediator Systems

NARCIS (Netherlands)

Hilgers, Roelant; Vincken, Jean Paul; Gruppen, Harry; Kabel, Mirjam A.

2018-01-01

Laccase-mediator systems (LMS) have been widely studied for their capacity to oxidize the nonphenolic subunits of lignin (70-90% of the polymer). The phenolic subunits (10-30% of the polymer), which can also be oxidized without mediators, have received considerably less attention. Consequently, it

Role of calcitonin gene-related peptide in cerebral vasospasm, and as a therapeutic approach to subarachnoid haemorrhage

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Stelios eKokkoris

2012-11-01

Full Text Available Calcitonin gene-related peptide (CGRP is one of the most potent microvascular vasodilators identified to date. Vascular relaxation and vasodilation is mediated via activation of the CGRP receptor. This atypical receptor is made up of a G-protein-coupled receptor called calcitonin receptor-like receptor (CLR, a single transmembrane protein called receptor activity-modifying protein (RAMP, and an additional protein that is required for Gas coupling, known as receptor component protein (RCP. Several mechanisms involved in CGRP mediated relaxation have been identified. These include nitric oxide (NO-dependent endothelium-dependent mechanisms or cAMP-mediated endothelium-independent pathways; the latter being more common. Subarachnoid haemorrhage (SAH is associated with cerebral vasoconstriction that occurs several days after the haemorrhage and is often fatal. The vasospasm occurs in 30–40% of patients and is the major cause of death from this condition. The vasoconstriction is associated with a decrease in CGRP levels in nerves and an increase in CGRP levels in draining blood, suggesting that CGRP is released from nerves to oppose the vasoconstriction. This evidence has led to the concept that exogenous CGRP may be beneficial in a condition that has proven hard to treat. The present article reviews: a the pathophysiology of delayed ischaemic neurologic deficit after SAH b the basics of the CGRP receptor structure, signal transduction and vasodilatation mechanisms and c the studies that have been conducted so far using CGRP in both animals and humans with SAH.

Oxidative stress mediated mitochondrial and vascular lesions as markers in the pathogenesis of Alzheimer disease.

Science.gov (United States)

Aliev, G; Priyadarshini, M; Reddy, V P; Grieg, N H; Kaminsky, Y; Cacabelos, R; Ashraf, G Md; Jabir, N R; Kamal, M A; Nikolenko, V N; Zamyatnin, A A; Benberin, V V; Bachurin, S O

2014-01-01

Mitochondrial dysfunction plausibly underlies the aging-associated brain degeneration. Mitochondria play a pivotal role in cellular bioenergetics and cell-survival. Oxidative stress consequent to chronic hypoperfusion induces mitochondrial damage, which is implicated as the primary cause of cerebrovascular accidents (CVA) mediated Alzheimer's disease (AD). The mitochondrial function deteriorates with aging, and the mitochondrial damage correlates with increased intracellular production of oxidants and pro-oxidants. The prolonged oxidative stress and the resultant hypoperfusion in the brain tissues stimulate the expression of nitric oxide synthase (NOS) enzymes, which further drives the formation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). The ROS and RNS collectively contributes to the dysfunction of the blood-brain barrier (BBB) and damage to the brain parenchymal cells. Delineating the molecular mechanisms of these processes may provide clues for the novel therapeutic targets for CVA and AD patients.

Comparison Between the Acute Pulmonary Vascular Effects of Oxygen with Nitric Oxide and Sildenafil

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Ronald W. Day

2015-03-01

Full Text Available Objective. Right heart catheterization is performed in patients with pulmonary arterial hypertension to determine the severity of disease and their pulmonary vascular reactivity. The acute pulmonary vascular effect of inhaled nitric oxide is frequently used to identify patients who will respond favorably to vasodilator therapy. This study sought to determine whether the acute pulmonary vascular effects of oxygen with nitric oxide and intravenous sildenafil are similar. Methods. A retrospective, descriptive study of 13 individuals with pulmonary hypertension who underwent heart catheterization and acute vasodilator testing was performed. The hemodynamic measurements during five phases (21% to 53% oxygen, 100% oxygen, 100% oxygen with 20 ppm nitric oxide, 21% to 51% oxygen, and 21% to 51% oxygen with 0.05 mg/kg to 0.29 mg/kg intravenous sildenafil of the procedures were compared.Results. Mean pulmonary arterial pressure and pulmonary vascular resistance acutely decreased with 100% oxygen with nitric oxide, and 21% to 51% oxygen with sildenafil. Mean pulmonary arterial pressure (mm Hg, mean ± standard error of the mean was 38 ± 4 during 21% to 53% oxygen, 32 ± 3 during 100% oxygen, 29 ± 2 during 100% oxygen with nitric oxide, 37 ± 3 during 21% to 51% oxygen, and 32 ± 2 during 21% to 51% oxygen with sildenafil. There was not a significant correlation between the percent change in pulmonary vascular resistance from baseline with oxygen and nitric oxide, and from baseline with sildenafil (r2 = 0.011, p = 0.738. Conclusions. Oxygen with nitric oxide and sildenafil decreased pulmonary vascular resistance. However, the pulmonary vascular effects of oxygen and nitric oxide cannot be used to predict the acute response to sildenafil. Additional studies are needed to determine whether the acute response to sildenafil can be used to predict the long-term response to treatment with an oral phosphodiesterase V inhibitor.

Enhanced Abscisic Acid-Mediated Responses in nia1nia2noa1-2 Triple Mutant Impaired in NIA/NR- and AtNOA1-Dependent Nitric Oxide Biosynthesis in Arabidopsis1[W

Science.gov (United States)

Lozano-Juste, Jorge; León, José

2010-01-01

Nitric oxide (NO) regulates a wide range of plant processes from development to environmental adaptation. Despite its reported regulatory functions, it remains unclear how NO is synthesized in plants. We have generated a triple nia1nia2noa1-2 mutant that is impaired in nitrate reductase (NIA/NR)- and Nitric Oxide-Associated1 (AtNOA1)-mediated NO biosynthetic pathways. NO content in roots of nia1nia2 and noa1-2 plants was lower than in wild-type plants and below the detection limit in nia1nia2noa1-2 plants. NIA/NR- and AtNOA1-mediated biosynthesis of NO were thus active and responsible for most of the NO production in Arabidopsis (Arabidopsis thaliana). The nia1nia2noa1-2 plants displayed reduced size, fertility, and seed germination potential but increased dormancy and resistance to water deficit. The increasing deficiency in NO of nia1nia2, noa1-2, and nia1nia2noa1-2 plants correlated with increased seed dormancy, hypersensitivity to abscisic acid (ABA) in seed germination and establishment, as well as dehydration resistance. In nia1nia2noa1-2 plants, enhanced drought tolerance was due to a very efficient stomata closure and inhibition of opening by ABA, thus uncoupling NO from ABA-triggered responses in NO-deficient guard cells. The NO-deficient mutants in NIA/NR- and AtNOA1-mediated pathways in combination with the triple mutant will be useful tools to functionally characterize the role of NO and the contribution of both biosynthetic pathways in regulating plant development and defense. PMID:20007448

Influence of nitrogen oxides NO and NO2 on singlet delta oxygen production in pulsed discharge

International Nuclear Information System (INIS)

Ionin, A A; Klimachev, Yu M; Kozlov, A Yu; Kotkov, A A; Rulev, O A; Seleznev, L V; Sinitsyn, D V; Vagin, N P; Yuryshev, N N; Kochetov, I V; Napartovich, A P

2009-01-01

The influence of nitrogen oxides NO and NO 2 on the specific input energy (SIE) and the time behaviour of singlet delta oxygen (SDO) luminescence excited by a pulsed e-beam sustained discharge in oxygen were experimentally and theoretically studied. NO and NO 2 addition into oxygen results in a small increase and decrease in the SIE, respectively, the latter being connected with a large energy of electron affinity to NO 2 . The addition of 0.1-0.3% nitrogen oxides was experimentally and theoretically demonstrated to result in a notable enhancement of the SDO lifetime, which is related to a decrease in the atomic oxygen concentration in afterglow. It was experimentally demonstrated that to get a high SDO concentration at the gas pressure 30-60 Torr for a time interval of less than ∼0.5 s one needs to add not less than 0.2% nitrogen oxides into oxygen. The temperature dependence of the relaxation constant for SDO quenching by unexcited oxygen was estimated by using experimental data on the time behaviour of SDO luminescence.

The complex contribution of NOS interneurons in the physiology of cerebrovascular regulation

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Sonia eDuchemin

2012-08-01

Full Text Available Following the discovery of the vasorelaxant properties of nitric oxide (NO by Furchgott and Ignarro, the finding by Bredt and coll. of a constitutively expressed NO synthase in neurons (nNOS led to the presumption that neuronal NO may control cerebrovascular functions. Consequently, numerous studies have sought to determine whether neuraly-derived NO is involved in the regulation of cerebral blood flow. Anatomically, axons, dendrites or somata of NO neurons have been found to contact the basement membrane of blood vessels or perivascular astrocytes in all segments of the cortical microcirculation. Functionally, various experimental approaches support a role of neuronal NO in the maintenance of resting cerebral blood flow as well as in the vascular response to neuronal activity. Since decades, it has been assumed that neuronal NO simply diffuses to the local blood vessels and produce vasodilation through a cGMP-PKG dependent mechanism. However, NO is not the sole mediator of vasodilation in the cerebral microcirculation and is known to interact with a myriad of signaling pathways also involved in vascular control. In addition, cerebrovascular regulation is the result of a complex orchestration between all components of the neurovascular unit (i.e. neuronal, glial and vascular cells also known to produce NO. In this review article, the role of NO interneuron in the regulation of cortical microcirculation will be discussed in the context of the neurovascular unit.

Comparison of Oxidative Stresses Mediated by Different Crystalline Forms and Surface Modification of Titanium Dioxide Nanoparticles

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Karim Samy El-Said

2015-01-01

Full Text Available Titanium dioxide nanoparticles (TiO2 NPs are manufactured worldwide for use in a wide range of applications. There are two common crystalline forms of TiO2 anatase and rutile with different physical and chemical characteristics. We previously demonstrated that an increased DNA damage response is mediated by anatase crystalline form compared to rutile. In the present study, we conjugated TiO2 NPs with polyethylene glycol (PEG in order to reduce the genotoxicity and we evaluated some oxidative stress parameters to obtain information on the cellular mechanisms of DNA damage that operate in response to TiO2 NPs different crystalline forms exposure in hepatocarcinoma cell lines (HepG2. Our results indicated a significant increase in oxidative stress mediated by the anatase form of TiO2 NPs compared to rutile form. On the other hand, PEG modified TiO2 NPs showed a significant decrease in oxidative stress as compared to TiO2 NPs. These data suggested that the genotoxic potential of TiO2 NPs varies with crystalline form and surface modification.

Shape-dependent bactericidal activity of copper oxide nanoparticle mediated by DNA and membrane damage

International Nuclear Information System (INIS)

Laha, Dipranjan; Pramanik, Arindam; Laskar, Aparna; Jana, Madhurya; Pramanik, Panchanan; Karmakar, Parimal

2014-01-01

Highlights: • Spherical and sheet shaped copper oxide nanoparticles were synthesized. • Physical characterizations of these nanoparticles were done by TEM, DLS, XRD, FTIR. • They showed shape dependent antibacterial activity on different bacterial strain. • They induced both membrane damage and ROS mediated DNA damage in bacteria. - Abstract: In this work, we synthesized spherical and sheet shaped copper oxide nanoparticles and their physical characterizations were done by the X-ray diffraction, fourier transform infrared spectroscopy, transmission electron microscopy and dynamic light scattering. The antibacterial activity of these nanoparticles was determined on both gram positive and gram negative bacterial. Spherical shaped copper oxide nanoparticles showed more antibacterial property on gram positive bacteria where as sheet shaped copper oxide nanoparticles are more active on gram negative bacteria. We also demonstrated that copper oxide nanoparticles produced reactive oxygen species in both gram negative and gram positive bacteria. Furthermore, they induced membrane damage as determined by atomic force microscopy and scanning electron microscopy. Thus production of and membrane damage are major mechanisms of the bactericidal activity of these copper oxide nanoparticles. Finally it was concluded that antibacterial activity of nanoparticles depend on physicochemical properties of copper oxide nanoparticles and bacterial strain

Shape-dependent bactericidal activity of copper oxide nanoparticle mediated by DNA and membrane damage

Energy Technology Data Exchange (ETDEWEB)

Laha, Dipranjan; Pramanik, Arindam [Department of Life Science and Biotechnology, Jadavpur University, 188, Raja S C Mallick Road, Kolkata 700032 (India); Laskar, Aparna [CSIR-Indian Institute of Chemical Biology, Kolkata 700032 (India); Jana, Madhurya [Department of Life Science and Biotechnology, Jadavpur University, 188, Raja S C Mallick Road, Kolkata 700032 (India); Pramanik, Panchanan [Department of Chemistry, Indian Institute of Technology, Kharagpur 721302 (India); Karmakar, Parimal, E-mail: pkarmakar_28@yahoo.co.in [Department of Life Science and Biotechnology, Jadavpur University, 188, Raja S C Mallick Road, Kolkata 700032 (India)

2014-11-15

Highlights: • Spherical and sheet shaped copper oxide nanoparticles were synthesized. • Physical characterizations of these nanoparticles were done by TEM, DLS, XRD, FTIR. • They showed shape dependent antibacterial activity on different bacterial strain. • They induced both membrane damage and ROS mediated DNA damage in bacteria. - Abstract: In this work, we synthesized spherical and sheet shaped copper oxide nanoparticles and their physical characterizations were done by the X-ray diffraction, fourier transform infrared spectroscopy, transmission electron microscopy and dynamic light scattering. The antibacterial activity of these nanoparticles was determined on both gram positive and gram negative bacterial. Spherical shaped copper oxide nanoparticles showed more antibacterial property on gram positive bacteria where as sheet shaped copper oxide nanoparticles are more active on gram negative bacteria. We also demonstrated that copper oxide nanoparticles produced reactive oxygen species in both gram negative and gram positive bacteria. Furthermore, they induced membrane damage as determined by atomic force microscopy and scanning electron microscopy. Thus production of and membrane damage are major mechanisms of the bactericidal activity of these copper oxide nanoparticles. Finally it was concluded that antibacterial activity of nanoparticles depend on physicochemical properties of copper oxide nanoparticles and bacterial strain.

NO oxidation on Zeolite Supported Cu Catalysts: Formation and Reactivity of Surface Nitrates

Energy Technology Data Exchange (ETDEWEB)

Chen, Hai-Ying; Wei, Zhehao; Kollar, Marton; Gao, Feng; Wang, Yilin; Szanyi, Janos; Peden, Charles HF

2016-04-18

The comparative activities of a small-pore Cu-CHA and a large-pore Cu-BEA catalyst for the selective catalytic reduction (SCR) of NOx with NH3, and for the oxidation of NO to NO2 and the subsequent formation of surface nitrates were investigated. Although both catalysts are highly active in SCR reactions, they exhibit very low NO oxidation activity. Furthermore, Cu-CHA is even less active than Cu-BEA in catalyzing NO oxidation but is clearly more active for SCR reactions. Temperature-programed desorption (TPD) experiments following the adsorption of (NO2 + NO + O2) with different NO2:NO ratios reveal that the poor NO oxidation activity of the two catalysts is not due to the formation of stable surface nitrates. On the contrary, NO is found to reduce and decompose the surface nitrates on both catalysts. To monitor the reaction pathways, isotope exchange experiments were conducted by using 15NO to react with 14N-nitrate covered catalyst surfaces. The evolution of FTIR spectra during the isotope exchange process demonstrates that 14N-nitrates are simply displaced with no formation of 15N-nitrates on the Cu-CHA sample, which is clearly different from that observed on the Cu-BEA sample where formation of 15N-nitrates is apparent. The results suggest that the formal oxidation state of N during the NO oxidation on Cu-CHA mainly proceeds from its original +2 to a +3 oxidation state, whereas reaching a higher oxidation state for N, such as +4 or +5, is possible on Cu-BEA. The authors at PNNL gratefully acknowledge the US Department of Energy (DOE), Energy Efficiency and Renewable Energy, Vehicle Technologies Office for the support of this work. The research described in this paper was performed at the Environmental Molecular Sciences Laboratory (EMSL), a national scientific user facility sponsored by the DOE’s Office of Biological and Environmental Research and located at Pacific Northwest National Laboratory (PNNL). PNNL is operated for the US DOE by Battelle.

Phase coherence of 0.1 Hz microvascular tone oscillations during the local heating

Science.gov (United States)

Mizeva, I. A.

2017-06-01

The origin of the mechanisms of blood flow oscillations at low frequencies is discussed. It is known that even isolated arteriole demonstrates oscillations with the frequency close to 0.1 Hz, which is caused by the synchronous activity of myocyte cells. On the other hand, oscillations with close frequency are found in the heart rate, which are associated with quite different mechanism. The main purpose of this work is to study phase coherence of the blood flow oscillations in the peripheral vessels under basal and perturbed conditions. Local heating which locally influences the microvascular tone, as one of currently elucidated in sufficient detail physiological test, was chosen. During such provocation blood flow though the small vessels significantly increases because of vasodilation induced by the local synthesis of nitric oxide. In the first part of the paper microvascular response to the local test is quantified in healthy and pathological conditions of diabetes mellitus type 1. It is obtained that regardless of the pathology, subjects with high basal perfusion had lower reserve for vasodilation, which can be caused by the low elasticity of microvascular structure. Further synchronization of pulsations of the heated and undisturbed skin was evaluated on the base of wavelet phase coherency analysis. Being highly synchronised in basal conditions 0.1 Hz pulsations became more independent during heating, especially during NO-mediated vasodilation.

Natural resistance to ascorbic acid induced oxidative stress is mainly mediated by catalase activity in human cancer cells and catalase-silencing sensitizes to oxidative stress

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Klingelhoeffer Christoph

2012-05-01

Full Text Available Abstract Background Ascorbic acid demonstrates a cytotoxic effect by generating hydrogen peroxide, a reactive oxygen species (ROS involved in oxidative cell stress. A panel of eleven human cancer cell lines, glioblastoma and carcinoma, were exposed to serial dilutions of ascorbic acid (5-100 mmol/L. The purpose of this study was to analyse the impact of catalase, an important hydrogen peroxide-detoxifying enzyme, on the resistance of cancer cells to ascorbic acid mediated oxidative stress. Methods Effective concentration (EC50 values, which indicate the concentration of ascorbic acid that reduced the number of viable cells by 50%, were detected with the crystal violet assay. The level of intracellular catalase protein and enzyme activity was determined. Expression of catalase was silenced by catalase-specific short hairpin RNA (sh-RNA in BT-20 breast carcinoma cells. Oxidative cell stress induced apoptosis was measured by a caspase luminescent assay. Results The tested human cancer cell lines demonstrated obvious differences in their resistance to ascorbic acid mediated oxidative cell stress. Forty-five percent of the cell lines had an EC50 > 20 mmol/L and fifty-five percent had an EC50 50 of 2.6–5.5 mmol/L, glioblastoma cells were the most susceptible cancer cell lines analysed in this study. A correlation between catalase activity and the susceptibility to ascorbic acid was observed. To study the possible protective role of catalase on the resistance of cancer cells to oxidative cell stress, the expression of catalase in the breast carcinoma cell line BT-20, which cells were highly resistant to the exposure to ascorbic acid (EC50: 94,9 mmol/L, was silenced with specific sh-RNA. The effect was that catalase-silenced BT-20 cells (BT-20 KD-CAT became more susceptible to high concentrations of ascorbic acid (50 and 100 mmol/L. Conclusions Fifty-five percent of the human cancer cell lines tested were unable to protect themselves

C-X-C Chemokine Receptor Type 4 Plays a Crucial Role in Mediating Oxidative Stress-Induced Podocyte Injury.

Science.gov (United States)

Mo, Hongyan; Wu, Qinyu; Miao, Jinhua; Luo, Congwei; Hong, Xue; Wang, Yongping; Tang, Lan; Hou, Fan Fan; Liu, Youhua; Zhou, Lili

2017-08-20

Oxidative stress plays a role in mediating podocyte injury and proteinuria. However, the underlying mechanism remains poorly understood. In this study, we investigated the potential role of C-X-C chemokine receptor type 4 (CXCR4), the receptor for stromal cell-derived factor 1α (SDF-1α), in mediating oxidative stress-induced podocyte injury. In mouse model of adriamycin nephropathy (ADR), CXCR4 expression was significantly induced in podocytes as early as 3 days. This was accompanied by an increased upregulation of oxidative stress in podocyte, as demonstrated by malondialdehyde assay, nitrotyrosine staining and secretion of 8-hydroxy-2'-deoxyguanosine in urine, and induction of NOX2 and NOX4, major subunits of NADPH oxidase. CXCR4 was also induced in human kidney biopsies with proteinuric kidney diseases and colocalized with advanced oxidation protein products (AOPPs), an established oxidative stress trigger. Using cultured podocytes and mouse model, we found that AOPPs induced significant loss of podocyte marker Wilms tumor 1 (WT1), nephrin, and podocalyxin, accompanied by upregulation of desmin both in vitro and in vivo. Furthermore, AOPPs worsened proteinuria and aggravated glomerulosclerosis in ADR. These effects were associated with marked activation of SDF-1α/CXCR4 axis in podocytes. Administration of AMD3100, a specific inhibitor of CXCR4, reduced proteinuria and ameliorated podocyte dysfunction and renal fibrosis triggered by AOPPs in mice. In glomerular miniorgan culture, AOPPs also induced CXCR4 expression and downregulated nephrin and WT1. Innovation and Conclusion: These results suggest that chemokine receptor CXCR4 plays a crucial role in mediating oxidative stress-induced podocyte injury, proteinuria, and renal fibrosis. CXCR4 could be a new target for mitigating podocyte injury, proteinuria, and glomerular sclerosis in proteinuric chronic kidney disease. Antioxid. Redox Signal. 27, 345-362.

Diving response in rats: role of the subthalamic vasodilator area.

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Eugene Golanov

2016-09-01

Full Text Available Diving response is a powerful integrative response targeted toward survival of the hypoxic/anoxic conditions. Being present in all animals and humans it allows to survive adverse conditions like diving. Earlier we discovered that forehead stimulation affords neuroprotective effect decreasing infarction volume triggered by permanent occlusion of the middle cerebral artery in rats. We hypothesized that cold stimulation of the forehead induces diving response in rats, which, in turn, exerts neuroprotection. We compared autonomic (AP, HR, CBF and EEG responses to the known diving response-triggering stimulus, ammonia stimulation of the nasal mucosa, cold stimulation of the forehead, and cold stimulation of the glabrous skin of the tail base in anesthetized rats. Responses in AP, HR, CBF and EEG to cold stimulation of the forehead and ammonia vapors instillation into the nasal cavity were comparable and differed significantly from responses to the cold stimulation of the tail base. Excitotoxic lesion of the subthalamic vasodilator area, which is known to participate in CBF regulation and to afford neuroprotection upon excitation, failed to affect autonomic components of the diving response evoked by forehead cold stimulation or nasal mucosa ammonia stimulation. We conclude that cold stimulation of the forehead triggers physiological response comparable to the response evoked by ammonia vapor instillation into the nasal cavity, which considered as stimulus triggering protective diving response. These observations may explain the neuroprotective effect of the forehead stimulation. Data demonstrate that subthalamic vasodilator area does not directly participate in the autonomic adjustments accompanying diving response, however, it is involved in diving-evoked modulation of EEG. We suggest that forehead stimulation can be employed as a stimulus capable of triggering oxygen-conserving diving response and can be used for neuroprotective therapy.

Enhanced microbial decolorization of methyl red with oxidized carbon fiber as redox mediator

Energy Technology Data Exchange (ETDEWEB)

Emilia Rios-Del Toro, E. [División de Ciencias Ambientales, Instituto Potosino de Investigación Científica y Tecnológica (IPICyT), Camino a la Presa San José 2055, Col. Lomas 4a Sección, San Luis Potosí, SLP 78216 (Mexico); Celis, Lourdes B. [División de Geociencias Aplicadas, Instituto Potosino de Investigación Científica y Tecnológica (IPICyT), Camino a la Presa San José 2055, Col. Lomas 4a Sección, San Luis Potosí, SLP 78216 (Mexico); Cervantes, Francisco J. [División de Ciencias Ambientales, Instituto Potosino de Investigación Científica y Tecnológica (IPICyT), Camino a la Presa San José 2055, Col. Lomas 4a Sección, San Luis Potosí, SLP 78216 (Mexico); Rangel-Mendez, J. Rene, E-mail: rene@ipicyt.edu.mx [División de Ciencias Ambientales, Instituto Potosino de Investigación Científica y Tecnológica (IPICyT), Camino a la Presa San José 2055, Col. Lomas 4a Sección, San Luis Potosí, SLP 78216 (Mexico)

2013-09-15

Highlights: • Activated carbon fibers (ACFs) act as redox mediator. • Electron accepting capacity increased with oxidation time of ACF. •ACFs increased 8-fold the reduction of methyl red in biological assays. •Biofilm formed on the ACFs partly blocked their redox mediator capacity. -- Abstract: The anaerobic degradation of azo dyes under anaerobic conditions is possible but at a slow rate. Redox mediators (quinones, activated carbon) are used to improve the reduction rate. The aim of this work was to use activated carbon fiber (ACF) as a redox mediator for the anaerobic reduction of the azo dye methyl red. ACF was chemically modified with 8 M HNO{sub 3} to increase its redox-mediating capacity and used in chemical and anaerobic biological batch assays for the reduction of methyl red. ACF increased its redox-mediating capacity up to 3-fold in chemical assays; in biological assays ACF increased the reduction rate up to 8-fold compared to controls without ACF. However, since the ACF served as support for biomass, a biofilm formed on the fiber significantly reduced its redox-mediating capacity; substrate consumption suggested that the electron transport from ACF to methyl red was the rate-limiting step in the process. These results are the first evidence of the role of ACF as a redox mediator in the reductive decolorization of methyl red, in addition to the effect of biofilm attached to ACF on methyl red reduction. Due to the versatile characteristics of ACF and its redox-mediating capacity, carbon fibers could be used in biological wastewater treatment systems to accelerate the reductive transformation of pollutants commonly found in industrial effluents.

Enhanced microbial decolorization of methyl red with oxidized carbon fiber as redox mediator

International Nuclear Information System (INIS)

Emilia Rios-Del Toro, E.; Celis, Lourdes B.; Cervantes, Francisco J.; Rangel-Mendez, J. Rene

2013-01-01

Highlights: • Activated carbon fibers (ACFs) act as redox mediator. • Electron accepting capacity increased with oxidation time of ACF. •ACFs increased 8-fold the reduction of methyl red in biological assays. •Biofilm formed on the ACFs partly blocked their redox mediator capacity. -- Abstract: The anaerobic degradation of azo dyes under anaerobic conditions is possible but at a slow rate. Redox mediators (quinones, activated carbon) are used to improve the reduction rate. The aim of this work was to use activated carbon fiber (ACF) as a redox mediator for the anaerobic reduction of the azo dye methyl red. ACF was chemically modified with 8 M HNO 3 to increase its redox-mediating capacity and used in chemical and anaerobic biological batch assays for the reduction of methyl red. ACF increased its redox-mediating capacity up to 3-fold in chemical assays; in biological assays ACF increased the reduction rate up to 8-fold compared to controls without ACF. However, since the ACF served as support for biomass, a biofilm formed on the fiber significantly reduced its redox-mediating capacity; substrate consumption suggested that the electron transport from ACF to methyl red was the rate-limiting step in the process. These results are the first evidence of the role of ACF as a redox mediator in the reductive decolorization of methyl red, in addition to the effect of biofilm attached to ACF on methyl red reduction. Due to the versatile characteristics of ACF and its redox-mediating capacity, carbon fibers could be used in biological wastewater treatment systems to accelerate the reductive transformation of pollutants commonly found in industrial effluents

Oxidative stress and S-100B protein in children with bacterial meningitis

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Hamed Enas A

2009-10-01

Full Text Available Abstract Background Bacterial meningitis is often associated with cerebral compromise which may be responsible for neurological sequelae in nearly half of the survivors. Little is known about the mechanisms of CNS involvement in bacterial meningitis. Several studies have provided substantial evidence for the key role of nitric oxide (NO and reactive oxygen species in the complex pathophysiology of bacterial meningitis. Methods In the present study, serum and CSF levels of NO, lipid peroxide (LPO (mediators for oxidative stress and lipid peroxidation; total thiol, superoxide dismutase (SOD (antioxidant mediators and S-100B protein (mediator of astrocytes activation and injury, were investigated in children with bacterial meningitis (n = 40. Albumin ratio (CSF/serum is a marker of blood-CSF barriers integrity, while mediator index (mediator ratio/albumin ratio is indicative of intrathecal synthesis. Results Compared to normal children (n = 20, patients had lower serum albumin but higher NO, LPO, total thiol, SOD and S-100B. The ratios and indices of NO and LPO indicate blood-CSF barriers dysfunction, while the ratio of S-100B indicates intrathecal synthesis. Changes were marked among patients with positive culture and those with neurological complications. Positive correlation was found between NO index with CSF WBCs (r = 0.319, p Conclusion This study suggests that loss of integrity of brain-CSF barriers, oxidative stress and S-100B may contribute to the severity and neurological complications of bacterial meningitis.

Plasma-mediated vascular dysfunction in the reduced uterine perfusion pressure model of preeclampsia: a microvascular characterization.

LENUS (Irish Health Repository)

Walsh, Sarah K

2012-01-31

Preeclampsia is associated with widespread maternal vascular dysfunction, which is thought to be mediated by circulating factor(s). The aim of the study was to characterize vascular function in the reduced uterine perfusion pressure (RUPP) rat model of preeclampsia and to investigate the role of plasma factors in mediating any observed changes in vascular reactivity. Mean arterial blood pressure and vascular function were measured in RUPP and control rats. Mesenteric vessels from both virgin and pregnant rats were exposed for 1 hour or overnight to plasma from both RUPP and control rats and their vascular function assessed. RUPP rats were characterized by severe hypertension, restricted fetal growth, and reduced placental weight (P<0.001). Vasorelaxation was impaired in resistance vessels from RUPP compared with control rats (acetylcholine: R(max) 70+\\/-3 versus 92+\\/-1 [NP] and 93+\\/-3% [sham], P<0.01; bradykinin: 40+\\/-2 versus 62+\\/-2 [NP] and 59+\\/-4% [sham], P<0.001). Incubation of vessels from pregnant (but not virgin) animals with RUPP plasma overnight resulted in an attenuation of vasorelaxant responses (acetylcholine: 63+\\/-7 versus 86+\\/-2%, P<0.05; bradykinin: 35+\\/-5 versus 55+\\/-6%, P<0.001). The residual relaxant response in RUPP plasma-treated vessels was not further attenuated after treatment with N(omega)-nitro-l-arginine methyl ester (acetylcholine: 57+\\/-7 versus 63+\\/-7%, ns; bradykinin: 37+\\/-5 versus 35+\\/-5%, ns). The RUPP rat model is characterized by an impaired response to vasodilators which may be attributable to one or more circulating factors. This plasma-mediated endothelial dysfunction appears to be a pregnancy-dependent effect. Furthermore, nitric oxide-mediated vasorelaxation appears to be absent in RUPP plasma-treated vessels.

Mediated electrochemical oxidation of mixed wastes

International Nuclear Information System (INIS)

Chiba, Z.

1993-04-01

The Mediated Electrochemical Oxidation (MEO) process was studied for destroying low-level combustible mixed wastes at Rocky Flats Plant. Tests were performed with non-radioactive surrogate materials: Trimsol for contaminated cutting oils, and reagent-grade cellulose for contaminated cellulosic wastes. Extensive testing was carried out on Trimsol in both small laboratory-scale apparatus and on a large-scale system incorporating an industrial-size electrochemical cell. Preliminary tests were also carried out in the small-scale system with cellulose. Operating and system parameters that were studied were: use of a silver-nitric acid versus a cobalt-sulfuric acid system, effect of electrolyte temperature, effect of acid concentration, and effect of current density. Destruction and coulombic efficiencies were calculated using data obtained from continuous carbon dioxide monitors and total organic carbon (TOC) analysis of electrolyte samples. For Trimsol, the best performance was achieved with the silver-nitrate system at high acid concentrations, temperatures, and current densities. Destruction efficiencies of 99% or greater, and coulombic efficiencies up to 70% were obtained. For the cellulose, high destruction efficiencies and reasonable coulombic efficiencies were obtained for both silver-nitrate and cobalt-sulfate systems

Polydopamine-mediated surface-functionalization of graphene oxide for heavy metal ions removal

International Nuclear Information System (INIS)

Dong, Zhihui; Zhang, Feng; Wang, Dong; Liu, Xia; Jin, Jian

2015-01-01

By utilizing polydopamine (PD) nano-thick interlayer as mediator, polyethylenimine (PEI) brushes with abundant amine groups were grafted onto the surface of PD coated graphene oxide (GO) uniformly via a Michael-Addition reaction and produced a PEI–PD/GO composite nanosheets. The PEI–PD/GO composite exhibited an improved performance for adsorption of heavy metal ions as compared to PEI-coated GO and pure GO. The adsorption capacities for Cu 2+ , Cd 2+ , Pb 2+ , Hg 2+ are up to 87, 106, 197, and 110 mg/g, respectively. To further make the GO based composite operable, PEI–PD/RGO aerogel was prepared through hydrothermal and achieved a high surface area up to 373 m 2 /g. Although the adsorption capacity of PEI–PD/RGO aerogel for heavy metal ions decreases a little as compared to PEI–PD/GO composite dispersion (38, 32, 95, 113 mg/g corresponding to Cu 2+ , Cd 2+ , Pb 2+ , and Hg 2+ , respectively), it could be recycled several times in a simple way by releasing adsorbed metal ions, indicating its potential application for cleaning wastewater. - Graphical abstract: Polyethylenimine (PEI) brushes were grafted onto the surface of graphene oxide (GO) uniformly via a Michael-Addition reaction between the PEI and polydopamine interlayer coated on GO surface. The PEI–PD/GO composite exhibited an improved performance for adsorption of heavy metal ions compared to PEI-coated GO and pure GO. - Highlights: • We prepared polyethylenimine grafted polydopamine-mediated graphene oxide composites. • Introduction of PD layer increases metal ions adsorption capacity. • PEI–PD/RGO aerogel exhibited a superior adsorption performance. • PEI–PD/RGO aerogel can be recycled several times in a simple way

Effects of Buddhism walking meditation on depression, functional fitness, and endothelium-dependent vasodilation in depressed elderly.

Science.gov (United States)

Prakhinkit, Susaree; Suppapitiporn, Siriluck; Tanaka, Hirofumi; Suksom, Daroonwan

2014-05-01

The objectives of this study were to determine the effects of the novel Buddhism-based walking meditation (BWM) and the traditional walking exercise (TWE) on depression, functional fitness, and vascular reactivity. This was a randomized exercise intervention study. The study was conducted in a university hospital setting. Forty-five elderly participants aged 60-90 years with mild-to-moderate depressive symptoms were randomly allocated to the sedentary control, TWE, and BWM groups. The BWM program was based on aerobic walking exercise incorporating the Buddhist meditations performed 3 times/week for 12 weeks. Depression score, functional fitness, and endothelium-dependent vasodilation as measured by the flow-mediated dilation (FMD) were the outcome measures used. Muscle strength, flexibility, agility, dynamic balance, and cardiorespiratory endurance increased in both exercise groups (p<0.05). Depression score decreased (p<0.05) only in the BWM group. FMD improved (p<0.05) in both exercise groups. Significant reduction in plasma cholesterol, triglyceride, high-density lipoprotein cholesterol, and C-reactive protein were found in both exercise groups, whereas low-density lipoprotein cholesterol, cortisol, and interleukin-6 concentrations decreased only in the BWM group. Buddhist walking meditation was effective in reducing depression, improving functional fitness and vascular reactivity, and appears to confer greater overall improvements than the traditional walking program.

Mango Supplementation Has No Effects on Inflammatory Mediators in Obese Adults

Science.gov (United States)

Evans, Shirley F; Beebe, Maureen; Mahmood, Maryam; Janthachotikun, Sawanya; Eldoumi, Heba; Peterson, Sandra; Payton, Mark; Perkins-Veazie, Penelope; Smith, Brenda J; Lucas, Edralin A

2017-01-01

This pilot study examined the effects of freeze-dried mango (Mangifera indica L.) supplementation on anthropometric measurements, lipid parameters, and inflammatory mediators in obese individuals. A total of 20 obese (body mass index [BMI]: 30-35 kg/m2) adults (11 men and 9 women), aged 20 to 50 years, received 10 g/d of ground freeze-dried mango pulp for 12 weeks. Anthropometrics, lipids, and inflammatory mediators were assessed at baseline and after 12 weeks of mango supplementation. There were no differences between baseline and final visits in inflammatory mediators, lipids, diet, physical activity, and anthropometrics. Relationships were present at baseline and final visits between adiponectin and high-density lipoprotein cholesterol and between leptin and fat mass. Correlations were found after 12 weeks of mango supplementation between leptin and the following variables: waist-to-height ratio, BMI, percent fat, and fat mass. Our findings demonstrate that 12-week consumption of freeze-dried mango by obese individuals has no impact on obesity-related inflammation. PMID:28983188

Organ-Protective Effects of Red Wine Extract, Resveratrol, in Oxidative Stress-Mediated Reperfusion Injury

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Fu-Chao Liu

2015-01-01

Full Text Available Resveratrol, a polyphenol extracted from red wine, possesses potential antioxidative and anti-inflammatory effects, including the reduction of free radicals and proinflammatory mediators overproduction, the alteration of the expression of adhesion molecules, and the inhibition of neutrophil function. A growing body of evidence indicates that resveratrol plays an important role in reducing organ damage following ischemia- and hemorrhage-induced reperfusion injury. Such protective phenomenon is reported to be implicated in decreasing the formation and reaction of reactive oxygen species and pro-nflammatory cytokines, as well as the mediation of a variety of intracellular signaling pathways, including the nitric oxide synthase, nicotinamide adenine dinucleotide phosphate oxidase, deacetylase sirtuin 1, mitogen-activated protein kinase, peroxisome proliferator-activated receptor-gamma coactivator 1 alpha, hemeoxygenase-1, and estrogen receptor-related pathways. Reperfusion injury is a complex pathophysiological process that involves multiple factors and pathways. The resveratrol is an effective reactive oxygen species scavenger that exhibits an antioxidative property. In this review, the organ-protective effects of resveratrol in oxidative stress-related reperfusion injury will be discussed.

Activation of glutathione peroxidase via Nrf1 mediates genistein's protection against oxidative endothelial cell injury

International Nuclear Information System (INIS)

Hernandez-Montes, Eva; Pollard, Susan E.; Vauzour, David; Jofre-Montseny, Laia; Rota, Cristina; Rimbach, Gerald; Weinberg, Peter D.; Spencer, Jeremy P.E.

2006-01-01

Cellular actions of isoflavones may mediate the beneficial health effects associated with high soy consumption. We have investigated protection by genistein and daidzein against oxidative stress-induced endothelial injury. Genistein but not daidzein protected endothelial cells from damage induced by oxidative stress. This protection was accompanied by decreases in intracellular glutathione levels that could be explained by the generation of glutathionyl conjugates of the oxidised genistein metabolite, 5,7,3',4'-tetrahydroxyisoflavone. Both isoflavones evoked increased protein expression of γ-glutamylcysteine synthetase-heavy subunit (γ-GCS-HS) and increased cytosolic accumulation and nuclear translocation of Nrf2. However, only genistein led to increases in the cytosolic accumulation and nuclear translocation of Nrf1 and the increased expression of and activity of glutathione peroxidase. These results suggest that genistein-induced protective effects depend primarily on the activation of glutathione peroxidase mediated by Nrf1 activation, and not on Nrf2 activation or increases in glutathione synthesis

Successful use of continuous vasodilator infusion to treat critical vasospasm threatening a distal bypass

OpenAIRE

Gregory A. Magee, MD, MSc; Anastasia Plotkin, MD; Jeniann A. Yi, MD, MS; Kathryn E. Bowser, MD; David P. Kuwayama, MD, MPA

2018-01-01

Vasospasm immediately after lower extremity arterial bypass may represent an uncommon cause of early graft failure. We report a successful case of catheter-directed, intra-arterial continuous vasodilator infusion to salvage a bypass graft threatened by severe, refractory vasospasm after incomplete response to nicardipine, verapamil, and nitroglycerin boluses. A continuous nitroglycerin infusion was administered for 24 hours, by which time the vasospasm resolved. At 12 months postoperatively, ...

The allosteric behavior of Fur mediates oxidative stress signal transduction in Helicobacter pylori

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Simone ePelliciari

2015-08-01

Full Text Available The microaerophilic gastric pathogen Helicobacter pylori is exposed to oxidative stress originating from the aerobic environment, the oxidative burst of phagocytes and the formation of reactive oxygen species, catalyzed by iron excess. Accordingly, the expression of genes involved in oxidative stress defense have been repeatedly linked to the ferric uptake regulator Fur. Moreover, mutations in the Fur protein affect the resistance to metronidazole, likely due to loss-of-function in the regulation of genes involved in redox control. Although many advances in the molecular understanding of HpFur function were made, little is known about the mechanisms that enable Fur to mediate the responses to oxidative stress.Here we show that iron-inducible, apo-Fur repressed genes, such as pfr and hydA, are induced shortly after oxidative stress, while their oxidative induction is lost in a fur knockout strain. On the contrary, holo-Fur repressed genes, such as frpB1 and fecA1, vary modestly in response to oxidative stress. This indicates that the oxidative stress signal specifically targets apo-Fur repressed genes, rather than impairing indiscriminately the regulatory function of Fur. Footprinting analyses showed that the oxidative signal strongly impairs the binding affinity of Fur towards apo-operators, while the binding towards holo-operators is less affected. Further evidence is presented that a reduced state of Fur is needed to maintain apo-repression, while oxidative conditions shift the preferred binding architecture of Fur towards the holo-operator binding conformation, even in the absence of iron. Together the results demonstrate that the allosteric regulation of Fur enables transduction of oxidative stress signals in H. pylori, supporting the concept that apo-Fur repressed genes can be considered oxidation inducible Fur regulatory targets. These findings may have important implications in the study of H. pylori treatment and resistance to

Nitric oxide and bcl-2 mediated the apoptosis induced by nickel(II) in human T hybridoma cells

International Nuclear Information System (INIS)

Guan Fuqin; Zhang Dongmei; Wang Xinchang; Chen Junhui

2007-01-01

Although effects of nickel(II) on the immune system have long been recognized, little is known about the effects of nickel(II) on the induction of apoptosis and related signaling events in T cells. In the present study, we investigated the roles and signaling pathways of nickel(II) in the induction of apoptosis in a human T cell line jurkat. The results showed that the cytotoxic effects of Ni involved significant morphological changes and chromosomal condensation (Hoechst 33258 staining). Analyses of hypodiploid cells and FITC-Annexin V and PI double staining showed significant increase of apoptosis in jurkat cells 6, 12 and 24 h after nickel(II) treatment. Flow cytometry analysis also revealed that the loss of mitochondrial membrane potential (MMP) occurred concomitantly with the onset of NiCl 2 -induced apoptosis. Induction of apoptotic cell death by nickel was mediated by reduction of bcl-2 expression. Furthermore, nickel stimulated the generation of nitric oxide (NO). These results suggest that nickel(II) chloride induces jurkat cells apoptosis via nitric oxide generation, mitochondrial depolarization and bcl-2 suppression

Suppression of Human T Cell Proliferation Mediated by the Cathepsin B Inhibitor, z-FA-FMK Is Due to Oxidative Stress.

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Tanuja Rajah

Full Text Available The cathepsin B inhibitor, benzyloxycarbonyl-phenylalanine-alanine-fluoromethyl ketone (z-FA-FMK readily inhibits anti-CD3-induced human T cell proliferation, whereas the analogue benzyloxycarbonyl-phenylalanine-alanine-diazomethyl ketone (z-FA-DMK had no effect. In contrast, benzyloxycarbonyl-phenylalanine-alanine-chloromethyl ketone (z-FA-CMK was toxic. The inhibition of T cell proliferation mediated by z-FA-FMK requires not only the FMK moiety, but also the benzyloxycarbonyl group at the N-terminal, suggesting some degree of specificity in z-FA-FMK-induced inhibition of primary T cell proliferation. We showed that z-FA-FMK treatment leads to a decrease in intracellular glutathione (GSH with a concomitant increase in reactive oxygen species (ROS levels in activated T cells. The inhibition of anti-CD3-induced T cell proliferation mediated by z-FA-FMK was abolished by the presence of low molecular weight thiols such as GSH, N-acetylcysteine (NAC and L-cysteine, whereas D-cysteine which cannot be metabolised to GSH has no effect. The inhibition of anti-CD3-induced up-regulation of CD25 and CD69 expression mediated by z-FA-FMK was also attenuated in the presence of exogenous GSH. Similar to cell proliferation, GSH, NAC and L-cysteine but not D-cysteine, completely restored the processing of caspase-8 and caspase-3 to their respective subunits in z-FA-FMK-treated activated T cells. Our collective results demonstrated that the inhibition of T cell activation and proliferation mediated by z-FA-FMK is due to oxidative stress via the depletion of GSH.

Promotion of Water-mediated Carbon Removal by Nanostructured Barium Oxide/nickel Interfaces

Energy Technology Data Exchange (ETDEWEB)

L Yang; Y Choi; W Qin; H Chen; K Blinn; M Liu; P Liu; J Bai; T Tyson; M Liu

2011-12-31

The existing Ni-yttria-stabilized zirconia anodes in solid oxide fuel cells (SOFCs) perform poorly in carbon-containing fuels because of coking and deactivation at desired operating temperatures. Here we report a new anode with nanostructured barium oxide/nickel (BaO/Ni) interfaces for low-cost SOFCs, demonstrating high power density and stability in C{sub 3}H{sub 8}, CO and gasified carbon fuels at 750 C. Synchrotron-based X-ray analyses and microscopy reveal that nanosized BaO islands grow on the Ni surface, creating numerous nanostructured BaO/Ni interfaces that readily adsorb water and facilitate water-mediated carbon removal reactions. Density functional theory calculations predict that the dissociated OH from H2O on BaO reacts with C on Ni near the BaO/Ni interface to produce CO and H species, which are then electrochemically oxidized at the triple-phase boundaries of the anode. This anode offers potential for ushering in a new generation of SOFCs for efficient, low-emission conversion of readily available fuels to electricity.

Pu-erh Tea Reduces Nitric Oxide Levels in Rats by Inhibiting Inducible Nitric Oxide Synthase Expression through Toll-Like Receptor 4

Science.gov (United States)

Xu, Yang; Wang, Guan; Li, Chunjie; Zhang, Min; Zhao, Hang; Sheng, Jun; Shi, Wei

2012-01-01

Pu-erh tea undergoes a unique fermentation process and contains theabrownins, polysaccharides and caffeine; although it is unclear about which component is associated with the down regulation of nitric oxide levels or how this process is mediated. To address this question we examined the effects of pu-erh tea on nitric oxide synthase (NOS) genes. Cohorts of rats were separately given four-week treatments of water as control, pu-erh tea, or the tea components: theabrownins, caffeine or polysaccharides. Five experimental groups were injected with lipopolysaccharides (LPS) to induce nitric oxide (NO) production, while the corresponding five control groups were injected with saline as a negative control. The serum and liver NO concentrations were examined and the NOS expression of both mRNA and protein was measured in liver. The results showed that the rats which were fed pu-erh tea or polysaccharides had lower levels of NO which corresponded with the down-regulation of inducible nitric oxide synthase (iNOS) expression. We further demonstrate that this effect is mediated through reduction of Toll-like receptor 4 (TLR4) signaling. Thus we find that the polysaccharide components in pu-erh tea reduce NO levels in an animal model by inhibiting the iNOS expression via signaling through TLR4. PMID:22837686

Mediated electrochemical hazardous waste destruction

International Nuclear Information System (INIS)

Hickman, R.G.; Farmer, J.C.; Wang, F.T.

1992-03-01

There are few permitted processes for mixed waste (radioactive plus chemically hazardous) treatment. We are developing an electrochemical process, based upon mediated electrochemical oxidation (MEO), that converts toxic organic components of mixed waste to water, carbon dioxide, and chloride or chloride precipitates. Aggressive oxidizer ions such as Ag 2+ , Co 3+ , or Fe 3+ are produced at an anode. These can attack organic molecules directly, and may also produce hydroxyl free radicals that promote destruction. Solid and liquid radioactive waste streams containing only inorganic radionuclide forms may be treated with existing technology and prepared for final disposal. The coulombic efficiency of the process has been determined, as well as the destruction efficiency for ethylene glycol, a surrogate waste. In addition, hazardous organic materials are becoming very expensive to dispose of and when they are combined with transuranic radioactive elements no processes are presently permitted. Mediated electrochemical oxidation is an ambient- temperature aqueous-phase process that can be used to oxidize organic components of mixed wastes. Problems associated with incineration, such as high-temperature volatilization of radionuclides, are avoided. Historically, Ag(II) has been used as a mediator in this process. Fe(III) and Co(III) are attractive alternatives to Ag(II) since they form soluble chlorides during the destruction of chlorinated solvents. Furthermore, silver itself is toxic heavy metal. Quantitative data have been obtained for the complete oxidation of ethylene glycol by Fe(III) and Co(III). Though ethylene glycol is a nonhalogenated organic, these data have enabled us to make direct comparisons of activities of Fe(III) and Co(III) with Ag(II). Very good quantitative data for the oxidation of ethylene glycol by Ag(II) had already been collected

Iron oxide-mediated semiconductor photocatalysis vs. heterogeneous photo-Fenton treatment of viruses in wastewater. Impact of the oxide particle size.

Science.gov (United States)

Giannakis, Stefanos; Liu, Siting; Carratalà, Anna; Rtimi, Sami; Talebi Amiri, Masoud; Bensimon, Michaël; Pulgarin, César

2017-10-05

The photo-Fenton process is recognized as a promising technique towards microorganism disinfection in wastewater, but its efficiency is hampered at near-neutral pH operating values. In this work, we overcome these obstacles by using the heterogeneous photo-Fenton process as the default disinfecting technique, targeting MS2 coliphage in wastewater. The use of low concentrations of iron oxides in wastewater without H 2 O 2 (wüstite, maghemite, magnetite) has demonstrated limited semiconductor-mediated MS2 inactivation. Changing the operational pH and the size of the oxide particles indicated that the isoelectric point of the iron oxides and the active surface area are crucial in the success of the process, and the possible underlying mechanisms are investigated. Furthermore, the addition of low amounts of Fe-oxides (1mgL -1 ) and H 2 O 2 in the system (1, 5 and 10mgL -1 ) greatly enhanced the inactivation process, leading to heterogeneous photo-Fenton processes on the surface of the magnetically separable oxides used. Additionally, photo-dissolution of iron in the bulk, lead to homogeneous photo-Fenton, further aided by the complexation by the dissolved organic matter in the solution. Finally, we assess the impact of the presence of the bacterial host and the difference caused by the different iron sources (salts, oxides) and the Fe-oxide size (normal, nano-sized). Copyright © 2017 Elsevier B.V. All rights reserved.

Nitric oxide is an obligate bacterial nitrification intermediate produced by hydroxylamine oxidoreductase.

Science.gov (United States)

Caranto, Jonathan D; Lancaster, Kyle M

2017-08-01

Ammonia (NH 3 )-oxidizing bacteria (AOB) emit substantial amounts of nitric oxide (NO) and nitrous oxide (N 2 O), both of which contribute to the harmful environmental side effects of large-scale agriculture. The currently accepted model for AOB metabolism involves NH 3 oxidation to nitrite (NO 2 - ) via a single obligate intermediate, hydroxylamine (NH 2 OH). Within this model, the multiheme enzyme hydroxylamine oxidoreductase (HAO) catalyzes the four-electron oxidation of NH 2 OH to NO 2 - We provide evidence that HAO oxidizes NH 2 OH by only three electrons to NO under both anaerobic and aerobic conditions. NO 2 - observed in HAO activity assays is a nonenzymatic product resulting from the oxidation of NO by O 2 under aerobic conditions. Our present study implies that aerobic NH 3 oxidation by AOB occurs via two obligate intermediates, NH 2 OH and NO, necessitating a mediator of the third enzymatic step.

Characterization of TEMPO-oxidized bacterial cellulose scaffolds for tissue engineering applications

International Nuclear Information System (INIS)

Luo, Honglin; Xiong, Guangyao; Hu, Da; Ren, Kaijing; Yao, Fanglian; Zhu, Yong; Gao, Chuan; Wan, Yizao

2013-01-01

Introduction of active groups on the surface of bacterial cellulose (BC) nanofibers is one of the promising routes of tailoring the performance of BC scaffolds for tissue engineering. This paper reported the introduction of aldehyde groups to BC nanofibers by 2,2,6,6-tetramethylpyperidine-1-oxy radical (TEMPO)-mediated oxidation and evaluation of the potential of the TEMPO-oxidized BC as tissue engineering scaffolds. Periodate oxidation was also conducted for comparison. Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) analyses were carried out to determine the existence of aldehyde groups on BC nanofibers and the crystallinity. In addition, properties relevant to scaffold applications such as morphology, fiber diameter, mechanical properties, and in vitro degradation were characterized. The results indicated that periodate oxidation could introduce free aldehyde to BC nanofibers and the free aldehyde groups on the TEMPO-oxidized BC tended to transfer to acetal groups. It was also found that the advantageous 3D structure of BC scaffolds remained unchanged and that no significant changes in morphology, fiber diameter, tensile structure and in vitro degradation were found after TEMPO-mediated oxidation while significant differences were observed upon periodate oxidation. The present study revealed that TEMPO-oxidation could impart BC scaffolds with new functions while did not degrade their intrinsic advantages. - Highlights: • TEMPO-mediated oxidation on BC scaffold for tissue engineering use was conducted. • TEMPO-mediated oxidation did not degrade the intrinsic advantages of BC scaffold. • TEMPO-mediated oxidation could impart BC scaffold with new functional groups. • Feasibility of TEMPO-oxidized BC as tissue engineering scaffold was confirmed

Kinetics and thermodynamics of oxidation mediated reaction in L-cysteine and its methyl and ethyl esters in dimethyl sulfoxide-d6 by NMR spectroscopy

Science.gov (United States)

Dougherty, Ryan J.; Singh, Jaideep; Krishnan, V. V.

2017-03-01

L-Cysteine (L-Cys), L-Cysteine methyl ester (L-CysME) or L-Cysteine ethyl ester (L-CysEE), when dissolved in dimethyl sulfoxide, undergoes an oxidation process. This process is slow enough and leads to nuclear magnetic resonance (NMR) spectral changes that could be monitored in real time. The oxidation mediated transition is modeled as a pseudo-first order kinetics and the thermodynamic parameters are estimated using the Eyring's formulation. L-Cysteine and their esters are often used as biological models due to the remarkable thiol group that can be found in different oxidation states. This oxidation mediated transition is due to the combination of thiol oxidation to a disulfide followed by solvent-induced effects may be relevant in designing cysteine-based molecular models.

Controlled exposure to particulate matter from urban street air is associated with decreased vasodilation and heart rate variability in overweight and older adults

DEFF Research Database (Denmark)

Hemmingsen, Jette Gjerke; Rissler, Jenny; Lykkesfeldt, Jens

2015-01-01

, age 55 to 83 years, body mass index > 25 kg/m(2)) were included in a cross-over study with 5 hours of exposure to particle- or sham-filtered air from a busy street using an exposure-chamber. The sham- versus particle-filtered air had average particle number concentrations of ~23.000 versus ~1800/cm(3...... counts). RESULTS: Nitroglycerin-induced vasodilation was reduced by 12% [95% confidence interval: -22%; -1.0%] following PM exposure, whereas hyperemia-induced vasodilation was reduced by 5% [95% confidence interval: -11.6%; 1.6%]. Moreover, HRV measurements showed that the high and low frequency domains...

The air we breathe: three vital respiratory gases and the red blood cell: oxygen, nitric oxide, and carbon dioxide.

Science.gov (United States)

Dzik, Walter H

2011-04-01

Three vital respiratory gases-oxygen (O(2)), nitric oxide (NO), and carbon dioxide (CO(2))-intersect at the level of the human red blood cell (RBC). In addition to hemoglobin (Hb)'s central role in O(2) transport, interaction of Hb with the Band 3 metabolon balances RBC energy flow. 2,3-Diphosphoglycerate enhances O(2) transport across the placenta and plays an important role in regulating RBC plasticity. NO is a key mediator of hypoxic vasodilation, but the precise role of RBC Hb remains controversial. In addition to established theories that depend on RBC uptake, delivery, and discharge of NO or its metabolites, an alternative hypothesis based on RBC permeability is suggested. NO depletion by free Hb may account for several clinical features seen during intravascular hemolysis or during deliberate infusion of Hb solutions used as RBC substitutes. CO(2) released by tissues triggers oxygen release through a series of well-coordinated reactions centered on the Band 3 metabolon. While RBC carbonic anhydrase and the Band 3 anion exchanger are central to this process, there is surprisingly little research on the kinetics of CO(2) clearance by transfusion. The three RBC gases are directly related to the three principal gases of Earth's atmosphere. Human fossil fuel consumption dumps 90 million metric tons of carbon into the atmosphere annually. Increasing CO(2) levels are linked to global warming, melting Arctic ice, rising sea levels, and climate instability. Just as individual cells depend on balance of the three vital gases, so too will their balance determine survival of life on Earth. © 2011 American Association of Blood Banks.

Nitric oxide-mediated maintenance of redox homeostasis contributes to NPR1-dependent plant innate immunity triggered by lipopolysaccharides.

Science.gov (United States)

Sun, Aizhen; Nie, Shengjun; Xing, Da

2012-10-01

The perception of lipopolysaccharides (LPS) by plant cells can lead to nitric oxide (NO) production and defense gene induction. However, the signaling cascades underlying these cellular responses have not yet been resolved. This work investigated the biosynthetic origin of NO and the role of NONEXPRESSOR OF PATHOGENESIS-RELATED GENES1 (NPR1) to gain insight into the mechanism involved in LPS-induced resistance of Arabidopsis (Arabidopsis thaliana). Analysis of inhibitors and mutants showed that LPS-induced NO synthesis was mainly mediated by an arginine-utilizing source of NO generation. Furthermore, LPS-induced NO caused transcript accumulation of alternative oxidase genes and increased antioxidant enzyme activity, which enhanced antioxidant capacity and modulated redox state. We also analyzed the subcellular localization of NPR1 to identify the mechanism for protein-modulated plant innate immunity triggered by LPS. LPS-activated defense responses, including callose deposition and defense-related gene expression, were found to be regulated through an NPR1-dependent pathway. In summary, a significant NO synthesis induced by LPS contributes to the LPS-induced defense responses by up-regulation of defense genes and modulation of cellular redox state. Moreover, NPR1 plays an important role in LPS-triggered plant innate immunity.

Dityrosine, 3,4-Dihydroxyphenylalanine (DOPA), and radical formation from tyrosine residues on milk proteins with globular and flexible structures as a result of riboflavin-mediated photo-oxidation

DEFF Research Database (Denmark)

Dalsgaard, Trine Kastrup; Nielsen, Jacob Holm; Brown, Bronwyn

2011-01-01

Riboflavin-mediated photo-oxidative damage to protein Tyr residues has been examined to determine whether protein structure influences competing protein oxidation pathways in single proteins and protein mixtures. EPR studies resulted in the detection of Tyr-derived o-semiquione radicals, with thi......Riboflavin-mediated photo-oxidative damage to protein Tyr residues has been examined to determine whether protein structure influences competing protein oxidation pathways in single proteins and protein mixtures. EPR studies resulted in the detection of Tyr-derived o-semiquione radicals...

Possible involvement of membrane lipids peroxidation and oxidation of catalytically essential thiols of the cerebral transmembrane sodium pump as component mechanisms of iron-mediated oxidative stress-linked dysfunction of the pump's activity

Directory of Open Access Journals (Sweden)

T.I. Omotayo

2015-04-01

Full Text Available The precise molecular events defining the complex role of oxidative stress in the inactivation of the cerebral sodium pump in radical-induced neurodegenerative diseases is yet to be fully clarified and thus still open. Herein we investigated the modulation of the activity of the cerebral transmembrane electrogenic enzyme in Fe2+-mediated in vitro oxidative stress model. The results show that Fe2+ inhibited the transmembrane enzyme in a concentration dependent manner and this effect was accompanied by a biphasic generation of aldehydic product of lipid peroxidation. While dithiothreitol prevented both Fe2+ inhibitory effect on the pump and lipid peroxidation, vitamin E prevented only lipid peroxidation but not inhibition of the pump. Besides, malondialdehyde (MDA inhibited the pump by a mechanism not related to oxidation of its critical thiols. Apparently, the low activity of the pump in degenerative diseases mediated by Fe2+ may involve complex multi-component mechanisms which may partly involve an initial oxidation of the critical thiols of the enzyme directly mediated by Fe2+ and during severe progression of such diseases; aldehydic products of lipid peroxidation such as MDA may further exacerbate this inhibitory effect by a mechanism that is likely not related to the oxidation of the catalytically essential thiols of the ouabain-sensitive cerebral electrogenic pump.

Role of oxidative stress in methamphetamine-induced dopaminergic toxicity mediated by protein kinase Cδ.

Science.gov (United States)

Shin, Eun-Joo; Duong, Chu Xuan; Nguyen, Xuan-Khanh Thi; Li, Zhengyi; Bing, Guoying; Bach, Jae-Hyung; Park, Dae Hun; Nakayama, Keiichi; Ali, Syed F; Kanthasamy, Anumantha G; Cadet, Jean Lud; Nabeshima, Toshitaka; Kim, Hyoung-Chun

2012-06-15

This study examined the role of protein kinase C (PKC) isozymes in methamphetamine (MA)-induced dopaminergic toxicity. Multiple-dose administration of MA did not significantly alter PKCα, PKCβI, PKCβII, or PKCζ expression in the striatum, but did significantly increase PKCδ expression. Gö6976 (a co-inhibitor of PKCα and -β), hispidin (PKCβ inhibitor), and PKCζ pseudosubstrate inhibitor (PKCζ inhibitor) did not significantly alter MA-induced behavioral impairments. However, rottlerin (PKCδ inhibitor) significantly attenuated behavioral impairments in a dose-dependent manner. In addition, MA-induced behavioral impairments were not apparent in PKCδ knockout (-/-) mice. MA-induced oxidative stress (i.e., lipid peroxidation and protein oxidation) was significantly attenuated in rottlerin-treated mice and was not apparent in PKCδ (-/-) mice. Consistent with this, MA-induced apoptosis (i.e., terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive apoptotic cells) was significantly attenuated in rottlerin-treated mice. Furthermore, MA-induced increases in the dopamine (DA) turnover rate and decreases in tyrosine hydroxylase (TH) activity and the expression of TH, dopamine transporter (DAT), and vesicular monoamine transporter 2 (VMAT2) were not significantly observed in rottlerin-treated or PKCδ (-/-) mice. Our results suggest that PKCδ gene expression is a key mediator of oxidative stress and dopaminergic damage induced by MA. Thus, inhibition of PKCδ may be a useful target for protection against MA-induced neurotoxicity. Copyright © 2012 Elsevier B.V. All rights reserved.

Molecular basis for arsenic-Induced alteration in nitric oxide production and oxidative stress: implication of endothelial dysfunction

International Nuclear Information System (INIS)

Kumagai, Yoshito; Pi Jingbo

2004-01-01

Accumulated epidemiological studies have suggested that prolonged exposure of humans to arsenic in drinking water is associated with vascular diseases. The exact mechanism of how this occurs currently unknown. Nitric oxide (NO), formed by endothelial NO synthase (eNOS), plays a crucial role in the vascular system. Decreased availability of biologically active NO in the endothelium is implicated in the pathophysiology of several vascular diseases and inhibition of eNOS by arsenic is one of the proposed mechanism s for arsenic-induced vascular diseases. In addition, during exposure to arsenic, overproduction of reactive oxygen species (ROS) can occur, resulting in oxidative stress, which is another major risk factor for vascular dysfunction. The molecular basis for decreased NO levels and increased oxidative stress during arsenic exposure is poorly understood. In this article, evidence for arsenic-mediated alteration in NO production and oxidative stress is reviewed. The results of a cross-sectional study in an endemic area of chronic arsenic poisoning and experimental animal studies to elucidate a potential mechanism for the impairment of NO formation and oxidative stress caused by prolonged exposure to arsenate in the drinking water are also reviewed

Asociación entre enfermedad periodontal y disfunción endotelial valorada por vasodilatación mediada por flujo en la arteria braquial: Estudio piloto Association between periodontal disease and endothelial dysfunction assessed by flow-mediated dilation in the brachial artery: Pilot study

Directory of Open Access Journals (Sweden)

Álvaro J Ruiz

2013-02-01

Full Text Available Objetivo: evaluar la disfunción endotelial a través de la vasodilatación mediada por flujo (VMF en la arteria braquial en pacientes fumadores con periodontitis crónica avanzada y compararla con pacientes fumadores sin enfermedad periodontal, para determinar si hay diferencias en cuando a disfunción endotelial entre quienes presentan o no periodontitis crónica avanzada. Métodos: se incluyeron 30 pacientes con hábito de tabaquismo, 15 con periodontitis crónica avanzada y 15 sin periodontitis. Se realizó historia clínica completa, exámenes de laboratorio y prueba de vasodilatación mediada por flujo de la arteria braquial. Resultados: el estudio mostró que había diferencias significativas en los diámetros finales, resultantes de vasodilatación mediada por flujo (p=0,0328, con menores valores finales para quienes tenían enfermedad periodontal. Las diferencias en las respuestas porcentuales y en el número de personas con disfunción determinada dicotómicamente, no alcanzaron significación estadística. Conclusión: se observó que el grupo de pacientes con periodontitis crónica avanzada tuvo diámetros resultantes luego de la prueba que fueron significativamente menores que los del grupo de controles. Aunque al evaluar las diferencias en porcentajes no se alcanzó significación estadística, el estudio mostró una respuesta claramente menor en vasodilatación en el grupo con enfermedad periodontal.Objective: To evaluate endothelial dysfunction through flow-mediated vasodilation (FMD in the brachial artery in smokers with advanced chronic periodontitis and compare it with smokers without periodontal disease, to determine whether there are differences in endothelial dysfunction among those with or without advanced chronic periodontitis. Methods: We included 30 patients with smoking habit, 15 with advanced chronic periodontitis and 15 without periodontal disease. We performed a complete medical history, laboratory tests and flow-mediated

Activation of Proinflammatory Responses in Cells of the Airway Mucosa by Particulate Matter: Oxidant- and Non-Oxidant-Mediated Triggering Mechanisms

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Johan Øvrevik

2015-07-01

Full Text Available Inflammation is considered to play a central role in a diverse range of disease outcomes associated with exposure to various types of inhalable particulates. The initial mechanisms through which particles trigger cellular responses leading to activation of inflammatory responses are crucial to clarify in order to understand what physico-chemical characteristics govern the inflammogenic activity of particulate matter and why some particles are more harmful than others. Recent research suggests that molecular triggering mechanisms involved in activation of proinflammatory genes and onset of inflammatory reactions by particles or soluble particle components can be categorized into direct formation of reactive oxygen species (ROS with subsequent oxidative stress, interaction with the lipid layer of cellular membranes, activation of cell surface receptors, and direct interactions with intracellular molecular targets. The present review focuses on the immediate effects and responses in cells exposed to particles and central down-stream signaling mechanisms involved in regulation of proinflammatory genes, with special emphasis on the role of oxidant and non-oxidant triggering mechanisms. Importantly, ROS act as a central second-messenger in a variety of signaling pathways. Even non-oxidant mediated triggering mechanisms are therefore also likely to activate downstream redox-regulated events.

Portable Nitric Oxide (NO) Generator Based on Electrochemical Reduction of Nitrite for Potential Applications in Inhaled NO Therapy and Cardiopulmonary Bypass Surgery.

Science.gov (United States)

Qin, Yu; Zajda, Joanna; Brisbois, Elizabeth J; Ren, Hang; Toomasian, John M; Major, Terry C; Rojas-Pena, Alvaro; Carr, Benjamin; Johnson, Thomas; Haft, Jonathan W; Bartlett, Robert H; Hunt, Andrew P; Lehnert, Nicolai; Meyerhoff, Mark E

2017-11-06

A new portable gas phase nitric oxide (NO) generator is described for potential applications in inhaled NO (INO) therapy and during cardiopulmonary bypass (CPB) surgery. In this system, NO is produced at the surface of a large-area mesh working electrode by electrochemical reduction of nitrite ions in the presence of a soluble copper(II)-ligand electron transfer mediator complex. The NO generated is then transported into gas phase by either direct purging with nitrogen/air or via circulating the electrolyte/nitrite solution through a gas extraction silicone fiber-based membrane-dialyzer assembly. Gas phase NO concentrations can be tuned in the range of 5-1000 ppm (parts per million by volume for gaseous species), in proportion to a constant cathodic current applied between the working and counter electrodes. This new NO generation process has the advantages of rapid production times (5 min to steady-state), high Faraday NO production efficiency (ca. 93%), excellent stability, and very low cost when using air as the carrier gas for NO (in the membrane dialyzer configuration), enabling the development of potentially portable INO devices. In this initial work, the new system is examined for the effectiveness of gaseous NO to reduce the systemic inflammatory response (SIR) during CPB, where 500 ppm of NO added to the sweep gas of the oxygenator or to the cardiotomy suction air in a CPB system is shown to prevent activation of white blood cells (granulocytes and monocytes) during extracorporeal circulation with cardiotomy suction conducted with five pigs.

Rygestop i graviditeten, nyfødtes størrelse og NO-syntase-aktivitet i navlesnorens endotelceller--sekundaerpublikation

DEFF Research Database (Denmark)

Andersen, Malene R; Simonsen, Ulf; Uldbjerg, Niels

2009-01-01

Newborns of smokers had a lower weight, a smaller head circumference, and were shorter than newborns of smokers and ex-smokers, who stopped smoking early in pregnancy. The activity and concentration of the enzyme which produces the vasodilator nitric oxide were 36% and 47% lower, respectively......, in endothelial cells of the umbilical vein from smokers compared with that from nonsmokers and ex-smokers. The findings suggest that smoking reduces nitric oxide production in the foetal vascular bed, contributing to retarded foetal growth caused by the reduction of vasodilatory capacity. Udgivelsesdato: 2009...

Polyamine modification by acrolein exclusively produces 1,5-diazacyclooctanes: a previously unrecognized mechanism for acrolein-mediated oxidative stress.

Science.gov (United States)

Tsutsui, Ayumi; Imamaki, Rie; Kitazume, Shinobu; Hanashima, Shinya; Yamaguchi, Yoshiki; Kaneda, Masato; Oishi, Shinya; Fujii, Nobutaka; Kurbangalieva, Almira; Taniguchi, Naoyuki; Tanaka, Katsunori

2014-07-28

Acrolein, a toxic unsaturated aldehyde generated as a result of oxidative stress, readily reacts with a variety of nucleophilic biomolecules. Polyamines, which produced acrolein in the presence of amine oxidase, were then found to react with acrolein to produce 1,5-diazacyclooctane, a previously unrecognized but significant downstream product of oxidative stress. Although diazacyclooctane formation effectively neutralized acrolein toxicity, the diazacyclooctane hydrogel produced through a sequential diazacyclooctane polymerization reaction was highly cytotoxic. This study suggests that diazacyclooctane formation is involved in the mechanism underlying acrolein-mediated oxidative stress.

ROS-mediated inhibition of S-nitrosoglutathione reductase contributes to the activation of anti-oxidative mechanisms

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Izabella Kovacs

2016-11-01

Full Text Available Nitric oxide (NO has emerged as a signaling molecule in plants being involved in diverse physiological processes like germination, root growth, stomata closing and response to biotic and abiotic stress. S-nitrosoglutathione (GSNO as a biological NO donor has a very important function in NO signaling since it can transfer its NO moiety to other proteins (trans-nitrosylation. Such trans-nitrosylation reactions are equilibrium reactions and depend on GSNO level. The breakdown of GSNO and thus the level of S-nitrosylated proteins are regulated by GSNO-reductase (GSNOR. In this way, this enzyme controls S-nitrosothiol levels and regulates NO signaling. Here we report that Arabidopsis thaliana GSNOR activity is reversibly inhibited by H2O2 in-vitro and by paraquat-induced oxidative stress in-vivo. Light scattering analyses of reduced and oxidized recombinant GSNOR demonstrated that GSNOR proteins form dimers under both reducing and oxidizing conditions. Moreover, mass spectrometric analyses revealed that H2O2-treatment increased the amount of oxidative modifications on Zn2+-coordinating Cys47 and Cys177. Inhibition of GSNOR results in enhanced levels of S-nitrosothiols followed by accumulation of glutathione. Moreover, transcript levels of redox-regulated genes and activities of glutathione-dependent enzymes are increased in gsnor-ko plants, which may contribute to the enhanced resistance against oxidative stress. In sum, our results demonstrate that ROS-dependent inhibition of GSNOR is playing an important role in activation of anti-oxidative mechanisms to damping oxidative damage and imply a direct crosstalk between ROS- and NO-signaling.

Mulberry Leaf Extract Attenuates Oxidative Stress-Mediated Testosterone Depletion in Streptozotocin-Induced Diabetic Rats

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Mohammad Reza Hajizadeh

2014-03-01

Full Text Available Background: It has been proposed that oxidative stress may contribute to the development of testicular abnormalities in diabetes. Morus alba leaf extract (MAE has hypoglycemic and antioxidant properties. We, therefore, explored the impact of the administration of MAE on steroidogenesis in diabetic rats. Methods: To address this hypothesis, we measured the serum level of glucose, insulin, and free testosterone (Ts as well as oxidative stress parameters (including glutathione peroxidase, glutathione reductase, total antioxidant capacity, and malondialdehyde in the testis of control, untreated and MAE-treated (1 g/day/kg diabetic rats. In order to determine the likely mechanism of MAE action on Ts levels, we analyzed the quantitative mRNA expression level of the two key steroidogenic proteins, namely steroid acute regulatory protein (StAR and P450 cholesterol side-chain cleavage enzyme (P450scc, by real-time PCR. Results: The MAE-treated diabetic rats had significantly decreased glucose levels and on the other hand increased insulin and free Ts levels than the untreated diabetic rats. In addition, the administration of MAE to the diabetic rats restored the oxidative stress parameters toward control. Induction of diabetes decreased testicular StAR mRNA expression by 66% and MAE treatment enhanced mRNA expression to the same level of the control group. However, the expression of P540scc was not significantly decreased in the diabetic group as compared to the control group. Conclusion: Our findings indicated that MAE significantly increased Ts production in the diabetic rats, probably through the induction of StAR mRNA expression levels. Administration of MAE to experimental models of diabetes can effectively attenuate oxidative stress-mediated testosterone depletion. Please cite this article as: Hajizadeh MR, Eftekhar E, Zal F, Jaffarian A, Mostafavi-Pour Z. Mulberry Leaf Extract Attenuates Oxidative Stress-Mediated Testosterone Depletion in

MECHANISMS IN ENDOCRINOLOGY: Nutrition as a mediator of oxidative stress in metabolic and reproductive disorders in women.

Science.gov (United States)

Diamanti-Kandarakis, Evanthia; Papalou, Olga; Kandaraki, Eleni A; Kassi, Georgia

2017-02-01

Nutrition can generate oxidative stress and trigger a cascade of molecular events that can disrupt oxidative and hormonal balance. Nutrient ingestion promotes a major inflammatory and oxidative response at the cellular level in the postprandial state, altering the metabolic state of tissues. A domino of unfavorable metabolic changes is orchestrated in the main metabolic organs, including adipose tissue, skeletal muscle, liver and pancreas, where subclinical inflammation, endothelial dysfunction, mitochondrial deregulation and impaired insulin response and secretion take place. Simultaneously, in reproductive tissues, nutrition-induced oxidative stress can potentially violate delicate oxidative balance that is mandatory to secure normal reproductive function. Taken all the above into account, nutrition and its accompanying postprandial oxidative stress, in the unique context of female hormonal background, can potentially compromise normal metabolic and reproductive functions in women and may act as an active mediator of various metabolic and reproductive disorders. © 2017 European Society of Endocrinology.

Serum nitric oxide metabolites and disease activity in patients with systemic sclerosis.

Science.gov (United States)

Mok, Mo Yin; Fung, Peter Chin Wah; Ooi, Clara; Tse, Hung Fat; Wong, Yik; Lam, Yui Ming; Wong, Woon Sing; Lau, Chak Sing

2008-03-01

There is no surrogate marker in serum for defining disease activity in scleroderma (SSc). Nitric oxide (NO), which regulates vasodilation and possesses pro-inflammatory actions, has been implicated in the pathogenesis of SSc. We compared serum NO(x) (total nitrate and nitrite) level in SSc patients to healthy controls and evaluated its correlation with detailed symptomatology and scoring systems for various organ involvement. Symptoms and physical findings that suggested disease activity in regard to various organs were documented. Lung function test, high-resolution computed tomographic (HRCT) scan of thorax and echocardiography were performed. Serum NO(x) was measured by chemiluminescence. Serum NO(x) levels in SSc (n = 43) were significantly higher (72.4 +/- 47.8 microM) than age- and sex-matched controls (n = 41; 37.1 +/- 13.5 microM; p n = 9; OR 145.3, p = 0.01) were predictive factors for elevated serum NO(x). Prednisolone use was associated with lower serum NO(x) level (OR 0.06, p = 0.04). Elevated PAP of increasing severity was found to be associated with higher level of serum NO(x) (p = 0.004 by trend). Serum NO(x) in SSc patients were elevated compared to healthy controls. Serum NO(x) level was determined by multiple factors including age, prednisolone use, and elevated PAP.

Arsenic triggers the nitric oxide (NO) and S-nitrosoglutathione (GSNO) metabolism in Arabidopsis

International Nuclear Information System (INIS)

Leterrier, Marina; Airaki, Morad; Palma, José M.; Chaki, Mounira; Barroso, Juan B.; Corpas, Francisco J.

2012-01-01

Environmental contamination by arsenic constitutes a problem in many countries, and its accumulation in food crops may pose health complications for humans. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are involved at various levels in the mechanism of responding to environmental stress in higher plants. Using Arabidopsis seedlings exposed to different arsenate concentrations, physiological and biochemical parameters were analyzed to determine the status of ROS and RNS metabolisms. Arsenate provoked a significant reduction in growth parameters and an increase in lipid oxidation. These changes were accompanied by an alteration in antioxidative enzymes and the nitric oxide (NO) metabolism, with a significant increase in NO content, S-nitrosoglutathione reductase (GSNOR) activity and protein tyrosine nitration as well as a concomitant reduction in glutathione and S-nitrosoglutathione (GSNO) content. Our results indicate that 500 μM arsenate (AsV) causes nitro-oxidative stress in Arabidopsis, being the glutathione reductase and the GSNOR activities clearly affected. - Highlights: ► In Arabidopsis, arsenate provokes damages in the membrane integrity of root cells. ► As induces an oxidative stress according to an increase in lipid oxidation. ► NO content and protein tyrosine nitration increases under arsenate stress. ► Arsenate provokes a reduction of GSH, GSSG and GSNO content. ► Arsenate induces a nitro-oxidative stress in Arabidopsis. - Arsenic stress affects nitric oxide (NO) and glutathione (GSH) metabolism which provokes a nitro-oxidative stress.

β-Amyloid promotes accumulation of lipid peroxides by inhibiting CD36-mediated clearance of oxidized lipoproteins

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Khan Tayeba

2004-11-01

Full Text Available Abstract Background Recent studies suggest that hypercholesterolemia, an established risk factor for atherosclerosis, is also a risk factor for Alzheimer's disease. The myeloid scavenger receptor CD36 binds oxidized lipoproteins that accumulate with hypercholesterolemia and mediates their clearance from the circulation and peripheral tissues. Recently, we demonstrated that CD36 also binds fibrillar β-amyloid and initiates a signaling cascade that regulates microglial recruitment and activation. As increased lipoprotein oxidation and accumulation of lipid peroxidation products have been reported in Alzheimer's disease, we investigated whether β-amyloid altered oxidized lipoprotein clearance via CD36. Methods The availability of mice genetically deficient in class A (SRAI & II and class B (CD36 scavenger receptors has facilitated studies to discriminate their individual actions. Using primary microglia and macrophages, we assessed the impact of Aβ on: (a cholesterol ester accumulation by GC-MS and neutral lipid staining, (b binding, uptake and degradation of 125I-labeled oxidized lipoproteins via CD36, SR-A and CD36/SR-A-independent pathways, (c expression of SR-A and CD36. In addition, using mice with targeted deletions in essential kinases in the CD36-signaling cascade, we investigated whether Aβ-CD36 signaling altered metabolism of oxidized lipoproteins. Results In primary microglia and macrophages, Aβ inhibited binding, uptake and degradation of oxidized low density lipoprotein (oxLDL in a dose-dependent manner. While untreated cells accumulated abundant cholesterol ester in the presence of oxLDL, cells treated with Aβ were devoid of cholesterol ester. Pretreatment of cells with Aβ did not affect subsequent degradation of oxidized lipoproteins, indicating that lysosomal accumulation of Aβ did not disrupt this degradation pathway. Using mice with targeted deletions of the scavenger receptors, we demonstrated that Aβ inhibited oxidized

The feasible study of vasodilators in portal vein targeting infusion for treating portal hypertension

International Nuclear Information System (INIS)

Wu Hanping; Liang Huiming; Zheng Chuansheng; Feng Gansheng

2002-01-01

Objective: To find out the ideal portal vein tar getting injection routes for portal hypertension treatment. Methods: 28 cirrhotic rat models with portal hypertension induced by CCl 4 were divided into 4 groups: inferior caval vein injection group, portal vein injection group, hepatic artery injection group, spleen injection group. The changes in portal vein pressure (PVP), inferior caval vein pressure (ICVP), mean artery pressure (MAP) and heart rate (HR) were monitored before and after prazosin injection. Results: After intra-portal, intra-hepatic arterial or spleen injection of prazosin, larger decrease in PVP and lesser effects on MAP than intravenous injection had been induced. The effect on HR showed no difference among these four groups. Conclusions: Hepatic artery and spleen prazosin administration have the same advantages on treatment of portal hypertension as those of intra-portal infusion, that is the greater decrease on portal vein pressure, the lesser effects on systemic hemodynamics. Vasodilation drugs for hepatic artery infusion through percutaneous port catheter system by hepatic artery implantation would be an ideal method for portal hypertension treatment

Plasma and catalyst for the oxidation of NOx

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Jõgi, Indrek; Erme, Kalev; Levoll, Erik; Raud, Jüri; Stamate, Eugen

2018-03-01

Efficient exhaust gas cleaning from NO x (NO and NO2) by absorption and adsorption based methods requires the oxidation of NO. The application of non-thermal plasma is considered as a promising oxidation method but the oxidation of NO by direct plasma remains limited due to the back-reaction of NO2 to NO mediated by O radicals in plasma. Indirect NO oxidation by plasma produced ozone allows to circumvent the back-reaction and further oxidize NO2 to N2O5 but the slow reaction rate for the latter process limits the efficiency of this process. Present paper gives an overview of the role of metal-oxide catalysts in the improvement of oxidation efficiency for both direct and indirect plasma oxidation of NO x . The plasma produced active oxygen species (O, O3) were shown to play an important role in the reactions taking place on the catalyst surfaces while the exact mechanism and extent of the effect were different for direct and indirect oxidation. In the case of direct plasma oxidation, both short and long lifetime oxygen species could reach the catalyst and participate in the oxidation of NO to NO2. The back-reaction in the plasma phase remained still important factor and limited the effect of catalyst. In the case of indirect oxidation, only ozone could reach the catalyst surface and improve the oxidation of NO2 to N2O5. The effect of catalyst at different experimental conditions was quantitatively described with the aid of simple global chemical kinetic models derived for the NO x oxidation either by plasma or ozone. The models allowed to compare the effect of different catalysts and to analyze the limitations for the efficiency improvement by catalyst.

N-Acetylcysteine protects against trichloroethene-mediated autoimmunity by attenuating oxidative stress

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Wang, Gangduo; Wang, Jianling; Ma, Huaxian; Ansari, G.A.S.; Khan, M. Firoze, E-mail: mfkhan@utmb.edu

2013-11-15

Exposure to trichloroethene (TCE), a ubiquitous environmental contaminant, is known to induce autoimmunity both in humans and animal models. However, mechanisms underlying TCE-mediated autoimmunity remain largely unknown. Previous studies from our laboratory in MRL +/+ mice suggest that oxidative stress may contribute to TCE-induced autoimmune response. The current study was undertaken to further assess the role of oxidative stress in TCE-induced autoimmunity by supplementing with an antioxidant N-acetylcysteine (NAC). Groups of female MRL +/+ mice were given TCE, NAC or TCE + NAC for 6 weeks (TCE, 10 mmol/kg, i.p., every 4th day; NAC, 250 mg/kg/day through drinking water). TCE exposure led to significant increases in serum levels of anti-nuclear, anti-dsDNA and anti-Sm antibodies. TCE exposure also led to significant induction of anti-malondiadelhyde (MDA)- and anti-hydroxynonenal (HNE)-protein adduct antibodies which were associated with increased ANA in the sera along with increased MDA-/HNE-protein adducts in the livers and kidneys, and increases in protein oxidation (carbonylation) in the sera, livers and kidneys, suggesting an overall increase in oxidative stress. Moreover, TCE exposure also resulted in increased release of IL-17 from splenocytes and increases in IL-17 mRNA expression. Remarkably, NAC supplementation attenuated not only the TCE-induced oxidative stress, IL-17 release and mRNA expression, but also the markers of autoimmunity, as evident from decreased levels of ANA, anti-dsDNA and anti-Sm antibodies in the sera. These results provide further support to a role of oxidative stress in TCE-induced autoimmune response. Attenuation of TCE-induced autoimmunity in mice by NAC provides an approach for preventive and/or therapeutic strategies. - Highlights: • TCE led to increased autoantibodies, supporting its potential to induce autoimmunity. • TCE exposure led to increases in lipid perioxidation and protein carbonyls. • TCE exposure resulted in

N-Acetylcysteine protects against trichloroethene-mediated autoimmunity by attenuating oxidative stress

International Nuclear Information System (INIS)

Wang, Gangduo; Wang, Jianling; Ma, Huaxian; Ansari, G.A.S.; Khan, M. Firoze

2013-01-01

Exposure to trichloroethene (TCE), a ubiquitous environmental contaminant, is known to induce autoimmunity both in humans and animal models. However, mechanisms underlying TCE-mediated autoimmunity remain largely unknown. Previous studies from our laboratory in MRL +/+ mice suggest that oxidative stress may contribute to TCE-induced autoimmune response. The current study was undertaken to further assess the role of oxidative stress in TCE-induced autoimmunity by supplementing with an antioxidant N-acetylcysteine (NAC). Groups of female MRL +/+ mice were given TCE, NAC or TCE + NAC for 6 weeks (TCE, 10 mmol/kg, i.p., every 4th day; NAC, 250 mg/kg/day through drinking water). TCE exposure led to significant increases in serum levels of anti-nuclear, anti-dsDNA and anti-Sm antibodies. TCE exposure also led to significant induction of anti-malondiadelhyde (MDA)- and anti-hydroxynonenal (HNE)-protein adduct antibodies which were associated with increased ANA in the sera along with increased MDA-/HNE-protein adducts in the livers and kidneys, and increases in protein oxidation (carbonylation) in the sera, livers and kidneys, suggesting an overall increase in oxidative stress. Moreover, TCE exposure also resulted in increased release of IL-17 from splenocytes and increases in IL-17 mRNA expression. Remarkably, NAC supplementation attenuated not only the TCE-induced oxidative stress, IL-17 release and mRNA expression, but also the markers of autoimmunity, as evident from decreased levels of ANA, anti-dsDNA and anti-Sm antibodies in the sera. These results provide further support to a role of oxidative stress in TCE-induced autoimmune response. Attenuation of TCE-induced autoimmunity in mice by NAC provides an approach for preventive and/or therapeutic strategies. - Highlights: • TCE led to increased autoantibodies, supporting its potential to induce autoimmunity. • TCE exposure led to increases in lipid perioxidation and protein carbonyls. • TCE exposure resulted in

Exercise promotes collateral artery growth mediated by monocytic nitric oxide.

Science.gov (United States)

Schirmer, Stephan H; Millenaar, Dominic N; Werner, Christian; Schuh, Lisa; Degen, Achim; Bettink, Stephanie I; Lipp, Peter; van Rooijen, Nico; Meyer, Tim; Böhm, Michael; Laufs, Ulrich

2015-08-01

Collateral artery growth (arteriogenesis) is an important adaptive response to hampered arterial perfusion. It is unknown whether preventive physical exercise before limb ischemia can improve arteriogenesis and modulate mononuclear cell function. This study aimed at investigating the effects of endurance exercise before arterial occlusion on MNC function and collateral artery growth. After 3 weeks of voluntary treadmill exercise, ligation of the right femoral artery was performed in mice. Hindlimb perfusion immediately after surgery did not differ from sedentary mice. However, previous exercise improved perfusion restoration ≤7 days after femoral artery ligation, also when exercise was stopped at ligation. This was accompanied by an accumulation of peri-collateral macrophages and increased expression of endothelial nitric oxide synthase and inducible nitric oxide synthase (iNOS) in hindlimb collateral and in MNC of blood and spleen. Systemic monocyte and macrophage depletion by liposomal clodronate but not splenectomy attenuated exercise-induced perfusion restoration, collateral artery growth, peri-collateral macrophage accumulation, and upregulation of iNOS. iNOS-deficient mice did not show exercise-induced perfusion restoration. Transplantation of bone marrow-derived MNC from iNOS-deficient mice into wild-type animals inhibited exercise-induced collateral artery growth. In contrast to sedentary controls, thrice weekly aerobic exercise training for 6 months in humans increased peripheral blood MNC iNOS expression. Circulating mononuclear cell-derived inducible nitric oxide is an important mediator of exercise-induced collateral artery growth. © 2015 American Heart Association, Inc.

The Effect of Being Aerobically Active vs. Inactive on Cutaneous Vascular Conductance during Local Heat Stress in an Older Population

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Ulrike H. Mitchell

2017-10-01

Full Text Available Objective: To test the hypothesis that long- term aerobically trained elderly individuals have a greater amount of bioavailable nitric oxide (NO and have a larger cutaneous vasodilation during local heat stress compared to their inactive elderly counterparts.Methods: Eight aerobically trained and 8 inactive older men (>60 years old participated in this study. NO bioavailability in blood and intradermal dialysate were measured with an ozone based chemiluminescence NO analyzer. Cutaneous vasodilator response to local heating was obtained using laser Doppler velocimetry.Results: Whole blood NO were similar in older- trained and inactive subjects (0.75 ± 0.56 and 0.38 ± 0.32 μM, respectively; Mann–Whitney, p = 0.153, as was intradermal dialysate NO before (7.82 ± 6.32 and 4.18 ± 1.89 μM, respectively and after local heating (7.16 ± 6.27 and 5.88 ± 3.97 μM, respectively, p = 0.354. The cutaneous vasodilator response of the older- inactive group was smaller than the older- trained group [Group-Time interaction, F(24, 264 = 12.0, p < 0.0001]. When compared to a young group the peak vasodilator response of the older- trained subjects was similar. However, the time to initial dilation was 3.1 and 2.2 times longer (p < 0.05 in older- inactive and older- trained subjects, respectively, compared to young subjects.Conclusions: Our data support the hypothesis that the age-related reductions in cutaneous vasodilation can possibly be restored by maintaining an aerobic training regimen (at least 3 years. However, some residual effects of aging remain, specifically a delayed cutaneous vasodilator response to local heating is still present in active older adults. We found no evidence for an increase in systemic or local NO-bioavailability with an extended commitment to aerobic fitness.

The Effect of Being Aerobically Active vs. Inactive on Cutaneous Vascular Conductance during Local Heat Stress in an Older Population.

Science.gov (United States)

Mitchell, Ulrike H; Burton, Samantha; Gordon, Christopher; Mack, Gary W

2017-01-01

Objective: To test the hypothesis that long- term aerobically trained elderly individuals have a greater amount of bioavailable nitric oxide (NO) and have a larger cutaneous vasodilation during local heat stress compared to their inactive elderly counterparts. Methods: Eight aerobically trained and 8 inactive older men (>60 years old) participated in this study. NO bioavailability in blood and intradermal dialysate were measured with an ozone based chemiluminescence NO analyzer. Cutaneous vasodilator response to local heating was obtained using laser Doppler velocimetry. Results: Whole blood NO were similar in older- trained and inactive subjects (0.75 ± 0.56 and 0.38 ± 0.32 μM, respectively; Mann-Whitney, p = 0.153), as was intradermal dialysate NO before (7.82 ± 6.32 and 4.18 ± 1.89 μM, respectively) and after local heating (7.16 ± 6.27 and 5.88 ± 3.97 μM, respectively, p = 0.354). The cutaneous vasodilator response of the older- inactive group was smaller than the older- trained group [Group-Time interaction, F (24, 264) = 12.0, p < 0.0001]. When compared to a young group the peak vasodilator response of the older- trained subjects was similar. However, the time to initial dilation was 3.1 and 2.2 times longer ( p < 0.05) in older- inactive and older- trained subjects, respectively, compared to young subjects. Conclusions: Our data support the hypothesis that the age-related reductions in cutaneous vasodilation can possibly be restored by maintaining an aerobic training regimen (at least 3 years). However, some residual effects of aging remain, specifically a delayed cutaneous vasodilator response to local heating is still present in active older adults. We found no evidence for an increase in systemic or local NO-bioavailability with an extended commitment to aerobic fitness.

Regulation of the skeletal muscle blood flow in humans

DEFF Research Database (Denmark)

Mortensen, Stefan; Saltin, Bengt

2014-01-01

In humans, skeletal muscle blood flow is regulated by an interaction between several locally formed vasodilators including nitric oxide (NO) and prostaglandins. In plasma, ATP is a potent vasodilator that stimulates the formation of NO and prostaglandins and very importantly can offset local...... concentration does not increase during exercise. In the skeletal muscle interstitium, there is a marked increase in the concentration of ATP and adenosine and this increase is tightly coupled to the increase in blood flow. The sources of interstitial ATP and adenosine are thought to be skeletal muscle cells...... hyperaemia whereas the role of ATP remains uncertain due to lack of specific purinergic receptor blockers for human use. The purpose of this review is to address the interaction between vasodilator systems and to discuss the multiple proposed roles of ATP in human skeletal muscle blood flow regulation...

Bromide-free TEMPO-mediated oxidation of primary alcohol groups in starch and methyl alpha-D-glucopyranoside.

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Bragd, P L; Besemer, A C; van Bekkum, H

2000-09-22

TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl)-mediated oxidation of potato starch and methyl alpha-D-glucopyranoside (MGP) was performed in the absence of sodium bromide (NaBr) as co-catalyst, solely using sodium hypochlorite (NaOCl) as the primary oxidant. The low reaction rate associated with a bromide-free process was increased by performing the oxidation at increased temperatures. The reaction proceeded stoichiometrically and with high selectivity and with only minor depolymerisation, provided that temperature and pH were kept or = 25 degrees C) and under more alkaline conditions (pH > or = 9.0) degradation of the starch skeleton occurred. Simultaneously, side-reactions of the nitrosonium ion lowered the yield of the oxidation. Despite the absence of the NaBr catalyst, the reaction rate-controlling step was found to be the oxidation of the primary hydroxyl groups with the nitrosonium ion. The reaction was first-order in MGP and in TEMPO.

Uncoupling of Vascular Nitric Oxide Synthase Caused by Intermittent Hypoxia

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Mohammad Badran

2016-01-01

Full Text Available Objective. Obstructive sleep apnea (OSA, characterized by chronic intermittent hypoxia (CIH, is often present in diabetic (DB patients. Both conditions are associated with endothelial dysfunction and cardiovascular disease. We hypothesized that diabetic endothelial dysfunction is further compromised by CIH. Methods. Adult male diabetic (BKS.Cg-Dock7m +/+ Leprdb/J (db/db mice (10 weeks old and their heterozygote littermates were subjected to CIH or intermittent air (IA for 8 weeks. Mice were separated into 4 groups: IA (intermittent air nondiabetic, IH (intermittent hypoxia nondiabetic, IADB (intermittent air diabetic, and IHDB (intermittent hypoxia diabetic groups. Endothelium-dependent and endothelium-independent relaxation and modulation by basal nitric oxide (NO were analyzed using wire myograph. Plasma 8-isoprostane, interleukin-6 (IL-6, and asymmetric dimethylarginine (ADMA were measured using ELISA. Uncoupling of eNOS was measured using dihydroethidium (DHE staining. Results. Endothelium-dependent vasodilation and basal NO production were significantly impaired in the IH and IADB group compared to IA group but was more pronounced in IHDB group. Levels of 8-isoprostane, IL-6, ADMA, and eNOS uncoupling were ≈2-fold higher in IH and IADB groups and were further increased in the IHDB group. Conclusion. Endothelial dysfunction is more pronounced in diabetic mice subjected to CIH compared to diabetic or CIH mice alone. Oxidative stress, ADMA, and eNOS uncoupling were exacerbated by CIH in diabetic mice.

Assessment of nitric oxide (NO) redox reactions contribution to nitrous oxide (N2 O) formation during nitrification using a multispecies metabolic network model.

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Perez-Garcia, Octavio; Chandran, Kartik; Villas-Boas, Silas G; Singhal, Naresh

2016-05-01

Over the coming decades nitrous oxide (N2O) is expected to become a dominant greenhouse gas and atmospheric ozone depleting substance. In wastewater treatment systems, N2O is majorly produced by nitrifying microbes through biochemical reduction of nitrite (NO2(-)) and nitric oxide (NO). However it is unknown if the amount of N2O formed is affected by alternative NO redox reactions catalyzed by oxidative nitrite oxidoreductase (NirK), cytochromes (i.e., P460 [CytP460] and 554 [Cyt554 ]) and flavohemoglobins (Hmp) in ammonia- and nitrite-oxidizing bacteria (AOB and NOB, respectively). In this study, a mathematical model is developed to assess how N2O formation is affected by such alternative nitrogen redox transformations. The developed multispecies metabolic network model captures the nitrogen respiratory pathways inferred from genomes of eight AOB and NOB species. The performance of model variants, obtained as different combinations of active NO redox reactions, was assessed against nine experimental datasets for nitrifying cultures producing N2O at different concentration of electron donor and acceptor. Model predicted metabolic fluxes show that only variants that included NO oxidation to NO2(-) by CytP460 and Hmp in AOB gave statistically similar estimates to observed production rates of N2O, NO, NO2(-) and nitrate (NO3(-)), together with fractions of AOB and NOB species in biomass. Simulations showed that NO oxidation to NO2(-) decreased N2O formation by 60% without changing culture's NO2(-) production rate. Model variants including NO reduction to N2O by Cyt554 and cNor in NOB did not improve the accuracy of experimental datasets estimates, suggesting null N2O production by NOB during nitrification. Finally, the analysis shows that in nitrifying cultures transitioning from dissolved oxygen levels above 3.8 ± 0.38 to <1.5 ± 0.8 mg/L, NOB cells can oxidize the NO produced by AOB through reactions catalyzed by oxidative NirK. © 2015 Wiley Periodicals, Inc.

Rat duodenal motility in vitro: Prokinetic effects of DL-homocysteine thiolactone and modulation of nitric oxide mediated inhibition

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Stojanović Marija

2013-01-01

Full Text Available Homocysteine is a significant but modifiable risk factor for vascular diseases. As gastrointestinal smooth musculature is similar to blood vessel muscles, we investigated how elevated homocysteine levels affect nitric oxide-mediated neurotransmission in the gut. There is accumulated evidence that a dysfunction of NO neurons in the myenteric plexus may cause various diseases in the gastrointestinal tract such as achalasia, diabetic gastroparesis and infantile hypertrophic pyloric stenosis. In the present study, we aimed to assess the effects of homocysteine on NO-mediated responses in vitro, and to examine the effects of DL-homocysteine thiolactone on the spontaneous motility of rat duodenum and nitrergic neurotransmission. DL-homocysteine thiolactone concentration of 10 μmol/L leads to the immediate increase in tone, amplitude and frequency of spontaneous movements in isolated rat duodenum. L-NAME (30 μmol/L leads to an increase in basal tone, amplitude and frequency of spontaneous contractions. The relaxations induced by EFS were significantly reduced in duodenal segments incubated in DL-homocysteine thiolactone compared with the control group. EFS-induced relaxations were inhibited by L-NAME in both experimental and control groups. These results suggest that a high level of homocysteine causes an important impairment of non-adrenergic non-cholinergic innervation of the rat duodenum. [Projekat Ministarstva nauke Republike Srbije, br. 175043

Contraction-evoked vasodilation and functional hyperaemia are compromised in branching skeletal muscle arterioles of young pre-diabetic mice.

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Novielli, N M; Jackson, D N

2014-06-01

To investigate the effects of pre-diabetes on microvascular network function in contracting skeletal muscle. We hypothesized that pre-diabetes compromises contraction-evoked vasodilation of branching second-order (2A), third-order (3A) and fourth-order (4A) arterioles, where distal arterioles would be affected the greatest. Intravital video microscopy was used to measure arteriolar diameter (in 2A, 3A and 4A) and blood flow (in 2A and 3A) changes to electrical field stimulation of the gluteus maximus muscle in pre-diabetic (The Pound Mouse, PD) and control (c57bl6, CTRL) mice. Baseline diameter and blood flow were similar between groups (2A: ~20 μm, 3A: ~14 μm and 4A: ~8 μm; 2A: ~1 nL s(-1) and 3A: ~0.5 nL s(-1) ). Single tetanic contraction (100 Hz; 200, 400, 800 ms duration) evoked rapid-onset vasodilation (ROV) and blood flow responses that were blunted by ~50% and up to 81%, respectively, in PD vs. CTRL (P contraction (2 and 8 Hz, 30 s) evoked vasodilatory and blood flow responses that were also attenuated by ~50% and up to 71%, respectively, in PD vs. CTRL (P contraction was also up to 2.5-fold greater at 4A vs. 2A in CTRL; however spatial differences in vasodilation across arteriolar branch orders was disrupted in PD. Arteriolar dysregulation in pre-diabetes causes deficits in contraction-evoked dilation and blood flow, where greatest deficits occur at distal arterioles. © 2014 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Arylboronate ester based diazeniumdiolates (BORO/NO), a class of hydrogen peroxide inducible nitric oxide (NO) donors.

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Dharmaraja, Allimuthu T; Ravikumar, Govindan; Chakrapani, Harinath

2014-05-16

Here, we report the design, synthesis, and evaluation of arylboronate ester based diazeniumdiolates (BORO/NO), a class of nitric oxide (NO) donors activated by hydrogen peroxide (H2O2), a reactive oxygen species (ROS), to generate NO. We provide evidence for the NO donors' ability to permeate bacteria to produce NO when exposed to H2O2 supporting possible applications for BORO/NO to study molecular mechanisms of NO generation in response to elevated ROS.

A novel theory: biological processes mostly involve two types of mediators, namely general and specific mediators Endogenous small radicals such as superoxide and nitric oxide may play a role of general mediator in biological processes.

Science.gov (United States)

Mo, Jian

2005-01-01

A great number of papers have shown that free radicals as well as bioactive molecules can play a role of mediator in a wide spectrum of biological processes, but the biological actions and chemical reactivity of the free radicals are quite different from that of the bioactive molecules, and that a wide variety of bioactive molecules can be easily modified by free radicals due to having functional groups sensitive to redox, and the significance of the interaction between the free radicals and the bioactive molecules in biological processes has been confirmed by the results of some in vitro and in vivo studies. Based on these evidence, this article presented a novel theory about the mediators of biological processes. The essentials of the theory are: (a) mediators of biological processes can be classified into general and specific mediators; the general mediators include two types of free radicals, namely superoxide and nitric oxide; the specific mediators include a wide variety of bioactive molecules, such as specific enzymes, transcription factors, cytokines and eicosanoids; (b) a general mediator can modify almost any class of the biomolecules, and thus play a role of mediator in nearly every biological process via diverse mechanisms; a specific mediator always acts selectively on certain classes of the biomolecules, and may play a role of mediator in different biological processes via a same mechanism; (c) biological processes are mostly controlled by networks of their mediators, so the free radicals can regulate the last consequence of a biological process by modifying some types of the bioactive molecules, or in cooperation with these bioactive molecules; the biological actions of superoxide and nitric oxide may be synergistic or antagonistic. According to this theory, keeping the integrity of these networks and the balance between the free radicals and the bioactive molecules as well as the balance between the free radicals and the free radical scavengers

Nitric oxide (NO) is an endogenous anticonvulsant but not a mediator of the increase in cerebral blood flow accompanying bicuculline-induced seizures in rats

DEFF Research Database (Denmark)

Wang, Qian; Theard, M A; Pelligrino, D A

1994-01-01

Neurons synthesize NO, which may act as a retrograde messenger, involved in either potentiating or depressing neuronal excitability. NO may also play a role in the cerebral vasodilatory response to increased neuronal activity (i.e., seizures). In this study, two questions were asked: (1) is NO an......Neurons synthesize NO, which may act as a retrograde messenger, involved in either potentiating or depressing neuronal excitability. NO may also play a role in the cerebral vasodilatory response to increased neuronal activity (i.e., seizures). In this study, two questions were asked: (1......) is NO an endogenous anticonvulsant or proconvulsant substance? and (2) is the cerebral blood flow (CBF) increase accompanying bicuculline (BC)-induced seizures mediated by NO? The experiments were performed in 300-400-g Wistar rats anesthetized with 0.6% halothane and 70% N2O/30% O2. CBF was measured using...

Enhanced transfection by antioxidative polymeric gene carrier that reduces polyplex-mediated cellular oxidative stress.

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Lee, Min Sang; Kim, Nak Won; Lee, Kyuri; Kim, Hongtae; Jeong, Ji Hoon

2013-06-01

To test the hypothesis in which polyplex-induced oxidative stress may affect overall transfection efficiency, an antioxidative transfection system minimizing cellular oxidative stress was designed for enhanced transfection. An amphiphilic copolymer (PEI-PLGA) was synthesized and used as a micelle-type gene carrier containing hydrophobic antioxidant, α-tocopherol. Cellular oxidative stress and the change of mitochondrial membrane potential after transfection was measured by using a fluorescent probe (H₂DCFDA) and lipophilic cationic probe (JC-1), respectively. Transfection efficiency was determined by measuring a reporter gene (luciferase) expression level. The initial transfection study with conventional PEI/plasmid DNA polyplex showed significant generation of reactive oxygen species (ROS). The PEI-PLGA copolymer successfully carried out the simultaneous delivery of α-tocopherol and plasmid DNA (PEI-PLGA/Toco/pDNA polyplex) into cells, resulting in a significant reduction in cellular ROS generation after transfection and helped to maintain the mitochondrial membrane potential (ΔΨ). In addition, the transfection efficiency was dramatically increased using the antioxidative transfection system. This work showed that oxidative stress would be one of the important factors that should be considered in designing non-viral gene carriers and suggested a possible way to reduce the carrier-mediated oxidative stress, which consequently leads to enhanced transfection.

Oxidative and nitrosative stress in trichloroethene-mediated autoimmune response

International Nuclear Information System (INIS)

Wang Gangduo; Cai Ping; Ansari, G.A.S.; Khan, M. Firoze

2007-01-01

Reactive oxygen and nitrogen species (RONS) are implicated in the pathogenesis of several autoimmune diseases. Also, increased lipid peroxidation and protein nitration are reported in systemic autoimmune diseases. Lipid peroxidation-derived aldehydes (LPDAs) such as malondialdehyde (MDA) and 4-hydroxynonenal (HNE) are highly reactive and bind proteins covalently, but their potential to elicit an autoimmune response and contribution to disease pathogenesis remain unclear. Similarly, nitration of protein could also contribute to disease pathogenesis. To assess the status of lipid peroxidation and/or RONS, autoimmune-prone female MRL+/+ mice (5-week old) were treated with trichloroethene (TCE), an environmental contaminant known to induce autoimmune response, for 48 weeks (0.5 mg/ml via drinking water), and formation of antibodies to LPDA-protein adducts was followed in the sera of control and TCE-treated mice. TCE treatment led to greater formation of both anti-MDA- and -HNE-protein adduct antibodies and higher serum iNOS and nitrotyrosine levels. The increase in TCE-induced oxidative stress was associated with increases in anti-nuclear-, anti-ssDNA- and anti-dsDNA-antibodies. These findings suggest that TCE exposure not only leads to oxidative/nitrosative stress, but is also associated with induction/exacerbation of autoimmune response in MRL+/+ mice. Further interventional studies are needed to establish a causal role of RONS in TCE-mediated autoimmunity

Far-infrared radiation acutely increases nitric oxide production by increasing Ca2+ mobilization and Ca2+/calmodulin-dependent protein kinase II-mediated phosphorylation of endothelial nitric oxide synthase at serine 1179

International Nuclear Information System (INIS)

Park, Jung-Hyun; Lee, Sangmi; Cho, Du-Hyong; Park, Young Mi; Kang, Duk-Hee; Jo, Inho

2013-01-01

Highlights: •Far-infrared (FIR) radiation increases eNOS-Ser 1179 phosphorylation and NO production in BAEC. •CaMKII and PKA mediate FIR-stimulated increases in eNOS-Ser 1179 phosphorylation. •FIR increases intracellular Ca 2+ levels. •Thermo-sensitive TRPV Ca 2+ channels are unlikely to be involved in the FIR-mediated eNOS-Ser 1179 phosphorylation pathway. -- Abstract: Repeated thermal therapy manifested by far-infrared (FIR) radiation improves vascular function in both patients and mouse model with coronary heart disease, but its underlying mechanism is not fully understood. Using FIR as a thermal therapy agent, we investigate the molecular mechanism of its effect on endothelial nitric oxide synthase (eNOS) activity and NO production. FIR increased the phosphorylation of eNOS at serine 1179 (eNOS-Ser 1179 ) in a time-dependent manner (up to 40 min of FIR radiation) in bovine aortic endothelial cells (BAEC) without alterations in eNOS expression. This increase was accompanied by increases in NO production and intracellular Ca 2+ levels. Treatment with KN-93, a selective inhibitor of Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) and H-89, a protein kinase A inhibitor, inhibited FIR radiation-stimulated eNOS-Ser 1179 phosphorylation. FIR radiation itself also increased the temperature of culture medium. As transient receptors potential vanilloid (TRPV) ion channels are known to be temperature-sensitive calcium channels, we explore whether TRPV channels mediate these observed effects. Reverse transcription-PCR assay revealed two TRPV isoforms in BAEC, TRPV2 and TRPV4. Although ruthenium red, a pan-TRPV inhibitor, completely reversed the observed effect of FIR radiation, a partial attenuation (∼20%) was found in cells treated with Tranilast, TRPV2 inhibitor. However, ectopic expression of siRNA of TRPV2 showed no significant alteration in FIR radiation-stimulated eNOS-Ser 1179 phosphorylation. This study suggests that FIR radiation increases NO

Anti-oxidative and anti-neuroinflammatory effects of ethyl acetate ...

African Journals Online (AJOL)

Tropical Journal of Pharmaceutical Research June 2016; 15 (6): 1175-1181 ... microglia were used to study the expression and production of inflammatory mediators, including nitric oxide (NO) ... Parkinson's disease (PD), multiple sclerosis.

Effect of Interleukin-10 and Laminar Shear Stress on Endothelial Nitric Oxide Synthase and Nitric Oxide in African American Human Umbilical Vein Endothelial Cells.

Science.gov (United States)

Babbitt, Dianne M; Kim, Ji-Seok; Forrester, Steven J; Brown, Michael D; Park, Joon-Young

2015-11-05

African Americans have a predisposition to heightened systemic inflammation and a high prevalence of hypertension. The purpose of this study was to evaluate the influence of interleukin-10 (IL-10) and laminar shear stress (LSS) on African American endothelial cells by measuring total endothelial nitric oxide synthase (eNOS) protein expression and its phosphorylated form (p-eNOS) at Serine 1177, and nitric oxide (NO) levels, in response to IL-10 incubation and high physiological levels of LSS, used as an in vitro mimetic for aerobic exercise training (AEXT). Human umbilical vein endothelial cells (HUVEC) from an African American donor were cultured. The experimental conditions included Static, Static with IL-10 Incubation, LSS at 20 dynes/cm², and LSS at 20 dynes/cm² with IL-10 Incubation. Western blotting was used to measure eNOS and p-eNOS protein expression in the cells. A modified Griess assay was used to measure NO metabolites in the cell culture media. There were significant increases in p-eNOS, eNOS, and NO in the LSS at 20 dynes/cm² and LSS at 20 dynes/cm² with IL-10 Incubation experimental conditions when compared to the Static experimental condition. There were no other statistically significant differences demonstrating that IL-10 did not have an additive effect on eNOS activity in our study. The significant increases in p-eNOS, eNOS, and NO as a result of LSS in African American HUVECs suggest that AEXT may be a viable, nonpharmacologic method to improve vascular inflammation status and vasodilation, and thereby contribute to hypertension reduction in the African American population.

Differential regulation of BACE1 expression by oxidative and nitrosative signals

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Xu Huaxi

2011-03-01

Full Text Available Abstract Background It is well established that both cerebral hypoperfusion/stroke and type 2 diabetes are risk factors for Alzheimer's disease (AD. Recently, the molecular link between ischemia/hypoxia and amyloid precursor protein (APP processing has begun to be established. However, the role of the key common denominator, namely nitric oxide (NO, in AD is largely unknown. In this study, we investigated redox regulation of BACE1, the rate-limiting enzyme responsible for the β-cleavage of APP to Aβ peptides. Results Herein, we studied events such as S-nitrosylation, a covalent modification of cysteine residues by NO, and H2O2-mediated oxidation. We found that NO and H2O2 differentially modulate BACE1 expression and enzymatic activity: NO at low concentrations (2O2 (1-10 μM induces BACE1 expression via transcriptional activation, resulting in increased enzymatic activity. The differential effects of NO and H2O2 on BACE1 expression and activity are also reflected in their opposing effects on Aβ generation in cultured neurons in a dose-dependent manner. Furthermore, we found that BACE1 is highly S-nitrosylated in normal aging brains while S-nitrosylation is markedly reduced in AD brains. Conclusion This study demonstrates for the first time that BACE1 is highly modified by NO via multiple mechanisms: low and high levels of NO suppress BACE1 via transcriptional and post translational regulation, in contrast with the upregulation of BACE1 by H2O2-mediated oxidation. These novel NO-mediated regulatory mechanisms likely protect BACE1 from being further oxidized by excessive oxidative stress, as from H2O2 and peroxynitrite which are known to upregulate BACE1 and activate the enzyme, resulting in excessive cleavage of APP and Aβ generation; they likely represent the crucial house-keeping mechanism for BACE1 expression/activation under physiological conditions.

Urea- Hydrogen Peroxide (UHP Oxidation of Thiols to the Corresponding Disulfides Promoted by Maleic Anhydride as Mediator

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M. H. Habibi

2005-10-01

Full Text Available Urea-hydrogen peroxide (UHP was used in the presence of maleic anhydride as mediator in a simple and convenient method for the oxidation in high yield of some thiols to the corresponding disulfides. Peroxymaleic acid formed in situ from the reaction of UHP with maleic anhydride has a key role in this oxidation. Performance of the reaction in various solvents showed that methanol was the solvent of choice at 0 oC. The products were isolated by simple filtration on silica gel.

New Modalities for the Administration of Inhaled Nitric Oxide in Intensive Care Units After Cardiac Surgery or for Neonatal Indications: A Prospective Observational Study.

Science.gov (United States)

Gaudard, Philippe; Barbanti, Claudio; Rozec, Bertrand; Mauriat, Philippe; M'rini, Mimoun; Cambonie, Gilles; Liet, Jean Michel; Girard, Claude; Leger, Pierre Louis; Assaf, Ziad; Damas, Pierre; Loron, Gauthier; Lecourt, Laurent; Amour, Julien; Pouard, Philippe

2018-04-01

Nitric oxide (NO) has a well-known efficacy in pulmonary hypertension (PH), with wide use for 20 years in many countries. The objective of this study was to describe the current use of NO in real life and the gap with the guidelines. This is a multicenter, prospective, observational study on inhaled NO administered through an integrated delivery and monitoring device and indicated for PH according to the market authorizations. The characteristics of NO therapy and ventilation modes were observed. Concomitant pulmonary vasodilator treatments, safety data, and outcome were also collected. Quantitative data are expressed as median (25th, 75th percentile). Over 1 year, 236 patients were included from 14 equipped and trained centers: 117 adults and 81 children with PH associated with cardiac surgery and 38 neonates with persistent PH of the newborn. Inhaled NO was initiated before intensive care unit (ICU) admission in 57%, 12.7%, and 38.9% with an initial dose of 10 (10, 15) ppm, 20 (18, 20) ppm, and 17 (11, 20) ppm, and a median duration of administration of 3.9 (1.9, 6.1) days, 3.8 (1.8, 6.8) days, and 3.1 (1.0, 5.7) days, respectively, for the adult population, pediatric cardiac group, and newborns. The treatment was performed using administration synchronized to the mechanical ventilation. The dose was gradually decreased before withdrawal in 86% of the cases according to the usual procedure of each center. Adverse events included rebound effect for 3.4% (95% confidence interval [CI], 0.9%-8.5%) of adults, 1.2% (95% CI, 0.0%-6.7%) of children, and 2.6% (95% CI, 0.1%-13.8%) of neonates and methemoglobinemia exceeded 2.5% for 5 of 62 monitored patients. Other pulmonary vasodilators were associated with NO in 23% of adults, 95% of children, and 23.7% of neonates. ICU stay was respectively 10 (6, 22) days, 7.5 (5.5, 15) days, and 9 (8, 15) days and ICU mortality was 22.2%, 6.2%, and 7.9% for adults, children, and neonates, respectively. This study confirms the safety

Antioxidant-mediated up-regulation of OGG1 via NRF2 induction is associated with inhibition of oxidative DNA damage in estrogen-induced breast cancer

International Nuclear Information System (INIS)

Singh, Bhupendra; Chatterjee, Anwesha; Ronghe, Amruta M; Bhat, Nimee K; Bhat, Hari K

2013-01-01

Estrogen metabolism-mediated oxidative stress is suggested to play an important role in estrogen-induced breast carcinogenesis. We have earlier demonstrated that antioxidants, vitamin C (Vit C) and butylated hydroxyanisole (BHA) inhibit 17β-estradiol (E2)-mediated oxidative stress and oxidative DNA damage, and breast carcinogenesis in female August Copenhagen Irish (ACI) rats. The objective of the present study was to characterize the mechanism by which above antioxidants prevent DNA damage during breast carcinogenesis. Female ACI rats were treated with E2; Vit C; Vit C + E2; BHA; and BHA + E2 for up to 240 days. mRNA and protein levels of a DNA repair enzyme 8-Oxoguanine DNA glycosylase (OGG1) and a transcription factor NRF2 were quantified in the mammary and mammary tumor tissues of rats after treatment with E2 and compared with that of rats treated with antioxidants either alone or in combination with E2. The expression of OGG1 was suppressed in mammary tissues and in mammary tumors of rats treated with E2. Expression of NRF2 was also significantly suppressed in E2-treated mammary tissues and in mammary tumors. Vitamin C or BHA treatment prevented E2-mediated decrease in OGG1 and NRF2 levels in the mammary tissues. Chromatin immunoprecipitation analysis confirmed that antioxidant-mediated induction of OGG1 was through increased direct binding of NRF2 to the promoter region of OGG1. Studies using silencer RNA confirmed the role of OGG1 in inhibition of oxidative DNA damage. Our studies suggest that antioxidants Vit C and BHA provide protection against oxidative DNA damage and E2-induced mammary carcinogenesis, at least in part, through NRF2-mediated induction of OGG1

Polar compounds isolated from the leaves of Calea prunifolia H.B.K. and their anti-adrenergic related vasodilator activity

International Nuclear Information System (INIS)

Puebla, Pilar; San Feliciano, Arturo; Aranguren, Nataly; Rincon, Javier; Rojas, Maritza; Guerrero, Mario

2011-01-01

The leaves of Calea prunifolia H.B.K., medicinal specie used in Colombian folk medicine for hypertension have been analysed for their chemical constituents, resulting in the isolation of one flavonoid glycoside, one quinic acid derivative and one kaurane diterpenoid glycoside. Their chemical structures were elucidated on the basis of spectral analysis, including HRMS, 1D- and 2D-NMR data. The vasodilator effect related to anti adrenergic activity of the three compounds was evaluated in isolated aortic rings from Wistar rats contracted cumulatively with phenylephrine (from 1 x 10 -9 to 5 x 10 -5 mol L -1 ). Although these compounds were devoid of significant vasodilator activity when they were tested alone (1 μg mL-1), mixtures of them (1:1:1) and the own EtOH extract exerted preventive anti-adrenergic activity increasing the phenylephrine CE 50 from 2.3 x 10 -8 to 1.3 x 10 -7 and 8.0 x 10 -7 mol L -1 , respectively. (author)

Solar-mediated thermo-electrochemical oxidation of sodium dodecyl benzene sulfonate by modulating the effective oxidation potential and pathway for green remediation of wastewater

Science.gov (United States)

Gu, Di; Gao, Simeng; Jiang, TingTing; Wang, Baohui

2017-01-01

To match the relentless pursuit of three research hot points - efficient solar utilization, green and sustainable remediation of wastewater and advanced oxidation processes, solar-mediated thermo-electrochemical oxidation of surfactant was proposed and developed for green remediation of surfactant wastewater. The solar thermal electrochemical process (STEP), fully driven with solar energy to electric energy and heat and without an input of other energy, sustainably serves as efficient thermo-electrochemical oxidation of surfactant, exemplified by SDBS, in wastewater with the synergistic production of hydrogen. The electrooxidation-resistant surfactant is thermo-electrochemically oxidized to CO2 while hydrogen gas is generated by lowing effective oxidation potential and suppressing the oxidation activation energy originated from the combination of thermochemical and electrochemical effect. A clear conclusion on the mechanism of SDBS degradation can be proposed and discussed based on the theoretical analysis of electrochemical potential by quantum chemical method and experimental analysis of the CV, TG, GC, FT-IR, UV-vis, Fluorescence spectra and TOC. The degradation data provide a pilot for the treatment of SDBS wastewater that appears to occur via desulfonation followed by aromatic-ring opening. The solar thermal utilization that can initiate the desulfonation and activation of SDBS becomes one key step in the degradation process. PMID:28294180

Local arginase inhibition during early reperfusion mediates cardioprotection via increased nitric oxide production.

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Adrian T Gonon

Full Text Available Consumption of L-arginine contributes to reduced bioavailability of nitric oxide (NO that is critical for the development of ischemia-reperfusion injury. The aim of the study was to determine myocardial arginase expression and activity in ischemic-reperfusion myocardium and whether local inhibition of arginase within the ischemic myocardium results in increased NO production and protection against myocardial ischemia-reperfusion. Anesthetized pigs were subjected to coronary artery occlusion for 40 min followed by 4 h reperfusion. The pigs were randomized to intracoronary infusion of vehicle (n = 7, the arginase inhibitor N-hydroxy-nor-L-arginine (nor-NOHA, 2 mg/min, n = 7, the combination of nor-NOHA and the NO synthase inhibitor N(G-monomethyl-L-arginine (L-NMMA, 0.35 mg/min, n = 6 into the jeopardized myocardial area or systemic intravenous infusion of nor-NOHA (2 mg/min, n = 5 at the end of ischemia and start of reperfusion. The infarct size of the vehicle group was 80 ± 4% of the area at risk. Intracoronary nor-NOHA reduced infarct size to 46 ± 5% (P<0.01. Co-administration of L-NMMA abrogated the cardioprotective effect mediated by nor-NOHA (infarct size 72 ± 6%. Intravenous nor-NOHA did not reduce infarct size. Arginase I and II were expressed in cardiomyocytes, endothelial, smooth muscle and poylmorphonuclear cells. There was no difference in cytosolic arginase I or mitochondrial arginase II expression between ischemic-reperfused and non-ischemic myocardium. Arginase activity increased 2-fold in the ischemic-reperfused myocardium in comparison with non-ischemic myocardium. In conclusion, ischemia-reperfusion increases arginase activity without affecting cytosolic arginase I or mitochondrial arginase II expression. Local arginase inhibition during early reperfusion reduces infarct size via a mechanism that is dependent on increased bioavailability of NO.