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Sample records for controlled nitric oxide

  1. Nitric oxide fumigation for postharvest pest control

    Science.gov (United States)

    Nitric oxide fumigation is effective against all arthropod pests at various life stages tested. Nine insect pests at various life stages and bulb mites were subjected to nitric oxide fumigation treatments under ultralow oxygen conditions of =50 ppm O2 in 1.9L glass jars as fumigation chambers. The ...

  2. [Nitric oxide].

    Science.gov (United States)

    Rovira, I

    1995-01-01

    Nitric oxide was identified as the relaxing factor derived from the endothelium in 1987. Nitric oxide synthesis allows the vascular system to maintain a state of vasodilation, thereby regulating arterial pressure. Nitric oxide is also found in platelets, where it inhibits adhesion and aggregation; in the immune system, where it is responsible for the cytotoxic action of macrophages; and in the nervous system, where it acts as neurotransmitter. A deficit in endogenous synthesis of nitric oxide contributes to such conditions as essential arterial hypertension, pulmonary hypertension and heart disease. An excess of nitrous oxide induced by endotoxins and cytokinins, meanwhile, is believed to be responsible for hypotension in septic shock and for hyperdynamic circulatory state in cirrhosis of the liver. Nitric oxide has also been implicated in the rejection of transplanted organs and in cell damage after reperfusion. Inhaled nitrous oxide gas reduces pulmonary hypertension without triggering systemic hypotension in both experimental and clinical conditions. It also produces selective vasodilation when used to ventilate specific pulmonary areas, thereby improving the ventilation/perfusion ratio and, hence, oxygenation. Nitric oxide inhalation is effective in pulmonary hypertension-coincident with chronic obstructive lung disease, in persistent neonatal pulmonary hypertension and in pulmonary hypertension with congenital or acquired heart disease. Likewise, it reduces intrapulmonary shunt in acute respiratory failure and improves gas exchange. Under experimental conditions nitric oxide acts as a bronchodilator, although it seems to be less effective for this purpose in clinical use.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Nitric oxide as a potent fumigant for postharvest pest control

    Science.gov (United States)

    There is a great demand for safe and effective alternative fumigants to replace methyl bromide and other toxic fumigants for pest control. Nitric oxide, a common signal molecule in biological systems, was found to be effective and safe to control insects under ultralow oxygen conditions. Fumigatio...

  4. 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 transports NO as dinitrosyl-dithiol-iron complexes (DNICs) composed of iron, NO and glutathione (GSH). Hence, this gas with contrasting anti- and pro-tumor effects, which has been assumed to be freely diffusible, is a tightly-regulated species in M1-MØs. These control systems prevent NO cytotoxicity and may...

  5. Nitric oxide supersensitivity

    DEFF Research Database (Denmark)

    Olesen, J; Iversen, Helle Klingenberg; Thomsen, L L

    1993-01-01

    in a double blind design to 17 migraine patients, 17 age and sex matched healthy controls and 9 subjects with tension-type headache. The nitroglycerin-induced headache was significantly more severe in migraine sufferers, lasted longer and fulfilled diagnostic criteria for migraine more often. We have...... previously shown a similar supersensitivity to histamine which in human cerebral arteries activates endothelial H1 receptors and causes endothelial production of nitric oxide. Migraine patients are thus supersensitive to exogenous nitric oxide from nitroglycerin as well as to endothelially produced nitric...

  6. Auxin and nitric oxide control indeterminate nodule formation

    Directory of Open Access Journals (Sweden)

    Spena Angelo

    2007-05-01

    Full Text Available Abstract Background Rhizobia symbionts elicit root nodule formation in leguminous plants. Nodule development requires local accumulation of auxin. Both plants and rhizobia synthesise auxin. We have addressed the effects of bacterial auxin (IAA on nodulation by using Sinorhizobium meliloti and Rhizobium leguminosarum bacteria genetically engineered for increased auxin synthesis. Results IAA-overproducing S. meliloti increased nodulation in Medicago species, whilst the increased auxin synthesis of R. leguminosarum had no effect on nodulation in Phaseolus vulgaris, a legume bearing determinate nodules. Indeterminate legumes (Medicago species bearing IAA-overproducing nodules showed an enhanced lateral root development, a process known to be regulated by both IAA and nitric oxide (NO. Higher NO levels were detected in indeterminate nodules of Medicago plants formed by the IAA-overproducing rhizobia. The specific NO scavenger cPTIO markedly reduced nodulation induced by wild type and IAA-overproducing strains. Conclusion The data hereby presented demonstrate that auxin synthesised by rhizobia and nitric oxide positively affect indeterminate nodule formation and, together with the observation of increased expression of an auxin efflux carrier in roots bearing nodules with higher IAA and NO content, support a model of nodule formation that involves auxin transport regulation and NO synthesis.

  7. Nitric oxide and cardiovascular system.

    Science.gov (United States)

    Cengel, Atiye; Sahinarslan, Asife

    2006-12-01

    Endothelium has many important functions including the control of blood-tissue permeability and vascular tonus, regulation of vascular surface properties for homeostasis and inflammation. Nitric oxide is the chief molecule in regulation of endothelial functions. Nitric oxide deficiency, which is also known as endothelial dysfunction, is the first step for the occurrence of many disease states in cardiovascular system including heart failure, hypertension, dyslipidemia, insulin resistance, diabetes mellitus, hyperhomocysteinemia and smoking. This review deals with the importance of nitric oxide for cardiovascular system. It also includes the latest improvements in the diagnosis and treatment of endothelial dysfunction.

  8. Efficacy of Nitric Oxide Fumigation for Controlling Codling Moth in Apples

    OpenAIRE

    Yong-Biao Liu; Xiangbing Yang; Gregory Simmons

    2016-01-01

    Nitric oxide (NO) fumigation under ultralow oxygen (ULO) conditions was studied for its efficacy in controlling codling moth and effects on postharvest quality of apples. NO fumigation was effective against eggs and larvae of different sizes on artificial diet in 48 h treatments. Small larvae were more susceptible to nitric oxide than other stages at 0.5% NO concentration. There were no significant differences among life stages at 1.0% to 2.0% NO concentrations. In 24 h treatments of eggs, 3....

  9. Nitric oxide as a fumigant for postharvest pest control and its safety to postharvest quality of fresh products

    Science.gov (United States)

    Nitric oxide fumigation under ultralow oxygen atmospheres was discovered recently to be effective for pest control. It is effective against all life stages of insects and mites and against both external and internal feeders. Nitric oxide fumigation comes with additional but acceptable costs associ...

  10. Development of novel agents based on nitric oxide for the control of colon cancer

    Institute of Scientific and Technical Information of China (English)

    Vassiliki KOZONI; Theophilos ROSENBERG; Basil RIGAS

    2007-01-01

    Nitric oxide-donating nonsteroidal anti-inflammatory drugs (NO-NSAIDs) repre-sent a novel class of compounds that hold promise as agents for the control of colon cancer. They are derivatives of conventional NSAIDs that have been modi-fied by adding to them, via a spacer molecule, a nitric oxide releasing moiety. The expectation is that the combined effects of NO and the NSAID moiety will exceed those of each structural component alone. Extensive work has demonstrated their potency and efficacy in preclinical models of colon cancer. The mechanism of action of NO-NSAIDs involves the modulation of several critical cellular signaling pathways, whereas the induction of a state of oxidative stress, at least by NO-aspirin, appears to be a major proximal event. Clinical trials are needed to assess the role of NO-NSAIDs in the control of colon cancer.

  11. Inhaled nitric oxide for prevention of bronchopulmonary dysplasia in premature babies (EUNO) : a randomised controlled trial

    NARCIS (Netherlands)

    Mercier, Jean-Christophe; Hummler, Helmut; Durrmeyer, Xavier; Sanchez-Luna, Manuel; Carnielli, Virgilio; Field, David; Greenough, Anne; Van Overmeire, Bart; Jonsson, Baldvin; Hallman, Mikko; Baldassarre, James

    2010-01-01

    Background In animal models, inhaled nitric oxide improved gas exchange and lung structural development, but its use in premature infants at risk of developing bronchopulmonary dysplasia remains controversial. We therefore tested the hypothesis that inhaled nitric oxide at a low concentration, start

  12. Inhaled nitric oxide for the adjunctive therapy of severe malaria: Protocol for a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Lavery James V

    2011-07-01

    Full Text Available Abstract Background Severe malaria remains a major cause of global morbidity and mortality. Despite the use of potent anti-parasitic agents, the mortality rate in severe malaria remains high. Adjunctive therapies that target the underlying pathophysiology of severe malaria may further reduce morbidity and mortality. Endothelial activation plays a central role in the pathogenesis of severe malaria, of which angiopoietin-2 (Ang-2 has recently been shown to function as a key regulator. Nitric oxide (NO is a major inhibitor of Ang-2 release from endothelium and has been shown to decrease endothelial inflammation and reduce the adhesion of parasitized erythrocytes. Low-flow inhaled nitric oxide (iNO gas is a US FDA-approved treatment for hypoxic respiratory failure in neonates. Methods/Design This prospective, parallel arm, randomized, placebo-controlled, blinded clinical trial compares adjunctive continuous inhaled nitric oxide at 80 ppm to placebo (both arms receiving standard anti-malarial therapy, among Ugandan children aged 1-10 years of age with severe malaria. The primary endpoint is the longitudinal change in Ang-2, an objective and quantitative biomarker of malaria severity, which will be analysed using a mixed-effects linear model. Secondary endpoints include mortality, recovery time, parasite clearance and neurocognitive sequelae. Discussion Noteworthy aspects of this trial design include its efficient sample size supported by a computer simulation study to evaluate statistical power, meticulous attention to complex ethical issues in a cross-cultural setting, and innovative strategies for safety monitoring and blinding to treatment allocation in a resource-constrained setting in sub-Saharan Africa. Trial Registration ClinicalTrials.gov Identifier: NCT01255215

  13. Efficacy of Nitric Oxide Fumigation for Controlling Codling Moth in Apples

    Directory of Open Access Journals (Sweden)

    Yong-Biao Liu

    2016-12-01

    Full Text Available Nitric oxide (NO fumigation under ultralow oxygen (ULO conditions was studied for its efficacy in controlling codling moth and effects on postharvest quality of apples. NO fumigation was effective against eggs and larvae of different sizes on artificial diet in 48 h treatments. Small larvae were more susceptible to nitric oxide than other stages at 0.5% NO concentration. There were no significant differences among life stages at 1.0% to 2.0% NO concentrations. In 24 h treatments of eggs, 3.0% NO fumigation at 2 °C achieved 100% egg mortality. Two 24 h fumigation treatments of infested apples containing medium and large larvae with 3.0% and 5.0% NO resulted in 98% and 100% mortalities respectively. Sound apples were also fumigated with 5.0% NO for 24 h at 2 °C to determine effects on apple quality. The fumigation treatment was terminated by flushing with nitrogen and had no negative impact on postharvest quality of apples as measured by firmness and color at 2 and 4 weeks after fumigation. This study demonstrated that NO fumigation was effective against codling moth and safe to apple quality, and therefore has potential to become a practical alternative to methyl bromide fumigation for control of codling moth in apples.

  14. Efficacy of Nitric Oxide Fumigation for Controlling Codling Moth in Apples

    Science.gov (United States)

    Liu, Yong-Biao; Yang, Xiangbing; Simmons, Gregory

    2016-01-01

    Nitric oxide (NO) fumigation under ultralow oxygen (ULO) conditions was studied for its efficacy in controlling codling moth and effects on postharvest quality of apples. NO fumigation was effective against eggs and larvae of different sizes on artificial diet in 48 h treatments. Small larvae were more susceptible to nitric oxide than other stages at 0.5% NO concentration. There were no significant differences among life stages at 1.0% to 2.0% NO concentrations. In 24 h treatments of eggs, 3.0% NO fumigation at 2 °C achieved 100% egg mortality. Two 24 h fumigation treatments of infested apples containing medium and large larvae with 3.0% and 5.0% NO resulted in 98% and 100% mortalities respectively. Sound apples were also fumigated with 5.0% NO for 24 h at 2 °C to determine effects on apple quality. The fumigation treatment was terminated by flushing with nitrogen and had no negative impact on postharvest quality of apples as measured by firmness and color at 2 and 4 weeks after fumigation. This study demonstrated that NO fumigation was effective against codling moth and safe to apple quality, and therefore has potential to become a practical alternative to methyl bromide fumigation for control of codling moth in apples. PMID:27918417

  15. Control of superoxide and nitric oxide formation during human sperm capacitation.

    Science.gov (United States)

    de Lamirande, Eve; Lamothe, Geneviève; Villemure, Michèle

    2009-05-15

    We studied the modulation of superoxide anion (O(2).(-)) and nitric oxide (NO.) generation during human sperm capacitation (changes needed for the acquisition of fertility). The production of NO. (diaminofluorescein-2 fluorescence assay), but not that of O(2).(-) (luminescence assay), related to sperm capacitation was blocked by inhibitors of protein kinase C, Akt, protein tyrosine kinase, etc., but not by those of protein kinase A. Extracellular calcium (Ca(2+)) controlled O(2).(-) synthesis but extra- and intracellular Ca(2+) regulated NO. formation. Zinc inhibited capacitation and formation of O(2).(-) and NO.. Zinc chelators (TPEN and EDTA) and sulfhydryl-targeted compounds (diamide and N-ethylmaleimide) stimulated capacitation and formation of O(2).(-) and NO.; superoxide dismutase (SOD) and nitric oxide synthase inhibitor (L-NMMA) prevented these events. Diphenyliodonium (flavoenzyme inhibitor) blocked capacitation and related O(2).(-) synthesis but promoted NO. formation, an effect canceled by SOD and L-NMMA. NADPH induced capacitation and NO. (but not O(2).(-)) synthesis and these events were blocked by L-NMMA and not by SOD. Integration of these data on O(2).(-) and NO. production during capacitation reinforces the concept that a complex, but flexible, network of factors is involved and probably is associated with rescue mechanisms, so that spermatozoa can achieve successful fertilization.

  16. The Study of Nitric Oxide Effects in Control of Mouse Preimplantation Embryonic Defects in High Glucosis Media

    Directory of Open Access Journals (Sweden)

    I. Amiri

    2003-10-01

    Full Text Available Pregnancy in diabetic females causes delay in early stages of embryonic growth and development and higher incidence of congenital malformations and spontaneous miscarriage compared with those of non- diabetic conditions. High glucosis tratogenicity seems to be related to reduction of Nitric Oxide production (NO in hyperglycemic condition. The goal of present work was study of nitric oxid role in control of mouse preimplantation embryonic defects in high glucosis media. In order to test above hypothesis, 2-cell stage embryos of normal mice were cultured with high concentration of glucose (30mM and different concentrations of L-arginine (5,10,20 mM or L-NAME (An antagonist of L- arginine. After 96h culture, the morphology of embryos was assessed by an inverted microscope then blastocysts were stained by TUNEL. After TUNEL the total cell number and apoptotic cells were counted by use a Fluorescence microscope. Finally the amount of nitrite in the media was assayed by Greiss method. The results indicated that high glucose decreases the blastocyst formation and Nitric Oxide production and increases their apoptotic index, but 10-20mM L-arginine significantly increases the developmental potential and nitric oxide production and significantly decreases apoptosis. On the contrary L-NAME significantly inhibits the development of pre-implantation embryos . It seems that during pregnancy supplementation of high glucose media with L-arginine increases Nitric Oxide production and prevents high glucosis embryotoxicity.

  17. Nitrous-Oxide Flux from Nitric-Acid-Treated Cattle Slurry Applied to Grassland under Semi-Controlled Conditions

    NARCIS (Netherlands)

    Velthof, G.L.; Oenema, O.

    1993-01-01

    Nitrous oxide (N2O) fluxes from cattle slurry after surface application to grassland were measured under semi-controlled environmental conditions during three periods in 1991. Three types of cattle slurry were examined; untreated slurry and slurries treated with nitric acid (HNO3) to pH 6.0 and 4.5.

  18. Forearm vascular response to nitric oxide and calcitonin gene-related peptide: comparison between migraine patients and control subjects.

    NARCIS (Netherlands)

    Hoon, J.N. de; Smits, P.; Troost, J.; Struijker-Boudier, H.A.; Bortel, L.M. van

    2006-01-01

    The forearm vascular response to nitric oxide (NO) and calcitonin gene-related peptide (CGRP) was investigated in 10 migraine patients and 10 matched control subjects. Changes in forearm blood flow (FBF) during intrabrachial infusion of: (i) serotonin (releasing endogenous NO), (ii) sodium nitroprus

  19. Control of cell respiration by nitric oxide in Ataxia Telangiectasia lymphoblastoid cells.

    Science.gov (United States)

    Masci, Alessandra; Mastronicola, Daniela; Arese, Marzia; Piane, Maria; De Amicis, Andrea; Blanck, Thomas J J; Chessa, Luciana; Sarti, Paolo

    2008-01-01

    Ataxia Telangiectasia (AT) patients are particularly sensitive to oxidative-nitrosative stress. Nitric oxide (NO) controls mitochondrial respiration via the reversible inhibition of complex IV. The mitochondrial response to NO of AT lymphoblastoid cells was investigated. Cells isolated from three patients and three intrafamilial healthy controls were selected showing within each group a normal diploid karyotype and homogeneous telomere length. Different complex IV NO-inhibition patterns were induced by varying the electron flux through the respiratory chain, using exogenous cell membrane permeable electron donors. Under conditions of high electron flux the mitochondrial NO inhibition of respiration was greater in AT than in control cells (P< or =0.05). This property appears peculiar to AT, and correlates well to the higher concentration of cytochrome c detected in the AT cells. This finding is discussed on the basis of the proposed mechanism of reaction of NO with complex IV. It is suggested that the peculiar response of AT mitochondria to NO stress may be relevant to the mitochondrial metabolism of AT patients.

  20. Efficacy and residue analysis of nitric oxide fumigation of strawberries for control of Drosophila suzukii

    Science.gov (United States)

    Nitric oxide (NO) has been demonstrated as an effective fumigant against various insect pests on postharvest products under ultralow oxygen (ULO) conditions. NO showed efficacy against all life stages of insect pests with varied fumigation time and temperature, and had feasible cost-effectiveness to...

  1. Exhaled nitric oxide predicts control in patients with difficult-to-treat asthma.

    Science.gov (United States)

    Pérez-de-Llano, L A; Carballada, F; Castro Añón, O; Pizarro, M; Golpe, R; Baloira, A; Vázquez Caruncho, M; Boquete, M

    2010-06-01

    We aimed to evaluate the accuracy of baseline exhaled nitric oxide fraction (F(eNO)) to recognise individuals with difficult-to-treat asthma who have the potential to achieve control with a guideline-based stepwise strategy. 102 consecutive patients with suboptimal asthma control underwent stepwise increase in the treatment with maximal fluticasone/salmeterol combination dose for 1 month. Then, those who remained uncontrolled received oral corticosteroids for an additional month. With this approach, 53 patients (52%) gained control. Those who achieved control were more likely to have positive skin results (60.4% versus 34%; p = 0.01), positive bronchodilator test (57.1% versus 35.8%; p = 0.02) and peak expiratory flow variability > or =20% (71.1% versus 49.1%; p = 0.04). Conversely, depression was more frequent in those who remained uncontrolled (18.4 % versus 43.4 %; p = 0.01). An F(eNO) value > or =30 ppb demonstrated a sensitivity of 87.5% (95% CI 73.9-94.5%) and a specificity of 90.6% (95% CI 79.7-95.9%) for the identification of responsive asthmatics. The current results suggest that F(eNO) can identify patients with difficult-to-treat asthma and the potential to respond to high doses of inhaled corticosteroids or systemic steroids.

  2. 49 CFR 173.337 - Nitric oxide.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Nitric oxide. 173.337 Section 173.337... SHIPMENTS AND PACKAGINGS Gases; Preparation and Packaging § 173.337 Nitric oxide. (a) Nitric oxide must be... valve and valve seat that will not deteriorate in contact with nitric oxide. Cylinders or valves may...

  3. Nitric oxide in the control of luminescence from lantern shark (Etmopterus spinax) photophores.

    Science.gov (United States)

    Claes, Julien M; Krönström, Jenny; Holmgren, Susanne; Mallefet, Jérôme

    2010-09-01

    Photophores (photogenic organs) of the lantern shark Etmopterus spinax are under hormonal control, with prolactin (PRL) and melatonin (MT) triggering the light emission. Differential sensitivity to these hormones in adult individuals suggests, however, that the luminescence of this shark is controlled by an additional mechanism. In this study, different techniques were used to investigate a potential modulator of E. spinax luminescence - nitric oxide (NO). NO synthase (NOS)-like immunoreactivity (IR) was found in the photocytes (photogenic cells) of the photophores. In addition, acetylated tubulin IR also supported the presence of nerves running through the photogenic tissue and innervating different structural elements of the photophores: photocytes, pigmented cells from the iris-like structure and lens cells. Pharmacological experiments confirmed a modulatory action of NO on the hormonally induced luminescence: NO donors sodium nitroprusside (SNP) and hydroxylamine decreased the time to reach the maximum amplitude (TL(max)) of MT-induced luminescence while these substances decreased the maximum amplitude of PRL-induced luminescence (and also the TL(max) in the case of SNP). The small impact of the NOS inhibitor l-NAME on hormonally induced luminescence suggests that NO is only produced on demand. The cGMP analogue 8BrcGMP mimicked the effects of NO donors suggesting that the effects of NO are mediated by cGMP.

  4. Nitric Oxide Homeostasis in Neurodegenerative Diseases.

    Science.gov (United States)

    Hannibal, Luciana

    2016-01-01

    The role of nitric oxide in the pathogenesis and progression of neurodegenerative illnesses such as Parkinson's and Alzheimer's diseases has become prominent over the years. Increased activity of the enzymes that produce reactive oxygen species, decreased activity of antioxidant enzymes and imbalances in glutathione pools mediate and mark the neurodegenerative process. Much of the oxidative damage of proteins is brought about by the overproduction of nitric oxide by nitric oxide synthases (NOS) and its subsequent reactivity with reactive oxygen species. Proteomic methods have advanced the field tremendously, by facilitating the quantitative assessment of differential expression patterns and oxidative modifications of proteins and alongside, mapping their non-canonical functions. As a signaling molecule involved in multiple biochemical pathways, the level of nitric oxide is subject to tight regulation. All three NOS isoforms display aberrant patterns of expression in Alzheimer's disease, altering intracellular signaling and routing oxidative stress in directions that are uncompounded. This review discusses the prime factors that control nitric oxide biosynthesis, reactivity footprints and ensuing effects in the development of neurodegenerative diseases.

  5. The application of nitric oxide to control biofouling of membrane bioreactors.

    Science.gov (United States)

    Luo, Jinxue; Zhang, Jinsong; Barnes, Robert J; Tan, Xiaohui; McDougald, Diane; Fane, Anthony G; Zhuang, Guoqiang; Kjelleberg, Staffan; Cohen, Yehuda; Rice, Scott A

    2015-05-01

    A novel strategy to control membrane bioreactor (MBR) biofouling using the nitric oxide (NO) donor compound PROLI NONOate was examined. When the biofilm was pre-established on membranes at transmembrane pressure (TMP) of 88-90 kPa, backwashing of the membrane module with 80 μM PROLI NONOate for 45 min once daily for 37 days reduced the fouling resistance (Rf ) by 56%. Similarly, a daily, 1 h exposure of the membrane to 80 μM PROLI NONOate from the commencement of MBR operation for 85 days resulted in reduction of the TMP and Rf by 32.3% and 28.2%. The microbial community in the control MBR was observed to change from days 71 to 85, which correlates with the rapid TMP increase. Interestingly, NO-treated biofilms at 85 days had a higher similarity with the control biofilms at 71 days relative to the control biofilms at 85 days, indicating that the NO treatment delayed the development of biofilm bacterial community. Despite this difference, sequence analysis indicated that NO treatment did not result in a significant shift in the dominant fouling species. Confocal microscopy revealed that the biomass of biopolymers and microorganisms in biofilms were all reduced on the PROLI NONOate-treated membranes, where there were reductions of 37.7% for proteins and 66.7% for microbial cells, which correlates with the reduction in TMP. These results suggest that NO treatment could be a promising strategy to control biofouling in MBRs.

  6. Modulatory role of nitric oxide in cardiac performance

    Directory of Open Access Journals (Sweden)

    Smiljić Sonja

    2014-01-01

    Full Text Available Nitric oxide is produced by almost all cardiac cells, endothelial cells, cardiomyocytes and nerve fibers. It is synthesized by an enzyme, a nitric oxide synthase, which occurs in endothelial, neural and inducible form. The distribution of nitric oxide synthase in the heart is characterized by a pronounced non-uniformity. Nitric oxide exerts its effects in physiological and pathophysiological conditions. The physiological effects of low concentrations of nitric oxide, which is released in the normal conditions under the influence of constituent enzymes, occur via cyclic guanosine monophosphate. The synthesized nitric oxide exhibits its effect in the cells where it is produced, in an autocrine manner, or by diffusing into the neighboring cells, in a paracrine manner. Nitric oxide acts by regulating the coronary vessel tonus, affecting the contractility of cardiomyocytes, generating an inotropic effect in a dose-dependent manner and controlling the cellular respiration. Other effects of nitric oxide in the cardiovascular system include the hyperpolarization of the smooth muscle cells in blood vessels, the inhibition of the monocyte adhesion, the inhibition of platelet migration, adhesion and aggregation and the proliferation of smooth muscle cells and fibroblasts. The anti-atherosclerotic effects of nitric oxide are based on these effects. Nitric oxide is a weak free radical in gaseous state, and the cytotoxic and/or the cytoprotective effects of the higher concentrations of nitric oxide are related to the chemical structure of nitric oxide as a free radical. The excessive production of nitric oxide by the activation of inducible nitric oxide synthase can lead to major irregularities in the function of cardiomyocytes and cardiac insufficiency. Understanding the nitric oxide molecular mechanisms of signaling pathways in the heart can provide a new strategic approach to prevention and treatment of cardiovascular diseases.

  7. Nitric Oxide Treatment for the Control of Reverse Osmosis Membrane Biofouling

    Science.gov (United States)

    Barnes, Robert J.; Low, Jiun Hui; Bandi, Ratnaharika R.; Tay, Martin; Chua, Felicia; Aung, Theingi; Fane, Anthony G.; Kjelleberg, Staffan

    2015-01-01

    Biofouling remains a key challenge for membrane-based water treatment systems. This study investigated the dispersal potential of the nitric oxide (NO) donor compound, PROLI NONOate, on single- and mixed-species biofilms formed by bacteria isolated from industrial membrane bioreactor and reverse osmosis (RO) membranes. The potential of PROLI NONOate to control RO membrane biofouling was also examined. Confocal microscopy revealed that PROLI NONOate exposure induced biofilm dispersal in all but two of the bacteria tested and successfully dispersed mixed-species biofilms. The addition of 40 μM PROLI NONOate at 24-h intervals to a laboratory-scale RO system led to a 92% reduction in the rate of biofouling (pressure rise over a given period) by a bacterial community cultured from an industrial RO membrane. Confocal microscopy and extracellular polymeric substances (EPS) extraction revealed that PROLI NONOate treatment led to a 48% reduction in polysaccharides, a 66% reduction in proteins, and a 29% reduction in microbial cells compared to the untreated control. A reduction in biofilm surface coverage (59% compared to 98%, treated compared to control) and average thickness (20 μm compared to 26 μm, treated compared to control) was also observed. The addition of PROLI NONOate led to a 22% increase in the time required for the RO module to reach its maximum transmembrane pressure (TMP), further indicating that NO treatment delayed fouling. Pyrosequencing analysis revealed that the NO treatment did not significantly alter the microbial community composition of the membrane biofilm. These results present strong evidence for the application of PROLI NONOate for prevention of RO biofouling. PMID:25636842

  8. Nitric oxide treatment for the control of reverse osmosis membrane biofouling.

    Science.gov (United States)

    Barnes, Robert J; Low, Jiun Hui; Bandi, Ratnaharika R; Tay, Martin; Chua, Felicia; Aung, Theingi; Fane, Anthony G; Kjelleberg, Staffan; Rice, Scott A

    2015-04-01

    Biofouling remains a key challenge for membrane-based water treatment systems. This study investigated the dispersal potential of the nitric oxide (NO) donor compound, PROLI NONOate, on single- and mixed-species biofilms formed by bacteria isolated from industrial membrane bioreactor and reverse osmosis (RO) membranes. The potential of PROLI NONOate to control RO membrane biofouling was also examined. Confocal microscopy revealed that PROLI NONOate exposure induced biofilm dispersal in all but two of the bacteria tested and successfully dispersed mixed-species biofilms. The addition of 40 μM PROLI NONOate at 24-h intervals to a laboratory-scale RO system led to a 92% reduction in the rate of biofouling (pressure rise over a given period) by a bacterial community cultured from an industrial RO membrane. Confocal microscopy and extracellular polymeric substances (EPS) extraction revealed that PROLI NONOate treatment led to a 48% reduction in polysaccharides, a 66% reduction in proteins, and a 29% reduction in microbial cells compared to the untreated control. A reduction in biofilm surface coverage (59% compared to 98%, treated compared to control) and average thickness (20 μm compared to 26 μm, treated compared to control) was also observed. The addition of PROLI NONOate led to a 22% increase in the time required for the RO module to reach its maximum transmembrane pressure (TMP), further indicating that NO treatment delayed fouling. Pyrosequencing analysis revealed that the NO treatment did not significantly alter the microbial community composition of the membrane biofilm. These results present strong evidence for the application of PROLI NONOate for prevention of RO biofouling.

  9. Wireless platform for controlled nitric oxide releasing optical fibers for mediating biological response to implanted devices.

    Science.gov (United States)

    Starrett, Michael A; Nielsen, Matthew; Smeenge, David M; Romanowicz, Genevieve E; Frost, Megan C

    2012-12-01

    Despite the documented potential to leverage nitric oxide generation to improve in vivo performance of implanted devices, a key limitation to current NO releasing materials tested thus far is that there has not been a means to modulate the level of NO release after it has been initiated. We report the fabrication of a wireless platform that uses light to release NO from a polymethylmethacrylate (PMMA) optical fiber coated with an S-nitroso-N-acetylpenicillamine derivatized polydimethylsiloxane (SNAP-PDMS). We demonstrate that a VAOL-5GSBY4 LED (λ(dominant)=460 nm) can be used as a dynamic trigger to vary the level of NO released from 500 μm diameter coated PMMA. The ability to generate programmable sequences of NO flux from the surface of these coated fibers offers precise spatial and temporal control over NO release and provides a platform to begin the systematic study of in vivo physiological response to implanted devices. NO surface fluxes up to 3.88 ± 0.57 × 10(-10)mol cm(-2)min(-1) were achieved with -100 μm thick coatings on the fibers and NO flux was pulsed, ramped and held steady using the wireless platform developed. We demonstrate the NO release is linearly proportional to the drive current applied to the LED (and therefore level of light produced from the LED). This system allow the surface flux of NO from the fibers to be continuously changed, providing a means to determine the level and duration of NO needed to mediate physiological response to blood contacting and subcutaneous implants and will ultimately lead to the intelligent design of NO releasing materials tailored to specific patterns of NO release needed to achieve reliable in vivo performance for intravascular and subcutaneous sensors and potentially for a wide variety of other implanted biomedical devices.

  10. Nitric oxide, an iceberg in cardiovascular physiology: far beyond vessel tone control.

    Science.gov (United States)

    Rubio, Armando Rojas; Morales-Segura, Miguel A

    2004-01-01

    The endothelium is now recognized not only as a physical barrier between blood and vascular wall, but also as an important and strategically located organ with multiple endocrine and paracrine functions. By releasing vasoactive substances, the endothelium acts as an inhibitory regulator of vascular contraction, leukocyte adhesion, vascular smooth muscle cell growth, and platelet aggregation. This review intends to demonstrate how much the picture of the biological functions of nitric oxide has changed in cardiovascular physiology, extending beyond its vessel-relaxing activity, as well as to highlight new insights into the factors affecting its bioavailability and regulation in relation with many cardiovascular diseases.

  11. Controlled Nitric Oxide Production via O(1D) + N2O Reactions for Use in Oxidation Flow Reactor Studies

    Science.gov (United States)

    Lambe, Andrew; Massoli, Paola; Zhang, Xuan; Canagaratna, Manjula; Nowak, John; Daube, Conner; Yan, Chao; Nie, Wei; Onasch, Timothy; Jayne, John; hide

    2017-01-01

    Oxidation flow reactors that use low-pressure mercury lamps to produce hydroxyl (OH) radicals are an emerging technique for studying the oxidative aging of organic aerosols. Here, ozone (O3) is photolyzed at 254 nm to produce O(1D) radicals, which react with water vapor to produce OH. However, the need to use parts-per-million levels of O3 hinders the ability of oxidation flow reactors to simulate NOx-dependent secondary organic aerosol (SOA) formation pathways. Simple addition of nitric oxide (NO) results in fast conversion of NOx (NO+NO2) to nitric acid (HNO3), making it impossible to sustain NOx at levels that are sufficient to compete with hydroperoxy (HO2) radicals as a sink for organic peroxy (RO2) radicals. We developed a new method that is well suited to the characterization of NOx-dependent SOA formation pathways in oxidation flow reactors. NO and NO2 are produced via the reaction O(1D)+N2O->2NO, followed by the reaction NO+O3->NO2+O2. Laboratory measurements coupled with photochemical model simulations suggest that O(1D)+N2O reactions can be used to systematically vary the relative branching ratio of RO2 +NO reactions relative to RO2 +HO2 and/or RO2+RO2 reactions over a range of conditions relevant to atmospheric SOA formation. We demonstrate proof of concept using high-resolution time-of-flight chemical ionization mass spectrometer (HR-ToF-CIMS) measurements with nitrate (NO-3 ) reagent ion to detect gas-phase oxidation products of isoprene and -pinene previously observed in NOx-influenced environments and in laboratory chamber experiments.

  12. Controlled nitric oxide production via O(1D) + N2O reactions for use in oxidation flow reactor studies

    Science.gov (United States)

    Lambe, Andrew; Massoli, Paola; Zhang, Xuan; Canagaratna, Manjula; Nowak, John; Daube, Conner; Yan, Chao; Nie, Wei; Onasch, Timothy; Jayne, John; Kolb, Charles; Davidovits, Paul; Worsnop, Douglas; Brune, William

    2017-06-01

    Oxidation flow reactors that use low-pressure mercury lamps to produce hydroxyl (OH) radicals are an emerging technique for studying the oxidative aging of organic aerosols. Here, ozone (O3) is photolyzed at 254 nm to produce O(1D) radicals, which react with water vapor to produce OH. However, the need to use parts-per-million levels of O3 hinders the ability of oxidation flow reactors to simulate NOx-dependent secondary organic aerosol (SOA) formation pathways. Simple addition of nitric oxide (NO) results in fast conversion of NOx (NO + NO2) to nitric acid (HNO3), making it impossible to sustain NOx at levels that are sufficient to compete with hydroperoxy (HO2) radicals as a sink for organic peroxy (RO2) radicals. We developed a new method that is well suited to the characterization of NOx-dependent SOA formation pathways in oxidation flow reactors. NO and NO2 are produced via the reaction O(1D) + N2O → 2NO, followed by the reaction NO + O3 → NO2 + O2. Laboratory measurements coupled with photochemical model simulations suggest that O(1D) + N2O reactions can be used to systematically vary the relative branching ratio of RO2 + NO reactions relative to RO2 + HO2 and/or RO2 + RO2 reactions over a range of conditions relevant to atmospheric SOA formation. We demonstrate proof of concept using high-resolution time-of-flight chemical ionization mass spectrometer (HR-ToF-CIMS) measurements with nitrate (NO3-) reagent ion to detect gas-phase oxidation products of isoprene and α-pinene previously observed in NOx-influenced environments and in laboratory chamber experiments.

  13. INDUCTION OF NITRIC OXIDE SYNTHASE AND ASSOCIATED TOXICITY IN LIVERS OF HARDHEAD CATFISH, ARIUS FELIS, FROM CONTROL AND EPIZOOTIC SITES

    Science.gov (United States)

    Earlier work with a live channel catfish (Ictalurus punctatus) pathogen, Edwardsiella ictaluri, demonstrated the induction of nitric oxide synthase (NOS) in the head kidney, paralleling enteric septicemia (Hawke et al. 1981; Schoor and Plumb 1994). However, another study exposing...

  14. Role of nitric oxide in control of prolactin release by the adenohypophysis.

    Science.gov (United States)

    Duvilanski, B H; Zambruno, C; Seilicovich, A; Pisera, D; Lasaga, M; Diaz, M C; Belova, N; Rettori, V; McCann, S M

    1995-01-01

    Nitric oxide synthase-containing cells were visualized in the anterior pituitary gland by immunocytochemistry. Consequently, we began an evaluation of the possible role of NO in the control of anterior pituitary function. Prolactin is normally under inhibitory hypothalamic control, and in vitro the gland secretes large quantities of the hormone. When hemipituitaries were incubated for 30 min in the presence of sodium nitroprusside, a releaser of NO, prolactin release was inhibited. This suppression was completely blocked by the scavenger of NO, hemoglobin. Analogs of arginine, such as NG-monomethyl-L-arginine (NMMA, where NG is the terminal guanidino nitrogen) and nitroarginine methyl ester, inhibit NO synthase. Incubation of hemipituitaries with either of these compounds significantly increased prolactin release. Since in other tissues most of the actions of NO are mediated by activation of soluble guanylate cyclase with the formation of cyclic GMP, we evaluated the effects of cyclic GMP on prolactin release. Cyclic GMP (10 mM) produced an approximately 40% reduction in prolactin release. Prolactin release in vivo and in vitro can be stimulated by several peptides, which include vasoactive intestinal polypeptide and substance P. Consequently, we evaluated the possible role of NO in these stimulations by incubating the glands in the presence of either of these peptides alone or in combination with NMMA. In the case of vasoactive intestinal polypeptide, the significant stimulation of prolactin release was augmented by NMMA to give an additive effect. In the case of substance P, there was a smaller but significant release of prolactin that was not significantly augmented by NMMA. We conclude that NO has little effect on the stimulatory action of these two peptides on prolactin release. Dopamine (0.1 microM), an inhibitor of prolactin release, reduced prolactin release, and this inhibitory action was significantly blocked by either hemoglobin (20 micrograms/ml) or

  15. A Comparison of the Effects of Neuronal Nitric Oxide Synthase and Inducible Nitric Oxide Synthase Inhibition on Cartilage Damage

    Directory of Open Access Journals (Sweden)

    Nevzat Selim Gokay

    2016-01-01

    Full Text Available The objective of this study was to investigate the effects of selective inducible nitric oxide synthase and neuronal nitric oxide synthase inhibitors on cartilage regeneration. The study involved 27 Wistar rats that were divided into five groups. On Day 1, both knees of 3 rats were resected and placed in a formalin solution as a control group. The remaining 24 rats were separated into 4 groups, and their right knees were surgically damaged. Depending on the groups, the rats were injected with intra-articular normal saline solution, neuronal nitric oxide synthase inhibitor 7-nitroindazole (50 mg/kg, inducible nitric oxide synthase inhibitor amino-guanidine (30 mg/kg, or nitric oxide precursor L-arginine (200 mg/kg. After 21 days, the right and left knees of the rats were resected and placed in formalin solution. The samples were histopathologically examined by a blinded evaluator and scored on 8 parameters. Although selective neuronal nitric oxide synthase inhibition exhibited significant (P=0.044 positive effects on cartilage regeneration following cartilage damage, it was determined that inducible nitric oxide synthase inhibition had no statistically significant effect on cartilage regeneration. It was observed that the nitric oxide synthase activation triggered advanced arthrosis symptoms, such as osteophyte formation. The fact that selective neuronal nitric oxide synthase inhibitors were observed to have mitigating effects on the severity of the damage may, in the future, influence the development of new agents to be used in the treatment of cartilage disorders.

  16. [Nitric oxide and lipid peroxidation].

    Science.gov (United States)

    Cristol, J P; Maggi, M F; Guérin, M C; Torreilles, J; Descomps, B

    1995-01-01

    Nitric oxide (NO) is a free radical produced enzymatically in biological systems from the guanidino group of L-arginine. Its large spectrum of biological effects is achieved through chemical interactions with different targets including oxygen (O2), superoxide (O2o-) and other oxygen reactive species (ROS), transition metals and thiols. Superoxide anions and other ROS have been reported to react with NO to produce peroxynitrite anions that can decompose to form nitrogen dioxide (NO2) and hydroxyl radial (OHo). Thus, NO has been reported to have a dual effect on lipid peroxidation (prooxidant via the peroxynitrite or antioxydant via the chelation of ROS). In the present study we have investigated in different models the in vitro and in vivo action of NO on lipid peroxidation. Copper-induced LDL oxidation were used as an in vitro model. Human LDL (100 micrograms ApoB/ml) were incubated in oxygene-saturated PBS buffer in presence or absence of Cu2+ (2.5 microM) with increasing concentrations of NO donnors (sodium nitroprussiate or nitroso-glutathione). LDL oxidation was monitored continuously for conjugated diene formation (234 nm) and 4-hydroxynonenal (HNE) accumulation. Exogenous NO prevents in a dose dependent manner the progress of copper-induced oxidation. Ischaemia-reperfusion injury (I/R), characterized by an overproduction of ROS, is used as an in vivo model. Anaesthetized rats were submitted to 1 hour renal ischaemia following by 2 hours of reperfusion. Sham-operated rats (SOP) were used as control. Lipid peroxidation was evaluated by measuring the HNE accumulated in rats kidneys in presence or absence of L-arginine or D-arginine infusion. L-arginine, but not D-arginine, enhances HNE accumulation in I/R but not in SOP (< 0.050 pmol/g tissue in SOP versus 0.6 nmol/g tissue in I/R), showing that, in this experimental conditions, NO produced from L-arginine, enhances the toxicity of ROS. This study shows that the pro- or antioxydant effects of NO are different

  17. Nitric oxide controls fat deposition in dystrophic skeletal muscle by regulating fibro-adipogenic precursor differentiation.

    Science.gov (United States)

    Cordani, Nicoletta; Pisa, Viviana; Pozzi, Laura; Sciorati, Clara; Clementi, Emilio

    2014-04-01

    Duchenne muscular dystrophy (DMD) is an hereditary disease characterized by loss of muscle fibers and their progressive substitution by fat and fibrous tissue. Mesenchymal fibro-adipogenic progenitors (FAPs) expressing the platelet-derived growth factor receptor alpha (PDGFRα) are an important source of fibrosis and adipogenesis in dystrophic skeletal muscle. Among the therapies suggested for dystrophy are those based on nitric oxide (NO) donating drugs, the administration of which slows disease progression. NO has been shown to act by enhancing the regenerative potential of the diseased muscle. Whether it acts also by inhibiting fibrosis and adipogenesis was not known. Here, we show in vitro that NO regulates FAP fate through inhibition of their differentiation into adipocytes. In mdx mice, an animal model of DMD, treatment with the NO donating drug molsidomine reduced the number of PDGFRα(+) cells as well as the deposition of both skeletal muscle fat and connective tissues. Inhibition of adipogenesis was due to NO-induced increased expression of miR-27b leading to downregulation of peroxisome proliferator-activated receptors gamma (Pparγ1) expression in a pathway independent of cGMP generation. These findings reveal an additional effect of NO in dystrophic muscle that conceivably synergizes with its known effects on regeneration improvement and explain why NO-based therapies appear effective in the treatment of muscular dystrophy.

  18. Control of Disease Tolerance to Malaria by Nitric Oxide and Carbon Monoxide

    Directory of Open Access Journals (Sweden)

    Viktória Jeney

    2014-07-01

    Full Text Available Nitric oxide (NO and carbon monoxide (CO are gasotransmitters that suppress the development of severe forms of malaria associated with Plasmodium infection. Here, we addressed the mechanism underlying their protective effect against experimental cerebral malaria (ECM, a severe form of malaria that develops in Plasmodium-infected mice, which resembles, in many aspects, human cerebral malaria (CM. NO suppresses the pathogenesis of ECM via a mechanism involving (1 the transcription factor nuclear factor erythroid 2-related factor 2 (NRF-2, (2 induction of heme oxygenase-1 (HO-1, and (3 CO production via heme catabolism by HO-1. The protection afforded by NO is associated with inhibition of CD4+ T helper (TH and CD8+ cytotoxic (TC T cell activation in response to Plasmodium infection via a mechanism involving HO-1 and CO. The protective effect of NO and CO is not associated with modulation of host pathogen load, suggesting that these gasotransmitters establish a crosstalk-conferring disease tolerance to Plasmodium infection.

  19. Resveratrol and Endothelial Nitric Oxide

    Directory of Open Access Journals (Sweden)

    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.

  20. Novel device for continuous spatial control and temporal delivery of nitric oxide for in vitro cell culture

    Directory of Open Access Journals (Sweden)

    Genevieve E. Romanowicz

    2013-01-01

    Full Text Available Nitric oxide (NO is an ubiquitous signaling molecule of intense interest in many physiological processes. Nitric oxide is a highly reactive free radical gas that is difficult to deliver with precise control over the level and timing that cells actually experience. We describe and characterize a device that allows tunable fluxes and patterns of NO to be generated across the surface upon which cells are cultured. The system is based on a quartz microscope slide that allows for controlled light levels to be applied to a previously described photosensitive NO-releasing polydimethylsiloxane (PDMS. Cells are cultured in separate wells that are either NO-releasing or a chemically similar PDMS that does not release NO. Both wells are then top coated with DowCorning RTV-3140 PDMS and a polydopamine/gelatin layer to allow cells to grow in the culture wells. When the waveguide is illuminated, the surface of the quartz slide propagates light such that the photosensitive polymer is evenly irradiated and generates NO across the surface of the cell culture well and no light penetrates into the volume of the wells where cells are growing. Mouse smooth muscle cells (MOVAS were grown in the system in a proof of principle experiment, whereby 60% of the cells were present in the NO-releasing well compared to control wells after 17 h. The compelling advantage of illuminating the NO-releasing polymers with the waveguide system is that light can be used to tunably control NO release while avoiding exposing cells to optical radiation. This device provides means to quantitatively control the surface flux, timing and duration of NO cells experience and allows for systematic study of cellular response to NO generated at the cell/surface interface in a wide variety of studies.

  1. 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

  2. Reactive Oxygen Species and Nitric Oxide Control Early Steps of the Legume – Rhizobium Symbiotic Interaction

    Science.gov (United States)

    Damiani, Isabelle; Pauly, Nicolas; Puppo, Alain; Brouquisse, Renaud; Boscari, Alexandre

    2016-01-01

    The symbiotic interaction between legumes and nitrogen-fixing rhizobium bacteria leads to the formation of a new organ, the nodule. Early steps of the interaction are characterized by the production of bacterial Nod factors, the reorientation of root-hair tip growth, the formation of an infection thread (IT) in the root hair, and the induction of cell division in inner cortical cells of the root, leading to a nodule primordium formation. Reactive oxygen species (ROS) and nitric oxide (NO) have been detected in early steps of the interaction. ROS/NO are determinant signals to arbitrate the specificity of this mutualistic association and modifications in their content impair the development of the symbiotic association. The decrease of ROS level prevents root hair curling and ITs formation, and that of NO conducts to delayed nodule formation. In root hairs, NADPH oxidases were shown to produce ROS which could be involved in the hair tip growth process. The use of enzyme inhibitors suggests that nitrate reductase and NO synthase-like enzymes are the main route for NO production during the early steps of the interaction. Transcriptomic analyses point to the involvement of ROS and NO in the success of the infection process, the induction of early nodulin gene expression, and the repression of plant defense, thereby favoring the establishment of the symbiosis. The occurrence of an interplay between ROS and NO was further supported by the finding of both S-sulfenylated and S-nitrosylated proteins during early symbiotic interaction, linking ROS/NO production to a redox-based regulation of the symbiotic process. PMID:27092165

  3. Quantum Diffusion-Controlled Chemistry: Reactions of Atomic Hydrogen with Nitric Oxide in Solid Parahydrogen.

    Science.gov (United States)

    Ruzi, Mahmut; Anderson, David T

    2015-12-17

    Our group has been working to develop parahydrogen (pH2) matrix isolation spectroscopy as a method to study low-temperature condensed-phase reactions of atomic hydrogen with various reaction partners. Guided by the well-defined studies of cold atom chemistry in rare-gas solids, the special properties of quantum hosts such as solid pH2 afford new opportunities to study the analogous chemical reactions under quantum diffusion conditions in hopes of discovering new types of chemical reaction mechanisms. In this study, we present Fourier transform infrared spectroscopic studies of the 193 nm photoinduced chemistry of nitric oxide (NO) isolated in solid pH2 over the 1.8 to 4.3 K temperature range. Upon short-term in situ irradiation the NO readily undergoes photolysis to yield HNO, NOH, NH, NH3, H2O, and H atoms. We map the postphotolysis reactions of mobile H atoms with NO and document first-order growth in HNO and NOH reaction products for up to 5 h after photolysis. We perform three experiments at 4.3 K and one at 1.8 K to permit the temperature dependence of the reaction kinetics to be quantified. We observe Arrhenius-type behavior with a pre-exponential factor of A = 0.036(2) min(-1) and Ea = 2.39(1) cm(-1). This is in sharp contrast to previous H atom reactions we have studied in solid pH2 that display definitively non-Arrhenius behavior. The contrasting temperature dependence measured for the H + NO reaction is likely related to the details of H atom quantum diffusion in solid pH2 and deserves further study.

  4. Reactive oxygen species and nitric oxide control early steps of the legume – Rhizobium symbiotic interaction

    Directory of Open Access Journals (Sweden)

    Isabelle eDamiani

    2016-04-01

    Full Text Available The symbiotic interaction between legumes and nitrogen-fixing rhizobium bacteria leads to the formation of a new organ, the nodule. Early steps of the interaction are characterized by the production of bacterial Nod factors, the reorientation of root-hair tip growth, the formation of an infection thread in the root hair, and the induction of cell division in inner cortical cells of the root, leading to a nodule primordium formation. Reactive oxygen species (ROS and nitric oxide (NO have been detected in early steps of the interaction. ROS/NO are determinant signals to arbitrate the specificity of this mutualistic association and modifications in their content impair the development of the symbiotic association. The decrease of ROS level prevents root hair curling and infection threads formation, and that of NO conducts to delayed nodule formation. In root hairs, NADPH oxidases were shown to produce ROS which could be involved in the hair tip growth process. The use of enzyme inhibitors suggests that nitrate reductase and NO synthase-like enzymes are the main route for NO production during the early steps of the interaction. Transcriptomic analyses point to the involvement of ROS and NO in the success of the infection process, the induction of early nodulin gene expression, and the repression of plant defense, thereby favoring the establishment of the symbiosis. The occurrence of an interplay between ROS and NO was further supported by the finding of both S-sulfenylated and S-nitrosylated proteins during early symbiotic interaction, linking ROS/NO production to a redox-based regulation of the symbiotic process.

  5. Double blind, randomized controlled trial, to evaluate the effectiveness of a controlled nitric oxide releasing patch versus meglumine antimoniate in the treatment of cutaneous leishmaniasis [NCT00317629

    Directory of Open Access Journals (Sweden)

    Silva Federico A

    2006-05-01

    Full Text Available Abstract Background Cutaneous Leishmaniasis is a worldwide disease, endemic in 88 countries, that has shown an increasing incidence over the last two decades. So far, pentavalent antimony compounds have been considered the treatment of choice, with a percentage of cure of about 85%. However, the high efficacy of these drugs is counteracted by their many disadvantages and adverse events. Previous studies have shown nitric oxide to be a potential alternative treatment when administered topically with no serious adverse events. However, due to the unstable nitric oxide release, the topical donors needed to be applied frequently, making the adherence to the treatment difficult. The electrospinning technique has allowed the production of a multilayer transdermal patch that produces a continuous and stable nitric oxide release. The main objective of this study is to evaluate this novel nitric oxide topical donor for the treatment of cutaneous leishmaniasis. Methods and design A double-blind, randomized, double-masked, placebo-controlled clinical trial, including 620 patients from endemic areas for Leishmaniasis in Colombia was designed to investigate whether this patch is as effective as meglumine antimoniate for the treatment of cutaneous leishmaniasis but with less adverse events. Subjects with ulcers characteristic of cutaneous leishmaniasis will be medically evaluated and laboratory tests and parasitological confirmation performed. After checking the inclusion/exclusion criteria, the patients will be randomly assigned to one of two groups. During 20 days Group 1 will receive simultaneously meglumine antimoniate and placebo of nitric oxide patches while Group 2 will receive placebo of meglumine antimoniate and active nitric oxide patches. During the treatment visits, the medications will be daily administered and the presence of adverse events assessed. During the follow-up, the research group will visit the patients at days 21, 45, 90 and 180. The

  6. Copper Complex in Poly(vinyl chloride) as a Nitric Oxide-Generating Catalyst for the Control of Nitrifying Bacterial Biofilms.

    Science.gov (United States)

    Wonoputri, Vita; Gunawan, Cindy; Liu, Sanly; Barraud, Nicolas; Yee, Lachlan H; Lim, May; Amal, Rose

    2015-10-14

    In this study, catalytic generation of nitric oxide by a copper(II) complex embedded within a poly(vinyl chloride) matrix in the presence of nitrite (source of nitric oxide) and ascorbic acid (reducing agent) was shown to effectively control the formation and dispersion of nitrifying bacteria biofilms. Amperometric measurements indicated increased and prolonged generation of nitric oxide with the addition of the copper complex when compared to that with nitrite and ascorbic acid alone. The effectiveness of the copper complex-nitrite-ascorbic acid system for biofilm control was quantified using protein analysis, which showed enhanced biofilm suppression when the copper complex was used in comparison to that with nitrite and ascorbic acid treatment alone. Confocal laser scanning microscopy (CLSM) and LIVE/DEAD staining revealed a reduction in cell surface coverage without a loss of viability with the copper complex and up to 5 mM of nitrite and ascorbic acid, suggesting that the nitric oxide generated from the system inhibits proliferation of the cells on surfaces. Induction of nitric oxide production by the copper complex system also triggered the dispersal of pre-established biofilms. However, the addition of a high concentration of nitrite and ascorbic acid to a pre-established biofilm induced bacterial membrane damage and strongly decreased the metabolic activity of planktonic and biofilm cells, as revealed by CLSM with LIVE/DEAD staining and intracellular adenosine triphosphate measurements, respectively. This study highlights the utility of the catalytic generation of nitric oxide for the long-term suppression and removal of nitrifying bacterial biofilms.

  7. Inducible nitric oxide synthase in renal transplantation

    NARCIS (Netherlands)

    Joles, JA; Vos, IH; Grone, HJ; Rabelink, TJ

    2002-01-01

    The importance of the endothelial isoform of nitric oxide synthase (eNOS) has been well established. Endothelium-derived nitric oxide has been shown to be essential for vascular homeostasis and modulation of eNOS has thus become a target in prevention of cardiovascular disease. The role of the induc

  8. Nitric oxide and chronic colitis

    Directory of Open Access Journals (Sweden)

    Matthew B Grisham

    1996-01-01

    Full Text Available Nitric oxide (NO is thought to play an important role in modulating the inflammatory response by virtue of its ability to affect bloodflow, leukocyte function and cell viability. The objective of this study was to assess the role that NO may play in mediating the mucosal injury and inflammation in a model of chronic granulomatous colitis using two pharmacologically different inhibitors of nitric oxide synthase (NOS. Chronic granulomatous colitis with liver and spleen inflammation was induced in female Lewis rats via the subserosal (intramural injection of peptidoglycan/polysaccharide (PG/PS derived from group A streptococci. Chronic NOS inhibition by oral administration of NG-nitro-L-arginine methyl ester (L-NAME (15 µmol/kg/day or amino-guanidine (AG (15 µmol/ kg/day was found to attenuate the PG/PS-induced increases in macroscopic colonic inflammation scores and colonic myeloperoxidase activity. Only AG -- not L-NAME – attenuated the PG/PS-induced increases in colon dry weight. Both L-NAME and AG significantly attenuated the PG/PS-induced increases in spleen weight whereas neither was effective at significantly attenuating the PG/PS-induced increases in liver weight. Although both L-NAME and AG inhibited NO production in vivo, as measured by decreases in plasma nitrite and nitrate levels, only AG produced significantly lower values (38±3 versus 83±8 µM, respectively, P<0.05. Finally, L-NAME, but not AG, administration significantly increased mean arterial pressure from 83 mmHg in colitic animals to 105 mmHg in the PG/PS+ L-NAME-treated animals (P<0.05. It is concluded that NO may play an important role in mediating some of the pathophysiology associated with this model of chronic granulomatous colitis.

  9. Serum nitric oxide and homocysteine as biomarkers of ectopic pregnancy

    OpenAIRE

    Kavitha Meiyappan; Pooja Dhiman; Soundravally Rajendiren; Krishnalatha Thayagarajan; Soundara Raghavan S

    2015-01-01

    Background: Aim of current study was to evaluate the role of serum homocysteine and nitric oxide in the diagnosis of ectopic pregnancy. Methods: The study included 32 patients with ruptured ectopic, 29 miscarriage patients and 30 normal pregnant women as controls. Fasting plasma homocysteine, serum folate, vitamin B12 levels and nitric oxide levels were estimated at the time of admission. Results: Plasma homocysteine levels were significantly lower in patients with ectopic pregnancy t...

  10. Nitric oxide bioavailability in malaria.

    Science.gov (United States)

    Sobolewski, Peter; Gramaglia, Irene; Frangos, John; Intaglietta, Marcos; van der Heyde, Henri C

    2005-09-01

    Rational development of adjunct or anti-disease therapy for severe Plasmodium falciparum malaria requires cellular and molecular definition of malarial pathogenesis. Nitric oxide (NO) is a potential target for such therapy but its role during malaria is controversial. It has been proposed that NO is produced at high levels to kill Plasmodium parasites, although the unfortunate consequence of elevated NO levels might be impaired neuronal signaling, oxidant damage and red blood cell damage that leads to anemia. In this case, inhibitors of NO production or NO scavengers might be an effective adjunct therapy. However, increasing amounts of evidence support the alternate hypothesis that NO production is limited during malaria. Furthermore, the well-documented NO scavenging by cell-free plasma hemoglobin and superoxide, the levels of which are elevated during malaria, has not been considered. Low NO bioavailability in the vasculature during malaria might contribute to pathologic activation of the immune system, the endothelium and the coagulation system: factors required for malarial pathogenesis. Therefore, restoring NO bioavailability might represent an effective anti-disease therapy.

  11. Serum nitric oxide and homocysteine as biomarkers of ectopic pregnancy

    Directory of Open Access Journals (Sweden)

    Kavitha Meiyappan

    2015-02-01

    Full Text Available Background: Aim of current study was to evaluate the role of serum homocysteine and nitric oxide in the diagnosis of ectopic pregnancy. Methods: The study included 32 patients with ruptured ectopic, 29 miscarriage patients and 30 normal pregnant women as controls. Fasting plasma homocysteine, serum folate, vitamin B12 levels and nitric oxide levels were estimated at the time of admission. Results: Plasma homocysteine levels were significantly lower in patients with ectopic pregnancy than normal pregnancy. Nitric oxide levels were significantly lower in patients with abortion. Conclusions: Patients with abortion have decreased circulating nitric oxide levels in serum while those with ectopic pregnancies have decreased homocysteine levels. [Int J Reprod Contracept Obstet Gynecol 2015; 4(1.000: 66-70

  12. 21 CFR 868.2380 - Nitric oxide analyzer.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Nitric oxide analyzer. 868.2380 Section 868.2380...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2380 Nitric oxide analyzer. (a) Identification. The nitric oxide analyzer is a device intended to measure the concentration of nitric oxide...

  13. 21 CFR 862.3080 - Breath nitric oxide test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Breath nitric oxide test system. 862.3080 Section... Systems § 862.3080 Breath nitric oxide test system. (a) Identification. A breath nitric oxide test system is a device intended to measure fractional nitric oxide in human breath. Measurement of changes...

  14. Exogenous nitric oxide inhibits Rho-associated kinase activity in patients with angina pectoris: a randomized controlled trial.

    Science.gov (United States)

    Maruhashi, Tatsuya; Noma, Kensuke; Fujimura, Noritaka; Kajikawa, Masato; Matsumoto, Takeshi; Hidaka, Takayuki; Nakashima, Ayumu; Kihara, Yasuki; Liao, James K; Higashi, Yukihito

    2015-07-01

    The RhoA/Rho-associated kinase (ROCK) pathway has a key physiological role in the pathogenesis of atherosclerosis. Increased ROCK activity is associated with cardiovascular diseases. Endogenous nitric oxide (NO) has an anti-atherosclerotic effect, whereas the exogenous NO-mediated cardiovascular effect still remains controversial. The purpose of this study was to evaluate the effect of exogenous NO on ROCK activity in patients with angina pectoris. This is a prospective, open-label, randomized, controlled study. A total of 30 patients with angina pectoris were randomly assigned to receive 40 mg day(-1) of isosorbide mononitrate (n=15, 12 men and 3 women, mean age of 63±12 years, isosorbide mononitrate group) or conventional treatment (n=15, 13 men and 2 women, mean age of 64±13 years, control group) for 12 weeks. ROCK activity in peripheral leukocytes was measured by western blot analysis. ROCK activities at 4 and 12 weeks after treatment were decreased in the isosorbide mononitrate group (0.82±0.33 at 0 week, 0.62±0.20 at 4 weeks, 0.61±0.19 at 12 weeks, n=15 in each group, Pangina pectoris.

  15. Anticonvulsant drugs, oxidative stress and nitric oxide.

    Science.gov (United States)

    Vega Rasgado, L A; Ceballos Reyes, G M; Vega-Diaz, M F

    2011-01-01

    Nitric Oxide (NO) is thought to play a fundamental role in the genesis and the spreading of epileptiform hyperactivity, although its function is unclear and controversial. As a free radical, NO may cause oxidative stress, which is emerging as an important mechanism in the etiology of seizure-induced neuronal death. Here we investigated the role of NO in seizure mechanisms through oxidative stress generation by studying the effect of anticonvulsant drugs such as amino oxyacetic acid (AAOA), valproate (VALP), diazepam (DIAZ) and gabapentin (GBPTNA) on oxidative stress in the brain, estimated as free carbonyls by the method of Dalle and Rossi, and by measuring NO by the indirect method based on the Griess reaction. Results show that, except for AAOA and VALP, anticonvulsants did not significantly affect or decreased free carbonyls, but reversed the oxidative stress produced by pentylenetetrazole (PTZ) induced convulsions. Anticonvulsants except AAOA diminished NO levels and with the exception of VALP, counteracted the increase in NO generated by PTZ. Anticonvulsants decreased oxidative stress and NO especially in hippocampus (HI) and cortex (CX), and reversed PTZ effects on both parameters. PTZ diminished NO in HI, which could be explained since PTZ caused an increase on endothelial NO synthase but a decrease in neuronal NOS expression in this brain area. Since the drugs studied are modulating GABA levels, our results suggest that seizures generated by alterations in GABAergic transmission produce oxidative stress caused by NO, which can be reversed by anticonvulsants. The effects described differ among the brain regions studied and the NO synthase isoform affected.

  16. Processes regulating nitric oxide emissions from soils

    DEFF Research Database (Denmark)

    Pilegaard, Kim

    2013-01-01

    Nitric oxide (NO) is a reactive gas that plays an important role in atmospheric chemistry by influencing the production and destruction of ozone and thereby the oxidizing capacity of the atmosphere. NO also contributes by its oxidation products to the formation of acid rain. The major sources...

  17. NITRIC OXIDE SYNTHESIS IN MYOCARDIUM FOLLOWING BURN INJURY IN RATS

    Institute of Scientific and Technical Information of China (English)

    王卫东; 陈宗荣; 李蓉; 楼淑芳

    1998-01-01

    The nitric oxide and cyclic GMP production in myocardium early after burn injury in tats were investigated. Nitric oxide synthase activity was measured in cytosols from the left ventricular wall of burned rats.Cytosols from the control group animals were shown to contain mainly Ca2+ dependent nitric oxide synthase (cNOS) with small amount of Ca2+ independent nitric oxide synthase (iNOS). Following burn injury,there was a marked increase in iNOS activity with a peak at 8h post-butyl, however, myocardial cNOS activity was found to decline obviously. Parallel to iNOS induction there was a significant increase in myocardial nitric oxide and cyelic GMP production. All these chenges were alleviated by treatment of the rats with dexamethasone. Since increases in cyclic GMP levels in the heart were associated with reduced myocardial contractility, it is possible that enhanced production of nitric oxide by a Ca2+ independent NO synthase accounts, at least in part, for the depression of myocardial contractility seen in burn animals and patients.

  18. Useful and harmful effects of nitric oxide

    Directory of Open Access Journals (Sweden)

    Jović Slavoljub

    2013-01-01

    Full Text Available In living sistems synthesis of nitric oxide occurs during metabolism from Larginin, nitrite and ascorbate. Being very significant carrier of information within numerous both physiological and pathological proceses in mammals' organisms, nitric oxid could possibly be useful as well as harmful. Nitric oxide synthesis is adjuvant in a healthy organism because it represents the basic molecule for understanding numerous processes in neurology, psychology, immunology and varios related fields. In other words, nitric oxide participate in number of physiological processes, such as: transmission of nerve signals (neurotransmitter role, regulation of smooth muscle tissue relaxation (eg. vasodilatation, peristaltic movements, immunomodulation, mastocyte activation, development of inflammatory response, apoptosis regulation, angiogenesis and glucose metabolism, normal heart functioning and antioxidation role. Besides being useful, nitric oxide can be harmful as well, because it has one unpaired electron, so consequently it is susceptible to oxidation becoming a stable free radical. Being such, it reacts quickly with superoxide-anion radical, givind at first an extremely reactive peroxinitrite anion, and subsequently peroxidnitrite acid. This acid is very dangerous causing thiol groups oxidation, tyrosine and phenylalanine nitrosylation, lipid oxidation, DNK chain splitting, nitrification and nucleic bases deamination. These damages of macromolecules can cause a series of undesirable changes which subsequently distub functions of molecules, and thus of cells, tissues and even organs. [Projekat Ministarstva nauke Republike Srbije, br. 173034 i br. 31085

  19. Fractional exhaled nitric oxide has a good correlation with asthma control and lung function in latino children with asthma.

    Science.gov (United States)

    Soto-Ramos, Mario; Castro-Rodríguez, Jose A; Hinojos-Gallardo, Luis Carlos; Hernández-Saldaña, Raul; Cisneros-Castolo, Martin; Carrillo-Rodríguez, Victor

    2013-08-01

    Although the measurement of fractional exhaled nitric oxide (FE(NO)) has been recommended for observational studies and clinical trials of asthma, FE(NO) has not been examined in studies of childhood asthma in Latin America, To examine the relationship between FE(NO) and indicators of disease control or severity [asthma control test/childhood asthma control test (ACT/C-ACT), lung function, and exercise challenge test (ECT)] in Mexican children with persistent asthma, Children (6-18 years of age) with persistent asthma were consecutively recruited in a tertiary asthma clinic and divided into two groups, e.g. FE(NO) ppb) and ≥20 ppb.Adequate FE(NO) measurements were obtained in 134 (83.2%) of 161 eligible children, Children with FE(NO)ppb had significantly higher scores on the ACT/C-ACT than those with FE(NO) ≥ 20 ppb (median [interquartile range] :23 [20.8-25] vs. 21 [18-24], p = .002, respectively). Compared to children with FE(NO) ≥20 ppb, those with FE(NO) ppb had a higher baseline predicted forced expiratory volume (FEV(1)) [94% (92.5%-99.4%) vs. 83% (81%-89.9%), p = .001] and a lower probability of having a positive ECT (42.7% vs. 71.2%, p = .001). In addition, FE(NO) was significantly inversely correlated with the participants' ACT/C-ACT score and predicted FEV1, and directly correlated with positive ECT, CONCLUSION: Among Mexican children with persistent asthma, low levels of FE(NO) ( ppb) are associated with better asthma control, and higher lung function.

  20. The Oxidation of Hydrazine by Nitric Acid

    Energy Technology Data Exchange (ETDEWEB)

    Karraker, D.G.

    2001-07-02

    Hydrazine nitrate-nitric acid solutions are used in the ion exchange process for separating Pu-238 and Np-237 and have been found to dissolve plutonium metal in a manner advantageous to SRP metal recovery operations. Laboratory tests on the stability of hydrazine in nitric acid solutions were performed to obtain accurate data, and the results of these tests are reported here. These tests provide sufficient information to specify temperature control for hydrazine-nitric acid solutions in plant processes.

  1. Nitric oxide facilitates GABAergic neurotransmission in the cat oculomotor system: a physiological mechanism in eye movement control.

    Science.gov (United States)

    Moreno-López, Bernardo; Escudero, Miguel; Estrada, Carmen

    2002-04-01

    Nitric oxide (NO) synthesis by prepositus hypoglossi (PH) neurons is necessary for the normal performance of horizontal eye movements. We have previously shown that unilateral injections of NO synthase (NOS) inhibitors into the PH nucleus of alert cats produce velocity imbalance without alteration of the eye position control, both during spontaneous eye movements and the vestibulo-ocular reflex (VOR). This NO effect is exerted on the dorsal PH neuropil, whose fibres increase their cGMP content when stimulated by NO. In an attempt to determine whether NO acts by modulation of a specific neurotransmission system, we have now compared the oculomotor effects of NOS inhibition with those produced by local blockade of glutamatergic, GABAergic or glycinergic receptors in the PH nucleus of alert cats. Both glutamatergic antagonists used, 2-amino-5-phosphonovaleric acid (APV) and 2,3-dihydro-6-nitro-7-sulphamoyl-benzo quinoxaline (NBQX), induced a nystagmus contralateral to that observed upon NOS inhibition, and caused exponential eye position drift. In contrast, bicuculline and strychnine induced eye velocity alterations similar to those produced by NOS inhibitors, suggesting that NO oculomotor effects were due to facilitation of some inhibitory input to the PH nucleus. To investigate the anatomical location of the putative NO target neurons, the retrograde tracer Fast Blue was injected in one PH nucleus, and the brainstem sections containing Fast Blue-positive neurons were stained with double immunohistochemistry for NO-sensitive cGMP and glutamic acid decarboxylase. GABAergic neurons projecting to the PH nucleus and containing NO-sensitive cGMP were found almost exclusively in the ipsilateral medial vestibular nucleus and marginal zone. The results suggest that the nitrergic PH neurons control their own firing rate by a NO-mediated facilitation of GABAergic afferents from the ipsilateral medial vestibular nucleus. This self-control mechanism could play an important role

  2. Autotrophic Biofilters for Oxidation of Nitric Oxide

    Institute of Scientific and Technical Information of China (English)

    陈建孟; 陈浚; LanceHershman; 王家德; DanielP.Y.Chang

    2004-01-01

    Carbon foam—a kind of new engineering material as packing material was adopted in three biofilters with different pore dimensions and adapted autotrophic nitrite nitrobacteria to investigate the purification of nitric oxide (NO) in a gas stream. The biofilm was developed on the surface of carbon foams using nitrite as its only nitric source. The moisture in the filter was maintained by ultrasonic aerosol equipment which can minimize the thickness of the liquid film. The liquid phase nitrification test was conducted to determine the variability and the potential of performance among the three carbon foam biofilters. The investigation showed that during the NO2-—N inlet concentration of 200 g·L-1·min-1 to 800 g·L-1·min-1, the 24PPC (pores per centimeter) carbon foam biofilter had the greatest potential, achieving the NO2-—N removal efficiency of 94% to 98%. The 8PPC and 18PPC carbon foam biofilters achieved the NO2-—N removal efficiency of 15% to 21% and of 30% to 40%, respectively. The potential for this system to remove NO from a gas stream was shown on the basis of a steady removal efficiency of 41% to 50% which was attained for the 24PPC carbon foam biofilter at specified NO inlet concentration of 66.97 mg·m-3 to 267.86mg·m-3 and an empty-bed residence time of 3.5 min.

  3. Inducible nitric oxide synthase is responsible for nitric oxide release from murine pituicytes

    DEFF Research Database (Denmark)

    Kjeldsen, T H; Rivier, C; Lee, S;

    2003-01-01

    This study investigated whether pituicytes were able to produce and release nitric oxide (NO), and which type of nitric oxide synthase (NOS) would be responsible for this phenomenon. Lipopolysaccharide (LPS) 1 micro g/ml was used as inflammatory mediator. Because pituicytes are known to secrete...

  4. Effects of inhaled nitric oxide on hemostasis in healthy adults treated with heparin: a randomized, controlled, blinded crossover study

    Directory of Open Access Journals (Sweden)

    Goldstein Brahm

    2012-01-01

    Full Text Available Abstract Background Effects of nitric oxide (NO on hemostasis have been studied in various investigational settings, but data regarding inhaled NO on bleeding and platelet function are conflicting. It is not known if inhaled NO has an effect when administered with drugs that influence hemostasis. This trial evaluated effects of inhaled NO on hemostasis in the presence of heparin using aspirin as a positive control. Patients/Methods Twelve healthy adult males were enrolled in a single-center, randomized, single-blind, four-way crossover trial. Subjects received 80 ppm NO or medical air (placebo inhalation for 30 min with simultaneous injection of placebo or heparin. Aspirin capsules were used as a positive control. Parameters of hemostasis were measured before treatment and at post-treatment intervals. Results Activated clotting time (ACT, prothrombin time (PT and activated partial thromboplastin time (aPTT increased only in groups that received heparin. Areas under the curve for ACT in heparin groups receiving inhaled NO were judged to be equivalent to those receiving medical air for both 0- to 4-h (ratio: 1.00; 90% CI, 0.90-1.11 and 0- to 24-h time intervals (ratio: 1.01; 90% CI, 0.92-1.12. Changes in bleeding time and platelet aggregation were observed only in aspirin groups. No clinically significant changes in hemoglobin, red blood cell counts or haematocrit were observed in any group. Conclusions Inhaled NO, when administered with heparin, exhibited no significant additive effects on ACT, PT, aPTT, bleeding time or platelet aggregation.

  5. Light-controlled relaxation of the rat penile corpus cavernosum using NOBL-1, a novel nitric oxide releaser

    Directory of Open Access Journals (Sweden)

    Yuji Hotta

    2016-05-01

    Full Text Available Purpose: To investigate whether relaxation of the rat penile corpus cavernosum could be controlled with NOBL-1, a novel, lightcontrollable nitric oxide (NO releaser. Materials and Methods: Fifteen-week-old male Wistar-ST rats were used. The penile corpus cavernosum was prepared and used in an isometric tension study. After noradrenaline (10−5 M achieved precontraction, the penile corpus cavernosum was irradiated by light (470–500 nm with and without NOBL-1 (10−6 M. In addition, we noted rats’ responses to light with vardenafil (10−6 M, a phosphodiesterase-5 (PDE-5 inhibitor. Next, responses to light in the presence of a guanylate cyclase inhibitor, ODQ (1H-[1,2,4] oxadiazolo[4,3-a]quinoxalin-1-one (10−5 M, were measured. All measurements were performed in pretreated L-NAME (10−4 M conditions to inhibit endogenous NO production. Results: Corpus cavernosal smooth muscle, precontracted with noradrenaline, was unchanged by light irradiation in the absence of NOBL-1. However, in the presence of NOBL-1, corpus cavernosal smooth muscle, precontracted with noradrenaline, relaxed in response to light irradiation. After blue light irradiation ceased, tension returned. In addition, the light response was obviously enhanced in the presence of a PDE-5 inhibitor. Conclusions: This study showed that rat corpus cavernosal smooth muscle relaxation can be light-controlled using NOBL-1, a novel, light sensitive NO releaser. Though further in vivo studies are needed to investigate possible usefulness, NOBL-1 may be prove to be a useful tool for erectile dysfunction therapy, specifically in the field of penile rehabilitation.

  6. Central exogenous nitric oxide decreases cardiac sympathetic drive and improves baroreflex control of heart rate in ovine heart failure.

    Science.gov (United States)

    Ramchandra, Rohit; Hood, Sally G; May, Clive N

    2014-08-01

    Heart failure (HF) is associated with increased cardiac and renal sympathetic drive, which are both independent predictors of poor prognosis. A candidate mechanism for the centrally mediated sympathoexcitation in HF is reduced synthesis of the inhibitory neuromodulator nitric oxide (NO), resulting from downregulation of neuronal NO synthase (nNOS). Therefore, we investigated the effects of increasing the levels of NO in the brain, or selectively in the paraventricular nucleus of the hypothalamus (PVN), on cardiac sympathetic nerve activity (CSNA) and baroreflex control of CSNA and heart rate in ovine pacing-induced HF. The resting level of CSNA was significantly higher in the HF than in the normal group, but the resting level of RSNA was unchanged. Intracerebroventricular infusion of the NO donor sodium nitroprusside (SNP; 500 μg · ml(-1)· h(-1)) in conscious normal sheep and sheep in HF inhibited CSNA and restored baroreflex control of heart rate, but there was no change in RSNA. Microinjection of SNP into the PVN did not cause a similar cardiac sympathoinhibition in either group, although the number of nNOS-positive cells was decreased in the PVN of sheep in HF. Reduction of endogenous NO with intracerebroventricular infusion of N(ω)-nitro-l-arginine methyl ester decreased CSNA in normal but not in HF sheep and caused no change in RSNA in either group. These findings indicate that endogenous NO in the brain provides tonic excitatory drive to increase resting CSNA in the normal state, but not in HF. In contrast, exogenously administered NO inhibited CSNA in both the normal and HF groups via an action on sites other than the PVN. Copyright © 2014 the American Physiological Society.

  7. Nitric oxide, inducible nitric oxide synthase and inflammation in veterinary medicine.

    Science.gov (United States)

    Hunter, Robert P

    2002-12-01

    Inflammation is a process consisting of a complex of cytological and chemical reactions which occur in and around affected blood vessels and adjacent tissues in response to an injury caused by a physical, chemical or biological insult. Much work has been performed in the past several years investigating inducible nitric oxide synthase (NOS, EC 1.14.13.39) and nitric oxide in inflammation. This has resulted in a rapid increase in knowledge about iNOS and nitric oxide. Nitric oxide formation from inducible NOS is regulated by numerous inflammatory mediators, often with contradictory effects, depending upon the type and duration of the inflammatory insult. Equine medicine appears to have benefited the most from the increased interest in this small, inflammatory mediator. Most of the information on nitric oxide in traditional veterinary species has been produced using models or naturally occurring inflammatory diseases of this species.

  8. Patterns of osteocytic endothelial nitric oxide synthase expression in the femoral neck cortex: differences between cases of intracapsular hip fracture and controls.

    Science.gov (United States)

    Loveridge, N; Fletcher, S; Power, J; Caballero-Alías, A M; Das-Gupta, V; Rushton, N; Parker, M; Reeve, J; Pitsillides, A A

    2002-06-01

    Evidence indicates that extensive amalgamation of adjacent resorbing osteons is responsible for destroying the microstructural integrity of the femoral neck's inferior cortex in osteoporotic hip fracture. Such osteonal amalgamation is likely to involve a failure to limit excessive resorption, but its mechanistic basis remains enigmatic. Nitric oxide (NO) inhibits osteoclastic bone destruction, and in normal bone cells its generation by endothelial nitric oxide synthase (eNOS, the predominant bone isoform) is enhanced by mechanical stimuli and estrogen, which both protect against fracture. To determine whether eNOS expression in osteocytes reflects their proposed role in regulating remodeling, we have examined patterns of osteocyte eNOS immunolabeling in the femoral neck cortex of seven cases of hip fracture and seven controls (females aged 68-96 years). The density of eNOS+ cells (mm(-2)) was 53% lower in the inferior cortex of the fracture cases (p bone.

  9. Nitric oxide turnover in permeable river sediment

    DEFF Research Database (Denmark)

    Schreiber, Frank; Stief, Peter; Kuypers, Marcel M M

    2014-01-01

    We measured nitric oxide (NO) microprofiles in relation to oxygen (O2) and all major dissolved N-species (ammonium, nitrate, nitrite, and nitrous oxide [N2O]) in a permeable, freshwater sediment (River Weser, Germany). NO reaches peak concentrations of 0.13 μmol L-1 in the oxic zone and is consumed...

  10. Exhaled breath condensate nitric oxide end products and pH in controlled asthma

    Directory of Open Access Journals (Sweden)

    Ahmed Elhefny

    2012-10-01

    Conclusion: EBC-NOx is significantly higher and EBC-pH is significantly lower in asthmatic patients than in control subjects. Asthmatics receiving ICS have a lower EBC-NOx level than those not. EBC-NOx and EBC-pH were significantly correlated and both of them showed significant correlations with spirometric parameters of airway obstruction.

  11. Nitric oxide control of lower vertebrate blood vessels by vasomotor nerves.

    Science.gov (United States)

    Donald, John A; Broughton, Brad R S

    2005-10-01

    In mammals, much is understood about the endothelial and neural NO control mechanisms in the vasculature. In contrast, NO control of blood vessels in lower vertebrates is poorly understood, with the majority of research focusing on the presence of an endothelial NO system; however, its presence remains controversial. This study examined the mechanisms by which NO regulates the large blood vessels of non-mammalian vertebrates. In all species examined, the arteries and veins contained a plexus of NOS-positive perivascular nerves that included nerve bundles and fine, varicose nerve terminals. However, in the large arteries and veins of various species of fishes and amphibians, no anatomical evidence was found for endothelial NOS using both NADPH-diaphorase and eNOS immunohistochemistry. In contrast, perinuclear NOS staining was readily apparent in blue-tongue lizard, pigeon and rat, which suggested that eNOS first appeared in reptiles. Physiological analysis of NO signalling in the vascular smooth muscle of short-finned eel and cane toad could not find any evidence for endothelial NO signalling. In contrast, it appears that activation of the nitrergic vasomotor nerves is responsible for NO control of the blood vessels.

  12. Fractional exhaled nitric oxide and forced expiratory flow between 25% and 75% of vital capacity in children with controlled asthma

    Directory of Open Access Journals (Sweden)

    Ji-Yong Yoon

    2012-09-01

    Full Text Available &lt;B&gt;Purpose:&lt;/B&gt; Fractional exhaled nitric oxide (FeNO and forced expiratory flow between 25% and 75% of vital capacity (FEF&lt;sub&gt;25-75&lt;/sub&gt; are not included in routine monitoring of asthma control. We observed changes in FeNO level and FEF&lt;sub&gt;25-75&lt;/sub&gt; after FeNO-based treatment with inhaled corticosteroid (ICS in children with controlled asthma (CA. &lt;B&gt;Methods:&lt;/B&gt; We recruited 148 children with asthma (age, 8 to 16 years who had maintained asthma control and normal forced expiratory volume in the first second (FEV1 without control medication for ?#243; months. Patients with FeNO levels &gt;25 ppb were allocated to the ICStreated (FeNO-based management or untreated group (guideline-based management. Changes in spirometric values and FeNO levels from baseline were evaluated after 6 weeks. &lt;B&gt;Results:&lt;/B&gt; Ninety-three patients had FeNO levels &gt;25 ppb. These patients had lower FEF&lt;sub&gt;25-75&lt;/sub&gt; % predicted values than those with FeNO levels ?#178;5 ppb (P&lt;0.01. After 6 weeks, the geometric mean (GM FeNO level in the ICS-treated group was 45% lower than the baseline value, and the mean percent increase in FEF&lt;sub&gt;25-75&lt;/sub&gt; was 18.7% which was greater than that in other spirometric values. There was a negative correlation between percent changes in FEF&lt;sub&gt;25-75&lt;/sub&gt; and FeNO (r=-0.368, P=0.001. In contrast, the GM FeNO and spirometric values were not significantly different from the baseline values in the untreated group. &lt;B&gt;Conclusion:&lt;/B&gt; The anti-inflammatory treatment simultaneously improved the FeNO levels and FEF&lt;sub&gt;25-75&lt;/sub&gt; in CA patients when their FeNO levels were &gt;25 ppb.

  13. Nitrate tolerance impairs nitric oxide-mediated vasodilation in vivo

    DEFF Research Database (Denmark)

    Laursen, Jørn Bech; Boesgaard, Søren; Poulsen, Henrik E.;

    1996-01-01

    Nitrates, Nitrate tolerence, Nitric oxide, acetylcholine, N-acetylcholine, N-acetylcysteine, L-NAME, Rat, Anesthetized......Nitrates, Nitrate tolerence, Nitric oxide, acetylcholine, N-acetylcholine, N-acetylcysteine, L-NAME, Rat, Anesthetized...

  14. Double blind, randomized, placebo controlled clinical trial for the treatment of diabetic foot ulcers, using a nitric oxide releasing patch: PATHON

    Science.gov (United States)

    Silva, Sandra Y; Rueda, Ligia C; Márquez, Gustavo A; López, Marcos; Smith, Daniel J; Calderón, Carlos A; Castillo, Juan C; Matute, Jaime; Rueda-Clausen, Christian F; Orduz, Arturo; Silva, Federico A; Kampeerapappun, Piyaporn; Bhide, Mahesh; López-Jaramillo, Patricio

    2007-01-01

    Background Diabetes Mellitus constitutes one of the most important public health problems due to its high prevalence and enormous social and economic consequences. Diabetic foot ulcers are one of the chronic complications of diabetes mellitus and constitute the most important cause of non-traumatic amputation of inferior limbs. It is estimated that 15% of the diabetic population will develop an ulcer sometime in their lives. Although novel therapies have been proposed, there is no effective treatment for this pathology. Naturally produced nitric oxide participates in the wound healing process by stimulating the synthesis of collagen, triggering the release of chemotactic cytokines, increasing blood vessels permeability, promoting angiogenic activity, stimulating the release of epidermical growth factors, and by interfering with the bacterial mitochondrial respiratory chain. Topically administered nitric oxide has demonstrated to be effective and safe for the treatment of chronic ulcers secondary to cutaneous leishmaniasis. However, due to their unstable nitric oxide release, the topical donors needed to be applied frequently, diminishing the adherence to the treatment. This difficulty has led to the development of a multilayer polymeric transdermal patch produced by electrospinning technique that guarantees a constant nitric oxide release. The main objective of this study is to evaluate the effectiveness and safety of this novel nitric oxide releasing wound dressing for the treatment of diabetic foot ulcers. Methods and design A double-blind, placebo-controlled clinical trial, including 100 diabetic patients was designed. At the time of enrollment, a complete medical evaluation and laboratory tests will be performed, and those patients who meet the inclusion criteria randomly assigned to one of two groups. Over the course of 90 days group 1 will receive active patches and group 2 placebo patches. The patients will be seen by the research group at least every two

  15. Double blind, randomized, placebo controlled clinical trial for the treatment of diabetic foot ulcers, using a nitric oxide releasing patch: PATHON

    Directory of Open Access Journals (Sweden)

    Silva Federico A

    2007-09-01

    Full Text Available Abstract Background Diabetes Mellitus constitutes one of the most important public health problems due to its high prevalence and enormous social and economic consequences. Diabetic foot ulcers are one of the chronic complications of diabetes mellitus and constitute the most important cause of non-traumatic amputation of inferior limbs. It is estimated that 15% of the diabetic population will develop an ulcer sometime in their lives. Although novel therapies have been proposed, there is no effective treatment for this pathology. Naturally produced nitric oxide participates in the wound healing process by stimulating the synthesis of collagen, triggering the release of chemotactic cytokines, increasing blood vessels permeability, promoting angiogenic activity, stimulating the release of epidermical growth factors, and by interfering with the bacterial mitochondrial respiratory chain. Topically administered nitric oxide has demonstrated to be effective and safe for the treatment of chronic ulcers secondary to cutaneous leishmaniasis. However, due to their unstable nitric oxide release, the topical donors needed to be applied frequently, diminishing the adherence to the treatment. This difficulty has led to the development of a multilayer polymeric transdermal patch produced by electrospinning technique that guarantees a constant nitric oxide release. The main objective of this study is to evaluate the effectiveness and safety of this novel nitric oxide releasing wound dressing for the treatment of diabetic foot ulcers. Methods and design A double-blind, placebo-controlled clinical trial, including 100 diabetic patients was designed. At the time of enrollment, a complete medical evaluation and laboratory tests will be performed, and those patients who meet the inclusion criteria randomly assigned to one of two groups. Over the course of 90 days group 1 will receive active patches and group 2 placebo patches. The patients will be seen by the

  16. Nitric Oxide in Mammary Tumor Progression

    Science.gov (United States)

    1998-07-01

    de Miguel L, Monton M, Casado S, Lopez -Farre A: Endothelial cytosolic proteins bind to the 3’-untranslated region of endothelial nitric oxide...Vazquez AM. Cabrera L, Barral AM, Gen- 38. Morgan DA, Ruscetti FW, Gallo R: Selective in vitro delman R, Jondal M: Toxic effects of interleukin-2

  17. Nitric Oxide Synthase Inhibitors as Antidepressants

    DEFF Research Database (Denmark)

    Wegener, Gregers; Volke, Vallo

    2010-01-01

    been suggested to play major roles in the pathophysiology of mood and stress-related disorders. However, a few clinical and several pre-clinical studies, strongly suggest involvement of the nitric oxide (NO) signaling pathway in these disorders. Moreover, several of the conventional neurotransmitters...

  18. Nitric Oxide and the Central Nervous System

    NARCIS (Netherlands)

    E. Dzoljic (Eleonora)

    1998-01-01

    textabstractDuring the last ten years, several investigators have reported that biological effects of endothelium-derived relaxing factor (EDRF; Furchgott and Zawadzki, 1980) are actually activities of a signal molecule, nitric oxide (NO; Moncada el al., 1988). This molecule is synthesised by endoth

  19. Circulating nitric oxide products do not solely reflect nitric oxide release in cirrhosis and portal hypertension

    DEFF Research Database (Denmark)

    Afzelius, Pia; Bazeghi, Nassim; Bie, Peter;

    2011-01-01

    Patients with cirrhosis often develop a systemic vasodilatation and a hyperdynamic circulation with activation of vasoconstrictor systems such as the renin-angiotensin-aldosterone system (RAAS), and vasopressin. Increased nitric oxide (NO) synthesis has been implicated in the development...

  20. 21 CFR 868.5165 - Nitric oxide administration apparatus.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Nitric oxide administration apparatus. 868.5165... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5165 Nitric oxide administration apparatus. (a) Identification. The nitric oxide administration apparatus is a device used to add...

  1. Asymmetric dimethylarginine, oxidative stress, and vascular nitric oxide synthase in essential hypertension

    DEFF Research Database (Denmark)

    Wang, Dan; Strandgaard, Svend; Iversen, Jens

    2009-01-01

    We reported impaired endothelium-derived relaxation factor/nitric oxide (EDRF/NO) responses and constitutive nitric oxide synthase (cNOS) activity in subcutaneous vessels dissected from patients with essential hypertension (n = 9) compared with normal controls (n = 10). We now test the hypothesis...... and hypertensive subjects, the individual values for plasma levels of ADMA and HODE were both significantly (P stress in a group of hypertensive...

  2. Increased nitric oxide release and expression of endothelial and inducible nitric oxide synthases in mildly changed porcine mitral valve leaflets

    DEFF Research Database (Denmark)

    Moesgaard, Sophia G; Olsen, Lisbeth H; Viuff, Birgitte M

    2007-01-01

    BACKGROUND AND AIM OF THE STUDY: Little is known of the local role of nitric oxide (NO) in heart valves in relation to heart valve diseases. The study aim was to examine NO release and the expression of both endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) in re...

  3. Increased nitric oxide release and expression of endothelial and inducible nitric oxide synthases in mildly changed porcine mitral valve leaflets

    DEFF Research Database (Denmark)

    Moesgaard, Sophia Gry; Olsen, Lisbeth Høier; Viuff, Birgitte;

    2007-01-01

    Background and aim of the study: Little is known of the local role of nitric oxide (NO) in heart valves in relation to heart valve diseases. The study aim was to examine NO release and the expression of both endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (i...

  4. Nitric oxide-releasing polymer incorporated ointment for cutaneous wound healing.

    Science.gov (United States)

    Kang, Youngnam; Kim, Jihoon; Lee, Yeong Mi; Im, Sooseok; Park, Hansoo; Kim, Won Jong

    2015-12-28

    This work demonstrates the development of nitric oxide-releasing ointment and its potential on efficient wound healing. Nitric oxide-releasing polymer was successfully synthesized, which is composed of biocompatible Pluronic F127, branched polyethylenimine and 1-substituted diazen-1-ium-1,2-diolates. The synthesized nitric oxide-releasing polymer was incorporated into the PEG-based ointment which not only facilitated nitric oxide release in a slow manner, but also served as a moisturizer to enhance the wound healing. As compared to control groups, the nitric oxide-releasing ointment showed the accelerated wound closure with enhanced re-epithelialization, collagen deposition, and blood vessel formation in vivo. Therefore, this nitric oxide-based ointment presents the promising potential for the efficient strategy to heal the cutaneous wound.

  5. Nitric Oxide Synthases in Heart Failure

    Science.gov (United States)

    Carnicer, Ricardo; Crabtree, Mark J.; Sivakumaran, Vidhya

    2013-01-01

    Abstract Significance: The regulation of myocardial function by constitutive nitric oxide synthases (NOS) is important for the maintenance of myocardial Ca2+ homeostasis, relaxation and distensibility, and protection from arrhythmia and abnormal stress stimuli. However, sustained insults such as diabetes, hypertension, hemodynamic overload, and atrial fibrillation lead to dysfunctional NOS activity with superoxide produced instead of NO and worse pathophysiology. Recent Advances: Major strides in understanding the role of normal and abnormal constitutive NOS in the heart have revealed molecular targets by which NO modulates myocyte function and morphology, the role and nature of post-translational modifications of NOS, and factors controlling nitroso-redox balance. Localized and differential signaling from NOS1 (neuronal) versus NOS3 (endothelial) isoforms are being identified, as are methods to restore NOS function in heart disease. Critical Issues: Abnormal NOS signaling plays a key role in many cardiac disorders, while targeted modulation may potentially reverse this pathogenic source of oxidative stress. Future Directions: Improvements in the clinical translation of potent modulators of NOS function/dysfunction may ultimately provide a powerful new treatment for many hearts diseases that are fueled by nitroso-redox imbalance. Antioxid. Redox Signal. 18, 1078–1099. PMID:22871241

  6. How the location of superoxide generation influences the β-cell response to nitric oxide.

    Science.gov (United States)

    Broniowska, Katarzyna A; Oleson, Bryndon J; McGraw, Jennifer; Naatz, Aaron; Mathews, Clayton E; Corbett, John A

    2015-03-20

    Cytokines impair the function and decrease the viability of insulin-producing β-cells by a pathway that requires the expression of inducible nitric oxide synthase (iNOS) and generation of high levels of nitric oxide. In addition to nitric oxide, excessive formation of reactive oxygen species, such as superoxide and hydrogen peroxide, has been shown to cause β-cell damage. Although the reaction of nitric oxide with superoxide results in the formation of peroxynitrite, we have shown that β-cells do not have the capacity to produce this powerful oxidant in response to cytokines. When β-cells are forced to generate peroxynitrite using nitric oxide donors and superoxide-generating redox cycling agents, superoxide scavenges nitric oxide and prevents the inhibitory and destructive actions of nitric oxide on mitochondrial oxidative metabolism and β-cell viability. In this study, we show that the β-cell response to nitric oxide is regulated by the location of superoxide generation. Nitric oxide freely diffuses through cell membranes, and it reacts with superoxide produced within cells and in the extracellular space, generating peroxynitrite. However, only when it is produced within cells does superoxide attenuate nitric oxide-induced mitochondrial dysfunction, gene expression, and toxicity. These findings suggest that the location of radical generation and the site of radical reactions are key determinants in the functional response of β-cells to reactive oxygen species and reactive nitrogen species. Although nitric oxide is freely diffusible, its biological function can be controlled by the local generation of superoxide, such that when this reaction occurs within β-cells, superoxide protects β-cells by scavenging nitric oxide.

  7. CHANGES OF NITRIC OXIDE AND PROTECTIVE EFFECTS OF NITRIC OXIDE INHIBITORS IN NEWBORN RATS WITH SEPSIS

    Institute of Scientific and Technical Information of China (English)

    史源; 李华强; 潘捷; 沈际皋

    1995-01-01

    In a newborn rat model of sepsis, the changes of nitric oxide and the protective effects of methylene blue or/and dexaraethason were investigated. The results revealed that plasma nitric oxide levels were ele-cted at 6 h and peaked at 12 h after bacterial challenge. The treatment with methylene or/and dexam-etbasone was found to Munt hypoglycenua and hyperlacdcemla, to reduce the occurrence rate of loss ot re-sponse to pain, and to prolong the survival time. Moreover, therapy by dexamethasone was shown to de-crease the 24 h mortality. The results suggested that nitric coide play an important role during the course of fatal P. aeruginosa sepsis, hut it is clear that the clinical value of nitric oxide and its inhibitors need to be further studied.

  8. Nitric oxide and cardiovascular risk factors

    Directory of Open Access Journals (Sweden)

    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”.

  9. Nitric oxide and pH modulation in gynaecological cancer.

    Science.gov (United States)

    Sanhueza, Carlos; Araos, Joaquín; Naranjo, Luciano; Barros, Eric; Subiabre, Mario; Toledo, Fernando; Gutiérrez, Jaime; Chiarello, Delia I; Pardo, Fabián; Leiva, Andrea; Sobrevia, Luis

    2016-12-01

    Nitric oxide plays several roles in cellular physiology, including control of the vascular tone and defence against pathogen infection. Neuronal, inducible and endothelial nitric oxide synthase (NOS) isoforms synthesize nitric oxide. Cells generate acid and base equivalents, whose physiological intracellular concentrations are kept due to membrane transport systems, including Na(+) /H(+) exchangers and Na(+) /HCO3(-) transporters, thus maintaining a physiological pH at the intracellular (~7.0) and extracellular (~7.4) medium. In several pathologies, including cancer, cells are exposed to an extracellular acidic microenvironment, and the role for these membrane transport mechanisms in this phenomenon is likely. As altered NOS expression and activity is seen in cancer cells and because this gas promotes a glycolytic phenotype leading to extracellular acidosis in gynaecological cancer cells, a pro-inflammatory microenvironment increasing inducible NOS expression in this cell type is feasible. However, whether abnormal control of intracellular and extracellular pH by cancer cells regards with their ability to synthesize or respond to nitric oxide is unknown. We, here, discuss a potential link between pH alterations, pH controlling membrane transport systems and NOS function. We propose a potential association between inducible NOS induction and Na(+) /H(+) exchanger expression and activity in human ovary cancer. A potentiation between nitric oxide generation and the maintenance of a low extracellular pH (i.e. acidic) is proposed to establish a sequence of events in ovarian cancer cells, thus preserving a pro-proliferative acidic tumour extracellular microenvironment. We suggest that pharmacological therapeutic targeting of Na(+) /H(+) exchangers and inducible NOS may have benefits in human epithelial ovarian cancer.

  10. Controlled nitric oxide production via O(1D  + N2O reactions for use in oxidation flow reactor studies

    Directory of Open Access Journals (Sweden)

    A. Lambe

    2017-06-01

    Full Text Available Oxidation flow reactors that use low-pressure mercury lamps to produce hydroxyl (OH radicals are an emerging technique for studying the oxidative aging of organic aerosols. Here, ozone (O3 is photolyzed at 254 nm to produce O(1D radicals, which react with water vapor to produce OH. However, the need to use parts-per-million levels of O3 hinders the ability of oxidation flow reactors to simulate NOx-dependent secondary organic aerosol (SOA formation pathways. Simple addition of nitric oxide (NO results in fast conversion of NOx (NO + NO2 to nitric acid (HNO3, making it impossible to sustain NOx at levels that are sufficient to compete with hydroperoxy (HO2 radicals as a sink for organic peroxy (RO2 radicals. We developed a new method that is well suited to the characterization of NOx-dependent SOA formation pathways in oxidation flow reactors. NO and NO2 are produced via the reaction O(1D + N2O  →  2NO, followed by the reaction NO + O3  →  NO2 + O2. Laboratory measurements coupled with photochemical model simulations suggest that O(1D + N2O reactions can be used to systematically vary the relative branching ratio of RO2 + NO reactions relative to RO2 + HO2 and/or RO2 + RO2 reactions over a range of conditions relevant to atmospheric SOA formation. We demonstrate proof of concept using high-resolution time-of-flight chemical ionization mass spectrometer (HR-ToF-CIMS measurements with nitrate (NO3− reagent ion to detect gas-phase oxidation products of isoprene and α-pinene previously observed in NOx-influenced environments and in laboratory chamber experiments.

  11. Endothelial nitric oxide synthase in the microcirculation.

    Science.gov (United States)

    Shu, Xiaohong; Keller, T C Stevenson; Begandt, Daniela; Butcher, Joshua T; Biwer, Lauren; Keller, Alexander S; Columbus, Linda; Isakson, Brant E

    2015-12-01

    Endothelial nitric oxide synthase (eNOS, NOS3) is responsible for producing nitric oxide (NO)--a key molecule that can directly (or indirectly) act as a vasodilator and anti-inflammatory mediator. In this review, we examine the structural effects of regulation of the eNOS enzyme, including post-translational modifications and subcellular localization. After production, NO diffuses to surrounding cells with a variety of effects. We focus on the physiological role of NO and NO-derived molecules, including microvascular effects on vessel tone and immune response. Regulation of eNOS and NO action is complicated; we address endogenous and exogenous mechanisms of NO regulation with a discussion of pharmacological agents used in clinical and laboratory settings and a proposed role for eNOS in circulating red blood cells.

  12. Autoxidation kinetics of aqueous nitric oxide

    OpenAIRE

    1993-01-01

    Reports on the kinetics of the autoxidation of aqueous nitric oxide are discussed. It is concluded that the correct rate law is -d[NO]/dt = 4kaq[NO]2 [O2] with kaq = 2 × 106 M-2 · s-1 at 25°C and that a recent report of a rate law zero order in NO is incorrect. © 1993.

  13. Nitric Oxide Scavenging by Red Cell Microparticles

    OpenAIRE

    Liu, Chen; Zhao, Weixin; George J Christ; Gladwin, Mark T.; Kim-Shapiro, Daniel B.

    2013-01-01

    Red cell microparticles form during the storage of red blood cells and in diseases associated with red cell breakdown and asplenia, including hemolytic anemias such as sickle cell disease. These small phospholipid vesicles that are derived from red blood cells have been implicated in the pathogenesis of transfusion of aged stored blood and hemolytic diseases, via activation of the hemostatic system and effects on nitric oxide (NO) bioavailability. Red cell microparticles react with the import...

  14. The levels of nitric oxide in megaloblastic anemia

    Directory of Open Access Journals (Sweden)

    Emin Kaya

    2009-12-01

    Full Text Available Objective: The purpose of this study was to investigate the relationship between nitric oxide degradation products (nitrate and nitrite levels and megaloblastic anemia which is treated with cyalocobalamin. Materials and Methods: A total of 30 patients with megaloblastic anemia (16 Male, 14 Female were included in the study. Cyanocobalamin was administered (1.000 µg/day intramuscularly until the reticulocyte crisis occurred to the normal range. The control group consisted of 30 healthy subjects (15 Male, 15 Female. Nitric oxide levels were measured before treatment and compared with the values obtained during peak reticulocyte count. Results: Plasma direct nitrite, total nitrite and nitrate levels were 24,86±3,87, 60.56±7,01 and 36,02±5,24 in before treatment versus 15,48±3,05, 38,92±6,44 and 22,77±6,04 μmol/dl in after treatment, respectively. Plasma direct nitrite, total nitrite and nitrate levels were significantly lower in after treatment compared with the before treatment (p<0.001. Conclusion: Nitric oxide levels are seen to increase in megaloblastic anemia. This study suggested that abnormalities in the nitric oxide levels in megaloblastic anemia are restored by vitamin B12 replacement therapy.

  15. Oxygen, nitric oxide and articular cartilage

    Directory of Open Access Journals (Sweden)

    B Fermor

    2007-04-01

    Full Text Available Molecular oxygen is required for the production of nitric oxide (NO, a pro-inflammatory mediator that is associated with osteoarthritis and rheumatoid arthritis. To date there has been little consideration of the role of oxygen tension in the regulation of nitric oxide production associated with arthritis. Oxygen tension may be particularly relevant to articular cartilage since it is avascular and therefore exists at a reduced oxygen tension. The superficial zone exists at approximately 6% O2, while the deep zone exists at less than 1% O2. Furthermore, oxygen tension can alter matrix synthesis, and the material properties of articular cartilage in vitro.The increase in nitric oxide associated with arthritis can be caused by pro-inflammatory cytokines and mechanical stress. Oxygen tension significantly alters endogenous NO production in articular cartilage, as well as the stimulation of NO in response to both mechanical loading and pro-inflammatory cytokines. Mechanical loading and pro-inflammatory cytokines also increase the production of prostaglandin E2 (PGE2. There is a complex interaction between NO and PGE2, and oxygen tension can alter this interaction. These findings suggest that the relatively low levels of oxygen within the joint may have significant influences on the metabolic activity, and inflammatory response of cartilage as compared to ambient levels. A better understanding of the role of oxygen in the production of inflammatory mediators in response to mechanical loading, or pro-inflammatory cytokines, may aid in the development of strategies for therapeutic intervention in arthritis.

  16. Nitric oxide turnover in permeable river sediment

    DEFF Research Database (Denmark)

    Schreiber, Frank; Stief, Peter; Kuypers, Marcel M M;

    2014-01-01

    We measured nitric oxide (NO) microprofiles in relation to oxygen (O2) and all major dissolved N-species (ammonium, nitrate, nitrite, and nitrous oxide [N2O]) in a permeable, freshwater sediment (River Weser, Germany). NO reaches peak concentrations of 0.13 μmol L-1 in the oxic zone and is consumed...... in the oxic-anoxic transition zone. Apparently, NO is produced by ammonia oxidizers under oxic conditions and consumed by denitrification under microoxic conditions. Experimental percolation of sediment cores with aerated surface water resulted in an initial rate of NO production that was 12 times higher than...... the net NO production rate in steady state. This initial NO production rate is in the same range as the net ammonia oxidation rate, indicating that NO is transiently the main product of ammonia oxidizers. Stable isotope labeling experiments with the 15N-labeled chemical NO donor S...

  17. Sinorhizobium meliloti Controls Nitric Oxide-Mediated Post-Translational Modification of a Medicago truncatula Nodule Protein.

    Science.gov (United States)

    Blanquet, Pauline; Silva, Liliana; Catrice, Olivier; Bruand, Claude; Carvalho, Helena; Meilhoc, Eliane

    2015-12-01

    Nitric oxide (NO) is involved in various plant-microbe interactions. In the symbiosis between soil bacterium Sinorhizobium meliloti and model legume Medicago truncatula, NO is required for an optimal establishment of the interaction but is also a signal for nodule senescence. Little is known about the molecular mechanisms responsible for NO effects in the legume-rhizobium interaction. Here, we investigate the contribution of the bacterial NO response to the modulation of a plant protein post-translational modification in nitrogen-fixing nodules. We made use of different bacterial mutants to finely modulate NO levels inside M. truncatula root nodules and to examine the consequence on tyrosine nitration of the plant glutamine synthetase, a protein responsible for assimilation of the ammonia released by nitrogen fixation. Our results reveal that S. meliloti possesses several proteins that limit inactivation of plant enzyme activity via NO-mediated post-translational modifications. This is the first demonstration that rhizobia can impact the course of nitrogen fixation by modulating the activity of a plant protein.

  18. Nitric oxide control of steroidogenesis: Endocrine effects of N sup G -nitro-L-arginine and comparisons to alcohol

    Energy Technology Data Exchange (ETDEWEB)

    Adams, M.L.; Nock, B.; Truong, R.; Cicero, T.J. (Washington Univ., St. Louis, MO (United States))

    1992-01-01

    Recent studies suggest that nitric oxide (NO) may regulate hormone biosynthesis and secretion. This was tested by treating male rats with N{sup G}-nitro-L-arginine methyl ester (NAME), a NO synthase inhibitor, and measuring serum and testicular interstitial fluid testosterone and serum corticosterone, luteinizing hormone (LH), and prolactin (PRL). The effect of N{sup G}-nitro-L-arginine (NA), a less-soluble form of the same NO synthase inhibitor, on the reproductive suppressant actions of alcohol was also examined. NAME increased testosterone and corticosterone secretion dose-dependently without affecting LH and PRL secretion. The alcohol-induced suppression of testosterone or LH secretion was not altered by treatment with NA. Although effects of NAME and NA on other systems may be involved, these results indicate that testicular and adrenal steroidogenesis are negatively regulated by endogenous NO and that NO does not regulate LH and PRL secretion or inhibit the testicular steroidogenic pathway in the same way as alcohol.

  19. Brain purine metabolism and xanthine dehydrogenase/oxidase conversion in hyperammonemia are under control of NMDA receptors and nitric oxide.

    Science.gov (United States)

    Kaminsky, Yury; Kosenko, Elena

    2009-10-19

    In hyperammonemia, a decrease in brain ATP can be a result of adenine nucleotide catabolism. Xanthine dehydrogenase (XD) and xanthine oxidase (XO) are the end steps in the purine catabolic pathway and directly involved in depletion of the adenylate pool in the cell. Besides, XD can easily be converted to XO to produce reactive oxygen species in the cell. In this study, the effects of acute ammonia intoxication in vivo on brain adenine nucleotide pool and xanthine and hypoxanthine, the end degradation products of adenine nucleotides, during the conversion of XD to XO were studied. Injection of rats with ammonium acetate was shown to lead to the dramatic decrease in the ATP level, adenine nucleotide pool size and adenylate energy charge and to the great increase in hypoxanthine and xanthine 11 min after the lethal dose indicating rapid degradation of adenylates. Conversion of XD to XO in hyperammonemic rat brain was evidenced by elevated XO/XD activity ratio. Injection of MK-801, a NMDA receptor blocker, prevented ammonia-induced catabolism of adenine nucleotides and conversion of XD to XO suggesting that in vivo these processes are mediated by activation of NMDA receptors. The in vitro dose-dependent effects of sodium nitroprusside, a NO donor, on XD and XO activities are indicative of the direct modification of the enzymes by nitric oxide. This is the first report evidencing the increase in brain xanthine and hypoxanthine levels and adenine nucleotide breakdown in acute ammonia intoxication and NMDA receptor-mediated prevention of these alterations.

  20. Nitric oxide negatively regulates mammalian adult neurogenesis

    Science.gov (United States)

    Packer, Michael A.; Stasiv, Yuri; Benraiss, Abdellatif; Chmielnicki, Eva; Grinberg, Alexander; Westphal, Heiner; Goldman, Steven A.; Enikolopov, Grigori

    2003-08-01

    Neural progenitor cells are widespread throughout the adult central nervous system but only give rise to neurons in specific loci. Negative regulators of neurogenesis have therefore been postulated, but none have yet been identified as subserving a significant role in the adult brain. Here we report that nitric oxide (NO) acts as an important negative regulator of cell proliferation in the adult mammalian brain. We used two independent approaches to examine the function of NO in adult neurogenesis. In a pharmacological approach, we suppressed NO production in the rat brain by intraventricular infusion of an NO synthase inhibitor. In a genetic approach, we generated a null mutant neuronal NO synthase knockout mouse line by targeting the exon encoding active center of the enzyme. In both models, the number of new cells generated in neurogenic areas of the adult brain, the olfactory subependyma and the dentate gyrus, was strongly augmented, which indicates that division of neural stem cells in the adult brain is controlled by NO and suggests a strategy for enhancing neurogenesis in the adult central nervous system.

  1. Superhydrophobic nitric oxide-releasing xerogels.

    Science.gov (United States)

    Storm, Wesley L; Youn, Jonghae; Reighard, Katelyn P; Worley, Brittany V; Lodaya, Hetali M; Shin, Jae Ho; Schoenfisch, Mark H

    2014-08-01

    Superhydrophobic nitric oxide (NO)-releasing xerogels were prepared by spray-coating a fluorinated silane/silica composite onto N-diazeniumdiolate NO donor-modified xerogels. The thickness of the superhydrophobic layer was used to extend NO release durations from 59 to 105h. The resulting xerogels were stable, maintaining superhydrophobicity for up to 1month (the longest duration tested) when immersed in solution, with no leaching of silica or undesirable fragmentation detected. The combination of superhydrophobicity and NO release reduced viable Pseudomonas aeruginosa adhesion by >2-logs. The killing effect of NO was demonstrated at longer bacterial contact times, with superhydrophobic NO-releasing xerogels resulting in 3.8-log reductions in adhered viable bacteria vs. controls. With no observed toxicity to L929 murine fibroblasts, NO-releasing superhydrophobic membranes may be valuable antibacterial coatings for implants as they both reduce adhesion and kill bacteria that do adhere. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  2. Genetic variants in nitric oxide synthase genes and the risk of male infertility in a Chinese population: a case-control study.

    Directory of Open Access Journals (Sweden)

    Lifeng Yan

    Full Text Available In recent years, oxidative stress has been studied extensively as a main contributing factor to male infertility. Nitric Oxide, a highly reactive free radical gas, is potentially detrimental to sperm function and sperm DNA integrity at high levels. Thus, the aim of this study was to investigate the associations between five polymorphisms in nitric oxide synthase genes (NOSs and the risk of male infertility and sperm DNA damage as well.Genotypes were determined by the OpenArray platform. Sperm DNA fragmentation was detected using the Tdt-mediated dUTP nick-end labeling assay, and the level of 8-hydroxydeoxyguanosine (8-OHdG in sperm DNA was measured using immunofluorescence. The adjusted odds ratio (OR and 95% confidence interval (CI were estimated using unconditional logistic regression.Our results revealed a statistically significant difference between the cases and controls in both genotypic distribution (P<0.001 and allelic frequency (P = 0.021 only for the NOS3 rs1799983 SNP. Multivariate logistic regression analyses revealed that rs1799983 was associated with a borderline significantly increased risk of male infertility (GT vs. GG: adjusted OR = 1.30, 95% CI: 1.00-1.70; GT+TT vs. GG: adjusted OR = 1.34, 95% CI: 1.03-1.74; P trend = 0.020. Moreover, NOS3 rs1799983 was positively associated with higher levels of sperm DNA fragmentation (β = 0.223, P = 0.044. However, the other 4 polymorphisms (NOS1 rs2682826, NOS1 rs1047735, NOS2 rs2297518, and NOS2 rs10459953 were not found to have any apparent relationships with male infertility risk.Of five NOS gene polymorphisms investigated in the present study, we found NOS3 rs1799983 might cause oxidative sperm DNA damage, thereby contributing to male infertility.

  3. Nitric Oxide Prevents Mouse Embryonic Stem Cell Differentiation Through Regulation of Gene Expression, Cell Signaling, and Control of Cell Proliferation.

    Science.gov (United States)

    Tapia-Limonchi, Rafael; Cahuana, Gladys M; Caballano-Infantes, Estefania; Salguero-Aranda, Carmen; Beltran-Povea, Amparo; Hitos, Ana B; Hmadcha, Abdelkrim; Martin, Franz; Soria, Bernat; Bedoya, Francisco J; Tejedo, Juan R

    2016-09-01

    Nitric oxide (NO) delays mouse embryonic stem cell (mESC) differentiation by regulating genes linked to pluripotency and differentiation. Nevertheless, no profound study has been conducted on cell differentiation regulation by this molecule through signaling on essential biological functions. We sought to demonstrate that NO positively regulates the pluripotency transcriptional core, enforcing changes in the chromatin structure, in addition to regulating cell proliferation, and signaling pathways with key roles in stemness. Culturing mESCs with 2 μM of the NO donor diethylenetriamine/NO (DETA/NO) in the absence of leukemia inhibitory factor (LIF) induced significant changes in the expression of 16 genes of the pluripotency transcriptional core. Furthermore, treatment with DETA/NO resulted in a high occupancy of activating H3K4me3 at the Oct4 and Nanog promoters and repressive H3K9me3 and H3k27me3 at the Brachyury promoter. Additionally, the activation of signaling pathways involved in pluripotency, such as Gsk3-β/β-catenin, was observed, in addition to activation of PI3 K/Akt, which is consistent with the protection of mESCs from cell death. Finally, a decrease in cell proliferation coincides with cell cycle arrest in G2/M. Our results provide novel insights into NO-mediated gene regulation and cell proliferation and suggest that NO is necessary but not sufficient for the maintenance of pluripotency and the prevention of cell differentiation. J. Cell. Biochem. 117: 2078-2088, 2016. © 2016 Wiley Periodicals, Inc.

  4. Updated role of nitric oxide in disorders of erythrocyte function.

    Science.gov (United States)

    Kahn, Marc J; Maley, Jason H; Lasker, George F; Kadowitz, Philip J

    2013-03-01

    Nitric oxide is a potent vasodilator that plays a critical role in disorders of erythrocyte function. Sickle cell disease, paroxysmal nocturnal hemoglobinuria and banked blood preservation are three conditions where nitric oxide is intimately related to dysfunctional erythrocytes. These conditions are accompanied by hemolysis, thrombosis and vasoocclusion. Our understanding of the interaction between nitric oxide, hemoglobin, and the vasculature is constantly evolving, and by defining this role we can better direct trials aimed at improving the treatments of disorders of erythrocyte function. Here we briefly discuss nitric oxide's interaction with hemoglobin through the hypothesis regarding Snitrosohemoglobin, deoxyhemoglobin, and myoglobin as nitrite reductases. We then review the current understanding of the role of nitric oxide in sickle cell disease, paroxysmal nocturnal hemoglobinuria, and banked blood, and discuss therapeutics in development to target nitric oxide in the treatment of some of these disorders.

  5. Reactive Oxygen Species and Nitric Oxide in Cutaneous Leishmaniasis

    OpenAIRE

    Maria Fátima Horta; Bárbara Pinheiro Mendes; Eric Henrique Roma; Fátima Soares Motta Noronha; Juan Pereira Macêdo; Luciana Souza Oliveira; Myrian Morato Duarte; Leda Quercia Vieira

    2012-01-01

    Cutaneous leishmaniasis affects millions of people around the world. Several species of Leishmania infect mouse strains, and murine models closely reproduce the cutaneous lesions caused by the parasite in humans. Mouse models have enabled studies on the pathogenesis and effector mechanisms of host resistance to infection. Here, we review the role of nitric oxide (NO), reactive oxygen species (ROS), and peroxynitrite (ONOO−) in the control of parasites by macrophages, which are both the host c...

  6. Transport of nitric oxide by perfluorocarbon emulsion.

    Science.gov (United States)

    Ortiz, Daniel; Cabrales, Pedro; Briceño, Juan C

    2013-01-01

    Perfluorocarbon (PFC) emulsions can transport and release various gases based on concentration gradients. The objective of this study was to determine the possibility of carrying and delivering exogenous nitric oxide (NO) into the circulation by simply loading PFC emulsion with NO prior infusion. PFC was equilibrated with room air (PFC) or 300 ppm NO (PFC-NO) at atmospheric pressure. Isotonic saline solution was used as a volume control (Saline). PFC and PFC-NO were infused at a dose of 3.5 mL/kg in the hamster window chamber model. Blood chemistry, and systemic and microvascular hemodynamic response were measured. Infusion of PFC preloaded with NO reduced blood pressure, induced microvascular vasodilation and increased capillary perfusion; although these changes lasted less than 30 min post infusion. On the other hand, infusion of PFC (without NO) produced vasoconstriction; however, the vasoconstriction was followed by vasodilatation at 30 min post infusion. Plasma nitrite and nitrate increased 15 min after infusion of NO preloaded PFC compared with PFC, 60 min after infusion nitrite and nitrate were not different, and 90 min after infusion plasma S-nitrosothiols increased in both groups. Infusion of NO preloaded PFC resulted in acute vascular relaxation, where as infusion of PFC (without NO) produced vasoconstriction, potentially due to NO sequestration by the PFC micelles. The late effects of PFC infusion are due to NO redistribution and plasma S-nitrosothiols. Gas solubility in PFC can provide a tool to modulate plasma vasoactive NO forms availability and improve microcirculatory function and promote increased blood flow.

  7. Nitric oxide in liver inflammation and regeneration.

    Science.gov (United States)

    Martin-Sanz, Paloma; Hortelano, Sonsoles; Callejas, Nuria A; Goren, Nora; Casado, Marta; Zeini, Miriam; Boscá, Lisardo

    2002-12-01

    Hepatocytes express and release inflammatory mediators after challenge with bacterial cell wall molecules and proinflammatory cytokines. Nitric oxide synthase-2 (NOS-2) is expressed under these conditions and the high-output NO synthesis that follows contributes to the inflammatory response in this tissue and participates in the onset of several hepatopathies. However, in the course of liver regeneration, for example, after partial hepatectomy, NOS-2 is expressed at moderate levels and contributes to inhibit apoptosis and to favor progression in the cell cycle until the organ size and function are restored. The mechanisms involved in the regulation of NOS-2 expression under these conditions are revised.

  8. Nitric oxide and plant iron homeostasis.

    Science.gov (United States)

    Buet, Agustina; Simontacchi, Marcela

    2015-03-01

    Like all living organisms, plants demand iron (Fe) for important biochemical and metabolic processes. Internal imbalances, as a consequence of insufficient or excess Fe in the environment, lead to growth restriction and affect crop yield. Knowledge of signals and factors affecting each step in Fe uptake from the soil and distribution (long-distance transport, remobilization from old to young leaves, and storage in seeds) is necessary to improve our understanding of plant mineral nutrition. In this context, the role of nitric oxide (NO) is discussed as a key player in maintaining Fe homeostasis through its cross talk with hormones, ferritin, and frataxin and the ability to form nitrosyl-iron complexes.

  9. Nitric oxide synthase inhibition and cerebrovascular regulation

    DEFF Research Database (Denmark)

    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...

  10. Regulation and control of nitric oxide (NO) in macrophages: Protecting the "professional killer cell" from its own cytotoxic arsenal via MRP1 and GSTP1.

    Science.gov (United States)

    Kovacevic, Z; Sahni, S; Lok, H; Davies, M J; Wink, D A; Richardson, D R

    2017-02-17

    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 transports NO as dinitrosyl-dithiol-iron complexes (DNICs) composed of iron, NO and glutathione (GSH). Hence, this gas with contrasting anti- and pro-tumor effects, which has been assumed to be freely diffusible, is a tightly-regulated species in M1-MØs. These control systems prevent NO cytotoxicity and may be responsible for delivering cytotoxic NO as DNICs via MRP1 from M1-MØs, to tumor cell targets.

  11. Arginine and Nitric Oxide Pathways in Obesity-Associated Asthma

    Directory of Open Access Journals (Sweden)

    Fernando Holguin

    2013-01-01

    Full Text Available Obesity is a comorbidity that adversely affects asthma severity and control by mechanisms that are not fully understood. This review will discuss evidence supporting a role for nitric oxide (NO as a potential mechanistic link between obesity and late-onset asthma (>12 years. Several studies have shown that there is an inverse association between increasing body mass index (BMI and reduced exhaled NO. Newer evidence suggests that a potential explanation for this paradoxical relationship is related to nitric oxide synthase (NOS uncoupling, which occurs due to an imbalance between L-arginine (NOS substrate and its endogenous inhibitor, asymmetric di-methyl arginine (ADMA. The review will propose a theoretical framework to understand the relevance of this pathway and how it may differ between early and late-onset obese asthmatics. Finally, the paper will discuss potential new therapeutic approaches, based on these paradigms, for improving the respiratory health of obese subjects with asthma.

  12. The role of nitric oxide in cancer

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Nitric oxide (NO) is a pleiotropic regulator, critical to numerous biological processes, including va-sodilatation, neurotransmission and macrophage-mediated immunity. The family of nitric oxide synthases(NOS) comprises inducible NOS (iNOS), endothelial NOS (eNOS), and neuronal NOS (nNOS). Interest-ingly, various studies have shown that all three isoforms can be involved in promoting or inhibiting theetiology of cancer. NOS activity has been detected in tumour cells of various histogenetic origins and hasbeen associated with tumour grade, proliferation rate and expression of important signaling componentsassociated with cancer development such as the oestrogen receptor. It appears that high levels of NOSexpression (for example, generated by activated macrophages) may be cytostatic or cytotoxic for tumorcells, whereas low level activity can have the opposite effect and promote tumour growth. Paradoxicallytherefore, NO (and related reactive nitrogen species) may have both genotoxic and angiogenic properties.Increased NO-generation in a cell may select mutant p53 cells and contribute to tumour angiogenesis byupregulating VEGF. In addition, NO may modulate tumour DNA repair mechanisms by upregulating p53,poly(ADP-ribose) polymerase (PARP) and the DNA-dependent protein kinase (DNA-PK). An understand-ing at the molecular level of the role of NO in cancer will have profound therapeutic implications for thediagnosis and treatment of disease.

  13. Expired nitric oxide levels in adult asthmatics

    Directory of Open Access Journals (Sweden)

    Chiharu Okada

    1996-01-01

    Full Text Available The expired nitric oxide (NO concentration is known to be higher in asthmatic subjects than in normal subjects. To elucidate the role of NO in asthma, we examined the expired NO concentrations in relation to the type (atopic, mixed, non- atopic, and severity (mild, moderate, severe of asthmatics, as well as the influence of steroid treatment. Twenty-seven normal subjects, 48 asthmatics, 8 subjects with allergic rhinitis, and 13 subjects with pulmonary emphysema participated in the study. The expired NO concentration was significantly higher in asthmatics and patients with allergic rhinitis than in normal subjects (P<0.01. No significant difference was observed between the expired NO concentration in patients with pulmonary emphysema and that of normal subjects. The expired NO concentrations were significantly lower in non- atopic asthma than in atopic asthma. Nitric oxide levels were significantly lower in severe asthma than in mild asthma. High doses of steroid treatment are often used in severe asthma. The dose of inhaled beclomethasone and expired NO concentrations showed a negative correlation (r= −0.51587, P<0.004. Drip infusion of hydrocortisone tended to increase the exhaled NO concentration just after drip infusion, however, it decreased after 24 h. These results suggest that steroid treatment decreases the expired NO concentrations in asthmatics, although it cannot be concluded that NO increases the severity of asthma. The measurement of expired NO concentrations is an easy, non-invasive test, which may be a useful tool for monitoring the condition of asthmatics.

  14. Hypoxia tolerance, nitric oxide, and nitrite

    DEFF Research Database (Denmark)

    Fago, Angela; Jensen, Frank Bo

    2015-01-01

    Among vertebrates able to tolerate periods of oxygen deprivation, the painted and red-eared slider turtles (Chrysemys picta and Trachemys scripta) and the crucian carp (Carassius carassius) are the most extreme and can survive even months of total lack of oxygen during winter. The key to hypoxia...... survival resides in concerted physiological responses, including strong metabolic depression, protection against oxidative damage and – in air breathing animals - redistribution of blood flow. Each of these responses is known to be tightly regulated by nitric oxide (NO) and during hypoxia by its metabolite...... nitrite. The aim of this review is to highlight recent work illustrating the widespread roles of NO and nitrite in the tolerance to extreme oxygen deprivation, in particular in the red-eared slider turtle and crucian carp, but also in diving marine mammals. The emerging picture underscores the importance...

  15. Melatonin and its precursors scavenge nitric oxide

    Energy Technology Data Exchange (ETDEWEB)

    Noda, Y.; Mori, A.; Liburdy, R.; Packer, L.

    1998-12-01

    Nitric oxide (NO) scavenging activity of melatonin, N-acetyl-5-hydroxytryptamine, serotonin, 5-hydroxytryptophan and L-tryptophan was examined by the Griess reaction using flow injection analysis. 1-Hydroxy-2-oxo-3-(N-methyl-3-aminopropyl)-3-methyl-1-triazene(NOC-7) was used as NO generator. The Griess reagent stoichiometrically reacts with NO2-, which was converted by a cadmium-copper reduction column from the stable end products of NO oxidation. Except for tryptophan, all the compounds examined scavenged NO in a dose-dependent manner. Melatonin, which has a methoxy group in the 5-position and an acetyl side chain, exhibited the most potent scavenging activity among the compounds tested. Serotonin, N-acetyl-5-hydroxytryptamine, and 5-hydroxytryptophan, respectively, showed moderate scavenging activity compared to melatonin. Tryptophan, which has neither a methoxy nor a hydroxyl group in the 5-position, exhibited the least NO scavenging activity.

  16. Hypoxia tolerance, nitric oxide, and nitrite

    DEFF Research Database (Denmark)

    Fago, Angela; Jensen, Frank Bo

    2015-01-01

    Among vertebrates able to tolerate periods of oxygen deprivation, the painted and red-eared slider turtles (Chrysemys picta and Trachemys scripta) and the crucian carp (Carassius carassius) are the most extreme and can survive even months of total lack of oxygen during winter. The key to hypoxia ...... of NO and nitrite signaling in the adaptive response to hypoxia in vertebrate animals....... survival resides in concerted physiological responses, including strong metabolic depression, protection against oxidative damage and – in air breathing animals - redistribution of blood flow. Each of these responses is known to be tightly regulated by nitric oxide (NO) and during hypoxia by its metabolite...... nitrite. The aim of this review is to highlight recent work illustrating the widespread roles of NO and nitrite in the tolerance to extreme oxygen deprivation, in particular in the red-eared slider turtle and crucian carp, but also in diving marine mammals. The emerging picture underscores the importance...

  17. Elevated levels of the serum endogenous inhibitor of nitric oxide synthase and metabolic control in rats with streptozotocin-induced diabetes.

    Science.gov (United States)

    Xiong, Yan; Fu, Yun-feng; Fu, Si-hai; Zhou, Hong-hao

    2003-08-01

    This study was designed to determine the relationship between elevated levels of the endogenous inhibitor of nitric oxide synthase, asymmetric dimethylarginine (ADMA), and metabolic control in rats with streptozotocin-induced diabetes. Serum levels of ADMA were measured by high-performance liquid chromatography at 8 weeks after diabetes was induced. Endothelium-dependent relaxation to acetylcholine was tested in aortic rings from nondiabetic age-matched control, untreated diabetic, and insulin-treated diabetic rats to evaluate endothelial function. Serum concentrations of glucose, glycosylated serum protein, and malondialdehyde were examined to estimate metabolic control. Serum levels of ADMA increased dramatically in untreated diabetic rats compared with control rats. This elevation in ADMA levels was accompanied by impairment of the endothelium-dependent relaxation response to acetylcholine in aortic rings. Long-term insulin treatment not only prevented the elevation of serum ADMA levels, but also improved the impairment of endothelium-dependent relaxation in diabetic rats. Serum levels of glucose, glycosylated serum protein, and malondialdehyde were significantly increased in parallel with the elevation of ADMA in untreated diabetic rats compared with control rats. These parameters were normalized after diabetic rats received insulin treatment for 8 weeks. These results provide the first evidence that an elevation in the concentration of ADMA in rats with streptozotocin-induced diabetes is closely related to metabolic control of the disease.

  18. Current concepts in the pathophysiology of fibromyalgia: the potential role of oxidative stress and nitric oxide.

    Science.gov (United States)

    Ozgocmen, Salih; Ozyurt, Huseyin; Sogut, Sadik; Akyol, Omer

    2006-05-01

    Fibromyalgia (FM) is a common chronic pain syndrome with an unknown etiology. Recent years added new information to our understanding of FM pathophysiology. Researches on genetics, biogenic amines, neurotransmitters, hypothalamic-pituitary-adrenal axis hormones, oxidative stress, and mechanisms of pain modulation, central sensitization, and autonomic functions in FM revealed various abnormalities indicating that multiple factors and mechanisms are involved in the pathogenesis of FM. Oxidative stress and nitric oxide may play an important role in FM pathophysiology, however it is still not clear whether oxidative stress abnormalities documented in FM are the cause or the effect. This should encourage further researches evaluating the potential role of oxidative stress and nitric oxide in the pathophysiology of FM and the efficacy of antioxidant treatments (omega-3 and -6 fatty acids, vitamins and others) in double blind and placebo controlled trials. These future researches will enhance our understanding of the complex pathophysiology of this disorder.

  19. Adrenoceptor-activated nitric oxide synthesis in salivary acinar cells

    DEFF Research Database (Denmark)

    Looms, Dagnia; Dissing, Steen; Tritsaris, Katerina

    2000-01-01

    We investigated the cellular regulation of nitric oxide synthase (NOS) activity in isolated acinar cells from rat parotid and human labial salivary glands, using the newly developed fluorescent nitric oxide (NO) indicator, DAF-2. We found that sympathetic stimulation with norepinephrine (NE) caus...

  20. Catalytic abatement of nitrous oxide from nitric and production

    NARCIS (Netherlands)

    Oonk, J.

    1998-01-01

    Nitric acid production is identified as a main source of nitrous oxide. Options for emission reduction however are not available. TNO and Hydro Agri studied the technological and economic feasibility of catalytic decomposition of nitrous oxide in nitric acid tail-gases. Although in literature promis

  1. Consumption of both low and high (-)-epicatechin apple puree attenuates platelet reactivity and increases plasma concentrations of nitric oxide metabolites: A randomized controlled trial

    NARCIS (Netherlands)

    Gasper, A.; Hollands, W.; Casgrain, A.; Saha, S.; Teucher, B.; Dainty, J.R.; Venema, D.P.; Hollman, P.C.H.

    2014-01-01

    We hypothesised that consumption of flavanol-containing apple puree would modulate platelet activity and increase nitric oxide metabolite status, and that high flavanol apple puree would exert a greater effect than low flavanol apple puree. 25 subjects consumed 230 g of apple puree containing 25 and

  2. Consumption of both low and high (-)-epicatechin apple puree attenuates platelet reactivity and increases plasma concentrations of nitric oxide metabolites: A randomized controlled trial

    NARCIS (Netherlands)

    Gasper, A.; Hollands, W.; Casgrain, A.; Saha, S.; Teucher, B.; Dainty, J.R.; Venema, D.P.; Hollman, P.C.H.

    2014-01-01

    We hypothesised that consumption of flavanol-containing apple puree would modulate platelet activity and increase nitric oxide metabolite status, and that high flavanol apple puree would exert a greater effect than low flavanol apple puree. 25 subjects consumed 230 g of apple puree containing 25 and

  3. A new method for sustained generation of ultra-pure nitric oxide-containing gas mixtures via controlled UVA-photolysis of nitrite solutions

    NARCIS (Netherlands)

    Opländer, C.; Baschin, M.; van Faassen, E.E.H.; Born, M.; Möller, M.; Pallua, N.; Suschek, C.V.

    2010-01-01

    Exogenous gaseous nitric oxide (gNO) is an FDA approved drug for treatment of a variety of human pathologies like Persistent Pulmonary Hypertension in neonates and premature babies, skin lesions and fungal dermatophyte infections. Substantial disadvantages of current gNO-based therapies are the high

  4. Light activated nitric oxide releasing materials

    Science.gov (United States)

    Muizzi Casanas, Dayana Andreina

    The ability to control the location and dosage of biologically active molecules inside the human body can be critical to maximizing effective treatment of cardiovascular diseases like angina. The current standard of treatment relies on the metabolism of organonitrate drugs into nitric oxide (NO), which are not specific, and also show problems with densitization with long-term use. There is a need then to create a treatment method that gives targeted release of NO. Metal-nitrosyl (M-NO) complexes can be used for delivery of NO since the release of NO can be controlled with light. However, the NO-releasing drug must be activated with red light to ensure maximum penetration of light through tissue. However, the release of NO from M-NO complexes with red-light activation is a significant challenge since the energy required to break the metal-NO bond is usually larger than the energy provided by red light. The goal of this project was to create red- sensitive, NO-releasing materials based on Ru-salen-nitrosyl compounds. Our approach was to first modify Ru salen complexes to sensitize the photochemistry for release of NO after red light irradiation. Next, we pursued polymerization of the Ru-salen complexes. We report the synthesis and quantitative photochemical characterization of a series of ruthenium salen nitrosyl complexes. These complexes were modified by incorporating electron donating groups in the salen ligand structure at key locations to increase electron density on the Ru. Complexes with either an --OH or --OCH3 substituent showed an improvement in the quantum yield of release of NO upon blue light irradiation compared to the unmodified salen. These --OH and --OCH3 complexes were also sensitized for NO release after red light activation, however the red-sensitive complexes were unstable and showed ligand substitution on the order of minutes. The substituted complexes remained sensitive for NO release, but only after blue light irradiation. The Ru

  5. The levels of nitric oxide in megaloblastic anemia.

    Science.gov (United States)

    Erkurt, Mehmet Ali; Aydoğdu, İsmet; Bayraktar, Nihayet; Kuku, İrfan; Kuku, İrfan; Kaya, Emin

    2009-12-05

    The purpose of this study was to investigate the relationship between nitric oxide degradation products (nitrate and nitrite) levels and megaloblastic anemia which is treated with cyalocobalamin. A total of 30 patients with megaloblastic anemia (16 Male, 14 Female) were included in the study. Cyanocobalamin was administered (1.000 µg/day intramuscularly) until the reticulocyte crisis occurred to the normal range. The control group consisted of 30 healthy subjects (15 Male, 15 Female). Nitric oxide levels were measured before treatment and compared with the values obtained during peak reticulocyte count. Plasma direct nitrite, total nitrite and nitrate levels were 24,86±3,87, 60.56±7,01 and 36,02±5,24 in before treatment versus 15,48±3,05, 38,92±6,44 and 22,77±6,04 μmol/dl in after treatment, respectively. Plasma direct nitrite, total nitrite and nitrate levels were significantly lower in after treatment compared with the before treatment (pmegaloblastic anemia. This study suggested that abnormalities in the nitric oxide levels in megaloblastic anemia are restored by vitamin B12 replacement therapy.

  6. Increased serum nitric oxide and malondialdehyde levels in patients with acute intestinal amebiasis.

    Science.gov (United States)

    Namıduru, E S; Tarakçıoğlu, M; Namıduru, M; Kocabaş, R; Erbağcı, B; Meram, I; Karaoğlan, I; Yılmaz, N; Cekmen, M

    2011-12-01

    To determine the level of oxygen-nitrogen stress parameters in the pathogenesis of amebiasis. Twenty-four acute intestinal amebiasis patients and 20 healthy controls were enrolled in the present study. Serum malondialdehyde and nitric oxide levels were determined spectrophotometrically. Serum malondialdehyde and nitric oxide levels were significantly higher in acute intestinal amebiasis patients than healthy controls (Pamebiasis patients. Also these parameters can be used to supplement the conventional microscopic method for reliable diagnosis of intestinal amebiasis.

  7. Direct measurements of nitric oxide release in relation to expression of endothelial nitric oxide synthase in isolated porcine mitral valves

    DEFF Research Database (Denmark)

    Moesgaard, Sophia Gry; Olsen, Lisbeth Høier; Aasted, Bent;

    2007-01-01

    The aim of this study was to measure the direct release of nitric oxide (NO) from the porcine mitral valve using a NO microelectrode. Furthermore, the expression and localization of endothelial nitric oxide synthase (eNOS) in the mitral valve was studied using immunohistochemistry, Western blotting...

  8. Role of Nitric Oxide and Nitric Oxide Synthases in Ischemia-reperfusion Injury in Rat Organotypic Hippocampus Slice

    Institute of Scientific and Technical Information of China (English)

    MENG Xianfang; SHI Jing; LIU Xiaochun; ZHANG Jing; SUN Ning

    2005-01-01

    To investigate the effects of ischemia-reperfusion on the levels of nitric oxide and nitric oxide synthase isoforms (nNOS and iNOS), rat organotypic hippocampus slice were cultured in vitro and subjected to ischemia by oxygen glucose deprivation (OGD) for 30 min and then placed in the normal culture condition. The ischemia-reperfusion produced a time-dependent increase in nitrite levels in the culture medium. Reverse transcriptional-polymerase chain reaction showed augmented levels of mRNA for both nNOS and iNOS when compared with control at 12 h and remained increase at 36 h after OGD (P<0.05). The protein levels of both nitric oxide synthase isoforms increased significantly as determined by Western Blot. OGD also caused neurotoxicity in this model as revealed by the elevated lactate dehydrogenase (LDH) efflux into the incubation solution. The results suggest that organotypic hippocampus slice is a useful model in studying ischemia-reperfusion brain injury. NO and NOS may play a critical role in the ischemia-reperfusion brain damage in vitro.

  9. Role of neuronal nitric oxide synthase and inducible nitric oxide synthase in intestinal injury in neonatal rats

    Institute of Scientific and Technical Information of China (English)

    Hui LU; Bing Zhu; Xin-Dong Xue

    2006-01-01

    AIM: To investigate the dynamic change and role of neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) in neonatal rat with intestinal injury and to define whether necrotizing enterocolitis (NEC) is associated with the levels of nitric oxide synthase (NOS) in the mucosa of the affected intestine tissue.METHODS: Wistar rats less than 24 h in age received an intraperitoneal injection with 5 mg/kg lipopolysaccharide (LPS). Ileum tissues were collected at 1, 3, 6, 12 and 24 h following LPS challenge for histological evaluation of NEC and for measurements of nNOS and iNOS. The correlation between the degree of intestinal injury and levels of NOS was determined.RESULTS: The LPS-injected pups showed a significant increase in injury scores versus the control. The expression of nNOS protein and mRNA was diminished after LPS injection. There was a negative significant correlation between the nNOS protein and the grade of median intestinal injury within 24 h. The expression of iNOS protein and mRNA was significantly increased in the peak of intestinal injury.CONCLUSION: nNOS and iNOS play different roles in LPS-induced intestinal injury. Caution should be exerted concerning potential therapeutic uses of NOS inhibitors in NEC.

  10. Production of Nitric Oxide and Expression of Inducible Nitric Oxide Synthase in Ovarian Cystic Tumors

    Directory of Open Access Journals (Sweden)

    Rosekeila Simões Nomelini

    2008-01-01

    Full Text Available Tumor sections from nonneoplastic (n=15, benign (n=28, and malignant ovarian tumors (n=20 were obtained from 63 women. Immunohistochemistry of the tumor sections demonstrated that inducible nitric oxide synthase (iNOS expression was increased in ovarian cancer samples compared to nonneoplastic or benign tumor samples. Using the Griess method, nitric oxide (NO metabolite levels were also found to be elevated in malignant tumor samples compared to benign tumor samples (P80 μM were more frequent than NO levels <80 μM, and iNOS expression in well-differentiated carcinomas was greater than in moderately/poorly differentiated carcinomas (P<.05. These data suggest an important role for NO in ovarian carcinogenesis.

  11. Hypertension, nitric oxide, oxidants, and dietary plant polyphenols.

    Science.gov (United States)

    Galleano, Monica; Pechanova, Olga; Fraga, Cesar G

    2010-12-01

    Fruits and vegetables are key foods whose high ingestion is associated with the improvement of numerous pathological conditions, including hypertension. Such health promoting actions have been increasingly ascribed to the antioxidant characteristics of different polyphenols in fruits and vegetables. Consequently, based on this assumption, many beverages and foods rich in polyphenols, grape, tea, cocoa, and soy products and many of their chemical constituents purified, are being studied both, as antioxidants and antihypertensive agents. This paper reviews the current evidence linking high polyphenol consumption with reductions in blood pressure. Basic chemical aspects of flavanols, flavonols, isoflavones and stilbenes, as possible responsible for the observed effects of those foods on blood pressure are included. Human interventions studies by using grapes and wine, cocoa and chocolate, black and green tea, soy products, and purified compounds ((+)-catequin, quercetin, (-)-epigallocatechin gallate) are summarized. The discussed hypothesis, strongly supported by experimental data in animals, is that by regulating nitric oxide bioavailability, polyphenols present in fruits and vegetables affect endothelial function and as a consequence, blood pressure. Even when data are not definitive and many questions remain open, the whole evidence is encouraging to start considering diets that can provide a benefit to hypertensive subjects, and those benefits will be more significant in people that do not have controlled his/her elevated blood pressure.

  12. The role of nitric oxide in reproduction

    Directory of Open Access Journals (Sweden)

    McCann S.M.

    1999-01-01

    Full Text Available Nitric oxide (NO plays a crucial role in reproduction at every level in the organism. In the brain, it activates the release of luteinizing hormone-releasing hormone (LHRH. The axons of the LHRH neurons project to the mating centers in the brain stem and by afferent pathways evoke the lordosis reflex in female rats. In males, there is activation of NOergic terminals that release NO in the corpora cavernosa penis to induce erection by generation of cyclic guanosine monophosphate (cGMP. NO also activates the release of LHRH which reaches the pituitary and activates the release of gonadotropins by activating neural NO synthase (nNOS in the pituitary gland. In the gonad, NO plays an important role in inducing ovulation and in causing luteolysis, whereas in the reproductive tract, it relaxes uterine muscle via cGMP and constricts it via prostaglandins (PG.

  13. Nitric oxide-releasing porous silicon nanoparticles

    Science.gov (United States)

    Kafshgari, Morteza Hasanzadeh; Cavallaro, Alex; Delalat, Bahman; Harding, Frances J.; McInnes, Steven JP; Mäkilä, Ermei; Salonen, Jarno; Vasilev, Krasimir; Voelcker, Nicolas H.

    2014-07-01

    In this study, the ability of porous silicon nanoparticles (PSi NPs) to entrap and deliver nitric oxide (NO) as an effective antibacterial agent is tested against different Gram-positive and Gram-negative bacteria. NO was entrapped inside PSi NPs functionalized by means of the thermal hydrocarbonization (THC) process. Subsequent reduction of nitrite in the presence of d-glucose led to the production of large NO payloads without reducing the biocompatibility of the PSi NPs with mammalian cells. The resulting PSi NPs demonstrated sustained release of NO and showed remarkable antibacterial efficiency and anti-biofilm-forming properties. These results will set the stage to develop antimicrobial nanoparticle formulations for applications in chronic wound treatment.

  14. Nitric Oxide and Respiratory Helminthic Diseases

    Directory of Open Access Journals (Sweden)

    Antonio Muro

    2010-01-01

    Full Text Available Nitric oxide (NO is a very simple molecule that displays very important functions both in helminths (mainly those involved in respiratory pathology and in mammalian hosts. In this paper we review four issues related to interaction of NO and lung helminthic diseases. Firstly, we evaluated data available on the NO synthesis and release by helminths and their biological role. Next, we summarized the effect of antigens obtained from different phases of the biological cycle on NO production by host mammalian cells (mainly from human sources. Thirdly, we revised the evaluation of NO on the biological activities and/or the viability of respiratory helminths. Lastly, the deleterious consequences of increased production of NO during helminthic human infection are detailed.

  15. Nitric Oxide Synthase Inhibitors as Antidepressants

    Directory of Open Access Journals (Sweden)

    Vallo Volke

    2010-01-01

    Full Text Available Affective and anxiety disorders are widely distributed disorders with severe social and economic effects. Evidence is emphatic that effective treatment helps to restore function and quality of life. Due to the action of most modern antidepressant drugs, serotonergic mechanisms have traditionally been suggested to play major roles in the pathophysiology of mood and stress-related disorders. However, a few clinical and several pre-clinical studies, strongly suggest involvement of the nitric oxide (NO signaling pathway in these disorders. Moreover, several of the conventional neurotransmitters, including serotonin, glutamate and GABA, are intimately regulated by NO, and distinct classes of antidepressants have been found to modulate the hippocampal NO level in vivo. The NO system is therefore a potential target for antidepressant and anxiolytic drug action in acute therapy as well as in prophylaxis. This paper reviews the effect of drugs modulating NO synthesis in anxiety and depression.

  16. The nitric oxide synthase of mouse spermatozoa.

    Science.gov (United States)

    Herrero, M B; Goin, J C; Boquet, M; Canteros, M G; Franchi, A M; Perez Martinez, S; Polak, J M; Viggiano, J M; Gimeno, M A

    1997-07-01

    Nitric oxide synthase (NOS) was evidenced in mature mouse spermatozoa by means of biochemical techniques and Western blot. During 120 min of incubation, 10(7) spermatozoa synthesized 7 +/- 2 pmol of L-[14C]citrulline. Besides, L-citrulline formation depended on the incubation time and on the concentration of L-arginine present in the incubation medium. Different concentrations of N(G)-nitro-L-arginine methyl ester (L-NAME) but not aminoguanidine, inhibited L-[14C]citrulline formation. Western-blot analysis of solubilized sperm proteins revealed a unique band of M(r)=140 kDa with the neural, endothelial and inducible NOS antisera tested. These results provide evidence that mature mouse sperm contains a NOS isoform and that spermatozoa have the potential ability to synthesize NO, suggesting a role for endogenous NO on mammalian sperm function.

  17. Nitric oxide in liver fibrosis: The role of inducible nitric oxide synthase.

    Science.gov (United States)

    Iwakiri, Yasuko

    2015-12-01

    The inducible form of nitric oxide synthase (iNOS) is expressed in hepatic cells in pathological conditions. Its induction is involved in the development of liver fibrosis, and thus iNOS could be a therapeutic target for liver fibrosis. This review summarizes the role of iNOS in liver fibrosis, focusing on 1) iNOS biology, 2) iNOS-expressing liver cells, 3) iNOS-related therapeutic strategies, and 4) future directions.

  18. Study of the correlations between fractional exhaled nitric oxide in exhaled breath and atopic status, blood eosinophils, FCER2 mutation, and asthma control in Vietnamese children

    Directory of Open Access Journals (Sweden)

    Nguyen-Thi-Bich H

    2016-09-01

    Full Text Available Hanh Nguyen-Thi-Bich,1 Huong Duong-Thi-Ly,2 Vu Thi Thom,2 Nhung Pham-Thi-Hong,2 Long Doan Dinh,2 Huong Le-Thi-Minh,1 Timothy John Craig,3 Sy Duong-Quy3,4 1Department of Immunology, Allergology, and Rheumatology, National Hospital of Pediatrics, Hanoi, Vietnam; 2School of Medicine and Pharmacy, Vietnam National University Hanoi, Vietnam; 3Department of Medicine, Penn State University, Hershey, PA, USA; 4Department of Respiratory Diseases, Lam Dong Medical College, Dalat, Vietnam Introduction: Fractional exhaled nitric oxide (FENO is a biomarker of airway inflammation in asthma. The measurement of FENO is utilized to assist in the diagnosis and treatment of children with asthma, especially for those treated with inhaled corticosteroids. Objectives: The aims of this study were to evaluate the correlations between FENO and atopic status, blood eosinophil levels, FCER2 mutation, and asthma control in Vietnamese children. Subjects and methods: This was a prospective and descriptive study approved by the local Ethical Board. All children with uncontrolled asthma, seen in the National Hospital of Pediatrics (Hanoi, Vietnam, were included. Exhaled breath FENO, blood eosinophils, skin prick test, total IgE, asthma control test (ACT, and FCER2 gene polymorphism were performed at inclusion. They were followed up at 3 months to evaluate clinical status, FENO levels, and ACT. Results: Forty-two children with uncontrolled asthma with a mean age of 10±3 years (6–16 years were included. The male/female ratio was 2.5/1. The mean FENO levels were 26±25 ppb. FENO was significantly higher in patients with a positive skin prick test for respiratory allergens (P<0.05. FENO was significantly correlated with blood eosinophil levels (r=0.5217; P=0.0004. Five of the 32 subjects (15.6% had a mutation of FCER2 gene (rs28364072 SNP. In this group, the levels of FENO were highest (37±10 ppb; P<0.05. The levels of FENO were significantly decreased after 3 months of

  19. Nitric oxide in the psychobiology of mental disorders

    Directory of Open Access Journals (Sweden)

    Altan Eşsizoğlu

    2009-03-01

    Full Text Available Nitric oxide is in a gaseous form and is widespread in the human body. It functions by acting as a secondary messenger in the modulatory activities of neuronal functions of the central nervous system. Nitric oxide is the first identified neurotransmitter of the nontraditional neurotransmitter family.Studies conducted on experimental animals demonstrate that nitric oxide has a neuromodulatory efficacy on the secretions of other neurotransmitters and that it has an effect on learning and memory functions, and on various neuronal mechanisms. Many studies have been conducted to investigate the location of nitric oxide in the central nervous system, its effect on anxiety and depression, its relationship with other neurotransmitters, and also about its role on neurotoxicity. There are clinical studies concerning the level of nitrate, a product of nitric oxide metabolism, and also experimental studies concerning its rewarding effect of alcohol and substance use, in patients with depression and schizophrenia. However, limited studies have been conducted to investigate its relationship with stress, which is an important factor in the etiology of psychiatric disorders. These studies demonstrate that nitric oxide is closely related with stress physiology.Nitric oxide is a neuromodulator, which is frequently being mentioned about nowadays in psychiatry. Clinical and experimental studies play an important role in the psychobiology of psychiatric disorders.

  20. Exhaled and nasal nitric oxide in laryngectomized patients

    Directory of Open Access Journals (Sweden)

    Jörres Rudolf A

    2010-01-01

    Full Text Available Abstract Background Nitric oxide (NO shows differing concentrations in lower and upper airways. Patients after total laryngectomy are the only individuals, in whom a complete separation of upper and lower airways is guaranteed. Thus the objective of our study was to assess exhaled and nasal NO in these patients. Methods Exhaled bronchial NO (FENO and nasal nitric oxide (nNO were measured in patients after total laryngectomy (n = 14 and healthy controls (n = 24. To assess lung function we additionally performed spirometry. Co-factors possibly influencing NO, such as smoking, infections, and atopy were excluded. Results There was a markedly (p NO in patients after total laryngectomy (median (range: 4 (1-22 ppb compared to healthy controls 21 (9-41 ppb. In contrast, nNO was comparable between groups (1368 versus 1380 in controls but showed higher variability in subjects after laryngectomy. Conclusions Our data suggest that either bronchial NO production in patients who underwent laryngectomy is very low, possibly due to alterations of the mucosa or oxidant production/inflammation, or that substantial contributions to FENO arise from the larynx, pharynx and mouth, raising FENO despite velum closure. The data fit to those indicating a substantial contribution to FENO by the mouth in healthy subjects. The broader range of nNO values found in subjects after laryngectomy may indicate chronic alteration or oligo-symptomatic inflammation of nasal mucosa, as frequently found after total laryngectomy.

  1. Biomimetic and microbial reduction of nitric oxide

    Energy Technology Data Exchange (ETDEWEB)

    Potter, W.T.; Le, U.; Ronda, S. [Univ. of Tulsa, OK (United States)] [and others

    1995-12-31

    The biomimetic reduction of nitric oxide (NO) to nitrous oxide (N{sub 2}O) by dithiothreitol in the presence of cyanocobalamin and cobalt-centered porphyrins has been investigated. Reactions were monitored directly using Fourier Transform Infrared (FTIR) Spectroscopy vapor-phase spectra. Reaction rates were twofold faster for the corrin than for the cobalt-centered porphyrins. The stoichiometry showed the loss of two molecules of NO per molecule of N{sub 2}O produced. We have also demonstrated that the facultative anaerobe and chemoautotroph, Thiobacillus denitrificans, can be cultured anoxically in batch reactors using NO as a terminal electron acceptor with reduction to elemental nitrogen (N{sub 2}). We have proposed that the concentrated stream of NO{sub x}, as obtained from certain regenerable processes for the gas desulfurization and NO{sub x} removal, could be converted to N{sub 2} for disposal by contact with a culture of T. denitrificans. Four heterotrophic bacteria have also been identified that may be grown in batch cultures with succinate, yeast extract, or heat and alkali pretreated sewage sludge as carbon and energy sources and NO as a terminal electron acceptor. These are Paracoccus dentrificans, Pseudomonas denitrificans, Alcaligens denitrificans, and Thiophaera pantotropha.

  2. Management based on exhaled nitric oxide levels adjusted for atopy reduces asthma exacerbations in children: A dual centre randomized controlled trial.

    Science.gov (United States)

    Petsky, Helen L; Li, Albert M; Au, Chun T; Kynaston, Jennifer A; Turner, Catherine; Chang, Anne B

    2015-06-01

    While several randomized control trials (RCTs) have evaluated the use of fractional exhaled nitric oxide (FeNO) to improve asthma outcomes, none used FeNO cut-offs adjusted for atopy, a determinant of FeNO levels. In a dual center RCT, we assessed whether a treatment strategy based on FeNO levels, adjusted for atopy, reduces asthma exacerbations compared with the symptoms-based management (controls). Children with asthma from hospital clinics of two hospitals were randomly allocated to receive an a-priori determined treatment hierarchy based on symptoms or FeNO levels. There was a 2-week run-in period and they were then reviewed 10 times over 12-months. The primary outcome was the number of children with exacerbations over 12-months. Sixty-three children were randomized (FeNO = 31, controls = 32); 55 (86%) completed the study. Although we did achieve our planned sample size, significantly fewer children in the FeNO group (6 of 27) had an asthma exacerbation compared to controls (15 of 28), P = 0.021; number to treat for benefit = 4 (95% CI 3-24). There was no difference between groups for any secondary outcomes (quality of life, symptoms, FEV1 ). The final daily inhaled corticosteroids (ICS) dose was significantly (P = 0.037) higher in the FeNO group (median 400 µg, IQR 250-600) compared to the controls (200, IQR100-400). Taking atopy into account when using FeNO to tailor asthma medications is likely beneficial in reducing the number of children with severe exacerbations at the expense of increased ICS use. However, the strategy is unlikely beneficial for improving asthma control. A larger study is required to confirm or refute our findings. © 2014 Wiley Periodicals, Inc.

  3. Acute cocoa Flavanols intake has minimal effects on exercise-induced oxidative stress and nitric oxide production in healthy cyclists: a randomized controlled trial.

    Science.gov (United States)

    Decroix, Lieselot; Tonoli, Cajsa; Soares, Danusa Dias; Descat, Amandine; Drittij-Reijnders, Marie-José; Weseler, Antje R; Bast, Aalt; Stahl, Wilhelm; Heyman, Elsa; Meeusen, Romain

    2017-01-01

    Cocoa flavanols (CF) can stimulate vasodilation by improved nitric oxide (NO) synthesis and have antioxidant and anti-inflammatory capacities. This study aimed to examine whether acute CF intake can affect exercise-induced changes in antioxidant capacity, oxidative stress, inflammation and NO production, as well as exercise performance and recovery in well-trained cyclists. Twelve well-trained male cyclists (mean ± SD age, VO2max: 30 ± 3 years, 63.0 ± 3.5 ml/kg/min) participated in this randomized, double-blind, cross over study. On 2 separate occasions, subjects performed two 30-min time trials 1.5 (TT1) and 3 (TT2) hours after CF (900 mg CF) or placebo (PL, 13 mg CF) intake, interposed by passive rest. Lactate, glucose, heartrate, rating of perceived exertion (RPE) and power output were measured during the TTs. Blood was drawn at baseline, before and after each TT and analyzed for epicatechin serum concentrations, trolox equivalent antioxidative capacity (TEAC), uric acid (UA), malonaldehyde (MDA), L-arginine/ADMA, citrulline, interleukin (IL)-1, IL-6 and tumor necrosis factor (TNF)-α plasma concentrations. Relative changes in blood markers and pacing strategy during TT were analysed by repeated measured ANOVA. TT performance was compared between PL and CF by paired t-test. Epicatechin concentrations were increased by CF intake. Exercise-induced increase in TEAC/UA was improved by CF intake (F(1) = 5.57; p = .038) (post-TT1: PL: 113.34 ± 3.9%, CF: 117.64 ± 3.96%, post-TT2: PL: 108.59 ± 3.95%, CF: 123.72 ± 7.4% to baseline), while exercise-induced increases in MDA, IL-1 and IL-6 were not affected by CF intake. TNF-α was unaltered by exercise and by CF. Exercise-induced decreases in L-arginine/ADMA and increases in citrulline were not affected by CF intake. TT1 and TT2 performance and exercise-induced physiological changes were unaffected by CF intake. Acute CF intake increased total antioxidant capacity in rest and during exercise

  4. Localization of nitric oxide synthase in human skeletal muscle

    DEFF Research Database (Denmark)

    Frandsen, Ulrik; Lopez-Figueroa, M.; Hellsten, Ylva

    1996-01-01

    The present study investigated the cellular localization of the neuronal type I and endothelial type III nitric oxide synthase in human skeletal muscle. Type I NO synthase immunoreactivity was found in the sarcolemma and the cytoplasm of all muscle fibres. Stronger immunoreactivity was expressed...... I NO synthase immunoreactivity and NADPH diaphorase activity. Type III NO synthase immunoreactivity was observed both in the endothelium of larger vessels and of microvessels. The results establish that human skeletal muscle expresses two different constitutive isoforms of NO synthase in different...... endothelium is consistent with a role for NO in the control of blood flow in human skeletal muscle....

  5. Nitric oxide synthase expression and enzymatic activity in multiple sclerosis

    DEFF Research Database (Denmark)

    Broholm, H; Andersen, B; Wanscher, B

    2004-01-01

    and endothelial nitric oxide synthase (NOS)], and enzymatic NO synthase activity. MRI guided biopsies documented more active plaques than macroscopic examination, and histological examination revealed further lesions. Inducible NOS (iNOS) was the dominant IR isoform, while reactive astrocytes were the dominant i......NOS expressing cells in active lesions. NOS IR expressing cells were widely distributed in plaques, in white and gray matter that appeared normal macroscopically, and on MR. Endothelial NOS (eNOS) was highly expressed in intraparenchymal vascular endothelial cells of MS patients. A control group matched for age...

  6. Effect of glutathione on brain nitric oxide levels in an experimental epilepsy mouse model

    Institute of Scientific and Technical Information of China (English)

    Aylin Akcali; Sadrettin Pence; Naciye Kurtul; Mehmet Bosnak; Munife Neyal

    2009-01-01

    BACKGROUND: Oxidative stress plays an important role in the pathophysiology of epilepsy. Glutathione, known as one of the compounds of antioxidant defense, has been shown to inhibit convulsions. Nitric oxide has a proconvulsant effect on a pentylenetetrazole-induced animal model. OBJECTIVE: To evaluate the effects of glutathione administration on nitric oxide levels in brain regions of convulsive and kindling pentylenetetrazole-induced seizure models. DESIGN, TIME, AND SETTING: A randomized, controlled, animal experiment. The study was performed at the Department of Physiology, Gaziantep University and Department of Chemistry-Biochemistry, Kahramamaras Sutcu Imam University in 2006.MATERIALS: Pentylenetetrazole and glutathione were purchased from Sigma, USA. METHODS: A total of 80 mice were assigned to 8 groups (n=10): normal control, saline control (1 mL normal saline), convulsive pentylenetetrazole (single intraperitoneal administration of pentylenetetrazole, 60 mg/kg), convulsive pentylenetrazole plus glutathione (single administration of 60 mg/kg pentylenetetrazole and 200 mg/kg glutathione), five-dose glutathione (intraperitoneal injection of 200 mg/kg glutathione respectively at 1, 3, 5, 7, and 10 days), single-dose glutathione (single administration of 200 mg/kg glutathione), pentylenetetrazole kindling (intraperitoneal administration of pentylenetetrazole of 40 mg/kg at 1, 3, 5, 7, and 10 days), and pentylenetetrazole kindling plus glutathione group (intraperitoneal injection of 40 mg/kg pentylenetetrazole and 200 mg/kg glutathione respectively at 1, 3, 5, 7, and 10 days). MAIN OUTCOME MEASURES: All mice were sacrificed 1 hour after the last administration. Brain nitric oxide levels were determined by spectrophotometry. RESULTS: There were no significant differences in nitric oxide levels between the normal control, saline control, five-dose glutathione, and single-dose glutathione groups (P>0.05). Nitric oxide levels in the cerebral hemisphere and

  7. Nitric oxide synthase and nitric oxide alterations in chronically stressed rats: a model for nitric oxide in major depressive disorder.

    Science.gov (United States)

    Gao, Shang-Feng; Lu, Yun-Rong; Shi, Li-Gen; Wu, Xue-Yan; Sun, Bo; Fu, Xin-Yan; Luo, Jian-Hong; Bao, Ai-Min

    2014-09-01

    Nitric oxide (NO) and NO synthase-1 (NOS1) are involved in the stress response and in depression. We compared NOS-NO alterations in rats exposed to chronic unpredictable stress (CUS) with alterations in major depressive disorder (MDD) in humans. In the hypothalamus of male CUS rats we determined NOS activity, and in the paraventricular nucleus (PVN) we determined NOS1-immunoreactive (ir) cell densities and co-localization of NOS1 with stress-related neuropeptides corticotropin-releasing hormone (CRH), vasopressin (AVP) or oxytocin (OXT). We measured plasma NO levels and cortisol in male medicine-naïve MDD patients and plasma NO and corticosterone (CORT) in CUS rats. In the CUS rat total NOS activity in the hypothalamus (P=0.018) and NOS1-ir cell density in the PVN were both significantly decreased (P=0.018), while NOS1 staining was mainly expressed in OXT-ir neurons in this nucleus. Interestingly, plasma NO levels were significantly increased both in male CUS rats (P=0.001) and in male MDD patients (Pdepression.

  8. The Effect of Nitric Oxide on the Growth of Marine Phytoplankton

    Institute of Scientific and Technical Information of China (English)

    ZHANG Zhengbin; LIN Cai; LIU Chunying; SUN Mingyi; DING Haibing

    2003-01-01

    The incubation experiments of Skeletonema costatum, Dicrateria zhanjiangensis nov. sp., and Platymonas subcordiformis, and those of Emiliania huxleyi were carried out in the Marine Physical Chemistry Laboratory in Ocean University of China and in the Marine Organic Geochemistry Laboratory in the University of Georgia respectively. Nitric oxide was added into the media when these marine microalgae were growing. We found the grovth of these four microalgae were promoted or inhibited when nitric oxide of different concentrations was added one or two times each day during the cultivation process. The results are consistent with the influence of nitric oxide on the growth of high plants. The results show that nitric oxide may be a new factor of regulation and control for the phytoplankton growth in seawater.

  9. The effect of inhaled nitric oxide in acute respiratory distress syndrome in children and adults

    DEFF Research Database (Denmark)

    Karam, O; Gebistorf, F; Wetterslev, J

    2017-01-01

    Acute respiratory distress syndrome is associated with high mortality and morbidity. Inhaled nitric oxide has been used to improve oxygenation but its role remains controversial. Our primary objective in this systematic review was to examine the effects of inhaled nitric oxide administration...... on mortality in adults and children with acute respiratory distress syndrome. We included all randomised, controlled trials, irrespective of date of publication, blinding status, outcomes reported or language. Our primary outcome measure was all-cause mortality. We performed several subgroup and sensitivity......% CI) 1.59 (1.17-2.16)) with inhaled nitric oxide. In conclusion, there is insufficient evidence to support inhaled nitric oxide in any category of critically ill patients with acute respiratory distress syndrome despite a transient improvement in oxygenation, since mortality is not reduced and it may...

  10. Nitric Oxide and eNOS Gene in Essential Hypertension

    Directory of Open Access Journals (Sweden)

    Kamna Srivastava

    2009-04-01

    Full Text Available Background: Currently hypertension grips around 25% of the entire world population. More than 90% of the hypertensive patients suffer from essential hypertension. In Asian Indians hypertension is the predominant risk factor for Coronary Artery Disease among others. Nitric Oxide (NO is synonymous with endothelial derived relaxation factor. Acting via cGMP (cyclic guanosine monophosphate it causes smooth muscle relaxation, prevents platelet aggregation and acts as an anti-inflammatory agent. iNOS (inducible Nitric oxide synthase, nNOS(neuronal nitric oxide synthase and eNOS (endothelial nitric oxide synthase are the three enzymes producing the gas nitric oxide in the human body. eNOS is the main source of NO under physiological conditions. It is known to have a number of polymorphisms. The most well known ones being the G to T polymorphism in exon 7, the T to C polymorphism in the promoter region and the a/b polymorphism in the intron 4. While the G to T polymorphism has been associated with hypertension in many races including the north Indian population, the association of other polymorphisms has been more of a controversy. Not much study has been done on the Asians especially those in India regarding these polymorphisms. Aims: To elucidate the association between the intron4a/b polymorphism in the eNOS gene and nitric oxide levels and essential hypertension. Objectives: 1. To determine the genotype frequencies of the above mentioned polymorphism in patients and controls2. To study the levels of NO in the plasma of the patients and controls3. To find out correlation if any between this polymorphism and plasma NO levels4. To find a correlation if any between this polymorphism and essential hypertension Materials and Methods: The study design was a case control study. 10 ml of venous blood was taken from 45 patients (selected from the department of Cardiology All India Institute of Medical Sciences, ages between 25 to 55 yrs and not on any

  11. Evaluation of Salivary Nitric Oxide Levels in Smokers, Tobacco Chewers and Patients with Oral Lichenoid Reactions

    Science.gov (United States)

    Jose, Joy Idiculla; Sivapathasundharam, B.; Sabarinath, B.

    2016-01-01

    Introduction Nitric oxide (NO), a free radical, acts as a signalling molecule affecting numerous physiological and pathological processes. Role of nitric oxide as a mediator in tobacco related habits and the resultant oral lichenoid reactions was assessed. Aim The aim of the study is to evaluate and compare the salivary nitric oxide levels in normal patients with that of smokers, tobacco chewers and patients with oral lichenoid reactions. Materials and Methods One hundred and twenty patients were enrolled in the study which included 30 healthy patients without any chronic inflammatory lesion and habit as controls (group I), 30 smokers without the habit of tobacco/betel nut chewing and any oral lesion (group II), 30 tobacco chewers without the habit of smoking and any oral lesion (group III) and 30 histologically confirmed cases of oral lichenoid reaction with the habit of tobacco usage (group IV). Saliva from these patients was collected and the nitrite concentration was assessed. Results Our results concluded that there was highly significant increase in the nitric oxide levels in smokers, tobacco chewers and patients with oral lichenoid reactions compared to that of controls. Also, there was a significant increase in nitric oxide levels in patients with smoking associated oral lichenoid reactions in comparison with smokers and in patients with lichenoid reactions associated with tobacco chewing in comparison with tobacco chewers. Conclusion Estimation of salivary nitric oxide levels is a simple, non-invasive procedure and could be analysed to suggest the role of nitric oxide in the pathogenesis of these lesions. The increased activity of the enzyme may indicate that nitric oxide has a pathophysiological role in these lesions. PMID:26894179

  12. Nitric oxide metabolites in goldfish under normoxic and hypoxic conditions

    DEFF Research Database (Denmark)

    Hansen, Marie N.; Jensen, Frank Bo

    2010-01-01

    Nitric oxide (NO), produced by nitric oxide synthases (NOS enzymes), regulates multiple physiological functions in animals. NO exerts its effects by binding to iron (Fe) of heme groups (exemplified by the activation of soluble guanylyl cyclase) and by S-nitrosylation of proteins – and it is metab......Nitric oxide (NO), produced by nitric oxide synthases (NOS enzymes), regulates multiple physiological functions in animals. NO exerts its effects by binding to iron (Fe) of heme groups (exemplified by the activation of soluble guanylyl cyclase) and by S-nitrosylation of proteins...... levels was assessed from metabolic and respiratory variables. In normoxic goldfish, the concentrations of NO metabolites in plasma and tissues were comparable with values reported in mammals, indicative of similar NOS activity. Exposure to hypoxia [at PO2 (partial pressure of O2) values close...

  13. The Effect of Nitric Oxide Donor in Diabetic Wound Healing

    Directory of Open Access Journals (Sweden)

    N Dashti

    2003-10-01

    Full Text Available Diabetes is characterized by a nitric oxide deficiency at the wound site. Diabetes is a factor that influences all stages of wound healing. In animals with acute experimental diabetes induced by streptozotocin (STZ, the early inflammatory responses after wounding is impaired, fibroblast and endothelial cell proliferation is reduced as well as accumulation of reparative collagen and gain in wound breaking strenght. This study investigated whether exogenous nitric oxide supplimentation with nitric oxide donor DETA NONOate could reverse impaired healing in diabetes. The results suggest nitric oxide donor DETA NONOate can reverse impaired healing associated with diabetes (P<0.001 and urinary nitrate (NO-3 output may reflect the extent of repair in this wound model (P<0.001.

  14. Inducible nitric oxide synthase mediates bone loss in ovariectomized mice.

    NARCIS (Netherlands)

    Cuzzocrea, S.; Mazzon, E.; Dugo, L.; Genovese, T.; Paola, R. Di; Ruggeri, Z.; Vegeto, E.; Caputi, A.P.; Loo, F.A.J. van de; Puzzolo, D.; Maggi, A.

    2003-01-01

    Several clinical studies have shown that bone loss may be attributed to osteoclast recruitment induced by mediators of inflammation. In different experimental paradigms we have recently demonstrated that estrogen exhibits antiinflammatory activity by preventing the induction of inducible nitric oxid

  15. Adhesion Development and the Expression of Endothelial Nitric Oxide Synthase

    Directory of Open Access Journals (Sweden)

    David M. Svinarich

    2001-01-01

    Full Text Available Objective: This study was conducted to determine whether nitric oxide (NO, a potent vasodilator and inhibitor of thrombus formation, is involved in the formation and maintenance of adhesions.

  16. Nitric oxide damages neuronal mitochondria and induces apoptosis in neurons

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The cytotoxic effect of nitric oxide on primarily cultured rat cerebellar granule cells was studied,and the mechanisms were discussed.The results showed that nitric oxide donor S-nitroso-N-acetyl-penicillamine (SNAP; 500 μmol/L) could induce apoptosis in immature cultures of cerebellar granule cells.Flow cytometry and HPLC analyses revealed that after treatment with SNAP,the mitochondrial transmembrane potential and the cellular ATP content decreased significantly.Nitric oxide scavenger hemoglobin could effectively prevent the neuronal mitochondria from dysfunction and attenuate apoptosis.The results suggested that nitric oxide activated the apoptotic program by inhibiting the activity of mitochondrial respiratory chain and thus decreasing the cellular ATP content.

  17. Potassium softens vascular endothelium and increases nitric oxide release

    OpenAIRE

    2009-01-01

    In the presence of aldosterone, plasma sodium in the high physiological range stiffens endothelial cells and reduces the release of nitric oxide. We now demonstrate effects of extracellular potassium on stiffness of individual cultured bovine aortic endothelial cells by using the tip of an atomic force microscope as a mechanical nanosensor. An acute increase of potassium in the physiological range swells and softens the endothelial cell and increases the release of nitric oxide. A high physio...

  18. Hemoglobin: A Nitric-Oxide Dioxygenase

    Directory of Open Access Journals (Sweden)

    Paul R. Gardner

    2012-01-01

    Full Text Available Members of the hemoglobin superfamily efficiently catalyze nitric-oxide dioxygenation, and when paired with native electron donors, function as NO dioxygenases (NODs. Indeed, the NOD function has emerged as a more common and ancient function than the well-known role in O2 transport-storage. Novel hemoglobins possessing a NOD function continue to be discovered in diverse life forms. Unique hemoglobin structures evolved, in part, for catalysis with different electron donors. The mechanism of NOD catalysis by representative single domain hemoglobins and multidomain flavohemoglobin occurs through a multistep mechanism involving O2 migration to the heme pocket, O2 binding-reduction, NO migration, radical-radical coupling, O-atom rearrangement, nitrate release, and heme iron re-reduction. Unraveling the physiological functions of multiple NODs with varying expression in organisms and the complexity of NO as both a poison and signaling molecule remain grand challenges for the NO field. NOD knockout organisms and cells expressing recombinant NODs are helping to advance our understanding of NO actions in microbial infection, plant senescence, cancer, mitochondrial function, iron metabolism, and tissue O2 homeostasis. NOD inhibitors are being pursued for therapeutic applications as antibiotics and antitumor agents. Transgenic NOD-expressing plants, fish, algae, and microbes are being developed for agriculture, aquaculture, and industry.

  19. Nitric oxide and teratogenesis: an update.

    Science.gov (United States)

    Tiboni, Gian Mario; Ponzano, Adalisa

    2014-01-01

    Nitric oxide (NO), generated by NO synthase (NOS) enzymes, is an important bioactive molecule involved in the regulation of several biological phenomena that are crucial for organogenesis, including gene expression, cell growth, matrix remolding, proliferation, differentiation and apoptosis. The expression of NOS isoforms in embryonic tissues is temporally and spatially regulated, and disruption of endogenous NO can lead to developmental defects. Maternal treatment with pan NOS inhibitors during early organogenesis caused severe malformations of the axial skeleton. In utero exposure during the fetal period induced limb reduction defects of vascular origin. Knock-out mice have been used to define the role of the various NOS isoforms on the origin of the abnormal development. Cardiovascular malformations, limb reduction defects, reduced growth and reduced survival have been observed in knock-out mice with targeted disruption of endothelial NOS (eNOS). Limited morphological changes were observed in mice lacking inducible NOS (iNOS) or neuronal NOS n(NOS). Results obtained with in vitro studies suggest that optimal levels of NO are required for neural tube closure. Disregulation of NO production was also recently proposed as a contributing mechanism in the origin of malformations associated with exposure to known environmental teratogens, such as valproic acid, thalidomide, copper deficiency, and diabetes.

  20. Dietary Nitrate, Nitric Oxide, and Cardiovascular Health.

    Science.gov (United States)

    Bondonno, Catherine P; Croft, Kevin D; Hodgson, Jonathan M

    2016-09-09

    Emerging evidence strongly suggests that dietary nitrate, derived in the diet primarily from vegetables, could contribute to cardiovascular health via effects on nitric oxide (NO) status. NO plays an essential role in cardiovascular health. It is produced via the classical L-arginine-NO-synthase pathway and the recently discovered enterosalivary nitrate-nitrite-NO pathway. The discovery of this alternate pathway has highlighted dietary nitrate as a candidate for the cardioprotective effect of a diet rich in fruit and vegetables. Clinical trials with dietary nitrate have observed improvements in blood pressure, endothelial function, ischemia-reperfusion injury, arterial stiffness, platelet function, and exercise performance with a concomitant augmentation of markers of NO status. While these results are indicative of cardiovascular benefits with dietary nitrate intake, there is still a lingering concern about nitrate in relation to methemoglobinemia, cancer, and cardiovascular disease. It is the purpose of this review to present an overview of NO and its critical role in cardiovascular health; to detail the observed vascular benefits of dietary nitrate intake through effects on NO status as well as to discuss the controversy surrounding the possible toxic effects of nitrate.

  1. Endothelial nitric oxide synthase activation and nitric oxide function: new light through old windows.

    Science.gov (United States)

    Bird, Ian M

    2011-09-01

    The principle mechanisms operating at the level of endothelial nitric oxide synthase (eNOS) itself to control its activity are phosphorylation, the auto-regulatory properties of the protein itself, and Ca(2)(+)/calmodulin binding. It is now clear that activation of eNOS is greatest when phosphorylation of certain serine and threonine residues is accompanied by elevation of cytosolic [Ca2+](i). While eNOS also contains an autoinhibitory loop, Rafikov et al. (2011) present the evidence for a newly identified 'flexible arm' that operates in response to redox state. Boeldt et al. (2011) also review the evidence that changes in the nature of endothelial Ca(2)(+) signaling itself in different physiologic states can extend both the amplitude and duration of NO output, and a failure to change these responses in pregnancy is associated with preeclampsia. The change in Ca(2)(+) signaling is mediated through altering capacitative entry mechanisms inherent in the cell, and so many agonist responses using this mechanism are altered. The term 'adaptive cell signaling' is also introduced for the first time to describe this phenomenon. Finally NO is classically regarded as a regulator of vascular function, but NO has other actions. One proposed role is regulation of steroid biosynthesis but the physiologic relevance was unclear. Ducsay & Myers (2011) now present new evidence that NO may provide the adrenal with a mechanism to regulate cortisol output according to exposure to hypoxia. One thing all three of these reviews show is that even after several decades of study into NO biosynthesis and function, there are clearly still many things left to discover.

  2. Inhaled nitric oxide in full-term and nearly full-term infants with hypoxic respiratory failure

    NARCIS (Netherlands)

    Stork, E; Gorjanc, E; Verter, J; Younes, N; Stenzel, BA; Powers, T; Sokol, G; Wright, LL; Yaffe, SJ; Catz, C; Rhine, W; Ball, B; Brilli, R; Moles, L; Crowley, M; Backstrom, C; Crouse, D; Hudson, T; Konduri, G; Bara, R; Kleinman, M; Hensman, A; Rothstein, RW; Ehrenkranz, RA; Solimano, A; Germain, F; Walker, R; Ramirez, AM; Singhal, N; Bourcier, L; Fajardo, C; Cook, [No Value; Kirpalani, H; Monkman, S; Johnston, A; Mullahoo, K; Finer, NN; Peliowski, A; Etches, P; Kamstra, B; Sankarhan, K; Riehl, A; Blanchard, P; Gouin, R; Wearden, M; Gomez, M; Moon, Y; Bauer, CR; Donovan, EF; Fanaroff, AA; Korones, SB; Lemons, JA; Oh, W; Papile, LA; Shankaran, S; Stoll, BJ; Tyson, JE; Avery, G; DAlton, M; Bracken, MB; Gleason, CA; Maguire, M; Redmond, C; Silverman, W; Sinclair, J

    1997-01-01

    Background Neonates with pulmonary hypertension have been treated with inhaled nitric oxide because of studies suggesting that it is a selective pulmonary vasodilator. We conducted a randomized, multicenter, controlled trial to determine whether inhaled nitric oxide would reduce mortality or the ini

  3. Serum nitric oxide metabolite (NO(x)) levels in hypertensive patients at rest: a comparison of age, gender, blood pressure and complications using normotensive controls.

    Science.gov (United States)

    Higashino, Hideaki; Miya, Hirohisa; Mukai, Hidenori; Miya, Yoshihisa

    2007-08-01

    1. Hypertensive patients have pathophysiological changes such as atherosclerosis, endothelial dysfunction and inflammations. The patients' serum nitric oxide metabolite (nitrate/nitrite; NO(x)) levels were measured in peripheral blood using normotensive controls for comparison. 2. The NO(x) levels in 175 hypertensive patients with or without comorbid diseases (aged 37-95 years; average 50.6 +/- 0.8 years) were compared with those in 80 normotensive controls (aged 25-73 years; average 37.1 +/- 1.8 years). 3. The NO(x) levels increased with age in both the normotensive and hypertensive women, but not in men. No difference was noted in the NO(x) levels between the normotensive and hypertensive patients without comorbid diseases. The mean value of NO(x) in male hypertensive patients aged under 50 years was close to that of female patients aged 51-60 years. Hypertensive males aged 61-70 years showed almost the same NO(x) levels as those of female patients aged over 81 years. A male group of hypertensive patients with diabetes, hyperlipaemia and renal disorder had a significantly higher NO(x) level compared with a normotensive control group. However, in female groups, only hypertensive patients with hyperlipaemia showed higher serum NO(x) values compared with the normotensive group. 4. These findings suggest that: (i) the occurrence of NO(x) in the serum is not solely the outcome of high blood pressure; (ii) higher serum NO(x) levels in older women are because of an oestrogen deficiency-induced cardiovascular disease; (iii) ageing effects on the circulation system are more apparent in men than in women; and (iv) measurement of NO(x) levels in the serum is helpful for understanding the pathological progress in male hypertensive patients with diseases such as diabetes mellitus, hyperlipaemia and renal disorder.

  4. Nitric oxide in adaptation to altitude.

    Science.gov (United States)

    Beall, Cynthia M; Laskowski, Daniel; Erzurum, Serpil C

    2012-04-01

    This review summarizes published information on the levels of nitric oxide gas (NO) in the lungs and NO-derived liquid-phase molecules in the acclimatization of visitors newly arrived at altitudes of 2500 m or more and adaptation of populations whose ancestors arrived thousands of years ago. Studies of acutely exposed visitors to high altitude focus on the first 24-48 h with just a few extending to days or weeks. Among healthy visitors, NO levels in the lung, plasma, and/or red blood cells fell within 2h, but then returned toward baseline or slightly higher by 48 h and increased above baseline by 5 days. Among visitors ill with high-altitude pulmonary edema at the time of the study or in the past, NO levels were lower than those of their healthy counterparts. As for highland populations, Tibetans had NO levels in the lung, plasma, and red blood cells that were at least double and in some cases orders of magnitude greater than other populations regardless of altitude. Red blood cell-associated nitrogen oxides were more than 200 times higher. Other highland populations had generally higher levels although not to the degree shown by Tibetans. Overall, responses of those acclimatized and those presumed to be adapted are in the same direction, although the Tibetans have much larger responses. Missing are long-term data on lowlanders at altitude showing how similar they become to the Tibetan phenotype. Also missing are data on Tibetans at low altitude to see the extent to which their phenotype is a response to the immediate environment or expressed constitutively. The mechanisms causing the visitors' and the Tibetans' high levels of NO and NO-derived molecules at altitude remain unknown. Limited data suggest processes including hypoxic upregulation of NO synthase gene expression, hemoglobin-NO reactions, and genetic variation. Gains in understanding will require integrating appropriate methods and measurement techniques with indicators of adaptive function under hypoxic

  5. Antioxidant Functions of Nitric Oxide Synthase in a Methicillin Sensitive Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Manisha Vaish

    2013-01-01

    Full Text Available Nitric oxide and its derivative peroxynitrites are generated by host defense system to control bacterial infection. However certain Gram positive bacteria including Staphylococcus aureus possess a gene encoding nitric oxide synthase (SaNOS in their chromosome. In this study it was determined that under normal growth conditions, expression of SaNOS was highest during early exponential phase of the bacterial growth. In oxidative stress studies, deletion of SaNOS led to increased susceptibility of the mutant cells compared to wild-type S. aureus. While inhibition of SaNOS activity by the addition of L-NAME increased sensitivity of the wild-type S. aureus to oxidative stress, the addition of a nitric oxide donor, sodium nitroprusside, restored oxidative stress tolerance of the SaNOS mutant. The SaNOS mutant also showed reduced survival after phagocytosis by PMN cells with respect to wild-type S. aureus.

  6. Effect of Korean red ginseng on blood pressure and nitric oxide production

    Institute of Scientific and Technical Information of China (English)

    JEON Byeong Hwa; KIM Cuk Seong; KIM Hoe-Suk; PARK Jin-Bong; NAM Ki Yeul; CHANG Seok Jong

    2000-01-01

    AIM: To investigate the effect of crude saponin and nonsaponin fraction of Korean red ginseng (KRG) on the blood pressure and nitric oxide (NO) production in the conscious rats and cultured endothelial cell line, FCV 304 cells. METHODS: Systolic blood pressure and heart rate were monitored in the conscious rats. Nitric oxide levels and the expression of nitric oxide synthase were measured by a spectrophotometric assay using Griess reagents and Western blotting, respectively. Nitric-oxide synthase activity was measured based on the conversion rate of [3H]arginine to [3H]citmlline. RESUITS: Systolic blood pressure was decreased by crude saponin (100 mg/kg, iv) of KRG in the conscious control and one-kidney, one-clip Goldblatt hypertensive (1K, 1C-GBH) rats. The hypotensive effect induced by crude saponin of KRG reached maximum at 2 - 4 min and slowly recovered after 20 min to the initial level in both groups. Crude saponin of KRG induced tacliycardia in the conscious rats but induced bradycardia in the anesthetized rats. In contrast to crude saponin of KRG, hypotensive effect induced by saponin-free fraction was minimal. Nitric oxide concentrations were increased by the treaunent of crude saponin in conscious rats as well as in the cultured FCV 304 cells. The protein expression level of endothelial constitutive nitric-oxide synthase (eNOS) in the aorta of rats was not increased by crude saponin (100 mg/kg, ip for 3 d). However, nitric-oxide synthase activity was increased by crude saponin of KRG in the aortic homogenate of rats. CONCLUSION: The hypotensive effect of red ginseng is mainly due to saponin fraction of KRG in the conscious rats, and this effect may be due to an increase in the nitric-oxide production by KRG.

  7. Oral nitric-oxide donor glyceryl-trinitrate induces sensitization in spinal cord pain processing in migraineurs: a double-blind, placebo-controlled, cross-over study.

    Science.gov (United States)

    Perrotta, Armando; Serrao, Mariano; Tassorelli, Cristina; Arce-Leal, Natalia; Guaschino, Elena; Sances, Grazia; Rossi, Paolo; Bartolo, Michelangelo; Pierelli, Francesco; Sandrini, Giorgio; Nappi, Giuseppe

    2011-05-01

    Nitric-oxide donor glyceryl-trinitrate (GTN) modulates cerebral and spinal regions that are involved in migraine and pain processing. We hypothesized that in migraineurs, the susceptibility to develop a migraine attack after GTN administration should parallel with an high sensitivity to GTN-induced change in the pain processing at spinal level. We used the temporal summation threshold (TST) of the lower limb nociceptive withdrawal reflex (NWR) and the related pain sensation to study in parallel the time-course of the effect of the GTN administration on the pain processing at spinal level in migraine and healthy subjects. Twenty-eight (21 F; 7M; mean age 34.2 ± 8.2) migraine and 15 (11 F; 4M; mean age 35.9 ± 8.9) healthy subjects were recruited in a double-blind, placebo-controlled, cross-over trial. Neurophysiological examinations were carried out before (baseline) and 30', 60', 120', 180' and 240' after GTN (0.9 mg sublingual) or placebo administration during two different sessions. In migraineurs, GTN administration was associated to a significant facilitation in temporal summation of pain (reduced TST and increased painful sensation) 60', 120' and 180' after drug intake when compared to baseline, to placebo condition and to controls after GTN intake. Furthermore, in migraineurs who developed migraine after GTN, a significant facilitation in temporal summation of pain was detected 60', 120' and 180' after drug intake when compared to patients without clinical response. In migraineurs the susceptibility to develop migraine attack after GTN administration seems to be a specific trait of a subgroup of patients linked to a supersensitivity of the pain system to GTN.

  8. Biodegradable poly(lactic-co-glycolic acid) microspheres loaded with S-nitroso-N-acetyl-D-penicillamine for controlled nitric oxide delivery.

    Science.gov (United States)

    Lautner, Gergely; Meyerhoff, Mark E; Schwendeman, Steven P

    2016-03-10

    Nitric oxide (NO) is a fascinating and important endogenous free-radical gas with potent antimicrobial, vasodilating, smooth muscle relaxant, and growth factor stimulating effects. However, its wider biomedical applicability is hindered by its cumbersome administration, since NO is unstable especially in biological environments. In this work, to ultimately develop site-specific controlled release vehicles for NO, the NO donor S-nitroso-N-acetyl-D-penicillamine (SNAP) was encapsulated within poly(lactic-co-glycolic acid) 50:50 (PLGA) microspheres by using a solid-in-oil-in-water emulsion solvent evaporation method. The highest payload was 0.56(±0.01) μmol SNAP/mg microspheres. The in vitro release kinetics of the donor were controlled by the bioerosion of the PLGA microspheres. By using an uncapped PLGA (Mw=24,000-38,000) SNAP was slowly released for over 10days, whereas by using the ester capped PLGA (Mw=38,000-54,000) the release lasted for over 4weeks. The presence of copper ions and/or ascorbate in solution was necessary to efficiently decompose the released NO donor and obtain sustained NO release. It was also demonstrated that light can be used to induce rapid NO release from the microspheres over several hours. SNAP exhibited excellent storage stability when encapsulated in the PLGA microspheres. These new microsphere formulations may be useful for site-specific administration and treatment of pathologies associated with dysfunction in endogenous NO production, e.g. treatment of diabetic wounds, or in diseases involving other biological functions of NO including vasodilation, antimicrobial, anticancer, and neurotransmission. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Piper sarmentosum increases nitric oxide production in oxidative stress: a study on human umbilical vein endothelial cells

    Directory of Open Access Journals (Sweden)

    Azizah Ugusman

    2010-01-01

    Full Text Available OBJECTIVE: Nitric oxide produced by endothelial nitric oxide synthase (eNOS possesses multiple anti-atherosclerotic properties. Hence, enhanced expression of eNOS and increased Nitric oxide levels may protect against the development of atherosclerosis. Piper sarmentosum is a tropical plant with antioxidant and anti-inflammatory activities. This study aimed to investigate the effects of Piper sarmentosum on the eNOS and Nitric oxide pathway in cultured human umbilical vein endothelial cells (HUVECs. METHODS: HUVECs were divided into four groups: control, treatment with 180 μM hydrogen peroxide (H2O2, treatment with 150 μg/mL aqueous extract of Piper sarmentosum, and concomitant treatment with aqueous extract of PS and H2O2 for 24 hours. Subsequently, HUVECs were harvested and eNOS mRNA expression was determined using qPCR. The eNOS protein level was measured using ELISA, and the eNOS activity and Nitric oxide level were determined by the Griess reaction. RESULTS: Human umbilical vein endothelial cells treated with aqueous extract of Piper sarmentosum showed a marked induction of Nitric oxide. Treatment with PS also resulted in increased eNOS mRNA expression, eNOS protein level and eNOS activity in HUVECs. CONCLUSION: Aqueous extract of Piper sarmentosum may improve endothelial function by promoting NO production in HUVECs.

  10. Piper sarmentosum increases nitric oxide production in oxidative stress: a study on human umbilical vein endothelial cells.

    Science.gov (United States)

    Ugusman, Azizah; Zakaria, Zaiton; Hui, Chua Kien; Nordin, Nor Anita Megat Mohd

    2010-07-01

    Nitric oxide produced by endothelial nitric oxide synthase (eNOS) possesses multiple anti-atherosclerotic properties. Hence, enhanced expression of eNOS and increased Nitric oxide levels may protect against the development of atherosclerosis. Piper sarmentosum is a tropical plant with antioxidant and anti-inflammatory activities. This study aimed to investigate the effects of Piper sarmentosum on the eNOS and Nitric oxide pathway in cultured human umbilical vein endothelial cells (HUVECs). HUVECS WERE DIVIDED INTO FOUR GROUPS: control, treatment with 180 microM hydrogen peroxide (H(2)O(2)), treatment with 150 microg/mL aqueous extract of Piper sarmentosum, and concomitant treatment with aqueous extract of PS and H(2)O(2) for 24 hours. Subsequently, HUVECs were harvested and eNOS mRNA expression was determined using qPCR. The eNOS protein level was measured using ELISA, and the eNOS activity and Nitric oxide level were determined by the Griess reaction. Human umbilical vein endothelial cells treated with aqueous extract of Piper sarmentosum showed a marked induction of Nitric oxide. Treatment with PS also resulted in increased eNOS mRNA expression, eNOS protein level and eNOS activity in HUVECs. Aqueous extract of Piper sarmentosum may improve endothelial function by promoting NO production in HUVECs.

  11. Nitric oxide production and nitric oxide synthase immunoreactivity in Naegleria fowleri.

    Science.gov (United States)

    Rojas-Hernández, Saúl; Rodríguez-Monroy, Marco A; Moreno-Fierros, Leticia; Jarillo-Luna, Adriana; Carrasco-Yepez, Marisela; Miliar-García, Angel; Campos-Rodríguez, Rafael

    2007-07-01

    Free-living ameba Naegleria fowleri produces an acute and fatal infectious disease called primary amebic meningoencephalitis (PAM), whose pathophysiological mechanism is largely unknown. The aim of this study was to investigate the role of nitric oxide (NO) in PAM. Although NO has a cytotoxic effect on various parasites, it is produced by others as part of the pathology, as is the case with Entamoeba histolytica. To test for the production of NO, we analyzed whether antibodies against mammalian NO synthase isoforms (neuronal, inducible, and endothelial) presented immunoreactivity to N. fowleri proteins. We found that the trophozoites produced NO in vitro. The Western blot results, which showed N. fowleri trophozoites, contained proteins that share epitopes with the three described mammalian NOS, but have relative molecular weights different than those described in the literature, suggesting that N. fowleri may contain undescribed NOS isoforms. Moreover, we found that trophozoites reacted to the NOS2 antibody, in amebic cultures as well as in the mouse brain infected with N. fowleri, suggesting that nitric oxide may participate in the pathogenesis of PAM. Further research aimed at determining whether N. fowleri contains active novel NOS isoforms could lead to the design of new therapies against this parasite.

  12. Nitric oxide permits hypoxia-induced lymphatic perfusion by controlling arterial-lymphatic conduits in zebrafish and glass catfish

    DEFF Research Database (Denmark)

    Dahl Ejby Jensen, Lasse; Cao, Renhai; Hedlund, Eva-Maria

    2009-01-01

    The blood and lymphatic vasculatures are structurally and functionally coupled in controlling tissue perfusion, extracellular interstitial fluids, and immune surveillance. Little is known, however, about the molecular mechanisms that underlie the regulation of bloodlymphatic vessel connections...

  13. Nitric oxide: an intermediate in nitrate reduction in Klebsiella pneumoniae

    Energy Technology Data Exchange (ETDEWEB)

    Al-Abdulla, J.M.; Aleem, M.I.H.

    1977-01-01

    When K. pneumoniae cells were grown anaerobically with nitrate as the final electron acceptor, there was a rapid reduction of nitrate to nitrite. The latter was further reduced to hydroxylamine and finally to ammonia. Nitrate, nitrite and nitric oxide, but not nitrous oxide, could accept electrons from the respiratory chain. During growth of the organism it was possible to trap nitric oxide with alkaline permanganate. The trapped gas represented only a small portion of the reduced electron acceptor. It would appear that a major portion of nitric oxide produced from nitrite reduction must be converted to an unknown nitrogenous intermediate with an oxidation state of +1 before its reduction to hydroxylamine. The possible nature of this elusive intermediate should be discussed.

  14. Concentrations of Nitric Oxide in Rat Brain Tissues after Diffuse Brain Injury and Neuroprotection by the Selective Inducible Nitric Oxide Synthase Inhibitor Aminoguanidine

    Institute of Scientific and Technical Information of China (English)

    Yi-bao Wang; Shao-wu Ou; Guang-yu Li; Yun-hui Liu

    2005-01-01

    @@ To investigate the effects of nitric oxide (NO) and the selective inducible nitric oxide synthase (iNOS) inhibitor aminoguanidine (AG) on trauma, we explored the concentrations of nitric oxide in rat brain tissues at different time stamps after diffuse brain injury (DBI) with or without AG treatment.

  15. Nitric oxide scavenging by red cell microparticles.

    Science.gov (United States)

    Liu, Chen; Zhao, Weixin; Christ, George J; Gladwin, Mark T; Kim-Shapiro, Daniel B

    2013-12-01

    Red cell microparticles form during the storage of red blood cells and in diseases associated with red cell breakdown and asplenia, including hemolytic anemias such as sickle cell disease. These small phospholipid vesicles that are derived from red blood cells have been implicated in the pathogenesis of transfusion of aged stored blood and hemolytic diseases, via activation of the hemostatic system and effects on nitric oxide (NO) bioavailability. Red cell microparticles react with the important signaling molecule NO almost as fast as cell-free hemoglobin, about 1000 times faster than red-cell-encapsulated hemoglobin. The degree to which this fast reaction with NO by red cell microparticles influences NO bioavailability depends on several factors that are explored here. In the context of stored blood preserved in ADSOL, we find that both cell-free hemoglobin and red cell microparticles increase as a function of duration of storage, and the proportion of extra erythrocytic hemoglobin in the red cell microparticle fraction is about 20% throughout storage. Normalized by hemoglobin concentration, the NO-scavenging ability of cell-free hemoglobin is slightly higher than that of red cell microparticles as determined by a chemiluminescence NO-scavenging assay. Computational simulations show that the degree to which red cell microparticles scavenge NO will depend substantially on whether they enter the cell-free zone next to the endothelial cells. Single-microvessel myography experiments performed under laminar flow conditions demonstrate that microparticles significantly enter the cell-free zone and inhibit acetylcholine, endothelial-dependent, and NO-dependent vasodilation. Taken together, these data suggest that as little as 5 μM hemoglobin in red cell microparticles, an amount formed after the infusion of one unit of aged stored packed red blood cells, has the potential to reduce NO bioavailability and impair endothelial-dependent vasodilation.

  16. Expression of inducible nitric oxide in human lung epithelial cells.

    Science.gov (United States)

    Robbins, R A; Barnes, P J; Springall, D R; Warren, J B; Kwon, O J; Buttery, L D; Wilson, A J; Geller, D A; Polak, J M

    1994-08-30

    Nitric oxide (NO) is increased in the exhaled air of subjects with several airway disorders. To determine if cytokines could stimulate epithelial cells accounting for the increased NO, the capacity of the proinflammatory cytokines (cytomix: tumor necrosis factor-alpha, interleukin-1 beta, and interferon-gamma) to increase inducible nitric oxide synthase (iNOS) was investigated in A549 and primary cultures of human bronchial epithelial cells. Cytomix induced a time-dependent increase in nitrite levels in culture supernatant fluids (p < 0.05). Increased numbers of cells stained for iNOS and increased iNOS mRNA was detected in the cytokine-stimulated cells compared to control (p < 0.05). Dexamethasone diminished the cytokine-induced increase in nitrite, iNOS by immunocytochemistry, and iNOS mRNA. These data demonstrate that cytokines, such as those released by mononuclear cells, can induce lung epithelial iNOS expression and NO release, and that this is attenuated by dexamethasone.

  17. Identification of gene variants related to the nitric oxide pathway in patients with acute coronary syndrome.

    Science.gov (United States)

    Umman, B; Cakmakoglu, B; Cincin, Z B; Kocaaga, M; Emet, S; Tamer, S; Gokkusu, C

    2015-12-10

    Dysfunction of vascular endothelium is known to have an essential role in the atherosclerotic process by releasing mediators including nitric oxide (NO). Nitric oxide maintains endothelial balance by controlling cellular processes of vascular smooth muscle cells. Evidence suggests that variations in the NO pathway could include atherosclerotic events. The objective of this study was to determine the possible effects of genes on the nitric oxide pathway in the development of acute coronary syndrome (ACS). The blood samples of 100 patients with ACS and 100 controls were collected at Istanbul University, Department of Cardiology. DNA samples were genotyped by using Illumina Cyto-SNP-12 BeadChip. The additive model and Correlation/Trend Test were selected for association analysis. Afterwards, a Q-Q graphic was drawn to compare expected and obtained values. A Manhattan plot was produced to display p-values that were generated by -log10(P) function for each SNP. The p-values under 1×10(-4) were selected as statistically significant SNPs while p-values under 5×10(-2) were considered as suspicious biomarker candidates. Nitric oxide pathway analysis was then used to find the single nucleotide polymorphisms (SNPs) related to ACS. As a result, death-associated protein kinase 3 (DAPK) (rs10426955) was found to be most statistically significant SNP. The most suspicious biomarker candidates associated with the nitric oxide pathway analysis were vascular endothelial growth factor A (VEGFA), methionine sulfoxide reductase A (MSRA), nitric oxide synthase 1 (NOS1), and GTP cyclohydrolase I (GCH-1). Further studies with large sample groups are necessary to clarify the exact role of nitric oxide in the development of disease.

  18. Study of nitric oxide catalytic oxidation on manganese oxides-loaded activated carbon at low temperature

    Science.gov (United States)

    You, Fu-Tian; Yu, Guang-Wei; Wang, Yin; Xing, Zhen-Jiao; Liu, Xue-Jiao; Li, Jie

    2017-08-01

    Nitric oxide (NO) is an air pollutant that is difficult to remove at low concentration and low temperature. Manganese oxides (MnOx)-loaded activated carbon (MLAC) was prepared by a co-precipitation method and studied as a new catalyst for NO oxidation at low temperature. Characterization of MLAC included X-ray diffraction (XRD), scanning electron microscopy (SEM), N2 adsorption/desorption and X-ray photoelectron spectroscopy (XPS). Activity tests demonstrated the influence of the amount of MnOx and the test conditions on the reaction. MLAC with 7.5 wt.% MnOx (MLAC003) exhibits the highest NO conversion (38.7%) at 1000 ppm NO, 20 vol.% O2, room temperature and GHSV ca. 16000 h-1. The NO conversion of MLAC003 was elevated by 26% compared with that of activated carbon. The results of the MLAC003 activity test under different test conditions demonstrated that NO conversion is also influenced by inlet NO concentration, inlet O2 concentration, reaction temperature and GHSV. The NO adsorption-desorption process in micropores of activated carbon is fundamental to NO oxidation, which can be controlled by pore structure and reaction temperature. The activity elevation caused by MnOx loading is assumed to be related to Mn4+/Mn3+ ratio. Finally, a mechanism of NO catalytic oxidation on MLAC based on NO adsorption-desorption and MnOx lattice O transfer is proposed.

  19. Nitric Oxide in Astrocyte-Neuron Signaling

    Energy Technology Data Exchange (ETDEWEB)

    Li, Nianzhen [Iowa State Univ., Ames, IA (United States)

    2002-01-01

    Astrocytes, a subtype of glial cell, have recently been shown to exhibit Ca2+ elevations in response to neurotransmitters. A Ca2+ elevation can propagate to adjacent astrocytes as a Ca2+ wave, which allows an astrocyte to communicate with its neighbors. Additionally, glutamate can be released from astrocytes via a Ca2+-dependent mechanism, thus modulating neuronal activity and synaptic transmission. In this dissertation, the author investigated the roles of another endogenous signal, nitric oxide (NO), in astrocyte-neuron signaling. First the author tested if NO is generated during astrocytic Ca2+ signaling by imaging NO in purified murine cortical astrocyte cultures. Physiological concentrations of a natural messenger, ATP, caused a Ca2+-dependent NO production. To test the roles of NO in astrocytic Ca2+ signaling, the author applied NO to astrocyte cultures via addition of a NO donor, S-nitrosol-N-acetylpenicillamine (SNAP). NO induced an influx of external Ca2+, possibly through store-operated Ca2+ channels. The NO-induced Ca2+ signaling is cGMP-independent since 8-Br-cGMP, an agonistic analog of cGMP, did not induce a detectable Ca2+ change. The consequence of this NO-induced Ca2+ influx was assessed by simultaneously monitoring of cytosolic and internal store Ca2+ using fluorescent Ca2+ indicators x-rhod-1 and mag-fluo-4. Blockage of NO signaling with the NO scavenger PTIO significantly reduced the refilling percentage of internal stores following ATP-induced Ca2+ release, suggesting that NO modulates internal store refilling. Furthermore, locally photo-release of NO to a single astrocyte led to a Ca2+ elevation in the stimulated astrocyte and a subsequent Ca2+ wave to neighbors. Finally, the author tested the role of NO inglutamate-mediated astrocyte-neuron signaling by

  20. Nitric Oxide in Astrocyte-Neuron Signaling

    Energy Technology Data Exchange (ETDEWEB)

    Nianzhen Li

    2002-06-27

    Astrocytes, a subtype of glial cell, have recently been shown to exhibit Ca{sup 2+} elevations in response to neurotransmitters. A Ca{sup 2+} elevation can propagate to adjacent astrocytes as a Ca{sup 2+} wave, which allows an astrocyte to communicate with its neighbors. Additionally, glutamate can be released from astrocytes via a Ca{sup 2+}-dependent mechanism, thus modulating neuronal activity and synaptic transmission. In this dissertation, the author investigated the roles of another endogenous signal, nitric oxide (NO), in astrocyte-neuron signaling. First the author tested if NO is generated during astrocytic Ca{sup 2+} signaling by imaging NO in purified murine cortical astrocyte cultures. Physiological concentrations of a natural messenger, ATP, caused a Ca{sup 2+}-dependent NO production. To test the roles of NO in astrocytic Ca{sup 2+} signaling, the author applied NO to astrocyte cultures via addition of a NO donor, S-nitrosol-N-acetylpenicillamine (SNAP). NO induced an influx of external Ca{sup 2+}, possibly through store-operated Ca{sup 2+} channels. The NO-induced Ca{sup 2+} signaling is cGMP-independent since 8-Br-cGMP, an agonistic analog of cGMP, did not induce a detectable Ca{sup 2+} change. The consequence of this NO-induced Ca{sup 2+} influx was assessed by simultaneously monitoring of cytosolic and internal store Ca{sup 2+} using fluorescent Ca{sup 2+} indicators x-rhod-1 and mag-fluo-4. Blockage of NO signaling with the NO scavenger PTIO significantly reduced the refilling percentage of internal stores following ATP-induced Ca{sup 2+} release, suggesting that NO modulates internal store refilling. Furthermore, locally photo-release of NO to a single astrocyte led to a Ca{sup 2+} elevation in the stimulated astrocyte and a subsequent Ca{sup 2+} wave to neighbors. Finally, the author tested the role of NO inglutamate-mediated astrocyte-neuron signaling by recording the astrocyte-evoked glutamate-dependent neuronal slow inward current (SIC

  1. Protection by nitric oxide against liver inflammatory injury in animals carrying a nitric oxide synthase-2 transgene.

    Science.gov (United States)

    Mojena, M; Hortelano, S; Castrillo, A; Diaz-Guerra, M J; Garcia-Barchino, M J; Saez, G T; Bosca, L

    2001-03-01

    The effect of pre-existent hepatic NO synthesis on liver injury induced by lipopolysaccharide was studied in animals carrying a nitric oxide synthase-2 (NOS-2) transgene under the control of the phosphoenolpyruvate carboxykinase (PEPCK) promoter. These animals expressed NOS-2 in liver cells under fasting conditions. Lipopolysaccharide-induced liver injury in D-galactosamine-conditioned mice, which enhanced notably the effect of the endotoxin on the liver, was impaired in animals expressing NOS-2. This protection against inflammatory liver damage was dependent on NO synthesis and was caused by an inhibition of nuclear factor kB (NF-kB) activity and an impairment of the synthesis of the proinflammatory cytokines tumor necrosis factor a and interleukin 1b. These data indicate that intrahepatic synthesis of NO protects liver by inhibiting the release of cascades of proinflammatory mediators and suggest a beneficial role for local delivery of NO in the control of liver injury.

  2. Use of aminoguanidine, a selective inducible nitric oxide synthase inhibitor, to evaluate the role of nitric oxide in periapical inflammation.

    Science.gov (United States)

    Farhad, Ali R; Razavi, Seyedmohammad; Jahadi, Sanaz; Saatchi, Masoud

    2011-06-01

    The purpose of this study was to evaluate the effects of aminoguanidine (AG) as a selective inhibitor of inducible nitric oxide synthase (iNOS) on the degree of inflammatory response in periapical lesions in the canine teeth of cats. Root canals from 52 cat canine teeth were exposed to the oral cavity and sealed after 7 days. One day before pulp exposure, cats were administered either AG (experimental group) or normal saline (control group), which was continued on a daily basis until the day of sacrifice. Animals were sacrificed at 28 days after pulp exposure. Inflammatory response in the periapical zones was analyzed histologically. The degree of periapical inflammation in the AG group was significantly lower than that in the control group (P < 0.05). Selective iNOS inhibitors such as AG thus reduce the intensity of inflammatory responses in periapical lesions.

  3. Pain modulation by nitric oxide in the spinal cord.

    Directory of Open Access Journals (Sweden)

    Marco Aurelio M Freire

    2009-09-01

    Full Text Available Nitric oxide (NO is a versatile messenger molecule first associated with endothelial relaxing effects. In the central nervous system (CNS, NO synthesis is primarily triggered by activation of N-methyl-D-aspartate (NMDA receptors and has a Janus face, with both beneficial and harmful properties, depending on concentration and the identity of its synthetic enzyme isoform. There are three isoforms of the NO synthesizing enzyme nitric oxide synthase (NOS: neuronal (nNOS, endothelial (eNOS, and inducible nitric oxide synthase (iNOS, each one involved with specific events in the brain. In CNS, nNOS is involved with modulation of synaptic transmission through long-term potentiation in several regions, including nociceptive circuits in the spinal cord. Here, we review the role played by NO on central pain sensitization.

  4. A nitric oxide donor (nitroglycerin) triggers genuine migraine attacks

    DEFF Research Database (Denmark)

    Thomsen, L L; Kruuse, C; Iversen, Helle Klingenberg

    1994-01-01

    Supersensitivity to induction of headache and arterial dilatation by a donor of nitric oxide (nitroglycerin) has recently been demonstrated in migraine sufferers. The aims of the present study were to examine whether the nitric oxide donor nitroglycerin may induce a typical migraine attack.......03). The time pattern of headache and estimated middle cerebral artery dilatation corresponded well. The study therefore demonstrates that activation of the nitric oxide cGMP pathway may cause typical migraine attacks......., to exclude placebo-related effects and to describe the relation between middle cerebral artery dilatation and provoked migraine. Nitroglycerin (0.5 μg/kg/min for 20 min) or placebo was infused into 12 migraine patients in a double-blind cross-over trial. Blood velocity in the middle cerebral artery...

  5. Nitric oxide as a carcinogen. Analysis by yeast functional assay of inactivating p53 mutations induced by nitric oxide

    Energy Technology Data Exchange (ETDEWEB)

    Murata, Jun-Ichi; Tada, Mitsuhiro; Sawamura, Yutaka; Shinohe, Yumiko; Abe, Hiroshi [Laboratory for Molecular Brain Research, Department of Neurosurgery, Hokkaido University School of Medicine, Sapporo (Japan); Iggo, Richard D. [Oncogene group, Swiss Institute for Experimental Cancer Research ISREC, Epalinges (Switzerland)

    1997-10-06

    We have used a yeast p53 functional assay to study induction of mutations in the p53 tumor suppressor gene by nitric oxide and cytosine methylation. The yeast assay identifies only biologically important p53 mutations. p53 cDNA was treated with the nitric oxide donor sydnonimine, PCR-amplified and transfected into yeast. Sydnonimine produced a significant, dose-dependent increase in C:G->A:T transversions. Many important p53 mutational hotspots are postulated to arise by deamination of methylCpG in tumors. We therefore examined nitric oxide induction of mutations in p53 cDNA methylated by PCR-mediated substitution of 5-methylcytosine for cytosine or by treatment with the SssI CpG methylase. Both methylation procedures increased the baseline mutation rate, and nitric oxide treatment produced a further increase in mutation yield. Sequence analysis showed that methylation alone led to C:G->T:A transitions, whereas nitric oxide treatment simply produced more C:G->A:T transversions. Thus the most important factor in C:G->T:A transition at CpG sites identified in this experimental system is cytosine methylation, consistent with spontaneous conversion of 5-methylcytosine to thymine by deamination

  6. Role of nitric oxide and inducible nitric oxide synthase in human abdominal aortic aneurysms: a preliminary study

    Institute of Scientific and Technical Information of China (English)

    LIAO Ming-fang; LI Xiao-yan; JING Zai-ping; BAO Jun-min; ZHAO Zhi-qing; MEI Zhi-jun; LU Qing-shen; Feng Xiang; FENG Rui; ZHANG Su-zen

    2006-01-01

    Background Nitric oxide (NO) is an important mediator in the pathophysiology of many vascular diseases. However, the definite role of NO in human abdominal aortic aneurysm (AAA) formation is unclear. The aim of this study was to investigate production of NO and expression of inducible nitric oxide synthase (iNOS), and their possible role in AAA.Methods A total of 28 patients with AAA, 10 healthy controls, and 8 patients with arterial occlusive disease were enrolled into this study. Standard colorimetric assay was used to examine NO concentration in plasma from patients with AAA and normal controls, and in cultured smooth muscle cells (SMCs). Expression of iNOS in aortas and cultured SMCs were detected by immunochemistry. The correlation of iNOS expression with age of the patient, size of aneurysm, and degree of inflammation was also investigated by Cochran-Mantel-Haenszelχ2 test and Kendall' Tau correlation.Results Expression of iNOS increased significantly in the wall of aneurism in the patients with AAA compared to the healthy controls (P<0.05) and the patients with occlusive arteries (P<0.05). iNOS protein and media NOx (nitrite+nitrate) also increased in cultured SMCs from human AAA (n=4, P<0.05), while plasma NOx decreased in patients with AAA (n=25) compared to the healthy controls (n=20). There was a positive correlation between iNOS protein and degree of inflammation in aneurismal wall (Kendall coefficient=0.5032, P=0.0029)Conclusions SMCs and inflammatory cells were main cellular sources of increased iNOS in AAA, and NO may play a part in pathogenesis in AAA through inflammation.

  7. Thyroid disorders and nitric oxide in cardiovascular adaptation to hypovolemia.

    Science.gov (United States)

    Ogonowski, Natalia; Piro, Giselle; Pessah, Déborah; Arreche, Noelia; Puchulu, Bernardita; Balaszczuk, Ana M; Fellet, Andrea L

    2016-08-01

    This study aimed to investigate whether nitric oxide participates in the cardiovascular function and haemodynamic adaptation to acute haemorrhage in animals with thyroid disorders. Sprague-Dawley rats aged 2months old treated with T3 (hyper, 20μg/100g body weight) or 0.02% methimazole (hypo, w/v) during 28days were pre-treated with N(G) nitro-l-arginine methyl ester (L-NAME) and submitted to 20% blood loss. Heart function was evaluated by echocardiography. Measurements of arterial blood pressure, heart rate, nitric oxide synthase activity and protein levels were performed. We found that hypo decreased fractional shortening and ejection fraction and increased left ventricle internal diameter. Hyper decreased ventricle diameter and no changes in cardiac contractility. Haemorrhage elicited a hypotension of similar magnitude within 10min. Then, this parameter was stabilized at about 30-40min and maintained until finalized, 120min. L-NAME rats showed that the immediate hypotension would be independent of nitric oxide. Nitric oxide synthase inhibition blunted the changes of heart rate induced by blood loss. Hyper and hypo had lower atrial enzyme activity associated with a decreased enzyme isoform in hypo. In ventricle, hyper and hypo had a higher enzyme activity, which was not correlated with changes in protein levels. Haemorrhage induced an increased heart nitric oxide production. We concluded that thyroid disorders were associated with hypertrophic remodelling which impacted differently on cardiac function and its adaptation to a hypovolemia. Hypovolemia triggered a nitric oxide synthase activation modulating the heart function to maintain haemodynamic homeostasis. This involvement depends on a specific enzyme isoform, cardiac chamber and thyroid state.

  8. Regulation of Injury-Induced Neurogenesis by Nitric Oxide

    Directory of Open Access Journals (Sweden)

    Bruno P. Carreira

    2012-01-01

    Full Text Available The finding that neural stem cells (NSCs are able to divide, migrate, and differentiate into several cellular types in the adult brain raised a new hope for restorative neurology. Nitric oxide (NO, a pleiotropic signaling molecule in the central nervous system (CNS, has been described to be able to modulate neurogenesis, acting as a pro- or antineurogenic agent. Some authors suggest that NO is a physiological inhibitor of neurogenesis, while others described NO to favor neurogenesis, particularly under inflammatory conditions. Thus, targeting the NO system may be a powerful strategy to control the formation of new neurons. However, the exact mechanisms by which NO regulates neural proliferation and differentiation are not yet completely clarified. In this paper we will discuss the potential interest of the modulation of the NO system for the treatment of neurodegenerative diseases or other pathological conditions that may affect the CNS.

  9. Nitric oxide and the enigma of cardiac hypertrophy.

    Science.gov (United States)

    Kempf, Tibor; Wollert, Kai C

    2004-06-01

    In pathological conditions associated with persistent increases in hemodynamic workload (old myocardial infarction, high blood pressure, valvular heart disease), a number of signalling pathways are activated in the heart, all of which promote hypertrophic growth of the heart, characterised at the cellular level by increases in individual cardiac myocyte size. Some of these pathways are required for a successful adaptation to cardiac injury. Other pathways are maladaptive, however, as they lead to progressive contractile dysfunction and heart failure. The free radical gas nitric oxide and natriuretic peptides, both of which are produced in the heart, have emerged as endogenous inhibitors of maladaptive hypertrophy signalling. Overall, it appears that cardiac hypertrophy is controlled by an interplay of pro- and antihypertrophic signalling networks. This delicate balance can tip towards adaptation or heart failure. In the future, patients living with cardiac disease may benefit from therapeutic strategies targeting maladaptive hypertrophy signalling pathways. Copyright 2004 Wiley Periodicals, Inc.

  10. Reactive Oxygen Species and Nitric Oxide in Cutaneous Leishmaniasis

    Directory of Open Access Journals (Sweden)

    Maria Fátima Horta

    2012-01-01

    Full Text Available Cutaneous leishmaniasis affects millions of people around the world. Several species of Leishmania infect mouse strains, and murine models closely reproduce the cutaneous lesions caused by the parasite in humans. Mouse models have enabled studies on the pathogenesis and effector mechanisms of host resistance to infection. Here, we review the role of nitric oxide (NO, reactive oxygen species (ROS, and peroxynitrite (ONOO− in the control of parasites by macrophages, which are both the host cells and the effector cells. We also discuss the role of neutrophil-derived oxygen and nitrogen reactive species during infection with Leishmania. We emphasize the role of these cells in the outcome of leishmaniasis early after infection, before the adaptive Th-cell immune response.

  11. Exhaled nitric oxide predicts exercise-induced bronchoconstriction in asthmatic school children

    DEFF Research Database (Denmark)

    Buchvald, Frederik; Hermansen, Mette N; Nielsen, Kim G;

    2005-01-01

    used in routine monitoring of pediatric asthma control. The fractional concentration of exhaled nitric oxide (FeNO) also reflects uncontrolled asthma. We hypothesized that FeNO may be used for prescreening of asthmatic children to exclude those with good asthma control unlikely to have EIB, thereby...

  12. Endothelial nitric oxide: protector of a healthy mind.

    Science.gov (United States)

    Katusic, Zvonimir S; Austin, Susan A

    2014-04-01

    Endothelial nitric oxide (NO) is generated by constitutively active endothelial nitric oxide synthase (eNOS), an essential enzyme responsible for cardiovascular homeostasis. Historically, endothelial NO was first recognized as a major vasodilator involved in control of vasomotor function and local blood flow. In this review, our attention is focused on the emerging role of endothelial NO in linking cerebrovascular function with cognition. We will discuss the recognized ability of endothelial NO to modulate processing of amyloid precursor protein (APP), influence functional status of microglia, and affect cognitive function. Existing evidence suggests that the loss of NO in cultured human cerebrovascular endothelium causes increased expression of APP and β-site APP-cleaving enzyme 1 (BACE1) thereby resulting in increased secretion of amyloid β peptides (Aβ1-40 and Aβ1-42). Furthermore, increased expression of APP and BACE1 as well as increased production of Aβ peptides was detected in the cerebral microvasculature and brain tissue of eNOS-deficient mice. Since Aβ peptides are considered major cytotoxic molecules responsible for the pathogenesis of Alzheimer's disease, these observations support the concept that a loss of endothelial NO might significantly contribute to the initiation and progression of cognitive decline. In addition, genetic inactivation of eNOS causes activation of microglia and promotes a pro-inflammatory phenotype in the brain. Behavioural analysis revealed that eNOS-deficient mice exhibit impaired cognitive performance thereby indicating that selective loss of endothelial NO has a detrimental effect on the function of neuronal cells. Together with findings from prior studies demonstrating the ability of endothelial NO to affect synaptic plasticity, mitochondrial biogenesis, and function of neuronal progenitor cells, it is becoming apparent that the role of endothelial NO in the control of central nervous system function is very complex. We

  13. Enhancement of dendritic branching in cultured hippocampal neurons by 17beta-estradiol is mediated by nitric oxide.

    Science.gov (United States)

    Audesirk, T; Cabell, L; Kern, M; Audesirk, G

    2003-06-01

    Both 17beta-estradiol (E2) and nitric oxide (NO) are important in neuronal development, learning and memory, and age-related memory changes. There is growing evidence that a number of estrogen receptor-mediated effects of estradiol utilize nitric oxide as an intermediary. The role of estradiol in hippocampal neuronal differentiation and function has particular implications for learning and memory. Low levels of estradiol (10nM) significantly increase dendritic branching in cultured embryonic rat hippocampal neurons (158% of control). This study investigates the hypothesis that the estrogen-stimulated increase in dendritic branching is mediated by nitric oxide. We found that nitric oxide donors also produce significantly increased dendritic branching S-nitroso-N-acetylpenicillamine (SNAP: 119%; 2,2'-(hydroxynitrosohydrazino)bis-ethanamine (NOC-18): 128% of control). We then determined that the increases in dendritic branching stimulated by estradiol or by a nitric oxide donor were both blocked by an inhibitor of guanylyl cyclase. Dendritic branching was also stimulated by a cell permeable analog of cyclic guanosine monophosphate (dibutyryl-cGMP: 173% of control). Estradiol-stimulated dendritic branching was reversed by the nitric oxide scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethyl imidazoline-1-oxyl 3-oxide (carboxy-PTIO). This study provides evidence that estradiol influences the development of embryonic hippocampal neurons in culture by increasing the production of nitric oxide or by increasing the sensitivity of the neurons to nitric oxide. Nitric oxide in turn stimulates dendritic branching via activation of guanylyl cyclase.

  14. Dual electroretinogram/nitric oxide carbon fiber microelectrode for direct measurement of nitric oxide in the in vivo retina.

    Science.gov (United States)

    Guthrie, Micah J; Kang-Mieler, Jennifer J

    2014-03-01

    Nitric oxide (NO) plays an important physiological role in normal and pathological retinas. Intraretinal NO concentrations have not been directly measured due to lack of NO electrodes capable of determining their location in the retina. The microelectrodes described here allow recording of the intraretinal electroretinogram (ERG) and NO concentration from the same location, with ERGs used to determine retinal depth. Double-barreled electrodes were constructed with one barrel serving as a reference/voltage recording barrel and the other containing a Nafion-coated carbon fiber used to detect NO amperometrically. Nafion coating imparted a high selectivity for NO versus ascorbic acid (2000:1). In vivo rodent experiments demonstrated that the electrodes could record intraretinal ERGs and NO current with minimal retinal thickness deformation (9%), allowing for retinal NO depth profile measurements. Comparison of NO depth profiles under control conditions and under nitric oxide synthase (NOS) inhibition by 5 mM L-NG-Nitroarginine methyl ester (L-NAME) verified that the recorded current was attributable to NO. NO concentrations from control profiles ( n = 4) were 2.37 ± 0.34 μM at the choroid and 1.12 ± 0.14 μM at the retinal surface. NO concentrations from L-NAME profiles ( n = 4) were significantly lower at 0.83 ± 0.15 μM at the choroid ( p = 0.006) and 0.27 ± 0.04 μM at the retinal surface ( p = 0.001). Localized regions of increased NO (100-400 nM) were seen in the inner retina under control conditions but not after L-NAME. The dual ERG-NO electrode may be a valuable tool in evaluating the role of NO in normal and diseased retinas.

  15. Inhibition of nitric oxide enhances ovine lentivirus replication in monocyte-derived macrophages.

    Science.gov (United States)

    Keane, Kevin A; Mason, Gary L; DeMartini, James C

    2002-12-01

    Ovine lentivirus (OvLV) also known as maedi-visna virus, infects and replicates primarily in macrophages. This investigation examined the role of nitric oxide in the replication of OvLV in cultured macrophages. Peripheral blood mononuclear cells were collected from OvLV-free sheep and cultured in Teflon coated flasks at a high concentration of lamb serum. The cells were subsequently infected with OvLV strain 85/34. OvLV replication was assessed under different experimental treatments by comparison of reverse transcriptase (RT) activity in culture supernatant. Cultures that were treated with exogenous nitric oxide via S-nitroso-acetylpenicillamine did not have altered levels of RT activity compared to cultures treated with the inactive control compound, acetylpenicillamine. However, blockage of nitric oxide production by treatment with aminoguanidine, a competitive inhibitor of inducible nitric oxide synthase (iNOS), led to a significant rise in RT activity. This rise in RT activity was partially reversed in aminoguanidine treated cultures by L-arginine, the normal substrate for iNOS. Finally, the number of viral antigen producing cells was also quantified after aminoguanidine treatment and found to be significantly higher than untreated cultures. Collectively, these results indicate that nitric oxide is a negative regulator of OvLV replication in macrophages.

  16. Measurement of luminal nitric oxide in the uterine cavity using a silicon balloon catheter.

    Science.gov (United States)

    Sioutas, Angelos; Gemzell-Danielsson, Kristina; Lundberg, Jon O; Ehrén, Ingrid

    2011-05-31

    The aim of this pilot case-control study was to measure nitric oxide (NO) gas in air incubated in a catheter balloon in the uterus of healthy women and patients with pelvic inflammatory disease, to determine the optimal time of incubation and to find whether NO level rises after manipulation in the uterine cavity. We measured nitric oxide levels in air incubated for 2-10 min in a catheter balloon in the uterine cavity in 6 non pregnant women from 22 to 50 years of age with lower abdominal pain and 10 healthy women with regular menstrual cycles. After an incubation time of just 2 min, intrauterine nitric oxide levels were significantly increased in patients with diagnosed pelvic inflammatory disease compared to healthy women. Uterine nitric oxide levels did not rise after manipulation in the uterine cavity. In conclusion, NO gas can be measured directly in the uterine cavity with a fast, simple, well-tolerated and safe method. The levels of nitric oxide are increased in women diagnosed with pelvic inflammatory disease already after an incubation time of 2 min.

  17. Exhaled nitric oxide in 4-year-old children : relationship with asthma and atopy

    NARCIS (Netherlands)

    Brussee, JE; Smit, HA; Kerkhof, M; Koopman, LP; Wijga, AH; Postma, DS; Gerritsen, J; Grobee, DE; Brunekreef, B; De Jongste, JC

    Airway inflammation is an early feature of asthma. Early detection and antiinflammatory treatment may have important therapeutic impact. Exhaled nitric oxide is a noninvasive marker of airway inflammation. The current study investigated the association between exhaled nitric oxide and asthma,

  18. Exhaled nitric oxide in 4-year-old children: relationship with asthma and atopy

    NARCIS (Netherlands)

    Brussee, J.E.; Smit, H.A.; Kerkhof, M.; Koopman, L.P.; Wijga, A.H.; Postma, D.S.; Gerritsen, J.; Grobbee, D.E.; Brunekreef, B.; Jongste, J.C. de

    2005-01-01

    Airway inflammation is an early feature of asthma. Early detection and antiinflammatory treatment may have important therapeutic impact. Exhaled nitric oxide is a noninvasive marker of airway inflammation. The current study investigated the association between exhaled nitric oxide and asthma,

  19. Elevated exhaled nitric oxide in high-risk neonates precedes transient early but not persistent wheeze

    DEFF Research Database (Denmark)

    Chawes, Bo L K; Buchvald, Frederik; Bischoff, Anne Louise;

    2010-01-01

    Elevated fractional exhaled nitric oxide (Fe(NO)) concentration has been suggested to predict early childhood wheeze and sensitization.......Elevated fractional exhaled nitric oxide (Fe(NO)) concentration has been suggested to predict early childhood wheeze and sensitization....

  20. An in vitro co-culture mouse model demonstrates efficient vaccine-mediated control of Francisella tularensis SCHU S4 and identifies nitric oxide as a predictor of efficacy

    Directory of Open Access Journals (Sweden)

    Igor Golovlev

    2016-11-01

    Full Text Available Francisella tularensis is a highly virulent intracellular bacterium and cell-mediated immunity is critical for protection, but mechanisms of protection against highly virulent variants, such as the prototypic strain F. tularensis strain SCHU S4, are poorly understood. To this end, we established a co-culture system, based on splenocytes from naïve or immunized mice and in vitro infected bone marrow-derived macrophages, that allowed assessment of mechanisms controlling infection with F. tularensis. We utilized the system to understand why the clpB gene deletion mutant, ΔclpB, of SCHU S4 shows superior efficacy as a vaccine in the mouse model as compared to the existing human vaccine, the live vaccine strain (LVS. Compared to naïve splenocytes, ΔclpB- or LVS-immune splenocytes conferred very significant control of a SCHU S4 infection and the ΔclpB-immune splenocytes were superior to the other splenocytes. Cultures with the latter splenocytes also contained higher levels of IFN-gamma and nitric oxide, and T cells expressing combinations of IFN-gamma, TNF-alpha, and IL-17 than did cultures with LVS-immune splenocytes. There was strong inverse correlation between bacterial replication and levels of nitrite, an end product of nitric oxide, and essentially no control was observed when BMDM from iNOS-/- mice were infected. Collectively, the mouse co-culture model identified a critical role of nitric oxide for protection against a highly virulent strain of F. tularensis.

  1. Interleukin 1 beta induces diabetes and fever in normal rats by nitric oxide via induction of different nitric oxide synthases

    DEFF Research Database (Denmark)

    Reimers, J I; Bjerre, U; Mandrup-Poulsen, T

    1994-01-01

    Substantial in vitro evidence suggests that nitric oxide may be a major mediator of interleukin 1 (IL-1) induced pancreatic beta-cell inhibition and destruction in the initial events leading to insulin-dependent diabetes mellitus. Using NG-nitro-L-arginine methyl ester, an inhibitor of both......, glucagon, corticosterone and leukocyte- and differential-counts in normal rats injected once daily for 5 days with interleukin 1 beta (IL-1 beta) (0.8 microgram/rat = 4.0 micrograms/kg). Inhibition of both the constitutive and the inducible forms of nitric oxide synthase prevented IL-1 beta-induced fever...

  2. Nitric oxide and disorders of the erythrocyte: emerging roles and therapeutic targets.

    Science.gov (United States)

    Maley, Jason H; Lasker, George F; Kadowitz, Philip J

    2010-12-01

    Nitric oxide (NO) plays an important role in states of erythrocyte dysfunction, including sickle cell disease (SCD), malaria, and banked blood preservation. By understanding the role of nitric oxide in these conditions, which are accompanied by hemolysis, vasoocclusion, and erythrocyte dysfunction, new therapeutic targets may be identified to treat complications of these disease states. Furthermore, the role of the erythrocyte in the controlled release of NO in hypoxic tissues is of particular interest, and two theories are discussed regarding this mechanism. In this article, the role of nitric oxide in erythrocyte function, sickle cell anemia, malaria, and damage to banked blood is reviewed, and the use of NO targeted therapies for erythrocyte disease states is discussed.

  3. Fe-Chlorophyllin Promotes the Growth of Wheat Roots Associated with Nitric Oxide Generation

    OpenAIRE

    Hui Jiang; Yong Ren; Liefeng Zhang; Yifan Wang; Min Tong

    2010-01-01

    : Effects of Fe-chlorophyllin on the growth of wheat root were investigated in this study. We found that Fe-chlorophyllin can promote root growth. The production of nitric oxide in wheat root was detected using DAF-2DA fluorescent emission. The intensity of fluorescent in the presence of 0.1 mg/L Fe-chlorophyllin was near to that observed with the positive control of sodium nitroprusside (SNP), the nitric oxide donor. IAA oxidase activity decreased with all treatments of Fe-chlorophyllin from...

  4. Relation between Endothelial Nitric Oxide Synthase Genotypes and Oxidative Stress Markers in Larynx Cancer

    Directory of Open Access Journals (Sweden)

    K. Yanar

    2016-01-01

    Full Text Available Nitric oxide synthase (eNOS/NOS3 is responsible for the endothelial synthesis of nitric oxide (NO•. G894T polymorphism leads to the amino acid substitution from Glu298Asp that causes lower NOS3 activity and basal NO• production in NOS3 894T (298Asp allele carriers compared with the GG homozygotes. NO• acts as an antioxidant protecting against Fenton’s reaction which generates highly reactive hydroxyl radicals. Allelic variation of NOS3 may influence an individual’s risk of laryngeal cancer (LC. In the current study we have examined the possible relationship between NOS3 G894T genotypes and various systemic oxidative damage markers such as protein carbonyl, advanced oxidation protein products, Cu, Zn-superoxide dismutase, thiol group fractions, and lipid hydroperoxides in LC patients. Genotyping was carried out by PCR-RFLP. In LC patients with TT genotype, Cu, Zn-superoxide dismutase activities and nonprotein thiol levels were significantly higher than the controls. In patients with GT and GG genotype, high levels of lipid hydroperoxides showed statistical significance when compared to controls. Our results indicate a potential relationship among G894T polymorphism of NOS3, and impaired redox homeostasis. Further studies are required to determine the role of NOS3 gene polymorphism and impaired plasma redox homeostasis.

  5. Effects of Nephritis No. 3 Recipe on Nitric Oxide, Nitric Oxide Synthase Secreted by Cultured Mesangial Cells in Rats and the Gene Expression of Inducible Nitric Oxide Synthase

    Institute of Scientific and Technical Information of China (English)

    陈志强; 黄怀鹏; 黄文政; 朱小棣; 林清棋

    2003-01-01

    Objective: To explore the effect of the Nephritis No. 3 (N-3) recipe on nitric oxide (NO),nitric oxide synthase (NOS) secreted by cultured mesangial cells (MC) and its gene expression of the inducible nitric oxide synthase (iNOS). Methods: The drug (nephritis No. 3)-containing serum was prepared with serum pharmacological technique, and then was applied to react on mesangial cells cultured in fetal calf serum (FCS) and cells cultured in FCS plus lipopolysaccharide. To observe the secretion of NO and NOS and the gene expression of iNOS by means of RT-PCR. Results: Under the two kinds of culture conditions, the content of NO and NOS in the groups with drug-containing serum were higher than those without drug-containing serum (P<0.05, P<0.01), and the expression of iNOS mRNA was up-regulated too. Conclusion: The N-3 could significantly promote the secretion of NO and NOS and the mRNA expression of iNOS in rats.

  6. Nitric oxide-induced signalling in rat lacrimal acinar cells

    DEFF Research Database (Denmark)

    Looms, Dagnia Karen; Tritsaris, K.; Dissing, S.

    2002-01-01

    The aim of the present study was to investigate the physiological role of nitric oxide (NO) in mediating secretory processes in rat lacrimal acinar cells. In addition, we wanted to determine whether the acinar cells possess endogenous nitric oxide synthase (NOS) activity by measuring NO productio...... not by itself causing fast transient increases in [Ca2+]i. In addition, we suggest that endogenously produced NO activated by ß-adrenergic receptor stimulation, plays an important role in signalling to the surrounding tissue.......The aim of the present study was to investigate the physiological role of nitric oxide (NO) in mediating secretory processes in rat lacrimal acinar cells. In addition, we wanted to determine whether the acinar cells possess endogenous nitric oxide synthase (NOS) activity by measuring NO production......-adrenergic stimulation and not by a rise in [Ca2+]i alone.   We show that in rat lacrimal acinar cells, NO and cGMP induce Ca2+ release from intracellular stores via G kinase activation. However, the changes in [Ca2+]i are relatively small, suggesting that this pathway plays a modulatory role in Ca2+ signalling, thus...

  7. Nitric oxide affects sarcoplasmic calcium release in skeletal myotubes.

    NARCIS (Netherlands)

    Heunks, L.M.A.; Machiels, H.A.; Dekhuijzen, P.N.R.; Prakash, Y.S.; Sieck, G.C.

    2001-01-01

    In the present study, we used real-time confocal microscopy to examine the effects of two nitric oxide (NO) donors on acetylcholine (ACh; 10 microM)- and caffeine (10 mM)-induced intracellular calcium concentration ([Ca2+]i) responses in C2C12 mouse skeletal myotubes. We hypothesized that NO reduces

  8. NITRIC OXIDE INTERFERES WITH HYPOXIA SIGNALING DURING COLONIC INFLAMMATION

    Directory of Open Access Journals (Sweden)

    Cintia Rabelo e Paiva CARIA

    2014-12-01

    Full Text Available Context Intestinal inflammation can induce a local reduction in oxygen levels that triggers an adaptive response centered on the expression of hypoxia-inducible factors (HIFs. Nitric oxide, a well-described inflammatory mediator, may interfere with hypoxia signaling. Objectives We aimed to evaluate the role of nitric oxide in hypoxia signaling during colonic inflammation. Methods Colitis was induced by single (acute or repeated (reactivated colitis trinitrobenzenosulfonic acid administration in rats. In addition, one group of rats with reactivated colitis was also treated with Nw-Nitro-L-arginine methyl ester hydrochloride to block nitric oxide synthase. Colitis was assessed by macroscopic score and myeloperoxidase activity in the colon samples. Hypoxia was determined using the oxygen-dependent probe, pimonidazole. The expression of HIF-1α and HIF-induced factors (vascular endothelial growth factor - VEGF and apelin was assessed using Western blotting. Results The single or repeated administration of trinitrobenzenosulfonic acid to rats induced colitis which was characterized by a high macroscopic score and myeloperoxidase activity. Hypoxia was observed with both protocols. During acute colitis, HIF-1α expression was not increased, but VEGF and apelin were increased. HIF-1α expression was inhibited during reactivated colitis, and VEGF and apelin were not increased. Nw-Nitro-L-arginine methyl ester hydrochloride blockade during reactivated colitis restored HIF-1α, VEGF and apelin expression. Conclusions Nitric oxide could interfere with hypoxia signaling during reactivated colitis inflammation modifying the expression of proteins regulated by HIF-1α.

  9. Nitric oxide and carbon monoxide diffusing capacity of the lung

    NARCIS (Netherlands)

    Lee, I. van der

    2006-01-01

    The single breath diffusion capacity of the lung for carbon monoxide (DLCO) is measure for gas uptake by the lung, and consists of a membrane and a vascular component. Nitric oxide (NO) binds 400 times faster to hemoglobin than carbon monoxide, thus the uptake of NO by the blood is very large.

  10. Arginine, citrulline and nitric oxide metabolism in sepsis

    Science.gov (United States)

    Arginine has vasodilatory effects, via its conversion by nitric oxide (NO) synthase into NO, and immunomodulatory actions that play important roles in sepsis. Protein breakdown affects arginine availability, and the release of asymmetric dimethylarginine, an inhibitor of NO synthase, may therefore a...

  11. Water vapour and carbon dioxide decrease nitric oxide readings

    NARCIS (Netherlands)

    vanderMark, TW; Kort, E; Meijer, RJ; Postma, DS; Koeter, GH

    Measurement of nitric oxide levels in exhaled ah-is commonly performed using a chemiluminescence detector. However, water vapour and carbon dioxide affect the chemiluminescence process, The influence of these gases at the concentrations present in exhaled air has not vet been studied. For this in

  12. Deficiency of nitric oxide in polycation-induced airway hyperreactivity

    NARCIS (Netherlands)

    Meurs, Herman; Schuurman, F.E; Duyvendak, M; Zaagsma, Hans

    1999-01-01

    Using a perfused guinea-pig tracheal tube preparation, we investigated the role of endogenous nitric oxide (NO) in polycation-induced airway hyperreactivity (AHR) to methacholine. Intraluminal (IL) administration of the NO synthase inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME; 100 mu M) c

  13. Evaluation of serum nitric oxide before and after local ...

    African Journals Online (AJOL)

    Hoda Aly Abd-El Moety

    2012-10-06

    Oct 6, 2012 ... Chronic hepatitis C virus is one of the main risk factors for the development of. Hepatocellular carcinoma ... either sub-Saharan Africa or in eastern Asia.1,2 Risk factors that lead to the ..... Yuen Man-Fung, Lai Ching-Lung. Serological .... Nitric oxide of human colorectal adenocarcinoma cell lines promotes ...

  14. Apple fruit responses following exposure to nitric oxide

    Science.gov (United States)

    Exogenous nitric oxide (.NO) applied as gas or generated from .NO releasing compounds has physiological activity in cut apple fruit tissues. Studies were conducted to characterize .NO production by whole fruit as well as to assess responses of whole fruit to exogenous .NO. .NO and ethylene product...

  15. Cross sections for electron collisions with nitric oxide

    Science.gov (United States)

    Itikawa, Yukikazu

    2016-09-01

    Cross section data are reviewed for electron collisions with nitric oxide. Collision processes considered are total scattering, elastic scattering, momentum transfer, excitations of rotational, vibrational, and electronic states, ionization, and dissociative electron attachment. After a survey of the literature (up to the end of 2015), recommended values of the cross section are determined, as far as possible.

  16. Generation of nitric oxide from nitrite by carbonic anhydrase:

    DEFF Research Database (Denmark)

    Aamand, Rasmus; Dalsgaard, Thomas; Jensen, Frank Bo;

    2009-01-01

    bicarbonate and nitrite, we hypothesized that CA uses nitrite as a substrate to produce the potent vasodilator nitric oxide (NO) to increase local blood flow to metabolically active tissues. Here we show that CA readily reacts with nitrite to generate NO, particularly at low pH, and that the NO produced...

  17. On EPR detection of nitric oxide in vivo

    NARCIS (Netherlands)

    van Faassen, E.E.H.

    2008-01-01

    Nitric oxide (NO ) is a peculiar radical: Ground state is not paramagnetic (g = 0 since orbital and spin magnetic moments cancel); low reactivity with other molecules except superoxide (O2 ); thermodynamically unstable; dimerizes to N2O2; difficult to detect in-vivo.

  18. Nitric oxide and carbon monoxide diffusing capacity of the lung

    NARCIS (Netherlands)

    Lee, I. van der

    2006-01-01

    The single breath diffusion capacity of the lung for carbon monoxide (DLCO) is measure for gas uptake by the lung, and consists of a membrane and a vascular component. Nitric oxide (NO) binds 400 times faster to hemoglobin than carbon monoxide, thus the uptake of NO by the blood is very large. There

  19. Inhibition of influenza virus replication by nitric oxide

    NARCIS (Netherlands)

    G.F. Rimmelzwaan (Guus); M.M.J.W. Baars (Marianne); P. de Lijster; R.A.M. Fouchier (Ron); A.D.M.E. Osterhaus (Albert)

    1999-01-01

    textabstractNitric oxide (NO) has been shown to contribute to the pathogenesis of influenza virus-induced pneumonia in mouse models. Here we show that replication of influenza A and B viruses in Mabin Darby canine kidney cells is severely impaired by the NO donor,

  20. Investigation on oxidative stress of nitric oxide synthase interacting protein from Clonorchis sinensis.

    Science.gov (United States)

    Bian, Meng; Xu, Qingxia; Xu, Yanquan; Li, Shan; Wang, Xiaoyun; Sheng, Jiahe; Wu, Zhongdao; Huang, Yan; Yu, Xinbing

    2016-01-01

    Numerous evidences indicate that excretory-secretory products (ESPs) from liver flukes trigger the generation of free radicals that are associated with the initial pathophysiological responses in host cells. In this study, we first constructed a Clonorchis sinensis (C. sinensis, Cs)-infected BALB/c mouse model and examined relative results respectively at 3, 5, 7, and 9 weeks postinfection (p.i.). Quantitative reverse transcription (RT)-PCR indicated that the transcriptional level of both endothelial nitric oxide synthase (eNOS) and superoxide dismutase (SOD) gradually decreased with lastingness of infection, while the transcriptional level of inducible NOS (iNOS) significantly increased. The level of malondialdehyde (MDA) in sera of infected mouse significantly increased versus the healthy control group. These results showed that the liver of C. sinensis-infected mouse was in a state with elevated levels of oxidation stress. Previously, C. sinensis NOS interacting protein coding gene (named CsNOSIP) has been isolated and recombinant CsNOSIP (rCsNOSIP) has been expressed in Escherichia coli, which has been confirmed to be a component present in CsESPs and confirmed to play important roles in immune regulation of the host. In the present paper, we investigated the effects of rCsNOSIP on the lipopolysaccharide (LPS)-induced activated RAW264.7, a murine macrophage cell line. We found that endotoxin-free rCsNOSIP significantly promoted the levels of nitric oxide (NO) and reactive oxygen species (ROS) after pretreated with rCsNOSIP, while the level of SOD decreased. Furthermore, rCsNOSIP could also increase the level of lipid peroxidation MDA. Taken together, these results suggested that CsNOSIP was a key molecule which was involved in the production of nitric oxide (NO) and its reactive intermediates, and played an important role in oxidative stress during C. sinensis infection.

  1. Production of nitric oxide using a microwave plasma torch and its application to fungal cell differentiation

    Science.gov (United States)

    Na, Young Ho; Kumar, Naresh; Kang, Min-Ho; Cho, Guang Sup; Choi, Eun Ha; Park, Gyungsoon; Uhm, Han Sup

    2015-03-01

    The generation of nitric oxide by a microwave plasma torch is proposed for its application to cell differentiation. A microwave plasma torch was developed based on basic kinetic theory. The analytical theory indicates that nitric oxide density is nearly proportional to oxygen molecular density and that the high-temperature flame is an effective means of generating nitric oxide. Experimental data pertaining to nitric oxide production are presented in terms of the oxygen input in units of cubic centimeters per minute. The apparent length of the torch flame increases as the oxygen input increases. The various levels of nitric oxide are observed depending on the flow rate of nitrogen gas, the mole fraction of oxygen gas, and the microwave power. In order to evaluate the potential of nitric oxide as an activator of cell differentiation, we applied nitric oxide generated from the microwave plasma torch to a model microbial cell (Neurospora crassa: non-pathogenic fungus). Germination and hyphal differentiation of fungal cells were not dramatically changed but there was a significant increase in spore formation after treatment with nitric oxide. In addition, the expression level of a sporulation related gene acon-3 was significantly elevated after 24 h upon nitric oxide treatment. Increase in the level of nitric oxide, nitrite and nitrate in water after nitric oxide treatment seems to be responsible for activation of fungal sporulation. Our results suggest that nitric oxide generated by plasma can be used as a possible activator of cell differentiation and development.

  2. Coordinate Properties of Nitric Oxide in Hemoglobin Solution Containing a Minimal Amount of Nitric Oxide

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    Nitric oxide (NO) has a very important physiological function, and it is the unique small diffusible signaling molecule.When NO molecules bind to heme irons in α subunits in hemoglobin (Hb), they have two coordinate forms for Fe2+: one is 5-coordinate, and the other is 6-coordinate.However, there is only 6-coordinate for Fe2+ when NO molecules bind to heme irons in β subunits.When the amount of NO is at a minimal concentration, NO molecules mainly bind to α subunits.The results show that NO molecules do not transfer from heme irons of nitrosylhemoglobin (HbNO) to the thiol groups of Cysteine residues β93 (Cysβ93) to form s-nitrosohemoglobin (Hb-SNO) in the presence of minimal NO in hemoglobin solution.The presence of minimal NO in hemoglobin solution does not decrease the transportation of oxygen, but it does improve its transport ability.It is still under further research whether this mechanism is underlying in the therapy for the disease of cardiovascular system.

  3. Significance of nitric oxide synthases: Lessons from triple nitric oxide synthases null mice.

    Science.gov (United States)

    Tsutsui, Masato; Tanimoto, Akihide; Tamura, Masahito; Mukae, Hiroshi; Yanagihara, Nobuyuki; Shimokawa, Hiroaki; Otsuji, Yutaka

    2015-01-01

    Nitric oxide (NO) is synthesized by three distinct NO synthases (neuronal, inducible, and endothelial NOSs), all of which are expressed in almost all tissues and organs in humans. The regulatory roles of NOSs in vivo have been investigated in pharmacological studies with non-selective NOS inhibitors. However, the specificity of the inhibitors continues to be an issue of debate, and the authentic significance of NOSs is still poorly understood. To address this issue, we generated mice in which all three NOS genes are completely disrupted. The triple NOSs null mice exhibited cardiovascular abnormalities, including hypertension, arteriosclerosis, myocardial infarction, cardiac hypertrophy, diastolic heart failure, and reduced EDHF responses, with a shorter survival. The triple NOSs null mice also displayed metabolic abnormalities, including metabolic syndrome and high-fat diet-induced severe dyslipidemia. Furthermore, the triple NOSs null mice showed renal abnormalities (nephrogenic diabetes insipidus and pathological renal remodeling), lung abnormalities (accelerated pulmonary fibrosis), and bone abnormalities (increased bone mineral density and bone turnover). These results provide evidence that NOSs play pivotal roles in the pathogenesis of a wide variety of disorders. This review summarizes the latest knowledge on the significance of NOSs in vivo, based on lessons learned from experiments with our triple mutant model.

  4. Discovery of nitric oxide in marine ecological system and the chemical characteristics of nitric oxide

    Institute of Scientific and Technical Information of China (English)

    ZHANG Zhengbin; XING Lei; WU Zhenzhen; LIU Chunying; LIN Cai; LIU Liansheng

    2006-01-01

    Nitric oxide was discovered in both the lab and the alga culture pond of Daya Bay (1-300 m3) before the growth of alga reached the maximum. The results included: (1) NO was detectd before the growth of alga reached the maximum in the case of red tide alga and food alga, and the concentration of NO decreased rapidly after the growth maximum; (2) the curve between NO concentration and time indicated that the concentration of NO in the daytime was more than that at night,and the maximal concentration of NO appeared in the midday (1-3 pm); (3) the growth of alga reached the maximum in the alga culture pond of Daya Bay in about 8- 10 d, and NO was discovered in 5-7 d; (4) the measured NO concentration was 10-9 mol/L, 10-9-10-8 mol/L, and 10-8 mol/L for Haeterosigma akashiwo, mixed alga in Daya Bay and Chaetoceros Curvisetus individually; (5) the relation of illumination with NO production was discussed.

  5. Significance of nitric oxide synthases: Lessons from triple nitric oxide synthases null mice

    Directory of Open Access Journals (Sweden)

    Masato Tsutsui

    2015-01-01

    Full Text Available Nitric oxide (NO is synthesized by three distinct NO synthases (neuronal, inducible, and endothelial NOSs, all of which are expressed in almost all tissues and organs in humans. The regulatory roles of NOSs in vivo have been investigated in pharmacological studies with non-selective NOS inhibitors. However, the specificity of the inhibitors continues to be an issue of debate, and the authentic significance of NOSs is still poorly understood. To address this issue, we generated mice in which all three NOS genes are completely disrupted. The triple NOSs null mice exhibited cardiovascular abnormalities, including hypertension, arteriosclerosis, myocardial infarction, cardiac hypertrophy, diastolic heart failure, and reduced EDHF responses, with a shorter survival. The triple NOSs null mice also displayed metabolic abnormalities, including metabolic syndrome and high-fat diet-induced severe dyslipidemia. Furthermore, the triple NOSs null mice showed renal abnormalities (nephrogenic diabetes insipidus and pathological renal remodeling, lung abnormalities (accelerated pulmonary fibrosis, and bone abnormalities (increased bone mineral density and bone turnover. These results provide evidence that NOSs play pivotal roles in the pathogenesis of a wide variety of disorders. This review summarizes the latest knowledge on the significance of NOSs in vivo, based on lessons learned from experiments with our triple mutant model.

  6. Significance of nitric oxide on the pathogenesis of steroid-induced femoral head necrosis

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    @@Steroid-induced femoral head necrosis is claimed to be an ischemic femoral head disease. But there is no discussion on the role of nitric oxide (NO) in the idiopathic disease. The concentration of NO indirectly in serum with steroid induced avascular necrosis of femoral head (ANFH) and in controls are studied in this article.

  7. Constitutive expression of inducible nitric oxide synthase in the normal human colonic epithelium

    DEFF Research Database (Denmark)

    Perner, A; Andresen, L; Normark, M

    2002-01-01

    Inducible nitric oxide synthase (iNOS) in the human colon is considered expressed only in inflammatory states such as ulcerative or collagenous colitis. As subtle iNOS labelling was previously observed in some colonic mucosal biopsies from a heterogeneous group of controls with non-inflamed bowel...

  8. Synthesis and bioactivity of novel nitric oxide-releasing ursolic acid derivatives

    Institute of Scientific and Technical Information of China (English)

    Li Chen; Wen Qiu; Jia Tang; Zhi Feng Wang; Shu Ying He

    2011-01-01

    A series of furoxan-based novel nitric oxide-donating ursolic acid (UA) derivatives (7a-f) were synthesized, and their cytotoxic activities against HepG2 cells in vitro were evaluated by MTT method. It was found that 7a-d and 7f showed more potent cytotoxic activities than control 5-fluorouracil and UA.

  9. Acute and chronic effects of dinner with alcoholic beverages on nitric oxide metabolites in healthy men

    NARCIS (Netherlands)

    Sierksma, A.; Gaag, M.S. van der; Grobbee, D.E.; Hendriks, H.F.J.

    2003-01-01

    1. The present study investigated the acute and chronic effect of dinner with alcoholic beverages on serum nitric oxide (NO) metabolites, namely nitrate and nitrite (NOx), in 11 healthy, non-smoking middle-aged men. 2. In a randomized, diet-controlled, cross-over trial, subjects consumed dinner with

  10. Constitutive expression of inducible nitric oxide synthase in the normal human colonic epithelium

    DEFF Research Database (Denmark)

    Perner, A; Andresen, Lars; Normark, M;

    2002-01-01

    Inducible nitric oxide synthase (iNOS) in the human colon is considered expressed only in inflammatory states such as ulcerative or collagenous colitis. As subtle iNOS labelling was previously observed in some colonic mucosal biopsies from a heterogeneous group of controls with non-inflamed bowel...

  11. Effects of glucocorticoid dexamethasone on serum nitric oxide synthase activity and nitric oxide levels in a rat model of lung disease-induced brain injury

    Institute of Scientific and Technical Information of China (English)

    Huajun Li; Ligang Jiang; Meng Xia; Haiping Li; Fanhua Meng; Wei Li; Lifeng Liu; Zhaohui Wang

    2011-01-01

    In this study, we investigated the effects of dexamethasone, pertussis toxin (a Gi protein inhibitor), and actinomycin (a transcription inhibitor) on serum nitric oxide synthase activity and nitric oxide content in a rat model of lung disease-induced brain injury. High-dose dexamethasone (13 mg/kg) and dexamethasone + actinomycin reduced lung water content, increased serum nitric oxide synthase activity and nitric oxide content, diminished inflammatory cell infiltration in pulmonary alveolar interstitium, attenuated meningeal vascular hyperemia, reduced glial cell infiltration, and decreased cerebral edema. These results demonstrate that high-dose glucocorticoid treatment can reduce the severity of lung disease-induced brain injury by increasing nitric oxide synthase activity and nitric oxide levels.

  12. Simvastatin Attenuates Contrast-Induced Nephropathy through Modulation of Oxidative Stress, Proinflammatory Myeloperoxidase, and Nitric Oxide

    Directory of Open Access Journals (Sweden)

    Ketab E. Al-Otaibi

    2012-01-01

    Full Text Available Contrast media- (CM- induced nephropathy is a serious complication of radiodiagnostic procedures. Available data suggests that the development of prophylaxis strategies is limited by poor understanding of pathophysiology of CM-induced nephropathy. Present study was designed to determine the role of oxidative stress, myeloperoxidase, and nitric oxide in the pathogenesis of iohexol model of nephropathy and its modification with simvastatin (SSTN. Adult Sprague Dawley rats were divided into seven groups. After 24 h of water deprivation, all the rats except in control and SSTN-only groups were injected (10 ml/kg with 25% glycerol. After 30 min, SSTN (15, 30, and 60 mg/kg was administered orally, daily for 4 days. Twenty-four hours after the glycerol injection, iohexol was infused (8 ml/kg through femoral vein over a period of 2 min. All the animals were sacrificed on day 5 and blood and kidneys were collected for biochemical and histological studies. The results showed that SSTN dose dependently attenuated CM-induced rise of creatinine, urea, and structural abnormalities suggesting its nephroprotective effect. A significant increase in oxidative stress (increased lipid hydroperoxides and reduced glutathione levels and myeloperoxidase (MPO and decreased nitric oxide in CM group were reversed by SSTN. These findings support the use of SSTN to combat CM-induced nephrotoxicity.

  13. An Abnormal Nitric Oxide Metabolism Contributes to Brain Oxidative Stress in the Mouse Model for the Fragile X Syndrome, a Possible Role in Intellectual Disability

    Science.gov (United States)

    Lima-Cabello, Elena; Garcia-Guirado, Francisco; Calvo-Medina, Rocio; el Bekay, Rajaa; Perez-Costillas, Lucia; Quintero-Navarro, Carolina; Sanchez-Salido, Lourdes

    2016-01-01

    Background. Fragile X syndrome is the most common genetic cause of mental disability. Although many research has been performed, the mechanism underlying the pathogenesis is unclear and needs further investigation. Oxidative stress played major roles in the syndrome. The aim was to investigate the nitric oxide metabolism, protein nitration level, the expression of NOS isoforms, and furthermore the activation of the nuclear factor NF-κB-p65 subunit in different brain areas on the fragile X mouse model. Methods. This study involved adult male Fmr1-knockout and wild-type mice as controls. We detected nitric oxide metabolism and the activation of the nuclear factor NF-κBp65 subunit, comparing the mRNA expression and protein content of the three NOS isoforms in different brain areas. Results. Fmr1-KO mice showed an abnormal nitric oxide metabolism and increased levels of protein tyrosine nitrosylation. Besides that, nuclear factor NF-κB-p65 and inducible nitric oxide synthase appeared significantly increased in the Fmr1-knockout mice. mRNA and protein levels of the neuronal nitric oxide synthase appeared significantly decreased in the knockout mice. However, the epithelial nitric oxide synthase isoform displayed no significant changes. Conclusions. These data suggest the potential involvement of an abnormal nitric oxide metabolism in the pathogenesis of the fragile X syndrome. PMID:26788253

  14. An Abnormal Nitric Oxide Metabolism Contributes to Brain Oxidative Stress in the Mouse Model for the Fragile X Syndrome, a Possible Role in Intellectual Disability

    Directory of Open Access Journals (Sweden)

    Elena Lima-Cabello

    2016-01-01

    Full Text Available Background. Fragile X syndrome is the most common genetic cause of mental disability. Although many research has been performed, the mechanism underlying the pathogenesis is unclear and needs further investigation. Oxidative stress played major roles in the syndrome. The aim was to investigate the nitric oxide metabolism, protein nitration level, the expression of NOS isoforms, and furthermore the activation of the nuclear factor NF-κB-p65 subunit in different brain areas on the fragile X mouse model. Methods. This study involved adult male Fmr1-knockout and wild-type mice as controls. We detected nitric oxide metabolism and the activation of the nuclear factor NF-κBp65 subunit, comparing the mRNA expression and protein content of the three NOS isoforms in different brain areas. Results. Fmr1-KO mice showed an abnormal nitric oxide metabolism and increased levels of protein tyrosine nitrosylation. Besides that, nuclear factor NF-κB-p65 and inducible nitric oxide synthase appeared significantly increased in the Fmr1-knockout mice. mRNA and protein levels of the neuronal nitric oxide synthase appeared significantly decreased in the knockout mice. However, the epithelial nitric oxide synthase isoform displayed no significant changes. Conclusions. These data suggest the potential involvement of an abnormal nitric oxide metabolism in the pathogenesis of the fragile X syndrome.

  15. The evidence for nitric oxide synthase immunopositivity in the monosynaptic Ia-motoneuron pathway of the dog.

    Science.gov (United States)

    Marsala, Jozef; Lukácová, Nadezda; Sulla, Igor; Wohlfahrt, Peter; Marsala, Martin

    2005-09-01

    size from 0.7 to >or=15.1 microm in length x 0.7 to 4.8 microm wide. Subsequent to identification of the afferent nitric oxide synthase immunoreactive limb of the monosynaptic Ia-motoneuron pathway on control sections, intramuscular injections of the retrograde tracer Fluorogold into the gastrocnemius-soleus muscles, combined with nitric oxide synthase immunohistochemistry of L7 and S1 dorsal root ganglia, confirmed the existence of a number of medium-sized nitric oxide synthase immunoreactive somata (1000-2000 microm(2) square area) in the dorsolateral part of both dorsal root ganglia, presumed to be proprioceptive Ia neurons. Concurrently, large nitric oxide synthase immunoreactive fibers were detected at the input and output side of both dorsal root ganglia. S1 and S2 dorsal rhizotomy caused a marked depletion of nitric oxide synthase immunoreactivity in the medial bundle of S1 and S2 dorsal roots and in the dorsal funiculus of S1, S2 and lower lumbar segments. In addition, anterograde degeneration of large nitric oxide synthase immunoreactive Ia fibers in the dorsal funiculus of L7-S2 segments produces direct evidence that the afferent limb of the soleus H-reflex is nitric oxide synthase immunoreactive and presents new immunohistochemical characteristics of the monosynaptic Ia-motoneuron pathway, unseparably coupled with the performance of the stretch reflex.

  16. Nitric Oxide as a Mediator of Oxidant Lung Injury Due to Paraquat

    Science.gov (United States)

    Berisha, Hasan I.; Pakbaz, Hedayatollah; Absood, Afaf; Said, Sami I.

    1994-08-01

    At low concentrations, nitric oxide is a physiological transmitter, but in excessive concentrations it may cause cell and tissue injury. We report that in acute oxidant injury induced by the herbicide paraquat in isolated guinea pig lungs, nitric oxide synthesis was markedly stimulated, as evidenced by increased levels of cyclic GMP in lung perfusate and of nitrite and L-citrulline production in lung tissue. All signs of injury, including increased airway and perfusion pressures, pulmonary edema, and protein leakage into the airspaces, were dose-dependently attenuated or totally prevented by either N^G-nitro-L-arginine methyl ester or N^ω-nitro-L-arginine, selective and competitive inhibitors of nitric oxide synthase. Protection was reversed by excess L-arginine but not by its enantiomer D-arginine. When blood was added to the lung perfusate, the paraquat injury was moderated or delayed as it was when paraquat was given to anesthetized guinea pigs. The rapid onset of injury and its failure to occur in the absence of Ca2+ suggest that constitutive rather than inducible nitric oxide synthase was responsible for the stimulated nitric oxide synthesis. The findings indicate that nitric oxide plays a critical role in the production of lung tissue injury due to paraquat, and it may be a pathogenetic factor in other forms of oxidant tissue injury.

  17. Oxidative damage involves in the inhibitory effect of nitric oxide on spore germination of Penicillium expansum.

    Science.gov (United States)

    Lai, Tongfei; Li, Boqiang; Qin, Guozheng; Tian, Shiping

    2011-01-01

    The effects of nitric oxide (NO) on spore germination of Penicillium expansum were investigated and a possible mechanism was evaluated. The results indicated that NO released by sodium nitroprusside (SNP) significantly suppressed fungal growth. With the use of an oxidant sensitive probe and Western blot analysis, an increased level of intracellular reactive oxygen species (ROS) and enhanced carbonylation damage were detected in spores of P. expansum under NO stress. Exogenous superoxide dismutase (SOD) and ascorbic acid (Vc) could increase the resistance of the spore to the inhibitory effect of NO. The activities of SOD and catalase (CAT), as well as ATP content in spores under NO stress were also lower than those in the control. We suggest that NO in high concentration induces the generation of ROS which subsequently causes severe oxidative damage to proteins crucial to the process of spore germination of P. expansum.

  18. Alterations in Nitric Oxide Synthase in the Aged CNS

    Directory of Open Access Journals (Sweden)

    Junyang Jung

    2012-01-01

    Full Text Available Aging is associated with neuronal loss, gross weight reduction of the brain, and glial proliferation in the cortex, all of which lead to functional changes in the brain. It is known that oxidative stress is a critical factor in the pathogenesis of aging; additionally, growing evidence suggests that excessive nitric oxide (NO production contributes to the aging process. However, it is still unclear how NO plays a role in the aging process. This paper describes age-related changes in the activity of NADPH-diaphorase (NADPH-d, a marker for neurons containing nitric oxide synthase (NOS, in many CNS regions. Understanding these changes may provide a novel perspective in identifying the aging mechanism.

  19. Nitric oxide in prepubertal rat ovary contribution of the ganglionic nitric oxide synthase system via superior ovarian nerve.

    Science.gov (United States)

    Casais, Marilina; Delgado, Silvia Marcela; Vallcaneras, Sandra; Sosa, Zulema; Rastrilla, Ana María

    2007-02-01

    Both peripheral innervation and nitric oxide (NO) participate in ovarian steroidogenesis. Considering the existence of the nitric oxide/ nitric oxide synthase system in the peripheral neural system and in the ovary, the aim of this work was to analyze if the liberation of NO in the ovarian compartment of prepubertal rats is of ovarian and/or ganglionic origin. The analysis is carried out from a physiological point of view using the experimental coeliac ganglion--Superior Ovarian Nerve--ovary model with and without ganglionic cholinergic stimulus Acetylcholine (Ach) 10(-6) M. Non selective and selective inhibitors of the synthase nitric oxide enzyme were added to the ovarian and ganglionic compartment, and the liberation of nitrites (soluble metabolite of the nitric oxide) in the ovarian incubation liquid was measured. We found that the non-selective inhibitor L-nitro-arginina methyl ester (L-NAME) in the ovarian compartment decreased the liberation of nitrites, and that Aminoguanidine (AG) in two concentrations in a non-dose dependent form provoked the same effect. The addition of Ach in ganglion magnified the effect of the inhibitors of the NOS enzyme. The most relevant results after the addition of inhibitors in ganglion were obtained with AG 400 and 800 microM. The inhibition was made evident with and without the joint action of Ach in ganglion. These data suggest that the greatest production of NO in the ovarian compartment comes from the ovary, mainly the iNOS isoform, though the coeliac ganglion also contributes through the superior ovarian nerve but with less quantity.

  20. Indirect evaluation of corneal apoptosis in contact lens wearers by estimation of nitric oxide and antioxidant enzymes in tears

    Directory of Open Access Journals (Sweden)

    R P Bhatia

    2010-01-01

    Full Text Available Background : Contact lens induced trauma to the corneal epithelium results in increased release of inflammatory mediators. The keratocyte apoptosis is directly related to epithelial injury and has been correlated with increased production of nitric oxide. Potent antioxidant enzymes protect cells from oxidative damage by inactivating reactive oxygen species and thus inhibiting apoptosis. This study aims at determination of total nitric oxide and antioxidant enzymes in tears which will be an indirect criteria for assessing apoptosis. Materials and Methods : Nitric oxide and antioxidant enzymes were estimated in tears of 25 soft contact lens wearers and compared with 25 age and sex matched controls. Results : Statistically significant increase of nitric oxide (P< 0.001, superoxide dismutase (P< 0.001 and glutathione peroxidase (P< 0.001 levels was seen in tears of contact lens wearers as compared to controls. There was also statistically significant increase in the levels of antioxidant enzymes, superoxide dismutase (P< 0.05 and glutathione peroxidase (P< 0.01, with increase in the total duration of contact lens wear in years. Conclusions : Increase in the level of nitric oxide and antioxidant enzymes in tears of contact lens wearers suggested that contact lens wear suppresses the process of apoptosis. However, it was also postulated that the increased levels of nitric oxide balances the anti-apoptotic activities of increased levels of antioxidant enzymes by its pro-apoptotic activity leading to protective outcomes in contact lens wearers.

  1. Nasal nitric oxide and nitric oxide synthase expression in primary ciliary dyskinesia.

    Science.gov (United States)

    Pifferi, M; Bush, A; Maggi, F; Michelucci, A; Ricci, V; Conidi, M E; Cangiotti, A M; Bodini, A; Simi, P; Macchia, P; Boner, A L

    2011-03-01

    No study has evaluated the correlation between different expression of nitric oxide synthase (NOS) isoforms in nasal epithelial cells and nasal NO (nNO) level in primary ciliary dyskinesia (PCD). Gene expression of endothelial (NOS3) and inducible NOS (NOS2) and their correlation with nNO level, ciliary function and morphology were studied in patients with PCD or secondary ciliary dyskinesia (SCD). NOS3 gene polymorphisms were studied in blood leukocytes. A total of 212 subjects were studied (48 with PCD, 161 with SCD and three normal subjects). nNO level correlated with mean ciliary beat frequency (p = 0.044; r = 0.174). The lower the nNO level the higher was the percentage of immotile cilia (p<0.001; r = -0.375). A significant positive correlation between NOS2 gene expression and nNO levels was demonstrated in all children (p = 0.001; r = 0.428), and this correlation was confirmed in patients with PCD (p = 0.019; r = 0.484). NOS2 gene expression was lower in PCD than in SCD (p = 0.04). The NOS3 isoform correlated with missing central microtubules (p = 0.048; r = 0.447). nNO levels were higher in PCD subjects with the NOS3 thymidine 894 mutation, and this was associated with a higher ciliary beat frequency (p = 0.045). These results demonstrate a relationship between nNO level, NOS mRNA expression and ciliary beat frequency.

  2. Nitric oxide promotes survival of cerebellar granule neurons cultured in vitro through the Akt pathway

    Institute of Scientific and Technical Information of China (English)

    Lin Wang; Mei Li; Lihua Zhou

    2011-01-01

    In this study, cerebellar granule neurons were used to examine the role of nitric oxide on cell survival. The N-methyl-D-aspartic acid receptor antagonist, MK-801, and the soluble guanylate cyclase antagonist, 1H-[1, 2, 4]oxadiazolo-[4, 3-a] quinoxalin-1-one, decreased cell viability, induced caspase-3, and decreased phosphorylated-Akt levels, suggesting that blockade of nitric oxide production promotes apoptosis of differentiating cerebellar granule neurons. After administration of sodium nitroprusside, an endogenous nitric oxide donor, cell viability recovered,caspase-3 expression was decreased, and phosphorylated-Akt levels increased. This study provides direct evidence that nitric oxide can sustain the survival of developing cerebellar granule neurons in vitro through the nitric oxide-Akt pathway. Moreover, endogenous nitric oxide exerts these effects in a cyclic guanosine monophosphate-dependent manner while exogenous nitric oxide does so in a cyclic guanosine monophosphate-independent manner.

  3. Effects of exposure of blood hemoglobin to nitric oxide

    Energy Technology Data Exchange (ETDEWEB)

    Chiodi, H.; Mohler, J.G.

    1985-08-01

    The effect of oxygen exposure on nitrosythemoglobin of whole human blood or its buffered solution has been determined. The amount of methemoglobin formed was determined by anaerobic modification of the Evelyn-Malloy method: 59% of the total hemoglobin of whole blood was oxidized to methemoglobin in the first 15 min of the oxygen exposure and 78% of the total hemoglobin was oxidized after 120 min of oxygen exposure. Similar results were obtained when nitrosylhemoglobin buffered solutions were exposed to the oxygen of the air. A comparison of the present in vitro results with these obtained by injecting nitric oxide into the rat peritoneal cavity and its implications are discussed.

  4. Pretreatment with Tongxinluo protects porcine myocardium from ischaemia/reperfusion injury through a nitric oxide related mechanism

    Institute of Scientific and Technical Information of China (English)

    CHENG Yu-tong; YANG Yue-jin; ZHANG Hai-tao; QIAN Hai-yan; ZHAO Jing-lin; MENG Xian-min; LUO Fu-liang; WU Yi-ling

    2009-01-01

    Background The traditional Chinese medicine Tongxinluo can protect myocardium against ischaemia/reperfusion injury, but the mechanism of its action is not well documented. We examined the involvement of nitric oxide in the protective role of Tongxinluo. Methods Miniswine were randomized to four groups of seven: sham, control, Tongxinluo and Tongxinluo coadministration with a nitric oxide synthase inhibitor Nω-nitro-L-arginine (L-NNA, 10 mg/kg i.v.). Three hours after administration of Tongxinluo, the animals were anaesthetised and the left anterior descending coronary artery ligated and maintained in situ for 90 minutes followed by 3 hours of reperfusion before death. Area of no reflow and necrosis and risk region were determined pathologically by planimetry. The degree of neutrophil accumulation in myocardium was obtained by measuring myeloperoxidase activity and histological analysis. Myocardial endothelial nitric oxide synthase activity and vascular endothelial cadherin content were measured by colorimetric method and immunoblotting analysis respectively.Results Tongxinluo significantly increased the local blood flow and limited the infarct and size of no reflow. Tongxinluo also attenuated myeloperoxidase activity and neutrophil accumulation in histological sections and maintained the level of vascular endothelial cadherin and endothelial nitric oxide synthase activity in the reflow region when compared with control group. The protection of Tongxinluo was counteracted by coadministration with L-NNA. Conclusions Tongxinluo may limit myocardial ischaemia and protect the heart against reperfusion injury. Tongxinluo regulates synthesis of nitric oxide by altering activity of endothelial nitric oxide synthase.

  5. NITRIC OXIDE AND ENDOTHELIN-1 IN CHILDREN WITH DIGESTIVE DISORDERS

    Directory of Open Access Journals (Sweden)

    I. V. Panova

    2012-01-01

    Full Text Available The important part in the group of biological compounds, participating in the regulation of the functions of the gastro-intestinal tract, is assigned to endothelial factors because of their impact on the majority of physiological and pathophysiological processes of the digestive system. The article provides information about physiological role of nitric oxide and endothelin-1 and presents a review of scientific data on the participation of nitric oxide and endothelin-1 in the pathogenesis of many digestive system diseases, emphasizing chronic inflammatory disorders of the upper gastrointestinal tract. The authors accentuate the importance of endothelium endocrine function research in children with esophagogastroduodenal disorders at the beginning of puberty, which is the critical period of ontogenesis.

  6. Nitric oxide-related drug targets in headache

    DEFF Research Database (Denmark)

    Olesen, Jes

    2010-01-01

    -called delayed headache that fulfils criteria for migraine without aura in migraine sufferers. Blockade of nitric oxide synthases (NOS) by L-nitromonomethylarginine effectively treats attacks of migraine without aura. Similar results have been obtained for chronic the tension-type headache and cluster headache....... Inhibition of the breakdown of cyclic guanylate phosphate (cGMP) also provokes migraine in sufferers, indicating that cGMP is the effector of NO-induced migraine. Similar evidence suggests an important role of NO in the tension-type headache and cluster headache. These very strong data from human......SUMMARY: Nitric oxide (NO) is a very important molecule in the regulation of cerebral and extra cerebral cranial blood flow and arterial diameters. It is also involved in nociceptive processing. Glyceryl trinitrate (GTN), a pro-drug for NO, causes headache in normal volunteers and a so...

  7. Nitric oxide: considerations for the treatment of ischemic stroke

    Science.gov (United States)

    Terpolilli, Nicole A; Moskowitz, Michael A; Plesnila, Nikolaus

    2012-01-01

    Some 40 years ago it was recognized by Furchgott and colleagues that the endothelium releases a vasodilator, endothelium-derived relaxing factor (EDRF). Later on, several groups identified EDRF to be a gas, nitric oxide (NO). Since then, NO was identified as one of the most versatile and unique molecules in animal and human biology. Nitric oxide mediates a plethora of physiological functions, for example, maintenance of vascular tone and inflammation. Apart from these physiological functions, NO is also involved in the pathophysiology of various disorders, specifically those in which regulation of blood flow and inflammation has a key role. The aim of the current review is to summarize the role of NO in cerebral ischemia, the most common cause of stroke. PMID:22333622

  8. Nitric oxide in female repro-ductive system

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    @@ Nitric oxide (NO), synthesized from L-arginine and oxygen by a family of enzymes known as nitric oxide synthase (NOS), is an effective and intercellular signal transduction molecule, and is ubiquitously present in vertebrates. To date, there are three distinct isoforms of NOS: neural NOS (nNOS), inducible NOS (iNOS), and endothelial NOS (eNOS). Among them, eNOS and nNOS, also called constitutive isoforms (cNOS), require calcium for activity, and are expressed constitutively in the physiological condition. The third isoforms, iNOS, whose activity is not dependent on calcium, are produced only in response to some stimulus, including cytokines and immune stimulating factors, etc.[1].

  9. INSULIN INDUCES NITRIC OXIDE PRODUCTION IN BOVINEAORTIC ENDOTHELIAL CELLS

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To examine the effects of insulin on cell proliferation, nitric oxide (NO) release and nitric oxide synthase (NOS) gene expression in bovine aortic endothelial cells ( BAEC ) . Methods The mi togenesis was assessed by MTT method; the products of NO in the culture media, by Griess reaction; and the levels of NOS mRNA in BAEC , by RT/PCR tech nique. Results BAEC were not responsive to the growth-promoting effects of insulin. Stimulation with insulin resulted a dose-dependent rise of NO in the culture supernatants 2h later, with a maximum at 12~24h and a decline at 24h. This rise was inhibited by an inhibitor of NOS (L-NAME). NOS mRNA increased slightly in BAEC without statistical significance. Conelu sion The study suggested that the insulin-induced NO release might be caused directly by NOS activation.

  10. Tuning the nitric oxide release from CPO-27 MOFs.

    Science.gov (United States)

    Cattaneo, Damiano; Warrender, Stewart J; Duncan, Morven J; Kelsall, Christopher J; Doherty, Mary K; Whitfield, Phillip D; Megson, Ian L; Morris, Russell E

    2016-02-13

    Nitric oxide (NO) storage and release measurements have been recorded for Ni-doped CPO-27 (Mg) and CPO-27 (Zn), and the biological effect of the released NO was assessed in porcine coronary artery relaxation tests. The results indicate that the doping strategy leads to increased levels of NO storage and delivery compared to the parent materials and that the NO dosage and biological response can be tuned via this approach to suit the requirements of particular applications.

  11. Weaning of inhaled nitric oxide: is there a best strategy?

    OpenAIRE

    Anita M. Ware; Golombek, Sergio G

    2015-01-01

    Background: Inhaled nitric oxide (iNO) has been used in the treatment of pulmonary hypertension in neonates for many years. iNO was approved by the FDA in 1999 for hypoxic respiratory failure (HRF) in term and near term infants, defined as > 34 weeks gestational age (GA). iNO is used for persistent pulmonary hypertension of the newborn (PPHN), secondary pulmonary hypertension caused by congenital heart disease (CHD), congenital diaphragmatic hernia (CDH), meconium aspiration syndrome (MAS)...

  12. Diazeniumdiolated carbamates: A novel class of nitric oxide donors

    Science.gov (United States)

    Nandurdikar, Rahul S.; Maciag, Anna E.; Cao, Zhao; Keefer, Larry K.; Saavedra, Joseph E.

    2012-01-01

    We report an indirect method for synthesis of previously inaccessible diazeniumdiolated carbamates. Synthesis involves use of previously reported triisopropylsilyloxymethylated isopropylamine diazeniumdiolate (TOM-ylated IPA/NO). These novel diazeniumdiolated carbamate prodrugs upon activation release nitric oxide (NO) similar to their secondary amine counterparts. They are also efficient sources of intracellular NO. These prodrugs may have potential applications as therapeutic NO-donors. PMID:22356735

  13. β-Adrenergic-mediated vasodilation in young men and women: cyclooxygenase restrains nitric oxide synthase.

    Science.gov (United States)

    Limberg, Jacqueline K; Johansson, Rebecca E; Peltonen, Garrett L; Harrell, John W; Kellawan, J Mikhail; Eldridge, Marlowe W; Sebranek, Joshua J; Schrage, William G

    2016-03-15

    We tested the hypothesis that women exhibit greater vasodilator responses to β-adrenoceptor stimulation compared with men. We further hypothesized women exhibit a greater contribution of nitric oxide synthase and cyclooxygenase to β-adrenergic-mediated vasodilation compared with men. Forearm blood flow (Doppler ultrasound) was measured in young men (n = 29, 26 ± 1 yr) and women (n = 33, 25 ± 1 yr) during intra-arterial infusion of isoproterenol (β-adrenergic agonist). In subset of subjects, isoproterenol responses were examined before and after local inhibition of nitric oxide synthase [N(G)-monomethyl-l-arginine (l-NMMA); 6 male/10 female] and/or cyclooxygenase (ketorolac; 5 male/5 female). Vascular conductance (blood flow ÷ mean arterial pressure) was calculated to assess vasodilation. Vascular conductance increased with isoproterenol infusion (P 0.99) or women (P = 0.21). In contrast, ketorolac infusion markedly increased isoproterenol-mediated responses in both men (P vasodilation is not different between men and women and sex differences in the independent contribution of nitric oxide synthase and cyclooxygenase to β-mediated vasodilation are not present. However, these data are the first to demonstrate β-adrenoceptor activation of cyclooxygenase suppresses nitric oxide synthase signaling in human forearm microcirculation and may have important implications for neurovascular control in both health and disease.

  14. The effect of nitric oxide releasing cream on healing pressure ulcers

    Science.gov (United States)

    Saidkhani, Vahid; Asadizaker, Marziyeh; Khodayar, Mohammad Javad; Latifi, Sayed Mahmoud

    2016-01-01

    Background: Pressure ulcer is one of the main concerns of nurses in medical centers around the world, which, if untreated, causes irreparable problems for patients. In recent years, nitric oxide (NO) has been proposed as an effective method for wound healing. This study was conducted to determine the effect of nitric oxide on pressure ulcer healing. Materials and Methods: In this clinical trial, 58 patients with pressure ulcer at hospitals affiliated to Ahvaz Jundishapur University of Medical Sciences were homogenized and later divided randomly into two groups of treatment (nitric oxide cream; n = 29) and control (placebo cream; n = 29). In this research, the data collection tool was the Pressure Ulcer Scale for Healing (PUSH). At the outset of the study (before using the cream), the patients' ulcers were examined weekly in terms of size, amount of exudates, and tissue type using the PUSH tool for 3 weeks. By integrating these three factors, wound healing was determined. Data were analyzed using SPSS. Results: Although no significant difference was found in terms of the mean of score size, the amount of exudates, and the tissue type between the two groups, the mean of total score (healing) between the two groups was statistically significant (P = 0.04). Conclusions: Nitric oxide cream seems to accelerate wound healing. Therefore, considering its easy availability and cost-effectiveness, it can be used for treating pressure ulcers in the future. PMID:27186212

  15. The effect of nitric oxide releasing cream on healing pressure ulcers.

    Science.gov (United States)

    Saidkhani, Vahid; Asadizaker, Marziyeh; Khodayar, Mohammad Javad; Latifi, Sayed Mahmoud

    2016-01-01

    Pressure ulcer is one of the main concerns of nurses in medical centers around the world, which, if untreated, causes irreparable problems for patients. In recent years, nitric oxide (NO) has been proposed as an effective method for wound healing. This study was conducted to determine the effect of nitric oxide on pressure ulcer healing. In this clinical trial, 58 patients with pressure ulcer at hospitals affiliated to Ahvaz Jundishapur University of Medical Sciences were homogenized and later divided randomly into two groups of treatment (nitric oxide cream; n = 29) and control (placebo cream; n = 29). In this research, the data collection tool was the Pressure Ulcer Scale for Healing (PUSH). At the outset of the study (before using the cream), the patients' ulcers were examined weekly in terms of size, amount of exudates, and tissue type using the PUSH tool for 3 weeks. By integrating these three factors, wound healing was determined. Data were analyzed using SPSS. Although no significant difference was found in terms of the mean of score size, the amount of exudates, and the tissue type between the two groups, the mean of total score (healing) between the two groups was statistically significant (P = 0.04). Nitric oxide cream seems to accelerate wound healing. Therefore, considering its easy availability and cost-effectiveness, it can be used for treating pressure ulcers in the future.

  16. Randomized, non-inferiority trial comparing a nitric oxide releasing solution with a macrolide antibiotic for control of bovine respiratory disease in beef feedlot calves at high-risk of developing respiratory tract disease.

    Science.gov (United States)

    Crepieux, T; Miller, C; Regev-Shoshani, G; Schaefer, A; Dorin, C; Alexander, T; Timsit, E

    2016-04-01

    Nitric oxide, a molecule produced in most mammalian cells, has bactericidal and virucidal properties. Nasal instillation of a nitric oxide releasing solution (NORS) on arrival at the feedlot was recently reported as non-inferior to a parenteral injection of a macrolide antibiotic, tilmicosin, for control of bovine respiratory disease (BRD) in cattle at low-to-moderate risk of developing BRD. The objective of this study was to evaluate whether NORS was non-inferior to tilmicosin for control of BRD in cattle at high-risk of developing BRD (the target population for many BRD control programs). High-risk Angus-cross heifers (n=840) were randomly allocated to 2 treatment groups on arrival at a feedlot and received either NORS or tilmicosin for BRD control. Non-inferiority was assessed by calculating the difference in prevalence of heifers diagnosed with BRD during the first 40 d after arrival between NORS and tilmicosin treatment groups. The non-inferiority margin (δ) was set at 8.5%. Thirty-six and 19% of heifers were diagnosed with BRD in the NORS and tilmicosin groups, respectively. Because the lower bound of the 2-sided 95% confidence interval (CI) of the difference in BRD prevalence between the 2 treatment groups (17%; 95% CI=11-23%) was higher than δ, an inferiority of NORS was concluded. Although on-arrival nasal administration of NORS can be viewed as a more rational control strategy than parental injection of antibiotics, further research is needed to improve NORS efficacy before it can be recommended to prevent BRD in high-risk cattle.

  17. A study on relationship of nitric oxide, oxidation, peroxidation, lipoperoxidation with chronic cholecystitis

    Institute of Scientific and Technical Information of China (English)

    Jun Fu Zhou; Dong Cai; Cheng Hong Peng; Yang Hai Yu; You Gen Zhu; Jin Lu Yang

    2000-01-01

    AIM To study relationship of injury induced by nitric oxide, oxidation, peroxidation, lipoperoxidation with chronic cholecystitis. METHODS The values of plasma nitric oxide (PNO), plasma vitamin C (P-VC), plasma vitamin E ( P-VE ), plasma β-carotene ( P-β-CAR ), plasma lipoperoxides (P-LPO), erythrocyte superoxide dismutase (E-SOD), erythrocyte catalase (ECAT), erythrocyte glutathione peroxidase (E-GSHPx) activities and erythrocyte lipoperoxides (ELPO) level in 77 patients with chronic cholecystitis and 80 healthy control subjects were determined, differences of the above average values between the patient group and the control group and differences of the average values between preoperative and postoperative patients were analyzed and compared, linear regression and correlation of the disease course with the above determination values as well as the stepwise regression and correlation of the course with the values were analyzed. RESULTS Compared with the control group, the average values of P-NO, P-LPO, E-LPO were significantly increased ( P < 0.01 ), and of P-VC, P-VE, P-β-CAR, E-SOD, E-CAT and E-GSH-Px decreased ( P < O. 01 ) in the patient group. The analysis of the linear regression and correlation showed that with prolonging of the course, the values of P-NO, P-LPO and E-LPO in the patients were gradually ascended and the values of P-VC, P-VE, P-β-CAR, E-SOD, E-CAT and E-GSH-Px descended (P < 0. 01 ). The analysis of the stepwise regression and correlation indicated that the correlation of the course with P-NO, P-VE and P-β-CAR values was the closest. Compared with the preoperative patients, the average values of PNO, P-LPO and E-LPO were significantly decreased (P < 0.01 ) and the average values of PVC, E-SOD, E-CAT and E-GSH-Px in postoperative patients increased ( P < 0.01) in postoperative patients. But there was no significant difference in the average values of P-VE, P-W-CAR preoperative and postoperative patients. CONCLUSION Chronic cholecystitis

  18. Nitric oxide availability in deeply hypoxic crucian carp

    DEFF Research Database (Denmark)

    Hansen, Marie Niemann; Gerber, Lucie; Jensen, Frank Bo

    2016-01-01

    Recent research suggest that anoxia-tolerant fish transfer extracellular nitrite into the tissues, where it is used for nitric oxide (NO) generation, iron-nitrosylation and S-nitrosation of proteins as part of the cytoprotective response towards prolonged oxygen lack and subsequent re-oxygenation......Recent research suggest that anoxia-tolerant fish transfer extracellular nitrite into the tissues, where it is used for nitric oxide (NO) generation, iron-nitrosylation and S-nitrosation of proteins as part of the cytoprotective response towards prolonged oxygen lack and subsequent re......(yl)ated compounds either increased or stayed constant, depending on O2 level and tissue type. Nitrite was notably increased in the heart during deep hypoxia, and the increase was amplified by elevated ambient [nitrite]. Raised nitrite also increased gill [nitrite] and decreased mRNA expression of an inducible...... nitric oxide synthase-2 gene variant. The data support that ambient nitrite is taken up across the gills to be distributed via the blood to tissues, particularly the heart, where it assists in cytoprotection and other functions. Cardiac nitrite was not elevated in acutely exposed fish, revealing...

  19. Nitric oxide-related drug targets in headache

    DEFF Research Database (Denmark)

    Olesen, Jes

    2010-01-01

    SUMMARY: Nitric oxide (NO) is a very important molecule in the regulation of cerebral and extra cerebral cranial blood flow and arterial diameters. It is also involved in nociceptive processing. Glyceryl trinitrate (GTN), a pro-drug for NO, causes headache in normal volunteers and a so-called del......SUMMARY: Nitric oxide (NO) is a very important molecule in the regulation of cerebral and extra cerebral cranial blood flow and arterial diameters. It is also involved in nociceptive processing. Glyceryl trinitrate (GTN), a pro-drug for NO, causes headache in normal volunteers and a so......-called delayed headache that fulfils criteria for migraine without aura in migraine sufferers. Blockade of nitric oxide synthases (NOS) by L-nitromonomethylarginine effectively treats attacks of migraine without aura. Similar results have been obtained for chronic the tension-type headache and cluster headache....... Inhibition of the breakdown of cyclic guanylate phosphate (cGMP) also provokes migraine in sufferers, indicating that cGMP is the effector of NO-induced migraine. Similar evidence suggests an important role of NO in the tension-type headache and cluster headache. These very strong data from human...

  20. A Novel Amperometric Nitric Oxide Sensor Based on Polythionine /Nation Modified Glassy Carbon Electrode

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    A novel amperometric sensor for the determination of nitric oxide was developed by coating polythionine / nafion on a glassy carbon electrode. This sensor exhibited a great enhancement to the oxidation of nitric oxide. The oxidation peak currents were linear to the concentration of nitric oxide over the wide range from 3.6×10-7 to 6.8×10-5 mol. L-1, and the detection limit was 7.2×10-8 mol. L-1. Experimental results showed that this nitric oxide sensor possessed excellent selectivity and longer stability. NO releasing from rat kidney was monitored by this sensor.

  1. Nitric Oxide Overproduction Reduces Insulin Secretion from Isolated Islets in Fetal Hypothyroid Rats.

    Science.gov (United States)

    Rouintan, Z; Farrokhfall, K; Karbalaei, N; Ghasemi, A

    2016-02-01

    Thyroid hormones have developmental effects during fetal life. Fetal hypothyroidism leads to glucose intolerance and reduced insulin secretion capacity. Activity of nitric oxide synthases follows a heterogeneous pattern in hypothyroidism. Overactivity of constitutive nitric oxide synthase (NOS), inhibits glucose-stimulated insulin release. The aim of this study was to examine if reduction in insulin secretion in fetal hypothyroidism is due to overproduction of nitric oxide. Pregnant Wistar rats were divided into 2 groups; the experimental group consumed water containing 0.02% of 6-propyl-2-thiouracil till delivery, while the control group consumed tap water. After delivery serum thyroid hormones were measured. Intravenous glucose tolerance test was performed in 6-month old offspring (n=8). After 3 weeks recovery, pancreatic islets were isolated and insulin secretion, inducible and constitutive nitric oxide synthase activity were measured (n=4). Compared to controls, during intravenous glucose tolerance test, fetal hypothyroid rats had high plasma glucose concentration (p=0.003) and low plasma insulin levels (p=0.012) at 5-20 min and their insulin secretion from isolated islets at basal glucose concentration and in the presence of l-arginine was lower. The nitric oxide synthase inhibitor, NG-nitro-l-arginine methyl ester significantly improved insulin secretion in fetal hypothyroid rats at basal glucose concentration and in the presence of l-arginine. The results showed higher NOS activities in fetal hypothyroid rats (constitutive 17.60±1.09 vs. 47.34±4.44 and inducible 4.09±0.96 vs. 19.97±1.14 pmol/min/mg proteins, p=0.002). In conclusion, NO overproduction through NOS participates in decreased insulin secretion in fetal hypothyroid rats.

  2. The nitric oxide redox sibling nitroxyl partially circumvents impairment of platelet nitric oxide responsiveness.

    Science.gov (United States)

    Dautov, R F; Ngo, D T M; Licari, G; Liu, S; Sverdlov, A L; Ritchie, R H; Kemp-Harper, B K; Horowitz, J D; Chirkov, Y Y

    2013-11-30

    Impaired platelet responsiveness to nitric oxide (NO resistance) is a common characteristic of many cardiovascular disease states and represents an independent risk factor for cardiac events and mortality. NO resistance reflects both scavenging of NO by superoxide (O2(-)), and impairment of the NO receptor, soluble guanylate cyclase (sGC). There is thus an urgent need for circumvention of NO resistance in order to improve clinical outcomes. Nitroxyl (HNO), like NO, produces vasodilator and anti-aggregatory effects, largely via sGC activation, but is not inactivated by O2(-). We tested the hypothesis that HNO circumvents NO resistance in human platelets. In 57 subjects with or without ischemic heart disease, platelet responses to the HNO donor isopropylamine NONOate (IPA/NO) and the NO donor sodium nitroprusside (SNP) were compared. While SNP (10μM) induced 29±3% (p<0.001) inhibition of platelet aggregation, IPA/NO (10μM) caused 75±4% inhibition (p<0.001). In NO-resistant subjects (n=28), the IPA/NO:SNP response ratio was markedly increased (p<0.01), consistent with partial circumvention of NO resistance. Similarly, cGMP accumulation in platelets was greater (p<0.001) with IPA/NO than with SNP stimulation. The NO scavenger carboxy-PTIO (CPTIO, 200μM) inhibited SNP and IPA/NO responses by 92±7% and 17±4% respectively (p<0.001 for differential inhibition), suggesting that effects of IPA/NO are only partially NO-mediated. ODQ (10μM) inhibited IPA/NO responses by 36±8% (p<0.001), consistent with a contribution of sGC/haem to IPA/NO inhibition of aggregation. There was no significant relationship between whole blood ROS content and IPA/NO responses. Thus the HNO donor IPA/NO substantially circumvents platelet NO resistance while acting, at least partially, as a haem-mediated sGC activator.

  3. Exogenous nitric oxide inhibits Crimean Congo hemorrhagic fever virus.

    Science.gov (United States)

    Simon, M; Falk, K I; Lundkvist, A; Mirazimi, A

    2006-09-01

    Crimean Congo hemorrhagic fever virus (CCHFV) is a geographically widespread pathogen that causes severe hemorrhagic fever with high mortality. Even though one of the main objectives focuses on the progress of antiviral agents, the research on CCHFV is strongly hampered due to its BSL-4 classification. Nitric oxide (NO), a mediator with broad biological effects, has been shown to possess inhibitory properties against various pathogens. The molecule constitutes a component of the innate immunity and serves to assist in the early immunological events where it contributes to clearance of microorganisms. In this study, we investigated the inhibitory properties of exogenous NO on CCHFV. We found that NO had a significant antiviral activity against CCHFV replication. By using the NO-donor S-nitroso-N-acetylpenicillamine (SNAP) we were able to show up to 99% reduction in virion progeny yield. In contrast, 3-morpholinosydnonimine hydrochloride (SIN-1), a peroxynitrite donor, had no significant antiviral activity against CCHFV. Furthermore the expression of viral proteins; the nucleocapsid protein and the glycoprotein, were clearly reduced with increasing concentrations of SNAP. We have also shown that the amount of total vRNA in SNAP-treated cells was reduced by about 50% compared to the controls.

  4. Potential use and perspectives of nitric oxide donors in agriculture.

    Science.gov (United States)

    Marvasi, Massimiliano

    2017-03-01

    Nitric oxide (NO) has emerged in the last 30 years as a key molecule involved in many physiological processes in plants, animals and bacteria. Current research has shown that NO can be delivered via donor molecules. In such cases, the NO release rate is dependent on the chemical structure of the donor itself and on the chemical environment. Despite NO's powerful signaling effect in plants and animals, the application of NO donors in agriculture is currently not implemented and research remains mainly at the experimental level. Technological development in the field of NO donors is rapidly expanding in scope to include controlling seed germination, plant development, ripening and increasing shelf-life of produce. Potential applications in animal production have also been identified. This concise review focuses on the use of donors that have shown potential biotechnological applications in agriculture. Insights are provided into (i) the role of donors in plant production, (ii) the potential use of donors in animal production and (iii) future approaches to explore the use and applications of donors for the benefit of agriculture. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  5. Exhaled nitric oxide levels in children with chronic adenotonsillar disease.

    Science.gov (United States)

    Torretta, S; Marchisio, P; Esposito, S; Garavello, W; Cappadona, M; Clemente, I A; Pignataro, L

    2011-01-01

    Exhaled nitric oxide (eNO) is a highly reactive biological mediator that has recently been associated with chronic tonsillar disease in adults, but there are no published data concerning eNO levels in their pediatric counterparts. The aim of this study is to measure mean eNO levels in children with chronic adenotonsillitis or adenotonsillar hypertrophy, and assess the effects of potential confounding factors. Children aged 3-17 years were divided into three groups (chronic adenotonsillitis, adenotonsillar hypertrophy and controls). Their eNO levels were measured in accordance with the international guidelines, and their other clinical and anamnestic characteristics were recorded. The mean eNO level in the children with chronic adenotonsillitis was slightly higher than that in the other groups, but there was no statistically significant between-group difference. Age (p=0.009), allergy (p=0.05) and body mass index (p=0.03), but not the mean grade of adenoidal or tonsil hypertrophy, were all statistically related to mean eNO levels. These preliminary results indicate the lack of an increase in mean eNO levels in children with chronic adenotonsillar disease, with no substantial difference between children with chronic adenotonsillitis and those with adenotonsillar hypertrophy.

  6. Inducible nitric oxide synthase is expressed in synovial fluid granulocytes.

    Science.gov (United States)

    Cedergren, J; Forslund, T; Sundqvist, T; Skogh, T

    2002-10-01

    The objective of the study was to evaluate the NO-producing potential of synovial fluid (SF) cells. SF from 15 patients with arthritis was compared with blood from the same individuals and with blood from 10 healthy controls. Cellular expression of inducible nitric oxide synthase (iNOS) was analysed by flow cytometry. High-performance liquid chromatography was used to measure l-arginine and l-citrulline. Nitrite and nitrate were measured colourimetrically utilizing the Griess' reaction. Compared to whole blood granulocytes in patients with chronic arthritis, a prominent iNOS expression was observed in SF granulocytes (P < 0.001). A slight, but statistically significant, increase in iNOS expression was also recorded in lymphocytes and monocytes from SF. l-arginine was elevated in SF compared to serum (257 +/- 78 versus 176 +/- 65 micro mol/l, P = 0.008), whereas a slight increase in l-citrulline (33 +/- 11 versus 26 +/- 9 micro mol/l), did not reach statistical significance. Great variations but no significant differences were observed comparing serum and SF levels of nitrite and nitrate, respectively, although the sum of nitrite and nitrate tended to be elevated in SF (19.2 +/- 20.7 versus 8.6 +/- 6.5 micro mol/l, P = 0.054). Synovial fluid leucocytes, in particular granulocytes, express iNOS and may thus contribute to intra-articular NO production in arthritis.

  7. Role of nitric oxide in hematosuppression and benzene-induced toxicity.

    OpenAIRE

    Laskin, D L; Heck, D E; Punjabi, C J; Laskin, J D

    1996-01-01

    It is becoming increasingly apparent that nitric oxide plays a multifunctional role in regulating inflammatory processes in the body. Although nitric oxide and its oxidation products are cytotoxic toward certain pathogens, they can also cause tissue injury and suppress proliferation. Cytokines and growth factors released at sites of inflammation or injury stimulate both immune and nonimmume cells to produce nitric oxide. Nowhere in the body is this more detrimental than in the bone marrow, fo...

  8. Expression of Nitric Oxide-Transporting Aquaporin-1 Is Controlled by KLF2 and Marks Non-Activated Endothelium In Vivo.

    Directory of Open Access Journals (Sweden)

    Ruud D Fontijn

    Full Text Available The flow-responsive transcription factor Krüppel-like factor 2 (KLF2 maintains an anti-coagulant, anti-inflammatory endothelium with sufficient nitric oxide (NO-bioavailability. In this study, we aimed to explore, both in vitro and in human vascular tissue, expression of the NO-transporting transmembrane pore aquaporin-1 (AQP1 and its regulation by atheroprotective KLF2 and atherogenic inflammatory stimuli. In silico analysis of gene expression profiles from studies that assessed the effects of KLF2 overexpression in vitro and atherosclerosis in vivo on endothelial cells, identifies AQP1 as KLF2 downstream gene with elevated expression in the plaque-free vessel wall. Biomechanical and pharmaceutical induction of KLF2 in vitro is accompanied by induction of AQP1. Chromosome immunoprecipitation (CHIP confirms binding of KLF2 to the AQP1 promoter. Inflammatory stimulation of endothelial cells leads to repression of AQP1 transcription, which is restrained by KLF2 overexpression. Immunohistochemistry reveals expression of aquaporin-1 in non-activated endothelium overlying macrophage-poor intimae, irrespective whether these intimae are characterized as being plaque-free or as containing advanced plaque. We conclude that AQP1 expression is subject to KLF2-mediated positive regulation by atheroprotective shear stress and is downregulated under inflammatory conditions both in vitro and in vivo. Thus, endothelial expression of AQP1 characterizes the atheroprotected, non-inflamed vessel wall. Our data provide support for a continuous role of KLF2 in stabilizing the vessel wall via co-temporal expression of eNOS and AQP1 both preceding and during the pathogenesis of atherosclerosis.

  9. Acute right heart failure after hemorrhagic shock and trauma pneumonectomy-a management approach: A blinded randomized controlled animal trial using inhaled nitric oxide.

    Science.gov (United States)

    Lubitz, Andrea L; Sjoholm, Lars O; Goldberg, Amy; Pathak, Abhijit; Santora, Thomas; Sharp, Thomas E; Wallner, Markus; Berretta, Remus M; Poole, Lauren A; Wu, Jichuan; Wolfson, Marla R

    2017-02-01

    Hemorrhagic shock and pneumonectomy causes an acute increase in pulmonary vascular resistance (PVR). The increase in PVR and right ventricular (RV) afterload leads to acute RV failure, thus reducing left ventricular (LV) preload and output. Inhaled nitric oxide (iNO) lowers PVR by relaxing pulmonary arterial smooth muscle without remarkable systemic vascular effects. We hypothesized that with hemorrhagic shock and pneumonectomy, iNO can be used to decrease PVR and mitigate right heart failure. A hemorrhagic shock and pneumonectomy model was developed using sheep. Sheep received lung protective ventilatory support and were instrumented to serially obtain measurements of hemodynamics, gas exchange, and blood chemistry. Heart function was assessed with echocardiography. After randomization to study gas of iNO 20 ppm (n = 9) or nitrogen as placebo (n = 9), baseline measurements were obtained. Hemorrhagic shock was initiated by exsanguination to a target of 50% of the baseline mean arterial pressure. The resuscitation phase was initiated, consisting of simultaneous left pulmonary hilum ligation, via median sternotomy, infusion of autologous blood and initiation of study gas. Animals were monitored for 4 hours. All animals had an initial increase in PVR. PVR remained elevated with placebo; with iNO, PVR decreased to baseline. Echo showed improved RV function in the iNO group while it remained impaired in the placebo group. After an initial increase in shunt and lactate and decrease in SvO2, all returned toward baseline in the iNO group but remained abnormal in the placebo group. These data indicate that by decreasing PVR, iNO decreased RV afterload, preserved RV and LV function, and tissue oxygenation in this hemorrhagic shock and pneumonectomy model. This suggests that iNO may be a useful clinical adjunct to mitigate right heart failure and improve survival when trauma pneumonectomy is required.

  10. Effects of aerosolized ketamine on the level of nitric oxide and nitric oxide synthetase in the lung tissue of rat with asthma

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective: To explore the effects of aerosolized ketamine on the level of nitric oxide and nitric oxide synthetase in the lung tissue in rat asthma model. Methods: Forty SD rats were randomly assigned to five groups: control group (group N), asthma model group (group A), two pretreated groups of different concentrations of ketamine (group K1, K2)and dexamethasone group(group D) with eight rats in each group. The rats in group A were sensitized by injection of ovalbumin (OA) together with aluminum hydroxide and bordetella pertussis as adjuvants. Two weeks after the sensitization, aerosolized OA was used to cause asthma. The rats in group K1 and K2 were sensitized with OA as group A , and then exposed to aerosol of ketamine , with the concentration of 25 g/L and 50 g/L respectively. Before using aerosolized OA, the rats in group D were exposed to aerosol of 0.01% dexamethasone . The level of NO2-/NO3- in lung tissues, inducible nitric oxide synthetase(iNOS) and constitute nitric oxide synthetase(cNOS) was measured in all groups. Results: The level of NO2-/NO3- and the activity of iNOS in lung tissues in group A were signiticantly higher than those in the other groups. The iNOS activity and the level of NO2-/NO3- in lung tissues were highly positively correlated. Conclusion: NO can induce airway hyperreactivity that may worsen asthma. Aerosolized ketamine can decrease the iNOS expression and reduce the level of NO in the lung tissue in rat asthma model.

  11. Tibetan patients with essential hypertension caused by underlying oxidative meta bolism dysfunction and depressed nitric oxide synthesis

    Institute of Scientific and Technical Information of China (English)

    李党生; 王雄伟; 符中明; 余军; 达文莉; 彭顺舟; 王先贵

    2003-01-01

    Objective To assess the role of oxidative metabolism and nitric oxide synthesis for elucid ating their pathophysiological mechanisms in a Tibetan patient with essential hyp ertension. Methods The serum levels of total superoxide dismutase (T-SOD), malondialdehyde (MDA), total antioxidant capacity (T-AOC), nitric oxide (NO) and nitric oxide synthase (NOS) were assayed in sixty native Tibetans (thirty hypertensive patients and t hirty healthy volunteers as control). Results The levels of T-SOD, T-AOC, NO and NOS were significantly lower in the patient group than in the control group (P<0.01); MDA was significantly higher in the patient group than in the control group (P<0.01). The level of MDA ha d a strong negative correlation with T-SOD, T-AOC, NO and NOS (r=-0.82, -0.76, -0.79, -0.73, respectively, P<0.001 for all). Conclusion Tibetan patients with essential hypertension (EH) may have underlying oxidative metabolism dysfunction and depressed NO synthesis, both responsible for the hype rtensive process.

  12. Nitric Oxide-Induced Polycystic Ovaries in The Wistar Rat

    Directory of Open Access Journals (Sweden)

    Fatemeh Hassani

    2012-01-01

    Full Text Available Background: Nitric oxide (NO involves in polycystic ovary syndrome (PCOS, a causeof infertility in women during the reproductive age. The PCOS is now categorized as aninflammatory phenomenon. The aim of this study was to evaluate the role of NO, a proinflammatoryagent, in this syndrome at histological and biochemical levels.Materials and Methods: In this experimental study, animals were female Wistar rats(weighing 200-250 g kept under standard conditions. L-Arginine (50-200 mg/kg, a precursorof NO, was injected intra-peritoneally (i.p. through a period ranging from 9 to14 days/once a day. The rats' estrous cycle was studied using Papanicolaou test; those showing phaseof Diestrous were grouped into experimental and control groups. The control group solelyreceived saline (1 ml/kg, i.p. throughout all experiments. To evaluate the inflammatory effectof NO, the rats were treated an anti-inflammatory agent, naloxone hydrochloride (0.4 mg/kg,i.p., prior to L-arginine. At the end of the treatment period all animals’ ovaries were assessedfor histopathological and histochemical investigations. Also, activation of NO synthase (NOSin the experiments was studied using NADPH-diaphorase technique.Results: The ovaries of rats treated with L-arginine showed polycystic characteristics incontrast to those collected from control or naloxone pretreated groups, based on image analysis.A difference in enzyme activation was also shown in the sections that belonged to thegroups that received L-arginine when compared with the pre-naloxone and control groups.Conclusion: Based on these results, we believe that NO may play a major role in thepathophysiology of PCOS.

  13. Dispersal of human and plant pathogens biofilms via nitric oxide donors at 4 °C.

    Science.gov (United States)

    Marvasi, Massimiliano; Durie, Ian A; Henríquez, Tania; Satkute, Aiste; Matuszewska, Marta; Prado, Raphael Carvalho

    2016-12-01

    Recent studies suggest that nitric oxide donors capable of manipulating nitric oxide-mediated signaling in bacteria could induce dispersal of biofilms. Encased in extracellular polymeric substances, human and plant pathogens within biofilms are significantly more resistant to sanitizers. This is particularly a problem in refrigerated environments where food is processed. In an exercise aimed to study the potential of nitric oxide donors as biofilm dispersal in refrigerated conditions, we compared the ability of different nitric oxide donors (SNAP, NO-aspirin and Noc-5) to dislodge biofilms formed by foodborne, human and plant pathogens treated at 4 °C. The donors SNAP and Noc-5 were efficient in dispersing biofilms formed by Salmonella enterica, pathogenic Escherichia coli and Listeria innocua. The biomasses were decreased up to 30 % when compared with the untreated controls. When the plant pathogens Pectobacterium sp. and Xanthomonas sp. were tested the dispersion was mainly limited to Pectobacterium carotovorum biofilms, decreasing up to 15 % after exposure to molsidomine. Finally, the association of selected nitric oxide donors with sanitizers (DiQuat, H2O2, peracetic acid and PhenoTek II) was effective in dispersing biofilms. The best dispersal was achieved by pre-treating P. carotovorum with molsidomine and then peracetic acid. The synergistic effect was estimated up to ~35 % in dispersal when compared with peracetic acid alone. The association of nitric oxide donors with sanitizers could provide a foundation for an improved sanitization procedure for cleaning refrigerate environments.

  14. Flavone inhibits nitric oxide synthase (NOS) activity, nitric oxide production and protein S-nitrosylation in breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Wenzhen; Yang, Bingwu; Fu, Huiling; Ma, Long; Liu, Tingting; Chai, Rongfei; Zheng, Zhaodi [Shandong Provincial Key Laboratory of Animal Resistant Biology, School of Life Sciences, Shandong Normal University, Jinan 250014 (China); Zhang, Qunye, E-mail: wz.zhangqy@sdu.edu.cn [Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, Shandong (China); Li, Guorong, E-mail: grli@sdnu.edu.cn [Shandong Provincial Key Laboratory of Animal Resistant Biology, School of Life Sciences, Shandong Normal University, Jinan 250014 (China)

    2015-03-13

    As the core structure of flavonoids, flavone has been proved to possess anticancer effects. Flavone's growth inhibitory functions are related to NO. NO is synthesized by nitric oxide synthase (NOS), and generally increased in a variety of cancer cells. NO regulates multiple cellular responses by S-nitrosylation. In this study, we explored flavone-induced regulations on nitric oxide (NO)-related cellular processes in breast cancer cells. Our results showed that, flavone suppresses breast cancer cell proliferation and induces apoptosis. Flavone restrains NO synthesis by does-dependent inhibiting NOS enzymatic activity. The decrease of NO generation was detected by fluorescence microscopy and flow cytometry. Flavone-induced inhibitory effect on NOS activity is dependent on intact cell structure. For the NO-induced protein modification, flavone treatment significantly down-regulated protein S-nitrosylation, which was detected by “Biotin-switch” method. The present study provides a novel, NO-related mechanism for the anticancer function of flavone. - Highlights: • Flavone inhibits proliferation and induces apoptosis in MCF-7 cells. • Flavone decreases nitric oxide production by inhibiting NOS enzymatic activity in breast cancer cells. • Flavone down-regulates protein S-nitrosylation.

  15. Cough and exhaled nitric oxide levels: what happens with exercise?

    Science.gov (United States)

    Petsky, Helen L; Kynaston, Jennifer Anne; McElrea, Margaret; Turner, Catherine; Isles, Alan; Chang, Anne B

    2013-01-01

    Cough associated with exertion is often used as a surrogate marker of asthma. However, to date there are no studies that have objectively measured cough in association with exercise in children. Our primary aim was to examine whether children with a pre-existing cough have an increase in cough frequency during and post-exercise. We hypothesized that children with any coughing illness will have an increase in cough frequency post-exercise regardless of the presence of exercise-induced broncho-constriction (EIB) or atopy. In addition, we hypothesized that Fractional exhaled nitric oxide (FeNO) levels decreases post-exercise regardless of the presence of EIB or atopy. Children with chronic cough and a control group without cough undertook an exercise challenge, FeNO measurements and a skin prick test, and wore a 24-h voice recorder to objectively measure cough frequency. The association between recorded cough frequency, exercise, atopy, and presence of EIB was tested. We also determined if the change in FeNO post exercise related to atopy or EIB. Of the 50 children recruited (35 with cough, 15 control), 7 had EIB. Children with cough had a significant increase in cough counts (median 7.0, inter-quartile ranges, 0.5, 24.5) compared to controls (2.0, IQR 0, 5.0, p = 0.028) post-exercise. Presence of atopy or EIB did not influence cough frequency. FeNO level was significantly lower post-exercise in both groups but the change was not influenced by atopy or EIB. Cough post-exertion is likely a generic response in children with a current cough. FeNO level decreases post-exercise irrespective of the presence of atopy or EIB. A larger study is necessary confirm or refute our findings.

  16. Nitric oxide stress in sporadic inclusion body myositis muscle fibres: inhibition of inducible nitric oxide synthase prevents interleukin-1β-induced accumulation of β-amyloid and cell death.

    Science.gov (United States)

    Schmidt, Jens; Barthel, Konstanze; Zschüntzsch, Jana; Muth, Ingrid E; Swindle, Emily J; Hombach, Anja; Sehmisch, Stephan; Wrede, Arne; Lühder, Fred; Gold, Ralf; Dalakas, Marinos C

    2012-04-01

    Sporadic inclusion body myositis is a severely disabling myopathy. The design of effective treatment strategies is hampered by insufficient understanding of the complex disease pathology. Particularly, the nature of interrelationships between inflammatory and degenerative pathomechanisms in sporadic inclusion body myositis has remained elusive. In Alzheimer's dementia, accumulation of β-amyloid has been shown to be associated with upregulation of nitric oxide. Using quantitative polymerase chain reaction, an overexpression of inducible nitric oxide synthase was observed in five out of ten patients with sporadic inclusion body myositis, two of eleven with dermatomyositis, three of eight with polymyositis, two of nine with muscular dystrophy and two of ten non-myopathic controls. Immunohistochemistry confirmed protein expression of inducible nitric oxide synthase and demonstrated intracellular nitration of tyrosine, an indicator for intra-fibre production of nitric oxide, in sporadic inclusion body myositis muscle samples, but much less in dermatomyositis or polymyositis, hardly in dystrophic muscle and not in non-myopathic controls. Using fluorescent double-labelling immunohistochemistry, a significant co-localization was observed in sporadic inclusion body myositis muscle between β-amyloid, thioflavine-S and nitrotyrosine. In primary cultures of human myotubes and in myoblasts, exposure to interleukin-1β in combination with interferon-γ induced a robust upregulation of inducible nitric oxide synthase messenger RNA. Using fluorescent detectors of reactive oxygen species and nitric oxide, dichlorofluorescein and diaminofluorescein, respectively, flow cytometry revealed that interleukin-1β combined with interferon-γ induced intracellular production of nitric oxide, which was associated with necrotic cell death in muscle cells. Intracellular nitration of tyrosine was noted, which partly co-localized with amyloid precursor protein, but not with desmin

  17. Propolis attenuates oxidative injury in brain and lung of nitric oxide synthase inhibited rats

    Directory of Open Access Journals (Sweden)

    Zeliha Selamoglu-Talas

    2015-10-01

    Full Text Available Background: The blocking of nitric oxide synthase (NOS activity may reason vasoconstriction with formation of reactive oxygen species. Propolis has biological and pharmacological properties, such as antioxidant. The aim of this study was to examine the antioxidant effects of propolis which natural product on biochemical parameters in brain and lung tissues of acute nitric oxide synthase inhibited rats by Nω-nitro-L-arginine methyl ester (L-NAME.Methods: Rats have been received L-NAME (40 mg/kg, intraperitoneally, NOS inhibitor for 15 days to produce hypertension and propolis (200mg/kg, by gavage the lastest 5 of 15 days.Results: There  were  the  increase  (P<0.001  in  the  malondialdehyde  levels  in  the  L-NAME treatment groups when compared to control rats, but the decrease (P<0.001 in the catalase activities in both brain and lung tissues. There were statistically changes (P<0.001 in these parameters of L-NAME+propolis treated rats as compared with L-NAME-treated group.Conclusion: The application of L-NAME to the Wistar rats resulted in well developed oxidative stress. Also, propolis may influence endothelial NO production. Identification of such compounds and characterisation of their cellular actions may increase our knowledge of the regulation of endothelial NO production and could provide valuable clues for the prevention or treatment of hypertensive diseases and oxidative stress.

  18. Nitric oxide adsorbed on zeolites: EPR studies.

    Science.gov (United States)

    Yahiro, Hidenori; Lund, Anders; Shiotani, Masaru

    2004-05-01

    CW-EPR studies of NO adsorbed on sodium ion-exchanged zeolites were focused on the geometrical structure of NO monoradical and (NO)2 biradical formed on zeolites. The EPR spectrum of NO monoradical adsorbed on zeolite can be characterized by the three different g-tensor components and the resolved y-component hyperfine coupling with the 14N nucleus. Among the g-tensor components, the value of g(zz) is very sensitive to the local environment of zeolite and becomes a measure of the electrostatic field in zeolite. The temperature dependence of the g-tensor demonstrated the presence of two states of the Na-NO adduct, in rigid and rotational states. The EPR spectra of NO adsorbed on alkaline metal ion-exchanged zeolite and their temperature dependency are essentially the same as that on sodium ion-exchanged zeolite. On the other hand, for NO adsorbed on copper ion-exchanged zeolite it is known that the magnetic interaction between NO molecule and paramagnetic copper ion are observable in the spectra recorded at low temperature. The signals assigned to (NO)2 biradical were detected for EPR spectrum of NO adsorbed on Na-LTA. CW-EPR spectra as well as their theoretical calculation suggested that the two NO molecules are aligned along their N-O bond axes. A new procedure for automatical EPR simulation is described which makes it possible to analyze EPR spectrum easily. In the last part of this paper, some instances when other nitrogen oxides were used as a probe molecule to characterize the zeolite structure, chemical properties of zeolites, and dynamics of small molecules were described on the basis of selected literature data reported recently.

  19. Nitric oxide formation from nitrite in zebrafish

    DEFF Research Database (Denmark)

    Jensen, Frank Bo

    2007-01-01

    nitrite levels for variable time periods, and changes in blood nitrosylhemoglobin (HbNO), methemoglobin (metHb), oxygenated hemoglobin (oxyHb) and deoxygenated hemoglobin (deoxyHb) were evaluated by spectral deconvolution. Blood HbNO (a biomarker of internal NO production) was low in controls, increased......, and the possibility that excess NO may inhibit mitochondrial respiration, whole animal routine oxygen consumption was not depressed....

  20. Role of Polymorphisms of Inducible Nitric Oxide Synthase and Endothelial Nitric Oxide Synthase in Idiopathic Environmental Intolerances

    Directory of Open Access Journals (Sweden)

    Chiara De Luca

    2015-01-01

    Full Text Available Oxidative stress and inflammation play a pathogenetic role in idiopathic environmental intolerances (IEI, namely, multiple chemical sensitivity (MCS, fibromyalgia (FM, and chronic fatigue syndrome (CFS. Given the reported association of nitric oxide synthase (NOS gene polymorphisms with inflammatory disorders, we aimed to investigate the distribution of NOS2A −2.5 kb (CCTTTn as well as Ser608Leu and NOS3 −786T>C variants and their correlation with nitrite/nitrate levels, in a study cohort including 170 MCS, 108 suspected MCS (SMCS, 89 FM/CFS, and 196 healthy subjects. Patients and controls had similar distributions of NOS2A Ser608Leu and NOS3 −786T>C polymorphisms. Interestingly, the NOS3 −786TT genotype was associated with increased nitrite/nitrate levels only in IEI patients. We also found that the NOS2A −2.5 kb (CCTTT11 allele represents a genetic determinant for FM/CFS, and the (CCTTT16 allele discriminates MCS from SMCS patients. Instead, the (CCTTT8 allele reduces by three-, six-, and tenfold, respectively, the risk for MCS, SMCS, and FM/CFS. Moreover, a short number of (CCTTT repeats is associated with higher concentrations of nitrites/nitrates. Here, we first demonstrate that NOS3 −786T>C variant affects nitrite/nitrate levels in IEI patients and that screening for NOS2A −2.5 kb (CCTTTn polymorphism may be useful for differential diagnosis of various IEI.

  1. Oxidative aromatization of 3,5-disubstituted 2-isoxazolines by nitric oxide

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    3,5-Disubstituted 2-isoxazolines were oxidized to corresponding isoxazoles by nitric oxide in dichloromethane. The reaction more likely occurred via a one-electron transfer process.(C) 2007 Long Min Wu. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

  2. Dynamics of Nitric Oxide and Nitrous Oxide Emission during Nitrogen Conversion Processes

    NARCIS (Netherlands)

    Kampschreur, M.J.

    2010-01-01

    Nitric oxide (NO) and nitrous oxide (N2O) emissions can be a serious threat to the environment. Rising levels of N2O in the atmosphere contribute to global warming and destruction of the ozone layer. This thesis describes an investigation on the emission of NO and N2O during nitrogen conversion proc

  3. Modulation of nitric oxide synthase isoenzymes inreperfused skeletal muscle

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To investigate the modulation of nitric oxide synthnse (NOS) isoenzymes in skeletal muscle during 3 h ischemia/reperfusion (I/R, 3 h ischemia followed by 3 h reperfusion). Methods: The extensor digitorum longuses (EDLs)from 20 adult rats were divided into 4 groups: the normal,the sham operation, the ischemia (3 h), and the ischemia/reperfusion group. One normal EDL from each rat was used as the non-operated control, and the opposite ones are distributed into the 3 remaining groups. All the samples were studied with Western blotting technique and immumohistochemistry staining. Results: Three sizes of protein bands verified with the proteins of relative molecule to be of 155 000, 140 000and 135 000, were detected in the EDL homogenate by Western blotting, which were comparable with the positive controls for nNOS, eNOS and iNOS, respectively. Immunostaining demonstrated that nNOS was present in the muscle fiber, with a similar location of the muscle stria, eNOS was found apparently in microvascular endothelia,but not found in muscle fibers, and iNOS was found in the leukocytes around the muscle fiber and some endothelia cells. Immunostaining paralleled the Western blotting results. Conclusions: It suggests that the constitutive nNOS and eNOS protein can be regulated by I/R, and I/R results in a down regulation of nNOS and up-regulation of eNOS and iNOS in reperfused skeletal muscle. The fact that nNOS is present around stria suggests that nNOS may have a close relationship with muscle function. The localization of eNOS in endothelial cell indicates its role in regulating blood supply of the muscle. Based on these findings, it is possible that NO produced by distinct NOS may play a different role in I/R injury.

  4. Inducible nitric oxide synthase haplotype associated with migraine and aura.

    Science.gov (United States)

    de O S Mansur, Thiago; Gonçalves, Flavia M; Martins-Oliveira, Alisson; Speciali, Jose G; Dach, Fabiola; Lacchini, Riccardo; Tanus-Santos, Jose E

    2012-05-01

    Migraine is a complex neurological disorder with a clear neurogenic inflammatory component apparently including enhanced nitric oxide (NO) formation. Excessive NO amounts possibly contributing to migraine are derived from increased expression and activity of inducible NO synthase (iNOS). We tested the hypothesis that two functional, clinically relevant iNOS genetic polymorphisms (C(-1026)A-rs2779249 and G2087A-rs2297518) are associated with migraine with or without aura. We studied 142 healthy women without migraine (control group) and 200 women with migraine divided into two groups: 148 with migraine without aura (MWA) and 52 with aura (MA). Genotypes were determined by real-time polymerase chain reaction using the Taqman(®) allele discrimination assays. The PHASE 2.1 software was used to estimate the haplotypes. The A allele for the G2087A polymorphism was more commonly found in the MA group than in the MWA group (28 vs. 18%; P 0.05). The haplotype combining both A alleles for the two polymorphisms was more commonly found in the MA group than in the control group or in the MWA group (19 vs. 10 or 8%; P = 0.0245 or 0.0027, respectively). Our findings indicate that the G2087A and the C(-1026)A polymorphism in the iNOS gene affect the susceptibility to migraine with aura when their effects are combined within haplotypes, whereas the G2087A affects the susceptibility to aura in migraine patients. These finding may have therapeutic implications when examining the effects of selective iNOS inhibitors.

  5. Inhaled nitric oxide decreases pulmonary endothelial nitric oxide synthase expression and activity in normal newborn rat lungs

    Directory of Open Access Journals (Sweden)

    Thông Hua-Huy

    2016-02-01

    Full Text Available Inhaled nitric oxide (iNO is commonly used in the treatment of very ill pre-term newborns. Previous studies showed that exogenous NO could affect endothelial NO synthase (eNOS activity and expression in vascular endothelial cell cultures or adult rat models, but this has never been fully described in newborn rat lungs. We therefore aimed to assess the effects of iNO on eNOS expression and activity in newborn rats. Rat pups, post-natal day (P 0 to P7, and their dams were placed in a chamber containing NO at 5 ppm (iNO-5 ppm group or 20 ppm (iNO-20 ppm group, or in room air (control group. Rat pups were sacrificed at P7 and P14 for evaluation of lung eNOS expression and activity. At P7, eNOS protein expression in total lung lysates, in bronchial and arterial sections, was significantly decreased in the iNO-20 ppm versus control group. At P14, eNOS expression was comparable among all three groups. The amounts of eNOS mRNA significantly differed at P7 between the iNO-20 ppm and control groups. NOS activity decreased in the iNO-20 ppm group at P7 and returned to normal levels at P14. There was an imbalance between superoxide dismutase and NOS activities in the iNO-20 ppm group at P7. Inhalation of NO at 20 ppm early after birth decreases eNOS gene transcription, protein expression and enzyme activity. This decrease might account for the rebound phenomenon observed in patients treated with iNO.

  6. Prednisolone reduces nitric oxide-induced migraine

    DEFF Research Database (Denmark)

    Tfelt-Hansen, P; Daugaard, D; Lassen, L H

    2009-01-01

    BACKGROUND AND PURPOSE: Glyceryl trinitrate (GTN) induces delayed migraine attacks in migraine patients. The purpose of this study was to investigate whether pre-treatment with prednisolon could decrease this effect of GTN. METHODS: In this double-blind, randomized and placebo-controlled, crossover...... study 15 migraineurs with migraine without aura were pre-treated with 150 mg of prednisolone or placebo followed by a 20-min infusion of GTN (0.5 ug/kg/min). One hour after the GTN-infusion, the participants were sent home, but continued to rate headache and possible associated symptoms by filling out...... a headache diary every hour for 12 h. There were two equal primary efficacy end-points: frequency of delayed migraine and intensity of delayed headache. RESULTS: Nine patients experienced a GTN headache fulfilling the diagnostic criteria for migraine without aura on the placebo day compared with four...

  7. Endogenous Nitric Oxide Production and Pulmonary Blood Flow : during different experimental lung conditions

    OpenAIRE

    Nilsson, Manja

    2011-01-01

    Nitric oxide (NO) is an important regulator of pulmonary blood flow and attenuates hypoxic pulmonary vasoconstriction (HPV). Nitric oxide is synthesized enzymatically in a number of tissues, including the lungs, and can also be generated from reduction of nitrite during hypoxia and acidosis. Inhaled nitric oxide (INO) is a selective pulmonary vasodilator, with no effects on systemic arterial blood pressure due to inactivation by hemoglobin in the blood. INO has distant effects both within the...

  8. Role of nitric oxide in experimental obliterative bronchiolitis (chronic rejection) in the rat.

    OpenAIRE

    Kallio, E A; Koskinen, P K; Aavik, E; Vaali, K; Lemstöm, K B

    1997-01-01

    The role of nitric oxide in obliterative bronchiolitis development, i.e., chronic rejection, was investigated in the heterotopic rat tracheal allograft model. An increase in the intragraft inducible nitric oxide synthase (iNOS) mRNA and mononuclear inflammatory cell iNOS immunoreactivity was demonstrated during progressive loss of respiratory epithelium and airway occlusion in nontreated allografts compared to syngeneic grafts. In nontreated allografts, however, intragraft nitric oxide produc...

  9. Synthesis and antitumor activity of nitric oxide releasing derivatives of AT1 antagonist

    Institute of Scientific and Technical Information of China (English)

    Yan Chun Zhang; Jin Pei Zhou; Xiao Ming Wu; Wei Hong Pan

    2009-01-01

    A series of novel nitric oxide-donating derivatives (7a-e, 8a-e) were synthesized by coupling furoxan and nitric oxide with irbesartan analogue and their cytotoxicity against BEL7402 cells in vitro were evaluated by MTI" method. It was found that 8c exhibits the most cytotoxic activities with IC.so value of 12.5 umol/L. The hybrids of ATI antagonist and nitric oxide donor appear to have beneficial effects on antitumor.

  10. Spectrophotometric activity microassay for pure and recombinant cytochrome P450-type nitric oxide reductase

    CSIR Research Space (South Africa)

    Garny, S

    2014-02-01

    Full Text Available Nitric oxide reductase (NOR) of the P450 oxidoreductase family accepts electrons directly from its cofactor, NADH, to reduce two nitric oxide (NO) molecules to one nitrous oxide molecule and water. The enzyme plays a key role in removal of radical...

  11. Changes in oxygenation and pulmonary haemodynamics in preterm infants treated with inhaled nitric oxide

    OpenAIRE

    Subhedar, N; Shaw, N

    1997-01-01

    AIM—To investigate changes in various cardiorespiratory variables with inhaled nitric oxide (NO), as part of a randomised controlled trial.
METHODS—Infants were treated with inhaled NO for 72 hours. Changes in oxygenation were assessed using the oxygenation index (OI). Serial changes in pulmonary artery pressure (PAP) were assessed using the Doppler derived acceleration time to right ventricular ejection time ratio (AT:RVET). Doppler measurements of right ventricular output, pulmonary blood f...

  12. Elevated levels of exhaled nitric oxide in patients with anorexia nervosa

    OpenAIRE

    Oświęcimska, Joanna; Ziora, Katarzyna; Ziora, Dariusz; Machura, Edyta; Smerdziński, Sebastian; Pyś-Spychała, Magdalena; Kasperski, Jacek; Zamłyński, Jacek; Kasperska-Zajac, Alicja

    2013-01-01

    Background Nitric oxide (NO) is involved in eating behavior and inflammatory response. Moreover, there is evidence that NO production is altered in patients with anorexia nervosa (AN). Aim To assess whether the overproduction of NO in AN can affect NO level in exhaled air. Materials and methods Exhaled NO level was studied in 23 girls with AN and compared with that of healthy age- and gender-matched nonatopic controls. Results Exhaled NO levels were significantly higher in girls with AN compa...

  13. Effects of nitric oxide on resistance to bacterial infection in mice

    Energy Technology Data Exchange (ETDEWEB)

    Azoulay, E. (INSERM, Paris, France); Bouley, G.; Blayo, M.C.

    1981-06-01

    Continuous exposure to 2 ppM nitric oxide (NO) for as long as 4 wk did not reduce the resistance of male mice to infection by aerosol inoculation with Pasteurella multocida. In contrast, mortality was slightly enhanced and survival shortened in NO-exposed compared to control female mice; however, the importance of these small differences is uncertain. These results suggest only that male and famale mice did not react similarly to the infectious challenge after exposure to NO.

  14. Nitric oxide and thermogenesis--challenge in molecular cell physiology.

    Science.gov (United States)

    Otasevic, Vesna; Korac, Aleksandra; Buzadzic, Biljana; Stancic, Ana; Jankovic, Aleksandra; Korac, Bato

    2011-06-01

    Only recently we can link thermogenesis, mitochondria, nitric oxide, and redox regulation in biochemical terms. Currently, we are discussing these processes from the aspect of fundamental principles of molecular physiology. Thus, the present article highlights both cell physiology and the principles of the maintenance of energy homeostasis in organisms. Energy homeostasis means much more than simple combustion; adipose tissues at this point of evolution development are related to a broad spectrum of metabolic disturbances and all aspects of cellular remodeling (i.e. structural, metabolic and endocrine changes). Therefore, this paper addresses not only thermogenesis but also energy homeostasis, oxidative phosphorylation and ATP production, proliferation and differentiation of brown adipocytes, their life and death, mitochondriogenesis and angiogenesis. These processes will be united by molecular players of oxidation/reduction reactions, thus creating the principles based on the redox regulation.

  15. Role of nitric oxide in coronary vasomotion during handgrip exercise.

    Science.gov (United States)

    Nishikawa, Y; Kanki, H; Ogawa, S

    1997-11-01

    Endothelium-dependent modulation of coronary vasomotion during increased sympathetic tone remains unclear in normal and atherosclerotic human coronory arteries. We evaluated the role of endothelium-derived nitric oxide in vasomotion during isometric exercise in normal subjects (n = 7) and in patients with coronary artery disease (CAD) (n = 10). Coronary blood flow and epicardial coronary artery diameter to the handgrip test were measured before and after intracoronary administration of 100 micromol/min of N(G)-monomethyl L-arginine (L-NMMA). Heart rate and aortic blood pressure increased during handgrip test. Handgrip test caused a significant dilation in the diameter of the epicardial coronary artery in normal subjects (9.9% +/- 3.9%, mean +/- SD) and in the diameter of smooth segments of patients with CAD (5% +/- 3.7%, p < 0.05 vs normal subjects). In contrast, the diameter of irregular segments in patients with CAD decreased during handgrip test (-9.8 +/- 3.9%). After L-NMMA, the epicardial coronary artery significantly increased during handgrip test compared with before L-NMMA in normal subjects. L-NMMA did not have any effect on handgrip test induced vasodilation in the smooth segments and vasoconstriction in the irregular segments in the patients with CAD. Handgrip test-induced increases in coronary blood flow did not change after L-NMMA in both groups. Nitric oxide does not play a major role in HNG-induced vasodilation in epicardial and microcirculatory vessels in normal human coronary circulation. Although the decreased release in nitric oxide may modulate the abnormal response of the epicardial coronary artery to handgrip test, this does not explain the paradoxic constrictive response from the depressed but still dilatory response in the patients with CAD.

  16. Reduction Rates for Higher Americium Oxidation States in Nitric Acid

    Energy Technology Data Exchange (ETDEWEB)

    Grimes, Travis Shane [Idaho National Lab. (INL), Idaho Falls, ID (United States); Mincher, Bruce Jay [Idaho National Lab. (INL), Idaho Falls, ID (United States); Schmitt, Nicholas C [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2015-09-30

    The stability of hexavalent americium was measured using multiple americium concentrations and nitric acid concentrations after contact with the strong oxidant sodium bismuthate. Contrary to our hypotheses Am(VI) was not reduced faster at higher americium concentrations, and the reduction was only zero-order at short time scales. Attempts to model the reduction kinetics using zero order kinetic models showed Am(VI) reduction in nitric acid is more complex than the autoreduction processes reported by others in perchloric acid. The classical zero-order reduction of Am(VI) was found here only for short times on the order of a few hours. We did show that the rate of Am(V) production was less than the rate of Am(VI) reduction, indicating that some Am(VI) undergoes two electron-reduction to Am(IV). We also monitored the Am(VI) reduction in contact with the organic diluent dodecane. A direct comparison of these results with those in the absence of the organic diluent showed the reduction rates for Am(VI) were not statistically different for both systems. Additional americium oxidations conducted in the presence of Ce(IV)/Ce(III) ions showed that Am(VI) is reduced without the typical growth of Am(V) observed in the systems sans Ce ion. This was an interesting result which suggests a potential new reduction/oxidation pathway for Am in the presence of Ce; however, these results were very preliminary, and will require additional experiments to understand the mechanism by which this occurs. Overall, these studies have shown that hexavalent americium is fundamentally stable enough in nitric acid to run a separations process. However, the complicated nature of the reduction pathways based on the system components is far from being rigorously understood.

  17. Characteristics of the nitric oxide synthase-catalyzed conversion of arginine to N-hydroxyarginine, the first oxygenation step in the enzymic synthesis of nitric oxide.

    Science.gov (United States)

    Campos, K L; Giovanelli, J; Kaufman, S

    1995-01-27

    The nitric oxide synthase-catalyzed conversion of L-arginine to L-citrulline and nitric oxide is known to be the sum of two partial reactions: oxygenation of arginine to N-hydroxyarginine, followed by oxygenation of N-hydroxyarginine to citrulline and nitric oxide. Whereas the conversion of N-hydroxyarginine to citrulline and nitric oxide has been the subject of a number of studies, the oxygenation of arginine to N-hydroxyarginine has received little attention. Here we show that substrate amounts of rat cerebellar nitric oxide synthase, in the absence of added NADPH, catalyze the conversion of arginine to N-hydroxyarginine as the dominant product. The product appears not to be tightly bound to the enzyme. A maximum of 0.16 mol of N-hydroxyarginine/mol of nitric oxide synthase subunit was formed. The reaction requires oxygen and the addition of Ca2+/calmodulin and is stimulated 3-fold by tetrahydrobiopterin. Upon addition of NADPH, citrulline is formed exclusively. Conversion of N-hydroxyarginine to citrulline, like the first partial reaction, requires Ca2+/calmodulin and is stimulated by tetrahydrobiopterin but differs from the first partial reaction in being completely dependent upon addition of NADPH. These results indicate that brain nitric oxide synthase contains an endogenous reductant that can support oxygenation of arginine but not of N-hydroxyarginine. The reductant is not NADPH, since the amount of nitric oxide synthase-bound NADPH is appreciably less than the amount required for N-hydroxyarginine synthesis. Possible candidates for this role are discussed in relation to proposed mechanisms of action of nitric oxide synthase.

  18. Increased angiogenesis in portal hypertensive rats: role of nitric oxide.

    Science.gov (United States)

    Sumanovski, L T; Battegay, E; Stumm, M; van der Kooij, M; Sieber, C C

    1999-04-01

    Systemic and especially splanchnic arterial vasodilation accompany chronic portal hypertension. Different soluble mediators causing this vasodilation have been proposed, the strongest evidence being for nitric oxide (NO). No data exist if structural vascular changes may partly account for this vasodilatory state. Here, we developed a new in vivo quantitative angiogenesis assay in the abdominal cavity and determined if: 1) portal hypertensive rats show increased angiogenesis; and 2) angiogenesis is altered by inhibiting NO formation. Portal hypertension was induced by partial portal vein ligation (PVL). Sham-operated rats served as controls (CON). During the index operation (day 0), a teflon ring filled with collagen I (Vitrogen 100) was sutured in the mesenteric cavity. After 16 days, rings were explanted, embedded in paraffin, and ingrown vessels counted using a morphometry system. The role of NO was tested by adding an antagonist of NO formation (Nomega-nitro-L-arginine [NNA], 3.3 mg/kg/d) into the drinking water. The mean number of ingrown vessels per implant was significantly higher in PVL rats compared with CON rats, i.e., 1,453 +/- 187 versus 888 +/- 116, respectively (P <.05; N = 5 per group). NNA significantly (P <.01) inhibited angiogenesis in PVL (202 +/- 124; N = 5) and in CON (174 +/- 25; N = 6) rats, respectively. In contrast, the beta-adrenergic blocker, propranolol, did not prevent angiogenesis either in PVL or CON rats in a separate set of experiments (data not shown). The conclusions drawn from this study are that: 1) rats with portal hypertension show increased angiogenesis; and 2) inhibition of NO formation significantly prevents angiogenesis in both PVL and CON rats. Therefore, splanchnic vasodilation in chronic portal hypertension may also be a result of structural changes.

  19. Nitric oxide and phytohormone interactions: current status and perspectives

    Directory of Open Access Journals (Sweden)

    Luciano eFreschi

    2013-10-01

    Full Text Available Nitric oxide (NO is currently considered a ubiquitous signal in plant systems, playing significant roles in a wide range of plant responses to environmental and endogenous cues. During the signaling events leading to these plant responses, NO frequently interacts with plant hormones and other endogenous molecules, at times originating remarkably complex signaling cascades. Accumulating evidence indicates that virtually all major classes of plant hormones may influence, at least to some degree, the endogenous levels of NO. In addition, studies conducted during the induction of diverse plant responses have demonstrated that NO may also affect biosynthesis, catabolism/conjugation, transport, perception and/or transduction of different phytohormones, such as auxins, gibberellins, cytokinins, abscisic acid, ethylene, salicylic acid, jasmonates and brassinosteroids. Although still not completely elucidated, the mechanisms underlying the interaction between NO and plant hormones have recently been investigated in a number of species and plant responses. This review specifically focuses on the current knowledge of the mechanisms implicated in NO-phytohormone interactions during the regulation of developmental and metabolic plant events. The modifications triggered by NO on the transcription of genes encoding biosynthetic/degradative enzymes as well as proteins involved in the transport and signal transduction of distinct plant hormones will be contextualized during the control of developmental, metabolic and defense responses in plants. Moreover, the direct post-translational modification of phytohormone biosynthetic enzymes and receptors through S-nitrosylation will also be discussed as a key mechanism for regulating plant physiological responses. Finally, some future perspectives toward a more complete understanding of NO-phytohormone interactions will also be presented and discussed.

  20. Nitric oxide, antioxidants and prooxidants in plant defence responses

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    Felicitas eGroß

    2013-10-01

    Full Text Available In plant cells the free radical nitric oxide (NO interacts both with anti- as well as prooxidants. This review provides a short survey of the central roles of ascorbate and glutathione – the latter alone or in conjunction with S-nitrosoglutathione reductase – in controlling NO bioavailability. Other major topics include the regulation of antioxidant enzymes by NO and the interplay between NO and reactive oxygen species (ROS. Under stress conditions NO regulates antioxidant enzymes at the level of activity and gene expression, which can cause either enhancement or reduction of the cellular redox status. For instance chronic NO production during salt stress induced the antioxidant system thereby increasing salt tolerance in various plants. In contrast, rapid NO accumulation in response to strong stress stimuli was occasionally linked to inhibition of antioxidant enzymes and a subsequent rise in hydrogen peroxide levels. Moreover, during incompatible Arabidopsis thaliana-Pseudomonas syringae interactions ROS burst and cell death progression were shown to be terminated by S-nitrosylation-triggered inhibition of NADPH oxidases, further highlighting the multiple roles of NO during redox-signalling. In chemical reactions between NO and ROS reactive nitrogen species arise with characteristics different from their precursors. Recently, peroxynitrite formed by the reaction of NO with superoxide has attracted much attention. We will describe putative functions of this molecule and other NO derivatives in plant cells. Non-symbiotic hemoglobins (nsHb were proposed to act in NO degradation. Additionally, like other oxidases nsHb is also capable of catalysing protein nitration through a nitrite- and hydrogen peroxide-dependent process. The physiological significance of the described findings under abiotic and biotic stress conditions will be discussed with a special emphasis on pathogen-induced programmed cell death.

  1. Interplay between connexin40 and nitric oxide signaling during hypertension.

    Science.gov (United States)

    Le Gal, Loïc; Alonso, Florian; Mazzolai, Lucia; Meda, Paolo; Haefliger, Jacques-Antoine

    2015-04-01

    Connexins (Cxs) and endothelial nitric oxide synthase (eNOS) contribute to the adaptation of endothelial and smooth muscle cells to hemodynamic changes. To decipher the in vivo interplay between these proteins, we studied Cx40-null mice, a model of renin-dependent hypertension which displays an altered endothelium-dependent relaxation of the aorta because of reduced eNOS levels. These mice, which were either untreated or subjected to the 1-kidney, 1-clip (1K1C) procedure, a model of volume-dependent hypertension, were compared with control mice submitted to either the 1K1C or the 2-kidney, 1-clip (2K1C) procedure, a model of renin-dependent hypertension. All operated mice became hypertensive and featured hypertrophy and altered Cx expression of the aorta. The combination of volume- and renin-dependent hypertension in Cx40-/- 1K1C mice raised blood pressure and cardiac weight index. Under these conditions, all aortas showed increased levels of Cx40 in endothelial cells and of both Cx37 and Cx45 in smooth muscle cells. In the wild-type 1K1C mice, the interactions between Cx40 and Cx37 with eNOS were enhanced, resulting in increased NO release. The Cx40-eNOS interaction could not be observed in mice lacking Cx40, which also featured decreased levels of eNOS. In these animals, the volume overload caused by the 1K1C procedure resulted in increased phosphorylation of eNOS and in a higher NO release. The findings provide evidence that Cx40 and Cx37 play an in vivo role in the regulation of eNOS.

  2. Nitric Oxide-Sensitive Pulmonary Hypertension in Congenital Rubella Syndrome

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    Francesco Raimondi

    2015-01-01

    Full Text Available Persistent pulmonary hypertension is a very rare presentation of congenital virus infection. We discuss the case of complete congenital rubella syndrome presenting at echocardiography with pulmonary hypertension that worsened after ductus ligation. Cardiac catheterization showed a normal pulmonary valve and vascular tree but a PAP=40 mmHg. The infant promptly responded to inhaled nitric oxide while on mechanical ventilation and was later shifted to oral sildenafil. It is not clear whether our observation may be due to direct viral damage to the endothelium or to the rubella virus increasing the vascular tone via a metabolic derangement.

  3. Nitric Oxide Signaling in Plant Responses to Abiotic Stresses

    Institute of Scientific and Technical Information of China (English)

    Weihua Qiao; LiuMin Fan

    2008-01-01

    Nitric oxide (NO) plays important roles in diverse physiological processes In plants. NO can provoke both beneficial and harmful effects, which depend on the concentration and location of NO in plant cells. This review is focused on NO synthesis and the functions of NO in plant responses to abiotic environmental stresses. Abiotic stresses mostly induce NO production in plants. NO alleviates the harmfulness of reactive oxygen species, and reacts with other target molecules, and regulates the expression of stress responsive genes under various stress conditions.

  4. H2S regulation of nitric oxide metabolism

    Science.gov (United States)

    Kolluru, Gopi K.; Yuan, Shuai; Shen, Xinggui; Kevil, Christopher G.

    2015-01-01

    Nitric oxide (NO) and hydrogen sulfide (H2S) are two major gaseous signaling molecules that regulate diverse physiological functions. Recent publications indicate the regulatory role of H2S on NO metabolism. In this chapter, we discuss the latest findings on H2S-NO interactions through formation of novel chemical derivatives, and experimental approaches to study these adducts. This chapter also addresses potential H2S interference on various NO detection techniques, along with precautions for analyzing biological samples from various sources. This information will facilitate critical evaluation and clearer insight into H2S regulation of NO signaling and its influence on various physiological functions. PMID:25725527

  5. Nitric Oxide Synthase-3 Promotes Embryonic Development of Atrioventricular Valves

    OpenAIRE

    Yin Liu; Xiangru Lu; Fu-Li Xiang; Man Lu; Qingping Feng

    2013-01-01

    Nitric oxide synthase-3 (NOS3) has recently been shown to promote endothelial-to-mesenchymal transition (EndMT) in the developing atrioventricular (AV) canal. The present study was aimed to investigate the role of NOS3 in embryonic development of AV valves. We hypothesized that NOS3 promotes embryonic development of AV valves via EndMT. To test this hypothesis, morphological and functional analysis of AV valves were performed in wild-type (WT) and NOS3(-/-) mice at postnatal day 0. Our data s...

  6. Nitric oxide and reactive oxygen species in limb vascular function

    DEFF Research Database (Denmark)

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

    2014-01-01

    Abstract Nitric oxide (NO) is known to be one of the most important regulatory compounds within the cardiovascular system where it is central for functions such as regulation of blood pressure, blood flow and vascular growth. The bioavailability of NO is determined by a balance between, on one hand......, the extent of enzymatic and non-enzymatic formation of NO and on the other hand, removal of NO, which in part is dependent on the reaction of NO with reactive oxygen species (ROS). The presence of ROS is dependent on the extent of ROS formation via mitochondria and/or enzymes such as NAD(P)H oxidase...

  7. Nitric Oxide Manipulation: A Therapeutic Target for Peripheral Arterial Disease?

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    Gareth Williams

    2012-01-01

    Full Text Available Peripheral Arterial Disease (PAD is a cause of significant morbidity and mortality in the Western world. Risk factor modification and endovascular and surgical revascularisation are the main treatment options at present. However, a significant number of patients still require major amputation. There is evidence that nitric oxide (NO and its endogenous inhibitor asymmetric dimethylarginine (ADMA play significant roles in the pathophysiology of PAD. This paper reviews experimental work implicating the ADMA-DDAH-NO pathway in PAD, focussing on both the vascular dysfunction and effects within the ischaemic muscle, and examines the potential of manipulating this pathway as a novel adjunct therapy in PAD.

  8. Nitric oxide-mediated intracellular growth restriction of pathogenic Rhodococcus equi can be prevented by iron.

    Science.gov (United States)

    von Bargen, Kristine; Wohlmann, Jens; Taylor, Gregory Alan; Utermöhlen, Olaf; Haas, Albert

    2011-05-01

    Rhodococcus equi is an intracellular pathogen which causes pneumonia in young horses and in immunocompromised humans. R. equi arrests phagosome maturation in macrophages at a prephagolysosome stage and grows inside a privileged compartment. Here, we show that, in murine macrophages activated with gamma interferon and lipopolysaccharide, R. equi does not multiply but stays viable for at least 24 h. Whereas infection control of other intracellular pathogens by activated macrophages is executed by enhanced phagosome acidification or phagolysosome formation, by autophagy or by the interferon-inducible GTPase Irgm1, none of these mechanisms seems to control R. equi infection. Growth control by macrophage activation is fully mimicked by treatment of resting macrophages with nitric oxide donors, and inhibition of bacterial multiplication by either activation or nitric oxide donors is annihilated by cotreatment of infected macrophages with ferrous sulfate. Transcriptional analysis of the R. equi iron-regulated gene iupT demonstrates that intracellular R. equi encounters iron stress in activated, but not in resting, macrophages and that this stress is relieved by extracellular addition of ferrous sulfate. Our results suggest that nitric oxide is central to the restriction of bacterial access to iron in activated macrophages.

  9. Nitric Oxide-Mediated Intracellular Growth Restriction of Pathogenic Rhodococcus equi Can Be Prevented by Iron▿

    Science.gov (United States)

    von Bargen, Kristine; Wohlmann, Jens; Taylor, Gregory Alan; Utermöhlen, Olaf; Haas, Albert

    2011-01-01

    Rhodococcus equi is an intracellular pathogen which causes pneumonia in young horses and in immunocompromised humans. R. equi arrests phagosome maturation in macrophages at a prephagolysosome stage and grows inside a privileged compartment. Here, we show that, in murine macrophages activated with gamma interferon and lipopolysaccharide, R. equi does not multiply but stays viable for at least 24 h. Whereas infection control of other intracellular pathogens by activated macrophages is executed by enhanced phagosome acidification or phagolysosome formation, by autophagy or by the interferon-inducible GTPase Irgm1, none of these mechanisms seems to control R. equi infection. Growth control by macrophage activation is fully mimicked by treatment of resting macrophages with nitric oxide donors, and inhibition of bacterial multiplication by either activation or nitric oxide donors is annihilated by cotreatment of infected macrophages with ferrous sulfate. Transcriptional analysis of the R. equi iron-regulated gene iupT demonstrates that intracellular R. equi encounters iron stress in activated, but not in resting, macrophages and that this stress is relieved by extracellular addition of ferrous sulfate. Our results suggest that nitric oxide is central to the restriction of bacterial access to iron in activated macrophages. PMID:21383050

  10. Nitric oxide and coronary vascular endothelium adaptations in hypertension

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    Andrew S Levy

    2009-12-01

    Full Text Available Andrew S Levy*, Justin CS Chung*, Jeffrey T Kroetsch*, James WE RushDepartment of Kinesiology, University of Waterloo, Waterloo, Ontario, Canada; *These authors contributed equally to this workAbstract: This review highlights a number of nitric oxide (NO-related mechanisms that contribute to coronary vascular function and that are likely affected by hypertension and thus become important clinically as potential considerations in prevention, diagnosis, and treatment of coronary complications of hypertension. Coronary vascular resistance is elevated in hypertension in part due to impaired endothelium-dependent function of coronary arteries. Several lines of evidence suggest that other NO synthase isoforms and dilators other than NO may compensate for impairments in endothelial NO synthase (eNOS to protect coronary artery function, and that NO-dependent function of coronary blood vessels depends on the position of the vessel in the vascular tree. Adaptations in NOS isoforms in the coronary circulation to hypertension are not well described so the compensatory relationship between these and eNOS in hypertensive vessels is not clear. It is important to understand potential functional consequences of these adaptations as they will impact the efficacy of treatments designed to control hypertension and coronary vascular disease. Polymorphisms of the eNOS gene result in significant associations with incidence of hypertension, although mechanistic details linking the polymorphisms with alterations in coronary vasomotor responses and adaptations to hypertension are not established. This understanding should be developed in order to better predict those individuals at the highest risk for coronary vascular complications of hypertension. Greater endothelium-dependent dilation observed in female coronary arteries is likely related to endothelial Ca2+ control and eNOS expression and activity. In hypertension models, the coronary vasculature has not been

  11. Enhanced stem cell-derived cardiomyocyte differentiation in suspension culture by delivery of nitric oxide using S-nitrosocysteine.

    Science.gov (United States)

    Hodge, Alexander J; Zhong, Juming; Lipke, Elizabeth A

    2016-04-01

    The development of cell-based treatments for heart disease relies on the creation of functionally mature stem cell-derived cardiomyocytes employing in vitro culture suspension systems, a process which remains a formidable and expensive endeavor. The use of nitric oxide as a signaling molecule during differentiation has demonstrated the potential for creating increased numbers of spontaneously contracting embryoid bodies in culture; however, the effects of nitric oxide signaling on the function and maturation of stem cell-derived cardiomyocytes is not well understood. In this study, the effects of nitric oxide on mouse embryonic stem cell-derived cardiomyocyte contractile activity, protein, and gene expression, and calcium handling were quantified. Embryoid bodies (EBs) formed using the hanging drop method, were treated with the soluble nitric oxide donor S-nitrosocysteine (CysNO) over a period of 18 days in suspension culture and spontaneous contractile activity was assessed. On day 8, selected EBs were dissociated to form monolayers for electrophysiological characterization using calcium transient mapping. Nitric oxide treatment led to increased numbers of stem cell-derived cardiomyocytes (SC-CMs) relative to non-treated EBs after 8 days in suspension culture. Increased incidence of spontaneous contraction and frequency of contraction were observed from days 8-14 in EBs receiving nitric oxide treatment in comparison to control. Expression of cardiac markers and functional proteins was visualized using immunocytochemistry and gene expression was assessed using qPCR. Cardiac-specific proteins were present in both CysNO-treated and control SC-CMs; however, CysNO treatment during differentiation significantly increased βMHC gene expression in SC-CMs relative to control SC-CMs. Furthermore, increased calcium transient velocity and decreased calcium transient duration was observed for CysNO-treated SC-CMs in comparison to control SC-CMs. Soluble nitric oxide donors

  12. Graft reconditioning with nitric oxide gas in rat liver transplantation from cardiac death donors.

    Science.gov (United States)

    Kageyama, Shoichi; Yagi, Shintaro; Tanaka, Hirokazu; Saito, Shunichi; Nagai, Kazuyuki; Hata, Koichiro; Fujimoto, Yasuhiro; Ogura, Yasuhiro; Tolba, Rene; Shinji, Uemoto

    2014-03-27

    Liver transplant outcomes using grafts donated after cardiac death (DCD) remain poor. We investigated the effects of ex vivo reconditioning of DCD grafts with venous systemic oxygen persufflation using nitric oxide gas (VSOP-NO) in rat liver transplants. Orthotopic liver transplants were performed in Lewis rats, using DCD grafts prepared using static cold storage alone (group-control) or reconditioning using VSOP-NO during cold storage (group-VSOP-NO). Experiment I: In a 30-min warm ischemia model, graft damage and hepatic expression of inflammatory cytokines, endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), and endothelin-1 (ET-1) were examined, and histologic analysis was performed 2, 6, 24, and 72 hr after transplantation. Experiment II: In a 60-min warm ischemia model, grafts were evaluated 2 hr after transplantation (6 rats/group), and survival was assessed (7 rats/group). Experiment I: Group-VSOP-NO had lower alanine aminotransferase (ALT) (PVSOP-NO.Experiment II: VSOP-NO decreased ET-1 and 8-hydroxy-2'deoxyguanosine (8-OHdG) expression and improved survival after transplantation by 71.4% (PVSOP-NO effectively reconditions warm ischemia-damaged grafts, presumably by decreasing ET-1 upregulation and oxidative damage.

  13. Targeting Nitric Oxide with Natural Derived Compounds as a Therapeutic Strategy in Vascular Diseases

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    Maurizio Forte

    2016-01-01

    Full Text Available Within the family of endogenous gasotransmitters, nitric oxide (NO is the smallest gaseous intercellular messenger involved in the modulation of several processes, such as blood flow and platelet aggregation control, essential to maintain vascular homeostasis. NO is produced by nitric oxide synthases (NOS and its effects are mediated by cGMP-dependent or cGMP-independent mechanisms. Growing evidence suggests a crosstalk between the NO signaling and the occurrence of oxidative stress in the onset and progression of vascular diseases, such as hypertension, heart failure, ischemia, and stroke. For these reasons, NO is considered as an emerging molecular target for developing therapeutic strategies for cardio- and cerebrovascular pathologies. Several natural derived compounds, such as polyphenols, are now proposed as modulators of NO-mediated pathways. The aim of this review is to highlight the experimental evidence on the involvement of nitric oxide in vascular homeostasis focusing on the therapeutic potential of targeting NO with some natural compounds in patients with vascular diseases.

  14. Targeting Nitric Oxide with Natural Derived Compounds as a Therapeutic Strategy in Vascular Diseases

    Science.gov (United States)

    Forte, Maurizio; Damato, Antonio; Ambrosio, Mariateresa; Puca, Annibale A.; Sciarretta, Sebastiano; Frati, Giacomo; Vecchione, Carmine

    2016-01-01

    Within the family of endogenous gasotransmitters, nitric oxide (NO) is the smallest gaseous intercellular messenger involved in the modulation of several processes, such as blood flow and platelet aggregation control, essential to maintain vascular homeostasis. NO is produced by nitric oxide synthases (NOS) and its effects are mediated by cGMP-dependent or cGMP-independent mechanisms. Growing evidence suggests a crosstalk between the NO signaling and the occurrence of oxidative stress in the onset and progression of vascular diseases, such as hypertension, heart failure, ischemia, and stroke. For these reasons, NO is considered as an emerging molecular target for developing therapeutic strategies for cardio- and cerebrovascular pathologies. Several natural derived compounds, such as polyphenols, are now proposed as modulators of NO-mediated pathways. The aim of this review is to highlight the experimental evidence on the involvement of nitric oxide in vascular homeostasis focusing on the therapeutic potential of targeting NO with some natural compounds in patients with vascular diseases. PMID:27651855

  15. The effect of Lead Acetate on the Nitric Oxide system in the rat Hippocampal cells: An in-vitro study

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    "Ghane T

    2001-05-01

    Full Text Available The mechanism by which lead may cause a perturbotion in the nevous system is through the nitric oxide synthase. In this study the effect of lead acetate on the hippocampal constitutive nitric oxide production was studied. The variation in the nitric oxide production may contribute to physiological lead neurotoxicity in vivo. Different concentrations of lead acetate (10-9 to 10-6 M, wre added to cultures of hippocampal pyramidal cell obtained from one-day newborn rats. Sodium acetate was used as control. In this range of stuy viability of cells did not alter when it was compared to control (P<0.05. In another part of study, cells were obtained from one day dams whose mothers were chronically intoxicated by lead acetate. The resuts showed that neither direct exposure of normal cells mor cells obtained from latter group could show andy increase in the amount of nitric oxide. Administration of lead to the cells 10 minute before measurement showed same results.These results showed that how concentration of lead acetate can not induce nitric oxide production in the pyramidal cells

  16. Expression and activity of inducible nitric oxide synthase and endothelial nitric oxide synthase correlate with ethanol-induced liver injury

    Institute of Scientific and Technical Information of China (English)

    Guang-Jin Yuan; Xiao-Rong Zhou; Zuo-Jiong Gong; Pin Zhang; Xiao-Mei Sun; Shi-Hua Zheng

    2006-01-01

    AIM: To study the expression and activity of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) in rats with ethanol-induced liver injury and their relation with liver damage, activation of nuclear factor-KB (NF-кB) and tumor necrosis factor-α (TNF-α)expression in the liver.METHODS: Female Sprague-Dawley rats were given fish oil (0.5 mL) along with ethanol or isocaloric dextrose daily via gastrogavage for 4 or 6 wk. Liver injury was assessed using serum alanine aminotransferase (ALT)activity and pathological analysis. Liver malondialdehyde (MDA), nitric oxide contents, iNOS and eNOS activity were determined. NF-KB p65, iNOS, eNOS and TNF-αprotein or mRNA expression in the liver were detected by immunohistochemistry or reverse transcriptase-polymerase chain reaction (RT-PCR).RESULTS: Chronic ethanol gavage for 4 wk caused steatosis, inflammation and necrosis in the liver, and elevated serum ALT activity. Prolonged ethanol administration (6 wk) enhanced the liver damage. These responses were accompanied with increased lipid peroxidation, NO contents, iNOS activity and reduced eNOS activity. NF-кB p65, iNOS and TNF-α protein or mRNA expression were markedly induced after chronic ethanol gavage, whereas eNOS mRNA expression remained unchanged. The enhanced iNOS activity and expression were positively correlated with the liver damage, especially the necro-inflammation, activation of NF-кB, and TNF-α mRNA expression.CONCLUSION: iNOS expression and activity are induced in the liver after chronic ethanol exposure in rats, which are correlated with the liver damage, especially the necro-inflammation, activation of NF-KB and TNF-αexpression. eNOS activity is reduced, but its mRNA expression is not affected.

  17. Fe-chlorophyllin promotes the growth of wheat roots associated with nitric oxide generation.

    Science.gov (United States)

    Tong, Min; Zhang, Liefeng; Wang, Yifan; Jiang, Hui; Ren, Yong

    2010-01-01

    Effects of Fe-chlorophyllin on the growth of wheat root were investigated in this study. We found that Fe-chlorophyllin can promote root growth. The production of nitric oxide in wheat root was detected using DAF-2DA fluorescent emission. The intensity of fluorescent in the presence of 0.1 mg/L Fe-chlorophyllin was near to that observed with the positive control of sodium nitroprusside (SNP), the nitric oxide donor. IAA oxidase activity decreased with all treatments of Fe-chlorophyllin from 0.01 to 10 mg/L. At the relatively lower Fe-chlorophyllin concentration of 0.1 mg/L, the activity of IAA oxidase displayed a remarkable decrease, being 40.1% lower than the control. Meanwhile, Fe-chlorophyllin treatment could increase the activities of reactive oxygen scavenging enzymes, such as superoxide dismutase (SOD) and peroxidase (POD), as determined using non-denaturing polyacrylamide gel electrophoresis. These results indicate that Fe-chlorophyllin contributes to the growth of wheat root associated with nitric oxide generation.

  18. Fe-Chlorophyllin Promotes the Growth of Wheat Roots Associated with Nitric Oxide Generation

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    Hui Jiang

    2010-12-01

    Full Text Available : Effects of Fe-chlorophyllin on the growth of wheat root were investigated in this study. We found that Fe-chlorophyllin can promote root growth. The production of nitric oxide in wheat root was detected using DAF-2DA fluorescent emission. The intensity of fluorescent in the presence of 0.1 mg/L Fe-chlorophyllin was near to that observed with the positive control of sodium nitroprusside (SNP, the nitric oxide donor. IAA oxidase activity decreased with all treatments of Fe-chlorophyllin from 0.01 to 10 mg/L. At the relatively lower Fe-chlorophyllin concentration of 0.1 mg/L, the activity of IAA oxidase displayed a remarkable decrease, being 40.1% lower than the control. Meanwhile, Fe-chlorophyllin treatment could increase the activities of reactive oxygen scavenging enzymes, such as superoxide dismutase (SOD and peroxidase (POD, as determined using non-denaturing polyacrylamide gel electrophoresis. These results indicate that Fe-chlorophyllin contributes to the growth of wheat root associated with nitric oxide generation.

  19. Investigating Sodium Nitrite Effect on Blood Nitric Oxide and Histopathologic Changes on Pulmonary Artery in Adult Male Rats

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    F Joibar

    2013-12-01

    Results: The outcome of nitric oxide plasmatic density measurement showed that nitric oxide level in animal ’s blood in 175 mg/kg/day dose recipient group and 350 mg/kg/day dose recipient group increased significantly compared with the control group at the level of P ≤ 0.05. Also thickness of media layer decreased in maximum dose group (350 mg/kg/day dose compared to the control group. Conclusion: Based on the results of different doses of sodium nitrite, the nitric oxide levels in the blood were increased, and the thickness of middle layer of the lung arteries at dose 350 mg of sodium nitrite was reduced.

  20. Neuronal and inducible nitric oxide synthase upregulation in the rat medial prefrontal cortex following acute restraint stress: A dataset

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    Jereme G. Spiers

    2016-03-01

    Full Text Available This data article provides additional evidence on gene expression changes in the neuronal and inducible isoforms of nitric oxide synthase in the medial prefrontal cortex following acute stress. Male Wistar rats aged 6–8 weeks were exposed to control or restraint stress conditions for up to four hours in the dark cycle after which the brain was removed and the medial prefrontal cortex isolated by cryodissection. Following RNA extraction and cDNA synthesis, gene expression data were measured using quantitative real-time PCR. The mRNA levels of the neuronal and inducible nitric oxide synthase isoforms, and the inhibitory subunit of NF-κB, I kappa B alpha were determined using the ΔΔCT method relative to control animals. This data article presents complementary results related to the research article entitled ‘Acute restraint stress induces specific changes in nitric oxide production and inflammatory markers in the rat hippocampus and striatum’ [1].

  1. Neuronal and inducible nitric oxide synthase upregulation in the rat medial prefrontal cortex following acute restraint stress: A dataset.

    Science.gov (United States)

    Spiers, Jereme G; Chen, Hsiao-Jou Cortina; Lee, Johnny K; Sernia, Conrad; Lavidis, Nickolas A

    2016-03-01

    This data article provides additional evidence on gene expression changes in the neuronal and inducible isoforms of nitric oxide synthase in the medial prefrontal cortex following acute stress. Male Wistar rats aged 6-8 weeks were exposed to control or restraint stress conditions for up to four hours in the dark cycle after which the brain was removed and the medial prefrontal cortex isolated by cryodissection. Following RNA extraction and cDNA synthesis, gene expression data were measured using quantitative real-time PCR. The mRNA levels of the neuronal and inducible nitric oxide synthase isoforms, and the inhibitory subunit of NF-κB, I kappa B alpha were determined using the ΔΔCT method relative to control animals. This data article presents complementary results related to the research article entitled 'Acute restraint stress induces specific changes in nitric oxide production and inflammatory markers in the rat hippocampus and striatum' [1].

  2. Environmental Effects on Fractional Exhaled Nitric Oxide in Allergic Children

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    Stefania La Grutta

    2012-01-01

    Full Text Available Fractional exhaled nitric oxide (FeNO is a non-invasive marker of airway inflammation in asthma and respiratory allergy. Environmental factors, especially indoor and outdoor air quality, may play an important role in triggering acute exacerbations of respiratory symptoms. The authors have reviewed the literature reporting effects of outdoor and indoor pollutants on FeNO in children. Although the findings are not consistent, urban and industrial pollution—mainly particles (PM2.5 and PM10, nitrogen dioxide (NO2, and sulfur dioxide (SO2—as well as formaldehyde and electric baseboard heating have been shown to increase FeNO, whilst ozone (O3 tends to decrease it. Among children exposed to Environmental Tobacco Smoke (ETS with a genetic polymorphisms in nitric oxide synthase genes (NOS, a higher nicotine exposure was associated with lower FeNO levels. Finally, although more studies are needed in order to better investigate the effect of gene and environment interactions which may affect the interpretation of FeNO values in the management of children with asthma, clinicians are recommended to consider environmental exposures when taking medical histories for asthma and respiratory allergy. Further research is also needed to assess the effects of remedial interventions aimed at reducing/abating environmental exposures in asthmatic/allergic patients.

  3. Exhaled nitric oxide in diagnosis and management of respiratory diseases

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    Abba Abdullah

    2009-01-01

    Full Text Available The analysis of biomarkers in exhaled breath constituents has recently become of great interest in the diagnosis, treatment and monitoring of many respiratory conditions. Of particular interest is the measurement of fractional exhaled nitric oxide (FENO in breath. Its measurement is noninvasive, easy and reproducible. The technique has recently been standardized by both American Thoracic Society and European Respiratory Society. The availability of cheap, portable and reliable equipment has made the assay possible in clinics by general physicians and, in the near future, at home by patients. The concentration of exhaled nitric oxide is markedly elevated in bronchial asthma and is positively related to the degree of esinophilic inflammation. Its measurement can be used in the diagnosis of bronchial asthma and titration of dose of steroids as well as to identify steroid responsive patients in chronic obstructive pulmonary disease. In primary ciliary dyskinesia, nasal NO is diagnostically low and of considerable value in diagnosis. Among lung transplant recipients, FENO can be of great value in the early detection of infection, bronchioloitis obliterans syndrome and rejection. This review discusses the biology, factors affecting measurement, and clinical application of FENO in the diagnosis and management of respiratory diseases.

  4. Hyperbaric oxygen upregulates cochlear constitutive nitric oxide synthase

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    Kao Ming-Ching

    2011-02-01

    Full Text Available Abstract Background Hyperbaric oxygen therapy (HBOT is a known adjuvant for treating ischemia-related inner ear diseases. Controversies still exist in the role of HBOT in cochlear diseases. Few studies to date have investigated the cellular changes that occur in inner ears after HBOT. Nitric oxide, which is synthesized by nitric oxide synthase (NOS, is an important signaling molecule in cochlear physiology and pathology. Here we investigated the effects of hyperbaric oxygen on eardrum morphology, cochlear function and expression of NOS isoforms in cochlear substructures after repetitive HBOT in guinea pigs. Results Minor changes in the eardrum were observed after repetitive HBOT, which did not result in a significant hearing threshold shift by tone burst auditory brainstem responses. A differential effect of HBOT on the expression of NOS isoforms was identified. Upregulation of constitutive NOS (nNOS and eNOS was found in the substructures of the cochlea after HBOT, but inducible NOS was not found in normal or HBOT animals, as shown by immunohistochemistry. There was no obvious DNA fragmentation present in this HBOT animal model. Conclusions The present evidence indicates that the customary HBOT protocol may increase constitutive NOS expression but such upregulation did not cause cell death in the treated cochlea. The cochlear morphology and auditory function are consequently not changed through the protocol.

  5. How to protect liver graft with nitric oxide

    Institute of Scientific and Technical Information of China (English)

    Hassen Ben Abdennebi; Mohamed Amine Zaoualí; Izabel Alfany-Fernandez; Donia Tabka; Joan Roselló-Catafau

    2011-01-01

    Organ preservation and ischemia reperfusion injury associated with liver transplantation play an important role in the induction of graft injury. One of the earliest events associated with the reperfusion injury is endothelial cell dysfunction. It is generally accepted that endothelial nitric oxide synthase (e-NOS) is cell-protective by mediating vasodilatation, whereas inducible nitric oxide synthase mediates liver graft injury after transplantation. We conducted a critical review of the literature evaluating the potential applications of regulating and promoting e-NOS activity in liver preservation and transplantation, showing the most current evidence to support the concept that enhanced bioavailability of NO derived from e-NOS is detrimental to ameliorate graft liver preservation, as well as preventing subsequent graft reperfusion injury. This review deals mainly with the beneficial effects of promoting "endogenous" pathways for NO generation, via e-NOS inducer drugs in cold preservation solution, surgical strategies such as ischemic preconditioning, and alternative "exogenous" pathways that focus on the enrichment of cold storage liquid with NO donors. Finally, we also provide a basic bench-to-bed side summary of the liver physiology and cell signalling mechanisms that account for explaining the e-NOS protective effects in liver preservation and transplantation.

  6. 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.

  7. Endomorphin-suppressed nitric oxide release from mice peritoneal macrophages.

    Science.gov (United States)

    Balog, Tihomir; Sarić, Ana; Sobocanec, Sandra; Kusić, Borka; Marotti, Tatjana

    2010-02-01

    Endomorphins are newly discovered mu-opioid receptor selective immunocompetent opioid peptides. Endomorphin 1 is predominantly distributed in brain, while endomorphin 2 is widely allocated in the spinal cord. Lately, endomorphins have been investigated as modulators of reactive oxygen and nitrogen species. Nitric oxide is short lived radical involved in various biological processes such as regulation of blood vessel contraction, inflammation, neurotransmission and apoptosis. The aim of this work was to investigate the in vivo effects of endomorphins on nitric oxide release and NOS 2 isoenzyme upregulation in mice peritoneal macrophages additionally challenged ex vivo with lipopolysaccharide. The results showed that endomorphin 1 or endomorphin 2 in vitro did not change NO release from peritoneal mouse macrophages during a 48 h incubation period. On the other hand in vivo endomorphins had suppressive effect on NO release as well as on NOS 2 and IL-1 protein concentration. The most of suppressive effect in vivo of both endomorphins was blocked with 30 min pretreatment with mu-receptor selective antagonist beta-FNA, which proved involvement of opioid receptor pathway in suppressive effects of endomorphins.

  8. Applications of plasma sources for nitric oxide medicine

    Science.gov (United States)

    Vasilets, Victor; Shekhter, Anatoly; Pekshev, Alexander

    2013-09-01

    Nitric oxide (NO) has important roles in the function of many tissues and organs. Wound healing processes are always accompanying by the increase of nitric oxide concentration in wound tissue. These facts suggest a possible therapeutic use of various NO donors for the acceleration of the wound healing and treatment of other diseases. Our previous studies indicated that gaseous NO flow produced by air-plasma generators acts beneficially on the wound healing. This beneficial effect could be caused by the mechanism involving peroxynitrite as an intermediate. As a result of mobilization of various antioxidant reactions more endogenous NO molecules become available as signaling molecules. to regulate the metabolic processes in wound tissue. In this paper different air plasma sources generated therapeutic concentrations of NO are discussed. The concentration of NO and other therapeutically important gas products are estimated by thermodynamic simulation. Synergy effects of NO with other plasma components are discussed as a factor enhancing therapeutic results. Some new medical application of plasma devices are presented. Advanced Plasma Therapies Inc.

  9. Nitric Oxide Signaling in Hypergravity-Induced Neuronal Plasticity

    Science.gov (United States)

    Holstein, Gay R.

    2003-01-01

    The goal of this research project was to identify the neurons and circuits in the vestibular nuclei and nucleus prepositus hypoglossi that utilize nitric oxide (NO) for intercellular signaling during gravity-induced plasticity. This objective was pursued using histochemical and immunocytochemical approaches to localize NO-producing neurons and characterize the fine morphology of the cells in ground-based studies of normal rats, rats adapted to hypergravity, and rats adapted to hypergravity and then re-adapted to the 1G environment. NO-producing neurons were identified and studied using four methodologies: i) immunocytochemistry employing polyclonal antibodies directed against neuronal nitric oxide synthase (nNOS), to provide an indication of the capacity of a cell for NO production; ii) immunocytochemistry employing a monoclonal antibody directed against L-citrulline, to provide an indirect index of the enzyme's activity; iii) histochemistry based on the NADPH-diaphorase reaction, for fuI1 cytological visualization of neurons; and iv) double immunofluorescence to co-localize nNOS and L-citrulline in individual vestibular nuclei (VN) and neurons.

  10. Mechanism of inducible nitric oxide synthase exclusion from mycobacterial phagosomes.

    Directory of Open Access Journals (Sweden)

    Alexander S Davis

    2007-12-01

    Full Text Available Mycobacterium tuberculosis is sensitive to nitric oxide generated by inducible nitric oxide synthase (iNOS. Consequently, to ensure its survival in macrophages, M. tuberculosis inhibits iNOS recruitment to its phagosome by an unknown mechanism. Here we report the mechanism underlying this process, whereby mycobacteria affect the scaffolding protein EBP50, which normally binds to iNOS and links it to the actin cytoskeleton. Phagosomes harboring live mycobacteria showed reduced capacity to retain EBP50, consistent with lower iNOS recruitment. EBP50 was found on purified phagosomes, and its expression increased upon macrophage activation, paralleling expression changes seen with iNOS. Overexpression of EBP50 increased while EBP50 knockdown decreased iNOS recruitment to phagosomes. Knockdown of EBP50 enhanced mycobacterial survival in activated macrophages. We tested another actin organizer, coronin-1, implicated in mycobacterium-macrophage interaction for contribution to iNOS exclusion. A knockdown of coronin-1 resulted in increased iNOS recruitment to model latex bead phagosomes but did not increase iNOS recruitment to phagosomes with live mycobacteria and did not affect mycobacterial survival. Our findings are consistent with a model for the block in iNOS association with mycobacterial phagosomes as a mechanism dependent primarily on reduced EBP50 recruitment.

  11. Nitric oxide synthase: non-canonical expression patterns

    Directory of Open Access Journals (Sweden)

    Mattila eJoshua

    2014-10-01

    Full Text Available Science can move ahead by questioning established or canonical views and, so it may be with the enzymes, nitric oxide synthases (NOS. Nitric oxide (NO is generated by NOS isoforms that are often described by their tissue-specific expression patterns. NOS1 (nNOS is abundant in neural tissue, NOS2 is upregulated in activated macrophages and known as inducible NOS (iNOS, and NOS3 (eNOS is abundant in endothelium where it regulates vascular tone. These isoforms are described as constitutive or inducible, but in this Perspective we question the broad application of these labels. Are there instances where ‘constitutive’ NOS (NOS1 and NOS3 are inducibly expressed; conversely, are there instances where NOS2 is constitutively expressed? NOS1 and NOS3 inducibility may be linked to post-translational regulation, making their actual patterns activity much more difficult to detect. Constitutive NOS2 expression has been observed several tissues, especially the human pulmonary epithelium where it may regulate airway tone. These data suggest expression of the three NOS enzymes may include non-established patterns. Such information should be useful in designing strategies to modulate these important enzymes in different disease states.

  12. Effects of nitric oxide on stem cell therapy.

    Science.gov (United States)

    Wang, Wuchen; Lee, Yugyung; Lee, Chi H

    2015-12-01

    The use of stem cells as a research tool and a therapeutic vehicle has demonstrated their great potential in the treatment of various diseases. With unveiling of nitric oxide synthase (NOS) universally present at various levels in nearly all types of body tissues, the potential therapeutic implication of nitric oxide (NO) has been magnified, and thus scientists have explored new treatment strategies involved with stem cells and NO against various diseases. As the functionality of NO encompasses cardiovascular, neuronal and immune systems, NO is involved in stem cell differentiation, epigenetic regulation and immune suppression. Stem cells trigger cellular responses to external signals on the basis of both NO specific pathways and concerted action with endogenous compounds including stem cell regulators. As potency and interaction of NO with stem cells generally depend on the concentrations of NO and the presence of the cofactors at the active site, the suitable carriers for NO delivery is integral for exerting maximal efficacy of stem cells. The innovative utilization of NO functionality and involved mechanisms would invariably alter the paradigm of therapeutic application of stem cells. Future prospects in NO-involved stem cell research which promises to enhance drug discovery efforts by opening new era to improve drug efficacy, reduce drug toxicity and understand disease mechanisms and pathways, were also addressed.

  13. 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.

  14. Nitric oxide heme interactions in nitrophorin from Cimex lectularius

    Science.gov (United States)

    Christmann, R.; Auerbach, H.; Berry, R. E.; Walker, F. A.; Schünemann, V.

    2016-12-01

    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 57Fe 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.

  15. Estimation of nitric oxide as an inflammatory marker in periodontitis

    Directory of Open Access Journals (Sweden)

    Menaka K

    2009-01-01

    Full Text Available Nitric oxide (NO is not only important in host defense and homeostasis but it is also regarded as harmful and has been implicated in the pathogenesis of a wide variety of inflammatory and autoimmune diseases. The presence of NO in periodontal disease may reflect the participation of an additional mediator of bone resorption responsible for disease progression. The aim of this study was to assess the level of NO in serum in chronic periodontitis, and correlate these levels with the severity of periodontal disease. Sixty subjects participated in the study and were divided into two groups. NO levels were assayed by measuring the accumulation of stable oxidative metabolite, nitrite with Griess reaction. Results showed subjects with periodontitis had significantly high nitrite in serum than healthy subjects. NO production is increased in periodontal disease, this will enable us to understand its role in disease progression and selective inhibition of NO may be of therapeutic utility in limiting the progression of periodontitis.

  16. Oxidative stress and nitric oxide in rats with alcohol-induced acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Gülnur Andican; Remisa Gelisgen; Gülden Burcak; Ethem Unal; Osman Baran Tortum; Tayfun Karahasanoglu

    2005-01-01

    AIM: Oxygen free radical mediated tissue damage is well established in pathogenesis of acute pancreatitis (AP).Whether nitric oxide (NO) plays a deleterious or a protective role is unknown. In alcohol-induced AP, we studied NO, lipooxidative damage and glutathione in pancreas, lung and circulation.METHODS: AP was induced in rats (n = 25) by injection of ethyl alcohol into the common biliary duct. A sham laparatomy was performed in controls (n = 15). After 24 h the animals were killed, blood and tissue sampling were done.RESULTS: Histopathologic evidence confirmed the development of AP. Marked changes were observed in the pulmonary tissue. Compared with controls, the AP group displayed higher values for NO metabolites in pancreas and lungs, and thiobarbituric acid reactive substances in circulation. Glutathione was lower in pancreas and in circulation. Glutathione and NO were positively correlated in pancreas and lungs of controls but negatively correlated in circulation of experimental group. In the experimental group, plasma thiobarbituric acid reactive substances were negatively correlated with pancreas thiobarbituric acid reactive substances but positively correlated with pancreas NO.CONCLUSION: NO increases in both pancreas and lungs in AP and NO contributes to the pathogenesis of AP under oxidative stress.

  17. Protective effect of nitric oxide against arsenic-induced oxidative ...

    African Journals Online (AJOL)

    STORAGESEVER

    2010-03-15

    Mar 15, 2010 ... alleviating arsenic-induced oxidative damage in tall fescue leaves were investigated. Arsenic (25 ... and it is distributed widely in natural environment. It occurred in a ... fertilizers, pesticides and sewage (Roberto et al., 2002).

  18. In-vitro susceptibility of hydatid cysts of Echinococcus granulosus to nitric oxide and the effect of the laminated layer on nitric oxide production.

    Science.gov (United States)

    Steers, N J; Rogan, M T; Heath, S

    2001-08-01

    Murine hydatid cysts of Echinococcus granulosus were incubated in vitro in the presence of nitric oxide produced from S-nitroso-N-acetylpenicillamine (SNAP) or interferon-gamma activated peritoneal macrophages. In both situations, evidence of cyst damage and death was observed by microscopy in over 77% of cysts after 3 days, indicating that intact hydatid cysts could be susceptible to a Th1 driven macrophage attack. A crude extract of the laminated layer from cysts was found to be able to reduce the production of nitric oxide from activated macrophages in vitro and in vivo and this may have been due to phagocytosis of laminated layer fragments by the macrophages. The results indicate that, although cysts may be susceptible to the effects of nitric oxide, the laminated layer may be involved in downregulating nitric oxide production.

  19. Endogenous nitric oxide synthesis: biological functions and pathophysiology.

    Science.gov (United States)

    Bredt, D S

    1999-12-01

    Modern molecular biology has revealed vast numbers of large and complex proteins and genes that regulate body function. By contrast, discoveries over the past ten years indicate that crucial features of neuronal communication, blood vessel modulation and immune response are mediated by a remarkably simple chemical, nitric oxide (NO). Endogenous NO is generated from arginine by a family of three distinct calmodulin- dependent NO synthase (NOS) enzymes. NOS from endothelial cells (eNOS) and neurons (nNOS) are both constitutively expressed enzymes, whose activities are stimulated by increases in intracellular calcium. Immune functions for NO are mediated by a calcium-independent inducible NOS (iNOS). Expression of iNOS protein requires transcriptional activation, which is mediated by specific combinations of cytokines. All three NOS use NADPH as an electron donor and employ five enzyme cofactors to catalyze a five-electron oxidation of arginine to NO with stoichiometric formation of citrulline. The highest levels of NO throughout the body are found in neurons, where NO functions as a unique messenger molecule. In the autonomic nervous system NO functions NO functions as a major non-adrenergic non-cholinergic (NANC) neurotransmitter. This NANC pathway plays a particularly important role in producing relaxation of smooth muscle in the cerebral circulation and the gastrointestinal, urogenital and respiratory tracts. Dysregulation of NOS activity in autonomic nerves plays a major role in diverse pathophysiological conditions including migraine headache, hypertrophic pyloric stenosis and male impotence. In the brain, NO functions as a neuromodulator and appears to mediate aspects of learning and memory. Although endogenous NO was originally appreciated as a mediator of smooth muscle relaxation, NO also plays a major role in skeletal muscle. Physiologically muscle-derived NO regulates skeletal muscle contractility and exercise-induced glucose uptake. nNOS occurs at the

  20. Inhaled Nitric Oxide for the Prevention of Impaired Arterial Oxygenation during Myocardial Revascularization with Extracorporeal Circulation

    Directory of Open Access Journals (Sweden)

    I. A. Kozlov

    2011-01-01

    Full Text Available Objective: to study the efficacy of inhaled nitric oxide used intraoperatively to prevent lung oxygenating dysfunction in patients with coronary heart disease after myocardial revascularization under extracorporeal circulation (EC. Subjects and methods. Thirty-two patients aged 55.0±2.0 years were examined. The inclusion criteria were the standard course of surgical intervention (the absence of hemorrhage, acute cardiovascular insufficiency, perioperative myocardial infarction, etc., a pulmonary artery wedge pressure of less than 15 – mm Hg throughout the study, and the baseline arterial partial oxygen tension/inspired mixture oxygen fraction (PaO2/FiO2 ratio of at least 350 mm Hg. There was a control group (n=21; Group 1 that used no special measures to prevent and/or to correct lung oxygenating dysfunction and Group 2 (n=11 that received inhaled nitric oxide. Ihe administration of inhaled nitric oxide at a concentration of 10 ppm was initiated after water anesthesia, stopped during EC, and resumed in the postperfusion period. Results. At the end, PaO2/FiO2 and intrapulmonary shunt fraction did not differ between the groups (p>0.05. Before EC, the patients receiving inhaled nitric oxide had a lower intrapulmonary blood shunting (8.9±0.7 and 11.7±1.0%; p<0.05. There were no intergroup differences in the values of PaO2/FiO2 at this stage. In the earliest postperfusion period, PaO2/FiO2 was higher in Group 2 than that in Group 1. At the end of operations, Groups 1 and 2 had a PaO2/FiO2 of 336.0±16.8 and 409.0±24.3 mm Hg, respectively (p<0.05 and an intrapulmonary shunt fraction of 14.5±1.0 and 10.4±1.0% (p<0.05. At the end of surgery, the rate of a reduction in PaO2/FiO2 to the level below 350 mm Hg was 52.4±11.1% in Group 1 and 18.2±11.6% in Group 2 (p<0.05. Six hours after surgery, PaO2/FiO2 values less than 300 mm Hg were diagnosed in 61.9±10.5% of Group 1 patients and in 27.3±13.4% of Group 2 ones (p<0.05. Conclusion. The

  1. Radio-resistance induced by nitric oxide to heavy ion irradiation in A172 human glioma cells

    Institute of Scientific and Technical Information of China (English)

    ZHOU Qingming; ZHANG Hong; ZHANG Xingxia

    2007-01-01

    To investigate effects of nitric oxide on cellular radio-sensitivity, three human glioma cell lines, i.e. A172,A172 transfected green fluorescence protein (EGFP) gene (EA172) and A172 transfected inducible nitric oxide synthesis (iNOS) gene (iA172), were irradiated by 12C6+ ions to 0, 1 or 2Gy. Productions of nitric oxide and glutathione (GSH) in A172, EA172 and iA172 were determined by chemical methods, cell cycle was analyzed by flow cytometry at the 24th hour after irradiation, and survival fraction of the cells was measured by colorimetric MTT assay at the 5th day after irradiation. The results showed that the concentrations of nitric oxide and GSH in iA172 were significantly higher than in A172 and EA172; the G2/M stage arrest induced by the 12C6+ ion irradiation was observed in A172 and EA172 but not in iA172 at the 24th hour after exposure; and the survival fraction of iA172 was higher than that of EA172 and iA172. Data suggest that the radio-sensitivity of the A172 was reduced after the iNOS gene transfection.The increase of GSH production and the change of cellular signals such as the cell cycle control induced by nitric oxide may be involved in this radio-resistance.

  2. Hemoglobin Effects on Nitric Oxide Mediated Hypoxic Vasodilation.

    Science.gov (United States)

    Rong, Zimei; Cooper, Chris E

    2016-01-01

    The brain responds to hypoxia with an increase in cerebral blood flow (CBF). However, such an increase is generally believed to start only after the oxygen tension decreases to a certain threshold level. Although many mechanisms (different vasodilator and different generation and metabolism mechanisms of the vasodilator) have been proposed at the molecular level, none of them has gained universal acceptance. Nitric oxide (NO) has been proposed to play a central role in the regulation of oxygen supply since it is a vasodilator whose production and metabolism are both oxygen dependent. We have used a computational model that simulates blood flow and oxygen metabolism in the brain (BRAINSIGNALS) to test mechanism by which NO may elucidate hypoxic vasodilation. The first model proposed that NO was produced by the enzyme nitric oxide synthase (NOS) and metabolized by the mitochondrial enzyme cytochrome c oxidase (CCO). NO production declined with decreasing oxygen concentration given that oxygen is a substrate for nitric oxide synthase (NOS). However, this was balanced by NO metabolism by CCO, which also declined with decreasing oxygen concentration. However, the NOS effect was dominant; the resulting model profiles of hypoxic vasodilation only approximated the experimental curves when an unfeasibly low K m for oxygen for NOS was input into the model. We therefore modified the model such that NO generation was via the nitrite reductase activity of deoxyhemoglobin instead of NOS, whilst keeping the metabolism of NO by CCO the same. NO production increased with decreasing oxygen concentration, leading to an improved reproduction of the experimental CBF versus PaO2 curve. However, the threshold phenomenon was not perfectly reproduced. In this present work, we incorporated a wider variety of oxygen dependent and independent NO production and removal mechanisms. We found that the addition of NO removal via oxidation to nitrate mediated by oxyhemoglobin resulted in the

  3. Hyperbaric oxygen therapy may overcome nitric oxide blockage during cyanide intoxication

    DEFF Research Database (Denmark)

    Polzik, Peter; Hansen, Marco Bo; Olsen, Niels Vidiendal

    2017-01-01

    PURPOSE: To determine the effects of a blockade of nitric oxide (NO) synthesis on hyperbaric oxygen (HBO₂) therapy during cyanide (CN) intoxication. METHODS: 39 anesthetized female Sprague-Dawley rats were exposed to CN intoxication (5.4 mg/kg intra-arterially) with or without previous nitric oxide...

  4. Modulation of cholinergic airway reactivity and nitric oxide production by endogenous arginase activity

    NARCIS (Netherlands)

    Meurs, Herman; Hamer, M.A M; Pethe, S; Vadon-Le Goff, S; Boucher, J.-L; Zaagsma, Hans

    2000-01-01

    1 Cholinergic airway constriction is functionally antagonized by agonist-induced constitutive nitric oxide synthase (cNOS)-derived nitric oxide (NO). Since cNOS and arginase, which hydrolyzes L-arginine to L-ornithine and urea, use L-arginine as a common substrate, competition between both enzymes f

  5. Polymorphisms In The Nitric-Oxide Synthase 2 Gene And Prostate Cancer Pathogenesis

    Directory of Open Access Journals (Sweden)

    Charlotta Ryk

    2015-08-01

    Conclusions: Nitric oxide can induce proliferation as well as apoptosis depending on cellular context. Our results suggest that NOS2 polymorphisms may influence the risk of aggressive prostate cancer and that these polymorphisms could have an impact on disease pathogenesis, possibly by affecting intracellular nitric oxide levels.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Romano, Giovanna; Costantini, Maria; Buttino, Isabella; Ianora, Adrianna; Palumbo, Anna

    2011-01-01

    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.

  8. HYPOTHALAMIC BLOOD-FLOW REMAINS UNALTERED FOLLOWING CHRONIC NITRIC-OXIDE SYNTHASE BLOCKADE IN RATS

    NARCIS (Netherlands)

    BENYO, Z; SZABO, C; STUIVER, BT; BOHUS, B; SANDOR, P

    1995-01-01

    The effect of the chronic oral application of N-G-nitro-L-arginine methyl eater (L-NAME), a potent inhibitor of nitric oxide (NO) production, was studied on hypothalamic blood flow (HBF) and hypothalamic nitric oxide synthase (NOS) activity in rats. L-NAME was dissolved in the drinking water, in a c

  9. Therapeutic photobiomodulation: nitric oxide and a novel function of mitochondrial cytochrome c oxidase.

    Science.gov (United States)

    Poyton, Robert O; Ball, Kerri A

    2011-02-01

    Currently, light therapies are widely used in both human and veterinarian medicine. The application of light to clinical therapeutics includes: photodynamic therapy, used to kill cancer cells; UVA therapies, used to treat a variety of skin diseases; and photobiomodulation, used to promote cell growth and recovery from injury. Photobiomodu-lation uses light emitting diodes (LEDs) or low energy lasers, which emit light in the visible red to near infrared range. Light in this range penetrates tissue reasonably well, lacks the carcinogenic/mutagenic properties of UV light, and acts on an endogenous photoreceptor which likely acts to initiate light-altered signaling pathways. Although early studies identified mitochondrial cytochrome c oxidase as an endogenous photoreceptor for photobiomodulation, the cellular and molecular mechanisms underlying photobiomodulation have not been clear. Three recent findings provide important new insight. First, nitric oxide has been implicated. Second, cytochrome c oxidase, an enzyme known to reduce oxygen to water at the end of the mitochondrial respiratory chain, has been shown to have a new enzymatic activity--the reduction of nitrite to nitric oxide. This nitrite reductase activity is elevated under hypoxic conditions but also occurs under normoxia. And third, low intensity light enhances nitric oxide synthesis by cytochrome c oxidase without altering its ability to reduce oxygen. From these findings, we propose that cytochrome c oxidase functions in photobiomodulation by producing nitric oxide, a signaling molecule which can then function in both intra- and extracellular signaling pathways. We also propose that the effectiveness of photobiomodulation is under the control of tissue oxygen and nitrite levels.

  10. Excitatory and inhibitory effects of nitric oxide on weight, size, and histological changes of rat cerebellum

    Directory of Open Access Journals (Sweden)

    Karambaksh A

    2013-01-01

    Full Text Available Background: Nitric oxide (NO is produced in different body organs in mammals and numerous physiological and pathological properties are attributed to this small molecule. The precursor of this substance in the body, L-arginine, is synthesized by the enzyme nitric oxide synthase (NOS, and it is catalyzed, and is inhibited by a substance called L-NG-nitroarginine methyl ester (L-NAME. In this study we investigated the qualitative and quantitative effects of nitric oxide on cerebellar histopathology in vivo environment via increasing and decreasing its production.Methods: Forty Wister rats, weighing 200- 250 gr with a mean age of 8 weeks, were divided into 5 groups after making sure the rats were pregnant. Except the control group, the other pregnant groups, respectively received: 2 ml/kg normal saline, 200 mg/kg L-arginine, 20 mg/kg L-NAME and a mixture of the same doses of L-arginine and L-NAME on the third, fourth and fifth days of pregnancy. On day 18 of pregnancy, we anesthetized the rats, excised the cerebellum after craniotomy and fixed the organs in 10% formalin. We later prepared 5 to 6-micron in thickness tissue sections and dyed them by the routine Hematoxylin and eosin (HE and Masson's Trichrom staining methods before studying them by light microscopy.Results: There was a significant difference between the rats receiving L-arginine and the rats in other groups (P<0.01. Conclusion: This study showed that L-NAME is capable of significantly decreasing the injury caused by nitric oxides in rat cerebellum.

  11. Role of nitric oxide in adenosine-induced vasodilation in humans

    Science.gov (United States)

    Costa, F.; Biaggioni, I.; Robertson, D. (Principal Investigator)

    1998-01-01

    Vasodilation is one of the most prominent effects of adenosine and one of the first to be recognized, but its mechanism of action is not completely understood. In particular, there is conflicting information about the potential contribution of endothelial factors. The purpose of this study was to explore the role of nitric oxide in the vasodilatory effect of adenosine. Forearm blood flow responses to intrabrachial adenosine infusion (125 microg/min) were assessed with venous occlusion plethysmography during intrabrachial infusion of saline or the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) (12.5 mg/min). Intrabrachial infusions of acetylcholine (50 microg/min) and nitroprusside (3 microg/min) were used as a positive and negative control, respectively. These doses were chosen to produce comparable levels of vasodilation. In a separate study, a second saline infusion was administered instead of L-NMMA to rule out time-related effects. As expected, pretreatment with L-NMMA reduced acetylcholine-induced vasodilation; 50 microg/min acetylcholine increased forearm blood flow by 150+/-43% and 51+/-12% during saline and L-NMMA infusion, respectively (Pvasodilation is not mediated by nitric oxide in the human forearm.

  12. The systemic inhibition of nitric oxide production rapidly regulates TRH mRNA concentration in the paraventricular nucleus of the hypothalamus and serum TSH concentration. Studies in control and cold-stressed rats.

    Science.gov (United States)

    Uribe, Rosa Maria; Cisneros, Miguel; Vargas, Miguel Angel; Lezama, Leticia; Cote-Vélez, Antonieta; Joseph-Bravo, Patricia; Charli, Jean-Louis

    2011-01-07

    Neurons of the paraventricular nuclei of the hypothalamus (PVN) that synthesize the peptide thyrotropin releasing hormone (TRH) control energy homeostasis. Identifying the circuits which regulate these neurons is critical to fully understand integration of metabolic information and the mechanisms that set thyroid hormone levels. We tested the hypothesis that nitric oxide (NO) acutely controls PVN TRH expression and thyrotropin (TSH) secretion by the anterior pituitary. The subcutaneous treatment of rats with N(G)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthases, enhanced PVN TRH mRNA and medio-basal hypothalamic TRH levels, and reduced serum TSH concentration. Analysis of the effect of a NO donor in primary cultures of hypothalamic or anterior pituitary cells suggested that the effect of NO includes a direct action on hypothalamic neurons. The cold stress-induced increase in TSH release was inhibited by sc L-NAME. Therefore, production of NO may control the activity of the hypothalamus-pituitary-thyroid axis. Copyright © 2010 Elsevier B.V. All rights reserved.

  13. The plasma level of nitric oxide and the expression of inducible nitric oxidesynthase in human hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Run Xuan Shao; Jiang Bin Wang; Jia He Guo

    2000-01-01

    AIM To study the relationship between nitric oxide (NO), nitric oxide synthase (NOS) and humanhepatocellular carcinoma (HCC).METHODS Plsama NO2-/NO3- was measured by Griess reaction in 122 patients with chronic hepatitis(CH) and compensated liver cirrhosis (LC), among which 62 patients were complicated with HCC(CH = 28, LC = 34), and the rest 60 patients were not (CH = 29, LC = 31). Thirty healthy persons served asnormal controls (NC). There were no prominent differences among the groups in sex, age and the ratio ofCH to LC. The expression of inducible nitric oxide synthase (iNOS) in HCC (n = 40), CH (n = 30) and LC(n = 30) samples obtained from liver biopsy or operation was compared with that in normal liver tissues byusing immunohistochemistry. Ten normal liver tissue samples obtained from liver operation served as normalcontrols. The samples were fixed in formalin and embeded in paraffin. Anti-iNOS antibody (Santacruzcompany) was served as antibody-Ⅰ in immunohistochemical assay of iNOS in tissue.RESULTS Plasma NO2-/NO3- level in normal was 11.5 μmol/L±4.2μmol/L. The plasma level ofNO2 /NO3- in CH (58.6±17.4 μmol/L) and LC (38.7±10.6μmol/L) accompanied with HCC wasnotably higher than in those patients without HCC (CH: 24.8±9.4 μmol/L; LC: 22.3±8.7μmol/L,t=2.901, 2.756, P<0.01). Plasma NO2-/NO3- level in HCC accompanied with CH was significantlyhigher than in those accompanied with LC ( t = 2.216, P<0.05). Positive rate of iNOS in HCC, CH and LCwas 95%, 93% and 57% respectively. iNOS was not expressed in normal liver tissues. The expression level ofiNOS in HCC (χ2=17.4, P<0.001) and CH (χ2=11.64, P<0.025) was much higher than in LC.CONCLUSION Plasma NO2 / NO3- level significantly increased in patients with HCC and theimmunohistochemical staining of iNOS was positive. This suggests that the liver secrets NO in the higherlevel may participate in the carcinogenesis and progression of HCC.

  14. Role of Rutin on Nitric Oxide Synthesis in Human Umbilical Vein Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Azizah Ugusman

    2014-01-01

    Full Text Available Nitric oxide (NO, produced by endothelial nitric oxide synthase (eNOS, is a major antiatherogenic factor in the blood vessel. Oxidative stress plays an important role in the pathogenesis of various cardiovascular diseases, including atherosclerosis. Decreased availability of endothelial NO promotes the progression of endothelial dysfunction and atherosclerosis. Rutin is a flavonoid with multiple cardiovascular protective effects. This study aimed to investigate the effects of rutin on eNOS and NO production in cultured human umbilical vein endothelial cells (HUVEC. HUVEC were divided into four groups: control; oxidative stress induction with 180 μM H2O2; treatment with 300 μM rutin; and concomitant induction with rutin and H2O2 for 24 hours. HUVEC treated with rutin produced higher amount of NO compared to control (P<0.01. In the oxidative stress-induced HUVEC, rutin successfully induced cells’ NO production (P<0.01. Rutin promoted NO production in HUVEC by inducing eNOS gene expression (P<0.05, eNOS protein synthesis (P<0.01, and eNOS activity (P<0.05. Treatment with rutin also led to increased gene and protein expression of basic fibroblast growth factor (bFGF in HUVEC. Therefore, upregulation of eNOS expression by rutin may be mediated by bFGF. The results showed that rutin may improve endothelial function by augmenting NO production in human endothelial cells.

  15. Dietary flavonoids and nitrate: effects on nitric oxide and vascular function.

    Science.gov (United States)

    Bondonno, Catherine P; Croft, Kevin D; Ward, Natalie; Considine, Michael J; Hodgson, Jonathan M

    2015-04-01

    Emerging evidence highlights dietary flavonoids and nitrate as candidates that may explain at least part of the cardioprotective effect of a fruit and vegetable diet. Nitric oxide plays a pivotal role in cardiovascular health. Components of a fruit and vegetable diet that are cardioprotective, in part through effects on nitric oxide status, could substantially reduce the cardiovascular risk profile of the general population with increased intake of such a diet. Epidemiological evidence suggests that dietary flavonoids and nitrate have a cardioprotective effect. Clinical trials with flavonoid- and nitrate-rich foods have shown benefits on measures of vascular health. While the molecular mechanisms by which flavonoids and nitrate are cardioprotective are not completely understood, recent evidence suggests both nonspecific and specific effects through nitric oxide pathways. This review presents an overview of nitric oxide and its key role in cardiovascular health and discusses the possible vascular benefits of flavonoids and nitrate, individually and in combination, through effects on nitric oxide status.

  16. Nitrones: not only extraordinary spin traps, but also good nitric oxide sources in vivo.

    Science.gov (United States)

    Croitoru, Mircea Dumitru; Petkes, Hermina Iulia; Fülöp, Ibolya; Cotârlan, Remus; Şerban, Oana Elena; Dogaru, Titica Maria; Gâz Florea, Şerban Andrei; Tőkés, Béla; Majdik, Cornelia

    2015-12-01

    Free radicals are involved in the development of reperfusion injuries. Using a spin trap, the intensity of such lesions can be reduced. Nitrones (effective in vivo spin traps) were tried in this work as in vivo nitric oxide donors. Nitrite and nitrate concentration values (rabbit blood) were used as biomarkers of nitric oxide production. Most nitrones did not increase plasma concentrations of nitrite and nitrate; on the contrary, reduced plasma concentrations of these indicators were noted. However, glyoxal isopropyldinitrone, in a dose of 50 mg kg-1, was highly effective in increasing nitric oxide production. At the same time, nitrones do not react with hepatic homogenates, proving that the release of nitric oxide takes place in the tissues and is not related to hepatic metabolism. Before using nitrones in vivo, they were tested in vitro for the ability to release nitric oxide following a reaction with the hydroxyl radical.

  17. Nitrones are able to release nitric oxide in aqueous environment under hydroxyl free radical attack.

    Science.gov (United States)

    Croitoru, Mircea Dumitru; Ibolya, Fülöp; Pop, Maria Cristiana; Dergez, Timea; Mitroi, Brânduşa; Dogaru, Maria Titica; Tokés, Béla

    2011-10-30

    Importance of a nitric oxide donor that can act as a spin trap might bring some new therapeutic possibilities regarding the treatment of ischemic diseases by reducing the intensity of free radical produced reperfusion lesions. These substances might be also used as a new type of photo protectors since they can absorb UV radiation, capture free radicals formed by interaction of UV radiation with tissue constituents, and tanning of the skin will be permitted due to nitric oxide release. The purpose of this work was to measure the ability of nitrones to release nitric oxide and how different factors (temperature, nitrone concentration, and free radicals) influence the releasing ability. Mostly, indirect determination of nitric oxide was carried out, by measuring nitrite and nitrate amounts (as decomposition products of nitric oxide), all nitrones proved to release significant amounts of nitric oxide. Nitrite measurements were made based on an HPLC-VIS method that uses pre-column derivatization of nitrite by forming an azo dye (limit of quantification: 5ng/ml). No good correlation was found between the amount of nitric oxide and temperature for most studied nitrones but between the formation of nitric oxide and nitrone concentration an asymptotic correlation was found. Fenton reagent also yielded formation of nitric oxide from nitrones and formed amounts were not different from those recorded for UV irradiation. Most of the nitrones effectively released about 0.5% of the maximum amount of nitric oxide that is chemically possible and estimated concentrations of 0.1μM were present in the solutions during decomposition.

  18. Inhaled nitric oxide in cardiac surgery: Evidence or tradition?

    Science.gov (United States)

    Benedetto, Maria; Romano, Rosalba; Baca, Georgiana; Sarridou, Despoina; Fischer, Andreas; Simon, Andre; Marczin, Nandor

    2015-09-15

    Inhaled nitric oxide (iNO) therapy as a selective pulmonary vasodilator in cardiac surgery has been one of the most significant pharmacological advances in managing pulmonary hemodynamics and life threatening right ventricular dysfunction and failure. However, this remarkable story has experienced a roller-coaster ride with high hopes and nearly universal demonstration of physiological benefits but disappointing translation of these benefits to harder clinical outcomes. Most of our understanding on the iNO field in cardiac surgery stems from small observational or single centre randomised trials and even the very few multicentre trials fail to ascertain strong evidence base. As a consequence, there are only weak clinical practice guidelines on the field and only European expert opinion for the use of iNO in routine and more specialised cardiac surgery such as heart and lung transplantation and left ventricular assist device (LVAD) insertion. In this review the authors from a specialised cardiac centre in the UK with a very high volume of iNO usage provide detailed information on the early observations leading to the European expert recommendations and reflect on the nature and background of these recommendations. We also provide a summary of the progress in each of the cardiac subspecialties for the last decade and initial survey data on the views of senior anaesthetic and intensive care colleagues on these recommendations. We conclude that the combination of high price tag associated with iNO therapy and lack of substantial clinical evidence is not sustainable on the current field and we are risking loosing this promising therapy from our daily practice. Overcoming the status quo will not be easy as there is not much room for controlled trials in heart transplantation or in the current atmosphere of LVAD implantation. However, we call for international cooperation to conduct definite studies to determine the place of iNO therapy in lung transplantation and high

  19. Nitric oxide-releasing polymeric nanoparticles against Trypanosoma cruzi

    Science.gov (United States)

    Seabra, A. B.; Kitice, N. A.; Pelegrino, M. T.; Lancheros, C. A. C.; Yamauchi, L. M.; Pinge-Filho, P.; Yamada-Ogatta, S. F.

    2015-05-01

    Chagas disease, also known as American trypanosomiasis, is a potentially life-threatening illness caused by the protozoan parasite, Trypanosoma cruzi (T. cruzi), and the disease remains a major health problem in many Latin American countries. Several papers report that the killing of the parasite is dependent on the production of nitric oxide (NO). The endogenous free radical NO is an important cellular signalling molecule that plays a key role in the defense against pathogens, including T. cruzi. As T. cruzi is able to compromise host macrophages decreasing endogenous NO production, the administration of exogenous NO donors represents an interesting strategy to combat Chagas disease. Thus, the aims of this study were to prepare and evaluate the antimicrobial activity of NO-releasing polymeric nanoparticles against T. cruzi. Biocompatible polymeric nanoparticles composed of chitosan/sodium tripolyphosphate(TPP) were prepared and used to encapsulate mercaptosuccinic acid (MSA), which is a thiol-containing molecule. Nitrosation of free thiols (SH) groups of MSA were performed by the addition of equimolar amount of sodium nitrite (NaNO2), leading to the formation of S-nitroso-MSA-containing nanoparticles. These polymeric nanoparticles act as spontaneous NO donors, with free NO release. The results show the formation of nanoparticles with average hydrodynamic diameter ranging from 270 to 500 nm, average of polydispersity index of 0.35, and encapsulation efficiency in the range of 99%. The NO release kinetics from the S-nitroso-MSA-containing nanoparticles showed sustained and controlled NO release over several hours. The microbicidal activity of S-nitroso-MSA-containing nanoparticles was evaluated by incubating NO-releasing nanoparticles (200 - 600 μg/mL) with replicative and non-infective epimastigote, and non-replicative and infective trypomastigote forms of T. cruzi. In addition, a significant decrease in the percentage of macrophage-infected (with amastigotes) and

  20. Oxidative stress modulates the nitric oxide defense promoted by Escherichia coli flavorubredoxin.

    Science.gov (United States)

    Baptista, Joana M; Justino, Marta C; Melo, Ana M P; Teixeira, Miguel; Saraiva, Lígia M

    2012-07-01

    Mammalian cells of innate immunity respond to pathogen invasion by activating proteins that generate a burst of oxidative and nitrosative stress. Pathogens defend themselves from the toxic compounds by triggering a variety of detoxifying enzymes. Escherichia coli flavorubredoxin is a nitric oxide reductase that is expressed under nitrosative stress conditions. We report that in contrast to nitrosative stress alone, exposure to both nitrosative and oxidative stresses abolishes the expression of flavorubredoxin. Electron paramagnetic resonance (EPR) experiments showed that under these conditions, the iron center of the flavorubredoxin transcription activator NorR loses the ability to bind nitric oxide. Accordingly, triggering of the NorR ATPase activity, a requisite for flavorubredoxin activation, was impaired by treatment of the protein with the double stress. Studies of macrophages revealed that the contribution of flavorubredoxin to the survival of E. coli depends on the stage of macrophage infection and that the lack of protection observed at the early phase is related to inhibition of NorR activity by the oxidative burst. We propose that the time-dependent activation of flavorubredoxin contributes to the adaptation of E. coli to the different fluxes of hydrogen peroxide and nitric oxide to which the bacterium is subjected during the course of macrophage infection.

  1. mtDNA haplogroup J Modulates telomere length and Nitric Oxide production

    Directory of Open Access Journals (Sweden)

    Fernández-Moreno Mercedes

    2011-12-01

    Full Text Available Abstract Background Oxidative stress due to the overproduction of nitric oxide (NO and other oxygen reactive species (ROS, play a main role in the initiation and progression of the OA disease and leads to the degeneration of mitochondria. Therefore, the goal of this work is to describe the difference in telomere length of peripheral blood leukocytes (PBLs and Nitric Oxide (NO production between mitochondrial DNA (mtDNA haplogroup J and non-J carriers, as indirect approaches of oxidative stress. Methods The telomere length of PBL was analyzed in DNA samples from 166 healthy controls (114 J and 52 non-J and 79 OA patients (41 J and 38 non-J by means of a validated qPCR method. The NO production was assessed in 7 carriers of the haplogroup J and 27 non-J carriers, by means of the colorimetric reaction of the Griess reagent in supernatants of cultured chondrocytes. Inducible nitric oxide synthase (iNOS mRNA from these samples was analyzed by qPCR. Appropiated statistical analyses were performed Results Carriers of the haplogroup J showed a significantly longer telomere length of PBLs than non-J carriers, regardless of age, gender and diagnosis (p = 0.025. Cultured chondrocytes carrying the mtDNA haplogroup J also showed a lower NO production than non-J carriers (p = 0.043. No significant correlations between age and telomore length of PBLs were detected neither for carriers of the haplogroup J nor for non-J carriers. A strong positive correlation between NO production and iNOS expression was also observed (correlation coefficient = 0.791, p Conclusion The protective effect of the mtDNA haplogroup J in the OA disease arise from a lower oxidative stress in carriers of this haplogroup, since this haplogroup is related to lower NO production and hence longer telomere length of PBLs too.

  2. Photopromoted and Thermal Decomposition of Nitric Oxide by Metal Oxides

    Science.gov (United States)

    1992-04-01

    Photocatalysis (U) n nMetal Oxides (U) NOx Removal (U) 9. ABSTRACT (Continue on reverse if necessary and identify by block number) This technical...for Photocatalysis and Photosynthesis: An Overview," in Energy Resources through Photochemistry and Catalysis, Graetzel, W., Ed., Academic Press, NY...1983, pp.217-260. 16. Courbon, H., and Pichat, P., "Room-temperature Interaction of N180 with Ultraviolet- illuminated TiO2 ," J. Chem. Soc., Faraday

  3. Reduction of nitric oxide and DNA/RNA oxidation products are associated with active disease in systemic lupus erythematosus patients.

    Science.gov (United States)

    Iriyoda, T M V; Stadtlober, N; Lozovoy, M A B; Delongui, F; Costa, N T; Reiche, E M V; Dichi, I; Simão, A N C

    2017-09-01

    The aims of the present study were to evaluate biomarkers of oxidative and nitrosative stress in systemic lupus erythematosus (SLE) patients, in particular products of DNA/RNA oxidative damage and their correlation with disease activity. This study included 188 controls and 203 patients; 153 with inactive SLE (SLEDAI Oxidative stress was assessed by tert-butyl hydroperoxide-initiated by chemiluminescence, advanced oxidation protein products (AOPP), total radical-trapping antioxidant parameter (TRAP), nitric oxide metabolites (NOx), and DNA/RNA oxidation products. Patients with SLE showed increased oxidative stress, as demonstrated by the augmentation of lipid hydroperoxides ( p oxidation products were inversely and independently associated with disease activity ( p oxidation products ( r(2):0.051; p = 0.002) and about 9% of this score by the levels of NOx ( r(2):0.091; p oxidation products and SLE disease activity, suggesting that oxidative/nitrosative stress markers may be useful in evaluating SLE disease activity and progression of the disease.

  4. Ethylene, nitric oxide and haemoglobins in plant tolerance to flooding

    DEFF Research Database (Denmark)

    Mur, Luis A J; Gupta, Kapuganti J; Hebelstrup, Kim

    2015-01-01

    As much as 12% of the world's soils may suffer excess water so that flooding is a major limiting factor on crop production in many areas. Plants attempt to deal with submergence by forming root aerenchyma to facilitate oxygen diffusion from the shoot to the root, initiating a hyponastic response...... where petiole elongation facilitates access to atmospheric oxygen or initiating a bio-energetically conserving quiescence phase. Ethylene has well established roles in the initiation of programmed cell death (PCD) to form air-spaces in aerenchyma and in the hyponastic responses in petioles. The flooding......-tolerant species Rumex palustris and the model plant Arabidopsis thaliana have been extensively exploited to reveal some key molecular events. Our groups have recently demonstrated that nitric oxide (NO) triggers the biosynthesis of ethylene during stress and that NO plays key roles in PCD and the hyponastic...

  5. Electrochemistry of xanthine oxidase and its interaction with nitric oxide.

    Science.gov (United States)

    Zhou, Hui; Xu, Yi; Chen, Ting; Suzuki, Iwao; Li, Genxi

    2006-02-01

    With the help of nanocrystalline TiO2, the direct electrochemistry of xanthine oxidase (XOD) was achieved and two pairs of redox waves were observed. The interaction between XOD and nitric oxide (NO) was also investigated. The experimental results reveal that NO can be reduced at a XOD-nano TiO2 film modified electrode. When the NO concentration was low, the reduced product, HNO, would inactivate the protein. However, when the NO concentration was high, HNO would continue to react with NO to form N2O2- and N3O3-, which would not inhibit XOD, and thus the amount of active protein did not decrease any further.

  6. Nitric oxide counters ethylene effects on ripening fruits.

    Science.gov (United States)

    Manjunatha, Girigowda; Gupta, Kapuganti J; Lokesh, Veeresh; Mur, Luis A J; Neelwarne, Bhagyalakshmi

    2012-04-01

    Ethylene plays a key role in promoting fruit ripening, so altering its biosynthesis/signaling could be an important means to delay this process. Nitric oxide (NO)-generated signals are now being shown to regulate ethylene pathways. NO signals have been shown to transcriptionally repress the expression of genes involved in ethylene biosynthesis enzymes and post-translationally modify methionine adenosyl transferase (MAT) activity through S-nitrosylation to reduce the availably of methyl groups required to produce ethylene. Additionally, NO cross-talks with plant hormones and other signal molecules and act to orchestrate the suppression of ethylene effects by modulating enzymes/proteins that are generally triggered by ethylene signaling at post-climacteric stage. Thus, medication of endogenous NO production is suggested as a strategy to postpone the climacteric stage of many tropical fruits.

  7. Nitric Oxide Regulates Neurogenesis in the Hippocampus following Seizures

    Directory of Open Access Journals (Sweden)

    Bruno P. Carreira

    2015-01-01

    Full Text Available Hippocampal neurogenesis is changed by brain injury. When neuroinflammation accompanies injury, activation of resident microglial cells promotes the release of inflammatory cytokines and reactive oxygen/nitrogen species like nitric oxide (NO. In these conditions, NO promotes proliferation of neural stem cells (NSC in the hippocampus. However, little is known about the role of NO in the survival and differentiation of newborn cells in the injured dentate gyrus. Here we investigated the role of NO following seizures in the regulation of proliferation, migration, differentiation, and survival of NSC in the hippocampus using the kainic acid (KA induced seizure mouse model. We show that NO increased the proliferation of NSC and the number of neuroblasts following seizures but was detrimental to the survival of newborn neurons. NO was also required for the maintenance of long-term neuroinflammation. Taken together, our data show that NO positively contributes to the initial stages of neurogenesis following seizures but compromises survival of newborn neurons.

  8. The role of nitric oxide in the object recognition memory.

    Science.gov (United States)

    Pitsikas, Nikolaos

    2015-05-15

    The novel object recognition task (NORT) assesses recognition memory in animals. It is a non-rewarded paradigm that it is based on spontaneous exploratory behavior in rodents. This procedure is widely used for testing the effects of compounds on recognition memory. Recognition memory is a type of memory severely compromised in schizophrenic and Alzheimer's disease patients. Nitric oxide (NO) is sought to be an intra- and inter-cellular messenger in the central nervous system and its implication in learning and memory is well documented. Here I intended to critically review the role of NO-related compounds on different aspects of recognition memory. Current analysis shows that both NO donors and NO synthase (NOS) inhibitors are involved in object recognition memory and suggests that NO might be a promising target for cognition impairments. However, the potential neurotoxicity of NO would add a note of caution in this context.

  9. Parameterization of Nitric Oxide Emissions in the Thermosphere

    Science.gov (United States)

    Lin, C. Y. T.; Deng, Y.; Venkataramani, K.; Yonker, J. D.; Bailey, S. M.

    2016-12-01

    Nitric oxide (NO), a minor species in the thermosphere, is an important indicator of energy balance. It also has the lowest ionization threshold so is the terminal ion in the ionospheric E-region. Discrepancies between observations and modeled results challenge current understanding of ionospheric and thermospheric energy budget especially during geophysical events. Work in the recent decades has significantly improved our understanding of the NO chemistry and in particular its relationship to energy inputs, such as the role of the excited state of nitrogen, N2(A), in the NO reactions. We update the NO chemical reactions and introduce N2(A) in the Global Ionosphere Thermosphere Model (GITM) to study NO density and cooling in the lower thermosphere. The results are compared with the TIMED SABER and GUVI measurements to identify the relative contribution from solar irradiance and geomagnetic activity to 5.3 µm emission by NO. A parameterization scheme is proposed to be used in a global circulation model.

  10. Nitric oxide: a newly discovered function on wound healing

    Institute of Scientific and Technical Information of China (English)

    Jian-dong LUO; Alex F CHEN

    2005-01-01

    Wound healing impairment represents a particularly challenging clinical problem to which no efficacious treatment regimens currently exist. The factors ensuring appropriate intercellular communication during wound repair are not completely understood. Although protein-type mediators are well-established players in this process, emerging evidence from both animal and human studies indicates that nitric oxide (NO) plays a key role in wound repair. The beneficial effects of NO on wound repair may be attributed to its functional influences on angiogenesis,inflammation, cell proliferation, matrix deposition, and remodeling. Recent findings from in vitro and in vivo studies of NO on wound repair are summarized in this review. The unveiled novel mechanisms support the use of NO-containing agents and/or NO synthase gene therapy as new therapeutic regimens for impaired wound healing.

  11. Weaning of inhaled nitric oxide: is there a best strategy?

    Directory of Open Access Journals (Sweden)

    Anita M. Ware

    2015-04-01

    Full Text Available Background: Inhaled nitric oxide (iNO has been used in the treatment of pulmonary hypertension in neonates for many years. iNO was approved by the FDA in 1999 for hypoxic respiratory failure (HRF in term and near term infants, defined as > 34 weeks gestational age (GA. iNO is used for persistent pulmonary hypertension of the newborn (PPHN, secondary pulmonary hypertension caused by congenital heart disease (CHD, congenital diaphragmatic hernia (CDH, meconium aspiration syndrome (MAS, pneumonia, respiratory distress syndrome (RDS, and other pathologies. iNO has its effect locally on the pulmonary vasculature and has been studied extensively regarding its effect on morbidities such as: need for extracorporeal membrane oxygenation (ECMO, oxygen requirements, and mechanical ventilatory support. However, protocols for weaning iNO and for the duration of iNO weaning have not been studied extensively. It has been shown that an abrupt discontinuation leads to rebound pulmonary hypertension.Methods: Electronic literature search and review of published articles on the use of iNO in the neonate.Results: Electronic databases including Medline and PubMed were searched from the years 1995-2015, using the keywords "iNO", "nitric oxide", "neonate", and "weaning nitric oxide." This search revealed 2,124 articles. Articles were determined to be eligible for review if they included a specific protocol for weaning iNO, and were published in English. 16 articles with specific protocols for iNO weaning have been identified and reviewed. The studies had enrolled a total of 1,735 neonates either at term either preterm and with a mean birth weight of 3.3 kg (± 2 kg. Main diagnoses included MAS, CHD (total anomalous pulmonary venous return [TAPVR], d-transposition of the great vessels [DTGV], atrial septal defect [ASD], pulmonary atresia [PA], hypoplastic left heart syndrome [HLH], pneumonia, RDS, hyaline membrane disease (HMD, PPHN, CDH, sepsis, pulmonary hypoplasia

  12. Transcriptomic Response to Nitric Oxide Treatment in Larix olgensis Henry

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    Xiaoqing Hu

    2015-12-01

    Full Text Available Larix olgensis Henry is an important coniferous species found in plantation forests in northeastern China, but it is vulnerable to pathogens. Nitric oxide (NO is an important molecule involved in plant resistance to pathogens. To study the regulatory role of NO at the transcriptional level, we characterized the transcriptomic response of L. olgensis seedlings to sodium nitroprusside (SNP, NO donor using Illumina sequencing and de novo transcriptome assembly. A significant number of putative metabolic pathways and functions associated with the unique sequences were identified. Genes related to plant pathogen infection (FLS2, WRKY33, MAPKKK, and PR1 were upregulated with SNP treatment. This report describes the potential contribution of NO to disease resistance in L. olgensis as induced by biotic stress. Our results provide a substantial contribution to the genomic and transcriptomic resources for L. olgensis, as well as expanding our understanding of the involvement of NO in defense responses at the transcriptional level.

  13. Transcriptomic Response to Nitric Oxide Treatment in Larix olgensis Henry.

    Science.gov (United States)

    Hu, Xiaoqing; Yang, Jingli; Li, Chenghao

    2015-12-02

    Larix olgensis Henry is an important coniferous species found in plantation forests in northeastern China, but it is vulnerable to pathogens. Nitric oxide (NO) is an important molecule involved in plant resistance to pathogens. To study the regulatory role of NO at the transcriptional level, we characterized the transcriptomic response of L. olgensis seedlings to sodium nitroprusside (SNP, NO donor) using Illumina sequencing and de novo transcriptome assembly. A significant number of putative metabolic pathways and functions associated with the unique sequences were identified. Genes related to plant pathogen infection (FLS2, WRKY33, MAPKKK, and PR1) were upregulated with SNP treatment. This report describes the potential contribution of NO to disease resistance in L. olgensis as induced by biotic stress. Our results provide a substantial contribution to the genomic and transcriptomic resources for L. olgensis, as well as expanding our understanding of the involvement of NO in defense responses at the transcriptional level.

  14. Interaction of nitric oxide wth the (1010) face of ruthenium

    Energy Technology Data Exchange (ETDEWEB)

    Orent, T.W.

    1977-02-01

    The low-energy electron diffraction (LEED) technique was used to probe the atomic geometry of the surfaces that resulted from the steady-state interaction of nitric oxide with Ru(10 anti 10) as a function of temperature and pressure. Auger electron spectroscopy (AES) was used to identify the atomic species present on these surfaces. Results were obtained at reactant partial pressures in the range from 10/sup -9/ to 10/sup -6/ torr and substrate temperatures from -25 to 950/sup 0/C. The interaction of molecular oxygen with the surface was also examined. A qualitative correlation exists between the observed structures and the reported enhancement in the catalytic activity of supported ruthenium after the catalyst had been pretreated with oxygen. (JRD)

  15. Nitric oxide: promoter or suppressor of programmed cell death?

    Science.gov (United States)

    Wang, Yiqin; Chen, Chen; Loake, Gary J; Chu, Chengcai

    2010-02-01

    Nitric oxide (NO) is a short-lived gaseous free radical that predominantly functions as a messenger and effector molecule. It affects a variety of physiological processes, including programmed cell death (PCD) through cyclic guanosine monophosphate (cGMP)-dependent and - independent pathways. In this field, dominant discoveries are the diverse apoptosis networks in mammalian cells, which involve signals primarily via death receptors (extrinsic pathway) or the mitochondria (intrinsic pathway) that recruit caspases as effector molecules. In plants, PCD shares some similarities with animal cells, but NO is involved in PCD induction via interacting with pathways of phytohormones. NO has both promoting and suppressing effects on cell death, depending on a variety of factors, such as cell type, cellular redox status, and the flux and dose of local NO. In this article, we focus on how NO regulates the apoptotic signal cascade through protein S-nitrosylation and review the recent progress on mechanisms of PCD in both mammalian and plant cells.

  16. Nitric oxide production and inducible nitric oxide synthase protein expression in human abdominal aortic aneurysms and cultured aneurismal smooth muscle cells

    Institute of Scientific and Technical Information of China (English)

    LIAO Ming-fang; JING Zai-ping; BAO Jun-min; ZHAO Zhi-qing; MEI Zhi-jun; LU Qing-sheng; CUI Jia-sen; QU Le-feng; ZHANG Su-zhen

    2006-01-01

    Objective:To investigate the production of nitric oxide(NO) and the expression of inducible nitric oxide synthase (iNOS), and their possible role in abdominal aortic aneurysm (AAA). Methods: A total of 28 patients with AAA, 10 healthy controls, and 8 patients with arterial occlusive disease were enrolled into this study. Standard colorimetric assay was used to examine NO concentration in plasma from patients with AAA and normal controls, and in cultured smooth muscle cells (SMCs). Expression of iNOS in aortas and cultured SMCs were detected by immunochemistry. The correlation of iNOS expression with age of the patient, size of aneurysm, and degree of inflammation was also investigated by CochranMantel-Haenszel x2 test and Kendall correlation. Results: Expression of iNOS increased significantly in the wall of aneurism in the patients with AAA compared to the healthy controls (P<0.05) and the patients with occlusive arteries (P<0. 05). iNOS protein and media NOx (nitrite+nitrate) also increased in cultured SMCs from human AAA (n=4, P<0.05), while plasma NOx decreased in patients with AAA (n=25) compared to the healthy controls (n= 20). There was a positive correlation between iNOS protein and the degree of inflammation in aneurismal wall (Kendall coefficient = 0. 5032, P = 0. 0029). Conclusion:SMCs and inflammatory cells are main cellular sources of increased iNOS in AAA, and NO may play a part in pathogenesis in AAA through inflammation, SMCs and oxidative stress.

  17. T-786c Polymorphism in nitric oxide synthase 3 gene and Nitrit Oxide Level of Diabetic Retinopathy in Javanese Population

    Directory of Open Access Journals (Sweden)

    Putri Widelia Welkriana

    2015-11-01

    Full Text Available AbstractComplication of retinopathy in type 2 DM is caused of lower level of NO. Nitric oxide level is synthesizedfrom L-arginin in reaction that catalyze Nitric oxide synthase (NOS 3. The T-786C mutation in NOS 3 genedecreases the expression of nitric oxide synthase (NOS 3 so decreases NO synthesis. To investigate theassociation between T-786C polymorphism in NOS 3 gene with NO level of diabetic retinopathy patients. Thisstudy was a case control study, consist of 40 patient of type 2 diabetic with DR (case group and 40 patient oftype 2 diabetic without DR (control group of Javanese ethnic. The genotyping of T-786C polymorphism wasperformed by PCR-RLFP. Level of NO was measured by spectrophotometry. Chi square test and odd ratiowere used to analyze the association of the T-786C polymorphism in NOS 3 gene with DR. Differences ofNO level between TT and TC genotypes were analyzed using independent t test. The distribution of T-786Cpolymorphism in NOS 3 gene of DR subjects showed that frequency of TT genotype was 22.5% and TC genotypewas 77.5%. Non DR subjects showed the frequency of TT genotype was 50% and TC genotype was 50%, (p=0.011. Frequency of T allele in DR group was 61.25% and C allele was 38.75%, and frequency of T allele in nonDR group was 75% and C allele was 25%, (p= 0.62. Odd ratio of TC genotype was 3.444(CI; 95% : 0.964-3.735and C allele was 1.898 (CI; 95% : 1.310-9.058. The NO level of TC genotype was 1.43+0.126 and TT genotypewas 11.27+5.87 (p=0.000. Level of NO between RD and non RD showed not different significantly (p=0.160for retinopathy. The T-786C polymorphism of NOS 3 gene is risk factor for retinopathy in type 2 DiabetesMellitus. Individual with TC genotype of NOS 3 gene has lower level of NO than TT genotype.Keywords : Diabetic Retinopathy, Polymorphism, Nitric Oxide, Nitric Oxide Synthase.

  18. Expression and regulation of endothelial nitric oxide synthase.

    Science.gov (United States)

    Sase, K; Michel, T

    1997-01-01

    Endothelium-derived nitric oxide (NO) is a key determinant of blood pressure homeostasis and platelet aggregation and is synthesized by the endothelial isoform of nitric oxide synthase (eNOS). In the vascular wall, eNOS is activated by diverse cell-surface receptors and by increases in blood flow, and the consequent generation of NO leads to vascular smooth-muscle relaxation. Endothelium-dependent vasorelaxation is deranged in a variety of disease states, including hypertension, diabetes, and atherosclerosis, but the roles of eNOS in endothelial dysfunction remain to be clearly defined. The past several years have witnessed important advances in understanding the molecular and cellular biology of eNOS regulation. In endothelial cells, eNOS undergoes a complex series of covalent modifications, including myristoylation, palmitoylation, and phosphorylation. Palmitoylation of eNOS dynamically targets the enzyme to distinct domains of the endothelial plasma membrane termed caveolae; caveolae may serve as sites for the sequestration of signal-transducing proteins and are themselves subject to dynamic regulation by ligands and lipids. Originally thought to be expressed only in endothelial cells, eNOS is now known to be expressed in a variety of tissues, including blood platelets, cardiac myocytes, and brain hippocampus. Paradigms established in endothelial cells for the molecular regulation and subcellular targeting of eNOS are being extended to the investigation of eNOS expressed in nonendothelial tissues. This review summarizes recent advances in understanding the molecular regulation of eNOS and the other NOS isoforms and identifies important parallels between eNOS and other cell-signaling molecules. © 1997, Elsevier Science Inc. (Trends Cardiovasc Med 1997;7:28-37).

  19. Nitric Oxide And Hypoxia Response In Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Estefanía Caballano Infantes

    2015-08-01

    Full Text Available The expansion of pluripotent cells (ESCs and iPSCs under conditions that maintain their pluripotency is necessary to implement a cell therapy program. Previously, we have described that low nitric oxide (NO donor diethylenetriamine/nitric oxide adduct (DETA-NO added to the culture medium, promote the expansion of these cell types. The molecular mechanisms are not yet known. We present evidences that ESC and iPSCs in normoxia in presence of low NO triggers a similar response to hypoxia, thus maintaining the pluripotency. We have studied the stability of HIF-1α (Hypoxia Inducible Factor in presence of low NO. Because of the close relationship between hypoxia, metabolism, mitochondrial function and pluripotency we have analyzed by q RT-PCR the expression of genes involved in the glucose metabolism such as: HK2, LDHA and PDK1; besides other HIF-1α target gene. We further analyzed the expression of genes involved in mitochondrial biogenesis such as PGC1α, TFAM and NRF1 and we have observed that low NO maintains the same pattern of expression that in hypoxia. The study of the mitochondrial membrane potential using Mito-Tracker dye showed that NO decrease the mitochondrial function. We will analyze other metabolic parameters, to determinate if low NO regulates mitochondrial function and mimics Hypoxia Response. The knowledge of the role of NO in the Hypoxia Response and the mechanism that helps to maintain self-renewal in pluripotent cells in normoxia, can help to the design of culture media where NO could be optimal for stem cell expansion in the performance of future cell therapies.

  20. Elevated levels of exhaled nitric oxide in patients with anorexia nervosa.

    Science.gov (United States)

    Oświęcimska, Joanna; Ziora, Katarzyna; Ziora, Dariusz; Machura, Edyta; Smerdziński, Sebastian; Pyś-Spychała, Magdalena; Kasperski, Jacek; Zamłyński, Jacek; Kasperska-Zajac, Alicja

    2014-09-01

    Nitric oxide (NO) is involved in eating behavior and inflammatory response. Moreover, there is evidence that NO production is altered in patients with anorexia nervosa (AN). To assess whether the overproduction of NO in AN can affect NO level in exhaled air. Exhaled NO level was studied in 23 girls with AN and compared with that of healthy age- and gender-matched nonatopic controls. Exhaled NO levels were significantly higher in girls with AN compared with healthy age-matched controls. It appears that anorexia nervosa was accompanied by a higher level of exhaled NO, likely resulting from a systemic increase in NO production because of the severe catabolic state.

  1. Subclinical mastitis causes alterations in nitric oxide, total oxidant and antioxidant capacity in cow milk.

    Science.gov (United States)

    Atakisi, Onur; Oral, Hasan; Atakisi, Emine; Merhan, Oguz; Metin Pancarci, S; Ozcan, Ayla; Marasli, Saban; Polat, Bulent; Colak, Armagan; Kaya, Semra

    2010-08-01

    The aim of this study was to investigate total antioxidant (TAC), and oxidant capacity (TOC) and nitric oxide (NO) levels in milk of cows with subclinical mastitis. Brown Swiss and Holstein breed cows were screened with California Mastitis Test (CMT) to determine mammary glands with subclinical mastitis. Moreover, somatic cell counts (SCC) were determined electronically in all milk samples. Mammary quarters were classified as healthy (n=25) or subclinical mastitis (n=35) based on CMT scores and somatic cell count (SCC: 200,000/ml) in milk. Nitric oxide, TOC and SCC levels were significantly higher (pmastitis compared to those from healthy mammary quarters. In conclusion, subclinical mastitis results in higher NO concentrations, TOC and SCC, and NO and TOC were positively correlated with SCC. Moreover, alterations in NO levels and TOC in milk could be used as an alternative diagnostic tool to screen for subclinical mastitis. Copyright 2010 Elsevier Ltd. All rights reserved.

  2. Modeling toxic compounds from nitric oxide emission measurements

    Science.gov (United States)

    Vallero, Daniel A.; Peirce, Jeffrey; Cho, Ki Don

    Determining the amount and rate of degradation of toxic pollutants in soil and groundwater is difficult and often requires invasive techniques, such as deploying extensive monitoring well networks. Even with these networks, degradation rates across entire systems cannot readily be extrapolated from the samples. When organic compounds are degraded by microbes, especially nitrifying bacteria, oxides or nitrogen (NO x) are released to the atmosphere. Thus, the flux of nitric oxide (NO) from the soil to the lower troposphere can be used to predict the rate at which organic compounds are degraded. By characterizing and applying biogenic and anthropogenic processes in soils the rates of degradation of organic compounds. Toluene was selected as a representative of toxic aromatic compounds, since it is inherently toxic, it is a substituted benzene compound and is listed as a hazardous air pollutant under Section 12 of the Clean Air Act Amendments of 1990. Measured toluene concentrations in soil, microbial population growth and NO fluxes in chamber studies were used to develop and parameterize a numerical model based on carbon and nitrogen cycling. These measurements, in turn, were used as indicators of bioremediation of air toxic (i.e. toluene) concentrations. The model found that chemical concentration, soil microbial abundance, and NO production can be directly related to the experimental results (significant at P hydrocarbons and oxides of nitrogen. As such, the model may be a tool for decision makers in ozone non-attainment areas.

  3. New nitric oxide donors based on ruthenium complexes

    Directory of Open Access Journals (Sweden)

    C.N. Lunardi

    2009-01-01

    Full Text Available Nitric oxide (NO donors produce NO-related activity when applied to biological systems. Among its diverse functions, NO has been implicated in vascular smooth muscle relaxation. Despite the great importance of NO in biological systems, its pharmacological and physiological studies have been limited due to its high reactivity and short half-life. In this review we will focus on our recent investigations of nitrosyl ruthenium complexes as NO-delivery agents and their effects on vascular smooth muscle cell relaxation. The high affinity of ruthenium for NO is a marked feature of its chemistry. The main signaling pathway responsible for the vascular relaxation induced by NO involves the activation of soluble guanylyl-cyclase, with subsequent accumulation of cGMP and activation of cGMP-dependent protein kinase. This in turn can activate several proteins such as K+ channels as well as induce vasodilatation by a decrease in cytosolic Ca2+. Oxidative stress and associated oxidative damage are mediators of vascular damage in several cardiovascular diseases, including hypertension. The increased production of the superoxide anion (O2- by the vascular wall has been observed in different animal models of hypertension. Vascular relaxation to the endogenous NO-related response or to NO released from NO deliverers is impaired in vessels from renal hypertensive (2K-1C rats. A growing amount of evidence supports the possibility that increased NO inactivation by excess O2- may account for the decreased NO bioavailability and vascular dysfunction in hypertension.

  4. Macrophages in lung tissue from patients with pulmonary emphysema express both inducible and endothelial nitric oxide synthase

    NARCIS (Netherlands)

    van Straaten, JFM; Postma, DS; Coers, W; Noordhoek, JA; Kauffman, HF; Timens, W

    1998-01-01

    To provide information concerning a possible biologic role of nitric oxide (NO) in smoking-related emphysema, we performed immunohistochemical studies in lung tissue from control subjects and patients with mild and severe emphysema We studied the presence of inducible and endothelial NO synthases (i

  5. Gentamicin induced nitric oxide-related oxidative damages on vestibular afferents in the guinea pig.

    Science.gov (United States)

    Hong, Sung Hwa; Park, Sook Kyung; Cho, Yang-Sun; Lee, Hyun-Seok; Kim, Ki Ryung; Kim, Myung Gu; Chung, Won-Ho

    2006-01-01

    Gentamicin is a well-known ototoxic aminoglycoside. However, the mechanism underlying this ototoxicity remains unclear. One of the mechanisms which may be responsible for this ototoxicity is excitotoxic damage to hair cells. The overstimulation of the N-methyl-d-aspartate (NMDA) receptors increases the production of nitric oxide (NO), which induces oxidative stress on hair cells. In order to determine the mechanism underlying this excitotoxicity, we treated guinea pigs with gentamicin by placing gentamicin (0.5 mg) pellets into a round window niche. After the sacrifice of the animals, which occurred at 3, 7 and 14 days after the treatment, the numbers of hair cells in the animals were counted with a scanning electron microscope. We then performed immunostaining using neuronal nitric oxide synthase (nNOS), inducible NOS (iNOS) and nitrotyrosine antibodies. The number of hair cells in the animals was found to decrease significantly after 7 days. nNOS and iNOS expression levels were observed to have increased 3 days after treatment. Nitrotyrosine was expressed primarily at the calyceal afferents of the type I hair cells 3 days after treatment. Terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) staining revealed positive hair cells 3 days after treatment. Our results suggest that inner ear treatment with gentamicin may upregulate nNOS and iNOS to induce oxidative stress in the calyceal afferents of type I hair cells, via nitric oxide overproduction.

  6. Osteopontin protects against hyperoxia-induced lung injury by inhibiting nitric oxide synthases.

    Science.gov (United States)

    Zhang, Xiang-Feng; Liu, Shuang; Zhou, Yu-Jie; Zhu, Guang-Fa; Foda, Hussein D

    2010-04-05

    Exposure of adult mice to more than 95% O(2) produces a lethal injury by 72 hours. Nitric oxide synthase (NOS) is thought to contribute to the pathophysiology of murine hyperoxia-induced acute lung injury (ALI). Osteopontin (OPN) is a phosphorylated glycoprotein produced principally by macrophages. OPN inhibits inducible nitric oxide synthase (iNOS), which generates large amounts of nitric oxide production. However, the relationship between nitric oxide and endogenous OPN in lung tissue during hyperoxia-induced ALI has not yet been elucidated, thus we examined the role that OPN plays in the hyperoxia-induced lung injury and its relationships with NOS. One hundred and forty-four osteopontin knock-out (KO) mice and their matched wild type background control (WT) were exposed in sealed cages > 95% oxygen or room air for 24- 72 hours, and the severity of lung injury was assessed; expression of OPN, endothelial nitric oxide synthase (eNOS) and iNOS mRNA in lung tissues at 24, 48 and 72 hours of hyperoxia were studied by reverse transcription-polymerase chain reaction (RT-PCR); immunohistochemistry (IHC) was performed for the detection of iNOS, eNOS, and OPN protein in lung tissues. OPN KO mice developed more severe acute lung injury at 72 hours of hyperoxia. The wet/dry weight ratio increased to 6.85 +/- 0.66 in the KO mice at 72 hours of hyperoxia as compared to 5.31 +/- 0.92 in the WT group (P < 0.05). iNOS mRNA (48 hours: 1.04 +/- 0.08 vs. 0.63 +/- 0.09, P < 0.01; 72 hours: 0.89 +/- 0.08 vs. 0.72 +/- 0.09, P < 0.05) and eNOS mRNA (48 hours: 0.62 +/- 0.08 vs. 0.43 +/- 0.09, P < 0.05; 72 hours: 0.67 +/- 0.08 vs. 0.45 +/- 0.09, P < 0.05) expression was more significantly increased in OPN KO mice than their matched WT mice when exposed to hyperoxia. IHC study showed higher expression of iNOS (20.54 +/- 3.18 vs. 12.52 +/- 2.46, P < 0.05) and eNOS (19.83 +/- 5.64 vs. 9.45 +/- 3.82, P < 0.05) in lung tissues of OPN KO mice at 72 hours of hyperoxia. OPN can protect against

  7. Indium Tin Oxide Resistor-Based Nitric Oxide Microsensors

    Science.gov (United States)

    Xu, Jennifer C.; Hunter, Gary W.; Gonzalez, Jose M., III; Liu, Chung-Chiun

    2012-01-01

    A sensitive resistor-based NO microsensor, with a wide detection range and a low detection limit, has been developed. Semiconductor microfabrication techniques were used to create a sensor that has a simple, robust structure with a sensing area of 1.10 0.99 mm. A Pt interdigitated structure was used for the electrodes to maximize the sensor signal output. N-type semiconductor indium tin oxide (ITO) thin film was sputter-deposited as a sensing material on the electrode surface, and between the electrode fingers. Alumina substrate (250 m in thickness) was sequentially used for sensor fabrication. The resulting sensor was tested by applying a voltage across the two electrodes and measuring the resulting current. The sensor was tested at different concentrations of NO-containing gas at a range of temperatures. Preliminary results showed that the sensor had a relatively high sensitivity to NO at 450 C and 1 V. NO concentrations from ppm to ppb ranges were detected with the low limit of near 159 ppb. Lower NO concentrations are being tested. Two sensing mechanisms were involved in the NO gas detection at ppm level: adsorption and oxidation reactions, whereas at ppb level of NO, only one sensing mechanism of adsorption was involved. The NO microsensor has the advantages of high sensitivity, small size, simple batch fabrication, high sensor yield, low cost, and low power consumption due to its microsize. The resistor-based thin-film sensor is meant for detection of low concentrations of NO gas, mainly in the ppb or lower range, and is being developed concurrently with other sensor technology for multispecies detection. This development demonstrates that ITO is a sensitive sensing material for NO detection. It also provides crucial information for future selection of nanostructured and nanosized NO sensing materials, which are expected to be more sensitive and to consume less power.

  8. Exhaled nitric oxide in pulmonary arterial hypertension associated with systemic sclerosis.

    Science.gov (United States)

    Cao, Zeling; Mathai, Stephen C; Hummers, Laura K; Shah, Ami A; Wigley, Fredrick M; Lechtzin, Noah; Hassoun, Paul M; Girgis, Reda E

    2016-12-01

    The fractional exhaled concentration of nitric oxide (FENO) has been shown to be reduced in idiopathic pulmonary arterial hypertension (PAH) but has not been adequately studied in PAH associated with systemic sclerosis (SSc). We measured FENO at an expiratory flow rate of 50 mL/s in 21 treatment-naive patients with SSc-associated PAH (SSc-PAH), 94 subjects with SSc without pulmonary involvement, and 84 healthy volunteers. Measurements of FENO at additional flow rates of 100, 150, and 250 mL/s were obtained to derive the flow-independent nitric oxide exchange parameters of maximal airway flux (J'awNO) and steady-state alveolar concentration (CANO). FENO at 50 mL/s was similar (P = 0.22) in the SSc-PAH group (19 ± 12 parts per billion [ppb]) compared with the SSc group (17 ± 12 ppb) and healthy control group (21 ± 11 ppb). No change was observed after 4 months of targeted PAH therapy in 14 SSc-PAH group patients (P = 0.9). J'awNO was modestly reduced in SSc group subjects without lung disease (1.2 ± 0.5 nl/s) compared with healthy controls (1.64 ± 0.9; P group. CANO was elevated in individuals with SSc-PAH (4.8 ± 2.6 ppb) compared with controls with SSc (3.3 ± 1.4 ppb) and healthy subjects (2.6 ± 1.5 ppb; P < 0.001 for both). However, after adjustment for the diffusing capacity of CO, there was no significant difference in CANO between individuals with SSc-PAH and controls with SSc. We conclude that FENO is not useful for the diagnosis of PAH in SSc. Increased alveolar nitric oxide in SSc-PAH likely represents impaired diffusion into pulmonary capillary blood.

  9. Protective effect of inducible nitric oxide synthase inhibitor on pancreas transplantation in rats

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To investigate the effect of inducible nitric oxide synthase inhibitor, aminoguanidine, on pancreas transplantation in rats.METHODS: A model of pancreas transplantation was established in rats. Streptozotocin-induced diabetic male Wistar rats were randomly assigned to sham-operation control group (n = 6), transplant control group (n=6), and aminoguanidine (AG) treatment group (n=18). In the AG group, aminoguanidine was added to intravascular infusion as the onset of reperfusion at the dose of 60 mg/kg, 80 mg/kg, 100 mg/kg body weight,respectively. Serum nitric oxide (NO) level, blood sugar and amylase activity were detected. Nitric oxide synthase (NOS) test kit was used to detect the pancreas cNOS and inducible NOS (iNOS) activity. Pancreas sections stained with HE and immunohistochemistry were evaluated under a light microscope.RESULTS: As compared with the transplant control group, the serum NO level and amylase activity decreased obviously and the evidence for pancreas injury was much less in the AG group. The AG (80 mg/kg body weight) group showed the most significant difference in NO and amylase (NO: 66.0 ± 16.6 vs 192.3 ± 60.0, P <0.01 and amylase: 1426 ± 177 vs 4477 ± 630, P<0.01).The expression and activity of tissue iNOS, and blood sugar in the AG (80 mg/kg body weight) group were much lower than those in the transplant control group (iNOS: 2.01 ± 0.23 vs 26.59 ± 5.78, P < 0.01 and blood sugar: 14.2 ± 0.9 vs 16.8 ± 1.1, P < 0.01).CONCLUSION: Selective iNOS inhibitor, aminoguanidine as a free radical, has a protective effect on pancreas transplantation in rats by inhibiting NO and reducing its toxicity.

  10. Surface modification of PLGA nanoparticles to deliver nitric oxide to inhibit Escherichia coli growth

    Science.gov (United States)

    Reger, Nina A.; Meng, Wilson S.; Gawalt, Ellen S.

    2017-04-01

    Polymer nanoparticles consisting of poly (DL-lactic-co-glycolic acid) were surface functionalized to deliver nitric oxide. These biodegradable and biocompatible nanoparticles were modified with an S-nitrosothiol molecule, S-nitrosocysteamine, as the nitric oxide delivery molecule. S-nitrosocysteamine was covalently immobilized on the nanoparticle surface using small organic molecule linkers and carbodiimide coupling. Nanoparticle size, zeta potential, and morphology were determined using dynamic light scattering and scanning electron microscopy, respectively. Subsequent attachment of the S-nitrosothiol resulted in a nitric oxide release of 37.1 ± 1.1 nmol per milligram of nanoparticles under physiological conditions. This low concentration of nitric oxide reduced Escherichia coli culture growth by 31.8%, indicating that the nitric oxide donor was effective at releasing nitric oxide even after attachment to the nanoparticle surface. Combining the nitric oxide modified nanoparticles with tetracycline, a commonly prescribed antibiotic for E. coli infections, increased the effectiveness of the antibiotic by 87.8%, which allows for lower doses of antibiotics to be used in order to achieve the same effect. The functionalized nanoparticles were not cytotoxic to mouse fibroblasts.

  11. Changes of nitric oxide synthase and cyclic guanosine monophosphate in form deprivation myopia in guinea pigs

    Institute of Scientific and Technical Information of China (English)

    WU Jie; LIU Qiong; YANG Xiao; YANG Hui; WANG Xin-mei; ZENG Jun-wen

    2007-01-01

    Background The form deprivation(FD)reduces spatial contrasts and induces myopia. Nitric oxide and cyclic guanosine monophosphate(cGMP)are involved in visual signal transmission.This study investigated changes in nitric oxide synthase(NOS)activity and cGMP concentration in ocular tissues in acute and chronic form deprivation myopia.Methods Guinea pigs had one eye covered by translucent glass for 7,14 or 21 days.Untreated litter mates were used as controls.NOS activity and cGMP concentrations in the retinal,choroidal and scleral tissues of FD eyes and controleyes were analyzed by radioimmunoassay after various durations of FD.The expression of NOS subtypes was identified by immunohistochemistry.Results Myopia was successfully induced in FD eyes after 14 days.Compared with control groups,the retinal NOS activity and cGMP concentrations in the FD eyes significantly increased after 14 and 21 days while the retinal NOS activity in the FD eyes was transiently suppressed by 7 days of FD.The NOS activity and cGMP concentrations of choroid and sclera in the FD eyes were higher than in the control groups at 21 days.The three isoenzymes of nitric oxide synthase were detected in the ocular tissues of guinea pigs.Conclusions The NOS activity and cGMP concentrations were upregulated after chronic FD and the retinal NOS activity was transiently suppressed at acute FD.The function of elevated NOS activity may be mediated by cGMP.

  12. Therapeutic application of inhaled nitric oxide in adult cardiac surgical patients.

    Science.gov (United States)

    Makker, Robina; Mehta, Yatin; Trehan, Naresh; Bapna, Rk

    2006-01-01

    Increased pulmonary vascular resistance can be detrimental to the cardiac output in post-operative cardiac surgical patients. Pulmonary vasodilator therapy by systemic pharmacologic agents is non-selective. Inhaled nitric oxide is a selective pulmonary vasodilator and does not cause systemic hypotension. In this prospective study, 14 adult post-operative cardiac surgical patients with pulmonary hypertension underwent inhaled nitric oxide therapy and their hemodynamic changes were evaluated. Inhaled nitric oxide was administered in doses of 5 ppm-25 ppm. The result was a decrease in pulmonary vascular resistance from 456.57 +/- 137.13 to 357.64 +/- 119.80 dynes-sec- Continued. - See Free Full Text.

  13. Exhaled nitric oxide (FeNO) as a non-invasive marker of airway inflammation.

    Science.gov (United States)

    Munakata, Mitsuru

    2012-09-01

    Nitric oxide (NO), previously very famous for being an environmental pollutant in the field of pulmonary medicine, is now known as the smallest, lightest, and most famed molecule to act as a biological messenger. Furthermore, recent basic researches have revealed the production mechanisms and physiological functions of nitric oxide in the lung, and clinical researches have been clarifying its tight relation to airway inflammation in asthma. On the bases of this knowledge, fractional nitric oxide (FeNO) has now been introduced as one of the most practical tools for the diagnosis and management of bronchial asthma.

  14. Exhaled Nitric Oxide (FeNO as a Non-Invasive Marker of Airway Inflammation

    Directory of Open Access Journals (Sweden)

    Mitsuru Munakata

    2012-01-01

    Full Text Available Nitric oxide (NO, previously very famous for being an environmental pollutant in the field of pulmonary medicine, is now known as the smallest, lightest, and most famed molecule to act as a biological messenger. Furthermore, recent basic researches have revealed the production mechanisms and physiological functions of nitric oxide in the lung, and clinical researches have been clarifying its tight relation to airway inflammation in asthma. On the bases of this knowledge, fractional nitric oxide (FeNO has now been introduced as one of the most practical tools for the diagnosis and management of bronchial asthma.

  15. Uncoupling of Vascular Nitric Oxide Synthase Caused by Intermittent Hypoxia

    Directory of Open Access Journals (Sweden)

    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.

  16. Role of nitric oxide, nitroxidative and oxidative stress in wound healing.

    Science.gov (United States)

    Soneja, Amit; Drews, Magdalena; Malinski, Tadeusz

    2005-01-01

    Redox-regulated processes are relevant to wound healing. A balance between bioavailable nitric oxide (NO) concentration and a level of oxidative and nitroxidative stress in wounds may be crucial in wound repair. The highly beneficial effect of bioavailable NO is attributed to scavenging of superoxide, which is the main component of oxidative stress. Also, the high level of NO can influence angiogenesis and endothelial/skeletal muscle cell remodeling and proliferation. However, under conditions of excessive and prolonged production of O(2)(-) in wounds, the supplementation of NO can be evolved in significant increase in nitroxidative stress due to production of peroxynitrite (ONOO(-)) and peroxynitrous acid (ONOOH). ONOOH can trigger a cascade of events leading to the generation of highly reactive and damaging radicals and oxidative species. These species (mainly CO(3)(.-), NO(2)(+), NO(2), N(2)O(3), OH(.)) can impose significant damage in biological milieu and impair the process of wound healing. Therefore, a general strategy for an acceleration of the wound healing process may include an intervention(s) leading to the decrease in oxidative stress (treatment with antioxidants and/or prevention of O(2)(-) generation by uncoupled constitutive nitric oxide synthase, cNOS) and delivery of NO (treatment with NO donors, cNOS gene therapy). Here we briefly review the role of NO, and focus on O(2)(-) and ONOOH (major components of oxidative and nitroxidative stress respectively) in the normal and impaired process of wound healing.

  17. Circulating nitric oxide products do not solely reflect nitric oxide release in cirrhosis and portal hypertension

    DEFF Research Database (Denmark)

    Afzelius, P.; Bazeghi, N.; Bie, P.

    2011-01-01

    (x) and exhaled NO were determined in the supine and sitting positions and related to haemodynamics, RAAS and lung diffusing capacity (D(L)CO). Eight matched healthy individuals served as controls. Results: All patients with cirrhosis had portal hypertension. We found no significant difference in exhaled...... NO between patients and controls and no changes from the supine to the sitting position. Exhaled NO in the patients correlated significantly with plasma volume, heart rate and DLCO. NO(x) concentrations were not significantly increased in the patients. NO(x) correlated with portal pressure and haemodynamic...

  18. RNA diversity has profound effects on the translation of neuronal nitric oxide synthase

    OpenAIRE

    Wang, Yang; Newton, Derek C.; Robb, G. Brett; Kau, Cheng-Lin; Miller, Tricia L.; Cheung, Anthony H.; Hall,Anne V.; VanDamme, Suzannah; Wilcox, Josiah N.; Marsden, Philip A.

    1999-01-01

    A comprehensive analysis of the structure of neuronal nitric oxide synthase (nNOS; EC 1.14.13.39) mRNA species revealed NOS1 to be the most structurally diverse human gene described to date in terms of promoter usage. Nine unique exon 1 variants are variously used for transcript initiation in diverse tissues, and each is expressed from a unique 5′-flanking region. The dependence on unique genomic regions to control transcription initiation in a cell-specific fashion burdens the transcripts wi...

  19. Effect of L-NAME on nitric oxide and gastrointestinal motility alterations in cirrhotic rats

    Institute of Scientific and Technical Information of China (English)

    Xin Wang; Jie Ding; Kai-Cun Wu; Bo-Rong Pan; Dai-Ming Fan; Yue-Xia Zhong; Zong-You Zhang; Ju Lu; Mei Lan; Ji-Yan Miao; Xue-Gang Guo; Yong-Quan Shi; Yan-Qiu Zhao

    2002-01-01

    AIM: To invsstigare the effect of L-NAME on nitric oxide andgastriubtestubal motility alterations in cirrhotic ratsMETHODS: Rats with cirrhosis induced by carbontetrachloride were randomly divided into two groups, one( n= 13) receiving 0. 5 mg@ kg-1 per clay of NG-nitro-L-argininemethyl ester (L-NAME), a nitric oxide synthase inhibitor,for 10 days, whereas the other group ( n = 13) and control( n = 10) rats were administrated the same volume of 9 g@ L-1saline.Half gastric emptying time and 2 h residual rate weremeasured by SPECT, using 99m Tc-DTPA-labeled bariumsuifate as test meal. Gastrointestinal transition time wasrecorded simultaneously. Serum concentration of nitrcoxide (NO) was determined by the kinetic cadmiunreduction and colorimetric methods. ImmunohistochemicalSABC method was used to observe the expression anddistribution of three types of nitric oxide synthase (NOS)isoforms in the mt gastrointestinal tract. Western blot wasused to detect expression of gastrointestinal NOS isoforms.RESULTS: Half gastric emptying time and trans-gastrointestinal time were significantly prolonged( 124.0 ± 26.4min; 33.7± 8.9min;72.1 ± 15.3 min; P<0.01), (12.4±0.5h; 9.5±0.3 h; 8.2±0.8 h; P<0.01), 2h residual rate wasraised in cirrhotic rots than in controls and cirrhotic ratstreated with L-NAME(54.9± 7.6 % ,13.7 ± 3.2 %, 34.9± 10.3%, P< 0.01). Serum concentration of NO was significantlyincreased in cirrhotic rots than in the other groups (8.20 ± 2.48)μmol@L-1, (5.94± 1.07) μmol@L-1 ,and control (5.66± 1.60) tμmol@L-1, P< 0.01. NOS staining intensities which weremainly located in the gastrointestinal tissues were markedlylower in cirrhotic rats than in the controls and cirrhotic ratsafter treated with L- NAME.CONCLUSION: Gastrointestinal motility was remarkablyinhibited in cirrhotic rats, which could he alleviated by L-NAME. Nitric oxide may play an important role in theinhibition of gastrointestinal motility in cirrhotic rats.

  20. Measurement of exhaled nitric oxide concentration in patients with obstructive sleep apnea

    Science.gov (United States)

    Zhang, Dongmei; Luo, Jinmei; Qiao, Yixian; Xiao, Yi; Huang, Rong; Zhong, Xu

    2017-01-01

    Abstract Background: Exhaled nitric oxide (eNO) has been proposed as a noninvasive measure of airway inflammation. However, its value in patients with obstructive sleep apnea (OSA) is still controversial. The authors aim to assess the difference in eNO levels between patients with OSA and controls by a meta-analysis. Methods: A systematic search was performed in the PubMed, EMBASE, the Cochrane Library, and MEDLINE databases to collect relevant studies published from 1996 to 2016. Eligible studies that reported eNO levels in patients with OSA were included. STATA (version 12.0) was used for data analysis. Results: Two hundred eighty-four studies were reviewed for inclusion, with 16 studies pooled for analysis (16 studies for fractional exhaled nitric oxide [FENO], 5 for alveolar nitric oxide [CANO], and 4 for the maximum airway wall flux of nitric oxide [J′awNO]). The FENO levels were significantly higher in patients with OSA compared with that in the control groups (6.32 ppb, 95% confidence interval [CI] 4.46–8.33, P < 0.001). Furthermore, FENO was significantly increased (4.00 ppb, 95% CI 1.74–6.27, P = 0.001) after overnight sleep in patients with OSA, but not in healthy controls. Additionally, long-term continuous positive airway pressure (CPAP) therapy reduced FENO levels (−5.82 ppb, 95% CI −9.6 to −2.01, P < 0.001). However, the CANO (−0.01 ppb, 95% CI −1.66 to 1.64, P = 0.989) and J’awNO levels (220.32 pl/s, 95% CI −49.31 to 489.94, P = 0.109) were not significantly different between the OSA groups and non-OSA groups. Conclusion: The results of the meta-analysis suggest that OSA is significantly associated with airway inflammation and elevated FENO levels can be modified by long-term CPAP therapy. J’awNO and CANO levels were not significantly different between the OSA groups and control groups. PMID:28328850

  1. Hypotrophy of conduit artery walls of the offspring of nitric oxide-defective rats

    OpenAIRE

    Kristek F.; Gerová M.

    2004-01-01

    The objective of the present study was to investigate the structure of the arterial walls of the offspring stemming from nitric oxide (NO)-defective hypertensive parents. The parents were treated with N G-nitro-L-arginine methyl ester (40 mg kg-1 day-1) for 5 weeks. Blood pressure was measured noninvasively in six 30-day-old rats and nine age-matched controls. The cardiovascular system was perfused with glutaraldehyde at 120 mmHg. The thoracic aorta and carotid artery were processed for elect...

  2. The role of nitric oxide and oxidative stress in intestinal damage induced by selenium deficiency in chickens.

    Science.gov (United States)

    Yu, Jiao; Yao, Haidong; Gao, Xuejiao; Zhang, Ziwei; Wang, Jiu-Feng; Xu, Shi-Wen

    2015-02-01

    Nitric oxide (NO) is an essential messenger molecule and is associated with inflammation and oxidative stress. Although NO has important biological functions in mammals, its role in the mechanism that occurs after intestinal injuries in chickens remains unknown. The objective of the present study was to investigate the real role of NO and oxidative stress in the intestinal injuries of chickens induced by selenium (Se) deficiency. A total 150 chickens were randomly divided into the following two groups: a low-Se group (L group, fed a Se-deficient diet containing 0.020 mg/kg Se) and a control group (C group, fed a commercial diet containing 0.2 mg/kg Se). The activities and mRNA levels of glutathione peroxidase (GSH-Px), the production of glutathione (GSH) and NO, and the protein and mRNA levels of inducible nitric oxide synthase (iNOS) were examined in the intestinal tissues (duodenum, jejunum, and rectum) at 15, 25, 35, 45, and 55 days. Methane dicarboxylic aldehyde (MDA) levels were also detected by assay kits. Then, the morphologies of the tissues were observed under the microscope after hematoxylin and eosin staining (H&E staining). The results showed that Se deficiency induced higher inflammatory damage and MDA levels (P chickens and that low levels of GSH-Px and high contents of NO may exert a major role in the injury of the intestinal tract induced by Se deficiency.

  3. Time-dependent effect of orchidectomy on vascular nitric oxide and thromboxane A2 release. Functional implications to control cell proliferation through activation of the epidermal growth factor receptor.

    Directory of Open Access Journals (Sweden)

    Marta del Campo

    Full Text Available This study analyzes whether the release of nitric oxide (NO and thromboxane A2 (TXA2 depends on the time lapsed since gonadal function is lost, and their correlation with the proliferation of vascular smooth muscle cells (VSMC mediated by the epidermal growth factor receptor (EGFR. For this purpose, aortic and mesenteric artery segments from control and 6-weeks or 5-months orchidectomized rats were used to measure NO and TXA2 release. The results showed that the basal and acetylcholine (ACh-induced NO release were decreased 6 weeks post-orchidectomy both in aorta and mesenteric artery, but were recovered 5 months thereafter up to levels similar to those found in arteries from control rats. The basal and ACh-induced TXA2 release increased in aorta and mesenteric artery 6 weeks post-orchidectomy, and was maintained at high levels 5 months thereafter. Since we previously observed that orchidectomy, which decreased testosterone level, enlarged the muscular layer of mesenteric arteries, the effect of testosterone on VSMC proliferation was analyzed. The results showed that treatment of cultured VSMC with testosterone downregulated mitogenic signaling pathways initiated by the ligand-dependent activation of the EGFR. In contrast, the EGFR pathways were constitutively active in mesenteric arteries of long-term orchidectomized rats. Thus, the exposure of mesenteric arteries from control rats to epidermal growth factor (EGF induced the activation of EGFR signaling pathways. However, the addition of EGF to arteries from orchidectomized rats failed to induce a further activation of these pathways. In conclusion, this study shows that the release of NO depends on the time lapsed since the gonadal function is lost, while the release of TXA2 is already increased after short periods post-orchidectomy. The alterations in these signaling molecules could contribute to the constitutive activation of the EGFR and its downstream signaling pathways after long period

  4. Time-dependent effect of orchidectomy on vascular nitric oxide and thromboxane A2 release. Functional implications to control cell proliferation through activation of the epidermal growth factor receptor.

    Science.gov (United States)

    del Campo, Marta; Sagredo, Ana; del Campo, Lara; Villalobo, Antonio; Ferrer, Mercedes

    2014-01-01

    This study analyzes whether the release of nitric oxide (NO) and thromboxane A2 (TXA2) depends on the time lapsed since gonadal function is lost, and their correlation with the proliferation of vascular smooth muscle cells (VSMC) mediated by the epidermal growth factor receptor (EGFR). For this purpose, aortic and mesenteric artery segments from control and 6-weeks or 5-months orchidectomized rats were used to measure NO and TXA2 release. The results showed that the basal and acetylcholine (ACh)-induced NO release were decreased 6 weeks post-orchidectomy both in aorta and mesenteric artery, but were recovered 5 months thereafter up to levels similar to those found in arteries from control rats. The basal and ACh-induced TXA2 release increased in aorta and mesenteric artery 6 weeks post-orchidectomy, and was maintained at high levels 5 months thereafter. Since we previously observed that orchidectomy, which decreased testosterone level, enlarged the muscular layer of mesenteric arteries, the effect of testosterone on VSMC proliferation was analyzed. The results showed that treatment of cultured VSMC with testosterone downregulated mitogenic signaling pathways initiated by the ligand-dependent activation of the EGFR. In contrast, the EGFR pathways were constitutively active in mesenteric arteries of long-term orchidectomized rats. Thus, the exposure of mesenteric arteries from control rats to epidermal growth factor (EGF) induced the activation of EGFR signaling pathways. However, the addition of EGF to arteries from orchidectomized rats failed to induce a further activation of these pathways. In conclusion, this study shows that the release of NO depends on the time lapsed since the gonadal function is lost, while the release of TXA2 is already increased after short periods post-orchidectomy. The alterations in these signaling molecules could contribute to the constitutive activation of the EGFR and its downstream signaling pathways after long period post

  5. Pigment Melanin Scavenges Nitric Oxide In Vitro: Possible Relevance to Keloid Formation

    Directory of Open Access Journals (Sweden)

    Julian M. Menter

    2008-01-01

    Full Text Available Recently, nitric oxide (NO has been implicated in the formation of keloids, preferentially formed in dark-skinned persons, and we suspected that pigment melanin itself may play a direct role by adsorbing NO. We tested the ability of cuttlefish sepia melanin to scavenge (adsorb NO, generated in situ by 2-(N.N Diethylamino diazeneolate-2-oxide (DEA/NO, through a dialysis membrane. NO was measured as NO2_ and NO3_ by the Griess method and as N2O3 by trapping experiments with the fluorogenic substrate 4,5-diaminofluorescein (DAF-2. Initial NO2_ and NO3_ concentrations were significantly lower in the test dialyzates than in controls. Scavenging of NO was rapid enough to compete with DAF adduct formation. Both analytical methods gave comparable results. Adsorbed NO and/or its oxidized products may undergo interactions with melanin, adsorbed O2, and/or dermal material that may lead to keloid formation.

  6. Nitric Oxide as a Regulator of B. anthracis Pathogenicity

    Directory of Open Access Journals (Sweden)

    Serguei G Popov

    2015-09-01

    Full Text Available Nitric oxide (NO is a key physiological regulator in eukaryotic and prokaryotic organisms. It can cause a variety of biological effects by reacting with its targets or/and indirectly inducing oxidative stress. NO can also be produced by bacteria including the pathogenic B. anthracis; however its role in the infectious process only begins to emerge. NO incapacitates macrophages by S-nitrosylating the intracellular proteins and protects B. anthracis from oxidative stress. It is also implicated in the formation of toxic peroxynitrite. In this study we further assessed the effects of B. anthracis NO produced by the NO synthase (bNOS on bacterial metabolism and host cells in experiments with the bNOS knockout Sterne strain. The mutation abrogated accumulation of nitrite and nitrate as tracer products of NO in the culture medium and markedly attenuated growth in both aerobic and microaerobic conditions. The regulatory role of NO was also suggested by the abnormally high rate of nitrate denitrification by the mutant in the presence of oxygen. Anaerobic regulation mediated by NO was reflected in reduced fermentation of glucose by the mutant correlating with the reduced toxicity of bacteria toward host cells in culture. The toxic effect of NO required permeabilization of the target cells as well as the activity of fermentation-derived metabolite in the conditions of reduced pH. The host cells demonstrated increased phosphorylation of major survivor protein kinase AKT correlating with reduced toxicity of the mutant in comparison with Sterne. Our global proteomic analysis of lymph from the lymph nodes of infected mice harboring bacteria revealed numerous changes in the pattern and levels of proteins associated with the activity of bNOS influencing key cell physiological processes relevant to energy metabolism, growth, signal transduction, stress response, septic shock and homeostasis. This is the first in vivo observation of the bacterial NO effect on the

  7. Influence of environmental ammonia on the production of nitric oxide and expression of inducible nitric oxide synthase in the freshwater air-breathing catfish (Heteropneustes fossilis)

    Energy Technology Data Exchange (ETDEWEB)

    Choudhury, Mahua G. [Biochemical Adaptation Laboratory, Department of Zoology, North-Eastern Hill University, Shillong 793022 (India); Saha, Nirmalendu, E-mail: nsaha@nehu.ac.in [Biochemical Adaptation Laboratory, Department of Zoology, North-Eastern Hill University, Shillong 793022 (India)

    2012-07-15

    Highlights: Black-Right-Pointing-Pointer High environmental ammonia caused more production and accumulation of NO in air-breathing catfish (Heteropneustes fossilis). Black-Right-Pointing-Pointer Hyper-ammonia stress caused induction and zonal specific expression of iNOS enzyme protein, mRNA expression in different tissues. Black-Right-Pointing-Pointer Activation of NF{kappa}B that resulted under hyper-ammonia stress was believed to be the cause of induction of iNOS gene. - Abstract: Nitric oxide (NO) is a highly versatile and unique ubiquitous signaling molecule, and is known to play diverse physiological functions in mammals including those of adaptation to various stresses. The present study reports on the influence of exposure to high external ammonia (HEA) on the production of nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS), that produces NO from L-arginine in the freshwater air-breathing catfish (Heteropneustes fossilis), which is reported to tolerate a very HEA. Some levels of NO were found to be present in all the tissues and also in plasma of control fish, which further enhanced significantly in fishes treated with high concentrations of environmental ammonia (25 and 50 mM ammonium chloride) for 7 days, accompanied by more efflux of NO from the perfused liver. This was accomplished by the induction of iNOS activity in different tissues of fish exposed to HEA, which otherwise was not detectable in control fish. Exposure to 25 mM ammonium chloride also led to a significant expression of iNOS protein in different tissues, followed by further increase at 50 mM ammonium chloride. Further, there was an increase in the expression of iNOS mRNA in ammonia-treated fish, thus suggesting that the expression of iNOS gene under hyper-ammonia stress was probably regulated at the transcriptional level. Immunocytochemical analysis indicated that the expression of iNOS in different tissues was zonal specific and not expressed uniformly

  8. The biogenic emission potential of nitric oxide from sandy soils

    Science.gov (United States)

    Yu, J. B.; Meixner, F. X.; Sun, Z. G.; Chen, X. B.; Mamtimin, B.

    2009-04-01

    There are about 160.9 Mha of sandy land in China, about 17.6% of total Chinese area, which mainly distributed in 35°-50° N. The western Songnen Plain, which located in the semi-arid region of Northeastern China, is one of the main sandy soil distribution regions. The changes of land use in sandy soil are accompanied by changes in biogeochemical cycles of nutrients, particularly of the air-surface exchange of trace gases like nitric oxide. Our study, based on results obtained by a laboratory incubation technique, focuses on (a) NO production and consumption in sandy soils from two types of land use as function of soil temperature and soil moisture, and (b) The biogenic emission potential of nitric oxide from sandy soils in semi-arid region. At 25˚C, average NO production (in terms of mass of N) was 0.016,and 0.013 ng kg-1s-1 in sandy soils from soybean land (SL) and man-made forest (MF), re¬spectively. NO consumption rate constant ranged from 0.26×10-6 to 7.28×10-6 m3 kg-1s-1. At 25˚C and under optimum soil moisture conditions for NO production, the NO compensation point mixing ratio was about 266 and 161 ug m-3 (465,and 281 ppb) for soils of SL and MF, respectively. Statistically sound relationships have been observed between NO fluxes and soil moisture (optimum curves). NO fluxes also increased exponentially with soil temperature at any given soil moisture. The optimum soil moisture for which maximum NO flux was observed was independent of soil temperature. The maximum of NO flux potentials for SL and MF soils (at 25°C) were 59.6 and 36.5 ng m-2s-1 at water-filled pore space (%WFPS) of 26 and 24, respectively. The NO flux potential was about 2 times larger for cropland soil than for man-made forest soils, most likely due to fertilizer application to the cropland soils.

  9. Increase nitric oxide and oxidative stress in dogs experimentally infected by Ehrlichia canis: effect on the pathogenesis of the disease.

    Science.gov (United States)

    Da Silva, Aleksandro S; Munhoz, Thiago D; Faria, Joice L M; Vargas-Hérnandez, Giovanni; Machado, Rosangela Z; Almeida, Taís C; Moresco, Rafael N; Stefani, Lenita M; Tinucci-Costa, Mirela

    2013-06-28

    The aim of this study was to evaluate nitric oxide levels, lipid peroxidation, protein oxidation and glutathione reductase activity in serum of dogs experimentally infected by Ehrlichia canis. Banked serum samples of dogs divided into two groups were used: negative control (n=5) and infected by E. canis (n=5). The concentration of nitrite/nitrate (NOx), lipid peroxidation (TBARS), advanced oxidation protein products (AOPP), and glutathione reductase (GR) activity in sera were evaluated. Samples were collected on days 0, 3, 6, 18 and 30 post-infection (PI). NOx and TBARS levels were significantly (Pcanis on days 18 and 30 PI. Based on the increased levels of NOx, TBARS, AOPP and GR activity we concluded that dogs experimentally infected by E. canis develop a state of redox imbalance and that these changes might be involved in the pathophysiology of the disease.

  10. The red-vine-leaf extract AS195 increases nitric oxide synthase-dependent nitric oxide generation and decreases oxidative stress in endothelial and red blood cells.

    Science.gov (United States)

    Grau, Marijke; Bölck, Birgit; Bizjak, Daniel Alexander; Stabenow, Christina Julia Annika; Bloch, Wilhelm

    2016-02-01

    The red-vine-leaf extract AS195 improves cutaneous oxygen supply and the microcirculation in patients suffering from chronic venous insufficiency. Regulation of blood flow was associated to nitric oxide synthase (NOS)-dependent NO (nitric oxide) production, and endothelial and red blood cells (RBC) have been shown to possess respective NOS isoforms. It was hypothesized that AS195 positively affects NOS activation in human umbilical vein endothelial cells (HUVECs) and RBC. Because patients with microvascular disorders show increased oxidative stress which limits NO bioavailability, it was further hypothesized that AS195 increases NO bioavailability by decreasing the content of reactive oxygen species (ROS) and increasing antioxidant capacity. Cultured HUVECs and RBCs from healthy volunteers were incubated with AS195 (100 μmol/L), tert-butylhydroperoxide (TBHP, 1 mmol/L) to induce oxidative stress and with both AS195 and TBHP. Endothelial and red blood cell-nitric oxide synthase (RBC-NOS) activation significantly increased after AS195 incubation. Nitrite concentration, a marker for NO production, increased in HUVEC but decreased in RBC after AS195 application possibly due to nitrite scavenging potential of flavonoids. S-nitrosylation of RBC cytoskeletal spectrins and RBC deformability were increased after AS195 incubation. TBHP-induced ROS were decreased by AS195, and antioxidative capacity was significantly increased in AS195-treated cells. TBHP also reduced RBC deformability, but reduction was attenuated by parallel incubation with AS195. Adhesion of HUVEC was also reduced after AS195 treatment. Red-vine-leaf extract AS195 increases NOS activation and decreases oxidative stress. Both mechanisms increase NO bioavailability, improve cell function, and may thus account for enhanced microcirculation in both health and disease.

  11. Effect of Helicobacter pylori infection on gastric mucosal pathologic change and level of nitric oxide and nitric oxide synthase

    Institute of Scientific and Technical Information of China (English)

    Yong-Fu Wang; Chun-Lin Guo; Li-Zhen Zhao; Guo-An Yang; Peng Chen; Hong-Kun Wang

    2005-01-01

    AIM: To investigate the level of nitric oxide (NO) and nitrous oxide synthase (NOS) enzyme and its effect on gastric mucosal pathologic change in patients infected with Helicobacter pylori (H pylori), and to study the pathogenic mechanism of H pylori.METHODS: The mucosal tissues of gastric antrum were taken by endoscopy, then their pathology, H pylori and anti-CagA-IgG were determined. Fifty H pyloripositive cases and 35 H pylori negative cases were randomly chosen.Serum level of NO and NOS was detected.RESULTS: One hundred and seven cases (71.33%) were anti-CagA-IgG positive in 150 H pyloripositive cases. The positive rate was higher especially in those with preneoplastic diseases, such as atrophy, intestinal metaplasia and dysplasia. The level of NO and NOS in positive group was higher than that in negative group, and apparently lower in active gastritis than in pre-neoplastic diseases such as atrophy, intestinal metaplasia and dysplasia.CONCLUSION: H pyloriis closely related with chronic gastric diseases, and type Ⅰ Hpylorimay be the real factor for Hpylori-related gastric diseases. Infection with H pylori can induce elevation of NOS, which produces NO.

  12. Diagnostic and prognostic value of serum nitric oxide, tumor necrosis factor-alpha, basic fibroblast growth factor and copper as angiogenic markers in premenopausal breast cancer patients: a case-control study.

    Science.gov (United States)

    Hewala, T I; Abd El-Moneim, N A; Ebied, S Abd El-Moneim; Sheta, M I; Soliman, K; Abu-Elenean, A

    2010-01-01

    Many studies demonstrate that increased microvessel density (MVD) surrounding primary tumour is associated with decreased overall survival in patients with breast cancer. This study compares the diagnostic and prognostic values of the angiogenic serum factors nitric oxide (NO), tumour necrosis factor-alpha (TNFalpha), basic fibroblast growth factor (bFGF) and copper with those of serum CA15-3 as the standard tumour marker in breast cancer patients. Microvessel density was estimated in CD31-immunostained sections from breast cancer patients. Before surgery, NO, TNFalpha, bFGF, copper and CA 15-3 were measured in serum samples from 30 premenopausal breast cancer patients in comparison with 15 healthy controls. The diagnostic values of the assayed parameters were compared using receiver operating characteristic (ROC) curve analysis. Univariate survival analysis of patients was assessed using the Kaplan-Meier method. Breast cancer tissues showed higher MVD than did normal breast tissues adjacent to the tumour (P = 0.008). Before surgery, tumour MVD correlated significantly with serum NO, TNFalpha, bFGF and copper (r = 0.458, P = .011; r = 0.379, P = .039; r = 0.513, P = .004 and r = 0.613, P = 0.000, respectively). Serum NO, TNFalpha, bFGF, copper and CA 15-3 levels in patients were significantly elevated compared with controls (P = 0.011, P = 0.004, P = 0.039, P = 0.000 and P = 0.001, respectively). Kaplan-Meier analysis revealed that patients with elevated serum TNFalpha, CA 15-3 and copper (P = 0.035, P = 0.040, P = 0.0339, respectively) had an overall survival significantly shorter than those who had lower levels of these parameters. These data suggest that serum TNFalpha, CA 15-3 and copper are useful predictive markers for overall survival in premenopausal breast cancer patients.

  13. Investigation on binding of nitric oxide to horseradish peroxidase by absorption spectrometry

    Science.gov (United States)

    Qiang, Li; Zhu, Shuhua; Ma, Hongmei; Zhou, Jie

    2010-01-01

    Binding of nitric oxide to horseradish peroxidase (HRP) has been investigated by absorption spectrometry in 0.2 M anaerobic phosphate buffer solution (pH 7.4). Based on this binding equilibrium, a model equation for evaluating the binding constant of nitric oxide to HRP is developed and the binding constant is calculated to be (1.55 ± 0.06) × 10 4 M -1, indicating that HRP can form a stable complex with nitric oxide. The type of inhibition by nitric oxide is validated on the basis of studying initial reaction rates of HRP-catalyzed oxidation of guaiacol in the presence of hydrogen peroxide and nitric oxide. The inhibition mechanism is found to follow an apparent non-competitive inhibition by Lineweaver-Burk method. Based on this kinetic mechanism, the binding constant is also calculated to be (5.22 ± 0.06) × 10 4 M -1. The values of the binding constant determined by the two methods are almost identical. The non-competitive inhibition model is also applicable to studying the effect of nitric oxide on other metalloenzymes, which catalyze the two-substrate reaction with the "ping-pong" mechanism.

  14. Effects of moderate electrical stimulation on reactive species production by primary rat skeletal muscle cells: cross talk between superoxide and nitric oxide production.

    Science.gov (United States)

    Lambertucci, Rafael Herling; Silveira, Leonardo Dos Reis; Hirabara, Sandro Massao; Curi, Rui; Sweeney, Gary; Pithon-Curi, Tania Cristina

    2012-06-01

    The effects of a moderate electrical stimulation on superoxide and nitric oxide production by primary cultured skeletal muscle cells were evaluated. The involvement of the main sites of these reactive species production and the relationship between superoxide and nitric oxide production were also examined. Production of superoxide was evaluated by cytochrome c reduction and dihydroethidium oxidation assays. Electrical stimulation increased superoxide production after 1 h incubation. A xanthine oxidase inhibitor caused a partial decrease of superoxide generation and a significant amount of mitochondria-derived superoxide was also observed. Nitric oxide production was assessed by nitrite measurement and by using 4,5-diaminofluorescein diacetate (DAF-2-DA) assay. Using both methods an increased production of nitric oxide was obtained after electrical stimulation, which was also able to induce an increase of iNOS content and NF-κB activation. The participation of superoxide in nitric oxide production was investigated by incubating cells with DAF-2-DA in the presence or absence of electrical stimulation, a superoxide generator system (xanthine-xanthine oxidase), a mixture of NOS inhibitors and SOD-PEG. Our data show that the induction of muscle contraction by a moderate electrical stimulation protocol led to an increased nitric oxide production that can be controlled by superoxide generation. The cross talk between these reactive species likely plays a role in exercise-induced maintenance and adaptation by regulating muscular glucose metabolism, force of contraction, fatigue, and antioxidant systems activities.

  15. Absorption of nitric oxide into aqueous solutions of ferrous chelates accompanied by instantaneous reaction

    NARCIS (Netherlands)

    Demmink, J.F; vanGils, I.C.F.; Beenackers, A.A C M

    1997-01-01

    The absorption of nitric oxide (NO) into aqueous solutions of ferrous chelates of nitrilotriacetic acid (NTA), ethylene diaminetetraacetic acid (EDTA), hydroxyethylenediaminetriacetic acid (HEDTA), and diethylenetriaminepentaacetic acid (DTPA) was studied in a stirred cell reactor. Experimental cond

  16. Lack of inhibition of endothelial nitric oxide synthase in the isolated rat aorta by doxorubicin.

    NARCIS (Netherlands)

    Hartog, den GJ; Boots, AW; Haenen, GR; Vijgh, van der W.J.F.

    2003-01-01

    Besides inducing cardiotoxicity, doxorubicin also affects the vasculature. Recent observations in cultured endothelial cells indicated that the endothelial form of nitric oxide synthase might be inhibited by doxorubicin thereby seriously interfering with vascular function. We have investigated the

  17. Hypotensive effect of hydroxylamine, an endogenous nitric oxide donor and SSAO inhibitor.

    Science.gov (United States)

    Vidrio, H; Medina, M

    2007-01-01

    The endogenous compound hydroxylamine relaxes vascular smooth muscle in vitro, apparently through conversion to the vasodilator factor nitric oxide, but its effect on blood pressure has not been characterized. We found that in the anesthetized rat the amine elicits dose-related hypotension when administered by continuous iv infusion. In experiments designed to explore the mechanism of this effect, hydroxylamine was compared with the nitric oxide donor nitroprusside and the direct-acting vasodilator hydralazine, using pretreatments known to modify diverse mechanisms of vasodilation. Hydroxylamine hypotension was enhanced by the SSAO inhibitor isoniazid and the SSAO substrate methylamine, a pattern shared by hydralazine. Responses were blocked by the guanylate cyclase inhibitor methylene blue and were increased by the nitric oxide synthase inhibitor L-NAME, a pattern shared by nitroprusside. It was concluded that hydroxylamine exerts hypotension partly through conversion to nitric oxide and partly by a "hydralazine-like" mechanism involving SSAO inhibition.

  18. Kinetic analysis of nitric oxide reduction using biogas as reburning fuel

    African Journals Online (AJOL)

    STORAGESEVER

    2009-05-18

    May 18, 2009 ... reburnning technology potential to reduce NO pollution. Key word: Biomass, biogas, kinetic analysis, modeling, nitric oxide, reburning. INTRODUCTION .... factor A, the temperature β, and the activation energy E are specified.

  19. Role of nitric oxide in capillary perfusion and oxygen delivery regulation during systemic hypoxia

    National Research Council Canada - National Science Library

    Silvia Bertuglia; Andrea Giusti

    2005-01-01

    The role of nitric oxide (NO) and reactive oxygen species (ROS) in regulating capillary perfusion was studied in the hamster cheek pouch model during normoxia and after 20 min of exposure to 10% O2-90% N2...

  20. Protective roles of nitric oxide on antioxidant systems in tall fescue ...

    African Journals Online (AJOL)

    ONOS

    2010-01-18

    Jan 18, 2010 ... Key words: Antioxidant, high-light stress, nitric oxide, tall fescue. INTRODUCTION ... effective molecular reaction or indirect effect of changing potential ... regime of 14/10 h and a photosynthetic photo flux density (PPFD).

  1. Absorption of nitric oxide into aqueous solutions of ferrous chelates accompanied by instantaneous reaction

    NARCIS (Netherlands)

    Demmink, J.F; vanGils, I.C.F.; Beenackers, A.A C M

    1997-01-01

    The absorption of nitric oxide (NO) into aqueous solutions of ferrous chelates of nitrilotriacetic acid (NTA), ethylene diaminetetraacetic acid (EDTA), hydroxyethylenediaminetriacetic acid (HEDTA), and diethylenetriaminepentaacetic acid (DTPA) was studied in a stirred cell reactor. Experimental

  2. Effect of diabetes and insulin treatment on nitric oxide synthase content in rat corpus cavemosum

    Institute of Scientific and Technical Information of China (English)

    Zhi-Shun XU; Qiang FU; Sheng-Tian ZHAO; Hai-Nan LIU

    2001-01-01

    Aim: To study the effect of diabetes mellitus and insulin treatment on rat penile nitric oxide synthase content.Methods: Male Wistar rats were divided at random into two groups: the Control ( n = 8) and the Diabetic ( n =17). Diabetes mellitus was induced by intraperitoneal injection of streptozotocin. The diabetic animals were then ran domly divided into two subgroups: diabetic rats without insulin treatment ( n = 7) and diabetic rats with insulin treat ment ( n = 10). The neuronal nitric oxide synthase (nNOS) in the penile corpus cavemosum were assayed by immrmo histochemical staining with specific antibody to nNOS and the nNOS-positive nerve fibers were counted semiquantita tively under a high power microscope. Results: The nNOS- positive nerve fibres in diabetic rats with treatment was higher than that in diabetic rats without treatment ( P < 0.05) and lower than that in the controls ( P < 0.01 ). The nNOS-positive nerve fibres in diabetic rat without treatment were also lower than that in the controls ( P < 0.01). Con clusion: In streptozotocin-induced diabetic rats, the nNOS content in the penile corpus cavernosum was significantly decre~ed. Insulin treatment at the dose level employed partially restores the penile nNOS content in these rats.

  3. Oxygen Effects on Thermophilic Microbial Populations in Biofilters Treating Nitric Oxide Containing Off-Gas Streams

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Brady Douglas; Apel, William Arnold; Smith, William Aaron

    2004-04-01

    Electricity generation from coal has increased by an average of 51 billion kWh per year over the past 3 years. For this reason cost-effective strategies to control nitrogen oxides (NOx) from coal-fired power plant combustion gases must be developed. Compost biofilters operated at 55°C at an empty bed contact time (EBCT) of 13 seconds were shown to be feasible for removal of nitric oxide (NO) from synthetic flue gas. Denitrifying microbial populations in these biofilters were shown to reduce influent NO feeds by 90 to 95% at inlet NO concentrations of 500 ppmv. Oxygen was shown to have a significant effect on the NO removal efficiency demonstrated by these biofilters. Two biofilters were set up under identical conditions for the purpose of monitoring NO removal as well as changes in the microbial population in the bed medium under anaerobic and aerobic conditions. Changes in the microbial population were monitored to determine the maximum oxygen tolerance of a denitrifying biofilter as well as methods of optimizing microbial populations capable of denitrification in the presence of low oxygen concentrations. Nitric oxide removal dropped to between 10 and 20% when oxygen was present in the influent stream. The inactive compost used to pack the biofilters may have also caused the decreased NO removal efficiency compared to previous biofiltration experiments. Analysis of the bed medium microbial population using environmental scanning electron microscopy indicated significant increases in biomass populating the surface of the compost when compared to unacclimated compost.

  4. Flunisolide Decreases Exhaled Nitric Oxide and Nitrotyrosine Levels in Asthmatic Children

    Science.gov (United States)

    Bodini, A.; Peroni, D. G.; Zardini, F.; Corradi, M.; Alinovi, R.; Boner, A. L.; Piacentini, G. L.

    2006-01-01

    Background. Exhaled nitric oxide (FeNO) has been reported to be elevated in the oxidative stress involved in asthmatic patients, and the reaction of nitric oxide (NO) with superoxide anions results in the formation of nitrotyrosine. The purpose of this study was to investigate the effect of inhaled steroid treatment on nitrotyrosine levels collected by exhaled breath condensate (EBC) and on FeNO. Methods. This was a single-blind placebo-controlled study. The lung function, FeNO, and nitrotyrosine levels were evaluated in 10 asthmatic children. Results. The nitrotyrosine levels were stable during the placebo period (T0 = 1.16 ng/ml versus T1 = 1.05 ng/ml; NS.), whereas they decreased after the treatment with flunisolide (T2 = 1.14 ng/ml versus T3 = 0.88 ng/ml; P < .001). No significant reduction in FeNO levels was observed after placebo treatment (T0 = 38.4 ppb versus T1 = 34.7 ppb, NS.). In contrast, FeNO values decreased significantly being at T3 = 14.9 ppb (T1 versus T3; P = .024). Conclusions. This study shows that corticosteroid treatment reduces nitrotyrosine levels in EBC of asthmatic subjects. PMID:17047290

  5. Expression of nitric oxide synthase in T-cell-dependent liver injury initiated by ConA in Kunming mice

    Institute of Scientific and Technical Information of China (English)

    张修礼; 曲建慧; 万谟彬; 权启镇; 孙自勤; 王要军; 江学良; 李文波

    2004-01-01

    Objective: To investigate whether nitric oxide synthase (NOS) is expressed in T-cell-dependent liver injury initiated by concanavalin A (ConA) in Kunming mice and study the possible effect of nitric oxide(NO) on liver injury models. Methods: Liver injury in Kunming mice was induced by administration of ConA through tail vein. Expression of NOS in the liver was detected by NADPH diaphorase staining method. The possible effect of NO on liver injury models was obtained by L-NAME injection to suppress synthesis of NO. Results: NOS has a strong expression in hepatocytes after ConA injection, especially in those close to the central vein, while only a weak expression was found in the epithelial cells in control group. Liver injury became more serious when NO synthesis was inhibited by L-NAME, accompanied by great malondialdehyde(MDA) increase in serum and severe intrahepatic vascular thrombosis. Conclusion: NOS markedly expressed in ConAinduced liver injury, which may subsequently promote nitric oxide synthesis. Increasement of nitric oxide has a protective effect on ConA-induced liver injury.

  6. The effect of piracetam on brain damage and serum nitric oxide levels in dogs submitted to hemorrhagic shock.

    Science.gov (United States)

    Ozkan, Seda; Ikizceli, Ibrahim; Sözüer, Erdoğan Mütevelli; Avşaroğullari, Levent; Oztürk, Figen; Muhtaroğlu, Sebahattin; Akdur, Okhan; Küçük, Can; Durukan, Polat

    2008-10-01

    To demonstrate the effect of piracetam on changes in brain tissue and serum nitric oxide levels in dogs submitted to hemorrhagic shock. The subjects were randomized into four subgroups each consisting of 10 dogs. Hemorrhagic shock was induced in Group I for 1 hour and no treatment was given to this group. Blood and saline solutions were administered to Group II following 1 hour hemorrhagic shock. Blood and piracetam were given to Group III following 1 hour shock. No shock was induced and no treatment was applied to Group IV. Blood samples were obtained at the onset of the experiment and at 60, 120 and 180 minutes for nitric oxide analysis. For histopathological examination, brain tissue samples were obtained at the end of the experiment. The observed improvement in blood pressure and pulse rates in Group III was more than in Group II. Nitric oxide levels were increased in Group I; however, no correlation between piracetam and nitric oxide levels was determined. It was seen that recovery in brain damage in Group III was greater than in the control group. Piracetam, added to the treatment, may ecrease ischemic damage in hemorrhagic shock.

  7. The Main Plasma Chemical Process of Nitric Oxide Production by Arc Discharge%The Main Plasma Chemical Process of Nitric Oxide Production by Arc Discharge

    Institute of Scientific and Technical Information of China (English)

    杨旗; 胡辉; 陈卫鹏; 许杰; 张锦丽; 吴双

    2011-01-01

    By adopting the optical multi-channel analyzer combined with fourier transform infrared (FTIR) spectrometer, the dominant free radicals and products generated by arc discharge were measured and studied, and the main plasma chemical reaction process in the nitric oxide production by arc discharge was identified. Plasma chemical kinetic curves of O, O2, N2, N and NO were simulated by using CHEMKIN and MATLAB. The results show that the main plasma chemical reaction process of nitric oxide production by arc discharge is a replacement reaction between O and N2, where NO can be generated instantaneously when discharging reaches stable.

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Neuronal nitric oxide synthase-deficient mice have impaired Renin release but normal blood pressure

    DEFF Research Database (Denmark)

    Sällström, Johan; Carlström, Mattias; Jensen, Boye L

    2008-01-01

    BackgroundNitric oxide deficiency is involved in the development of hypertension, but the mechanisms are currently unclear. This study was conducted to further elucidate the role of neuronal nitric oxide synthase (nNOS) in blood pressure regulation and renin release in relation to different sodiu......-116; doi:10.1038/ajh.2007.16American Journal of Hypertension (2008) 21 111-116; doi:10.1038/ajh.2007.16....

  10. Conversion of nitrite to nitric oxide at zinc via S-nitrosothiols.

    Science.gov (United States)

    Cardenas, Allan Jay P; Abelman, Rebecca; Warren, Timothy H

    2014-01-07

    Nitrite is an important reservoir of nitric oxide activity in the plasma and cells. Using a biomimetic model, we demonstrate the conversion of zinc-bound nitrite in the tris(pyrazolyl)borate complex (iPr2)TpZn(NO2) to the corresponding S-nitrosothiol RSNO and zinc thiolate (iPr2)TpZn-SR via reaction with thiols H-SR. Decomposition of the S-nitrosothiol formed releases nitric oxide gas.

  11. Nitric oxide synthetase and Helicobacter pylori in patients undergoing appendicectomy.

    LENUS (Irish Health Repository)

    Kell, M R

    2012-02-03

    BACKGROUND: This study was designed to determine whether Helicobacter pylori forms part of the normal microenvironment of the appendix, whether it plays a role in the pathogenesis of acute appendicitis, and whether it is associated with increased expression of inducible nitric oxide synthetase (iNOS) in appendicular macrophages. METHODS: Serology for H. pylori was performed on 51 consecutive patients undergoing emergency appendicectomy. Appendix samples were tested for urease activity, cultured and stained for H. pylori, graded according to the degree of inflammatory infiltrate, and probed immunohistochemically for iNOS expression. RESULTS: The mean age of the patients was 21 (range 7-51) years. Seventeen patients (33 per cent) were seropositive for H. pylori but no evidence of H. pylori was found in any appendix specimen. However, an enhanced inflammatory cell infiltration was observed in seropositive patients (P < 0.04) and the expression of macrophage iNOS in the mucosa of normal and inflamed appendix specimens was increased (P < 0.01). CONCLUSION: H. pylori does not colonize the appendix and is unlikely to be a pathogenic stimulus for appendicitis. Priming effects on mucosal immunology downstream from the foregut may occur after infection with H. pylori.

  12. Molecular regulation of tumour angiogenesis by nitric oxide.

    Science.gov (United States)

    Ziche, Marina; Morbidelli, Lucia

    2009-12-01

    As tumors grow, their original vasculature can be insufficient to supply the growing tissue mass, and consequently local hypoxia develops. Thus neovascularisation is a key feature determining growth and metastasis of malignant tumors. This is, at least in part, mediated by humoral factors known to stimulate angiogenesis, such as vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2). Among the multiple angiogenic modulators released by tumor and stromal cells, a key role is played by nitric oxide (NO). Beside its capacity to regulate permeability and blood flow, NO has been reported to exert angiogenic properties in various tumor models. The focus of this review will be the proangiogenic role of NO in the tumor microenvironment and its multiple mechanism of action on vascular endothelium. Particular attention will be devoted to the role of NO in regulating metalloproteinase activity on cultured microvascular endothelium and in the in vivo rabbit cornea assay. Finally, the potential clinical outcomes and expectations related to this topic will be discussed.

  13. Molecular dynamics simulation of nitric oxide in myoglobin

    Science.gov (United States)

    Lee, Myung Won; Meuwly, Markus

    2012-01-01

    The infrared (IR) spectroscopy and ligand migration of photodissociated nitric oxide (NO) in and around the active sites in myoglobin (Mb) are investigated. A distributed multipolar model for open-shell systems is developed and used, which allows one to realistically describe the charge distribution around the diatomic probe molecule. The IR spectra were computed from the trajectories for two conformational substates at various temperatures. The lines are narrow (width of 3–7 cm–1 at 20–100 K), in agreement with the experimental observations where they have widths of 4–5 cm–1 at 4 K. It is found that within one conformational substate (B or C) the splitting of the spectrum can be correctly described compared with recent experiments. Similar to photodissociated CO in Mb, additional substates exist for NO in Mb, which are separated by barriers below 1 kcal/mol. Contrary to full quantum mechanical calculations, however, the force field and mixed QM/MM simulations do not correctly describe the relative shifts between the B- and C-states relative to gas-phase NO. Free energy simulations establish that NO preferably localizes in the distal site and the barrier for migration to the neighboring Xe4 pocket is ΔGB→C = 1.7–2.0 kcal/mol. The reverse barrier is ΔGB←C = 0.7 kcal/mol, which agrees well with the experimental value of 0.7 kcal/mol, estimated from kinetic data.

  14. Regulation between nitric oxide and MAPK signal transduction in mammals

    Institute of Scientific and Technical Information of China (English)

    TAO Yong; ZHANG Meijia; HONG Haiyan; XIA Guoliang

    2005-01-01

    Nitric oxide (NO) is an important biological messenger in the regulation of tissue homeostasis. It exhibits a wide range of effects during physiological and pathophysiological processes. Typical beneficial properties of NO include the regulation of vascular tone,the protection of cells against apoptosis, the modulation of immune responses, and the killing of microbial pathogens. On the other hand,NO may cause severe vasodilation and myocardial depression during bacterial sepsis or act as a cytotoxic and tissue-damaging molecule in autoimmune diseases. Mitogen-activated protein kinase (MAPK) is a family of serine/threonine protein kinases that are widely distributed in mammalian cells. MAPK cascade plays pivotal roles in gene expression, cell proliferation, differentiation, neuronal survival and programmed cell death under a variety of experimental conditions. MAPKs transduce the signal for the cellular response to extracellular stresses or stimuli. The relation between them, however, has never been reviewed. Based on our researches and other reports in the field, we review their reciprocal regulatory functions.

  15. Excitatory response of rabbit myometrium to nitric oxide in vitro.

    Science.gov (United States)

    Nakanishi, H; Matsuoka, I; Ono, T; Okawa, T; Katahira, K; Nakahata, N

    1996-05-01

    Nitric oxide (NO) at high concentration (approx. 33 microM) produced a marked excitation: increase of tension development or increase in amplitude of spontaneous contraction, in 7 out of 8 rabbit nonpregnant myometrial strips. One case produced an inhibition: disappearance of spontaneous contraction. A latent period of several sec usually preceded the excitation. The response of the myometrium to NO approx. 33 microM associated with remarkable increase in tissue cyclic GMP levels. NO approx. 33 microM reduced an inhibition, in 1 out of 3 myometrial strips taken from ovariectomized rabbits. Two cases produced an excitatory. A precursor of NO, L-Arginine 100 microM or an inhibitor of NO synthase, NG-nitro-L-arginine 100 microM also produced a transient weak excitatory response. On the contrary, 8-bromo-cyclic GMP 100 microM produced an inhibition. The excitatory response to NO 33 microM was almost unaffected by pretreatment with indomethacin 10 microM, whereas the spontaneous motility was remarkably depressed. The contractile response of the isolated rabbit myometrium to electrical field stimulation was almost unaffected by the pretreatment with L-arginine 100 microM or NG-nitro-L-arginine 100 microM. The present findings may indicate that NO has inhibitory and excitatory components on the mechanical activity of the rabbit isolated myometrium.

  16. Reference values for exhaled nitric oxide (reveno study

    Directory of Open Access Journals (Sweden)

    Mutti Antonio

    2006-06-01

    Full Text Available Abstract Background Despite the widespread use of fractional exhaled nitric oxide (FENO as a biomarker of airways inflammation, there are no published papers describing normal FENO values in a large group of healthy adults. Objective The aim of this study was to establish adult FENO reference values according to the international guidelines. Methods FENO was measured in 204 healthy, non-smoking adults with normal spirometry values using the on-line single-breath technique, and the results were analysed chemiluminescently. Results The main result of the study was the significant difference in FENO values between men and women, thus indicating that gender-based reference FENO values are necessary. The FENO levels obtained at expiratory flows of 50 ml/s ranged from 2.6 to 28.8 ppb in men, and from 1.6 to 21.5 ppb in women. Conclusion We propose reference FENO values for healthy adult men and women that could be used for clinical and research purposes.

  17. Interplay Among Nitric Oxide and Reactive Oxygen Species

    Science.gov (United States)

    2007-01-01

    Programmed cell death (PCD) is an integrated cellular process occurring in plant growth, development, and defense responses to facilitate normal growth and development and better survival against various stresses as a whole. As universal toxic chemicals in plant and animal cells, reactive oxygen or nitrogen species (ROS or RNS), mainly superoxide anion (O2−•), hydrogen peroxide (H2O2) or nitric oxide (•NO), have been studied extensively for their roles in PCD induction. Physiological and genetic studies have convincingly shown their essential roles. However, the details and mechanisms by which ROS and •NO interplay and induce PCD are not well understood. Our recent study on Cupressus lusitanica culture cell death revealed the elicitor-induced co-accumulation of ROS and •NO and interactions between •NO and H2O2 or O2-• in different ways to regulate cell death. •NO and H2O2 reciprocally enhanced the production of each other whereas •NO and O2−• showed reciprocal suppression on each other's production. It was the interaction between •NO and O2-• but not between •NO and H2O2 that induced PCD, probably through peroxynitrite (ONOO−). In this addendum, some unsolved issues in the study were discussed based on recent studies on the complex network of ROS and •NO leading to PCD in animals and plants. PMID:19704554

  18. Hemolysis-Associated Nitric Oxide Dysregulation during Extracorporeal Membrane Oxygenation

    Science.gov (United States)

    Sulkowski, Jason P.; Cooper, Jennifer N.; Pearson, Erik G.; Connelly, James T.; Rintoul, Natalie; Kilbaugh, Todd J.; Deans, Katherine J.; Minneci, Peter C.

    2014-01-01

    Abstract: Acute intravascular hemolysis during extracorporeal membrane oxygenation (ECMO) leads to increased levels of cell-free hemoglobin (FHb). Our aim was to investigate whether FHb levels are associated with nitric oxide (NO) consumption and clinical outcomes. A prospective observational study was performed involving pediatric patients on ECMO. Blood samples were collected before, during, and after the ECMO run, and plasma was evaluated for FHb, oxyhemoglobin, and NO consumption. Clinical data were collected including baseline patient characteristics, indications for ECMO, circuit changes, and mortality. Correlations between laboratory measures and associations between laboratory measures and clinical observations were evaluated. Twenty-three patients (11 male, 17 neonates) were enrolled with a median weight of 3.1 kg (interquartile range, 2.8–14.0 kg) and median ECMO run of 12 days (interquartile range, 5–19 day). There was a significant increase in FHb over time on ECMO (p = .007), and significant correlations were present between NO consumption and both FHb (r = .41, p = .01) and oxyhemoglobin levels (r = .98, p hemolysis and type of ECMO (venovenous versus venoarterial) or mortality. For children on ECMO, we observed a strong correlation between increased levels of plasma FHb and elevations in oxyhemoglobin and NO consumption; however, these changes were not associated with increased mortality. Increased hemolysis before circuit changes may be both a marker and a contributor to circuit failure. PMID:26357787

  19. Adenovirus-mediated nitric oxide synthase gene transfer.

    Science.gov (United States)

    Raman, Kathleen G; Shapiro, Richard A; Tzeng, Edith; Kibbe, Melina R

    2004-01-01

    The varied biological effects of nitric oxide (NO) have led to intense research into its diverse physiologic and pathophysiologic roles in multiple disease processes. It has been implicated in the development of altered vasomotor tone, intimal hyperplasia, atherosclerosis, impotence, host defense, and wound healing. Using the modern technologies of recombinant DNA and gene transfer using adenoviral vectors, the effects of NO derived from various NO synthase (NOS) enzymes can be studied in a variety of tissues and the therapeutic applications of NOS is possible. Such uses of NOS gene transfer have been investigated extensively in the vasculature where NO is critical to regulating vascular homeostasis. NOS gene therapy has the theoretical advantage of allowing NO delivery to be localized, thereby limiting potential adverse effects of NO. The benefits of adenoviral vectors in gene transfer include relatively high transduction efficiencies, both replicating and nonreplicating cells may be infected, and the high titers of adenovirus that can be produced. The methods described in this chapter include the cloning of the iNOS cDNA into a recombinant adenoviral vector, large-scale production of that vector AdiNOS preparation, and the use of the vector to transduce tissue in vitro and in vivo.

  20. Disruption of Fas Receptor Signaling by Nitric Oxide in Eosinophils

    Science.gov (United States)

    Hebestreit, Holger; Dibbert, Birgit; Balatti, Ivo; Braun, Doris; Schapowal, Andreas; Blaser, Kurt; Simon, Hans-Uwe

    1998-01-01

    It has been suggested that Fas ligand–Fas receptor interactions are involved in the regulation of eosinophil apoptosis and that dysfunctions in this system could contribute to the accumulation of these cells in allergic and asthmatic diseases. Here, we demonstrate that nitric oxide (NO) specifically prevents Fas receptor–mediated apoptosis in freshly isolated human eosinophils. In contrast, rapid acceleration of eosinophil apoptosis by activation of the Fas receptor occurs in the presence of eosinophil hematopoietins. Analysis of the intracellular mechanisms revealed that NO disrupts Fas receptor–mediated signaling events at the level of, or proximal to, Jun kinase (JNK), but distal to sphingomyelinase (SMase) activation and ceramide generation. In addition, activation of SMase occurs downstream of an interleukin 1 converting enzyme–like (ICE-like) protease(s) that is not blocked by NO. However, NO prevents activation of a protease that targets lamin B1. These findings suggest a role for an additional NO-sensitive apoptotic signaling pathway that amplifies the proteolytic cascade initialized by activation of the Fas receptor. Therefore, NO concentrations within allergic inflammatory sites may be important in determining whether an eosinophil survives or undergoes apoptosis upon Fas ligand stimulation. PMID:9449721

  1. The Role of Nitric Oxide from Neurological Disease to Cancer.

    Science.gov (United States)

    Maher, Ahmed; Abdel Rahman, Mohamed F; Gad, Mohamed Z

    2017-01-01

    Until the beginning of the 1980s, nitric oxide (NO) was just a toxic molecule of a lengthy list of environmental pollutants such as cigarette smoke and smog. In fact, NO had a very bad reputation of being destroyer of ozone, suspected carcinogen and precursor of acid rain. However, by the early 1990s it was well recognized by the medical research community. Over the last two decades, the picture has been totally changed. Diverse lines of evidence have converged to show that this sometime poison is a fundamental player in the everyday business of the human body. NO activity was probed in the brain, arteries, immune system, liver, pancreas, uterus, peripheral nerves, lungs, and almost every system in the human body. NO is a major player in the cardiovascular system as it is involved in regulating blood pressure. In the CNS, it is involved in memory formation and the regulation of cerebral blood flow to ensure adequate supply of blood to the brain. Because NO is involved in many pathways, it has a role in several diseases related to modern life as hypertension, coronary heart diseases, Alzheimer's Disease, stroke and cancer. This chapter focuses on the discussion of the role of NO in neurological diseases and cancer and how can this Janus-faced molecule play a role in the pathology and personalized treatment of these diseases.

  2. Nitric oxide cycle in mammals and the cyclicity principle.

    Science.gov (United States)

    Reutov, V P

    2002-03-01

    This paper continues a series of reports considering nitric oxide (NO) and its cyclic conversions in mammals. Numerous facts are summarized with the goal of developing a general concept that would allow the statement of the multiple effects of NO on various systems of living organisms in the form of a short and comprehensive law. The current state of biological aspects of NO research is analyzed in term of elucidation of possible role of these studies in the system of biological sciences. The general concept is based on a notion on cyclic conversions of NO and its metabolites. NO cycles in living organisms and nitrogen turnover in the biosphere and also the Bethe nitrogen-carbon cycle in star matter are considered. A hypothesis that the cyclic organization of processes in living organisms and the biosphere reflects the evolution of life is proposed: the development of physiological functions and metabolism are suggested to be closely related to space and evolution of the Earth as a planet of the Solar System.

  3. Effect of Electrode Configuration on Nitric Oxide Gas Sensor Behavior

    Directory of Open Access Journals (Sweden)

    Ling Cui

    2015-09-01

    Full Text Available The influence of electrode configuration on the impedancemetric response of nitric oxide (NO gas sensors was investigated for solid electrochemical cells [Au/yttria-stabilized zirconia (YSZ/Au]. Fabrication of the sensors was carried out at 1050 °C in order to establish a porous YSZ electrolyte that enabled gas diffusion. Two electrode configurations were studied where Au wire electrodes were either embedded within or wrapped around the YSZ electrolyte. The electrical response of the sensors was collected via impedance spectroscopy under various operating conditions where gas concentrations ranged from 0 to 100 ppm NO and 1%–18% O2 at temperatures varying from 600 to 700 °C. Gas diffusion appeared to be a rate-limiting mechanism in sensors where the electrode configuration resulted in longer diffusion pathways. The temperature dependence of the NO sensors studied was independent of the electrode configuration. Analysis of the impedance data, along with equivalent circuit modeling indicated the electrode configuration of the sensor effected gas and ionic transport pathways, capacitance behavior, and NO sensitivity.

  4. The effect of high altitude on nasal nitric oxide levels.

    Science.gov (United States)

    Altundag, Aytug; Salihoglu, Murat; Cayonu, Melih; Cingi, Cemal; Tekeli, Hakan; Hummel, Thomas

    2014-09-01

    The aim of the present study was to investigate whether nasal nitric oxide (nNO) levels change in relation to high altitude in a natural setting where the weather conditions were favorable. The present study included 41 healthy volunteers without a history of acute rhinosinusitis within 3 weeks and nasal polyposis. The study group consisted of 31 males (76 %) and 10 females (24 %) and the mean age of the study population was 38 ± 10 years. The volunteers encamped for 2 days in a mountain village at an altitude of 1,500 m above sea level (masl) and proceeded to highlands at an altitude of 2,200 masl throughout the day. The measurements of nNO were done randomly, either first at the mountain village or at sea level. Each participant had nNO values both at sea level and at high altitude at the end of the study. The nNO values of sea level and high altitude were compared to investigate the effect of high altitude on nNO levels. The mean of average nNO measurements at the high altitude was 74.2 ± 41 parts-per-billion (ppb) and the mean of the measurements at sea level was 93.4 ± 45 ppb. The change in nNO depending on the altitude level was statistically significant (p high altitude even if the weather conditions were favorable, such as temperature, humidity, and wind.

  5. Nitric oxide synthase is induced in sporulation of Physarum polycephalum

    Science.gov (United States)

    Golderer, Georg; Werner, Ernst R.; Leitner, Stefan; Gröbner, Peter; Werner-Felmayer, Gabriele

    2001-01-01

    The myxomycete Physarum polycephalum expresses a calcium-independent nitric oxide (NO) synthase (NOS) resembling the inducible NOS isoenzyme in mammals. We have now cloned and sequenced this, the first nonanimal NOS to be identified, showing that it shares Physarum macroplasmodia during the 5-day starvation period needed to induce sporulation competence. Induction of both NOS and sporulation competence were inhibited by glucose, a growth signal and known repressor of sporulation, and by l-N6–(1-iminoethyl)-lysine (NIL), an inhibitor of inducible NOS. Sporulation, which is triggered after the starvation period by light exposure, was also prevented by 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ), an inhibitor of NO-sensitive guanylate cyclase. In addition, also expression of lig1, a sporulation-specific gene, was strongly attenuated by NIL or ODQ. 8-Bromo-cGMP, added 2 h before the light exposure, restored the capacity of NIL-treated macroplasmodia to express lig1 and to sporulate. This indicates that the second messenger used for NO signaling in sporulation of Physarum is cGMP and links this signaling pathway to expression of lig1. PMID:11358872

  6. Thermospheric Nitric Oxide Response to Shock-led Storms.

    Science.gov (United States)

    Knipp, D J; Pette, D V; Kilcommons, L M; Isaacs, T L; Cruz, A A; Mlynczak, M G; Hunt, L A; Lin, C Y

    2017-02-01

    We present a multi-year superposed epoch study of the Sounding of the Atmosphere using Broadband Emission Radiometry nitric oxide (NO) emission data. NO is a trace constituent in the thermosphere that acts as cooling agent via infrared (IR) emissions. The NO cooling competes with storm time thermospheric heating resulting in a thermostat effect. Our study of nearly 200 events reveals that shock-led interplanetary coronal mass ejections (ICMEs) are prone to early and excessive thermospheric NO production and IR emissions. Excess NO emissions can arrest thermospheric expansion by cooling the thermosphere during intense storms. The strongest events curtail the interval of neutral density increase and produce a phenomenon known as thermospheric 'overcooling'. We use Defense Meteorological Satellite Program particle precipitation data to show that interplanetary shocks and their ICME drivers can more than double the fluxes of precipitating particles that are known to trigger the production of thermospheric NO. Coincident increases in Joule heating likely amplify the effect. In turn, NO emissions more than double. We discuss the roles and features of shock/sheath structures that allow the thermosphere to temper the effects of extreme storm time energy input and explore the implication these structures may have on mesospheric NO. Shock-driven thermospheric NO IR cooling likely plays an important role in satellite drag forecasting challenges during extreme events.

  7. Nitric oxide and its role in ischaemic brain injury.

    Science.gov (United States)

    Keynes, Robert G; Garthwaite, John

    2004-03-01

    The role of the neural messenger nitric oxide (NO) in cerebral ischaemia has been investigated extensively in the past decade. NO may play either a protective or destructive role in ischaemia and the literature is plagued with contradictory findings. Working with NO presents many unique difficulties and here we review the potential artifacts that may have contributed to discrepancies and cause future problems for the unwary investigator. Recent evidence challenges the idea that NO from neurones builds up to levels (micromolar) sufficient to directly elicit cell death during the post-ischaemic period. Concomitantly, the case is strengthened for a role of NO in delayed death mediated post-ischaemia by the inducible NO synthase. Mechanistically it seems unlikely that NO is released in high enough quantities to inhibit respiration in vivo; the formation of reactive nitrogen species, such as peroxynitrite, represents the more likely pathway to cell death. The protective and restorative properties of NO have become of increasing interest. NO from endothelial cells may, via stimulating cGMP production, protect the ischaemic brain by acutely augmenting blood flow, and by helping to form new blood vessels in the longer term (angiogenesis). Elevated cGMP production may also stop cells dying by inhibiting apoptosis and help repair damage by stimulating neurogenesis. In addition NO may act as a direct antioxidant and participate in the triggering of protective gene expression programmes that underlie cerebral ischaemic preconditioning. Better understanding of the molecular mechanisms by which NO is protective may ultimately identify new potential therapeutic targets.

  8. Human leucocytes in asthenozoospermic patients: endothelial nitric oxide synthase expression.

    Science.gov (United States)

    Buldreghini, E; Hamada, A; Macrì, M L; Amoroso, S; Boscaro, M; Lenzi, A; Agarwal, A; Balercia, G

    2014-12-01

    In a basic study at the Andrology Unit, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, Ancona, Italy, we evaluated the pattern of mRNA endothelial nitric oxide synthase (eNOS) expression in human blood leucocytes isolated from normozoospermic fertile and asthenozoospermic infertile men to elucidate any pathogenic involvement in sperm cell motility. Forty infertile men with idiopathic asthenozoospermia and 45 normozoospermic fertile donors, age-matched, were included. Semen parameters were evaluated, and expression analysis of mRNA was performed in human leucocytes using reverse transcription polymerase chain reaction. Sperm volume, count, motility and morphology were determined, and eNOS expression and Western blotting analyses were performed. A positive correlation was observed between the concentrations of NO and the percentage of immotile spermatozoa. The mRNA of eNOS was more expressed in peripheral blood leucocytes isolated from asthenozoospermic infertile men versus those of fertile normozoospermic men (7.46 ± 0.38 versus 7.06 ± 0.56, P = 0.0355). A significant up-regulation of eNOS gene in peripheral blood leucocytes was 1.52-fold higher than that of fertile donors. It is concluded that eNOS expression and activity are enhanced in blood leucocytes in men with idiopathic asthenozoospermia.

  9. Nasal nitric oxide in children with recurrent acute otitis media.

    Science.gov (United States)

    Torretta, S; Marchisio, P; Capaccio, P; Pignataro, L

    2016-01-01

    Recently, reduced Nasal nitric oxide (nNO) nNO levels have been reported in children with adenoidal hypertrophy predisposing to chronic nasosinusal inflammation. Given the strict anatomic and physiopathologic link between the nasopharyngeal and middle ear compartments, and considering the high prevalence of otitis prone children among those affected with chronic adenoiditis, we designed a study aimed to test any possible difference in nNO levels between non-allergic children with and without recurrent acute otitis media (RAOM) associated with chronic adenoiditis. The study involved 54 children with RAOM (44.4% males; mean age= 7.5±3.5 years) and 51 children without RAOM (47.4% males; mean age= 7.0±3.8 years). nNO levels were significantly reduced in children with RAOM compared to children without RAOM (676.9±250.7 ppb vs 831.8±320.4 ppb, respectively; p= 0.02). Our results could be related to reduced NO production by the ciliated paranasal, nasopharyngeal and middle ear epithelium and the impaired sinusal ostial and Eustachian tube patency due to chronic inflammation, and seem to confirm the involvement of NO pathway in recurrent upper airway infections related to impaired ciliated respiratory mucosa.

  10. Factors affecting exhaled nitric oxide measurements: the effect of sex

    Directory of Open Access Journals (Sweden)

    Williamson Avis J

    2007-11-01

    Full Text Available Abstract Background Exhaled nitric oxide (FENO measurements are used as a surrogate marker for eosinophilic airway inflammation. However, many constitutional and environmental factors affect FENO, making it difficult to devise reference values. Our aim was to evaluate the relative importance of factors affecting FENO in a well characterised adult population. Methods Data were obtained from 895 members of the Dunedin Multidisciplinary Health and Development Study at age 32. The effects of sex, height, weight, lung function indices, smoking, atopy, asthma and rhinitis on FENO were explored by unadjusted and adjusted linear regression analyses. Results The effect of sex on FENO was both statistically and clinically significant, with FENO levels approximately 25% less in females. Overall, current smoking reduced FENO up to 50%, but this effect occurred predominantly in those who smoked on the day of the FENO measurement. Atopy increased FENO by 60%. The sex-related differences in FENO remained significant (p ENO. Conclusion Even after adjustment, FENO values are significantly different in males and females. The derivation of reference values and the interpretation of FENO in the clinical setting should be stratified by sex. Other common factors such as current smoking and atopy also require to be taken into account.

  11. REGULATION OF OBESITY AND INSULIN RESISTANCE BY NITRIC OXIDE

    Science.gov (United States)

    Sansbury, Brian E.; Hill, Bradford G.

    2014-01-01

    Obesity is a risk factor for developing type 2 diabetes and cardiovascular disease and has quickly become a world-wide pandemic with few tangible and safe treatment options. While it is generally accepted that the primary cause of obesity is energy imbalance, i.e., the calories consumed are greater than are utilized, understanding how caloric balance is regulated has proven a challenge. Many “distal” causes of obesity, such as the structural environment, occupation, and social influences, are exceedingly difficult to change or manipulate. Hence, molecular processes and pathways more proximal to the origins of obesity—those that directly regulate energy metabolism or caloric intake—appear to be more feasible targets for therapy. In particular, nitric oxide (NO) is emerging as a central regulator of energy metabolism and body composition. NO bioavailability is decreased in animal models of diet-induced obesity and in obese and insulin resistant patients, and increasing NO output has remarkable effects on obesity and insulin resistance. This review discusses the role of NO in regulating adiposity and insulin sensitivity and places its modes of action into context with the known causes and consequences of metabolic disease. PMID:24878261

  12. Exhaled nitric oxide - circadian variations in healthy subjects

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    Antosova M

    2009-12-01

    Full Text Available Abstract Objective Exhaled nitric oxide (eNO has been suggested as a marker of airway inflammatory diseases. The level of eNO is influenced by many various factor including age, sex, menstrual cycle, exercise, food, drugs, etc. The aim of our study was to investigate a potential influence of circadian variation on eNO level in healthy subjects. Methods Measurements were performed in 44 women and 10 men, non-smokers, without respiratory tract infection in last 2 weeks. The eNO was detected at 4-hour intervals from 6 a.m. to 10 p.m. using an NIOX analyzer. We followed the ATS/ERS guidelines for eNO measurement and analysis. Results Peak of eNO levels were observed at 10 a.m. (11.1 ± 7.2 ppb, the lowest value was detected at 10 p.m. (10.0 ± 5.8 ppb. The difference was statistically significant (paired t-test, P Conclusions The daily variations in eNO, with the peak in the morning hours, could be of importance in clinical practice regarding the choice of optimal time for monitoring eNO in patients with respiratory disease.

  13. Differential modulation of nitric oxide synthases in aging: therapeutic opportunities

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    Stêfany Bruno De Assis Cau

    2012-06-01

    Full Text Available Vascular aging is the term that describes the structural and functional disturbances of the vasculature with advancing aging. The molecular mechanisms of aging-associated endothelial dysfunction are complex, but reduced nitric oxide (NO bioavailability and altered vascular expression and activity of NO synthase (NOS enzymes have been implicated as major players. Impaired vascular relaxation in aging has been attributed to reduced endothelial NOS (eNOS-derived NO, while increased inducible NOS (iNOS expression seems to account for nitrosative stress and disrupted vascular homeostasis. Although eNOS is considered the main source of NO in the vascular endothelium, neuronal NOS (nNOS also contributes to endothelial cells-derived NO, a mechanism that is reduced in aging. Pharmacological modulation of NO generation and expression/activity of NOS isoforms may represent a therapeutic alternative to prevent the progression of cardiovascular diseases. Accordingly, this review will focus on drugs that modulate NO bioavailability, such as nitrite anions and NO-releasing non-steroidal anti-inflammatory drugs, hormones (dehydroepiandrosterone and estrogen, statins, resveratrol and folic acid, since they may be useful to treat/to prevent aging-associated vascular dysfunction. The impact of these therapies on life quality in elderly and longevity will be discussed.

  14. Circular dichroism in photoelectron images from aligned nitric oxide molecules

    Science.gov (United States)

    Sen, Ananya; Pratt, S. T.; Reid, K. L.

    2017-07-01

    We have used velocity map photoelectron imaging to study circular dichroism of the photoelectron angular distributions (PADs) of nitric oxide following two-color resonance-enhanced two-photon ionization via selected rotational levels of the A 2Σ+, v'=0 state. By using a circularly polarized pump beam and a counter-propagating, circularly polarized probe beam, cylindrical symmetry is preserved in the ionization process, and the images can be reconstructed using standard algorithms. The velocity map imaging set up enables individual ion rotational states to be resolved with excellent collection efficiency, rendering the measurements considerably simpler to perform than previous measurements conducted with a conventional photoelectron spectrometer. The results demonstrate that circular dichroism is observed even when cylindrical symmetry is maintained, and serve as a reminder that dichroism is a general feature of the multiphoton ionization of atoms and molecules. The observed PADs are in good agreement with calculations based on parameters extracted from previous experimental results obtained by using a time-of-flight electron spectrometer.

  15. Sodium nitrite: the "cure" for nitric oxide insufficiency.

    Science.gov (United States)

    Parthasarathy, Deepa K; Bryan, Nathan S

    2012-11-01

    This process of "curing" food is a long practice that dates back thousands of years long before refrigeration or food safety regulations. Today food safety and mass manufacturing are dependent upon safe and effective means to cure and preserve foods including meats. Nitrite remains the most effective curing agent to prevent food spoilage and bacterial contamination. Despite decades of rigorous research on its safety and efficacy as a curing agent, it is still regarded by many as a toxic undesirable food additive. However, research within the biomedical science community has revealed enormous therapeutic benefits of nitrite that is currently being developed as novel therapies for conditions associated with nitric oxide (NO) insufficiency. Much of the same biochemistry that has been understood for decades in the meat industry has been rediscovered in human physiology. This review will highlight the fundamental biochemistry of nitrite in human physiology and highlight the risk benefit evaluation surrounding nitrite in food and meat products. Foods or diets enriched with nitrite can have profound positive health benefits.

  16. Nitric oxide destabilizes Pias3 and regulates sumoylation.

    Directory of Open Access Journals (Sweden)

    Jing Qu

    Full Text Available Small ubiquitin-related protein modifiers (SUMO modification is an important mechanism for posttranslational regulation of protein function. However, it is largely unknown how the sumoylation pathway is regulated. Here, we report that nitric oxide (NO causes global hyposumoylation in mammalian cells. Both SUMO E2 conjugating enzyme Ubc9 and E3 ligase protein inhibitor of activated STAT3 (Pias3 were targets for S-nitrosation. S-nitrosation did not interfere with the SUMO conjugating activity of Ubc9, but promoted Pias3 degradation by facilitating its interaction with tripartite motif-containing 32 (Trim32, a ubiquitin E3 ligase. On the one hand, NO promoted Trim32-mediated Pias3 ubiquitination. On the other hand, NO enhanced the stimulatory effect of Pias3 on Trim32 autoubiquitination. The residue Cys459 of Pias3 was identified as a target site for S-nitrosation. Mutation of Cys459 abolished the stimulatory effect of NO on the Pias3-Trim32 interaction, indicating a requirement of S-nitrosation at Cys459 for positive regulation of the Pias3-Trim32 interplay. This study reveals a novel crosstalk between S-nitrosation, ubiquitination, and sumoylation, which may be crucial for NO-related physiological and pathological processes.

  17. Morphine stimulates nitric oxide release in human mitochondria.

    Science.gov (United States)

    Stefano, George B; Mantione, Kirk J; Capellan, Lismary; Casares, Federico M; Challenger, Sean; Ramin, Rohina; Samuel, Joshua M; Snyder, Christopher; Kream, Richard M

    2015-10-01

    The expression of morphine by plants, invertebrate, and vertebrate cells and organ systems, strongly indicates a high level of evolutionary conservation of morphine and related morphinan alkaloids as required for life. The prototype catecholamine, dopamine, serves as an essential chemical intermediate in morphine biosynthesis, both in plants and animals. We surmise that, before the emergence of specialized plant and animal cells/organ systems, primordial multi-potential cell types required selective mechanisms to limit their responsiveness to environmental cues. Accordingly, cellular systems that emerged with the potential for recruitment of the free radical gas nitric oxide (NO) as a multi-faceted autocrine/paracrine signaling molecule, were provided with extremely positive evolutionary advantages. Endogenous morphinergic signaling, in concert with NO-coupled signaling systems, has evolved as an autocrine/paracrine regulator of metabolic homeostasis, energy metabolism, mitochondrial respiration and energy production. Basic physiological processes involving morphinergic/NO-coupled regulation of mitochondrial function, with special emphasis on the cardiovascular system, are critical to all organismic survival. Key to this concept may be the phenomenon of mitochondrial enslavement in eukaryotic evolution via endogenous morphine.

  18. Nasal nitric oxide levels in healthy pre-school children.

    Science.gov (United States)

    Piacentini, G L; Bodini, A; Peroni, D G; Sandri, M; Brunelli, M; Pigozzi, R; Boner, A L

    2010-12-01

    The evaluation of nasal nitric oxide (nNO) has been proposed as a screening tool in children with clinically suspectable primary ciliary dyskinesia. Nevertheless, normal values have been reported for school-aged children. This study was designed to identify normal nNO levels in pre-school children. nNO was assessed in 300 healthy children aged between 1.5 and 7.2. Two hundred and fifty of them were unable to fulfill the guideline requirements for nNO measurement and were assessed by sampling the nasal air continuously with a constant trans-nasal aspiration flow for 30 s during tidal breathing. For those children who were able to cooperate, the average nNO concentration was calculated according to guidelines. A statistically significant relationship between nNO level and age was demonstrated in this study group of pre-school children (p < 0.001). An increase in nNO of about 100 ppb was observed in children older than 6 yr vs. those aged < 3. This study presents a description of normal nNO values in pre-school children. The effect of the age and the eventual presence of rhinitis and snoring need to be considered whenever nNO is evaluated in the clinical practice, in particular in non-cooperative children.

  19. [Nitric Oxide in Modulation of Crystallogenic Propeties of Biological Fluid].

    Science.gov (United States)

    Martusevich, A K; Kovaleva, L K; Davyduk, A V

    2016-01-01

    The aim of this work was a comparative analysis of the influence of different NO forms on dehydration structurization of human blood serum. Blood specimens from 15 healthy people were treated by NO-containing gas flow (800 and 80 ppm) generated with the "Plazon" unit, experimental NO-generator (20, 50, 75 and 100 ppm) and by water solution of thiol-containing dinitrosyl iron complexes (3 mM/L). The influence of blood sodium on blood serum crystallization in original and NO-treated blood specimens was estimated. It was found, that the effect of NO on crystallogenic properties of blood serum depends directly on its concentration and form (free or bound), as well as on the presence of reactive oxygen species in gas flow. The most pronounced stimulating effect was observed for the bound form of NO--dinitrosyl iron complexes with glutathione ligands. Low NO concentrations modulated crystallogenic properties of blood serum and the most optimal stimulating action was demonstrated in gas flow containing 20 ppm nitric oxide. In contrast, high NO concentration (800 ppm) inhibited the crystallogenic activity of biological fluid with multiply increasing of structural elements destruction leading to the formation of an additional belt in marginal zone of dehydrated specimens.

  20. Significant blood resistance to nitric oxide transfer in the lung.

    Science.gov (United States)

    Borland, Colin D R; Dunningham, Helen; Bottrill, Fiona; Vuylsteke, Alain; Yilmaz, Cuneyt; Dane, D Merrill; Hsia, Connie C W

    2010-05-01

    Lung diffusing capacity for nitric oxide (DLNO) is used to measure alveolar membrane conductance (DMNO), but disagreement remains as to whether DMNO=DLNO, and whether blood conductance (thetaNO)=infinity. Our previous in vitro and in vivo studies suggested that thetaNODLNO and DLCO were measured by a rebreathing technique before and after three successive equal volume-exchange transfusions with bovine Hb glutamer-200 (10 ml/kg each, total exchange 30 ml/kg). At baseline, DLNO/DLCO=4.5. After exchange transfusion, DLNO rose 57+/-16% (mean+/-SD, P=0.02) and DLNO/DLCO=7.1, whereas DLCO remained unchanged. Thus, in vitro and in vivo data directly demonstrate a finite thetaNO. We conclude that the erythrocyte and/or its immediate environment imposes considerable resistance to alveolar-capillary NO uptake. DLNO is sensitive to dynamic hematological factors and is not a pure index of conductance of the alveolar tissue membrane. With successive exchange transfusion, the estimated in vivo thetaNO [5.1 ml NO.(ml blood.min.Torr)(-1)] approached 4.5 ml NO.(ml blood.min.Torr)(-1), which was derived from in vitro measurements by Carlsen and Comroe (J Gen Physiol 42: 83-107, 1958). Therefore, we suggest use of thetaNO=4.5 ml NO.(min.Torr.ml blood)(-1) for calculation of DM(NO) and pulmonary capillary blood volume from DLNO and DLCO.

  1. Exhaled nitric oxide in childhood asthma: a review.

    Science.gov (United States)

    Pijnenburg, M W H; De Jongste, J C

    2008-02-01

    As an 'inflammometer', the fraction of nitric oxide in exhaled air (Fe(NO)) is increasingly used in the management of paediatric asthma. Fe(NO) provides us with valuable, additional information regarding the nature of underlying airway inflammation, and complements lung function testing and measurement of airway hyper-reactivity. This review focuses on clinical applications of Fe(NO) in paediatric asthma. First, Fe(NO) provides us with a practical tool to aid in the diagnosis of asthma and distinguish patients who will benefit from inhaled corticosteroids from those who will not. Second, Fe(NO) is helpful in predicting exacerbations, and predicting successful steroid reduction or withdrawal. In atopic asthmatic children Fe(NO) is beneficial in adjusting steroid doses, discerning those patients who require additional therapy from those whose medication dose could feasibly be reduced. In pre-school children Fe(NO) may be of help in the differential diagnosis of respiratory symptoms, and may potentially allow for better targeting and monitoring of anti-inflammatory treatment.

  2. Nitric Oxide: A Multitasked Signaling Gas in Plants

    KAUST Repository

    Domingos, Patricia

    2014-12-01

    Nitric oxide (NO) is a gaseous reactive oxygen species (ROS) that has evolved as a signaling hormone in many physiological processes in animals. In plants it has been demonstrated to be a crucial regulator of development, acting as a signaling molecule present at each step of the plant life cycle. NO has also been implicated as a signal in biotic and abiotic responses of plants to the environment. Remarkably, despite this plethora of effects and functional relationships, the fundamental knowledge of NO production, sensing, and transduction in plants remains largely unknown or inadequately characterized. In this review we cover the current understanding of NO production, perception, and action in different physiological scenarios. We especially address the issues of enzymatic and chemical generation of NO in plants, NO sensing and downstream signaling, namely the putative cGMP and Ca2+ pathways, ion-channel activity modulation, gene expression regulation, and the interface with other ROS, which can have a profound effect on both NO accumulation and function. We also focus on the importance of NO in cell–cell communication during developmental processes and sexual reproduction, namely in pollen tube guidance and embryo sac fertilization, pathogen defense, and responses to abiotic stress.

  3. New nitric oxide or hydrogen sulfide releasing aspirins.

    Science.gov (United States)

    Lazzarato, Loretta; Chegaev, Konstantin; Marini, Elisabetta; Rolando, Barbara; Borretto, Emily; Guglielmo, Stefano; Joseph, Sony; Di Stilo, Antonella; Fruttero, Roberta; Gasco, Alberto

    2011-08-11

    A new series of (((R-oxy)carbonyl)oxy)methyl esters of aspirin (ASA), bearing nitric oxide (NO) or hydrogen sulfide (H(2)S) releasing groups, was synthesized, and the compounds were evaluated as new ASA co-drugs. All the products were quite stable in buffered solution at pH 1 and 7.4. Conversely, they were all rapidly metabolized, producing ASA and the NO/H(2)S releasing moiety used for their preparation. Consequent on ASA release, the compounds were capable of inhibiting collagen-induced platelet aggregation of human platelet-rich plasma (PRP). The simple NO/H(2)S donor substructures were able to relax contracted rat aorta strips, with a NO- and H(2)S-dependent mechanism, respectively, but they either did not trigger antiaggregatory activity or displayed antiplatelet potency markedly below that of the related co-drug. The new products might provide a safer and improved alternative to the use of ASA principally in its anti-inflammatory and antithrombotic applications.

  4. Expression of inducible nitric oxide synthase and nitric oxide production in the mud-dwelled air-breathing singhi catfish, Heteropneustes fossilis under condition of water shortage.

    Science.gov (United States)

    Choudhury, Mahua G; Saha, Nirmalendu

    2012-12-01

    Nitric oxide (NO) is known to be an important regulator molecule for regulating the multiple signaling pathways and also to play diverse physiological functions in mammals including that of adaptation to various stresses. The present study reports on the production of nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS) enzyme that produces NO from l-arginine in the freshwater air-breathing catfish (Heteropneustes fossilis) while dwelling inside the mud peat under semidry conditions. Desiccation stress, due to mud-dwelling for 2 weeks, led to significant increase of NO concentration in different tissues and in plasma of singhi catfish, and also the increase of NO efflux from the perfused liver with an accompanying increase of toxic ammonia level in different tissues. Mud-dwelling also resulted to induction of iNOS activity, expression of iNOS protein in different tissues after 7 days with further increase after 14 days, which otherwise was not detectable in control fish. Further, mud-dwelling also resulted to a significant expression of iNOS mRNA after 7 days with a more increase of mRNA level after 14 days, suggesting that the desiccation stress caused transcriptional regulation of iNOS gene. Immunocytochemical analysis indicated the zonal specific expression of iNOS protein in different tissues. Desiccation stress also led to activation and nuclear translocation of nuclear factor кB (NFкB) in hepatic cells. These results suggest that the activation of iNOS gene under desiccation-induced stresses such as high ammonia load was probably mediated through the activation of one of the major transcription factors, the NFкB. This is the first report of desiccation-induced induction of iNOS gene, iNOS protein expression leading to more generation of NO while living inside the mud peat under condition of water shortage in any air-breathing teleosts. 2012 Elsevier Inc. All rights reserved

  5. Enhancement of fracture healing in the rat, modulated by compounds that stimulate inducible nitric oxide synthase

    Science.gov (United States)

    Rajfer, R. A.; Kilic, A.; Neviaser, A. S.; Schulte, L. M.; Hlaing, S. M.; Landeros, J.; Ferrini, M. G.; Ebramzadeh, E.

    2017-01-01

    Objectives We investigated the effects on fracture healing of two up-regulators of inducible nitric oxide synthase (iNOS) in a rat model of an open femoral osteotomy: tadalafil, a phosphodiesterase inhibitor, and the recently reported nutraceutical, COMB-4 (consisting of L-citrulline, Paullinia cupana, ginger and muira puama), given orally for either 14 or 42 days. Materials and Methods Unilateral femoral osteotomies were created in 58 male rats and fixed with an intramedullary compression nail. Rats were treated daily either with vehicle, tadalafil or COMB-4. Biomechanical testing of the healed fracture was performed on day 42. The volume, mineral content and bone density of the callus were measured by quantitative CT on days 14 and 42. Expression of iNOS was measured by immunohistochemistry. Results When compared with the control group, the COMB-4 group exhibited 46% higher maximum strength (t-test, p = 0.029) and 92% higher stiffness (t-test, p = 0.023), but no significant changes were observed in the tadalafil group. At days 14 and 42, there was no significant difference between the three groups with respect to callus volume, mineral content and bone density. Expression of iNOS at day 14 was significantly higher in the COMB-4 group which, as expected, had returned to baseline levels at day 42. Conclusion This study demonstrates an enhancement in fracture healing by an oral natural product known to augment iNOS expression. Cite this article: R. A. Rajfer, A. Kilic, A. S. Neviaser, L. M. Schulte, S. M. Hlaing, J. Landeros, M. G. Ferrini, E. Ebramzadeh, S-H. Park. Enhancement of fracture healing in the rat, modulated by compounds that stimulate inducible nitric oxide synthase: Acceleration of fracture healing via inducible nitric oxide synthase. Bone Joint Res 2017:6:–97. DOI: 10.1302/2046-3758.62.BJR-2016-0164.R2. PMID:28188129

  6. Rational Design of a Structural and Functional Nitric Oxide Reductase

    Energy Technology Data Exchange (ETDEWEB)

    Yeung, N.; Lin, Y; Gao, Y; Zhao, X; Russell, B; Lei, L; Miner, L; Robinson, H; Lu, Y

    2009-01-01

    Protein design provides a rigorous test of our knowledge about proteins and allows the creation of novel enzymes for biotechnological applications. Whereas progress has been made in designing proteins that mimic native proteins structurally, it is more difficult to design functional proteins. In comparison to recent successes in designing non-metalloproteins, it is even more challenging to rationally design metalloproteins that reproduce both the structure and function of native metalloenzymes. This is because protein metal-binding sites are much more varied than non-metal-containing sites, in terms of different metal ion oxidation states, preferred geometry and metal ion ligand donor sets. Because of their variability, it has been difficult to predict metal-binding site properties in silico, as many of the parameters, such as force fields, are ill-defined. Therefore, the successful design of a structural and functional metalloprotein would greatly advance the field of protein design and our understanding of enzymes. Here we report a successful, rational design of a structural and functional model of a metalloprotein, nitric oxide reductase (NOR), by introducing three histidines and one glutamate, predicted as ligands in the active site of NOR, into the distal pocket of myoglobin. A crystal structure of the designed protein confirms that the minimized computer model contains a haem/non-haem FeB centre that is remarkably similar to that in the crystal structure. This designed protein also exhibits NO reduction activity, and so models both the structure and function of NOR, offering insight that the active site glutamate is required for both iron binding and activity. These results show that structural and functional metalloproteins can be rationally designed in silico.

  7. Nitric oxide donors for cervical ripening and induction of labour.

    Science.gov (United States)

    Ghosh, Arpita; Lattey, Katherine R; Kelly, Anthony J

    2016-12-05

    Sometimes it is necessary to bring on labour artificially because of safety concerns for the mother or baby. This review is one of a series of reviews of methods of labour induction using a standardised protocol. To determine the effects of NO donors (isosorbide mononitrate (ISMN), isosorbide dinitrate (ISDN), nitroglycerin and sodium nitroprusside) for third trimester cervical ripening or induction of labour, in comparison with placebo or no treatment or other treatments from a predefined hierarchy. We searched Cochrane Pregnancy and Childbirth's Trials Register (15 August 2016) and the reference lists of trial reports. Clinical trials comparing NO donors for cervical ripening or labour induction with other methods listed above it on a predefined list of methods of labour induction. Interventions include NO donors (isosorbide mononitrate, isosorbide dinitrate, nitroglycerin and sodium nitroprusside) compared with other methods listed above it on a predefined list of methods of labour induction. This review is part of a series of reviews focusing on methods of induction of labour, based on a generic protocol. Three review authors independently assessed trials for inclusion, assessed risk of bias and extracted data. In this update, the quality of the evidence for the main comparison was assessed using the GRADE approach. We included 23 trials (including a total of 4777 women). Included studies compared NO donors with placebo, vaginal prostaglandin E2 (PGE2), intracervical PGE2, vaginal misoprostol and intracervical Foley catheter. The majority of the included studies were assessed as being at low risk of bias. Nitric oxide versus placebo There was no evidence of a difference for any of the primary outcomes analysed: vaginal delivery not achieved in 24 hours (risk ratio (RR) 0.97, 95% confidence interval (CI) 0.83 to 1.15; one trial, 238 women; low-quality evidence), uterine hyperstimulation with fetal heart rate (FHR) changes (RR 0.09, 95% CI 0.01 to 1.62; two

  8. Are exhaled nitric oxide measurements using the portable NIOX MINO repeatable?

    Directory of Open Access Journals (Sweden)

    Raza Abid

    2010-04-01

    Full Text Available Abstract Background Exhaled nitric oxide is a non-invasive marker of airway inflammation and a portable analyser, the NIOX MINO (Aerocrine AB, Solna, Sweden, is now available. This study aimed to assess the reproducibility of the NIOX MINO measurements across age, sex and lung function for both absolute and categorical exhaled nitric oxide values in two distinct groups of children and teenagers. Methods Paired exhaled nitric oxide readings were obtained from 494 teenagers, aged 16-18 years, enrolled in an unselected birth cohort and 65 young people, aged 6-17 years, with asthma enrolled in an interventional asthma management study. Results The birth cohort participants showed a high degree of variability between first and second exhaled nitric oxide readings (mean intra-participant difference 1.37 ppb, 95% limits of agreement -7.61 to 10.34 ppb, although there was very close agreement when values were categorised as low, normal, intermediate or high (kappa = 0.907, p Conclusions The reproducibility of exhaled nitric oxide is poor for absolute values but acceptable when values are categorised as low, normal, intermediate or high in children and teenagers. One measurement is therefore sufficient when using categorical exhaled nitric oxide values to direct asthma management but a mean of at least two measurements is required for absolute values.

  9. Nitric oxide emissions from a coal-fueled engine: Numerical results

    Energy Technology Data Exchange (ETDEWEB)

    Caton, J.A.; Schmidt, J.; Roth, J.; Bachman, F.

    1988-01-01

    A cycle simulation for coal-fueled, reciprocating, internal combustion engines has been expanded to include calculations of nitric oxide exhaust emissions. Calculations have been completed for a diesel oil and a coal-water slurry fuel. The fuels were assumed to be direct injected and compression ignited. The numerical simulation was based on a thermodynamic analysis with models for the injection, ignition, mixing, combustion, and heat transfer. The calculations of the nitric oxide formation and reduction reactions were based on the Zel'dovich mechanism. The engine performance parameters were in good agreement with published values in the literature. The computed exhaust nitric oxide concentrations for both the diesel and coal-water slurry fuels were in fair agreement with recent preliminary experimental values from the literature. In general, the exhaust nitric oxide concentrations were lower for the coal-water slurry fuel relative to the diesel fuel. The thermal nitric oxide production for the coal-water slurry fuel was a strong function of the coal/water mass ratio for the conditions examined. Also, rough estimates indicated that the nitric oxide from fuel-bound nitrogen could be significant for typical coal-water slurry fuels.

  10. Trypanosoma congolense Infections: Induced Nitric Oxide Inhibits Parasite Growth In Vivo

    Directory of Open Access Journals (Sweden)

    Wenfa Lu

    2011-01-01

    Full Text Available Wild-type (WT C57BL/6 mice infected intraperitoneally with 5×106 Trypanosoma congolense survive for more than 30 days. C57BL/6 mice deficient in inducible nitric oxide synthase (iNOS−/− and infected with 103 or 5×106 parasites do not control the parasitemia and survive for only 14±7 or 6.8±0.1 days, respectively. Bloodstream trypanosomes of iNOS−/− mice infected with 5×106  T. congolense had a significantly higher ratio of organisms in the S+G2+M phases of the cell cycle than trypanosomes in WT mice. We have reported that IgM anti-VSG-mediated phagocytosis of T. congolense by macrophages inhibits nitric oxide (NO synthesis via CR3 (CD11b/CD18. Here, we show that during the first parasitemia, but not at later stages of infection, T. congolense-infected CD11b−/− mice produce more NO and have a significantly lower parasitemia than infected WT mice. We conclude that induced NO contributes to the control of parasitemia by inhibiting the growth of the trypanosomes.

  11. Agave sisalana extract induces cell death in Aedes aegypti hemocytes increasing nitric oxide production

    Institute of Scientific and Technical Information of China (English)

    Fabrine Felipe Hilario; Gabriel Joventino Nascimento; Joo Paulo Saraiva Morais; Everaldo Paulo de Medeiros; Manoel Francisco de Sousa; Fabiola da Cruz Nunes

    2016-01-01

    Objective: To investigate the effects of Agave sisalana (A. sisalana) extract on Aedes aegypti (Ae. aegypti) primary cell culture. Methods: Cells of Ae. aegypti were exposed to different concentrations of A. sisalana crude extract (0.18–6.00 mg/mL) for 24 h. Then, the cells were labeled with propidium iodide and subjected to fluorescence microscopy to verify cell viability. In addition, nitric oxide production was measured. Results: Results showed that cells exposed to 6 mg/mL of the crude extract presented a greater percentage of death when compared to control (73.8%± 9.6%vs. 34.6%± 9.6%). Furthermore, there was an increase in the nitric oxide production in cells exposed to 6 mg/mL of A. sisalana crude extract [(0.81 ± 0.08) mmol/L] compared to control group [(0.41 ± 0.18) mmol/L]. Conclusions: The results show that A. sisalana is cytotoxic to Ae. aegypti and may be used as raw material for new eco-friendly and inexpensive insecticides, since sisal in-dustry discards the liquid waste for the extraction of plant fiber.

  12. Agave sisalana extract induces cell death in Aedes aegypti hemocytes increasing nitric oxide production

    Institute of Scientific and Technical Information of China (English)

    Louise Helena Guimar?es de Oliveira; Patricia Alexandria Paiva Silva de Sousa; Fabrine Felipe Hilario; Gabriel Joventino Nascimento; Jo?o Paulo Saraiva Morais; Everaldo Paulo de Medeiros; Manoel Francisco de Sousa; Fabiola da Cruz Nunes

    2016-01-01

    Objective: To investigate the effects of Agave sisalana(A. sisalana) extract on Aedes aegypti(Ae. aegypti) primary cell culture.Methods: Cells of Ae. aegypti were exposed to different concentrations of A. sisalana crude extract(0.18–6.00 mg/m L) for 24 h. Then, the cells were labeled with propidium iodide and subjected to fluorescence microscopy to verify cell viability. In addition, nitric oxide production was measured.Results: Results showed that cells exposed to 6 mg/m L of the crude extract presented a greater percentage of death when compared to control(73.8% ± 9.6% vs. 34.6% ± 9.6%).Furthermore, there was an increase in the nitric oxide production in cells exposed to 6 mg/m L of A. sisalana crude extract [(0.81 ± 0.08) mmol/L] compared to control group[(0.41 ± 0.18) mmol/L].Conclusions: The results show that A. sisalana is cytotoxic to Ae. aegypti and may be used as raw material for new eco-friendly and inexpensive insecticides, since sisal industry discards the liquid waste for the extraction of plant fiber.

  13. Extended nitric oxide measurements in exhaled air of cystic fibrosis and healthy adults.

    Science.gov (United States)

    Hofer, Markus; Mueller, Luzia; Rechsteiner, Thomas; Benden, Christian; Boehler, Annette

    2009-01-01

    In cystic fibrosis (CF) lung disease, exhaled nitric oxide (FeNO) is not raised, but rather is normal or even decreased when measured at a single expiratory flow. FeNO measurements at several flow rates allow differentiation between alveolar and bronchial nitric oxide (NO) production. Extended FeNO measurements therefore should be useful to localize the FeNO deficit in CF airways. FeNO was measured in stable CF adults with moderate lung disease and in healthy controls. Bronchial NO fluxes (J(NO,Br)) and alveolar NO concentrations (C(Alv)) were calculated from FeNO measurements at flow rates of 100, 150 and 200 ml/s using a method previously described. Thirty-two adults were included in the study, 12 of whom had CF. CF adults had significantly lower FeNO values at all flow rates. The median J(NO,Br) was significantly lower in CF adults than in healthy controls [0.31 nl/s (range = 0.11-0.63) vs. 0.70 nl/s (0.27-3.52); P alveolar and bronchial NO outputs in CF adults. The lower FeNO in adults with moderate to severe CF lung disease is likely to be the result of lower bronchial NO output.

  14. Effects of non-surgical periodontal treatment on the L-arginine-nitric oxide pathway and oxidative status in platelets.

    Science.gov (United States)

    Siqueira, Mariana Alves de Sá; Fischer, Ricardo Guimarães; Pereira, Natália Rodrigues; Martins, Marcela Anjos; Moss, Monique Bandeira; Mendes-Ribeiro, Antônio Cláudio; Figueredo, Carlos Marcelo da Silva; Brunini, Tatiana Marlowe Cunha

    2013-06-01

    Several studies have suggested an increase of cardiovascular disease (CVD) risk on periodontitis patients. An enhancement has been demonstrated on both platelet activation and oxidative stress on periodontitis patients, which may contribute for this association. Therefore, the aim of this study was to evaluate the effects of non-surgical periodontal treatment on the l-arginine-nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) pathway and oxidative status in platelets. A total of eight periodontitis patients and eight controls were included in this study. Clinical, laboratory and experimental evaluations were performed on baseline and 90 days after periodontal treatment (except for western blot analysis). The clinical periodontal evaluation included measurements of probing pocket depth (PPD), clinical attachment loss (CAL), % of sites with plaque and % of sites with bleeding on probing. We evaluated: l-[(3)H]arginine influx; nitric oxide synthase (NOS) and arginase enzymes activity and expression; expression of guanylate cyclase and phosphodiesterase-5 enzymes; cGMP levels; platelet aggregation; oxidative status through superoxide dismutase (SOD) and catalase activities, and measurement of reactive oxygen species (ROS) levels and C-reactive protein (CRP) levels. The initial results showed an activation of both l-arginine influx and via system y (+ )L associated with reduced intraplatelet cGMP levels in periodontitis patients and increased systemic levels of CRP. After periodontal treatment, there was a significant reduction of the % of sites with PPD 4-5mm, % of sites with CAL 4-5 mm, and an enhancement in cGMP levels and SOD activity. Moreover, CRP levels were reduced after treatment. Therefore, alterations in the intraplatelet l-arginine-NO-cGMP pathway and oxidant-antioxidant balance associated with a systemic inflammatory response may lead to platelet dysfunction, which may contribute to a higher risk of CVD in periodontitis.

  15. Study of serum Malondialdehyde, Nitric oxide, Vitamin E levels in patients with rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Jambale Triveni A, Halyal SS, Jayaprakash Murthy DS

    2014-04-01

    Full Text Available Background: Rheumatoid arthritis (RA is a chronic progressive autoimmune disorder characterized by symmetric erosive synovitis and sometimes shows multisystem involvement. The long-term outcome of the disease is characterized by significant morbidity and increased mortality. Elevated free radical generations in inflamed joints and impaired antioxidant system have been implicated in RA. Nitric oxide (NO can also induce tissue damage, especially after conversion into peroxynitrite radical (ONOO·. Aims: To estimate the serum levels of MDA, Nitric Oxide (NO and Vitamin E in patients with Rheumatoid Arthritis. Materials and Methods: The study includes 50 RA patients who were fulfilling the American Rheumatism Association 1987 revised criteria for classification of RA and 50 age and sex matched healthy subjects without any major illness were considered as controls. MDA, NO and Vitamin E were estimated in serum. Results: The estimated mean levels (mean ± SD of serum MDA, NO, Vitamin E, in control group were 3.55 ± 0.30, 36.23 ± 7.03, 14.61 ± 1.74, respectively and in patients with RA they were 5.39 ± 0.79, 78.81 ± 8.56, 10.56 ± 1.72, respectively. The statistical analysis by unpaired t-test shows that the levels of serum MDA and NO significantly increased (p< 0.001 and the vitamin E levels were significantly decreased (p < 0.001 in RA patients when compared to healthy controls. Conclusion: The serum values of MDA, NO and Vitamin E all together provided fairly useful index of oxidative stress in RA patients. The results of current study support the concept of oxidative stress leading to tissue damage.

  16. Tolerance to and Withdrawal from Anticonvulsant Action of Diazepam: Role of Nitric Oxide.

    Science.gov (United States)

    Nidhi, Gupta; Bhargava, V K.; Pandhi, P

    2000-08-01

    Tolerance to the anticonvulsant action of diazepam as a result of central nervous system adaptation limits its use in epilepsy. In Wistar rats, diazepam 5 mg/kg ip twice daily produced tolerance to its anticonvulsant action in 6 days. Abrupt withdrawal caused hyperexcitability. Tolerance manifested as a decrease in seizure threshold to near-control values, while withdrawal hyperexcitability was evidenced by a significant decrease in seizure threshold below the control value. This effect was seen both in the "same group design" and "separate group design." L-Arginine (a donor of nitric oxide) and N(omega)-nitro-L-arginine (an inhibitor of nitric oxide synthase) were given in doses of 150 and 8 mg/kg, respectively, on Days 1, 3, and 6 along with diazepam in the same group design. Their role in preventing the development of tolerance to the anticonvulsant effect was seen on Days 1, 3, and 6. Withdrawal hyperexcitability was seen on Days 1, 2, and 4 after cessation of drug therapy. Both electroshock and pentylenetetrazole (PTZ) infusion were used as models of epilepsy, and seizure thresholds were determined. The up and down method of A. W. Kimball, W. T. Burnett, and G. D. Doherty (Radiat Res 1957;7:1-12) was used to determine the seizure threshold in cases of electroshock-induced seizures. L-Arginine, when administered with diazepam, was found to inhibit tolerance as well as withdrawal hyperexcitability. N(omega)-nitro-L-arginine did not prevent the development of tolerance or withdrawal hyperexcitability in the electroshock model, while in the PTZ model inhibition of nitric synthesis prevented withdrawal hyperexcitability but had no effect on the development of tolerance.

  17. Is endothelial-nitric-oxide-synthase-derived nitric oxide involved in cardiac hypoxia/reoxygenation-related damage?

    Indian Academy of Sciences (India)

    A Rus; Ma Peinado; S Blanco; Ml Del Moral

    2011-03-01

    Nitric oxide (NO) has been reported to act both as a destructive and a protective agent in the pathogenesis of the injuries that occur during hypoxia/reoxygenation (H/R). It has been suggested that this dual role of NO depends directly on the isoform of NO synthase (NOS) involved. In this work, we investigate the role that NO derived from endothelial NOS (eNOS) plays in cardiac H/R-induced injury.Wistar rats were submitted to H/R (hypoxia for 30 min; reoxygenation of 0 h, 12 h and 5 days), with or without prior treatment using the selective eNOS inhibitor L-NIO (20 mg/kg). Lipid peroxidation, apoptosis and protein nitration, as well as NO production (NOx), were analysed. The results showed that L-NIO administration lowered NOx levels in all the experimental groups. However, no change was found in the lipid peroxidation level, the percentage of apoptotic cells or nitrated protein expression, implying that eNOS-derived NO may not be involved in the injuries occurring during H/R in the heart. We conclude that L-NIO would not be useful in alleviating the adverse effects of cardiac H/R.

  18. Diazeniumdiolate mediated nitrosative stress alters nitric oxide homeostasis through intracellular calcium and S-glutathionylation of nitric oxide synthetase.

    Directory of Open Access Journals (Sweden)

    Yefim Manevich

    Full Text Available BACKGROUND: PABA/NO is a diazeniumdiolate that acts as a direct nitrogen monoxide (NO donor and is in development as an anticancer drug. Its mechanism of action and effect on cells is not yet fully understood. METHODOLOGY/PRINCIPAL FINDINGS: We used HPLC and mass spectrometry to identify a primary nitroaromatic glutathione metabolite of PABA/NO and used fluorescent assays to characterize drug effects on calcium and NO homeostasis, relating these to endothelial nitric oxide synthase (eNOS activity. Unexpectedly, the glutathione conjugate was found to be a competitive inhibitor of sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA presumably at the same site as thapsigargin, increasing intracellular Ca2+ release and causing auto-regulation of eNOS through S-glutathionylation. CONCLUSIONS/SIGNIFICANCE: The initial direct release of NO after PABA/NO was followed by an eNOS-mediated generation of NO as a consequence of drug-induced increase in Ca2+ flux and calmodulin (CaM activation. PABA/NO has a unique dual mechanism of action with direct intracellular NO generation combined with metabolite driven regulation of eNOS activation.

  19. NO to cancer: The complex and multifaceted role of nitric oxide and the epigenetic nitric oxide donor, RRx-001☆

    Science.gov (United States)

    Scicinski, Jan; Oronsky, Bryan; Ning, Shoucheng; Knox, Susan; Peehl, Donna; Kim, Michelle M.; Langecker, Peter; Fanger, Gary

    2015-01-01

    The endogenous mediator of vasodilation, nitric oxide (NO), has been shown to be a potent radiosensitizer. However, the underlying mode of action for its role as a radiosensitizer – while not entirely understood – is believed to arise from increased tumor blood flow, effects on cellular respiration, on cell signaling, and on the production of reactive oxygen and nitrogen species (RONS), that can act as radiosensitizers in their own right. NO activity is surprisingly long-lived and more potent in comparison to oxygen. Reports of the effects of NO with radiation have often been contradictory leading to confusion about the true radiosensitizing nature of NO. Whether increasing or decreasing tumor blood flow, acting as radiosensitizer or radioprotector, the effects of NO have been controversial. Key to understanding the role of NO as a radiosensitizer is to recognize the importance of biological context. With a very short half-life and potent activity, the local effects of NO need to be carefully considered and understood when using NO as a radiosensitizer. The systemic effects of NO donors can cause extensive side effects, and also affect the local tumor microenvironment, both directly and indirectly. To minimize systemic effects and maximize effects on tumors, agents that deliver NO on demand selectively to tumors using hypoxia as a trigger may be of greater interest as radiosensitizers. Herein we discuss the multiple effects of NO and focus on the clinical molecule RRx-001, a hypoxia-activated NO donor currently being investigated as a radiosensitizer in the clinic. PMID:26164533

  20. Up-regulation of cardiac nitric oxide synthase 1-derived nitric oxide after myocardial infarction in senescent rats.

    Science.gov (United States)

    Damy, Thibaud; Ratajczak, Philippe; Robidel, Estelle; Bendall, Jennifer K; Oliviéro, Patricia; Boczkowski, Jorge; Ebrahimian, Talin; Marotte, Françoise; Samuel, Jane-Lise; Heymes, Christophe

    2003-10-01

    Nitric oxide (NO) has been implicated in the development of heart failure, although the source, significance, and functional role of the different NO synthase (NOS) isoforms in this pathology are controversial. The presence of a neuronal-type NOS isoform (NOS1) in the cardiac sarcoplasmic reticulum has been recently discovered, leading to the hypothesis that NOS1-derived NO may notably alter myocardial inotropy. However, the regulation and role(s) of NOS1 in cardiac diseases remain to be determined. Using an experimental model of myocardial infarction (MI) in senescent rats, we demonstrated a significant increase in cardiac NOS1 expression and activity in MI, coupled with the translocation of this enzyme to the sarcolemma through interactions with caveolin-3. The enhanced NOS1 activity counteracts the decrease in cardiac NOS3 expression and activity observed in heart failure. We demonstrated an increased interaction between NOS1 and its regulatory protein HSP90 in post-MI hearts, a potential mechanism for the higher NOS1 activity in this setting. Finally, preferential in vivo inhibition of NOS1 activity enhanced basal post-MI left ventricular dysfunction in senescent rats. These results provide the first evidence that increased NOS1-derived NO production may play a significant role in the autocrine regulation of myocardial contractility after MI in aging rats.

  1. Effect of aging on expression of nitric oxide synthase I and activity of nitric oxide synthase in rat penis

    Institute of Scientific and Technical Information of China (English)

    Jun-PingSHI; Yong-MeiZHAO; Yu-TongSONG

    2003-01-01

    Aim: To investigate the effect of aging on the expression of nitric oxide synthase I (NOS I) and the activity of NOS in rat penis. Methods: Sixty male rats from 3 age groups (adult, old and senescent) were investigated.The expression of NOS I protein and mRNA in rat penis were detected by Western blot and RT-PCR respectively and the NOS activity, with ultraviolet spectrophotometry. Results: In the old and senescent group, NOS I protein expression was significantly decreased as compared with the adult. NOS I mRNA expression was well correlated with the protein expression. NOS activity was not statistically different between the adult and old groups, but it was significantly reduced in the senescent compared with the adult group (P<0.01). Conclusion: The aging-induced decreases in NOS I expression and NOS activity may be one of the main mechanisms leading to erectile dysfunctionin the senescent rats. ( Asian J Androl 2003 Jun; 5: 117-120)

  2. NO to cancer: The complex and multifaceted role of nitric oxide and the epigenetic nitric oxide donor, RRx-001.

    Science.gov (United States)

    Scicinski, Jan; Oronsky, Bryan; Ning, Shoucheng; Knox, Susan; Peehl, Donna; Kim, Michelle M; Langecker, Peter; Fanger, Gary

    2015-12-01

    The endogenous mediator of vasodilation, nitric oxide (NO), has been shown to be a potent radiosensitizer. However, the underlying mode of action for its role as a radiosensitizer - while not entirely understood - is believed to arise from increased tumor blood flow, effects on cellular respiration, on cell signaling, and on the production of reactive oxygen and nitrogen species (RONS), that can act as radiosensitizers in their own right. NO activity is surprisingly long-lived and more potent in comparison to oxygen. Reports of the effects of NO with radiation have often been contradictory leading to confusion about the true radiosensitizing nature of NO. Whether increasing or decreasing tumor blood flow, acting as radiosensitizer or radioprotector, the effects of NO have been controversial. Key to understanding the role of NO as a radiosensitizer is to recognize the importance of biological context. With a very short half-life and potent activity, the local effects of NO need to be carefully considered and understood when using NO as a radiosensitizer. The systemic effects of NO donors can cause extensive side effects, and also affect the local tumor microenvironment, both directly and indirectly. To minimize systemic effects and maximize effects on tumors, agents that deliver NO on demand selectively to tumors using hypoxia as a trigger may be of greater interest as radiosensitizers. Herein we discuss the multiple effects of NO and focus on the clinical molecule RRx-001, a hypoxia-activated NO donor currently being investigated as a radiosensitizer in the clinic.

  3. Manganese-induced oxidative stress in two ontogenetic stages of chamomile and amelioration by nitric oxide.

    Science.gov (United States)

    Kováčik, Jozef; Babula, Petr; Hedbavny, Josef; Švec, Pavel

    2014-02-01

    Impact of manganese (Mn(2+)) excess (100, 500 and 1000 μM over 7 days) on two ontogenetic stages (7-week-old plants and 7-day-old seedlings) of Matricaria chamomilla was compared. Mn excess depressed growth of seedlings (but not germination) and stimulated oxidative stress (ROS and lipid peroxidation) in both plants and seedlings. Growth inhibition could be evoked by higher Mn uptake and higher translocation factor in seedlings than in plants. Total thiols staining revealed elevation in almost all treatments. In 7-week-old plants, activity of peroxidases increased slightly and rather decreased under high Mn doses. Superoxide rather than hydrogen peroxide contributed to visualized ROS presence. Fluorescence of nitric oxide (NO) showed stimulation in plants but decrease in seedlings. Impact of exogenous nitric oxide donor (sodium nitroprusside/SNP) was therefore tested and results showed amelioration of 1000 μM Mn-induced oxidative stress in seedlings (decrease in H2O2 and increase in NO content while antioxidative enzyme activities were variably affected) concomitantly with depleted Mn accumulation. It is concluded that NO participates in tolerance to Mn excess but negative effects of the highest SNP dose were also observed. Extensive fluorescence microscopy is also explanatively discussed.

  4. Effect of Blockade of Nitric Oxide Synthesis on the Renin Secretory Response to Frusemide in Conscious Rabbits

    Science.gov (United States)

    Reid, Ian A.; Chou, Lance

    1995-01-01

    The enzyme nitric oxide synthase is present in the macula densa and may participate in the control of renin secretion by the adjacent juxtagiomerular cells. In the present study, we investigated the effect of inhibiting nitric oxide synthase on the renin secretory response to frusemide, which stimulates renin secretion by blocking Na(+)-K(+)-2Cl(-) co-transport in the macula densa. Injection of frusemide in 12 conscious rabbits elicited a transient increase in mean arterial pressure from 84 +/- 2 to 92 +/-3 mm Hg at 5 min (P less than 0.01) and a sustained increase in heart rate from 246 +/- 6 to 281 +/- 10 beats/min at 45 min (P less than 0.01). Plasma renin activity increased from 8.0 +/- 1.2 to 14.3 +/- 1.8, 12.4 +/- 1.6 and 11.6 +/- 1.5 pmol/2h ml at 15, 30 and 45min respectively (P less than 0.01). There were no changes in plasma sodium and potassium concentrations or osmoiality. Inhibition of nitric oxide synthase with N(sup G)-nitro-L- arginine methyl ester increased mean arterial pressure by 9 mm Hg, decreased heart rate and plasma renin activity, and markedly suppressed the renin response to frusemide (from 4.6 +/- 0.7 to 7.6 +/- 1.7, 4.7 +/- 1.0 and 4.6 +/- 0.7pmol/2h ml at 15, 30 and 45 min respectively). By contrast, infusion of an equipressor dose of phenylephrine did not suppress the renin response to frusemide. Histochemical studies with the NADPH diaphorase technique confirmed the presence of nitric oxide synthase in the macula densa, and suggested that enzyme activity is increased by treatment with frusemide. These results are consistent with a role for the L- arginine-nitric oxide pathway in the modulation of renin secretion by the macula densa.

  5. Nitric oxide signalling and neuronal nitric oxide synthase in the heart under stress [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Yin Hua Zhang

    2017-05-01

    Full Text Available Nitric oxide (NO is an imperative regulator of the cardiovascular system and is a critical mechanism in preventing the pathogenesis and progression of the diseased heart. The scenario of bioavailable NO in the myocardium is complex: 1 NO is derived from both endogenous NO synthases (endothelial, neuronal, and/or inducible NOSs [eNOS, nNOS, and/or iNOS] and exogenous sources (entero-salivary NO pathway and the amount of NO from exogenous sources varies significantly; 2 NOSs are located at discrete compartments of cardiac myocytes and are regulated by distinctive mechanisms under stress; 3 NO regulates diverse target proteins through different modes of post-transcriptional modification (soluble guanylate cyclase [sGC]/cyclic guanosine monophosphate [cGMP]/protein kinase G [PKG]-dependent phosphorylation, S-nitrosylation, and transnitrosylation; 4 the downstream effectors of NO are multidimensional and vary from ion channels in the plasma membrane to signalling proteins and enzymes in the mitochondria, cytosol, nucleus, and myofilament; 5 NOS produces several radicals in addition to NO (e.g. superoxide, hydrogen peroxide, peroxynitrite, and different NO-related derivatives and triggers redox-dependent responses. However, nNOS inhibits cardiac oxidases to reduce the sources of oxidative stress in diseased hearts. Recent consensus indicates the importance of nNOS protein in cardiac protection under pathological stress. In addition, a dietary regime with high nitrate intake from fruit and vegetables together with unsaturated fatty acids is strongly associated with reduced cardiovascular events. Collectively, NO-dependent mechanisms in healthy and diseased hearts are better understood and shed light on the therapeutic prospects for NO and NOSs in clinical applications for fatal human heart diseases.

  6. Role of nitric oxide in long-term potentiation of the rat medial vestibular nuclei.

    Science.gov (United States)

    Grassi, S; Pettorossi, V E

    2000-01-01

    In rat brainstem slices, we investigated the role of nitric oxide in long-term potentiation induced in the ventral portion of the medial vestibular nuclei by high-frequency stimulation of the primary vestibular afferents. The nitric oxide scavenger [2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide ] and the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester were administered before and after induction of potentiation. Both drugs completely prevented long-term potentiation, whereas they did not impede the potentiation build-up, or affect the already established potentiation. These results demonstrate that the induction, but not the maintenance of vestibular long-term potentiation, depends on the synthesis and release into the extracellular medium of nitric oxide. In addition, we analysed the effect of the nitric oxide donor sodium nitroprusside on vestibular responses. Sodium nitroprusside induced long-term potentiation, as evidenced through the field potential enhancement and unit peak latency decrease. This potentiation was impeded by D, L-2-amino-5-phosphonopentanoic acid, and was reduced under blockade of synaptosomal platelet-activating factor receptors by ginkgolide B and group I metabotropic glutamate receptors by (R,S)-1-aminoindan-1, 5-dicarboxylic acid. When reduced, potentiation fully developed following the washout of antagonist, demonstrating an involvement of platelet-activating factor and group I metabotropic glutamate receptors in its full development. Potentiation induced by sodium nitroprusside was also associated with a decrease in the paired-pulse facilitation ratio, which persisted under ginkgolide B, indicating that nitric oxide increases glutamate release independently of platelet-activating factor-mediated presynaptic events. We suggest that nitric oxide, released after the activation of N-methyl-D-aspartate receptors, acts as a retrograde messenger leading to an enhancement of glutamate release to a

  7. Expression of inducible nitric oxide synthase and effects of L-arginine on colonic nitric oxide production and fluid transport in patients with "minimal colitis"

    DEFF Research Database (Denmark)

    Perner, Anders; Andresen, Lars; Normark, Michel;

    2005-01-01

    Some patients with idiopathic, chronic diarrhoea have minimal, non-specific colonic inflammation. As nitric oxide (NO) acts as a secretagogue in the colon, we studied the expression of inducible NO synthase (iNOS) in mucosal biopsies and the effects of NOS stimulation on colonic transfer of fluid...

  8. Oleic acid-dependent modulation of Nitric oxide associated 1 protein levels regulates nitric oxide-mediated defense signaling in Arabidopsis

    Science.gov (United States)

    The conserved cellular metabolites nitric oxide (NO) and oleic acid (18:1) are well-known regulators of disease physiologies in diverse organism. We show that NO production in plants is regulated via 18:1. Reduction in 18:1 levels, via a genetic mutation in the 18:1-synthesizing gene SUPPRESSOR OF S...

  9. Nitric oxide inhibitory substances from Curcuma mangga rhizomes

    Directory of Open Access Journals (Sweden)

    Kanidta Kaewkroek

    2009-08-01

    Full Text Available Curcuma mangga Val. & Zijp. is a member of the Zingiberaceae family commonly grown in Thailand. It is locally known as mango tumeric because of its mango-like smell when the fresh rhizomes are cut. C. mangga is a popular vegetable, the tips of the young rhizomes and shoots are consumed raw with rice. Medicinally, the rhizomes are used as a stomachic and for chest pains, fever, and general debility. It is also used in postpartum care. In the present study, we investigated the anti-inflammatory effect of the extract and compounds from C. mangga rhizomes against lipopolysaccharide (LPS-induced nitric oxide (NO production in RAW 264.7 cell line. From bioassay-guided fractionation, the chloroform fraction exhibited the most potent inhibitory activity with an IC50 value of 2.1 g/ml, followed by the hexane fraction (IC50 = 3.8 g/ml and the ethyl acetate fraction (IC50 = 23.5 g/ml, respectively. Demethoxycurcumin (1 and 3-buten-2-one, 4-[(1R, 4aR, 8aR-decahydro-5, 5, 8a-trimethyl-2-methylene-1-naphthalenyl]-, (3E-rel- (2 were isolated from the chloroform- and hexane fractions, respectively. Bisdemethoxycurcumin (3 whose structure is similar to that of 1 was also tested for NO inhibitory activity. Of the tested compounds, compound 1 exhibited the highest activity with an IC50 value of 12.1 μM, followed by 3(IC50 = 16.9 M and 2 (IC50 = 30.3 M. These results suggest that C. mangga and its compounds exert NO inhibitory activity and have a potential to be developed as a pharmaceutical preparation for treatment of inflammatory-related diseases. Moreover, this is the first report of compound 2 that was isolated from C. mangga rhizomes.

  10. Nitric Oxide and Prostaglandins Potentiate the Liver Regeneration Cascade

    Directory of Open Access Journals (Sweden)

    Jodi M Schoen Smith

    2006-01-01

    Full Text Available The liver has the remarkable ability to regenerate following damage or surgical resection. Although this feature of the liver has been studied for over 100 years, the trigger of the liver regeneration cascade remains controversial. Recent experimental evidence supports the hypothesis that nitric oxide (NO and prostaglandins (PGs, released secondary to an increase in the blood flow-to-liver mass ratio following two-thirds partial hepatectomy (PHx, work synergistically to trigger liver regeneration. To extend this research, the hypothesis that NO and PGs are potential therapeutic targets to potentiate the liver regeneration cascade is tested. The NO donor s-nitroso-n-acetylpenicillamine, the phosphodiesterase V antagonist zaprinast (ZAP and PGI2 each potentiated c-fos messenger RNA expression, an index of initiation of the liver regeneration cascade, following PHx. Also, the triple combination of s-nitroso-n-acetylpenicillamine, ZAP and PGI2 potentiated c-fos messenger RNA expression. These results support the hypothesis that NO and PGs can potentiate initiation of the regeneration cascade. An additional index of liver weight restoration 48 h after PHx was also used to test the hypothesis, because this index encompasses the entire liver regeneration cascade. ZAP and 6-keto-PGF1α, a stable metabolite of PGI2, and the combination of ZAP and 6-keto-PGF1α, each potentiated liver weight restoration 48 h after PHx. These results also provide support for the hypothesis that NO and PGs are possible therapeutic targets to potentiate liver regeneration following surgical resection.

  11. The effects of auroral precipitation on atmospheric nitric oxide concentration

    Science.gov (United States)

    Jones, S.; Lessard, M.; Fritz, B.

    2016-12-01

    The Pulsating Auroral Nitric Oxide Production in the Lower Ionosphere (PANOPLI) project addresses a science problem that has strong implications regarding the question of how solar variability may be related to climate change and terrestrial weather. Pulsating aurora is the ideal choice for studying auroral NO production since this type of aurora is caused by tens of keV electron precipitation (which is known to produce enhancements in thermospheric NO) and is a frequently occurring and long lasting phenomenon resulting in widespread auroral luminosity. The pulsating auroral precipitation results in a large transfer of power from the magnetosphere to the ionosphere-thermosphere and may be a significant contributor to thermospheric NO production, which is dependent on the energy flux and duration of the auroral precipitation. PANOPLI makes use of ground-based riometer measurements to characterize the electron precipitation causing pulsating aurora and determine the effects of pulsating aurora on the theremosphere-mesosphere NO reservoir. The inferred precipitating electron distribution function is input to a model to calculate the expected NO enhancement for comparison with NO enhancements inferred from ground-based Fabry-Perot interferometer measurements. This problem is particularly important because NO produced at low enough altitudes can transport downward to the stratosphere and chemically react with ozone causing depletion. Therefore, this work is a vital first step in quantifying the auroral contribution to ozone depletion. Previous studies have shown that the auroral contribution to atmospheric chemistry can be significant, with up to 60% of ozone depletion enhancements (above background levels) at 35-40 km altitude due to energetic electron precipitation (Randall et al., 2005).

  12. Dissecting structural and electronic effects in inducible nitric oxide synthase.

    Science.gov (United States)

    Hannibal, Luciana; Page, Richard C; Haque, Mohammad Mahfuzul; Bolisetty, Karthik; Yu, Zhihao; Misra, Saurav; Stuehr, Dennis J

    2015-04-01

    Nitric oxide synthases (NOSs) are haem-thiolate enzymes that catalyse the conversion of L-arginine (L-Arg) into NO and citrulline. Inducible NOS (iNOS) is responsible for delivery of NO in response to stressors during inflammation. The catalytic performance of iNOS is proposed to rely mainly on the haem midpoint potential and the ability of the substrate L-Arg to provide a hydrogen bond for oxygen activation (O-O scission). We present a study of native iNOS compared with iNOS-mesohaem, and investigate the formation of a low-spin ferric haem-aquo or -hydroxo species (P) in iNOS mutant W188H substituted with mesohaem. iNOS-mesohaem and W188H-mesohaem were stable and dimeric, and presented substrate-binding affinities comparable to those of their native counterparts. Single turnover reactions catalysed by iNOSoxy with L-Arg (first reaction step) or N-hydroxy-L-arginine (second reaction step) showed that mesohaem substitution triggered higher rates of Fe(II)O₂ conversion and altered other key kinetic parameters. We elucidated the first crystal structure of a NOS substituted with mesohaem and found essentially identical features compared with the structure of iNOS carrying native haem. This facilitated the dissection of structural and electronic effects. Mesohaem substitution substantially reduced the build-up of species P in W188H iNOS during catalysis, thus increasing its proficiency towards NO synthesis. The marked structural similarities of iNOSoxy containing native haem or mesohaem indicate that the kinetic behaviour observed in mesohaem-substituted iNOS is most heavily influenced by electronic effects rather than structural alterations.

  13. [Exhaled nitric oxide levels in school children of Beijing].

    Science.gov (United States)

    Li, Shuo; Lou, Xiao-shang; Ma, Yu; Han, Sheng-li; Liu, Chuan-he; Chen, Yu-zhi

    2010-02-01

    To learn the normal values of exhaled nitric oxide (eNO) in children. School children in Beijing from 11 to 18 years of age were included in the study. All the students were assigned into two groups: normal group and abnormal group (with allergic disease) according to the International Study of Asthma and Allergy in Childhood questionnaires. eNO, peak expiratory flow rate and sensitization were measured. Totally 395 students were screened out as normal subject (male: 177, female: 218). The eNO level was not significantly different between genders (P > 0.05), but was associated positively with age in both male and female group (P = 0.008 and P = 0.05 respectively) and associated with height in male students (P = 0.02). The geometric mean value of eNO was 11.22 ppb (parts per billion, ppb = 10(9)) in children aged from 11 to 14 years and 14.13 ppb in children aged from 14 to 18 years, with 95% confidence interval 4.17 - 30.20, 5.50 - 36.31 ppb. The eNO level was significantly increased in children who "ever had asthma or wheezing" (n = 68), and children who "ever had rhinitis" (n = 96) compared with normal subjects (P = 0.001 and P = 0.008). The geometric mean value of eNO was 16.98 ppb in children with positive skin prick test and was significantly increased as compared with children with negative skin prick test with eNO level at 11.75 ppb (P = 0.001). eNO level varied between 10.72 ppb and 13.80 ppb in normal children 11 - 18 years of age, and was positively associated with age and height, but not with gender. eNO level increased significantly in children with wheezing and atopy.

  14. Cerebral ischemia—induced neuronal apoptosis mediated by nitric oxide

    Institute of Scientific and Technical Information of China (English)

    NomuY

    2002-01-01

    To elucidate the cellular and molecular mechanism of cerebral ischemia-induced neuronal apoptosis mediated by nitric oxide (NO) in the brain,we investigated:(1)cell death in hippocampal CA1 neurons of rats after a rransient four vessel occlusion (4VO)/reperfusion and (2) apoptosis induced by NOC18(NO releaser) using SHSY5Y cells,a human neuroblastoma cell line.We found that 4VO caused expression of inducible type of NO synthase (iNOS) in glial cells and neuronal apoptosis in CA1 region of rats.Next we examined in vitro apoptotic effects of NOC18 on SHSY5Y cells and suggest that NO decrease mitochondrial membrane potential,release cytochrome C from mitochondria,activates caspase-3,degrade inhibitor of caspase-activated DNase(Icad),and activated DNase translocate into nucleus and induce DNA fragmentation.Thus we conclude that the excess amount of NO produced by glial iNOS at cerebral ischemia could be involved in neuronal apoptosis in CA1 region.Regarding NO action on neurons,we further obtained that NO propects neuronal apoptosis in PC12 cells perhaps by nitrosylation of caspase,subsequent reduction of proteolytic activity.Taken together,we suggest that NO seem to exert dual effects(toxic and beneficial) on neuronal apoptosis,the one (toxic);apoptosis-induction throuth the decrease in mitochondrial membrane potentials and cytochrome C release and the othe (beneficial);protection against apoptosis through the inhibition of caspase activity.

  15. Starved Escherichia coli preserve reducing power under nitric oxide stress

    Energy Technology Data Exchange (ETDEWEB)

    Gowers, Glen-Oliver F. [Department of Molecular Biology, Princeton University, Princeton, NJ (United States); Robinson, Jonathan L. [Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ (United States); Brynildsen, Mark P., E-mail: mbrynild@princeton.edu [Department of Molecular Biology, Princeton University, Princeton, NJ (United States); Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ (United States)

    2016-07-15

    Nitric oxide (NO) detoxification enzymes, such as NO dioxygenase (NOD) and NO reductase (NOR), are important to the virulence of numerous bacteria. Pathogens use these defense systems to ward off immune-generated NO, and they do so in environments that contain add