Science.gov

Sample records for determine nitric oxide

  1. Nitric oxide

    Integrated Risk Information System (IRIS)

    Nitric oxide ; CASRN 10102 - 43 - 9 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Ef

  2. Cortical Actin Nanodynamics Determines Nitric Oxide Release in Vascular Endothelium

    PubMed Central

    Fels, Johannes; Jeggle, Pia; Kusche-Vihrog, Kristina; Oberleithner, Hans

    2012-01-01

    The release of the main vasodilator nitric oxide (NO) by the endothelial NO synthase (eNOS) is a hallmark of endothelial function. We aim at elucidating the underlying mechanism how eNOS activity depends on cortical stiffness (Кcortex) of living endothelial cells. It is hypothesized that cortical actin dynamics determines Кcortex and directly influences eNOS activity. By combined atomic force microscopy and fluorescence imaging we generated mechanical and optical sections of single living cells. This approach allows the discrimination between Кcortex and bulk cell stiffness (Кbulk) and, additionally, the simultaneous analysis of submembranous actin web dynamics. We show that Кcortex softens when cortical F-actin depolymerizes and that this shift from a gel-like stiff cortex to a soft G-actin rich layer, triggers the stiffness-sensitive eNOS activity. The results implicate that stiffness changes in the ∼100 nm phase of the submembranous actin web, without affecting Кbulk, regulate NO release and thus determines endothelial function. PMID:22844486

  3. Nitric oxide inhibition strategies

    PubMed Central

    Wong, Vivian (Wai Chong); Lerner, Ethan

    2015-01-01

    Nitric oxide is involved in many physiologic processes. There are efforts, described elsewhere in this volume, to deliver nitric oxide to tissues as a therapy. Nitric oxide also contributes to pathophysiologic processes. Inhibiting nitric oxide or its production can thus also be of therapeutic benefit. This article addresses such inhibitory strategies. PMID:26634146

  4. Detection of nitric oxide pollution

    NASA Technical Reports Server (NTRS)

    Chackerian, C., Jr.; Weisbach, M. F.

    1973-01-01

    Studies of absorption spectra enhancement of certain atomic and molecular species inserter in dye-laser cavities have indicated that nitric oxide can be determined at low concentrations. Absorption coefficient of small amounts of nitric oxide in intra-laser-cavity absorption cell containing helium is enhanced by more than two orders of magnitude.

  5. Biofiltration of nitric oxide

    SciTech Connect

    Davidova, Y.B.; Schroeder, E.D.; Chang, D.P.Y.

    1997-12-31

    Results of recent experiments on nitrogen transformations in biofilters suggest that oxides of nitrogen may be both oxidized or reduced within these systems. Under the proper conditions, nitric oxide (+2) can be reduced to molecular nitrogen (0) through microbial denitrification, or nitric oxide can be sequentially oxidized to nitrite (+3) and then to nitrate (+5) through microbial nitrification. There are major implications of these findings for the use of biofilters as air pollution control devices since economical NO{sub x} control technologies may be possible and should be exploited. Oxidation of ammonia ({minus}3) to nitrite (+3) by bacteria of the genus Nitrosomonas and oxidation of nitrite (+3) to nitrate (+5) by bacteria of the genus Nitrobacter are ubiquitous reactions in soil and natural waters. The intermediates, nitrous oxide (+1) and nitric oxide (+2) are potentially oxidizable by nitrifying bacteria in the presence of atmospheric concentration of oxygen. The oxidation of nitric oxide within a biofilter was demonstrated. The authors have observed removal up to 70% in laboratory scale aerobic biofilters with a NO feed of 80 ppmv and an empty bed contact time of 12 minutes. Nitric oxide removal appears to be linear with nitric oxide concentration. Removal rates are a function of the flow rate of the gas, suggesting diffusion limitations. The biofilter system was sensitive to pH changes resulting from nitrification. Improved removal efficiency at shorter contact times may be possible with increased biomass and better distribution.

  6. Determination of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine in biological samples by HPLC.

    PubMed

    Teerlink, Tom

    2005-01-01

    Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of all isoforms of nitric oxide synthase, the enzyme that synthesizes nitric oxide from arginine. Elevated plasma concentrations of ADMA are associated with hypertension and other risk factors for cardiovascular disease. Symmetric dimethylarginine (SDMA), a stereoisomer of ADMA that does not inhibit nitric oxide synthase, is also present in plasma in concentrations that are almost equal to ADMA concentrations. Any analytical method used for the determination of ADMA should therefore be able to discriminate between ADMA and SDMA. In this chapter a high-performance liquid chromatography (HPLC) method for the simultaneous analysis of arginine, ADMA, and SDMA is described. Solid-phase extraction is used to isolate all basic amino acids. Subsequently, amino acids are converted into relatively stable adducts by derivatization with o-phthalaldehyde reagent containing mercaptopropionic acid. Derivatives are then separated by reversed-phase HPLC using isocratic elution and fluorescence detection. The method requires only 0.05-0.2 mL of sample, allowing the analysis of plasma from small laboratory animals. Because of its high precision, this method is particularly suited to detect small concentration differences between samples, e.g., in the assessment of ADMA metabolism at the organ level by measurement of arterio-venous concentration differences. PMID:16028689

  7. Nitric oxide as an antioxidant

    SciTech Connect

    Kanner, J.; Harel, S.; Granit, R. )

    1991-08-15

    Benzoate monohydroxy compounds, and in particular salicylate, were produced during interaction of ferrous complexes with hydrogen peroxide (Fenton reaction) in a N2 environment. These reactions were inhibited when Fe complexes were flushed, prior to the addition in the model system, by nitric oxide. Methionine oxidation to ethylene by Fenton reagents was also inhibited by nitric oxide. Myoglobin in several forms such as metmyoglobin, oxymyoglobin, and nitric oxide-myoglobin were interacted with an equimolar concentration of hydrogen peroxide. Spectra changes in the visible region and the changes in membrane (microsomes) lipid peroxidation by the accumulation of thiobarbituric acid-reactive substances (TBA-RS) were determined. The results showed that metmyoglobin and oxymyoglobin were activated by H2O2 to ferryl myoglobin, which initiates membrane lipid peroxidation; but not nitric oxide-myoglobin, which, during interaction with H2O2, did not form ferryl but metmyoglobin which only poorly affected lipid peroxidation. It is assumed that nitric oxide, liganded to ferrous complexes, acts to prevent the prooxidative reaction of these complexes with H2O2.

  8. Nitric oxide and cardiovascular disease.

    PubMed Central

    McIntyre, M.; Dominiczak, A. F.

    1997-01-01

    Endothelium-derived nitric oxide is an important regulatory molecule in cardiovascular function. Reduced availability of nitric oxide has been implicated in the pathogenesis of hypertension and atherosclerosis. PMID:9497971

  9. [Determining asthma treatment in children by monitoring fractional exhaled nitric oxide, sputum eosinophils and leukotriene B₄].

    PubMed

    Vizmanos-Lamotte, G; Cruz, M J; Gómez-Ollés, S; Muñoz, X; de Mir Messa, I; Moreno-Galdó, A

    2015-01-01

    Sputum eosinophils and exhaled fractional nitric oxide (FENO) are markers of airway inflammation in asthma. Cytokines, cysteinyl-leukotrienes and leukotriene B4 (LTB4) are responsible for this inflammation. The aim of this study is to determine the usefulness of these markers in monitoring asthma treatment in children. FENO, sputum eosinophils, and LTB4 in induced sputum were performed in 10 children (9-15 years old). These determinations were repeated four months later, after the beginning or an increase in the treatment. FENO values tended to decrease (P=.15), pulmonary function tended to improve (P=.10), and sputum eosinophils decreased (P=.003) compared to the first determination. There were no differences in LTB4 concentrations (P=.88). Sputum eosinophils seem to be more precise than FENO in the monitoring of inflammation in asthmatic children. PMID:24857428

  10. An improved method for the determination of dissolved nitric oxide (NO) in seawater samples

    NASA Astrophysics Data System (ADS)

    Lutterbeck, H. E.; Bange, H. W.

    2015-11-01

    Nitric oxide (NO) is a short-lived intermediate of the oceanic nitrogen cycle; however, due to its high reactivity, measurements of dissolved NO in seawater are rare. Here we present an improved method to determine NO concentrations in discrete seawater samples. The set-up of our system consisted of a chemiluminescence NO analyser connected to a stripping unit. The limit of detection for our method is 5 pmol NO in aqueous solution, which translates into 0.25 nmol L-1 when using a 20 mL seawater sample volume. Our method was applied to measure high-resolution depth profiles of dissolved NO during a cruise to the eastern tropical South Pacific Ocean. It is fast and comparably easy to handle; thus it opens the door for investigating the distribution of NO in the ocean, and it facilitates laboratory studies on NO pathways.

  11. Determinants of Children's Exhaled Nitric Oxide: New Insights from Quantile Regression

    PubMed Central

    Zhang, Yue; Berhane, Kiros; Eckel, Sandrah P.; Salam, Muhammad T.; Linn, William S.; Rappaport, Edward B.; Bastain, Theresa M.; Gilliland, Frank D.

    2015-01-01

    While the fractional concentration of exhaled nitric oxide (FeNO) has proven useful in asthma research, its exact role in clinical care remains unclear, in part due to unexplained inter-subject heterogeneity. In this study, we assessed the hypothesis that the effects of determinants of the fractional concentration of exhaled nitric oxide (FeNO) vary with differing levels of FeNO. In a population-based cohort of 1542 school children aged 12–15 from the Southern California Children's Health Study, we used quantile regression to investigate if the relationships of asthma, socio-demographic and clinical covariates with FeNO vary across its distribution. Differences in FeNO between children with and without asthma increased steeply as FeNO increased (Estimated asthma effects (in ppb) at selected 20th, 50th and 80th percentiles of FeNO are 2.4, 6.3 and 22.2, respectively) but the difference was steeper with increasing FeNO in boys and in children with active rhinitis (p-values<0.01). Active rhinitis also showed significantly larger effects on FeNO at higher concentrations of FeNO (Estimated active rhinitis effects (in ppb) at selected 20th, 50th and 80th percentiles of FeNO are 2.1, 5.7 and 14.3, respectively). Boys and children of Asian descent had higher FeNO than girls and non-Hispanic whites; these differences were significantly larger in those with higher FeNO (p-values<0.01). In summary, application of quantile regression techniques provides new insights into the determinants of FeNO showing substantially varying effects in those with high versus low concentrations. PMID:26214692

  12. Student Nitric Oxide Explorer

    NASA Astrophysics Data System (ADS)

    Solomon, Stanley C.; Barth, Charles A.; Axelrad, Penina; Bailey, Scott M.; Brown, Ronald; Davis, Randal L.; Holden, Timothy E.; Kohnert, Richard A.; Lacy, Frederick W.; McGrath, Michael T.; O'Connor, Darren C.; Perich, Jeffrey P.; Reed, Heather L.; Salada, Mark A.; Simpson, John; Srinivasan, Jeffrey M.; Stafford, George A.; Steg, Stephen R.; Tate, Gail A.; Westfall, James C.; White, Neil R.; Withnell, Peter R.; Woods, Thomas N.

    1996-10-01

    The Student Nitric Oxide Explorer (SNOE) is a small scientific spacecraft designed to launch on a PegasusTM XL vehicle for the Student Explorer Demonstration Initiative. Its scientific goals are to measure nitric oxide density in the lower thermosphere and to analyze the solar and magnetospheric influences that create it and cause its abundance to vary dramatically. The SNOE ('snowy') spacecraft and instrumentation is being designed and built at the University of Colorado Laboratory for Atmospheric and Space Physics (LASP) by a team of scientists, engineers, and students. The spacecraft is a compact hexagonal structure, 37' by 39', weighing approximately 280 lbs. It will be launched into a circular orbit, 550 km altitude, 97.5 degrees inclination for sun-synchronous precession at 10:30 AM ascending node. It is designed to spin at 5 rpm with the spin axis normal to the orbit plane. It carries three instruments: an ultraviolet spectrometer to measure nitric oxide altitude profiles on the limb, a two-channel ultraviolet photometer to measure auroral emissions in the nadir, and a five-channel solar soft x-ray photometer. An experimental GPS receiver is also included. The spacecraft structure is aluminum, with a center platform section for the instruments and subsystems. Static solar arrays are supported by a truss system. A spacecraft microprocessor handles all subsystem, instrument, and communications functions in an integrated fashion, including command decoding, attitude control, instrument commanding, data storage, and telemetry. The spacecraft is scheduled for launch in early 1997 and will be operated by students at LASP. For more information on the SNOE project, please visit http://lasp.colorado.edu/snoe/.

  13. Nitric oxide scavenging by curcuminoids.

    PubMed

    Sreejayan; Rao, M N

    1997-01-01

    Because curcumin, a compound with anti-inflammatory and anticancer activity, inhibits induction of nitric oxide synthase in activated macrophages and has been shown to be a potent scavenger of free radicals we have investigated whether it can scavenge nitric oxide directly. Curcumin reduced the amount of nitrite formed by the reaction between oxygen and nitric oxide generated from sodium nitroprusside. Other related compounds, e.g. demethoxycurcumin, bisdemethoxycurcumin and diacetylcurcumin were as active as curcumin, indicating that the methoxy and the phenolic groups are not essential for the scavenging activity. The results indicate curcumin to be a scavenger of nitric oxide. Because this compound is implicated in inflammation and cancer, the therapeutic properties of curcumin against these conditions might be at least partly explained by its free-radical scavenging properties, including those toward nitric oxide. PMID:9120760

  14. Nitric oxide signaling in plants.

    PubMed

    Shapiro, Allan D

    2005-01-01

    Plants have four nitric oxide synthase (NOS) enzymes. NOS1 appears mitochondrial, and inducible nitric oxide synthase (iNOS) chloroplastic. Distinct peroxisomal and apoplastic NOS enzymes are predicted. Nitrite-dependent NO synthesis is catalyzed by cytoplasmic nitrate reductase or a root plasma membrane enzyme, or occurs nonenzymatically. Nitric oxide undergoes both catalyzed and uncatalyzed oxidation. However, there is no evidence of reaction with superoxide, and S-nitrosylation reactions are unlikely except during hypoxia. The only proven direct targets of NO in plants are metalloenzymes and one metal complex. Nitric oxide inhibits apoplastic catalases/ascorbate peroxidases in some species but may stimulate these enzymes in others. Plants also have the NO response pathway involving cGMP, cADPR, and release of calcium from internal stores. Other known targets include chloroplast and mitochondrial electron transport. Nitric oxide suppresses Fenton chemistry by interacting with ferryl ion, preventing generation of hydroxyl radicals. Functions of NO in plant development, response to biotic and abiotic stressors, iron homeostasis, and regulation of respiration and photosynthesis may all be ascribed to interaction with one of these targets. Nitric oxide function in drought/abscisic acid (ABA)-induction of stomatal closure requires nitrate reductase and NOS1. Nitric oxide synthasel likely functions to produce sufficient NO to inhibit photosynthetic electron transport, allowing nitrite accumulation. Nitric oxide is produced during the hypersensitive response outside cells undergoing programmed cell death immediately prior to loss of plasma membrane integrity. A plasma membrane lipid-derived signal likely activates apoplastic NOS. Nitric oxide diffuses within the apoplast and signals neighboring cells via hydrogen peroxide (H2O2)-dependent induction of salicylic acid biosynthesis. Response to wounding appears to involve the same NOS and direct targets. PMID:16492476

  15. 49 CFR 173.337 - Nitric oxide.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 2 2011-10-01 2011-10-01 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...

  16. Nitric oxide and memory.

    PubMed

    Susswein, Abraham J; Katzoff, Ayelet; Miller, Nimrod; Hurwitz, Itay

    2004-04-01

    Nitric oxide (NO) is widely used in neural circuits giving rise to learning and memory. NO is an unusual neurotransmitter in its modes of release and action. Is its association with learning and memory related to its unusual properties? Reviewing the literature might allow the formulation of a general principle on how NO and memory are related. However, other than confirming that there is indeed a strong association between NO and memory, no simple rules emerge on the role of NO in learning and memory. The effects of NO are not associated with a particular stage or form of memory and are highly dependent on species, strain, and behavior or training paradigm. Nonetheless, a review does provide hints on why NO is associated with learning and memory. Unlike transmitters acting via receptors expressed only in neurons designed to respond to the transmitter, NO is a promiscuous signal that can affect a wide variety of neurons, via many molecular mechanisms. In circuits giving rise to learning and memory, it may be useful to signal some events via a promiscuous messenger having widespread effects. However, each circuit will use the promiscuous signal in a different way, to achieve different ends. PMID:15070489

  17. The Capacity of Red Blood Cells to Reduce Nitrite Determines Nitric Oxide Generation under Hypoxic Conditions

    PubMed Central

    Fens, Marcel H.; Larkin, Sandra K.; Oronsky, Bryan; Scicinski, Jan; Morris, Claudia R.; Kuypers, Frans A.

    2014-01-01

    Nitric oxide (NO) is a key regulator of vascular tone. Endothelial nitric oxide synthase (eNOS) is responsible for NO generation under normoxic conditions. Under hypoxia however, eNOS is inactive and red blood cells (RBC) provide an alternative NO generation pathway from nitrite to regulate hypoxic vasodilation. While nitrite reductase activity of hemoglobin is well acknowledged, little is known about generation of NO by intact RBC with physiological hemoglobin concentrations. We aimed to develop and apply a new approach to provide insights in the ability of RBC to convert nitrite into NO under hypoxic conditions. We established a novel experimental setup to evaluate nitrite uptake and the release of NO from RBC into the gas-phase under different conditions. NO measurements were similar to well-established clinical measurements of exhaled NO. Nitrite uptake was rapid, and after an initial lag phase NO release from RBC was constant in time under hypoxic conditions. The presence of oxygen greatly reduced NO release, whereas inhibition of eNOS and xanthine oxidoreductase (XOR) did not affect NO release. A decreased pH increased NO release under hypoxic conditions. Hypothermia lowered NO release, while hyperthermia increased NO release. Whereas fetal hemoglobin did not alter NO release compared to adult hemoglobin, sickle RBC showed an increased ability to release NO. Under all conditions nitrite uptake by RBC was similar. This study shows that nitrite uptake into RBC is rapid and release of NO into the gas-phase continues for prolonged periods of time under hypoxic conditions. Changes in the RBC environment such as pH, temperature or hemoglobin type, affect NO release. PMID:25007272

  18. Hepatocytes Determine the Hypoxic Microenvironment and Radiosensitivity of Colorectal Cancer Cells Through Production of Nitric Oxide That Targets Mitochondrial Respiration

    SciTech Connect

    Jiang, Heng; Verovski, Valeri N.; Leonard, Wim; Law, Ka Lun; Vermeersch, Marieke; Storme, Guy; Van den Berge, Dirk; Gevaert, Thierry; Sermeus, Alexandra; De Ridder, Mark

    2013-03-01

    Purpose: To determine whether host hepatocytes may reverse hypoxic radioresistance through nitric oxide (NO)-induced oxygen sparing, in a model relevant to colorectal cancer (CRC) liver metastases. Methods and Materials: Hepatocytes and a panel of CRC cells were incubated in a tissue-mimetic coculture system with diffusion-limited oxygenation, and oxygen levels were monitored by an oxygen-sensing fluorescence probe. To activate endogenous NO production, cocultures were exposed to a cytokine mixture, and the expression of inducible nitric oxide synthase was analyzed by reverse transcriptionpolymerase chain reaction, Western blotting, and NO/nitrite production. The mitochondrial targets of NO were examined by enzymatic activity. To assess hypoxic radioresponse, cocultures were irradiated and reseeded for colonies. Results: Resting hepatocytes consumed 10-40 times more oxygen than mouse CT26 and human DLD-1, HT29, HCT116, and SW480 CRC cells, and thus seemed to be the major effectors of hypoxic conditioning. As a result, hepatocytes caused uniform radioprotection of tumor cells at a 1:1 ratio. Conversely, NO-producing hepatocytes radiosensitized all CRC cell lines more than 1.5-fold, similar to the effect of selective mitochondrial inhibitors. The radiosensitizing effect was associated with a respiratory self-arrest of hepatocytes at the level of aconitase and complex II, which resulted in profound reoxygenation of tumor cells through oxygen sparing. Nitric oxideproducing hepatocytes were at least 10 times more active than NO-producing macrophages to reverse hypoxia-induced radioresistance. Conclusions: Hepatocytes were the major determinants of the hypoxic microenvironment and radioresponse of CRC cells in our model of metabolic hypoxia. We provide evidence that reoxygenation and radiosensitization of hypoxic CRC cells can be achieved through oxygen sparing induced by endogenous NO production in host hepatocytes.

  19. Nitric oxide deficiency determines global chromatin changes in Duchenne muscular dystrophy.

    PubMed

    Colussi, Claudia; Gurtner, Aymone; Rosati, Jessica; Illi, Barbara; Ragone, Gianluca; Piaggio, Giulia; Moggio, Maurizio; Lamperti, Costanza; D'Angelo, Grazia; Clementi, Emilio; Minetti, Giulia; Mozzetta, Chiara; Antonini, Annalisa; Capogrossi, Maurizio C; Puri, Pier Lorenzo; Gaetano, Carlo

    2009-07-01

    The present study provides evidence that abnormal patterns of global histone modification are present in the skeletal muscle nuclei of mdx mice and Duchenne muscular dystrophy (DMD) patients. A combination of specific histone H3 modifications, including Ser-10 phosphorylation, acetylation of Lys 9 and 14, and Lys 79 methylation, were found enriched in muscle biopsies from human patients affected by DMD and in late-term fetuses, early postnatal pups, or adult mdx mice. In this context, chromatin immunoprecipitation experiments showed an enrichment of these modifications at the loci of genes involved in proliferation or inflammation, suggesting a regulatory effect on gene expression. Remarkably, the reexpression of dystrophin induced by gentamicin treatment or the administration of nitric oxide (NO) donors reversed the abnormal pattern of H3 histone modifications. These findings suggest an unanticipated link between the dystrophin-activated NO signaling and the remodeling of chromatin. In this context, the regulation of class IIa histone deacetylases (HDACs) 4 and 5 was found altered as a consequence of the reduced NO-dependent protein phosphatase 2A activity, indicating that both NO and class IIa HDACs are important for satellite cell differentiation and gene expression in mdx mice. In conclusion, this work provides the first evidence of a role for NO as an epigenetic regulator in DMD. PMID:19264835

  20. Convergence of G Protein-Coupled Receptor and Nitric Oxide Pathways Determines the Outcome to Cardiac Ischemic Injury

    PubMed Central

    Huang, Z. Maggie; Gao, Erhe; Fonseca, Fabio; Hayashi, Hiroki; Shang, Xiying; Hoffman, Nicholas E.; Chuprun, J. Kurt; Tian, Xufan; Tilley, Doug G.; Madesh, Muniswamy; Lefer, David J.; Stamler, Jonathan S.; Koch, Walter J.

    2014-01-01

    Heart failure caused by ischemic heart disease is a leading cause of death in the developed world. Treatment is currently centered on regimens involving G protein-coupled receptors (GPCRs) or nitric oxide (NO). These regimens are thought to target distinct molecular pathways. We showed that these pathways were interdependent and converged on the effector GRK2 (GPCR kinase 2) to regulate myocyte survival and function. Ischemic injury coupled to GPCR activation, including GPCR desensitization and myocyte loss, requires GRK2 activation, and we found that cardioprotection mediated by S-nitrosylation and inhibition of GRK2 depended on endothelial nitric oxide synthase (eNOS). Conversely, the cardioprotective effects of NO bioactivity were absent in a knock-in mouse with a form of GRK2 that cannot be S-nitrosylated. Because GRK2 and eNOS inhibit each other, the balance of the activities these enzymes in the myocardium determined the outcome to ischemic injury. Our findings suggest new insights into the mechanism of action of classic drugs used to treat heart failure and new therapeutic approaches to ischemic heart disease. PMID:24170934

  1. A Kinetic Platform to Determine the Fate of Nitric Oxide in Escherichia coli

    PubMed Central

    Robinson, Jonathan L.; Brynildsen, Mark P.

    2013-01-01

    Nitric oxide (NO•) is generated by the innate immune response to neutralize pathogens. NO• and its autoxidation products have an extensive biochemical reaction network that includes reactions with iron-sulfur clusters, DNA, and thiols. The fate of NO• inside a pathogen depends on a kinetic competition among its many targets, and is of critical importance to infection outcomes. Due to the complexity of the NO• biochemical network, where many intermediates are short-lived and at extremely low concentrations, several species can be measured, but stable products are non-unique, and damaged biomolecules are continually repaired or regenerated, kinetic models are required to understand and predict the outcome of NO• treatment. Here, we have constructed a comprehensive kinetic model that encompasses the broad reactivity of NO• in Escherichia coli. The incorporation of spontaneous and enzymatic reactions, as well as damage and repair of biomolecules, allowed for a detailed analysis of how NO• distributes in E. coli cultures. The model was informed with experimental measurements of NO• dynamics, and used to identify control parameters of the NO• distribution. Simulations predicted that NO• dioxygenase (Hmp) functions as a dominant NO• consumption pathway at O2 concentrations as low as 35 µM (microaerobic), and interestingly, loses utility as the NO• delivery rate increases. We confirmed these predictions experimentally by measuring NO• dynamics in wild-type and mutant cultures at different NO• delivery rates and O2 concentrations. These data suggest that the kinetics of NO• metabolism must be considered when assessing the importance of cellular components to NO• tolerance, and that models such as the one described here are necessary to rigorously investigate NO• stress in microbes. This model provides a platform to identify novel strategies to potentiate the effects of NO•, and will serve as a template from which analogous models can be generated for other organisms. PMID:23658508

  2. Aqueous nitrite ion determination by selective reduction and gas phase nitric oxide chemiluminescence

    NASA Technical Reports Server (NTRS)

    Dunham, A. J.; Barkley, R. M.; Sievers, R. E.; Clarkson, T. W. (Principal Investigator)

    1995-01-01

    An improved method of flow injection analysis for aqueous nitrite ion exploits the sensitivity and selectivity of the nitric oxide (NO) chemilluminescence detector. Trace analysis of nitrite ion in a small sample (5-160 microL) is accomplished by conversion of nitrite ion to NO by aqueous iodide in acid. The resulting NO is transported to the gas phase through a semipermeable membrane and subsequently detected by monitoring the photoemission of the reaction between NO and ozone (O3). Chemiluminescence detection is selective for measurement of NO, and, since the detection occurs in the gas-phase, neither sample coloration nor turbidity interfere. The detection limit for a 100-microL sample is 0.04 ppb of nitrite ion. The precision at the 10 ppb level is 2% relative standard deviation, and 60-180 samples can be analyzed per hour. Samples of human saliva and food extracts were analyzed; the results from a standard colorimetric measurement are compared with those from the new chemiluminescence method in order to further validate the latter method. A high degree of selectivity is obtained due to the three discriminating steps in the process: (1) the nitrite ion to NO conversion conditions are virtually specific for nitrite ion, (2) only volatile products of the conversion will be swept to the gas phase (avoiding turbidity or color in spectrophotometric methods), and (3) the NO chemiluminescence detector selectively detects the emission from the NO + O3 reaction. The method is free of interferences, offers detection limits of low parts per billion of nitrite ion, and allows the analysis of up to 180 microL-sized samples per hour, with little sample preparation and no chromatographic separation. Much smaller samples can be analyzed by this method than in previously reported batch analysis methods, which typically require 5 mL or more of sample and often need chromatographic separations as well.

  3. BIOGENIC NITRIC OXIDE EMISSIONS FROM CROPLAND SOILS

    EPA Science Inventory

    Emissions of nitric oxide (NO) were determined during late spring and summer 1995 and the spring of 1996 from four agricultural soils on which four different crops were grown. These agricultural soils were located at four different sites throughout North Carolina. Emission rates ...

  4. Determination of motor activity and anxiety-related behaviour in rodents: methodological aspects and role of nitric oxide

    PubMed Central

    Sestakova, Natalia; Puzserova, Angelika; Kluknavsky, Michal

    2013-01-01

    In various areas of the bio-medical, pharmacological and psychological research a multitude of behavioural tests have been used to investigate the effects of environmental, genetic and epi-genetic factors as well as pharmacological substances or diseased states on behaviour and thus on the physiological and psycho-social status of experimental subjects. This article is reviewing the most frequently used behavioural tests in animal research (open field, elevated plus maze, zero maze, and black and white box). It provides a summary of common characteristics as well as differences in the methods used in various studies to determine motor activity, anxiety and emotionality. Additionally to methodological aspects, strain, sex and stress-related differences as well as the involvement of nitric oxide in modulation of motor activity and anxiety of rodents were briefly reviewed. PMID:24678249

  5. Nitric oxide releasing nanoparticle synthesis and characterization.

    PubMed

    Han, George; Friedman, Adam J; Friedman, Joel M

    2011-01-01

    While the potential applications of nitric oxide for both understanding human physiology and treating disease are far reaching, the development of a reliable, cost-effective, and practical sustained delivery system for nitric oxide has yet to emerge. Using a sol-gel/glass hybrid system, we have demonstrated controlled, sustained release of nitric oxide from a stable, dry powder. Upon exposure to an aqueous environment, the material begins releasing therapeutic levels of nitric oxide over several hours to days, making it an ideal material for evaluation of nitric oxide efficacy for both clinical and research applications. PMID:21161638

  6. Inflammatory monocytes determine endothelial nitric-oxide synthase uncoupling and nitro-oxidative stress induced by angiotensin II.

    PubMed

    Kossmann, Sabine; Hu, Hanhan; Steven, Sebastian; Schönfelder, Tanja; Fraccarollo, Daniela; Mikhed, Yuliya; Brähler, Melanie; Knorr, Maike; Brandt, Moritz; Karbach, Susanne H; Becker, Christian; Oelze, Matthias; Bauersachs, Johann; Widder, Julian; Münzel, Thomas; Daiber, Andreas; Wenzel, Philip

    2014-10-01

    Endothelial nitric-oxide synthase (eNOS) uncoupling and increased inducible NOS (iNOS) activity amplify vascular oxidative stress. The role of inflammatory myelomonocytic cells as mediators of these processes and their impact on tetrahydrobiopterin availability and function have not yet been defined. Angiotensin II (ATII, 1 mg/kg/day for 7 days) increased Ly6C(high) and CD11b(+)/iNOS(high) leukocytes and up-regulated levels of eNOS glutathionylation in aortas of C57BL/6 mice. Vascular iNOS-dependent NO formation was increased, whereas eNOS-dependent NO formation was decreased in aortas of ATII-infused mice as assessed by electron paramagnetic resonance (EPR) spectroscopy. Diphtheria toxin-mediated ablation of lysozyme M-positive (LysM(+)) monocytes in ATII-infused LysM(iDTR) transgenic mice prevented eNOS glutathionylation and eNOS-derived N(ω)-nitro-L-arginine methyl ester-sensitive superoxide formation in the endothelial layer. ATII increased vascular guanosine triphosphate cyclohydrolase I expression and biopterin synthesis in parallel, which was reduced in monocyte-depleted LysM(iDTR) mice. Vascular tetrahydrobiopterin was increased by ATII infusion but was even higher in monocyte-depleted ATII-infused mice, which was paralleled by a strong up-regulation of dihydrofolate reductase expression. EPR spectroscopy revealed that both vascular iNOS- and eNOS-dependent NO formation were normalized in ATII-infused mice following monocyte depletion. Additionally, deletion as well as pharmacologic inhibition of iNOS prevented ATII-induced endothelial dysfunction. In summary, ATII induces an inflammatory cell-dependent increase of iNOS, guanosine triphosphate cyclohydrolase I, tetrahydrobiopterin, NO formation, and nitro-oxidative stress as well as eNOS uncoupling in the vessel wall, which can be prevented by ablation of LysM(+) monocytes. PMID:25143378

  7. [Nitric oxide production in plants].

    PubMed

    Małolepsza, Urszula

    2007-01-01

    There are still many controversial observations and opinions on the cellular/subcellular localization and sources of endogenous nitric oxide synthesis in plant cells. NO can be produced in plants by non-enzymatic and enzymatic systems depending on plant species, organ or tissue as well as on physiological state of the plant and changing environmental conditions. The best documented reactions in plant that contribute to NO production are NO production from nitrite as a substrate by cytosolic (cNR) and membrane bound (PM-NR) nitrate reductases (NR), and NO production by several arginine-dependent nitric oxide synthase-like activities (NOS). The latest papers indicate that mitochondria are an important source of arginine- and nitrite-dependent NO production in plants. There are other potential enzymatic sources of NO in plants including xanthine oxidoreductase, peroxidase, cytochrome P450. PMID:18399354

  8. Arginine metabolism: nitric oxide and beyond.

    PubMed Central

    Wu, G; Morris, S M

    1998-01-01

    Arginine is one of the most versatile amino acids in animal cells, serving as a precursor for the synthesis not only of proteins but also of nitric oxide, urea, polyamines, proline, glutamate, creatine and agmatine. Of the enzymes that catalyse rate-controlling steps in arginine synthesis and catabolism, argininosuccinate synthase, the two arginase isoenzymes, the three nitric oxide synthase isoenzymes and arginine decarboxylase have been recognized in recent years as key factors in regulating newly identified aspects of arginine metabolism. In particular, changes in the activities of argininosuccinate synthase, the arginases, the inducible isoenzyme of nitric oxide synthase and also cationic amino acid transporters play major roles in determining the metabolic fates of arginine in health and disease, and recent studies have identified complex patterns of interaction among these enzymes. There is growing interest in the potential roles of the arginase isoenzymes as regulators of the synthesis of nitric oxide, polyamines, proline and glutamate. Physiological roles and relationships between the pathways of arginine synthesis and catabolism in vivo are complex and difficult to analyse, owing to compartmentalized expression of various enzymes at both organ (e.g. liver, small intestine and kidney) and subcellular (cytosol and mitochondria) levels, as well as to changes in expression during development and in response to diet, hormones and cytokines. The ongoing development of new cell lines and animal models using cDNA clones and genes for key arginine metabolic enzymes will provide new approaches more clearly elucidating the physiological roles of these enzymes. PMID:9806879

  9. Nitric oxide function in atherosclerosis

    PubMed Central

    Matthys, K. E.

    1997-01-01

    Atherosclerosis is a chronic inflammatory process in the intima of conduit arteries, which disturbs the endothelium-dependent regulation of the vascular tone by the labile liposoluble radical nitric oxide (NO) formed by the constitutive endothelial nitric oxide synthase (eNOS). This defect predisposes to coronary vasospasm and cardiac ischaemia, with anginal pain as the typical clinical manifestation. It is now appreciated that endothelial dysfunction is an early event in atherogenesis and that it may also involve the microcirculation, in which atherosclerotic lesions do not develop. On the other hand, the inflammatory environment in atherosclerotic plaques may result in the expression of the inducible NO synthase (iNOS) isozyme. Whether the dysfunction in endothelial NO production is causal to, or the result of, atherosclerotic lesion formation is still highly debated. Most evidence supports the hypothesis that constitutive endothelial NO release protects against atherogenesis e.g. by preventing smooth muscle cell proliferation and leukocyte adhesion. Nitric oxide generated by the inducible isozyme may be beneficial by replacing the failing endothelial production but excessive release may damage the vascular wall cells, especially in combination with reactive oxygen intermediates. PMID:18472828

  10. Nitric oxide: a challenge to chiropractic

    PubMed Central

    Morgan, Lon

    2000-01-01

    The 1998 Nobel Prize in Physiology or Medicine recognized the biological significance of nitric oxide. Nitric oxide is derived from the amino acid arginine. It is intimately involved with circulatory vessel dilation where, for example, it protects against heart attacks, and is the basis for new medications such as Sildenafil (Viagra). Nitric oxide acts as a neurotransmitter and can modulate many neurological reactions. The immune system uses nitric oxide to destroy pathogens by interfering with key enzymes. Nitric oxide is responsible for both osteoclastic and osteoblastic responses in bone and is a key player in the degenerative aspects of arthritis. The process of apoptosis employs nitric oxide in the orderly removal of unneeded cells. There is clear evidence that major signaling and control mechanisms exist in the body apart from the nervous system. Chiropractic is thus faced with the challenge of how to incorporate this new knowledge which conflicts with traditional chiropractic concepts.

  11. Measurement of nasal nitric oxide.

    PubMed

    Corbelli, Regula; Hammer, Jrg

    2007-09-01

    Nasal nitric oxide (nNO) is produced in high quantity in the upper airways. It is thought to be involved in host defence functions and regulation of mucociliary function, and to serve as a biochemical airborne transmitter. The measurement of nNO is easy and non-invasive. It has evolved as a screening test to exclude primary ciliary dyskinesia (PCD) in patients with suggestive symptoms, because nNO is extremely low in this condition. Nasal NO is also altered in other nasal, sinus and pulmonary pathologies, but is without diagnostic value outside of PCD. PMID:17868927

  12. Nitric oxide is required for determining root architecture and lignin composition in sunflower. Supporting evidence from microarray analyses.

    PubMed

    Corti Monzón, Georgina; Pinedo, Marcela; Di Rienzo, Julio; Novo-Uzal, Esther; Pomar, Federico; Lamattina, Lorenzo; de la Canal, Laura

    2014-05-30

    Nitric oxide (NO) is a signal molecule involved in several physiological processes in plants, including root development. Despite the importance of NO as a root growth regulator, the knowledge about the genes and metabolic pathways modulated by NO in this process is still limited. A constraint to unravel these pathways has been the use of exogenous applications of NO donors that may produce toxic effects. We have analyzed the role of NO in root architecture through the depletion of endogenous NO using the scavenger cPTIO. Sunflower seedlings growing in liquid medium supplemented with cPTIO showed unaltered primary root length while the number of lateral roots was deeply reduced; indicating that endogenous NO participates in determining root branching in sunflower. The transcriptional changes induced by NO depletion have been analyzed using a large-scale approach. A microarray analysis showed 330 genes regulated in the roots (p≤0.001) upon endogenous NO depletion. A general cPTIO-induced up-regulation of genes involved in the lignin biosynthetic pathway was observed. Even if no detectable changes in total lignin content could be detected, cell walls analyses revealed that the ratio G/S lignin increased in roots treated with cPTIO. This means that endogenous NO may control lignin composition in planta. Our results suggest that a fine tuning regulation of NO levels could be used by plants to regulate root architecture and lignin composition. The functional implications of these findings are discussed. PMID:24747108

  13. The Moraxella catarrhalis Nitric Oxide Reductase Is Essential for Nitric Oxide Detoxification▿

    PubMed Central

    Wang, Wei; Kinkel, Traci; Martens-Habbena, Willm; Stahl, David A.; Fang, Ferric C.; Hansen, Eric J.

    2011-01-01

    Moraxella catarrhalis is a Gram-negative obligate aerobe that is an important cause of human respiratory tract infections. The M. catarrhalis genome encodes a predicted truncated denitrification pathway that reduces nitrate to nitrous oxide. We have previously shown that expression of both the M. catarrhalis aniA (encoding a nitrite reductase) and norB (encoding a putative nitric oxide reductase) genes is repressed by the transcriptional regulator NsrR under aerobic conditions and that M. catarrhalis O35E nsrR mutants are unable to grow in the presence of low concentrations of nitrite (W. Wang, et al., J. Bacteriol. 190:7762–7772, 2008). In this study, we constructed an M. catarrhalis norB mutant and showed that planktonic growth of this mutant is inhibited by low levels of nitrite, whether or not an nsrR mutation is present. To determine the importance of NorB in this truncated denitrification pathway, we analyzed the metabolism of nitrogen oxides by norB, aniA norB, and nsrR norB mutants. We found that norB mutants are unable to reduce nitric oxide and produce little or no nitrous oxide from nitrite. Furthermore, nitric oxide produced from nitrite by the AniA protein is bactericidal for a Moraxella catarrhalis O35E norB mutant but not for wild-type O35E bacteria under aerobic growth conditions in vitro, suggesting that nitric oxide catabolism in M. catarrhalis is accomplished primarily by the norB gene product. Measurement of bacterial protein S-nitrosylation directly implicates nitrosative stress resulting from AniA-dependent nitric oxide formation as a cause of the growth inhibition of norB and nsrR mutants by nitrite. PMID:21441505

  14. Two Dimensional Polymer That Generates Nitric Oxide.

    DOEpatents

    McDonald, William F.; Koren, Amy B.

    2005-10-04

    A polymeric composition that generates nitric oxide and a process for rendering the surface of a substrate nonthrombogenic by applying a coating of the polymeric composition to the substrate are disclosed. The composition comprises: (1) a crosslinked chemical combination of (i) a polymer having amino group-containing side chains along a backbone forming the polymer, and (ii) a crosslinking agent containing functional groups capable of reacting with the amino groups; and (2) a plurality of nitric oxide generating functional groups associated with the crosslinked chemical combination. Once exposed to a physiological environment, the coating generates nitric oxide thereby inhibiting platelet aggregation. In one embodiment, the nitric oxide generating functional groups are provided by a nitrated compound (e.g., nitrocellulose) imbedded in the polymeric composition. In another embodiment, the nitric oxide generating functional groups comprise N2O2- groups covalently bonded to amino groups on the polymer.

  15. Role of oxidative stress and nitric oxide in atherothrombosis

    PubMed Central

    Lubos, Edith; Handy, Diane E.; Loscalzo, Joseph

    2008-01-01

    During the last decade basic and clinical research has highlighted the central role of reactive oxygen species (ROS) in cardiovascular disease. Enhanced production or attenuated degradation of ROS leads to oxidative stress, a process that affects endothelial and vascular function, and contributes to vascular disease. Nitric oxide (NO), a product of the normal endothelium, is a principal determinant of normal endothelial and vascular function. In states of inflammation, NO production by the vasculature increases considerably and, in conjunction with other ROS, contributes to oxidative stress. This review examines the role of oxidative stress and NO in mechanisms of endothelial and vascular dysfunction with an emphasis on atherothrombosis. PMID:18508590

  16. Triple point determinations of monomethylhydrazine and nitrogen tetroxide, 2.2 percent by weight nitric oxide

    NASA Technical Reports Server (NTRS)

    Smith, Irwin D.; Dhooge, Patrick M.

    1977-01-01

    A series of tests was performed to ascertain the triple points of monomethylhydrazine and nitrogen tetroxide. A laboratory method indicated a triple point for monomethylhydrazine, but tests in a large vacuum chamber indicated that a triple point does not occur in spacelike conditions because the mono-methylhydrazine tends to supercool. Instead, an effective freezing point (with agitation) was obtained. New experimental values for liquid monomethylhydrazine vapor pressure were determined for temperatures from 275.2 to 207.6 K. The values were used to derive vapor pressure equations. Tentative values were obtained for the effective freezing point of nitrogen tetroxide spacelike conditions.

  17. Nanocarriers for Nitric Oxide Delivery

    PubMed Central

    Saraiva, Juliana; Marotta-Oliveira, Samantha S.; Cicillini, Simone Aparecida; Eloy, Josimar de Oliveira; Marchetti, Juliana Maldonado

    2011-01-01

    Nitric oxide (NO) is a promising pharmaceutical agent that has vasodilative, antibacterial, and tumoricidal effects. To study the complex and wide-ranging roles of NO and to facilitate its therapeutic use, a great number of synthetic compounds (e.g., nitrosothiols, nitrosohydroxyamines, N-diazeniumdiolates, and nitrosyl metal complexes) have been developed to chemically stabilize and release NO in a controlled manner. Although NO is currently being exploited in many biomedical applications, its use is limited by several factors, including a short half-life, instability during storage, and potential toxicity. Additionally, efficient methods of both localized and systemic in vivo delivery and dose control are needed. One strategy for addressing these limitations and thus increasing the utility of NO donors is based on nanotechnology. PMID:21869934

  18. Analytical Chemistry of Nitric Oxide

    PubMed Central

    Hetrick, Evan M.

    2013-01-01

    Nitric oxide (NO) is the focus of intense research, owing primarily to its wide-ranging biological and physiological actions. A requirement for understanding its origin, activity, and regulation is the need for accurate and precise measurement techniques. Unfortunately, analytical assays for monitoring NO are challenged by NO’s unique chemical and physical properties, including its reactivity, rapid diffusion, and short half-life. Moreover, NO concentrations may span pM to µM in physiological milieu, requiring techniques with wide dynamic response ranges. Despite such challenges, many analytical techniques have emerged for the detection of NO. Herein, we review the most common spectroscopic and electrochemical methods, with special focus on the fundamentals behind each technique and approaches that have been coupled with modern analytical measurement tools or exploited to create novel NO sensors. PMID:20636069

  19. Genotype polymorphisms of genes regulating nitric oxide synthesis determine long-term arteriovenous fistula patency in male hemodialysis patients.

    PubMed

    Lee, Kuo-Hua; Tsai, Wen-Jung; Chen, Yu-Wei; Yang, Wu-Chang; Lee, Chiu-Yang; Ou, Shuo-Ming; Chen, Yung-Tai; Chien, Chih-Chiang; Lee, Pui-Ching; Chung, Ming-Yi; Lin, Chih-Ching

    2016-03-01

    Objectives Nitric oxide (NO) is a pivotal vasoactive substance modulating arteriovenous fistula (AVF) patency for hemodialysis (HD). Since genetic background could be the predicting factor of AVF malfunction, we aimed to investigate whether the NO-related genotype polymorphisms determine AVF survival rates. Methods This is a retrospective, observational, multi-center study involving eight HD units in Taiwan, enrolled 580 patients initiating maintenance HD via AVFs. Genotype polymorphisms of NO-biosynthesis regulating enzymes (DDAH-1, DDAH-2, eNOS and PRMT1) were compared between HD patients with (n = 161) and without (n = 419) history of AVF malfunction. Subgroup analyses by gender were performed to evaluate the genetic effect in difference sexes. Results In overall population, statistically significant associations were not found between AVF malfunction and the genetic polymorphisms. In the male subgroup (n = 313), a single nucleotide polymorphism (SNP) of PRMT1, rs10415880 (IVS9-193 A/G), showed a significant association with AVF malfunction. Male patients with AA/AG genotype had inferior AVF outcomes compared to GG genotype, regarding primary patency (70.6% vs. 40.9%, p = 0.001), assisted primary patency (81.0% vs. 58.4%, p < 0.001) and secondary patency (83.7% vs. 63.3%, p < 0.001) at a 5-year observation period. From multivariate Cox regression model, the AA/AG genotypes of PRMT1 were an independent risk factor for AVF malfunction in men (HR: 4.539, 95% CI 2.015-10.223; p < 0.001). However, such associations were not found in women. Conclusions rs10415880, the SNP of PRMT1 could be a novel genetic marker associated with AVF malfunction risk in male HD patients. Those with AA and AG genotypes of rs10415880 may predict a poorer long-term patency of AVF. PMID:26643995

  20. Nitric oxide and oxidative stress in placental explant cultures.

    PubMed

    Goncalves, Juvic M; Casart, Ysabel C; Camejo, María I

    2016-02-01

    Placental explant culture, and cellular cytolysis and cellular differentiation have been previously studied. However, oxidative stress and nitric oxide profiles have not been evaluated in these systems. The aim of this study was to determine the release of lipid peroxidation and nitric oxide from placental explants cultured over a seven day period. Placental explants were maintained for seven days in culture and the medium was changed every 24 hours. The response was assessed in terms of syncytiotrophoblast differentiation (human chorionic gonadotropin, hCG), cellular cytolysis (lactate dehydrogenase, LDH), oxidative stress (thiobarbituric acid reactive substances, TBARS), and nitric oxide (NO). Levels of hCG increased progressively from day two to attain its highest level on days four and five after which it decreased gradually. In contrast, the levels of LDH, TBARS, and NO were elevated in the early days of placental culture when new syncytiotrophoblast from cytotrophoblast were forming and also in the last days of culture when tissue was declining. In conclusion, the levels of NO and lipid peroxidation follow a pattern similar to LDH and contrary to hCG. Future placental explant studies to evaluate oxidative stress and NO should consider the physiological changes inherent during the time of culture. PMID:26366632

  1. Sampling nitric oxide from combustion gases.

    NASA Technical Reports Server (NTRS)

    England, C.; Houseman, J.; Teixeira, D. P.

    1973-01-01

    Experimental study of several sampling tube and probe material compositions and designs aimed at preventing nitric oxide reduction when sampling nitric oxide from combustion gases. A 250,000 Btu/h furnace fired with technical grade methane was used for testing the sampling probes over a wide range of air-fuel mixtures. The results obtained include the finding that the use of stainless steel in probes creates inaccuracies in near-stoichiometric and fuel-rich sampling in hydrocarbon flames. For very fuel-rich flames, water cooling is needed even in quartz probes to prevent significant reduction of nitric oxide.-

  2. Calculated Effects of Nitric Oxide Flow Contamination on Scramjet Performance

    NASA Technical Reports Server (NTRS)

    Fischer, Karen E.; Rock, Kenneth E.

    1995-01-01

    The level of nitric oxide contamination in the test gas of the NASA Langley Research Center Arc-Heated Scramjet Test Facility and the effect of the contamination on scramjet test engine performance were investigated analytically. The study was conducted for standard facility conditions corresponding to Mach 6, 7, and 8 flight simulations. The analytically determined levels of nitric oxide produced in the facility are compared with experimentally measured levels. Results of the analysis indicate that nitric oxide levels range from one to three mole percent, which corroborates the measured levels. A three-stream combustor code with finite rate chemistry was used to investigate how nitric oxide affects scramjet performance in terms of combustor pressure rise, heat release, and thrust performance. Results indicate minimal effects on engine performance for the test conditions of this investigation.

  3. 21 CFR 862.3080 - Breath nitric oxide test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 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...

  4. 21 CFR 862.3080 - Breath nitric oxide test system.

    Code of Federal Regulations, 2010 CFR

    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...

  5. 21 CFR 868.5165 - Nitric oxide administration apparatus.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Nitric oxide administration apparatus. 868.5165... apparatus. (a) Identification. The nitric oxide administration apparatus is a device used to add nitric oxide to gases that are to be breathed by a patient. The nitric oxide administration apparatus is to...

  6. 21 CFR 868.5165 - Nitric oxide administration apparatus.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Nitric oxide administration apparatus. 868.5165... apparatus. (a) Identification. The nitric oxide administration apparatus is a device used to add nitric oxide to gases that are to be breathed by a patient. The nitric oxide administration apparatus is to...

  7. Nitric oxide production by Tunguska meteor

    NASA Technical Reports Server (NTRS)

    Park, C.

    1978-01-01

    The nonequilibrium chemical processes of nitric oxide formation are computed for the wake of the Tunguska meteor of 1908. The wake characteristics are derived by carrying out an optically-thick radiation field analysis for ablation of the meteoroid. The wake flow field is approximated by a one-dimensional, well-stirred reactor model. Known characteristics of the Tunguska event are imposed as constraints, and three controlling parameters - chemical composition, density, and velocity - are varied over a range around the values derived by Korobeinikov et al. (1976) and Petrov and Stulov (1975). The calculation shows that at least 19 million tons of nitric oxide is produced between the altitudes of 10 and 50 km. The anomalous atmospheric phenomena following the event are attributed to the reactions involving nitric oxide thus produced and atmospheric ozone. It is speculated that the nitric oxide produced by the event fertilized the area near the fall, causing the observed rapid plant growth.

  8. Nitric Oxide Synthases and Atrial Fibrillation

    PubMed Central

    Bonilla, Ingrid M.; Sridhar, Arun; Györke, Sandor; Cardounel, Arturo J.; Carnes, Cynthia A.

    2012-01-01

    Oxidative stress has been implicated in the pathogenesis of atrial fibrillation. There are multiple systems in the myocardium which contribute to redox homeostasis, and loss of homeostasis can result in oxidative stress. Potential sources of oxidants include nitric oxide synthases (NOS), which normally produce nitric oxide in the heart. Two NOS isoforms (1 and 3) are normally expressed in the heart. During pathologies such as heart failure, there is induction of NOS 2 in multiple cell types in the myocardium. In certain conditions, the NOS enzymes may become uncoupled, shifting from production of nitric oxide to superoxide anion, a potent free radical and oxidant. Multiple lines of evidence suggest a role for NOS in the pathogenesis of atrial fibrillation. Therapeutic approaches to reduce atrial fibrillation by modulation of NOS activity may be beneficial, although further investigation of this strategy is needed. PMID:22536189

  9. Amplified laser absorption - Detection of nitric oxide.

    NASA Technical Reports Server (NTRS)

    Chackerian, C., Jr.; Weisbach, M. F.

    1973-01-01

    Experimental results are reported for the power loss of a carbon monoxide gas laser due to the absorption of small amounts of nitric oxide placed in an intra-laser-cavity absorption cell. It was found, for the particular experimental conditions employed, that the absorption coefficient of nitric oxide at 1900.04/cm is enhanced more than two orders of magnitude when it is in the intracavity cell. Finally, the experimental results are compared with theoretical calculations.

  10. [Nitric oxide and lipid peroxidation].

    PubMed

    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 in vivo and in vitro and could be driven by environmental conditions such as pH, relative concentrations of NO and ROS, ferryl species. PMID:8673627

  11. Nitric Oxide Homeostasis in Neurodegenerative Diseases.

    PubMed

    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. PMID:26391043

  12. Neural mechanisms in nitric-oxide-deficient hypertension

    NASA Technical Reports Server (NTRS)

    Sander, M.; Victor, R. G.; Blomqvist, C. G. (Principal Investigator)

    1999-01-01

    Nitric oxide is hypothesized to be an inhibitory modulator of central sympathetic nervous outflow, and deficient neuronal nitric oxide production to cause sympathetic overactivity, which then contributes to nitric-oxide-deficient hypertension. The biochemical and neuroanatomical basis for this concept revolves around nitric oxide modulation of glutamatergic neurotransmission within brainstem vasomotor centers. The functional consequence of neuronal nitric oxide in blood pressure regulation is, however, marked by an apparent conflict in the literature. On one hand, conscious animal studies using sympathetic blockade suggest a significant role for neuronal nitric oxide deficiency in the development of nitric-oxide-deficient hypertension, and on the other hand, there is evidence against such a role derived from 'knock-out' mice lacking nitric-oxide synthase 1, the major source of neuronal nitric oxide.

  13. The formation of a complex between calmodulin and neuronal nitric oxide synthase is determined by ESI-MS

    PubMed Central

    Shirran, Sally; Garnaud, Pierre; Daff, Simon; McMillan, Derek; Barran, Perdita

    2005-01-01

    Calmodulin (CaM) is an acidic ubiquitous calcium binding protein, involved in many intracellular processes, which often involve the formation of complexes with a variety of protein and peptide targets. One such system, activated by Ca2+ loaded CaM, is regulation of the nitric oxide synthase (NOS) enzymes, which in turn control the production of the signalling molecule and cytotoxin NO. A recent crystallographic study mapped the interaction of CaM with endothelial NOS (eNOS) using a 20 residue peptide comprising the binding site within eNOS. Here the interaction of CaM to the FMN domain of neuronal nitric oxide synthase (nNOS) has been investigated using electrospray ionization mass spectrometry (ESI-MS). The 46?kDa complex formed by CaMnNOS has been retained in the gas-phase, and is shown to be exclusively selective for CaM.4Ca2+. Further characterization of this important biological system has been afforded by examining a complex of CaM with a 22 residue synthetic peptide, which represents the linker region between the reductase and oxygenase domains of nNOS. This nNOS linker peptide, which is found to be random coil in aqueous solution by both circular dichroism and molecular modelling, also exhibits great discrimination for the form of CaM loaded with 4[Ca2+]. The peptide binding loop is presumed to be configured to an ?-helix on binding to CaM as was found for the related eNOS binding peptide. Our postulate is supported by gas-phase molecular dynamics calculations performed on the isolated nNOS peptide. Collision induced dissociation was employed to probe the strength of binding of the nNOS binding peptide to CaM.4Ca2+. The methodology taken here is a new approach in understanding the CaMnNOS binding site, which could be employed in future to inform the specificity of CaM binding to other NOS enzymes. PMID:16849206

  14. Cogeneration of electric energy and nitric oxide

    SciTech Connect

    Vayenas, C.G.; Farr, R.D.

    1980-05-09

    A solid electrolyte fuel cell operating on ammonia fuel has been constructed and tested. The yield of nitric oxide can exceed 60 percent with simultaneous electric energy production. Two dimensionless numbers have been identified which govern the product selectivity and power output of this fuel cell. The cell appears to be a promising candidate for nitric acid and electric energy cogeneration. The design and electrochemical reactions in the fuel cell are described.

  15. The Effect of Nitric Oxide on Bacteria

    PubMed Central

    Shank, J. L.; Silliker, J. H.; Harper, R. H.

    1962-01-01

    Nitric oxide, as well as several other oxides of nitrogen, were assayed for their antibacterial action. It is shown that nitric oxide has virtually no effect on bacteria, whereas both NaNO3 and NaNO2 appear to have either neutral or stimulatory effects. It is suggested that the formation of nitrous acid is mainly responsible for the quantitative as well as the qualitative changes that occur in the bacterial flora of cured meat. A pH-dependent “nitrite cycle” is presented to account for the production of nitrous acid in cured meat systems. PMID:13911227

  16. Nitric oxide is not the sole determinant of hypercapnic or metabolically driven vasodilation in the cerebral circulation.

    PubMed

    Goadsby, P J

    1994-09-01

    Nitric oxide (NO) has recently been suggested to play a major role in a number of circulatory responses both within and outside the central nervous system. It has been linked to hypercapnic vasodilatation, metabolically driven changes in cerebral blood flow and hypoxia-induced changes in brain blood flow. In the studies the question of role of NO in hypercapnic vasodilatation and metabolically driven changes in flow is examined in the cat. Animals were anaesthetised with halothane and alpha-chloralose and ventilated. Cardiorespiratory parameters were monitored and kept within normal limits. Cerebral blood flow was monitored with laser Doppler flowmetry (CBFLDF) in the parietal cortex which metabolic activity was contemporaneously and continuously monitored using electrophysiological techniques. Hypercapnia was induced by increasing the end-expiratory CO2 to 8.1 +/- 0.4% and this produced a brisk rise in CBFLDF of 153 +/- 23%. Metabolic activity was increased by superfusion of the cortical surface with bicuculline (10 pmol) which increased cell firing and CBFLDF. Local administration of NG-nitro-L-arginine methyl ester (L-NAME) did affect the metabolically driven change in CBFLDF and only attenuated by 20% overall the hypercapnic vasodilator response. These studies suggest that at least in the anaesthetised cat NO does not play the pivotal role in these important vasodilator functions. PMID:7836690

  17. Determination of exhaled nitric oxide distributions in a diverse sample population using tunable diode laser absorption spectroscopy

    NASA Astrophysics Data System (ADS)

    Namjou, K.; Roller, C. B.; Reich, T. E.; Jeffers, J. D.; McMillen, G. L.; McCann, P. J.; Camp, M. A.

    2006-11-01

    A liquid-nitrogen free mid-infrared tunable diode laser absorption spectroscopy (TDLAS) system equipped with a folded-optical-path astigmatic Herriott cell was used to measure levels of exhaled nitric oxide (eNO) and exhaled carbon dioxide (eCO2) in breath. Quantification of absolute eNO concentrations was performed using NO/CO2 absorption ratios measured by the TDLAS system coupled with absolute eCO2 concentrations measured with a non-dispersive infrared sensor. This technique eliminated the need for routine calibrations using standard cylinder gases. The TDLAS system was used to measure eNO in children and adults (n=799, ages 5 to 64) over a period of more than one year as part of a field study. Volunteers for the study self-reported data including age, height, weight, and health status. The resulting data were used to assess system performance and to generate eNO and eCO2 distributions, which were found to be log-normal and Gaussian, respectively. There were statistically significant differences in mean eNO levels for males and females as well as for healthy and steroid naïve asthmatic volunteers not taking corticosteroid therapies. Ambient NO levels affected measured eNO concentrations only slightly, but this effect was not statistically significant.

  18. Electrochemical assay for the determination of nitric oxide metabolites using copper(II) chlorophyllin modified screen printed electrodes.

    PubMed

    Balamurugan, Murugesan; Madasamy, Thangamuthu; Pandiaraj, Manickam; Bhargava, Kalpana; Sethy, Niroj Kumar; Karunakaran, Chandran

    2015-06-01

    This work presents a novel electrochemical assay for the collective measurement of nitric oxide (NO) and its metabolites nitrite (NO2(-)) and nitrate (NO3(-)) in volume miniaturized sample at low cost using copper(II) chlorophyllin (CuCP) modified sensor electrode. Zinc oxide (ZnO) incorporated screen printed carbon electrode (SPCE) was used as a host matrix for the immobilization of CuCP. The morphological changes of the ZnO and CuCP modified electrodes were investigated using scanning electron microscopy. The electrochemical characterization of CuCP-ZnO-SPCE exhibited the characteristic quasi-reversible redox peaks at the potential +0.06 V versus Ag/AgCl. This biosensor electrode showed a wide linear range of response over NO concentrations from 200 nM to 500 μM with a detection limit of 100 nM and sensitivity of 85.4 nA μM(-1). Furthermore, NO2(-) measurement showed linearity of 100 nM to 1mM with a detection limit of 100 nM for NO2(-) and sensitivity of 96.4 nA μM(-1). Then, the concentration of NO3(-) was measured after its enzymatic conversion into NO2(-). Using this assay, the concentrations of NO, NO2(-), and NO3(-) present in human plasma samples before and after beetroot supplement were estimated using suitable membrane coated CuCP-ZnO-SPCE and validated with the standard Griess method. PMID:25700865

  19. Inhaled Nitric Oxide and Related Therapies

    PubMed Central

    Barr, Frederick E.; Macrae, Duncan

    2010-01-01

    Children with congenital heart defects are at risk for perioperative pulmonary hypertension if they require corrective or palliative surgery in the first week of life or if they have defects associated with significant pulmonary over circulation. In addition children undergoing cavopulmonary connections for single ventricle lesions require low pulmonary vascular resistance for surgical success. Treatment of perioperative pulmonary hypertension with inhaled nitric oxide has become standard therapy in many centers. Related drugs that increase nitric oxide synthesis including arginine and citrulline have also been studied in the perioperative period. In this article, previous clinical trials of inhaled nitric oxide, intravenous arginine, and intravenous and oral citrulline in children with perioperative pulmonary hypertension or elevated pulmonary vascular resistance after a cavopulmonary connection are reviewed. In addition, recommendations are presented for each agent on the clinical use in the perioperative setting including clinical indications, assessment of clinical effect, and length of therapy. PMID:20216160

  20. Coordinated Endothelial Nitric Oxide Synthase activation by translocation and phosphorylation determines flow-induced NO production in resistance vessels

    PubMed Central

    Figueroa, Xavier F.; González, Daniel R.; Puebla, Mariela; Acevedo, Juan P.; Rojas-Libano, Daniel; Durán, Walter N.; Boric, Mauricio P.

    2013-01-01

    Background/Aims Endothelial nitric oxide synthase (eNOS) is associated with caveolin-1 (Cav-1) in plasma membrane. We tested the hypothesis that eNOS activation by shear stress in resistance vessels depends on synchronized phosphorylation, dissociation from Cav-1 and translocation of the membrane-bound enzyme to Golgi and cytosol. Methods In isolated, perfused rat arterial mesenteric beds, we evaluated the effect of changes in flow rate (2–10 mL/min), on NO production, eNOS phosphorylation at serine 1177, eNOS subcellular distribution and co-immunoprecipitation with Cav-1, in the presence or absence of extracellular Ca2+. Results Increases in flow induced a biphasic rise in NO production: a rapid transient phase (3–5-min) that peaked during the first 15-sec, followed by a sustained phase, which lasted until the end of stimulation. Concomitantly, flow caused a rapid translocation of eNOS from the microsomal compartment to the cytosol and Golgi, paralleled by an increase in eNOS phosphorylation and a reduction in eNOS-Cav-1 association. Transient NO production, eNOS translocation, and dissociation from Cav-1 depended on extracellular Ca2+, while sustained NO production was abolished by the PI3K-Akt blocker wortmannin. Conclusions In intact resistance vessels, changes in flow induce NO production by transient Ca2+-dependent eNOS translocation from membrane to intracellular compartments and sustained Ca2+-independent PI3K-Akt-mediated phosphorylation. PMID:24217770

  1. Nitric oxide methods in seed biology

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Nitric oxide (NO) is a gaseous, free radical that is involved in many aspects of plant growth, development, and responses to the environment. Compelling evidence points to a central role for NO in the loss of seed dormancy. NO is highly reactive, toxic at high concentrations, and unstable. Methods f...

  2. Copper deficiency attenuates endothelial nitric oxide release

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The attenuation of endothelium-dependent nitric oxide (NO)-mediated vasodilation is a consistent finding in both conduit and resistance vessels during dietary copper deficiency. While the effect is well established, evidence for the mechanism is still circumstantial. This study was designed to deter...

  3. Glutathione regulates nitric oxide synthase in cultured hepatocytes.

    PubMed Central

    Harbrecht, B G; Di Silvio, M; Chough, V; Kim, Y M; Simmons, R L; Billiar, T R

    1997-01-01

    OBJECTIVE: The authors determine the relationship between glutathione and nitric oxide (NO) synthesis in cultured hepatocytes. SUMMARY BACKGROUND DATA: Glutathione is a cofactor for a number of enzymes, and its presence is essential for maximal enzyme activity by the inducible macrophage nitric oxide synthase (iNOS), which produces the reactive nitric oxide radical. Hepatocytes contain substantial quantities of glutathione, and this important tripeptide is decreased in hepatocytes stressed by ischemia/reperfusion or endotoxemia. Endotoxemia also induces the synthesis of inflammatory cytokines that result in the production of nitric oxide from hepatocytes by iNOS, suggesting that hepatocytes may be attempting to synthesize nitric oxide at times when intracellular glutathione is reduced. METHODS: Hepatocytes were cultured with buthionine sulfoximine and 1,3-bis(chloroethyl)-1-nitrosourea (BCNU) to inhibit glutathione. After exposure to cytokines, NO synthesis was assessed by supernatant nitrite levels, cytosolic iNOS enzyme activity, and iNOS mRNA levels. RESULTS: Inhibition of glutathione synthesis with buthionine sulfoximine or inhibition of glutathione reductase activity with BCNU inhibited nitrite synthesis. Both buthionine sulfoximine and BCNU inhibited the induction of iNOS mRNA, as detected by Northern blot analysis. Exogenous glutathione increased cytokine-stimulated iNOS induction, overcame the inhibitory effects of BCNU, and increased nitrite production by intact hepatocytes, induced hepatocyte cytosol, and partially purified hepatocyte iNOS. CONCLUSIONS: In cultured hepatocytes, adequate glutathione levels are required for optimal nitric oxide synthesis. This finding is predominantly due to an effect on iNOS mRNA levels, although glutathione also participates in the regulation of iNOS enzyme activity. Images Figure 4. Figure 5. Figure 6. PMID:8998123

  4. A Finite Rate Chemical Analysis of Nitric Oxide Flow Contamination Effects on Scramjet Performance

    NASA Technical Reports Server (NTRS)

    Cabell, Karen F.; Rock, Kenneth E.

    2003-01-01

    The level of nitric oxide contamination in the test gas of the Langley Research Center Arc-Heated Scramjet Test Facility and the effect of the contamination on scramjet test engine performance were investigated analytically. A finite rate chemical analysis was performed to determine the levels of nitric oxide produced in the facility at conditions corresponding to Mach 6 to 8 flight simulations. Results indicate that nitric oxide levels range from one to three mole percent, corroborating previously obtained measurements. A three-stream combustor code with finite rate chemistry was used to investigate the effects of nitric oxide on scramjet performance. Results indicate that nitric oxide in the test gas causes a small increase in heat release and thrust performance for the test conditions investigated. However, a rate constant uncertainty analysis suggests that the effect of nitric oxide ranges from no net effect, to an increase of about 10 percent in thrust performance.

  5. Nitric oxide, S-nitrosylation and neurodegeneration.

    PubMed

    Chung, K K K; Dawson, T M; Dawson, V L

    2005-09-01

    Nitric oxide is a critically important signaling molecule, controlling a wide range of pathways and biological processes. Highly reactive nitric oxide mediates its function through reaction with different molecules directly or indirectly. One of these modifications is the S-nitrosylation of cysteine residues in proteins. S-nitrosylation is emerging as an important redox signaling mechanism and has been found to regulate a broad range of biologic, physiologic and cellular functions. One of the major findings in this area recently is the linkage of nitrosative stress to various neurodegenerative disorders. Oxidative stress has long been regarded as a prime mediator in the development of neurodegeneration as various indices of oxidative stress are readily observed in postmortem studies. A causative role for nitrosative stress in neurodegeneration is just now being appreciated. The direct connection of S-nitrosylation to the pathogenesis of Parkinson's disease in recent studies further provide insights into how imbalance in nitric oxide metabolism can contribute to the development of selective injury and disease. PMID:16191392

  6. Nitric oxide regulates neurogenesis in adult olfactory epithelium in vitro.

    PubMed

    Sülz, Lorena; Astorga, Guadalupe; Bellette, Bernadette; Iturriaga, Rodrigo; Mackay-Sim, Alan; Bacigalupo, Juan

    2009-06-01

    Nitric oxide regulates neurogenesis in the developing and adult brain. The olfactory epithelium is a site of neurogenesis in the adult and previous studies suggest a role for nitric oxide in this tissue during development. We investigated whether neuronal precursor proliferation and differentiation is regulated by nitric oxide using primary cultures of olfactory epithelial cells and an immortalized, clonal, neuronal precursor cell line derived from adult olfactory epithelium. In these cultures NOS inhibition reduced cell proliferation and stimulated neuronal differentiation, including expression of a voltage-dependent potassium conductance of the delayed rectifier type. In the neuronal precursor cell line, differentiation was associated with a significant decrease in nitric oxide release. In contrast, addition of nitric oxide stimulated proliferation and reduced neuronal differentiation. Nitric oxide regulated olfactory neurogenesis independently of added growth factors. Taken together these results indicate that nitric oxide levels can regulate cell proliferation and neuronal differentiation of olfactory precursor cells. PMID:19371594

  7. Activated Macrophages as a Novel Determinant of Tumor Cell Radioresponse: The Role of Nitric Oxide-Mediated Inhibition of Cellular Respiration and Oxygen Sparing

    SciTech Connect

    Jiang Heng; De Ridder, Mark; Verovski, Valeri N.; Sonveaux, Pierre; Jordan, Benedicte F.; Law, Kalun; Monsaert, Christinne; Van den Berge, Dirk L.; Verellen, Dirk; Feron, Olivier; Gallez, Bernard; Storme, Guy A.

    2010-04-15

    Purpose: Nitric oxide (NO), synthesized by the inducible nitric oxide synthase (iNOS), is known to inhibit metabolic oxygen consumption because of interference with mitochondrial respiratory activity. This study examined whether activation of iNOS (a) directly in tumor cells or (b) in bystander macrophages may improve radioresponse through sparing of oxygen. Methods and Materials: EMT-6 tumor cells and RAW 264.7 macrophages were exposed to bacterial lipopolysaccharide plus interferon-gamma, and examined for iNOS expression by reverse transcription polymerase chain reaction, Western blotting and enzymatic activity. Tumor cells alone, or combined with macrophages were subjected to metabolic hypoxia and analyzed for radiosensitivity by clonogenic assay, and for oxygen consumption by electron paramagnetic resonance and a Clark-type electrode. Results: Both tumor cells and macrophages displayed a coherent picture of iNOS induction at transcriptional/translational levels and NO/nitrite production, whereas macrophages showed also co-induction of the inducible heme oxygenase-1, which is associated with carbon monoxide (CO) and bilirubin production. Activation of iNOS in tumor cells resulted in a profound oxygen sparing and a 2.3-fold radiosensitization. Bystander NO-producing, but not CO-producing, macrophages were able to block oxygen consumption by 1.9-fold and to radiosensitize tumor cells by 2.2-fold. Both effects could be neutralized by aminoguanidine, a metabolic iNOS inhibitor. An improved radioresponse was clearly observed at macrophages to tumor cells ratios ranging between 1:16 to 1:1. Conclusions: Our study is the first, as far as we are aware, to provide evidence that iNOS may induce radiosensitization through oxygen sparing, and illuminates NO-producing macrophages as a novel determinant of tumor cell radioresponse within the hypoxic tumor microenvironment.

  8. Paraxanthine: Connecting Caffeine to Nitric Oxide Neurotransmission.

    PubMed

    Ferré, Sergi; Orrú, Marco; Guitart, Xavier

    2013-06-01

    Recent results obtained in our laboratory indicate that paraxanthine, the main metabolite of caffeine in humans, produces a significantly stronger locomotor activation in rats than caffeine. Furthermore, paraxanthine also produced a very significant increase in striatal extracellular concentrations of dopamine. Searching for an additional mechanism other than adenosine antagonism responsible for these psychostimulant-like effects, it was found that paraxanthine, but not caffeine, inhibited cGMP-preferring phosphodiesterases. Furthermore, interrupting nitric oxide neurotransmision (inhibiting nitric oxide synthase) significantly decreased both the locomotor-activating and the dopamine-releasing effects of paraxanthine. These results open up some obvious questions about the role of paraxanthine in the pharmacological effects of caffeine. PMID:24761277

  9. Paraxanthine: Connecting Caffeine to Nitric Oxide Neurotransmission

    PubMed Central

    Orrú, Marco; Guitart, Xavier

    2013-01-01

    Recent results obtained in our laboratory indicate that paraxanthine, the main metabolite of caffeine in humans, produces a significantly stronger locomotor activation in rats than caffeine. Furthermore, paraxanthine also produced a very significant increase in striatal extracellular concentrations of dopamine. Searching for an additional mechanism other than adenosine antagonism responsible for these psychostimulant-like effects, it was found that paraxanthine, but not caffeine, inhibited cGMP-preferring phosphodiesterases. Furthermore, interrupting nitric oxide neurotransmision (inhibiting nitric oxide synthase) significantly decreased both the locomotor-activating and the dopamine-releasing effects of paraxanthine. These results open up some obvious questions about the role of paraxanthine in the pharmacological effects of caffeine. PMID:24761277

  10. Nitroreductase-activated nitric oxide (NO) prodrugs.

    PubMed

    Sharma, Kavita; Sengupta, Kundan; Chakrapani, Harinath

    2013-11-01

    Due to the involvement of nitric oxide (NO) in numerous and diverse physiological processes, site-directed delivery of therapeutic NO in order to minimize unwanted side-effects is necessary. O(2)-(4-Nitrobenzyl) diazeniumdiolates are designed as substrates for Escherichia coli nitroreductase (NTR), an enzyme that is frequently used to facilitate directed delivery of cytotoxic species to cancers. O(2)-(4-Nitrobenzyl) diazeniumdiolates are found to be stable in aqueous buffer but are metabolized by NTR to produce NO. A cell viability assay revealed that cytotoxic effects of O(2)-(4-nitrobenzyl)1-(2-methylpiperidin-1-yl)diazen-1-ium-1,2-diolate (4b) towards two cancer cell lines is significantly enhanced in the presence of NTR suggesting the potential for use of this compound in nitric oxide-based directed prodrug therapy. PMID:24050886

  11. Analytical study of mechanisms for nitric oxide formation during combustion of methane in a jet-stirred combustor

    NASA Technical Reports Server (NTRS)

    Jachimowski, C. J.

    1975-01-01

    The role of chemical kinetics in the formation of nitric oxide during the combustion of methane was examined analytically by means of a detailed chemical mechanism for the oxidation of methane, for the reaction between hydrocarbon fragments, and for the formation of nitric oxide. By comparing predicted nitric oxide levels with values reported in the literature from jet-stirred combuster experiments, it was determined that the nitric oxide levels observed in fuel-rich flames cannot be described by a mechanism in which the rate of nitric oxide formation is controlled solely by the kinetics of oxygen atom formation. A proposed mechanism for the formation of nitric oxide in methane-rich flames reproduces the observed levels. The oxidation of hydrogen cyanide appears to be an important factor in nitric oxide formation.

  12. Chronic nitric oxide synthase inhibition prevents new coronary capillary generation.

    PubMed

    Girardot, Daphné; Jover, Bernard; Moles, Jean-Pierre; Deblois, Denis; Moreau, Pierre

    2004-09-01

    L-NAME-induced hypertension has been shown to produce concentric (eutrophic) remodeling of the heart despite an enhanced afterload. We postulated that nitric oxide synthase inhibition could limit coronary capillary growth to explain the nature of remodeling. To test our hypothesis, we aimed at determining the effect of endogenous and exogenous nitric oxide on coronary neovascularization. Aortic and coronary rings from normotensive animals were incubated in a three-dimensional type I collagen matrix in the presence of L-NAME or the nitric oxide donor SNAP. L-NAME inhibited, while SNAP stimulated, neovascularization from aortic and coronary rings after 12 days of in vitro incubation. In arterial rings harvested from rats treated with L-NAME for 14 days and in which no further in vitro treatment was added, only coronary rings showed a reduction in new capillary generation. While confirming that chronic L-NAME-treated rats develop concentric remodeling, the evaluation of capillary density did not reveal any difference as compared with the controls in 3 areas of the myocardium. In conclusion, chronic inhibition of nitric oxide synthesis in vivo produces a long-lasting reduction in the capacity of coronary arteries to generate new capillaries in vitro. Thus, our results lend support to the hypothesis that an inhibition of new capillary formation could prevent the development of compensatory ventricular hypertrophy, in favor of concentric remodeling. PMID:15475829

  13. Endogenous nitric oxide generation in protoplast chloroplasts.

    PubMed

    Tewari, Rajesh Kumar; Prommer, Judith; Watanabe, Masami

    2013-01-01

    KEY MESSAGE : NO generation is studied in the protoplast chloroplasts. NO, ONOO ( - ) and ROS (O ( 2 ) ( - ) and H ( 2 ) O ( 2 ) ) are generated in chloroplasts. Nitric oxide synthase-like protein appears to be involved in NO generation. Nitric oxide stimulates chlorophyll biosynthesis and chloroplast differentiation. The present study was conducted to better understand the process of NO generation in the leaf chloroplasts and protoplasts. NO, peroxynitrite and superoxide anion were investigated in the protoplasts and isolated chloroplasts using specific dyes, confocal laser scanning and light microscopy. The level of NO was highest after protoplast isolation and subsequently decreased during culture. Suppression of NO signal in the presence of PTIO, suggests that diaminofluorescein-2 diacetate (DAF-2DA) detected NO. Detection of peroxynitrite, a reaction product of NO and superoxide anion, further suggests NO generation. Moreover, generation of NO and peroxynitrite in the chloroplasts of wild-type Arabidopsis and their absence or weak signals in the leaf-derived protoplasts of Atnoa1 mutants confirmed the reactivity of DAF-2DA and aminophenyl fluorescein to NO and peroxynitrite, respectively. Isolated chloroplasts also showed signal of NO. Suppression of NO signal in the presence of 100 μM nitric oxide synthase inhibitors [L-NNA, Nω-nitro-L-arginine and PBIT, S,S'-1,3-phenylene-bis(1,2-ethanediyl)-bis-isothiourea] revealed that nitric oxide synthase-like system is involved in NO synthesis. Suppression of NO signal in the protoplasts isolated in the presence of cycloheximide suggests de novo synthesis of NO generating protein during the process of protoplast isolation. Furthermore, the lack of inhibition of NO production by sodium tungstate (250 μM) and inhibition by L-NNA, and PBIT suggest involvement NOS-like protein, but not nitrate reductase, in NO generation in the leaf chloroplasts and protoplasts. PMID:22971939

  14. Neuroprotective properties of nitric oxide and S-nitrosoglutathione

    SciTech Connect

    Rauhala, Pekka . E-mail: pekka.rauhala@helsinki.fi; Andoh, Tsugunobu; Chiueh, C.C.

    2005-09-01

    Oxidative stress and apoptosis may play an important role in the neurodegeneration. The present paper outlines antioxidative and antiapototic mechanisms of nitric oxide and S-nitrosothiols, which could mediate neuroprotection. Nitric oxide generated by nitric oxide synthase or released from an endogenous S-nitrosothiol, S-nitrosoglutathione may up-regulate antioxidative thioredoxin system and antiapototic Bcl-2 protein through a cGMP-dependent mechanism. Moreover, nitric oxide radicals have been shown to have direct antioxidant effect through their reaction with free radicals and iron-oxygen complexes. In addition to serving as a stabilizer and carrier of nitric oxide, S-nitrosoglutathione may have protective effect through transnitrosylation reactions. Based on these new findings, a hypothesis arises that the homeostasis of nitric oxide, S-nitrosothiols, glutathione, and thioredoxin systems is important for protection against oxidative stress, apoptosis, and related neurodegenerative disorders.

  15. Activation of constitutive nitric oxide synthases by oxidized calmodulin mutants.

    PubMed

    Montgomery, Heather J; Bartlett, Ryan; Perdicakis, Basil; Jervis, Eric; Squier, Thomas C; Guillemette, J Guy

    2003-07-01

    Several calmodulin (CaM) mutants were engineered in an effort to identify the functional implications of the oxidation of individual methionines in CaM on the activity of the constitutive isoforms of nitric oxide synthase (NOS). Site-directed mutagenesis was used to substitute the majority of methionines with leucines. Substitution of all nine methionine residues in CaM with leucines had minimal effects on the binding affinity or maximal enzyme activation for either the neuronal (nNOS) or endothelial (eNOS) isoform. Selective substitution permitted determination of the functional consequences of the site-specific oxidation of Met(144) and Met(145) on the regulation of electron transfer within nNOS and eNOS. Site-specific oxidation of Met(144) and Met(145) resulted in changes in the CaM concentration necessary for half-maximal activation of nNOS and eNOS, suggesting that these side chains are involved in stabilizing the productive association between CaM and NOS. However, the site-specific oxidation of Met(144) and Met(145) had essentially no effect on the maximal extent of eNOS activation in the presence of saturating concentrations of CaM. In contrast, the site-specific oxidation of Met(144) (but not Met(145)) resulted in a reduction in the level of nNOS activation that was associated with decreased rates of electron transfer within the reductase domain. Thus, nNOS and eNOS exhibit different functional sensitivities to conditions of oxidative stress that are expected to oxidize CaM. This may underlie some aspects of the observed differences in the sensitivities of proteins in vasculature and neuronal tissues to nitration that are linked to NOS activation and the associated generation of peroxynitrite. PMID:12820885

  16. Vascular nitric oxide: formation and function

    PubMed Central

    Jin, Richard C; Loscalzo, Joseph

    2010-01-01

    Nitric oxide (NO) is a structurally simple, highly versatile molecule that was originally discovered over 30 years ago as an endothelium-derived relaxing factor. In addition to its vasorelaxing effects, NO is now recognized as a key determinant of vascular health, exerting antiplatelet, antithrombotic, and anti-inflammatory properties within the vasculature. This short-lived molecule exerts its inhibitory effect on vascular smooth muscle cells and platelets largely through cyclic guanosine monophosphate-dependent mechanisms, resulting in a multitude of molecular effects by which platelet activation and aggregation are prevented. The biosynthesis of NO occurs via the catalytic activity of NO synthase, an oxidoreductase found in many cell types. NO insufficiency can be attributed to limited substrate/cofactor availability as well as interactions with reactive oxygen species. Impaired NO bioavailability represents the central feature of endothelial dysfunction, a common abnormality found in many vascular diseases. In this review, we present an overview of NO synthesis and biochemistry, discuss the mechanisms of action of NO in regulating platelet and endothelial function, and review the effects of vascular disease states on NO bioavailability. PMID:21572574

  17. Biological nitric oxide signalling: chemistry and terminology.

    PubMed

    Heinrich, Tassiele A; da Silva, Roberto S; Miranda, Katrina M; Switzer, Christopher H; Wink, David A; Fukuto, Jon M

    2013-08-01

    Biological nitrogen oxide signalling and stress is an area of extreme clinical, pharmacological, toxicological, biochemical and chemical research interest. The utility of nitric oxide and derived species as signalling agents is due to their novel and vast chemical interactions with a variety of biological targets. Herein, the chemistry associated with the interaction of the biologically relevant nitrogen oxide species with fundamental biochemical targets is discussed. Specifically, the chemical interactions of nitrogen oxides with nucleophiles (e.g. thiols), metals (e.g. hemeproteins) and paramagnetic species (e.g. dioxygen and superoxide) are addressed. Importantly, the terms associated with the mechanisms by which NO (and derived species) react with their respective biological targets have been defined by numerous past chemical studies. Thus, in order to assist researchers in referring to chemical processes associated with nitrogen oxide biology, the vernacular associated with these chemical interactions is addressed. PMID:23617570

  18. Biological nitric oxide signalling: chemistry and terminology

    PubMed Central

    Heinrich, Tassiele A; da Silva, Roberto S; Miranda, Katrina M; Switzer, Christopher H; Wink, David A; Fukuto, Jon M

    2013-01-01

    Biological nitrogen oxide signalling and stress is an area of extreme clinical, pharmacological, toxicological, biochemical and chemical research interest. The utility of nitric oxide and derived species as signalling agents is due to their novel and vast chemical interactions with a variety of biological targets. Herein, the chemistry associated with the interaction of the biologically relevant nitrogen oxide species with fundamental biochemical targets is discussed. Specifically, the chemical interactions of nitrogen oxides with nucleophiles (e.g. thiols), metals (e.g. hemeproteins) and paramagnetic species (e.g. dioxygen and superoxide) are addressed. Importantly, the terms associated with the mechanisms by which NO (and derived species) react with their respective biological targets have been defined by numerous past chemical studies. Thus, in order to assist researchers in referring to chemical processes associated with nitrogen oxide biology, the vernacular associated with these chemical interactions is addressed. PMID:23617570

  19. Kinetics and spectroscopy of bromine nitric oxide

    NASA Astrophysics Data System (ADS)

    Godfrey, Patrick Eugene

    1997-11-01

    The kinetics of BrNO formation and destruction were examined using time-resolved photolysis techniques. The equilibrium constant for the dark reaction Br2 + 2/ NO/leftrightarrow 2 BrNO was determined as Keq = 168/pm 23/ atm-1 and the rate constant for the forward reaction as kf = 1.40/pm .18/ 10-38/ cm6/molecule2-s at 293K. A novel technique for the fitting of the observed time profiles to the three-body kinetics was developed which utilizes the complete temporal profile to establish the rate coefficients. When an equilibrium mixture of Br2, NO and BrNO is disturbed by photolysis, BrNO is rapidly removed by reaction with atomic bromine. For continuous photolysis, a new photostationary condition is achieved which shifts the equilibrium toward Br2 and NO. A kinetic mechanism and rates for the photolysis of such mixtures has been validated for total pressures of 28-111 torr and nitric oxide to molecular bromine concentration ratios of 2.18-26.75, with an average Br, photolysis rate of 0.050 molecules/s. The rotation structure of the ν1 + ν2 -ν3,/ 2ν1 -ν3,/ 2ν1,/ 3ν1,/ 2ν1 + ν3 and 3ν1 + ν3 overtone and combination bands of BrNO were examined at high resolution (.005[-].01/ cm-1) using Fourier Transform Spectroscopy. Over 4900 spectral lines were recorded for the two isotopes 79BrNO and 81BrNO. The rotational and quartic distortion terms, inertia defects and asymmetry parameters were determined for the (200), (300), (001), (200), (301) and (110) vibrational levels. The first-order vibration- rotation interaction terms were also determined.

  20. Effect of endogenous nitric oxide on mitochondrial respiration of rat hepatocytes in vitro and in vivo

    SciTech Connect

    Stadler, J.; Curran, R.D.; Ochoa, J.B.; Harbrecht, B.G.; Hoffman, R.A.; Simmons, R.L.; Billiar, T.R. )

    1991-02-01

    Nitric oxide, a highly reactive radical, was recently identified as an intermediate of L-arginine metabolism in mammalian cells. We have shown that nitric oxide synthesis is induced in vitro in cultured hepatocytes by supernatants from activated Kupffer cells or in vivo by injecting rats with nonviable Corynebacterium parvum. In both cases, nitric oxide biosynthesis in hepatocytes was associated with suppression of total protein synthesis. This study attempts to determine the effect of nitric oxide biosynthesis on the activity of specific hepatocytic mitochondrial enzymes and to determine whether inhibition of protein synthesis is caused by suppression of energy metabolism. Exposure of hepatocytes to supernatants from activated Kupffer cells led to a 30% decrease of aconitase (Krebs cycle) and complex I (mitochondrial electron transport chain) activity. Using NG-monomethyl-L-arginine, an inhibitor of nitric oxide synthesis, we demonstrated that the inhibition of mitochondrial aconitase activity was due, in part, to the action of nitric oxide. In contrast, in vivo nitric oxide synthesis of hepatocytes from Corynebacterium parvum-treated animals had no effect on mitochondrial respiration. This suggests that inhibition of protein synthesis by nitric oxide is not likely to be mediated by inhibition of energy metabolism.

  1. Splenic B lymphocyte programmed cell death is prevented by nitric oxide release through mechanisms involving sustained Bcl-2 levels.

    PubMed Central

    Genaro, A M; Hortelano, S; Alvarez, A; Martínez, C; Boscá, L

    1995-01-01

    Incubation of ex vivo cultured mature B cells in the presence of nitric oxide or nitric oxide-donor substances delays programmed cell death as determined by the appearance of DNA laddering in agarose gel electrophoresis or by flow-cytometry analysis of DNA. Nitric oxide also rescues B cells from antigen-induced apoptosis but fails to provide a co-stimulatory signal that converts the signal elicited by the antigen into a proliferative response. The protective effects of nitric oxide against programmed cell death can be reproduced by treatment of the cells with permeant analogues of cyclic GMP. Regarding the mechanisms by which nitric oxide prevents apoptosis in B cells, we have observed that nitric oxide release prevents the drop in the expression of the protooncogene bcl-2, both at the mRNA and protein levels, suggesting the existence of an unknown pathway that links nitric oxide signaling with Bcl-2 expression. Images PMID:7706495

  2. Nitric oxide-dependent human acrosomal loss induced by PPCM (SAMMA) and by nitric oxide donors occurs by independent pathways: basis for synthesis of an improved contraceptive microbicide.

    PubMed

    Anderson, Robert A; Feathergill, Kenneth A; Chany, Calvin J; Jain, Sanjay; Krunic, Aleksej

    2009-01-01

    PPCM (previously designated sulfuric acid-modified mandelic acid [SAMMA]) is a contraceptive microbicide in preclinical development. Its contraceptive activity is attributable in part to its ability to promote premature acrosomal loss. Prior studies showed that PPCM-induced human acrosomal loss (PAL) is Ca(2+)-dependent. This study was carried out to determine transduction elements downstream from Ca(2+) entry. PAL is inhibited by inhibitors selective for endothelial-type nitric oxide synthase. PAL is completely inhibited by 0.1 microM ODQ (soluble guanylate cyclase inhibitor). PAL is inhibited by protein kinase G inhibitors with selectivity for the type II isotype. Several inhibitors of the nitric oxide/cyclic guanosine monophosphate (cGMP)/protein kinase G pathway induce Ca(2+)-dependent acrosomal loss when added alone. These responses are inhibited by nifedipine, a blocker of Ca(v1.x) voltage-dependent channels. Acrosomal loss induced by the nitric oxide donor SNAP (SNAL) does not require added Ca(2+). Sperm production of nitric oxide is increased by PPCM, an effect inhibited by nitro-L-arginine (nitric oxide synthase inhibitor). Although inhibited by ODQ, SNAL and acrosomal loss induced by other nitric oxide donors are unaffected by KT5823 (protein kinase G inhibitor). Unlike PAL, SNAL is partially inhibited by KT5720 (protein kinase A inhibitor) and genistein (protein tyrosine kinase inhibitor). Acrosomal loss response to PPCM and SNAP added in combination suggests that these agents act by independent mechanisms. A PPCM derivative was synthesized, in which a nitric oxide donor was esterified to PPCM (NOSPPA-23). NOSPPA-23 induces acrosomal loss with or without added Ca(2+). The ED(50) of NOSPPA-23 (4.8 nM) in the presence of Ca(2+) is 35-fold less than that of PPCM. These findings suggest the following: 1) elements responsible for PAL include endothelial nitric oxide synthase, soluble guanylate cyclase, and type II protein kinase G; 2) the resting state of the nitric oxide/cGMP/protein kinase G pathway is a determinant of acrosomal status; 3) PPCM and nitric oxide donors induce acrosomal loss via nitric oxide, but through independent pathways; and 4) covalent attachment of a nitric oxide donor to PPCM provides synergistic efficacy as a stimulus of acrosomal loss. Further studies with this novel prototype as an improved contraceptive microbicide are warranted. PMID:18974424

  3. Targeting of nitric oxide synthase to endothelial cell caveolae via palmitoylation: implications for nitric oxide signaling.

    PubMed Central

    García-Cardeña, G; Oh, P; Liu, J; Schnitzer, J E; Sessa, W C

    1996-01-01

    The membrane association of endothelial nitric oxide synthase (eNOS) plays an important role in the biosynthesis of nitric oxide (NO) in vascular endothelium. Previously, we have shown that in cultured endothelial cells and in intact blood vessels, eNOS is found primarily in the perinuclear region of the cells and in discrete regions of the plasma membrane, suggesting trafficking of the protein from the Golgi to specialized plasma membrane structures. Here, we show that eNOS is found in Triton X-100-insoluble membranes prepared from cultured bovine aortic endothelial cells and colocalizes with caveolin, a coat protein of caveolae, in cultured bovine lung microvascular endothelial cells as determined by confocal microscopy. To examine if eNOS is indeed in caveolae, we purified luminal endothelial cell plasma membranes and their caveolae directly from intact, perfused rat lungs. eNOS is found in the luminal plasma membranes and is markedly enriched in the purified caveolae. Because palmitoylation of eNOS does not significantly influence its membrane association, we next examined whether this modification can affect eNOS targeting to caveolae. Wild-type eNOS, but not the palmitoylation mutant form of the enzyme, colocalizes with caveolin on the cell surface in transfected NIH 3T3 cells, demonstrating that palmitoylation of eNOS is necessary for its targeting into caveolae. These data suggest that the subcellular targeting of eNOS to caveolae can restrict NO signaling to specific targets within a limited microenvironment at the cell surface and may influence signal transduction through caveolae. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:8692835

  4. Inhaled nitric oxide in chronic obstructive lung disease

    SciTech Connect

    Tiihonen, J.; Hakola, P.; Paanila, J.; Turtiainen . Dept. of Forensic Psychiatry)

    1993-01-30

    During an investigation of the effect of nitric oxide on the pulmonary circulation the authors had the opportunity to give nitric oxide to a patient with longstanding obstructive airway disease, with successful results. A 72-year-old man with chronic obstructive pulmonary disease was referred to the institution for assessment of pulmonary vascular reactivity to acetylcholine and nitric oxide. Acetylcholine was infused into the main pulmonary artery followed 15 min later by an inhalation of 80 parts per million (ppm) nitric oxide. Heart rate and systemic arterial and pulmonary arterial pressures were continuously monitored. Throughout the study the inspired oxygen concentration was kept constant at 98%. Nitrogen dioxide and nitric oxide concentrations were monitored while nitric oxide was delivered. The infusion of acetylcholine resulted in a small increase in pulmonary artery pressure and pulmonary vascular resistance. Nitric oxide produced a substantial fall in pulmonary artery pressure and pulmonary vascular resistance with a concomitant increase in systemic arterial oxygen tension. These results suggest that endothelium-dependent relaxation of the pulmonary vasculature was impaired in the patient and that exogenous nitric oxide was an effective pulmonary vasodilator. In-vitro investigation of explanted airways disease suggests not only that endothelium-dependent pulmonary artery relaxation is impaired but also that the dysfunction is related to pre-existing hypoxemia and hypercapnia. Nitric oxide inhibits proliferation of cultured vascular smooth muscle cells and might alter the pulmonary vascular remodeling characteristic of patients with chronic obstructive airways disease.

  5. Electrocatalytic reduction of nitric oxide at electrodes modified with electropolymerized films of [Cr(v-tpy){sub 2}]{sup 3+} and their application to cellular NO determinations

    SciTech Connect

    Maskus, M.; Wu, Q.; Shapleigh, J.P.; Abruna, H.D.; Pariente, F.; Toffanin, A.

    1996-09-15

    Nitric oxide can be electrocatalytically reduced at electrodes modified with electropolymerized films of [Cr(v-tpy){sub 2}]{sup 3+}. Upon further modification with a thin film of Nafion (to prevent interferences from anions, especially nitrite), these electrodes can be employed as NO sensors in solution with submicromolar detection limits and fast response. We have carried out preliminary studies of cellular NO release from Rhodobacter sphaeroides bacterial cells with excellent results. 21 refs., 7 figs., 1 tab.

  6. Role of nitric oxide in parasitic infections.

    PubMed Central

    James, S L

    1995-01-01

    Nitric oxide is produced by a number of different cell types in response to cytokine stimulation and thus has been found to play a role in immunologically mediated protection against a growing list of protozoan and helminth parasites in vitro and in animal models. The biochemical basis of its effects on the parasite targets appears to involve primarily inactivation of enzymes crucial to energy metabolism and growth, although it has other biologic activities as well. NO is produced not only by macrophages and macrophage-like cells commonly associated with the effector arm of cell-mediated immune reactivity but also by cells commonly considered to lie outside the immunologic network, such as hepatocytes and endothelial cells, which are intimately involved in the life cycle of a number of parasites. NO production is stimulated by gamma interferon in combination with tumor necrosis factor alpha or other secondary activation signals and is regulated by a number of cytokines (especially interleukin-4, interleukin-10, and transforming growth factor beta) and other mediators, as well as through its own inherent inhibitory activity. The potential for design of prevention and/or intervention approaches against parasitic infection (e.g., vaccination or combination chemo- and immunotherapy strategies) on the basis of induction of cell-mediated immunity and NO production appears to be great, but the possible pathogenic consequences of overproduction of NO must be taken into account. Moreover, more research on the role and regulation of NO in human parasitic infection is needed before its possible clinical relevance can be determined. PMID:8531884

  7. Fatty Acid Transduction of Nitric Oxide Signaling

    PubMed Central

    Baker, Paul R. S.; Lin, Yiming; Schopfer, Francisco J.; Woodcock, Steven R.; Groeger, Alison L.; Batthyany, Carlos; Sweeney, Scott; Long, Marshall H.; Iles, Karen E.; Baker, Laura M. S.; Branchaud, Bruce P.; Chen, Yuqing E.; Freeman, Bruce A.

    2007-01-01

    Mass spectrometric analysis of human plasma and urine revealed abundant nitrated derivatives of all principal unsaturated fatty acids. Nitrated palmitoleic, oleic, linoleic, linolenic, arachidonic and eicosapentaenoic acids were detected in concert with their nitrohydroxy derivatives. Two nitroalkene derivatives of the most prevalent fatty acid, oleic acid, were synthesized (9- and 10-nitro-9-cis-octadecenoic acid; OA-NO2), structurally characterized and determined to be identical to OA-NO2 found in plasma, red cells, and urine of healthy humans. These regioisomers of OA-NO2 were quantified in clinical samples using 13C isotope dilution. Plasma free and esterified OA-NO2 concentrations were 619 ± 52 and 302 ± 369 nM, respectively, and packed red blood cell free and esterified OA-NO2 was 59 ± 11 and 155 ± 65 nM. The OA-NO2 concentration of blood is ~50% greater than that of nitrated linoleic acid, with the combined free and esterified blood levels of these two fatty acid derivatives exceeding 1 μM. OA-NO2 is a potent ligand for peroxisome proliferator activated receptors at physiological concentrations. CV-1 cells co-transfected with the luciferase gene under peroxisome proliferator-activated receptor (PPAR) response element regulation, in concert with PPARγ, PPARα, or PPARδ expression plasmids, showed dose-dependent activation of all PPARs by OA-NO2. PPARγ showed the greatest response, with significant activation at 100 nM, while PPARα and PPARδ were activated at ~300 nM OA-NO2. OA-NO2 also induced PPARγ-dependent adipogenesis and deoxyglucose uptake in 3T3-L1 preadipocytes at a potency exceeding nitrolinoleic acid and rivaling synthetic thiazo-lidinediones. These data reveal that nitrated fatty acids comprise a class of nitric oxide-derived, receptor-dependent, cell signaling mediators that act within physiological concentration ranges. PMID:16227625

  8. Regulatory effects of anesthetics on nitric oxide.

    PubMed

    Fan, Wenguo; Liu, Qin; Zhu, Xiao; Wu, Zhi; Li, Dongpei; Huang, Fang; He, Hongwen

    2016-04-15

    Nitric oxide (NO) is a free radical gas in the biological system, which is produced by nitric oxide synthase (NOS) family. NO acts as a biological mediator and plays important roles in different systems in humans. The NO/NOS system exerts a broad spectrum of signaling functions involved in vasodilation, inflammation, oxidative stress, cardioprotection and neuroprotection. It has been demonstrated that intravenous and volatile anesthetics (such as propofol, ketamine, midazolam, isoflurane, sevoflurane, and desflurane, etc.) modulate NO production through multiple mechanisms that may influence physiological and pathophysiological processes. This review focuses on the effects of different anesthetics on NO/NOS regulation in different disease conditions. Possible cellular mechanisms and intermediate role of NO/NOS in anesthetic-mediated organ protection are also discussed. It would be interesting to clarify the impact of anesthetics on NO/NOS regulation. This review gives an overview of the effects of different anesthetics on NO/NOS regulation and function in different physiologic and pathophysiologic states. PMID:26946305

  9. Analysis of the ultraviolet emissions of nitric oxide from mid-latitude rocket observations. Master's thesis

    SciTech Connect

    Clayton, M.J.

    1990-06-01

    Ultraviolet emissions of the Earth's ionosphere in the wavelength range of 2000 A to 2500 A are analyzed. These data were obtained by a rocket-borne spectrograph flown on March 30, 1990 from the White Sands Missile Range, New Mexico. The gamma and epsilon bands of nitric oxide dominate this portion of the spectrum. Column densities of nitric oxide are determined by fitting eleven of the most prominent bands with synthetic spectra. Additionally, a temperature profile is found between the altitudes of 145 km and 195 km. From the data, corrections to the Franck-Condon factors are determined for three v (Z primes) progressions of the nitric oxide gamma bands.

  10. Vascular nitric oxide: Beyond eNOS.

    PubMed

    Zhao, Yingzi; Vanhoutte, Paul M; Leung, Susan W S

    2015-10-01

    As the first discovered gaseous signaling molecule, nitric oxide (NO) affects a number of cellular processes, including those involving vascular cells. This brief review summarizes the contribution of NO to the regulation of vascular tone and its sources in the blood vessel wall. NO regulates the degree of contraction of vascular smooth muscle cells mainly by stimulating soluble guanylyl cyclase (sGC) to produce cyclic guanosine monophosphate (cGMP), although cGMP-independent signaling [S-nitrosylation of target proteins, activation of sarco/endoplasmic reticulum calcium ATPase (SERCA) or production of cyclic inosine monophosphate (cIMP)] also can be involved. In the blood vessel wall, NO is produced mainly from l-arginine by the enzyme endothelial nitric oxide synthase (eNOS) but it can also be released non-enzymatically from S-nitrosothiols or from nitrate/nitrite. Dysfunction in the production and/or the bioavailability of NO characterizes endothelial dysfunction, which is associated with cardiovascular diseases such as hypertension and atherosclerosis. PMID:26499181

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

    PubMed

    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. PMID:21645628

  12. Nitric oxide rescues thalidomide mediated teratogenicity.

    PubMed

    Siamwala, Jamila H; Veeriah, Vimal; Priya, M Krishna; Rajendran, Saranya; Saran, Uttara; Sinha, Swaraj; Nagarajan, Shunmugam; Pradeep, T; Chatterjee, Suvro

    2012-01-01

    Thalidomide, a sedative drug given to pregnant women, unfortunately caused limb deformities in thousands of babies. Recently the drug was revived because of its therapeutic potential; however the search is still ongoing for an antidote against thalidomide induced limb deformities. In the current study we found that nitric oxide (NO) rescues thalidomide affected chick (Gallus gallus) and zebrafish (Danio rerio) embryos. This study confirms that NO reduced the number of thalidomide mediated limb deformities by 94% and 80% in chick and zebrafish embryos respectively. NO prevents limb deformities by promoting angiogenesis, reducing oxidative stress and inactivating caspase-3 dependent apoptosis. We conclude that NO secures angiogenesis in the thalidomide treated embryos to protect them from deformities. PMID:22997553

  13. Nitric oxide rescues thalidomide mediated teratogenicity

    PubMed Central

    Siamwala, Jamila H.; Veeriah, Vimal; Priya, M. Krishna; Rajendran, Saranya; Saran, Uttara; Sinha, Swaraj; Nagarajan, Shunmugam; T, Pradeep; Chatterjee, Suvro

    2012-01-01

    Thalidomide, a sedative drug given to pregnant women, unfortunately caused limb deformities in thousands of babies. Recently the drug was revived because of its therapeutic potential; however the search is still ongoing for an antidote against thalidomide induced limb deformities. In the current study we found that nitric oxide (NO) rescues thalidomide affected chick (Gallus gallus) and zebrafish (Danio rerio) embryos. This study confirms that NO reduced the number of thalidomide mediated limb deformities by 94% and 80% in chick and zebrafish embryos respectively. NO prevents limb deformities by promoting angiogenesis, reducing oxidative stress and inactivating caspase-3 dependent apoptosis. We conclude that NO secures angiogenesis in the thalidomide treated embryos to protect them from deformities. PMID:22997553

  14. Melatonin and its precursors scavenge nitric oxide

    SciTech Connect

    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.

  15. Nitric Oxide--Some Old and New Perspectives.

    ERIC Educational Resources Information Center

    Ainscough, Eric W.; Brodie, Andrew M.

    1995-01-01

    Because of the role it plays in physiology and neurobiology, there is a rebirth of interest in nitric oxide. It can affect enzyme and immune system regulation and cytotoxicity. Nitric oxide may represent a new class of signaling molecules--gases that pass through cells and vanish. Overactive neurons produce large amounts of NO which may be linked

  16. Nitric Oxide--Some Old and New Perspectives.

    ERIC Educational Resources Information Center

    Ainscough, Eric W.; Brodie, Andrew M.

    1995-01-01

    Because of the role it plays in physiology and neurobiology, there is a rebirth of interest in nitric oxide. It can affect enzyme and immune system regulation and cytotoxicity. Nitric oxide may represent a new class of signaling molecules--gases that pass through cells and vanish. Overactive neurons produce large amounts of NO which may be linked…

  17. DIFFERENTIAL NITRIC OXIDE PRODUCTION BY CHICKEN IMMUNE CELLS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Nitric oxide is a rapidly reacting free radical which has cytotoxic effects during inflammatory responses and regulatory effects as a component of signal transduction cascades. We quantified the production of nitrite, a stable metabolite of nitric oxide, in chicken heterophils, monocytes and macrop...

  18. 21 CFR 868.5165 - Nitric oxide administration apparatus.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Nitric oxide administration apparatus. 868.5165 Section 868.5165 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5165 Nitric oxide...

  19. 21 CFR 868.2380 - Nitric oxide analyzer.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Nitric oxide analyzer. 868.2380 Section 868.2380 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2380 Nitric oxide analyzer....

  20. 21 CFR 868.5165 - Nitric oxide administration apparatus.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Nitric oxide administration apparatus. 868.5165 Section 868.5165 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5165 Nitric oxide...

  1. 21 CFR 868.2380 - Nitric oxide analyzer.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Nitric oxide analyzer. 868.2380 Section 868.2380 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2380 Nitric oxide analyzer....

  2. 21 CFR 868.2380 - Nitric oxide analyzer.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Nitric oxide analyzer. 868.2380 Section 868.2380 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2380 Nitric oxide analyzer....

  3. 21 CFR 868.2380 - Nitric oxide analyzer.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Nitric oxide analyzer. 868.2380 Section 868.2380 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2380 Nitric oxide analyzer....

  4. 21 CFR 868.2380 - Nitric oxide analyzer.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Nitric oxide analyzer. 868.2380 Section 868.2380 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2380 Nitric oxide analyzer....

  5. 21 CFR 868.5165 - Nitric oxide administration apparatus.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Nitric oxide administration apparatus. 868.5165 Section 868.5165 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5165 Nitric oxide...

  6. The Iron-Catalyzed Oxidation of Hydrazine by Nitric Acid

    SciTech Connect

    Karraker, D.G.

    2001-07-17

    To assess the importance of iron to hydrazine stability, the study of hydrazine oxidation by nitric acid has been extended to investigate the iron-catalyzed oxidation. This report describes those results.

  7. Nitric oxide delta band absorption measurements in the lower thermosphere

    NASA Technical Reports Server (NTRS)

    Massie, S. T.

    1980-01-01

    The first successful measurements of nitric oxide band absorption in the earth's atmosphere have been made by using the high-resolution ultraviolet spectrometers on OSO 8. These measurements were conducted between January and August 1977 and between 30 deg north and south latitudes. The nitric oxide absorption data, at the (1,0) delta band wavelength of 1829.41 A, are numerically inverted to produce nitric oxide density profiles between 85 and 145 km. The major finding of the observations is that for altitudes below 95 km there is more nitric oxide at sunrise than at sunset. A numerical model, incorporating time-dependent ionospheric chemistry and vertical diffusive transport (both eddy and molecular), is used to simulate the OSO 8 nitric oxide profiles. The peak of the model sunset profile lies at 95-km altitude, in agreement with observation, if the vertical component of the eddy diffusion coefficient is 10 million sq cm/s near 100 km.

  8. Pharmacology of endothelium-derived nitric oxide and nitrovasodilators.

    PubMed Central

    Ignarro, L. J.; Ross, G.; Tillisch, J.

    1991-01-01

    Nitric oxide is the active chemical species responsible for the vasodilator action of nitroglycerin, nitroprusside, and related nitrovasodilators. The most potent vasodilator and inhibitor of platelet aggregation known, nitric oxide was recently discovered to occur endogenously as the endothelium-derived relaxing factor. The pharmacology of endothelium-derived nitric oxide is virtually identical to that of the clinically used nitrovasodilators. Although endothelium-derived relaxing factor or endothelium-derived nitric oxide seems to be important in animals, its significance in humans still needs to be shown. We review the recent discoveries in the identification, biosynthesis, metabolism, and biologic actions of endothelium-derived nitric oxide, its significance in humans, and its relation to the clinically used nitrovasodilators. PMID:1902612

  9. Therapeutic approaches using nitric oxide in infants and children

    PubMed Central

    Steinhorn, Robin H.

    2011-01-01

    Pulmonary hypertension contributes significantly to the morbidity and mortality associated with many pediatric pulmonary and cardiac diseases. Nitric oxide, a gas molecule, is a unique pharmaceutical agent that can be inhaled and thus delivered directly to the lung. Inhaled nitric oxide was approved by the FDA in 1999 as a therapy for infants with persistent pulmonary hypertension. Since then, the use of inhaled nitric oxide has expanded to other neonatal and pediatric conditions, and our knowledge of its properties and mechanisms of action has increased tremendously. This review will discuss the physiology of nitric oxide signaling, the most common indications for its clinical use, and promising new investigations that may enhance endogenous production of nitric oxide and/or improve vascular response to it. PMID:21237265

  10. Nitric oxide and peroxynitrite interactions with mitochondria.

    PubMed

    Radi, Rafael; Cassina, Adriana; Hodara, Roberto

    2002-01-01

    Nitric oxide (*NO) and peroxynitrite (ONOO-) avidly interact with mitochondrial components, leading to a range of biological responses spanning from the modulation of mitochondrial respiration, mitochondrial dysfunction to the signaling of apoptotic cell death. Physiological levels of *NO primarily interact with cytochrome c oxidase, leading to a competitive and reversible inhibition of mitochondrial oxygen uptake. In turn, this leads to alterations in electrochemical gradients, which affect calcium uptake and may regulate processes such as mitochondrial transition pore (MTP) opening and the release of pro-apoptotic proteins. Large or persistent levels of *NO in mitochondria promote mitochondrial oxidant formation. Peroxynitrite formed either extra- or intra-mitochondrially leads to oxidative damage, most notably at complexes I and II of the electron transport chain, ATPase, aconitase and Mn-superoxide dismutase. Mitochondrial scavenging systems for peroxynitrite and peroxynitrite-derived radicals such as carbonate (CO3*-) and nitrogen dioxide radicals (*NO2) include cytochrome c oxidase, glutathione and ubiquinol and serve to partially attenuate the reactions of these oxidants with critical mitochondrial targets. Detection of nitrated mitochondrial proteins in vivo supports the concept that mitochondria constitute central loci of the toxic effects of excess reactive nitrogen species. In this review we will provide an overview of the biochemical mechanisms by which *NO and ONOO- regulate or alter mitochondrial functions. PMID:12033431

  11. Plant pathogenic Streptomyces species produce nitric oxide synthase-derived nitric oxide in response to host signals

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Nitric oxide (NO) is a potent intercellular signal for defense, development and metabolism in animals and plants. In mammals, highly regulated nitric oxide synthases (NOSs) generate NO. NOS homologs exist in some prokaryotes, but direct evidence for NO production by these proteins has been lacking...

  12. Nitric Oxide Signaling in the Microcirculation

    PubMed Central

    Buerk, Donald G.; Barbee, Kenneth A.; Jaron, Dov

    2013-01-01

    Several apparent paradoxes are evident when one compares mathematical predictions from models of nitric oxide (NO) diffusion and convection in vasculature structures with experimental measurements of NO (or related metabolites) in animal and human studies. Values for NO predicted from mathematical models are generally much lower than in vivo NO values reported in the literature for experiments, specifically with NO microelectrodes positioned at perivascular locations next to different sizes of blood vessels in the microcirculation and NO electrodes inserted into a wide range of tissues supplied by the microcirculation of each specific organ system under investigation. There continues to be uncertainty about the roles of NO scavenging by hemoglobin versus a storage function that may conserve NO, and other signaling targets for NO need to be considered. This review describes model predictions and relevant experimental data with respect to several signaling pathways in the microcirculation that involve NO. PMID:22196161

  13. Nitric oxide and mitochondria in metabolic syndrome

    PubMed Central

    Litvinova, Larisa; Atochin, Dmitriy N.; Fattakhov, Nikolai; Vasilenko, Mariia; Zatolokin, Pavel; Kirienkova, Elena

    2015-01-01

    Metabolic syndrome (MS) is a cluster of metabolic disorders that collectively increase the risk of cardiovascular disease. Nitric oxide (NO) plays a crucial role in the pathogeneses of MS components and is involved in different mitochondrial signaling pathways that control respiration and apoptosis. The present review summarizes the recent information regarding the interrelations of mitochondria and NO in MS. Changes in the activities of different NO synthase isoforms lead to the formation of metabolic disorders and therefore are highlighted here. Reduced endothelial NOS activity and NO bioavailability, as the main factors underlying the endothelial dysfunction that occurs in MS, are discussed in this review in relation to mitochondrial dysfunction. We also focus on potential therapeutic strategies involving NO signaling pathways that can be used to treat patients with metabolic disorders associated with mitochondrial dysfunction. The article may help researchers develop new approaches for the diagnosis, prevention and treatment of MS. PMID:25741283

  14. Nitric oxide-releasing porous silicon nanoparticles

    PubMed Central

    2014-01-01

    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. PMID:25114633

  15. Recent developments in nitric oxide donor drugs

    PubMed Central

    Miller, M R; Megson, I L

    2007-01-01

    During the 1980s, the free radical, nitric oxide (NO), was discovered to be a crucial signalling molecule, with wide-ranging functions in the cardiovascular, nervous and immune systems. Aside from providing a credible explanation for the actions of organic nitrates and sodium nitroprusside that have long been used in the treatment of angina and hypertensive crises respectively, the discovery generated great hopes for new NO-based treatments for a wide variety of ailments. Decades later, however, we are still awaiting novel licensed agents in this arena, despite an enormous research effort to this end. This review explores some of the most promising recent advances in NO donor drug development and addresses the challenges associated with NO as a therapeutic agent. PMID:17401442

  16. Nitric Oxide Synthase in Spontaneously Hypertensive Rats.

    PubMed

    Wu, Ch.Ch.; Yen, M.-H.

    1997-01-01

    Since its discovery by Furchgott and Zawadzki in 1980 [18], endothelium-derived relaxing factor (EDRF) has been shown to play a central role in the cardiovascular system [10]. The endothelial product is chemically equivalent to nitric oxide (NO) [23, 40] or a biochemical congener thereof [48]. Fifteen years ago, this small, simple and highly toxic molecule was known as a lengthy list of environmental pollutants found in unsavory haunts such as smoke and smog, and even as destroyer of ozone, suspected carcinogen, and precursor of acid rain. In addition, NO seems an unlikely biological jack of all trades for most of the body's functions are regulated by extraordinarily large and complex proteins and compounds. But over the past decade, diverse lines of evidence have converged to show that this sometime poison is a fundamental player in the everyday business of the human body. PMID:12386387

  17. Nitric oxide and plant iron homeostasis.

    PubMed

    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. PMID:25612116

  18. Nitric oxide-releasing porous silicon nanoparticles

    NASA Astrophysics Data System (ADS)

    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.

  19. Nitric oxide generating/releasing materials

    PubMed Central

    Liang, Hongying; Nacharaju, Parimala; Friedman, Adam; Friedman, Joel M

    2015-01-01

    Harnessing the impressive therapeutic potential of nitric oxide (NO) remains an ongoing challenge. This paper describes several of the current strategies both with respect to the underlying chemistry and physics and to the applications where they have shown promise. Included in this overview are molecular systems such as NONOates that release NO through chemical reactions and delivery vehicles such as nanoparticles that can generate, store, transport and deliver NO and related bioactive forms of NO such as nitrosothiols. Although there has been much positive movement, it is clear that we are only at the early stages of knowing how to precisely produce, transport and deliver to targeted sites therapeutic levels of NO and related molecules. PMID:26855790

  20. Nitric Oxide Release Part II. Therapeutic Applications

    PubMed Central

    Carpenter, Alexis W.; Schoenfisch, Mark H.

    2012-01-01

    Summary A wide range of nitric oxide (NO)-releasing materials have emerged as potential therapeutics that exploit NO’s vast biological roles. Macromolecular NO-releasing scaffolds are particularly promising due to their ability to store and deliver larger NO payloads in a more controlled and effective manner compared to low molecular weight NO donors. While a variety of scaffolds (e.g., particles, dendrimers, and polymers/films) have been cleverly designed, the ultimate clinical utility of most NO-releasing macromolecules remains unrealized. Although not wholly predictive of clinical success, in vitro and in vivo investigations have enabled a preliminary evaluation of the therapeutic potential of such materials. Herein, we review the application of macromolecular NO therapies for cardiovascular disease, cancer, bacterial infections, and wound healing. PMID:22362384

  1. Modulation of nitric oxide by flavonoids.

    PubMed

    Duarte, J; Francisco, V; Perez-Vizcaino, F

    2014-08-01

    One of the main mechanisms by which dietary flavonoids are thought to influence cardiovascular disease is via protection of the bioactivity of the endothelium-derived nitric oxide (NO). Additionally, flavonoids may also interfere with the signalling cascades of inflammation and prevent overproduction of NO and its deleterious consequences in shock and ischemia-reperfusion injury. In the present paper we review the evidence of the effects of flavonoids on NO. Flavonoids exert complex actions on the synthesis and bioavailability of NO which may result both in enhanced or decreased NO levels: (1) in cell free systems, several flavonoids may scavenge NO via its pro-oxidant properties by increasing superoxide. However, under conditions of oxidative stress, flavonoids may also protect NO from superoxide-driven inactivation. (2) In intact healthy tissues, some flavonoids increase eNOS activity in endothelial cells. Paradoxically this effect involves a pro-oxidant effect which results in Ca(2+)-dependent activation of eNOS. As inhibitors of PI3K, flavonoids may potentially inhibit the PI3K/Akt-dependent activation of eNOS. (3) Under conditions of inflammation and oxidative stress, flavonoids may prevent the inflammatory signalling cascades via inhibition of NFκB and thereby downregulate iNOS. On the other hand, they also prevent the overexpression of ROS generating enzymes, reducing superoxide and peroxynitrite levels, and hence preventing superoxide-induced NO inactivation and eNOS uncoupling. Therefore, the final effect of flavonoids on NO levels will depend on the flavonoid structure and the concentrations used, on the cell type under study and particularly on the presence of inflammatory/oxidative conditions. PMID:24901042

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

    PubMed Central

    2015-01-01

    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. PMID:26770919

  3. Nitric Oxide Transport in Normal Human Thoracic Aorta: Effects of Hemodynamics and Nitric Oxide Scavengers

    PubMed Central

    Liu, Xiao; Wang, Zhenze; Zhao, Ping; Fan, Zhanming; Sun, Anqiang; Zhan, Fan; Fan, Yubo; Deng, Xiaoyan

    2014-01-01

    Despite the crucial role of nitric oxide (NO) in the homeostasis of the vasculature, little quantitative information exists concerning NO transport and distribution in medium and large-sized arteries where atherosclerosis and aneurysm occur and hemodynamics is complex. We hypothesized that local hemodynamics in arteries may govern NO transport and affect the distribution of NO in the arteries, hence playing an important role in the localization of vascular diseases. To substantiate this hypothesis, we presented a lumen/wall model of the human aorta based on its MRI images to simulate the production, transport and consumption of NO in the arterial lumen and within the aortic wall. The results demonstrated that the distribution of NO in the aorta was quite uneven with remarkably reduced NO bioavailability in regions of disturbed flow, and local hemodynamics could affect NO distribution mainly via flow dependent NO production rate of endothelium. In addition, erythrocytes in the blood could moderately modulate NO concentration in the aorta, especially at the endothelial surface. However, the reaction of NO within the wall could only slightly affect NO concentration on the luminal surface, but strongly reduce NO concentration within the aortic wall. A strong positive correlation was revealed between wall shear stress and NO concentration, which was affected by local hemodynamics and NO reaction rate. In conclusion, the distribution of NO in the aorta may be determined by local hemodynamics and modulated differently by NO scavengers in the lumen and within the wall. PMID:25405341

  4. Addition of Nitric Oxide Through Nitric Oxide-paracetamol Enhances Healing Rat Achilles Tendon

    PubMed Central

    Tang, Gongyao; Appleyard, Richard C.; del Soldato, Piero; Wang, Min-Xia

    2008-01-01

    Nitric oxide is an important messenger molecule in many physiological processes. The addition of NO via NO-flurbiprofen enhances the material properties of healing tendon, however, flurbiprofen has a detrimental effect on healing. We asked if NO delivered by a cyclooxygenase 3 inhibitor (paracetamol/acetaminophen) would enhance healing in a rat Achilles tendon healing model. Rats were injected subcutaneously daily with NO-paracetamol, paracetamol or vehicle from two days before surgery to the day of tissue harvesting. Paracetamol had no effect on tendon healing compared with vehicle alone. NO-paracetamol did not change the failure load, but did decrease the water content, enhance the collagen content, reduce the cross-sectional area and improve the ultimate stress of healing tendon compared with paracetamol and vehicle. The collagen organization of the healing tendon in the NO-paracetamol group, as determined by polarized light microscopy, was enhanced. Our data suggests NO-paracetamol increases the total collagen content and enhances organization while decreasing the cross-sectional area of healing rat Achilles tendon and is consistent with human clinical trials where NO has improved the symptoms and signs of tendinopathy. PMID:18463933

  5. Inhaled nitric oxide in neonatal and paediatric transport.

    PubMed

    Lutman, Daniel; Petros, Andy

    2008-11-01

    Since the first reports of the use of inhaled nitric oxide in the early 1990s its applications have been refined to a number of specific conditions. Pre-term and term neonates benefit significantly in the improvement of oxygenation in conditions such as hypoxic respiratory failure and persistent pulmonary hypertension of the neonate and the reduction in referral rates to extra corporeal membrane oxygenation. Many neonatal units still do not have the ability to administer inhaled nitric oxide though an increasing number of neonatal units have acquired the capability to deliver inhaled nitric oxide in recent years with commercially available delivering devices. In either case if the neonate needs transfer for further management or extra corporeal membrane oxygenation the journey can be improved if inhaled nitric oxide is introduced during transport or could deteriorate if inhaled nitric oxide was discontinued during transport. Delivery of inhaled nitric oxide during transport can be technically challenging and the consequences of increased or interrupted delivery can be dangerous. The different modes of transport either by road or air can influence the method of delivery. We describe our method of delivering inhaled nitric oxide during the retrievals we undertake and how this changes depending upon the type of journey performed. We also suggest guidelines for its use during transport and outline the precautions we take to ensure safety of patient and carers during transport. PMID:18945562

  6. Nitric Oxide Synthases in Heart Failure

    PubMed Central

    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

  7. The oral microbiome and nitric oxide homoeostasis.

    PubMed

    Hezel, M P; Weitzberg, E

    2015-01-01

    The tiny radical nitric oxide (NO) participates in a vast number of physiological functions including vasodilation, nerve transmission, host defence and cellular energetics. Classically produced by a family of specific enzymes, NO synthases (NOSs), NO signals via reactions with other radicals or transition metals. An alternative pathway for the generation of NO is the nitrate-nitrite-NO pathway in which the inorganic anions nitrate (NO(3)(-)) and nitrite (NO(2)(-)) are reduced to NO and other reactive nitrogen intermediates. Nitrate and nitrite are oxidation products from NOS-dependent NO generation but also constituents in our diet, mainly in leafy green vegetables. Irrespective of origin, active uptake of circulating nitrate in the salivary glands, excretion in saliva and subsequent reduction to nitrite by oral commensal bacteria are all necessary steps for further NO generation. This central role of the oral cavity in regulating NO generation from nitrate presents a new and intriguing aspect of the human microbiome in health and disease. In this review, we present recent advances in our understanding of the nitrate-nitrite-NO pathway and specifically highlight the importance of the oral cavity as a hub for its function. PMID:23837897

  8. Diabetes, oxidative stress, nitric oxide and mitochondria function.

    PubMed

    Friederich, Malou; Hansell, Peter; Palm, Fredrik

    2009-05-01

    The role of altered mitochondria function has recently emerged as an important mechanism for the development of diabetic complications. Altered mitochondria function has also been implicated in the ageing process, defective insulin secretion, hypertension, arteriosclerosis, ischemia-reperfusion injury and apoptosis. Normally, the mitochondria are associated with ATP production using primarily pyruvate as the substrate, but recent reports indicate that tissue specific preferences exist. Also, the mitochondria are a substantial source of superoxide production, preferentially during states of elevated intracellular glucose concentrations. The mitochondria function is regulated by several factors including nitric oxide, oxidative stress, mammalian target of rapamycin, ADP and P(i) availability, which result in a complex regulation of ATP production and oxygen consumption, but also superoxide generation. These factors seem to be tissue specific, which warrants a more diverse mechanistic model applying to that specific tissue or cell type. This review presents the basic functions of the mitochondria and focuses on the complex interplay between oxidative stress, nitric oxide and uncoupling proteins in regulating mitochondria function with special focus on diabetes-induced alterations occurring on the mitochondria level. PMID:19442097

  9. Nitric Oxide Measurement from Purified Enzymes and Estimation of Scavenging Activity by Gas Phase Chemiluminescence Method.

    PubMed

    Kumari, Aprajita; Gupta, Alok Kumar; Mishra, Sonal; Wany, Aakanksha; Gupta, Kapuganti Jagadis

    2016-01-01

    In plants, nitrate reductase (NR) is a key enzyme that produces nitric oxide (NO) using nitrite as a substrate. Lower plants such as algae are shown to have nitric oxide synthase enzyme and higher plants contain NOS activity but enzyme responsible for NO production in higher plants is subjected to debate. In plant nitric oxide research, it is very important to measure NO very precisely in order to determine its functional role. A significant amount of NO is being scavenged by various cell components. The net NO production depends in production minus scavenging. Here, we describe methods to measure NO from purified NR and inducible nitric oxide synthase from mouse (iNOS), we also describe a method of measure NO scavenging by tobacco cell suspensions and mitochondria from roots. PMID:27094408

  10. Nitric oxide scavengers differentially inhibit ammonia oxidation in ammonia-oxidizing archaea and bacteria.

    PubMed

    Sauder, Laura A; Ross, Ashley A; Neufeld, Josh D

    2016-04-01

    Differential inhibitors are important for measuring the relative contributions of microbial groups, such as ammonia-oxidizing bacteria (AOB) and ammonia-oxidizing archaea (AOA), to biogeochemical processes in environmental samples. In particular, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (PTIO) represents a nitric oxide scavenger used for the specific inhibition of AOA, implicating nitric oxide as an intermediate of thaumarchaeotal ammonia oxidation. This study investigated four alternative nitric oxide scavengers for their ability to differentially inhibit AOA and AOB in comparison to PTIO. Caffeic acid, curcumin, methylene blue hydrate and trolox were tested onNitrosopumilus maritimus, two unpublished AOA representatives (AOA-6f and AOA-G6) as well as the AOB representativeNitrosomonas europaea All four scavengers inhibited ammonia oxidation by AOA at lower concentrations than for AOB. In particular, differential inhibition of AOA and AOB by caffeic acid (100 μM) and methylene blue hydrate (3 μM) was comparable to carboxy-PTIO (100 μM) in pure and enrichment culture incubations. However, when added to aquarium sponge biofilm microcosms, both scavengers were unable to inhibit ammonia oxidation consistently, likely due to degradation of the inhibitors themselves. This study provides evidence that a variety of nitric oxide scavengers result in differential inhibition of ammonia oxidation in AOA and AOB, and provides support to the proposed role of nitric oxide as a key intermediate in the thaumarchaeotal ammonia oxidation pathway. PMID:26946536

  11. The Oxidation of Hydrazine by Nitric Acid

    SciTech Connect

    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.

  12. Partial baroreceptor dysfunction and low plasma nitric oxide bioavailability as determinants of salt-sensitive hypertension: a reverse translational rat study

    PubMed Central

    Rodríguez-Pérez, A.S.; López-Rodríguez, J.F.; Calvo-Turrubiartes, M.Z.; Saavedra-Alanís, V.M.; Llamazares-Azuara, L.; Rodríguez-Martínez, M.

    2013-01-01

    This study determined whether clinical salt-sensitive hypertension (cSSHT) results from the interaction between partial arterial baroreceptor impairment and a high-sodium (HNa) diet. In three series (S-I, S-II, S-III), mean arterial pressure (MAP) of conscious male Wistar ChR003 rats was measured once before (pdMAP) and twice after either sham (SHM) or bilateral aortic denervation (AD), following 7 days on a low-sodium (LNa) diet (LNaMAP) and then 21 days on a HNa diet (HNaMAP). The roles of plasma nitric oxide bioavailability (pNOB), renal medullary superoxide anion production (RMSAP), and mRNA expression of NAD(P)H oxidase and superoxide dismutase were also assessed. In SHM (n=11) and AD (n=15) groups of S-I, LNaMAP-pdMAP was 10.5±2.1 vs 23±2.1 mmHg (P<0.001), and the salt-sensitivity index (SSi; HNaMAP−LNaMAP) was 6.0±1.9 vs 12.7±1.9 mmHg (P=0.03), respectively. In the SHM group, all rats were normotensive, and 36% were salt sensitive (SSi≥10 mmHg), whereas in the AD group ∼50% showed cSSHT. A 45% reduction in pNOB (P≤0.004) was observed in both groups in dietary transit. RMSAP increased in the AD group on both diets but more so on the HNa diet (S-II, P<0.03) than on the LNa diet (S-III, P<0.04). MAP modeling in rats without a renal hypertensive genotype indicated that the AD*HNa diet interaction (P=0.008) increases the likelihood of developing cSSHT. Translationally, these findings help to explain why subjects with clinical salt-sensitive normotension may transition to cSSHT. PMID:24141614

  13. Nitric oxide synthases: regulation and function

    PubMed Central

    Förstermann, Ulrich; Sessa, William C.

    2012-01-01

    Nitric oxide (NO), the smallest signalling molecule known, is produced by three isoforms of NO synthase (NOS; EC 1.14.13.39). They all utilize l-arginine and molecular oxygen as substrates and require the cofactors reduced nicotinamide-adenine-dinucleotide phosphate (NADPH), flavin adenine dinucleotide (FAD), flavin mononucleotide (FMN), and (6R-)5,6,7,8-tetrahydrobiopterin (BH4). All NOS bind calmodulin and contain haem. Neuronal NOS (nNOS, NOS I) is constitutively expressed in central and peripheral neurons and some other cell types. Its functions include synaptic plasticity in the central nervous system (CNS), central regulation of blood pressure, smooth muscle relaxation, and vasodilatation via peripheral nitrergic nerves. Nitrergic nerves are of particular importance in the relaxation of corpus cavernosum and penile erection. Phosphodiesterase 5 inhibitors (sildenafil, vardenafil, and tadalafil) require at least a residual nNOS activity for their action. Inducible NOS (NOS II) can be expressed in many cell types in response to lipopolysaccharide, cytokines, or other agents. Inducible NOS generates large amounts of NO that have cytostatic effects on parasitic target cells. Inducible NOS contributes to the pathophysiology of inflammatory diseases and septic shock. Endothelial NOS (eNOS, NOS III) is mostly expressed in endothelial cells. It keeps blood vessels dilated, controls blood pressure, and has numerous other vasoprotective and anti-atherosclerotic effects. Many cardiovascular risk factors lead to oxidative stress, eNOS uncoupling, and endothelial dysfunction in the vasculature. Pharmacologically, vascular oxidative stress can be reduced and eNOS functionality restored with renin- and angiotensin-converting enzyme-inhibitors, with angiotensin receptor blockers, and with statins. PMID:21890489

  14. 21 CFR 862.3080 - Breath nitric oxide test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... fractional nitric oxide concentration in expired breath aids in evaluating an asthma patient's response to anti-inflammatory therapy, as an adjunct to established clinical and laboratory assessments of...

  15. 21 CFR 862.3080 - Breath nitric oxide test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... fractional nitric oxide concentration in expired breath aids in evaluating an asthma patient's response to anti-inflammatory therapy, as an adjunct to established clinical and laboratory assessments of...

  16. 21 CFR 862.3080 - Breath nitric oxide test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... fractional nitric oxide concentration in expired breath aids in evaluating an asthma patient's response to anti-inflammatory therapy, as an adjunct to established clinical and laboratory assessments of...

  17. Nitric oxide and quality and safety of muscle based foods.

    PubMed

    Skibsted, Leif H

    2011-05-31

    Preservation of meat with nitrite or nitrate has become important to mankind in controlling meat spoilage and in producing safe and palatable meat products with good keeping properties even at ambient temperature. Nitric oxide was early recognised as pivotal for colour and colour stability of such meat products. Later specific effects on microbial growth became evident, followed by an understanding of nitric oxide as an antioxidant in processed meat, while a future recognition of nitric oxide as modulator of transmetallisation reactions in meat seems possible. Central for all these functions of nitric oxide in meat is the heme cavity in the meat pigment myoglobin with its facile conversions among reactive oxygen and nitrogen species in certain cases assisted by curing additives such as ascorbate and with a possible involvement of nitroxyl. PMID:21605822

  18. REDUCED NITRIC OXIDE PRODUCTION AND INOS MRNA EXPRESSION IN IFN-G STIMULATED CHICKEN MACROPHAGES TRANSFECTED WITH INOS SIRNAS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Utilizing RNA interference technology with siRNA in the HD-11 macrophage cell line, we determined how the inhibition or knock-down of the iNOS (inducible nitric oxide synthase) gene affected IFN-y' induced macrophage production of nitric oxide (NO) and mRNA expression of genes involved in this biolo...

  19. Measurements of nitric oxide after a nuclear burst

    NASA Technical Reports Server (NTRS)

    Mcghan, M.; Shaw, A.; Megill, L. R.; Sedlacek, W.; Guthals, P. R.; Fowler, M. M.

    1981-01-01

    Measurements of ozone and nitric oxide in a nuclear cloud 7 days after the explosion are reported. No measurable increase above ambient density of either ozone or nitric oxide was found. Results from a chemistry model of the cloud do not agree with the measurement unless 'nonstandard' assumptions are made with regard to the operating chemical processes. A number of possible explanations of the results are discussed.

  20. Detection of Nitric Oxide by Electron Paramagnetic Resonance Spectroscopy

    PubMed Central

    Hogg, Neil

    2010-01-01

    Electron paramagnetic resonance (EPR) spectroscopy has been used in a number of ways to study nitric oxide chemistry and biology. As an intrinsically stable and relatively unreactive diatomic free radical, the challenges for detecting this species by EPR are somewhat different than those for transient radical species. This review gives a basic introduction to EPR spectroscopy and discusses its uses to assess and quantify nitric oxide formation in biological systems. PMID:20304044

  1. Synthesis of nitric oxide probes with fluorescence lifetime sensitivity

    PubMed Central

    Zhegalova, Natalia G.; Gonzales, Garrett; Berezin, Mikhail Y.

    2013-01-01

    We present the rationale, synthesis and evaluation of the first activatable fluorescent probe that utilizes fluorescence lifetime change for detection of nitric oxide. The new probe DAP-LT1 features a near-infrared polymethine skeleton with diaminobenzene functionality incorporated into the meso-position. The probe is partially quenched, and upon reaction with a nitric oxide shows an increase in the fluorescence lifetime from 1.08 ns to 1.24 ns. PMID:24166035

  2. Nitric oxide is required for tactile learning in Octopus vulgaris.

    PubMed

    Robertson, J D; Bonaventura, J; Kohm, A P

    1994-06-22

    Nitric oxide, produced by nitric oxide synthase in brain tissue, is essential for several different kinds of learning in vertebrates. We present the first evidence that it is also essential for learning in an invertebrate. Intramuscular injections of an inhibitor of the enzyme completely block touch learning in Octopus vulgaris. Eight control animals learned a touch paradigm, but none of eight synthase-inhibited ones learned it. PMID:7520179

  3. Structures of human constitutive nitric oxide synthases.

    PubMed

    Li, Huiying; Jamal, Joumana; Plaza, Carla; Pineda, Stephanie Hai; Chreifi, Georges; Jing, Qing; Cinelli, Maris A; Silverman, Richard B; Poulos, Thomas L

    2014-10-01

    Mammals produce three isoforms of nitric oxide synthase (NOS): neuronal NOS (nNOS), inducible NOS (iNOS) and endothelial NOS (eNOS). The overproduction of NO by nNOS is associated with a number of neurodegenerative disorders; therefore, a desirable therapeutic goal is the design of drugs that target nNOS but not the other isoforms. Crystallography, coupled with computational approaches and medicinal chemistry, has played a critical role in developing highly selective nNOS inhibitors that exhibit exceptional neuroprotective properties. For historic reasons, crystallography has focused on rat nNOS and bovine eNOS because these were available in high quality; thus, their structures have been used in structure-activity-relationship studies. Although these constitutive NOSs share more than 90% sequence identity across mammalian species for each NOS isoform, inhibitor-binding studies revealed that subtle differences near the heme active site in the same NOS isoform across species still impact enzyme-inhibitor interactions. Therefore, structures of the human constitutive NOSs are indispensible. Here, the first structure of human neuronal NOS at 2.03 Å resolution is reported and a different crystal form of human endothelial NOS is reported at 1.73 Å resolution. PMID:25286850

  4. Nitric oxide transport in an axisymmetric stenosis

    PubMed Central

    Liu, Xiao; Fan, Yubo; Xu, X. Yun; Deng, Xiaoyan

    2012-01-01

    To test the hypothesis that disturbed flow can impede the transport of nitric oxide (NO) in the artery and hence induce atherogenesis, we used a lumen–wall model of an idealized arterial stenosis with NO produced at the blood vessel–wall interface to study the transport of NO in the stenosis. Blood flows in the lumen and through the arterial wall were simulated by Navier–Stokes equations and Darcy's Law, respectively. Meanwhile, the transport of NO in the lumen and the transport of NO within the arterial wall were modelled by advection–diffusion reaction equations. Coupling of fluid dynamics at the endothelium was achieved by the Kedem–Katchalsky equations. The results showed that both the hydraulic conductivity of the endothelium and the non-Newtonian viscous behaviour of blood had little effect on the distribution of NO. However, the blood flow rate, stenosis severity, red blood cells (RBCs), RBC-free layer and NO production rate at the blood vessel–wall interface could significantly affect the transport of NO. The theoretical study revealed that the transport of NO was significantly hindered in the disturbed flow region distal to the stenosis. The reduced NO concentration in the disturbed flow region might play an important role in the localized genesis and development of atherosclerosis. PMID:22593099

  5. Hemoglobin-mediated nitric oxide signaling.

    PubMed

    Helms, Christine; Kim-Shapiro, Daniel B

    2013-08-01

    The rate that hemoglobin reacts with nitric oxide (NO) is limited by how fast NO can diffuse into the heme pocket. The reaction is as fast as any ligand/protein reaction can be and the result, when hemoglobin is in its oxygenated form, is formation of nitrate in what is known as the dioxygenation reaction. As nitrate, at the concentrations made through the dioxygenation reaction, is biologically inert, the only role hemoglobin was once thought to play in NO signaling was to inhibit it. However, there are now several mechanisms that have been discovered by which hemoglobin may preserve, control, and even create NO activity. These mechanisms involve compartmentalization of reacting species and conversion of NO from or into other species such as nitrosothiols or nitrite which could transport NO activity. Despite the tremendous amount of work devoted to this field, major questions concerning precise mechanisms of NO activity preservation as well as if and how Hb creates NO activity remain unanswered. PMID:23624304

  6. Vascular nitric oxide may lessen Alzheimer's risk.

    PubMed

    McCarty, M F

    1998-12-01

    Estrogen deficiency, hyperinsulinemia, type II diabetes, atherosclerosis, and a past history of elevated blood pressure may be associated with increased risk of Alzheimer's disease (AD). Common to all of these risk factors is a diminished capacity of vascular endothelium to generate nitric oxide (NO). Vascular NO has the potential to enhance the membrane polarization of cerebral neurons by increasing the open probability of calcium-activated potassium channels; this may protect neurons from the excessive calcium influx, potentiated by beta-amyloid peptides that is thought to mediate neuronal damage in AD. The possibility that NO/cyclic guanosine 3', 5'-phosphate (cGMP) may modulate the synthesis or processing of the amyloid precursor protein, also merits evaluation. Practical measures for promoting vascular NO production may include increased intakes of arginine, potassium, antioxidants, and fish-oil, as well as lifestyle measures that typically lower elevated blood pressure; potential benefits of chromium, glucosamine, and silicon should also be explored. In hypertensives, angiotensin-converting enzyme (ACE) inhibitors and sodium restriction may favorably influence endothelial function. Fish-oil should have the additional benefit of antagonizing the contribution of interleukin-1 to AD pathogenesis. Ancillary anti-excitotoxic measures such as magnesium, taurine, phenytoin, and vasodilators targeting ATP-dependent potassium (KATP) channels, may likewise reduce AD risk. Most of the nutritional measures suggested here would in any case be recommendable for preservation of vascular health. PMID:10052865

  7. Hemoglobin-mediated nitric oxide signaling

    PubMed Central

    Helms, Christine; Kim-Shapiro, Daniel B.

    2013-01-01

    The rate that hemoglobin reacts with nitric oxide (NO) is limited by how fast NO can diffuse into the heme pocket. The reaction is as fast as any ligand/protein reaction can be and the result, when hemoglobin is in its oxygenated form, is formation of nitrate in what is known as the dioxygenation reaction. As nitrate, at the concentrations made through the dioxygenation reaction, is biologically inert, the only role hemoglobin was once thought to play in NO signaling was to inhibit it. However, there are now several mechanisms that have been discovered by which hemoglobin may preserve, control, and even create NO activity. These mechanisms involve compartmentalization of reacting species and conversion of NO from or into other species such as nitrosothiols or nitrite which could transport NO activity. Despite the tremendous amount of work devoted to this field, major questions concerning precise mechanisms of NO activity preservation as well as if and how Hb creates NO activity remain unanswered. PMID:23624304

  8. Nitric oxide negatively regulates mammalian adult neurogenesis

    NASA Astrophysics Data System (ADS)

    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.

  9. Structures of human constitutive nitric oxide synthases

    PubMed Central

    Li, Huiying; Jamal, Joumana; Plaza, Carla; Pineda, Stephanie Hai; Chreifi, Georges; Jing, Qing; Cinelli, Maris A.; Silverman, Richard B.; Poulos, Thomas L.

    2014-01-01

    Mammals produce three isoforms of nitric oxide synthase (NOS): neuronal NOS (nNOS), inducible NOS (iNOS) and endothelial NOS (eNOS). The overproduction of NO by nNOS is associated with a number of neurodegenerative disorders; therefore, a desirable therapeutic goal is the design of drugs that target nNOS but not the other isoforms. Crystallography, coupled with computational approaches and medicinal chemistry, has played a critical role in developing highly selective nNOS inhibitors that exhibit exceptional neuroprotective properties. For historic reasons, crystallography has focused on rat nNOS and bovine eNOS because these were available in high quality; thus, their structures have been used in structure–activity–relationship studies. Although these constitutive NOSs share more than 90% sequence identity across mammalian species for each NOS isoform, inhibitor-binding studies revealed that subtle differences near the heme active site in the same NOS isoform across species still impact enzyme–inhibitor interactions. Therefore, structures of the human constitutive NOSs are indispensible. Here, the first structure of human neuronal NOS at 2.03 Å resolution is reported and a different crystal form of human endothelial NOS is reported at 1.73 Å resolution. PMID:25286850

  10. Hemoglobin: A Nitric-Oxide Dioxygenase

    PubMed Central

    Gardner, Paul R.

    2012-01-01

    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. PMID:24278729

  11. Nitric oxide in adaptation to altitude

    PubMed Central

    Laskowski, Daniel; Erzurum, Serpil C.

    2012-01-01

    This review summarizes published information on 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 2500m 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 hours 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 three hours, but then returned toward baseline or slightly higher by 48 hours, 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 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 two hundred times higher. Other highland populations had generally higher levels although not to the degree showed 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 stress. PMID:22300645

  12. Electrophysiological responses of neurons in the rat spinal cord to nitric oxide.

    PubMed

    Pehl, U; Schmid, H A

    1997-03-01

    The effects of nitric oxide-containing solution and different nitric oxide donors were investigated on spontaneously active neurons using extracellular recording technique in areas of rat spinal cord slices where high levels of nitric oxide synthase are present. In lamina X, 93% of all neurons investigated (n = 84) increased their firing rate and 2% decreased it by superfusion with the nitric oxide donor sodium nitroprusside. In contrast, 49% of all neurons in laminae I and II (n = 90) were inhibited and only 28% were activated. Both effects were due to the postsynaptic action of sodium nitroprusside, because they could still be observed in medium containing 0.3 mM Ca2+ and 9 mM Mg2+, known to block synaptic transmission. Application of 8-bromo-cyclic-GMP caused an excitation of every neuron which was excited by sodium nitroprusside and an inhibition of every cell which was inhibited by sodium nitroprusside (n = 25). This effect was different from the effect of 8-bromo-cyclic-AMP, which mimicked only the excitatory, but not the inhibitory response of sodium nitroprusside. These results provide evidence that nitric oxide in the spinal cord can directly cause an excitation or an inhibition of the electrical activity of spinal neurons. Another, more general conclusion from our results is that the nitric oxide-induced production of cyclic-GMP alone does not allow any prediction about an excitatory or inhibitory effect on the neuronal activity, which has to be determined separately. PMID:9472412

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

    PubMed Central

    Namıduru, ES; Tarakçıoğlu, M; Namıduru, M; Kocabaş, R; Erbağcı, B; Meram, I; Karaoğlan, I; Yılmaz, N; Çekmen, M

    2011-01-01

    Objective To determine the level of oxygen-nitrogen stress parameters in the pathogenesis of amebiasis. Methods 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. Results Serum malondialdehyde and nitric oxide levels were significantly higher in acute intestinal amebiasis patients than healthy controls (P<0.001). Conclusions These results suggest that oxidative and nitrosative stress may play a major role in tissue damage in acute intestinal amebiasis patients. Also these parameters can be used to supplement the conventional microscopic method for reliable diagnosis of intestinal amebiasis. PMID:23569817

  14. Nitric Oxide, Oxidative Stress and Inflammation in Pulmonary Arterial Hypertension

    PubMed Central

    Crosswhite, Patrick; Sun, Zhongjie

    2010-01-01

    Pulmonary arterial hypertension (PAH) is a chronic and progressive disease characterized by a persistent elevation of pulmonary artery pressure accompanied by right ventricular hypertrophy (RVH). The current treatment for pulmonary hypertension is limited and only provides symptomatic relief due to unknown etiology and pathogenesis of the disease. Both vasoconstriction and structural remodeling (enhanced proliferation of VSMC) of the pulmonary arteries contribute to the progressive course of PAH, irrespective of different underlying causes. The exact molecular mechanism of PAH, however, is not fully understood. The purpose of this review is to provide recent advances in the mechanistic investigation of PAH. Specifically, this review focuses on nitric oxide (NO), oxidative stress and inflammation and how these factors contribute to the development and progression of PAH. This review also discusses recent and potential therapeutic advancements for the treatment of PAH. PMID:20051913

  15. Measurement of nitric oxide production by the lesioned rat retina with a sensitive nitric oxide electrode.

    PubMed

    Groppe, Markus; Thanos, Solon; Schuhmann, Wolfgang; Heiduschka, Peter

    2003-07-01

    Nitric oxide (NO) plays multiple roles in the nervous system. It is produced as a result of damage or injury of the retina as a part of the central nervous system. Detailed knowledge of the extent and the time course of NO production is of great importance for the understanding of pathological processes and their appropriate medical treatment. Sections of rat retina were stained with antibodies against the three isoforms of NO synthase (NOS) at several time points after a lesion of the optic nerve. No significant changes of NOS expression could be seen at any of the checked time points. For the electrochemical detection of NO production, we modified small platinum electrodes with a NO-sensitive nickel porphyrin by electrochemical polymerisation. Compared to other substances, electrochemically polymerised eugenol was found to be most suitable for protection against interferences. For the measurements, differential pulse amperometry was used. The response to nitric oxide was linear.NO production of adult rat retinas was measured post axotomy after different time points with electrochemical electrodes ex vivo. With non-treated retinas, an NO concentration of approximately 15 microM was measured. NO concentration is elevated after an axotomy reaching its highest value of up to 30 microM 5 days after the lesion. The NO concentration is decreased below the initial value after 9-14 days post axotomy. PMID:12830363

  16. Autoinhibition of endothelial nitric oxide synthase (eNOS) in gut smooth muscle by nitric oxide

    PubMed Central

    Grider, John R.; Murthy, Karnam S.

    2016-01-01

    Nitric oxide in the gut is produced by nNOS in enteric neurons and by eNOS in smooth muscle cells. The eNOS in smooth muscle is activated by vasoactive intestinal peptide (VIP) released from enteric neurons. In the present study, we examined the effect of nitric oxide on VIP-induced eNOS activation in smooth muscle cells isolated from human intestine and rabbit stomach. NOS activity was measured as formation of the 1:1 co-product, l-citrulline from l-arginine. VIP caused an increase in l-citrulline production that was inhibited by NO in a concentration dependent manner (IC50~ 25 μM; maximal inhibition 72% at 100 μM NO). Basal l-citrulline production, however, was unaffected by NO. The effect was not mediated by cGMP/PKG since the PKG inhibitor KT5823 had no effect on eNOS autoinhibition. The autoinhibition was selective for NO since the co-product l-citrulline had no effect on VIP-induced NOS activation. Similar effects were obtained in rabbit gastric and human intestinal smooth muscle cells. The results suggest that NO produced in smooth muscle cells as a result of the activation of eNOS by VIP exerts an autoinhibitory restraint on eNOS thereby regulating the balance of the VIP/cAMP/PKA and NO/cGMP/PKG pathways that regulate the relaxation of gut smooth muscle. PMID:18926858

  17. Gentamicin induced nitric oxide-related oxidative damages on vestibular afferents in the guinea pig.

    PubMed

    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. PMID:16289993

  18. Nitric oxide synthases: structure, function and inhibition.

    PubMed Central

    Alderton, W K; Cooper, C E; Knowles, R G

    2001-01-01

    This review concentrates on advances in nitric oxide synthase (NOS) structure, function and inhibition made in the last seven years, during which time substantial advances have been made in our understanding of this enzyme family. There is now information on the enzyme structure at all levels from primary (amino acid sequence) to quaternary (dimerization, association with other proteins) structure. The crystal structures of the oxygenase domains of inducible NOS (iNOS) and vascular endothelial NOS (eNOS) allow us to interpret other information in the context of this important part of the enzyme, with its binding sites for iron protoporphyrin IX (haem), biopterin, L-arginine, and the many inhibitors which interact with them. The exact nature of the NOS reaction, its mechanism and its products continue to be sources of controversy. The role of the biopterin cofactor is now becoming clearer, with emerging data implicating one-electron redox cycling as well as the multiple allosteric effects on enzyme activity. Regulation of the NOSs has been described at all levels from gene transcription to covalent modification and allosteric regulation of the enzyme itself. A wide range of NOS inhibitors have been discussed, interacting with the enzyme in diverse ways in terms of site and mechanism of inhibition, time-dependence and selectivity for individual isoforms, although there are many pitfalls and misunderstandings of these aspects. Highly selective inhibitors of iNOS versus eNOS and neuronal NOS have been identified and some of these have potential in the treatment of a range of inflammatory and other conditions in which iNOS has been implicated. PMID:11463332

  19. Kinetics of the reaction of nitric oxide with hydrogen

    NASA Technical Reports Server (NTRS)

    Flower, W. L.; Hanson, R. K.; Kruger, C. H.

    1975-01-01

    The reaction of nitric oxide with hydrogen has been studied in the temperature range 2400-4500 K using a shock-tube technique. Mixtures of NO and H2 diluted in argon or krypton were heated by incident shock waves, and the infrared emission from the fundamental vibration-rotation band of NO at 5.3 microns was used to monitor the time-varying NO concentration. The decomposition of nitric oxide behind the shock was found to be modeled well by a fifteen-reaction system. A principal result of the study was the determination of the rate constant k1 for the reaction H + NO yields N + OH, which may be the rate-limiting step for NO removal in some combustion systems. Experimental values of k1 were obtained for each test through comparisons of measured and numerically predicted NO profiles. The data are fit closely by the expression k1 = 1.34 times 10 to the fourteenth power exp(-49 200/RT) cu cm/mole-sec. These data appear to be the first available for this rate constant.

  20. Replacement of physiologically autoinhaled nitric oxide in intubated patients.

    PubMed

    Röhrig, L; Kuhlen, R; Baumert, J; Rossaint, R

    2003-04-01

    Autoinhaled nitric oxide (NO) is produced mainly in the upper airways. Orotracheal intubation disrupts the natural autoinhalation of NO from the naso- and oropharynx. The effect of disrupting and then replacing autoinhaled NO on arterial oxygenation was investigated in intubated patients. Two groups of nine patients without lung disease were examined during anaesthesia using an inspired oxygen fraction of 0.50. In both groups, the individually produced NO of the whole respiratory tract and the upper airways was determined. The amount of NO normally autoinhaled from the upper airways was replaced for 5 min after orotracheal intubation in one group. The amount of NO from the upper respiratory tract was 47+/-19 parts per billion (ppb) in the test group and the replaced NO concentration was 48+/-20 ppb. No significant increase in arterial oxygen tension could be detected during the replacement of the autoinhaled NO. Haemodynamic parameters remained unchanged. In the control group, the NO from the upper airways was 34+/-16 ppb. In contrast to the test group, it was not replaced after intubation. These findings suggest that in healthy subjects the autoinhalation of nitric oxide does not play an important role in arterial oxygenation during anaesthesia. PMID:12762356

  1. SOIL NITROUS OXIDE, NITRIC OXIDE, AND AMMONIA EMISSIONS FROM A RECOVERING RIPARIAN ECOSYSTEM IN SOUTHERN APPALACHIA

    EPA Science Inventory

    The paper presents two years of seasonal nitric oxide, ammonia, and nitrous oxide trace gas fluxes measured in a recovering riparian zone with cattle excluded and in an adjacent riparian zone grazed by cattle. In the recovering riparian zone, average nitric oxide, ammonia, and ni...

  2. Implication of nitric oxide synthase in carcinogenesis: analysis of the human inducible nitric oxide synthase gene.

    PubMed

    Esumi, H; Ogura, T; Kurashima, Y; Adachi, H; Hokari, A; Weisz, A

    1995-01-01

    Nitric oxide (NO) is a newly identified, multifunctional biological mediator. However, it also has deleterious effects on biological materials. For instance, nucleic acids, proteins, and some prosthetic groups of enzymes can be modified by NO or its reaction products with other reactive oxygen species. Endogenous nitrosamine formation through the reaction of NO or its oxidized products with amines might be involved in carcinogenesis. These deleterious effects of NO are often associated with inflammatory processes both in experimental animals and human. We analyzed the molecular mechanism of control of expression of the inducible nitric oxide synthase (NOS) gene in mouse cells by cloning its putative promoter region. This promoter responded to various cytokines and endotoxin similarly to the endogenous NOS gene in mouse cells. No appreciable induction of NOS was observed in human peripheral blood cells, but induction was detected in a human glioblastoma cell line A-172. Therefore, the human inducible NOS cDNA was cloned from A-172 cells and its cDNA-deduced amino acid sequence found to have about 80% similarity to those of both mouse and rat inducible NOSs. The effects of various cytokines on the induction of the gene were somewhat different from those observed in mouse cells, but the mouse promoter responded to these cytokines similarly to the endogenous NOS gene in human cells, indicating functional similarity of cis-elements of the genes encoding both human and mouse inducible NOS. Structural analysis of the human inducible NOS gene by Southern blot analysis revealed putative genetic restriction fragment length polymorphism in intron 5.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7581489

  3. Development of anion- and nitric oxide-selective chemical sensors and biosensors

    NASA Astrophysics Data System (ADS)

    Barker, Susan Lynn Ritenour

    1999-11-01

    The biological roles of chloride, nitrite, and nitric oxide create the need for techniques which can provide fast, sensitive, and selective detection of these analytes. Small sensor size is advantageous in biological applications, and the coupling of fluorescence transduction with optical fiber technology has allowed the preparation of micrometer and submicromter sized chemical sensors and biosensors with good selectivity, fast response times, and excellent signal to noise ratios, which are utilized for in vitro and cellular applications. Micrometer and submicrometer size fiber optic nitrite and chloride sensors have been prepared, based on immobilized metalloporphyrins, using the ion correlation principle, and characterized with respect to selectivity, sensitivity, and reproducibility. The chloride sensors were applied in vitro to rat conceptuses. The hemoprotein cytochrome c' and the heme domain of soluble guanylate cyclase (sGC) have been labeled with a fluorescent dye and utilized for intensity and fluorescence lifetime-based nitric oxide sensing. Ratiometric fiber optic sensors have been prepared by attaching the dye-labeled cytochrome c' or heme domain of sGC to the fiber along with reference dye spheres. In addition, the fluorescence lifetime of the dye-labeled cytochrome c' in solution has been monitored. A second class of nitric oxide sensors has also been developed. These are dye-based chemical sensors with a response based on the interaction of nitric oxide with a fluorophore adsorbed on a gold surface. Such chemical sensors have the advantage of commercially available components and long-term stability. The nitric oxide bio- and chemical sensors have excellent signal to noise ratios and linear responses down to low micromolar nitric oxide. The various sensors show minimal interference from numerous other chemicals that are commonly found in the cellular environment. In addition, the sensors have low micromolar limits of detection, subsecond response times and complete reversibility, making these sensors applicable to dynamic measurements of cellular nitric oxide. Extra- and intracellular nitric oxide were measured in unactivated and activated macrophages. The macrophages were activated with interferon-γ (IFN-γ) and lipopolysaccharide (LPS), known stimulants of macrophage nitric oxide production. Both protein and dye-based fiber optic ratiometric sensors have been used to determine the macrophage produced extracellular nitric oxide concentration. For intracellular measurements, the dye- cytochrome c' complex was scrape- loaded into the cytoplasm of the macrophages.

  4. The Nitric Acid Oxidation of Selected Alcohols and Ketones.

    ERIC Educational Resources Information Center

    Field, Kurt W.; And Others

    1985-01-01

    Shows that nitric acid can be used as a rapid, versatile, and economical oxidant for selected organic substances. The experiments (with background information, procedures, and results provided) require one three-hour laboratory period but could serve as open-ended projects since substrates not described could be oxidized. (JN)

  5. Nitric oxide and exercise in the horse.

    PubMed Central

    Mills, P C; Marlin, D J; Demoncheaux, E; Scott, C; Casas, I; Smith, N C; Higenbottam, T

    1996-01-01

    1. The effects of exercise on the production rate of nitric oxide (NO) in exhaled air (VNO) and the effects of inhaled NO (80 p.p.m.) on cardiovascular and respiratory parameters were investigated in five Throughbred horses. 2. The concentration of NO ([NO]) in exhaled air collected from within the nasal opening was lower when collected at a high flow rate of 80 l min-1 than at a low flow rate of 20 l min-1: when trotting at 3.7 m s-1 the values were 0.78 +/- 0.15 and 1.23 +/- 9.14 p.p.b., respectively, and when cantering at 9 m s-1 the values were 1.69 +/- 0.31 and 2.25 +/- 0.32 p.p.b., respectively. 3. Nebulized methoxamine (40 mg ml-1 for 60 s), an alpha 1-adrenergic agonist, further reduced [NO] during the 9 m s-1 canter to 1.05 +/- 0.14 and 1.99 +/- 0.41 p.p.b. when collected at 80 and 20 l min-1, respectively, and induced cyclical changes in the breathing pattern. 4. Exercise induced a linear increase in VNO with work intensity to a maximum (428.1 +/- 31.6 pmol min-1 kg-1) which coincided with the maximal oxygen uptake for the horses (138.3 +/- 11.7 ml min-1 kg-1), although a further increase in VNO (779.3 +/- 38.4 pmol min-1 kg-1) occurred immediately after exercise. The changes in VNO correlated well with the tidal volume (r = 0.968; P < 0.01) and the haematocrit (r = 0.855; P < 0.01). 5. In the first 2 min of high intensity exercise, inhaled NO (80 p.p.m.) significantly (P < 0.05) reduced the pulmonary artery pressure: during the first minute, pulmonary artery pressure was 83.1 +/- 7.6 mmHg compared with a control value of 94.4 +/- 6.3 mmHg, and during the second minute, 84.2 +/- 7.1 mmHg compared with a control value of 98.4 +/- 4.7 mmHg. There were no other significant changes in cardiovascular or respiratory indices, including cardiac output, measured during exercise between control and inhaled NO tests. 6. The results show that exhaled NO is released from the airways of the horse and may contribute to the regulation of pulmonary vascular tone during exercise. PMID:8887788

  6. The nitric oxide hypothesis of brain aging.

    PubMed

    McCann, S M

    1997-01-01

    Nitric oxide synthase (NOS)-containing neurons are found in many loci throughout the central nervous system, which include the cerebral cortex, the cerebellum, the hippocampus, and the hypothalamus. NO plays a very important role in control of neuronal activity in all of these areas by diffusing into neurons where it activates soluble guanylate cyclase (sGC) leading to generation of cyclic guanosine monophosphate (cGMP) and cyclooxygenase 1 leading to generation of prostaglandins. Both of these active agents are involved in mediating the actions of NO, the first gaseous transmitter. In the cerebellum, NO is extremely important and it is also thought to mediate long-term potentiation in the hippocampus. Various stresses and corticoids have been shown in monkeys and also in rodents to cause neuronal cell death. This may be via the stimulation of glutamic acid release, which by N-methyl-D-aspartate (NMDA) receptors causes release of NO, which can lead to neuronal cell death. In the hypothalamus,. NO stimulates corticotropin-releasing hormone (CRH), prolactin releasing factor, growth hormone-releasing hormone (GHRH), and somatostatin, lutenizing hormone-releasing hormone (LHRH), but not follicle stimulating hormone-releasing factor (FSHRF) release. In situations of increased release of NO in the hypothalamus, it could cause neuronal cell death. Following bacterial or viral infections, toxic products of the ineffective agents, such as bacterial lipopolysaccharide (LPS), circulate to the brain, where they induce interleukin-1 and iNOS mRNA and synthesis. After several hours delay, massive quantities of NO are released. Induction of iNOS occurs in the choroid plexus, meninges, in circumventricular organs, and in large numbers of iNOS neurons in the arcuate and paraventricular nuclei. The large amounts of NO released by iNOS may well produce death not only of neurons but also glial. Repeated bouts of systemic infection even without direct neural involvement could result in induction of iNOS in the central nervous system and lead to large fall out of neurons in hippocampus to impair memory, hypothalamus to decrease fever, and neuroendocrine response to infection, and could play a role in the pathogenesis of degenerative neuronal diseases of aging, such as Alzheimers. The largest induction of iNOS occurs in the anterior pituitary and pineal glands. The damage to the pituitary could also impair responses to stress and infection, and the release of NO during infection could be responsible for the degenerative changes in the pineal and diminished release of melatonin, an antioxident, and consequently, an antiaging hormone, that occur with age. PMID:9315447

  7. Role of nitric oxide on motor behavior.

    PubMed

    Del Bel, E A; Guimarães, F S; Bermúdez-Echeverry, M; Gomes, M Z; Schiaveto-de-souza, A; Padovan-Neto, F E; Tumas, V; Barion-Cavalcanti, A P; Lazzarini, M; Nucci-da-Silva, L P; de Paula-Souza, D

    2005-03-01

    The present review paper describes results indicating the influence of nitric oxide (NO) on motor control. Our last studies showed that systemic injections of low doses of inhibitors of NO synthase (NOS), the enzyme responsible for NO formation, induce anxiolytic effects in the elevated plus maze whereas higher doses decrease maze exploration. Also, NOS inhibitors decrease locomotion and rearing in an open field arena. These results may involve motor effects of this compounds, since inhibitors of NOS, NG-nitro-L-arginine (L-NOARG), N(G)-nitro-L-arginine methylester (L-NAME), N(G)-monomethyl-L-arginine (L-NMMA), and 7-Nitroindazole (7-NIO), induced catalepsy in mice. This effect was also found in rats after systemic, intracebroventricular or intrastriatal administration. Acute administration of L-NOARG has an additive cataleptic effect with haloperidol, a dopamine D2 antagonist. The catalepsy is also potentiated by WAY 100135 (5-HT1a receptor antagonist), ketanserin (5HT2a and alfal adrenergic receptor antagonist), and ritanserin (5-HT2a and 5HT2c receptor antagonist). Atropine sulfate and biperiden, antimuscarinic drugs, block L-NOARG-induced catalepsy in mice. L-NOARG subchronic administration in mice induces rapid tolerance (3 days) to its cataleptic effects. It also produces cross-tolerance to haloperidol-induced catalepsy. After subchronic L-NOARG treatment there is an increase in the density NADPH-d positive neurons in the dorsal part of nucleus caudate-putamen, nucleus accumbens, and tegmental pedunculupontinus nucleus. In contrast, this treatment decreases NADPH-d neuronal number in the substantia nigra compacta. Considering these results we suggest that (i) NO may modulate motor behavior, probably by interfering with dopaminergic, serotonergic, and cholinergic neurotransmission in the striatum; (ii) Subchronic NO synthesis inhibition induces plastic changes in NO-producing neurons in brain areas related to motor control and causes cross-tolerance to the cataleptic effect of haloperidol, raising the possibility that such treatments could decrease motor side effects associated with antipsychotic medications. Finally, recent studies using experimental Parkinson's disease models suggest an interaction between NO system and neurodegenerative processes in the nigrostriatal pathway. It provides evidence of a protective role of NO. Together, our results indicate that NO may be a key participant on physiological and pathophysiological processes in the nigrostriatal system. PMID:16047547

  8. Nitric Oxide in Astrocyte-Neuron Signaling

    SciTech Connect

    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). Although NO is not required for the SIC,PTIO reduced SIC amplitude, suggesting that NO modulates glutamate release from astrocytes or glutamate receptor sensitivity of neurons.

  9. Light activated nitric oxide releasing materials

    NASA Astrophysics Data System (ADS)

    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-nitrosyl complexes could be regenerated by treatment of the complex with solutions of nitrite. Treatment of the exhaustively irradiated solutions with excess NO2- led to generation of a Ru-NO complex that was sensitive to blue light. Preliminary work on creating metallopolymers of Ru-salen-NO is also discussed.

  10. Regulation of neuronal nitric oxide synthase and identification of novel nitric oxide signaling pathways.

    PubMed

    Dawson, T M; Sasaki, M; Gonzalez-Zulueta, M; Dawson, V L

    1998-01-01

    Neuronal nitric oxide synthase (nNOS) participate in a variety of physiologic and pathologic processes in the nervous system. nNOS was originally felt to be a constitutively expressed enzyme, but recent observations suggest that its levels are dynamically controlled in response to neuronal development, plasticity and injury. nNOS expression is regulated through alternative promoter usage through alternative mRNA splicing and it is likely that this plays an important role in the inducibility of gene expression in response to extracellular stimuli. Emerging data also suggests that NO may be the key mediator linking activity to gene expression and long-lasting neuronal responses through NO activating p21Ras through redox-sensitive modulation. PMID:9932430

  11. Cardiovascular roles of nitric oxide: A review of insights from nitric oxide synthase gene disrupted mice†

    PubMed Central

    Liu, Victor W.T.; Huang, Paul L.

    2009-01-01

    Nitric oxide (NO) is a gaseous molecule that plays many key roles in the cardiovascular system. Each of the enzymes that generate NO—neuronal, inducible and endothelial NO synthase—has been genetically disrupted in mice. This review discusses the cardiovascular phenotypes of each of the NO synthase (NOS) gene knockout mice, and the insights gained into the roles of NO in the cardiovascular system. Mice lacking the endothelial isoform are hypertensive, have endothelial dysfunction and show a more severe outcome in response to vascular injury, to stroke and cerebral ischaemia, and to diet-induced atherosclerosis. Mice lacking the neuronal isoform show a less severe outcome in response to stroke and cerebral ischaemia but have increased diet-induced atherosclerosis. Mice lacking the inducible isoform show reduced hypotension to septic shock. Together, NOS gene knockout mice have been useful tools that complement our other approaches to studying the multiple roles of NO in the cardiovascular system. PMID:17658499

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

    PubMed

    Kjeldsen, T H; Rivier, C; Lee, S; Hansen, E W; Christensen, J D; Moesby, L

    2003-03-01

    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 interleukin (IL)-6 upon stimulation with LPS, this parameter was also investigated. Cultured pituicytes, from 4-week-old male mice, were stimulated with LPS for 6 h or 24 h. At 24 h, there was a significant increase in accumulated nitrite indicating NO formation. In contrast, IL-6 release was already significantly higher 6 h after stimulation and further increased at 24 h. The correlation between accumulated nitrite and secreted IL-6 was 0.84 after 24 h of incubation with LPS. The expression of inducible NOS (iNOS) mRNA in the pituicytes was significantly higher than the control level after 6 h and 24 h of exposure to LPS, with levels at 6 h being significantly higher than those at 24 h. There was no detected expression of endothelial NOS or neuronal NOS mRNA. Cultured pituicytes were also subjected to immunocytochemistry for iNOS protein at 6, 12, and 24 h after stimulation with LPS. Most cells were positive for iNOS, but there were no observable differences with the time points that we used. Collectively, these results show that pituicytes are able to produce NO, and that the inducible form of NOS is responsible for this production. Furthermore, there is a weak correlation between NO and IL-6 released from pituicytes after 24 h of stimulation with LPS. PMID:12588513

  13. Nitric oxide production and the expression of two nitric oxide synthases in the avian retina.

    PubMed

    Tekmen-Clark, Merve; Gleason, Evanna

    2013-05-01

    Nitric oxide (NO) is known to exert multiple effects on the function of many retinal neurons and their synapses. Therefore, it is equally important to understand the potential sources of NO within the retina. To explore this, we employ a combination of 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate (DAF-FM) based NO detection and immunohistochemistry for the NO synthetic enzymes, neuronal and endothelial nitric oxide synthase (nNOS and eNOS). We find DAF signals in photoreceptors, horizontal cells, amacrine cells, efferent synapses, Müller cells, and cells in the ganglion cell layer (GCL). nNOS immunoreactivity was consistent with the DAF signal with the exception that horizontal cells and Müller cells were not clearly labeled. eNOS-like immunoreactivity (eNOS-LI) was more widespread with photoreceptors, horizontal cells, occasional bipolar cells, amacrine cells, Müller cells, and cells in the GCL all showing labeling. Double labeling with antibodies raised against calretinin, syntaxin, and glutamine synthetase confirmed that horizontal cells, amacrine cells, and Müller cells (respectively) were expressing eNOS-LI. Although little or no nNOS labeling is observed in horizontal cells or Müller cells, the expression of eNOS-LI is consistent with the ability of these cells to produce NO. Together these results suggest that the capability to produce NO is widespread in the chicken retina. We propose that multiple forms of regulation for nNOS and eNOS play a role in the patterning of NO production in the chicken retina. PMID:23721886

  14. Depolarization of mitochondria in neurons promotes activation of nitric oxide synthase and generation of nitric oxide.

    PubMed

    Katakam, Prasad V G; Dutta, Somhrita; Sure, Venkata N; Grovenburg, Samuel M; Gordon, Angellica O; Peterson, Nicholas R; Rutkai, Ibolya; Busija, David W

    2016-05-01

    The diverse signaling events following mitochondrial depolarization in neurons are not clear. We examined for the first time the effects of mitochondrial depolarization on mitochondrial function, intracellular calcium, neuronal nitric oxide synthase (nNOS) activation, and nitric oxide (NO) production in cultured neurons and perivascular nerves. Cultured rat primary cortical neurons were studied on 7-10 days in vitro, and endothelium-denuded cerebral arteries of adult Sprague-Dawley rats were studied ex vivo. Diazoxide and BMS-191095 (BMS), activators of mitochondrial KATP channels, depolarized mitochondria in cultured neurons and increased cytosolic calcium levels. However, the mitochondrial oxygen consumption rate was unaffected by mitochondrial depolarization. In addition, diazoxide and BMS not only increased the nNOS phosphorylation at positive regulatory serine 1417 but also decreased nNOS phosphorylation at negative regulatory serine 847. Furthermore, diazoxide and BMS increased NO production in cultured neurons measured with both fluorescence microscopy and electron spin resonance spectroscopy, which was sensitive to inhibition by the selective nNOS inhibitor 7-nitroindazole (7-NI). Diazoxide also protected cultured neurons against oxygen-glucose deprivation, which was blocked by NOS inhibition and rescued by NO donors. Finally, BMS induced vasodilation of endothelium denuded, freshly isolated cerebral arteries that was diminished by 7-NI and tetrodotoxin. Thus pharmacological depolarization of mitochondria promotes activation of nNOS leading to generation of NO in cultured neurons and endothelium-denuded arteries. Mitochondrial-induced NO production leads to increased cellular resistance to lethal stress by cultured neurons and to vasodilation of denuded cerebral arteries. PMID:26945078

  15. Studies in nitric oxide mutagenesis in e. coli and s. typhimurium

    SciTech Connect

    Elespuru, R.K.; Mark, T.W.

    1995-11-01

    Nitric oxide (NO) is a toxic and bio-regulatory molecule produced endogenously in response to varying stimuli. It has been shown to deaminate DNA and to cause mutations shown to deaminate DNA and to cause mutations in Salmonella typhimurium as well as in mammalian systems. In exploring the mechanism of mutation generation by nitric oxide, several problems have become apparent. One arises from the evidence that different sources of nitric oxide, i.e. gaseous NO or No generated from drugs, behave differently both chemically and biologically. Hence, experiments with the two sources of NO are not comparable. In addition, an oxidation product of nitric oxide, No{sub 2}, is a DNA-strand breaking agent and may contribute to the genetic effects observed, especially from bubbled NO. While Salmonella typhimurium TA1535 is readily mutable by NO-delivering drugs, E. coli B strain WU3610 (wild type for DNA repair) has proved to be non-mutable. The experiments of Hartman and colleagues with sodium nitrite indicate a greatly enhanced sensitivity to mutation induction in UV repair-deficient strains and in certain target DNA sequences. We have sought to determine if the sodium nitrite model also fits nitric oxide. Contrary to expectations, however, the uvrA derivative of WU3610 is not mutable by SperNO, the most potent NO-delivering drug for Salmonella TA1535.

  16. Selective perovskite catalysts to oxidize ammonia to nitric oxide

    SciTech Connect

    Quinlan, M.A.; Ramanathan, R.; Wise, H.

    1989-03-14

    A process is described for the selective oxidation of ammonia to nitric oxide in about 90% or greater yield with a minimum of nitrogen or dinitrogen oxide (N/sub 2/O) as by-products, comprising: (1) contacting gaseous ammonia in an oxygen containing gas optionally with an inert gaseous diluent with a mixed metal perovskite catalyst of the general formula: ABO/sub 3/, wherein: A is selected from the alkali, alkaline earth, lanthanide, or actinide metals or a mixture of these metals having a relatively large ionic, radius, and B is selected from an element or a combination of elements selected from Groups IB, IVB, VB, VIB, VIIB, or VIII of the Periodic Table, wherein the perovskite phase of the catalyst has an equilibrium partial pressure of oxygen at 1000/sup 0/C of greater than about 10/sup -15/ bar; and (2) heating the reactants of step (1) at greater than about 500/sup 0/C under conditions of 10 to 100,000 hr/sup -1/ hourly space velocity.

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

    PubMed

    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 110(-4) were selected as statistically significant SNPs while p-values under 510(-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. PMID:26232608

  18. Nitric oxide inhibits isoproterenol-stimulated adipocyte lipolysis through oxidative inactivation of the beta-agonist.

    PubMed Central

    Klatt, P; Cacho, J; Crespo, M D; Herrera, E; Ramos, P

    2000-01-01

    Nitric oxide has been implicated in the inhibition of catecholamine-stimulated lipolysis in adipose tissue by as yet unknown mechanisms. In the present study, it is shown that the nitric oxide donor, 2,2-diethyl-1-nitroso-oxyhydrazine, antagonized isoproterenol (isoprenaline)-induced lipolysis in rat adipocytes, freshly isolated from white adipose tissue, by decreasing the potency of the beta-agonist without affecting its efficacy. These data suggest that nitric oxide did not act downstream of the beta-adrenoceptor but reduced the effective concentration of isoproterenol. In support of the latter hypothesis, we found that pre-treatment of isoproterenol with nitric oxide abolished the lipolytic activity of the catecholamine. Spectroscopic data and HPLC analysis confirmed that the nitric oxide-mediated inactivation of isoproterenol was in fact because of the modification of the catecholamine through a sequence of oxidation reactions, which apparently involved the generation of an aminochrome. Similarly, aminochrome was found to be the primary product of isoproterenol oxidation by 3-morpholinosydnonimine and peroxynitrite. Finally, it was shown that nitric oxide released from cytokine-stimulated adipocytes attenuated the lipolytic effect of isoproterenol by inactivating the catecholamine. In contrast with very recent findings, which suggest that nitric oxide impairs the beta-adrenergic action of isoproterenol through intracellular mechanisms and not through a chemical reaction between NO and the catecholamine, we showed that nitric oxide was able to attenuate the pharmacological activity of isoproterenol in vitro as well as in a nitric oxide-generating cellular system through oxidation of the beta-agonist. These findings should be taken into account in both the design and interpretation of studies used to investigate the role of nitric oxide as a modulator of isoproterenol-stimulated signal transduction pathways. PMID:11023835

  19. Nitric Oxide Catalysis of Diazene E/Z Isomerization.

    PubMed

    Bohle, D Scott; Rosadiuk, Kristopher A

    2015-08-01

    Nitric oxide is an efficient catalyst for the cis-trans (E/Z) isomerization of diazenes. We compare the effect of room temperature solutions bearing low concentrations of nitric oxide, nitrogen dioxide, or oxygen on the rate of cis-trans isomerization, CTI, of the alkene bond in stilbene and on the azo double bond in azobenzene, as well as in four azo derivatives as measured by UV-vis spectroscopy. These rate enhancements can be as large as 3 orders of magnitude for azobenzene in solution. A mechanism is proposed where catalysis is promoted by the interaction of the nitric oxide with the diazene nitrogen lone pairs. Density functional theory, B3LYP/6-311++g** suggests that the binding of NO to the diazene should be weak and reversible but that its NO adduct has an E/Z isomerization barrier of 7.5 kcal/mol. PMID:26200101

  20. Concentration of nitric oxide metabolites in middle ear effusion.

    PubMed

    John, E O; Russell, P T; Nam, B H; Jinn, T H; Jung, T T

    2001-07-30

    Free radicals such as nitric oxide (NO) seem to be important in the pathogenesis of otitis media with effusion (OME). NO can be quantitated by measuring its metabolites, nitrate (NO(3)(-)) and nitrite (NO(2)(-)). The purpose of this study is to determine the concentrations of NO in human middle ear effusion (MEE). Samples of human MEE were collected at the time of myringotomy and tympanostomy tube insertions. The type of MEE was classified as serous (SOM), mucoid (MOM) or purulent (POM) at the time of surgery. Samples of MEE were assayed for NO metabolites (nitrate and nitrite) with colorimetric assay (Griess method). Concentrations of NO metabolites were highest in MOM followed by SOM and POM. This study suggests that NO is present in human MEE and may play an important role in the pathogenesis of OME. PMID:11434954

  1. Pulsating Auroral Nitric Oxide Production in the Lower Ionosphere

    NASA Astrophysics Data System (ADS)

    Jones, S.; Lessard, M.; Hampton, D. L.; Michell, R.

    2013-12-01

    The Pulsating Auroral Nitric Oxide Production in the Lower Ionosphere (PANOPLI) mission addresses a science problem that has strong implications regarding the question of how solar variability may be related to climate change and terrestrial weather. PANOPLI will transit a region of pulsating aurora, outfitted with instruments that provide a characterization of the electron precipitation causing pulsating aurora and determine the effects of pulsating aurora on the mesospheric NO reservoir. The NO can then transport downward to the stratosphere and chemically react with ozone causing depletion; therefore, PANOPLI is a vital first step in quantifying the auroral contribution to ozone depletion. The auroral contribution to atmospheric chemistry is 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). This sounding rocket project for investigating NO production is proposed to the ROSES-2013 HTIDeS for an FY16 launch from Poker Flat Research Range.

  2. Salivary Nitric Oxide, a Biomarker for Stress and Anxiety?

    PubMed Central

    Al-Smadi, Ahmed Mohammad; Ashour, Ala Fawzi; Al-Awaida, Wajdy

    2016-01-01

    Objective To investigate if salivary nitrate correlates to the daily psychological stress and anxiety in a group of human subjects. Methods The convenient sample recruitment method was employed; data from seventy three subjects were analyzed. The Perceived Stress Scale (PSS) and Hamilton Anxiety Rating Scale (HAM-A) inventories were used to determine stress and anxiety scores respectively. Salivary nitric oxide was measured through nitrate (NOx) levels using the Griess reaction method. Results Although stress and anxiety were correlated. No significant correlation exists between salivary nitrate and daily psychological stress and anxiety in the study's participants. Conclusion While all previous studies focused NOx levels in acute stress models. This is the first study to investigate the correlation between salivary nitrates and daily psychological stress and anxiety. Although stress and anxiety were correlated, there is no correlation between salivary nitrates and daily psychological stress and anxiety. Further studies are required to investigate this correlation using other biological samples such as plasma.

  3. Mitochondrial oxidant stress in locus coeruleus is regulated by activity and nitric oxide synthase.

    PubMed

    Sanchez-Padilla, Javier; Guzman, Jaime N; Ilijic, Ema; Kondapalli, Jyothisri; Galtieri, Daniel J; Yang, Ben; Schieber, Simon; Oertel, Wolfgang; Wokosin, David; Schumacker, Paul T; Surmeier, D James

    2014-06-01

    Loss of noradrenergic locus coeruleus (LC) neurons is a prominent feature of aging-related neurodegenerative diseases, such as Parkinson's disease (PD). The basis of this vulnerability is not understood. To explore possible physiological determinants, we studied LC neurons using electrophysiological and optical approaches in ex vivo mouse brain slices. We found that autonomous activity in LC neurons was accompanied by oscillations in dendritic Ca(2+) concentration that were attributable to the opening of L-type Ca(2+) channels. This oscillation elevated mitochondrial oxidant stress and was attenuated by inhibition of nitric oxide synthase. The relationship between activity and stress was malleable, as arousal and carbon dioxide increased the spike rate but differentially affected mitochondrial oxidant stress. Oxidant stress was also increased in an animal model of PD. Thus, our results point to activity-dependent Ca(2+) entry and a resulting mitochondrial oxidant stress as factors contributing to the vulnerability of LC neurons. PMID:24816140

  4. Mitochondrial oxidant stress in locus coeruleus is regulated by activity and nitric oxide synthase

    PubMed Central

    Sanchez–Padilla, J.; Guzman, J.N.; Ilijic, E.; Kondapalli, J.; Galtieri, D.J.; Yang, B.; Schieber, S.; Oertel, W.; Wokosin, D.; Schumacker, P. T.; Surmeier, D. J.

    2014-01-01

    Summary Loss of noradrenergic locus coeruleus (LC) neurons is a prominent feature of aging–related neurodegenerative diseases, like Parkinson’s disease (PD). The basis of this vulnerability is not understood. To explore possible physiological determinants, LC neurons were studied using electrophysiological and optical approaches in ex vivo mouse brain slices. These studies revealed that autonomous activity in LC neurons was accompanied by oscillations in dendritic Ca2+ concentration attributable to opening of L–type Ca2+ channels. This oscillation elevated mitochondrial oxidant stress and was attenuated by inhibition of nitric oxide synthase. The relationship between activity and stress was malleable, as arousal and carbon dioxide, each increased the spike rate, but differentially affected mitochondrial oxidant stress. Oxidant stress also was increased in an animal model of PD. Thus, our results point to activity–dependent Ca2+ entry and a resulting mitochondrial oxidant stress as factors contributing to the vulnerability of LC neurons. PMID:24816140

  5. Role of nitric oxide synthases in elastase-induced emphysema.

    PubMed

    Boyer, Laurent; Plantier, Laurent; Dagouassat, Maylis; Lanone, Sophie; Goven, Delphine; Caramelle, Philippe; Berrehar, Franois; Kerbrat, Stephane; Dinh-Xuan, Anh-Tuan; Crestani, Bruno; Le Gouvello, Sabine; Boczkowski, Jorge

    2011-03-01

    Nitric oxide (NO) in combination with superoxide produces peroxynitrites and induces protein nitration, which participates in a number of chronic degenerative diseases. NO is produced at high levels in the human emphysematous lung, but its role in this disease is unknown. The aim of this study was to determine whether the NO synthases contribute to the development of elastase-induced emphysema in mice. nNOS, iNOS, and eNOS were quantified and immunolocalized in the lung after a tracheal instillation of elastase in mice. To determine whether eNOS or iNOS had a role in the development of emphysema, mice bearing a germline deletion of the eNOS and iNOS genes and mice treated with a pharmacological iNOS inhibitor were exposed to elastase. Protein nitration was determined by immunofluorescence, protein oxidation was determined by ELISA. Inflammation and MMP activity were quantified by cell counts, RT-PCR and zymography in bronchoalveolar lavage fluid. Cell proliferation was determined by Ki67 immunostaining. Emphysema was quantified morphometrically. iNOS and eNOS were diffusely upregulated in the lung of elastase-treated mice and a 12-fold increase in the number of 3-nitrotyrosine-expressing cells was observed. Over 80% of these cells were alveolar type 2 cells. In elastase-instilled mice, iNOS inactivation reduced protein nitration and increased protein oxidation but had no effect on inflammation, MMP activity, cell proliferation or the subsequent development of emphysema. eNOS inactivation had no effect. In conclusion, in the elastase-injured lung, iNOS mediates protein nitration in alveolar type 2 cells and alleviates oxidative injury. Neither eNOS nor iNOS are required for the development of elastase-induced emphysema. PMID:20956973

  6. The co-immobilization of P450-type nitric oxide reductase and glucose dehydrogenase for the continuous reduction of nitric oxide via cofactor recycling.

    PubMed

    Garny, Seike; Beeton-Kempen, Natasha; Gerber, Isak; Verschoor, Jan; Jordaan, Justin

    2016-04-01

    The co-immobilization of enzymes on target surfaces facilitates the development of self-contained, multi-enzyme biocatalytic platforms. This generally entails the co-immobilization of an enzyme with catalytic value in combination with another enzyme that performs a complementary function, such as the recycling of a critical cofactor. In this study, we co-immobilized two enzymes from different biological sources for the continuous reduction of nitric oxide, using epoxide- and carboxyl-functionalized hyper-porous microspheres. Successful co-immobilization of a fungal nitric oxide reductase (a member of the cytochrome P450 enzyme family) and a bacterial glucose dehydrogenase was obtained with the carboxyl-functionalized microspheres, with enzyme activity maintenance of 158% for nitric oxide reductase and 104% for glucose dehydrogenase. The optimal stoichiometric ratio of these two enzymes was subsequently determined to enable the two independent chemical reactions to be catalyzed concomitantly, allowing for near-synchronous cofactor conversion rates. This dual-enzyme system provides a novel research tool with potential for in vitro investigations of nitric oxide, and further demonstrates the successful immobilization of a P450 enzyme with potential application towards the immobilization of other cytochrome P450 enzymes. PMID:26920484

  7. Inhaled nitric oxide in preterm infants.

    PubMed Central

    Allen, Marilee C; Donohue, Pamela; Gilmore, Maureen; Cristofalo, Elizabeth; Wilson, Renee F; Weiner, Jonathan Z; Robinson, Karen

    2010-01-01

    OBJECTIVES To systematically review the evidence on the use of inhaled nitric oxide (iNO) in preterm infants born at or before 34 weeks gestation age who receive respiratory support. DATA SOURCES We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Studies (CENTRAL) and PsycInfo in June 2010. We also searched the proceedings of the 2009 and 2010 Pediatric Academic Societies Meeting and ClinicalTrials.gov. We identified additional studies from reference lists of eligible articles and relevant reviews, as well as from technical experts. REVIEW METHODS Questions were developed in collaboration with technical experts, including the chair of the upcoming National Institutes of Health Office of Medical Applications of Research Consensus Development Conference. We limited our review to randomized controlled trials (RCTs) for the question of survival or occurrence of bronchopulmonary dysplasia (BPD) and for the question on short-term risks. All study designs were considered for long-term pulmonary or neurodevelopmental outcomes, and for questions about whether outcomes varied by subpopulation or by intervention characteristics. Two investigators independently screened search results, and abstracted data from eligible articles. RESULTS We identified a total of 14 RCTs, reported in 23 articles, and eight observational studies. Mortality rates in the NICU did not differ for infants treated with iNO versus those not treated with iNO (RR 0.97 (95% CI 0.82, 1.15)). BPD at 36 weeks for iNO and control groups also did not differ (RR 0.93 (0.86, 1.003) for survivors). A small difference was found between iNO and control infants in the composite outcome of death or BPD (RR 0.93 (0.87, 0.99)). There was inconsistent evidence about the risk of brain injury from individual RCTs, but meta-analyses showed no difference between iNO and control groups. We found no evidence of differences in other short term risks. There was no evidence to suggest a difference in the incidence of cerebral palsy (RR 1.36 (0.88, 2.10)), neurodevelopmental impairment (RR 0.91 (0.77, 1.12)), or cognitive impairment (RR 0.72 (0.35, 1.45)). Evidence was limited on whether the effect of iNO varies by subpopulation or by characteristics of the therapy (timing, dose and duration, mode of delivery, or concurrent therapies). CONCLUSIONS There was a seven percent reduction in the risk of the composite outcome of death or BPD at 36 weeks PMA for infants treated with iNO compared to controls, but no reduction in death or BPD alone. Further studies are needed to explore particular subgroups of infants and to assess long term outcomes including function in childhood. There is currently no evidence to support the use of iNO in preterm infants with respiratory failure outside the context of rigorously conducted randomized clinical trials. PMID:23126546

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

    PubMed

    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. PMID:24043366

  9. Understanding the Latitude Structure of Nitric Oxide in the Mesosphere and Lower Thermosphere

    NASA Technical Reports Server (NTRS)

    Fuller-Rowell, T.J.

    1997-01-01

    The goal of the proposed work was to understand the latitude structure of nitric oxide in the mesosphere and lower thermosphere. The problem was portrayed by a clear difference between predictions of the nitric oxide distribution from chemical/dynamical models and data from observations made by the Solar Mesosphere Explorer (SMEE) in the early to mid eighties. The data exhibits a flat latitude structure of NO, the models tend to produce at equatorial maximum. The first task was to use the UARS-HALOE data to confirm the SME observations. The purpose of this first phase was to verify the UARS-NO structure is consistent with the SME data. The next task was to determine the cause of the discrepancy between modeled and observed nitric oxide latitude structure. The result from the final phase indicated that the latitude structure in the Photo-Electron (PE) production rate was the most important.

  10. Crystal structure of nitric oxide inhibited cytochrome c peroxidase

    SciTech Connect

    Edwards, S.L.; Kraut, J. ); Poulos, T.L. )

    1988-10-18

    The authors have collected X-ray diffraction data from a crystal of cytochrome c peroxidase (CCP) complexed with the inhibitor nitric oxide to a resolution of 2.55 {angstrom}. A difference Fourier map shows density indicating the NO ligand is bound to the heme iron at the sixth coordination site in a bent configuration. Structural adjustments were determined by least-squares refinement that yielded an agreement residual of R = 0.18. The orientation of the ligand, tilting toward Arg-48, causes adjustment in the position of this nearby polar side chain. As a model for the substrate hydrogen peroxide, this geometry is consistent with the suggestion that Arg-48 serves to polarize the O-O peroxide bond to promote heterolytic cleavage of the bond. Strong difference density is also observed near residues 190-194, especially around the indole ring of Trp-191. The density indicates movement of the indole ring away from the proximal His-175 imidazole ring by about 0.25 {angstrom}, which appears to cause perturbation of the neighboring residues. The response of Trp-191 on the proximal side of the heme to binding nitric oxide on the distal side probably results from delocalization of the electron density of the ligand. Relevant to this is the recent finding that a mutant in which Trp-191 is replaced by phenylalanine has dramatically reduced activity, less than 0.05% of the parent activity. Characterization of this mutant showed in particular that electron transfer from cytochrome c was severely hindered. This mutagenesis result combined with the sensitivity of the position of Trp-191 to the electronic character of the sixth coordination site ligand leads us to speculate on the role of Trp-191 in electron transfer.

  11. Anmindenols A and B, inducible nitric oxide synthase inhibitors from a marine-derived Streptomyces sp.

    PubMed

    Lee, Jihye; Kim, Hiyoung; Lee, Tae Gu; Yang, Inho; Won, Dong Hwan; Choi, Hyukjae; Nam, Sang-Jip; Kang, Heonjoong

    2014-06-27

    Anmindenols A (1) and B (2), inhibitors of inducible nitric oxide synthase (iNOS), were isolated from a marine-derived bacterium Streptomyces sp. Their chemical structures were elucidated by interpreting various spectroscopic data, including IR, MS, and NMR. Anmindenols A and B are sesquiterpenoids possessing an indene moiety with five- and six-membered rings derived from isoprenyl units. The absolute configuration of C-4 in anmindenol B was determined by electronic circular dichroism (ECD) of a dimolybdenum complex. Anmindenols A (1) and B (2) inhibited nitric oxide production in stimulated RAW 264.7 macrophage cells with IC50 values of 23 and 19 μM, respectively. PMID:24878306

  12. Arginine, citrulline and nitric oxide metabolism in sepsis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  13. Nitric oxide emissions from a central California dairy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Concentrations of nitric oxide (NO) were monitored downwind from a central California dairy facility during 2011 and 2012. NO concentrations at the dairy were significantly higher than the background levels during August 2011, but were indistinguishable from upwind concentrations during January, Apr...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  15. Estimates of nitric oxide production for lifting spacecraft reentry

    NASA Technical Reports Server (NTRS)

    Park, C.

    1971-01-01

    The amount of nitric oxide which may be produced by heating of air during an atmospheric reentry of a lifting spacecraft is estimated by three different methods. Two assume nitrogen fixation by the process of sudden freezing, and the third is a computer calculation using chemical rate equations.

  16. 75 FR 43535 - NIH Consensus Development Conference on Inhaled Nitric Oxide Therapy for Premature Infants

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-26

    ... (NIH) ``NIH Consensus Development Conference on Inhaled Nitric Oxide Therapy for Premature Infants'' to..., brain development, and brain function. Nitric oxide is a chemical compound in gas form that is sometimes used to treat infants with severe breathing problems. Inhaled nitric oxide therapy was approved by...

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    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. PMID:20874688

  19. Nitric oxide levels and endothelial nitric oxide synthase gene polymorphisms in Turkish women with idiopathic recurrent miscarriage

    PubMed Central

    Öztürk, Ebru; Balat, Özcan; Pehlivan, Sacide; Uğur, Mete Gürol; Özkan, Yelda; Sever, Tuğçe; Namıduru, Emine; Kul, Seval

    2011-01-01

    Objective To determine whether endothelial nitric oxide synthase (eNOS) gene polymorphisms are associated with an increased risk for Idiopathic Recurrent Miscarriage (IRM) in the Turkish population and to evaluate the association between Nitric Oxide (NO) levels and eNOS gene polymorphisms in women with IRM. Material and Methods A total of 120 Turkish women were enrolled in this study in four groups. Of these, 30 women were first trimester pregnant who had IRM (Group I). Thirty healthy multipara women were in the first trimester of pregnancy with no history of abortion (Group II). Thirty women were non pregnant with a history of IRM (Group III). The remaining 30 subjects were healthy multipara non-pregnant women with no history of abortion (Group IV). DNA analysis of four groups were performed for the two polymorphisms using the PCR and/or PCR-RFLPs method and NO levels were measured spectrophotometrically. Results We observed statistically significant decreased NO levels in the pregnant patient group (p=0.001) while elevated NO levels were measured in the non pregnant patient group (p=0.004). We demonstrated that, while there was no significant difference in terms of VNTR 4/eNOS genotype, there was a marginally significant difference in terms of Glu298Asp/eNOS genotype frequency (p=0.055) in patients with IRM in the Turkish population. We observed no association between NO levels and Glu298Asp/eNOS or VNTR 4/eNOS genotypes in any of the groups. Conclusion The Glu298Asp polymorphism of eNOS could be an intriguing susceptibility factor that modulates an individual’s risk of IRM in Turkish population. Further studies to explain the role of the NO pathway in the pathophysiology of IRM are needed. PMID:24592001

  20. Endothelial Cell-Derived Nitric Oxide Mobilization is Attenuated in Copper-Deficient Rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The attenuation of endothelium-dependent nitric oxide (NO)-mediated vasodilation is a consistent finding in both conduit and resistance vessels during dietary Cu deficiency. While the effect is well established, evidence for the mechanism is still circumstantial. This study was designed to determine...

  1. [Endogenous content of the nitric oxide in the cell layers of the eye retina].

    PubMed

    Kalamkarov, G P; Bugrova, A E; Konstantinova, T S; Shevchenko, T F

    2014-07-01

    Nitric oxide is a universal molecule that regulates many different functions in an organism. In the eye retina nitric oxide plays both a regulatory role by modulation of the synaptic transmission between photoreceptors and bipolar cells and a toxic role in apoptosis induction in the outer nuclear layer and in the layer of ganglion cells. In this paper there has been made the first attempt to estimate the endogenous NO concentration in retina layers in vivo. The concentration of the nitric oxide was determined by two indepen- dent techniques: ESR spectrometry using spin trap for in vivo determination and NO-sensitive microelectrode for in situ determination in the survival isolated frog retina. The distinct NO con- centration was detected only in the ganglion cells layer (~0.25 μM) and in the inner segments layer of the photoreceptors (~0.6 μM). The activity and the kinetic characteristic of the NO-synthase localized in the same layers were also determined. Key words: retina cells layers, nitric oxide, ESR, NO-sensitive microelectrodes. PMID:25669110

  2. HBOC Vasoactivity: Interplay Between Nitric Oxide Scavenging and Capacity to Generate Bioactive Nitric Oxide Species

    PubMed Central

    Friedman, Joel M.

    2013-01-01

    Abstract Significance: Despite many advances in blood substitute research, the development of materials that are effective in maintaining blood volume and oxygen delivery remains a priority for emergency care and trauma. Clinical trials on hemoglobin (Hb)-based oxygen carriers (HBOCs) have not provided information on the mechanism of toxicity, although all commercial formulations have safety concerns. Specifically, it is important to reconcile the different hypotheses of Hb toxicity, such as nitric oxide (NO) depletion and oxidative reactions, to provide a coherent molecular basis for designing a safe HBOC. Recent Advances: HBOCs with different sizes often exhibit differences in the degree of HBOC-induced vasoactivity. This has been attributed to differences in the degree of NO scavenging and in the extent of Hb extravasation. Additionally, it is appears that Hb can undergo reactions that compensate for NO scavenging by generating bioactive forms of NO. Critical Issues: Engineering modifications to enhance bioactive NO production can result in diminished oxygen delivery by virtue of increased oxygen affinity. This strategy can prevent the HBOC from fulfilling the intended goal on preserving oxygenation; however, the NO production effects will increase perfusion and oxygen transport. Future Directions: Hb modifications influence NO scavenging and the capacity of certain HBOCs to compensate for NO scavenging through nitrite-mediated reactions that generate bioactive NO. Based on the current understanding of these NO-related factors, possible synthetic strategies are presented that address how HBOC formulations can be prepared that: (i) effectively deliver oxygen, (ii) maintain tissue perfusion, and (iii) limit/reverse underlying inflammation within the vasculature. Antioxid. Redox Signal. 18, 2284–2297. PMID:23249305

  3. Process for combined control of mercury and nitric oxide.

    SciTech Connect

    Livengood, C. D.; Mendelsohn, M. H.

    1999-11-03

    Continuing concern about the effects of mercury in the environment may lead to requirements for the control of mercury emissions from coal-fired power plants. If such controls are mandated, the use of existing flue-gas cleanup systems, such as wet scrubbers currently employed for flue-gas desulfurization, would be desirable, Such scrubbers have been shown to be effective for capturing oxidized forms of mercury, but cannot capture the very insoluble elemental mercury (Hg{sup 0}) that can form a significant fraction of the total emissions. At Argonne National Laboratory, we have proposed and tested a concept for enhancing removal of Hg{sup 0}, as well as nitric oxide, through introduction of an oxidizing agent into the flue gas upstream of a scrubber, which readily absorbs the soluble reaction products. Recently, we developed a new method for introducing the oxidizing agent into the flue-gas stream that dramatically improved reactant utilization. The oxidizing agent employed was NOXSORB{trademark}, which is a commercial product containing chloric acid and sodium chlorate. When a dilute solution of this agent was introduced into a gas stream containing Hg{sup 0} and other typical flue-gas species at 300 F, we found that about 100% of the mercury was removed from the gas phase and recovered in process liquids. At the same time, approximately 80% of the nitric oxide was removed. The effect of sulfur dioxide on this process was also investigated and the results showed that it slightly decreased the amount of Hg{sup 0} oxidized while appearing to increase the removal of nitric oxide from the gas phase. We are currently testing the effects of variations in NOXSORB{trademark} concentration, sulfur dioxide concentration, nitric oxide concentration, and reaction time (residence time). Preliminary economic projections based on the results to date indicate that the chemical cost for nitric oxide oxidation could be less than $5,000/ton removed, while for Hg{sup 0} oxidation it would be about $20,000/lb removed.

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

    PubMed Central

    Yanar, K.; Çakatay, U.; Aydın, S.; Verim, A.; Atukeren, P.; Özkan, N. E.; Karatoprak, K.; Cebe, T.; Turan, S.; Ozkök, E.; Korkmaz, G.; Cacına, C.; Küçükhüseyin, O.; Yaylım, İ.

    2016-01-01

    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. PMID:26682008

  5. Detection of nitric oxide in exhaled air using cavity enhanced absorption spectroscopy

    NASA Astrophysics Data System (ADS)

    Medrzycki, R.; Wojtas, J.; Rutecka, B.; Bielecki, Z.

    2013-07-01

    The article describes an application one of the most sensitive optoelectronic method - Cavity Enhanced Absorption Spectroscopy in investigation of nitric oxide in exhaled breath. Measurement of nitric oxide concentration in exhaled breath is a quantitative, non-invasive, simple, and safe method of respiratory inflammation and asthma diagnosis. For detection of nitric oxide by developed optoelectronic sensor the vibronic molecular transitions were used. The wavelength ranges of these transitions are situated in the infrared spectral region. A setup consists of the optoelectronic nitric oxide sensor integrated with sampling and sample conditioning unit. The constructed detection system provides to measure nitric oxide in a sample of 0-97% relative humidity.

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

    NASA Astrophysics Data System (ADS)

    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.

  7. Nitric oxide as a mediator of oxidant lung injury due to paraquat.

    PubMed Central

    Berisha, H I; Pakbaz, H; Absood, A; Said, S I

    1994-01-01

    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 NG-nitro-L-arginine methyl ester or N omega-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. PMID:7519778

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

    PubMed Central

    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

  9. Synthesis, Nitric Oxide Release, and Anti-Leukemic Activity of Glutathione-Activated Nitric Oxide Prodrugs: Structural Analogues of PABA/NO, an Anti-Cancer Lead Compound

    PubMed Central

    Chakrapani, Harinath; Wilde, Thomas C.; Citro, Michael L.; Goodblatt, Michael M.; Keefer, Larry K.; Saavedra, Joseph E.

    2008-01-01

    Diazeniumdiolate anions and their prodrug forms are reliable sources of nitric oxide (NO) that have generated interest as promising therapeutic agents. A number of structural analogues of O2-(2,4-dinitro-5-(4-(N-methylamino)benzoyloxy)phenyl) 1-(N,N-dimethylamino)diazen-1-ium-1,2-diolate (PABA/NO), an anti-cancer lead compound that is designed to release NO upon activation by glutathione, were prepared. The nitric oxide release patterns of these O2-(2,4-dinitrophenyl) diazeniumdiolates in the presence of glutathione were tested and it was found that in the absence of competing pathways, these compounds release nearly quantitative amounts of NO. The ability of PABA/NO and its structural analogues to inhibit human leukemia cell proliferation was determined and it was found that compounds releasing elevated amounts of NO displayed superior cytotoxic effects. PMID:18060792

  10. Refractory Oxide Coatings on Titanium for Nitric Acid Applications

    NASA Astrophysics Data System (ADS)

    Ravi Shankar, A.; Kamachi Mudali, U.

    2014-07-01

    Tantalum and Niobium have good corrosion resistance in nitric acid as well as in molten chloride salt medium encountered in spent fuel nuclear reprocessing plants. Commercially, pure Ti (Cp-Ti) exhibits good corrosion resistance in nitric acid medium; however, in vapor condensates of nitric acid, significant corrosion was observed. In the present study, a thermochemical diffusion method was pursued to coat Ta2O5, Nb2O5, and Ta2O5 + Nb2O5 on Ti to improve the corrosion resistance and enhance the life of critical components in reprocessing plants. The coated samples were characterized by XRD, SEM, EDX, profilometry, micro-scratch test, and ASTM A262 Practice-C test in 65 pct boiling nitric acid. The SEM micrograph of the coated samples showed that uniform dense coating containing Ta2O5 and/or Nb2O5 was formed. XRD patterns indicated the formation of TiO2, Ta2O5/Nb2O5, and mixed oxide/solid solution phase on coated Ti samples. ASTM A262 Practice-C test revealed reproducible outstanding corrosion resistance of Ta2O5-coated sample in comparison to Nb2O5- and Ta2O5 + Nb2O5-coated sample. The hardness of the Ta2O5-coated Cp-Ti sample was found to be twice that of uncoated Cp-Ti. The SEM and XRD results confirmed the presence of protective oxide layer (Ta2O5, rutile TiO2, and mixed phase) on coated sample which improved the corrosion resistance remarkably in boiling liquid phase of nitric acid compared to uncoated Cp-Ti and Ti-5Ta-1.8Nb alloy. Three phase corrosion test conducted on Ta2O5-coated samples in boiling 11.5 M nitric acid showed poor corrosion resistance in vapor and condensate phases of nitric acid due to poor adhesion of the coating. The adhesive strength of the coated samples needs to be optimized in order to improve the corrosion resistance in vapor and condensate phases of nitric acid.

  11. Modeling toxic compounds from nitric oxide emission measurements

    NASA Astrophysics Data System (ADS)

    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 < 0.01) for all toluene concentrations tested. This indicates that the model may prove useful in monitoring and predicting the fate of toxic aromatic contaminants in a complex soil system. It may also be useful in predicting the release of ozone precursors, such as changes in reservoirs of hydrocarbons and oxides of nitrogen. As such, the model may be a tool for decision makers in ozone non-attainment areas.

  12. The role of nitric oxide in prostaglandin biology; update

    PubMed Central

    Kim, Sangwon F.

    2011-01-01

    The biosynthesis of nitric oxide (NO) and prostaglandin share many similarities. Two major forms of nitric oxide synthase (NOS) and cyclooxygenase (COX) have been identified: constitutive vs inducible. In general, the constitutive form functions in housekeeping and physiologic roles whereas the inducible form is up-regulated by mitogenic or inflammatory stimuli and is responsible for pathophysiological responses. The cross talk between the COX and NOS pathways was initially reported 1993 and since then, numerous studies have been undertaken to delineate the functional consequences of this interaction as well as the potential mechanism by which each pathway interacts. This review will focus in particular on recent advances in this field that extend our understanding of these two pathways under various systems. PMID:21820072

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

    PubMed Central

    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

  14. Nitric oxide in the upper stratosphere - Measurements and geophysical interpretation

    NASA Technical Reports Server (NTRS)

    Harvath, J. J.; Frederick, J. E.; Orsini, N.; Douglass, A. R.

    1983-01-01

    A rocket-borne parachute-deployed chemiluminescence instrument has obtained seven new measurements of atmospheric nitric oxide for altitudes between 30 and 50 km at mid-latitudes. These results, when combined with profiles measured by an earlier version of the instrument, cover all four seasons and provide a more comprehensive picture of upper stratospheric nitric oxide than has been available previously. At the highest altitudes studied, the vertical gradient in mixing ratio displays positive and negative values during different observations, with the largest values tending to appear at the greatest heights in summer. Examination of the differences among the profiles, which exceed a factor of 3 near the stratopause, suggests that they arise from the action of transport processes which carry air into the mid-latitude upper stratosphere from regions of the atmosphere that contain widely different odd-nitrogen abundances.

  15. Site-directed delivery of nitric oxide to cancers.

    PubMed

    Sharma, Kavita; Chakrapani, Harinath

    2014-12-01

    Nitric oxide (NO) is a reactive gaseous free radical which mediates numerous biological processes. At elevated levels, NO is found to be toxic to cancers and hence, a number of strategies for site-directed delivery of NO to cancers are in development during the past two decades. More recently, the focus of research has been to, in conjunction with other cancer drugs deliver NO to cancers for its secondary effects including inhibition of cellular drug efflux pumps. Among the various approaches toward site-selective delivery of exogenous NO sources, enzyme activated nitric oxide donors belonging to the diazeniumdiolate category afford unique advantages including exquisite control of rates of NO generation and selectivity of NO production. For this prodrug approach, enzymes including esterase, glutathione/glutathione S-transferase, DT-diaphorase, and nitroreductase are utilized. Here, we review the design and development of various approaches to enzymatic site-directed delivery of NO to cancers and their potential. PMID:25124221

  16. Cyclooxygenase-inhibiting nitric oxide donators for osteoarthritis.

    PubMed

    Wallace, John L; Viappiani, Serena; Bolla, Manlio

    2009-03-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) remain the most commonly used medications for the treatment of the symptoms of many chronic inflammatory diseases, including osteoarthritis. Unfortunately, the toxicity of NSAIDs substantially limits their long-term use. Some newer NSAIDs, namely selective cyclooxygenase (COX)-2 inhibitors, exhibit greater gastrointestinal safety, and concomitant use of anti-secretory drugs can also reduce NSAID-induced gastropathy. However, NSAIDs also adversely affect the cardiovascular system. A new class of anti-inflammatory drugs, COX-inhibiting nitric oxide donators (CINODs), has been designed to exert similar anti-inflammatory effects as NSAIDs, but with an improved safety profile. CINODs release nitric oxide, providing protective effects in the gastrointestinal tract and attenuating the detrimental effects on blood pressure normally associated with NSAIDs. We provide an outline of the rationale for CINODs and their activity, in addition to an overview of the pre-clinical and clinical profile of the most advanced CINOD, naproxcinod. PMID:19230986

  17. [Oxygen-binding capacities of hemoglobin and nitric oxide].

    PubMed

    Zinchuk, V V; Glutkina, N V

    2013-05-01

    The analysis of the literature and our own results indicates that a nitric oxide carries out a role the allosteric effector of hemoglobin, changing its affinity to oxygen and defining a condition of oxygen transport blood function. It is important point for modification of functional properties of hemoglobin and its participation in the flow of oxygen in tissues, which plays an important role in development of disadaption reactions at stress and decreased bioactivity of the nitric oxide at the endothelial dysfunction. These findings give possiblity to creat the new ways to correct hypoxical conditions through influence on oxygen-binding properties of the blood and activity of L-arginin-NO system. PMID:24459866

  18. Endothelial nitric oxide synthase: the Cinderella of inflammation?

    PubMed

    Cirino, Giuseppe; Fiorucci, Stefano; Sessa, William C

    2003-02-01

    A hallmark of inflammation is increased vascular permeability. Increases in vascular permeability and the migration of inflammatory cells are linked to complex interactions of inflammatory mediators with the vascular endothelium. Normally, endothelial nitric oxide synthase (eNOS) produces a tonic amount of nitric oxide (NO), which is responsible for the homeostasis between the endothelium and surrounding tissues. However, most agonists that act on endothelial cells cause a series of post-translational modifications that influence eNOS activity. Furthermore, stimulation by shear stress, autacoids or growth factors either induces eNOS or shifts it to a more active state, which produces a burst of NO. Here, we highlight recent findings about eNOS and propose how new pharmacological tools can be used to dissect the involvement and contribution of eNOS to inflammatory responses. PMID:12559774

  19. Microwave torch as a plasmachemical generator of nitric oxides

    SciTech Connect

    Gritsinin, S. I.; Knyazev, V. Yu.; Kossyi, I. A.; Popov, N. A.

    2006-06-15

    The possibility of using a microwave coaxial plasmatron (a microwave torch) as an efficient plasmachemical generator of nitric oxides in an air jet has been studied experimentally. A plasmachemical model of the generator is developed. Results of calculations by this model do not contradict experimental results. A conclusion about the mechanisms governing NO{sub x} production in a plasma torch is drawn by comparing the experimental and calculated results.

  20. Decreased Exhaled Nitric Oxide Levels in Patients with Mitochondrial Disorders

    PubMed Central

    Mosquera, Ricardo A.; Samuels, Cheryl L.; Harris, Tomika S.; Yadav, Aravind; Hashmi, S. Shahrukh; Knight, Melissa S.; Koenig, Mary Kay

    2013-01-01

    Background: Nitric oxide (NO) deficiency may occur in mitochondrial disorders (MD) and can contribute to the pathogenesis of the disease. It is difficult and invasive to measure systemic nitric oxide. NO is formed in the lungs and can be detected in expired air. Currently, hand-held fractional exhaled nitric oxide (FeNO) measurement devices are available enabling a fast in-office analysis of this non-invasive test. It was postulated that FeNO levels might be reduced in MD. Methods: Sixteen subjects with definite MD by modified Walker criteria (4 to 30 years of age) and sixteen healthy control subjects of similar age, race and body mass index (BMI) underwent measurement of FeNO in accordance with the American Thoracic Society guidelines. Results: Sixteen patient-control pairs were recruited. The median FeNO level was 6.5 ppm (IQR: 4-9.5) and 10.5 ppm (IQR: 8-20.5) in the MD and control groups, respectively. In 13 pairs (81%), the FeNO levels were lower in the MD cases than in the matched controls (p=0.021). Eleven (69%) cases had very low FeNO levels (≤7ppm) compared to only 1 control (p=0.001). All cases with enzymatic deficiencies in complex I had FeNO ≤7ppm. Conclusions: Single-breath exhaled nitric oxide recordings were decreased in patients with MD. This pilot study suggests that hand-held FeNO measurements could be an attractive non-invasive indicator of MD. In addition, measurement of FeNO could be used as a parameter to monitor therapeutic response in this population. PMID:23935767

  1. Nitric Oxide and Histone Acetylation –Shaping Craniofacial Development

    PubMed Central

    Berghella, L.; Puri, PL

    2014-01-01

    Summary Previous work linked nitric oxide (NO) signaling to histone deacetelyases (HDACs) in the control of tissue homeostasis, and suggested that deregulation of this signaling contributes to human diseases. In the previous issue, Liao et al. (2014) show that coordinated NO signaling and histone acetylation are required for propercranial neural crest development and craniofacial morphogenesis and suggest that alterations of NO/acetylation network can contribute to the pathogenesis of craniofacial malformations. PMID:24856136

  2. Tutorial Review: Electrochemical Nitric Oxide Sensors for Physiological Measurements

    PubMed Central

    Privett, Benjamin J.; Shin, Jae Ho; Schoenfisch, Mark H.

    2013-01-01

    Summary The important biological roles of nitric oxide (NO) have prompted the development of analytical techniques capable of sensitive and selective detection of NO. Electrochemical sensing, more than any other NO-detection method, embodies the parameters necessary for quantifying NO in challenging physiological environments such as blood and the brain. Herein, we provide a broad overview of the field of electrochemical NO sensors, including design, fabrication, and analytical performance characteristics. Both electrochemical sensors and biological applications are detailed. PMID:20502795

  3. Application of a Nitric Oxide Sensor in Biomedicine

    PubMed Central

    Saldanha, Carlota; Lopes de Almeida, José Pedro; Silva-Herdade, Ana Santos

    2014-01-01

    In the present study, we describe the biochemical properties and effects of nitric oxide (NO) in intact and dysfunctional arterial and venous endothelium. Application of the NO electrochemical sensor in vivo and in vitro in erythrocytes of healthy subjects and patients with vascular disease are reviewed. The electrochemical NO sensor device applied to human umbilical venous endothelial cells (HUVECs) and the description of others NO types of sensors are also mentioned. PMID:25587407

  4. NITRIC OXIDE PRODUCTION AND iNOS mRNA EXPRESSION IN IFN-8-STIMULATED CHICKEN MACROPHAGES TRANSFECTED WITH iNOS siRNAs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Utilizing RNA interference technology with siRNA in the HD-11 macrophage cell line, we determined how the knock-down of the iNOS (inducible nitric oxide synthase) gene affected IFN-' induced macrophage production of nitric oxide (NO) and mRNA expression of genes involved in this biological pathway i...

  5. The response of thermospheric nitric oxide to an auroral storm

    SciTech Connect

    Siskind, D.E.

    1988-01-01

    The response of thermospheric nitric oxide (NO) to the auroral storm of September 19, 1984 is analyzed. Measurements of nitric oxide from the Solar Mesosphere Explorer (SME) ultraviolet spectrometer are compared with the calculations of a one-dimensional photochemical model of the lower thermosphere. The NCAR Thermospheric General Circulation Model (TGCM) is used to calculate the response of the background neutral atmosphere to auroral forcings such as Joule and particle heating. The output of the TGCM is used as input to the photochemical model. The time history of the auroral energy input is assessed using particle data from the NOAA 6 and 7 satellites. The SME NO measurements were made from 100 km to 140 km along two orbital tracks: one over the United States and one over Europe. The observations show a factor of 3 increase in NO at auroral latitudes for both orbits as a result of the storm. Nitric oxide at mid-latitudes also increased by a factor of 3 but only over the United States. Calculations of the mid-latitude NO response show that temperature increases which result from Joule heating lead to NO enhancements. A larger response is initially seen for altitudes greater than 120 km.

  6. Role of nitric oxide in larval and juvenile fish.

    PubMed

    Eddy, F B

    2005-10-01

    Fish are known to express the three isoforms of nitric oxide synthase (NOS), the constitutive forms endothelial or eNOS, neuronal or nNOS and the inducible form iNOS. Most studies in fish have focussed on possible roles for NO in cardiovascular physiology although there has been recent attention on the role of nNOS in embryonic development. However compared to mammalian studies there have been relatively few studies on effects of nitric oxide (NO) on fish. Studies on heart and blood vessel preparations from various fish species appear to show results specific to the species or to the particular preparation. Possible roles of NO in the in vivo biology of adult fish or larval fish have received little attention. This article reviews effects of nitric oxide on cardiovascular physiology in fish with special emphasis on larval fish. It introduces some experimental work on possible signaling pathways in larval fish and introduces the possibility that NO could be an important environmental influence for some aquatic organisms. In higher vertebrates LPS (lipopolysaccharide) is known to activate the cytokine signaling system and stimulate increased expression of iNOS and increased production of NO, but this remains less investigated in fish. The effects of LPS on cardiovascular and osmoregulatory physiology of larval and juvenile salmonids are discussed and a possible role of NO in stress-induced drinking is suggested. PMID:15979364

  7. Defective nitric oxide production by alveolar macrophages during Pneumocystis pneumonia.

    PubMed

    Lasbury, Mark E; Liao, Chung-Ping; Hage, Chadi A; Durant, Pamela J; Tschang, Dennis; Wang, Shao-Hung; Zhang, Chen; Lee, Chao-Hung

    2011-04-01

    The effect of nitric oxide (NO) on Pneumocystis (Pc) organisms, the role of NO in the defense against infection with Pc, and the production of NO by alveolar macrophages (AMs) during Pneumocystis pneumonia (PCP) were investigated. The results indicate that NO was toxic to Pc organisms and inhibited their proliferation in culture. When the production of NO was inhibited by intraperitoneal injection of rats with the nitric oxide synthase inhibitor L-N(5)-(1-iminoethyl) ornithine, progression of Pc infection in immunocompetent rats was enhanced. Concentrations of NO in bronchoalveolar lavage fluids from immunosuppressed, Pc-infected rats and mice were greatly reduced, compared with those from uninfected animals, and AMs from these animals were defective in NO production. However, inducible nitric oxide synthase (iNOS) mRNA and protein concentrations were high in AMs from Pc-infected rats and mice. Immunoblot analysis showed that iNOS in AMs from Pc-infected rats existed primarily as a monomer, but the homo-dimerization of iNOS monomers was required for the production of NO. When iNOS dimerization cofactors, including calmodulin, were added to macrophage lysates, iNOS dimerization increased, whereas incubation of the same lysates with all cofactors except calmodulin did not rescue iNOS dimer formation. These data suggest that NO is important in the defense against Pc infection, but that the production of NO in AMs during PCP is defective because of the reduced dimerization of iNOS. PMID:20558778

  8. Arginine affects appetite via nitric oxide in ducks.

    PubMed

    Wang, C; Hou, S S; Huang, W; Xu, T S; Rong, G H; Xie, M

    2014-08-01

    The objective of the study was to investigate the mechanism by which arginine regulates feed intake in Pekin ducks. In experiment 1, one hundred forty-four 1-d-old male Pekin ducks were randomly allotted to 3 dietary treatments with 6 replicate pens of 8 birds per pen. Birds in each group were fed a corn-corn gluten meal diet containing 0.65, 0.95, and 1.45% arginine. Ducks fed the diet containing 0.65% arginine had lower feed intake and plasma nitric oxide level (P < 0.05) than the other 2 groups. In experiment 2, twenty 11-d-old ducks were allotted to 1 of 2 treatments. After 2 h fasting, birds in the 2 groups were intraperitoneally administrated saline and l-NG-nitro-arginine methyl ester HCl (L-NAME) for 3 d, respectively. Feed intake (P < 0.07) and plasma nitric oxide concentration (P < 0.05) 2 h postinjection in the L-NAME administered group were lower than those of the control group. In conclusion, the study implied that arginine modifies feeding behavior possibly through controlling endogenous synthesis of nitric oxide in Pekin ducks. PMID:24902706

  9. Ultra-sensitive detection of nitric oxide isotopologues

    NASA Astrophysics Data System (ADS)

    Mitscherling, Christoph; Maul, Christof; Gericke, Karl-Heinz

    2009-10-01

    This paper reviews recent technical advances of resonance enhanced multiphoton ionization (REMPI) spectroscopy and laser-induced fluorescence (LIF) spectroscopy, both extremely sensitive techniques for the determination of low nitric oxide (NO) concentrations. Because NO is involved in a multitude of biological functions, labeling and isotope-specific detection are important tools for elucidating chemical pathways. Mass selective REMPI discovers spectroscopic windows for monitoring the most abundant isotopologues such as 14N16O, 15N16O and 14N18O without these species interfering spectroscopically with each other. This has been realized by using the A2Σ+(v'=0)<--X2ΠΩ(v'' =0) transition (NO γ-band) in the ultraviolet region around 226 nm. Selected rovibrational transitions are employed for the ultra-sensitive and isotope-specific detection of exhaled NO by LIF. The detection limit for 14N18O has been improved to 0.8 parts per trillion. Furthermore, preliminary results from a study of the A2Σ+(v' =1)<--X2ΠΩ(v'' =0) transition interfering with the B2Π(v' =1)<--X2ΠΩ(v'' =0) transition are presented as an alternative approach for isotopologue selective measurements of 14N18O. From experimental data the rotational constant B=1.10310 cm- 1 and the spin-orbit coupling constant A=33.170 cm- 1 of 14N16O (B2Π(v' =1)) have been calculated.

  10. The role of nitric oxide in neurovascular coupling.

    PubMed

    Dormanns, K; Brown, R G; David, T

    2016-04-01

    Nitric oxide (NO) is a neurotransmitter known to act as a potent cerebral vasodilator. Its role in neurovascular coupling (NVC) is discussed controversially and one of the main unanswered questions is which cell type provides the governing source of NO for the regulation of vasodynamics. Mathematical modelling can be an appropriate tool to investigate the contribution of NO towards the key components of NVC and analyse underlying mechanisms. The lumped parameter model of a neurovascular unit, including neurons (NE), astrocytes (AC), smooth muscle cells (SMC) and endothelial cells (EC), was extended to model the NO signalling pathway. Results show that NO leads to a general shift of the resting regional blood flow by dilating the arteriolar radius. Furthermore, dilation during neuronal activation is enhanced. Simulations show that potassium release is responsible for the fast onset of vascular response, whereas NO-modulated mechanisms maintain dilation. Wall shear stress-activated NO release from the EC leads to a delayed return to the basal state of the arteriolar radius. The governing source of vasodilating NO that diffuses into the SMC, which determine the arteriolar radius, depends on neuronal activation. In the resting state the EC provides the major contribution towards vasorelaxation, whereas during neuronal stimulation NO produced by the NE dominates. PMID:26796228

  11. A pulsing electric field (PEF) increases human chondrocyte proliferation through a transduction pathway involving nitric oxide signaling.

    PubMed

    Fitzsimmons, Robert J; Gordon, Stephen L; Kronberg, James; Ganey, Timothy; Pilla, Arthur A

    2008-06-01

    A potential treatment modality for joint pain due to cartilage degradation is electromagnetic fields (EMF) that can be delivered, noninvasively, to chondrocytes buried within cartilage. A pulsed EMF in clinical use for recalcitrant bone fracture healing has been modified to be delivered as a pulsed electric field (PEF) through capacitive coupling. It was the objective of this study to determine whether the PEF signal could have a direct effect on chondrocytes in vitro. This study shows that a 30-min PEF treatment can increase DNA content of chondrocyte monolayer by approximately 150% at 72 h poststimulus. Studies intended to explore the biological mechanism showed this PEF signal increased nitric oxide measured in culture medium and cGMP measured in cell extract within the 30-min exposure period. Increasing calcium in the culture media or adding the calcium ionophore A23187, without PEF treatment, also significantly increased short-term nitric oxide production. The inhibitor W7, which blocks calcium/calmodulin, prevented the PEF-stimulated increase in both nitric oxide and cGMP. The inhibitor L-NAME, which blocks nitric oxide synthase, prevented the PEF-stimulated increase in nitric oxide, cGMP, and DNA content. An inhibitor of guanylate cyclase (LY83583) blocked the PEF-stimulated increase in cGMP and DNA content. A nitric oxide donor, when present for only 30 min, increased DNA content 72 h later. Taken together, these results suggest the transduction pathway for PEF-stimulated chondrocyte proliferation involves nitric oxide and the production of nitric oxide may be the result of a cascade that involves calcium, calmodulin, and cGMP production. PMID:18240331

  12. Effects of nitric oxide on the survival and neuritogenesis of cerebellar Purkinje neurons.

    PubMed

    Oldreive, Ceri E; Gaynor, Steven; Doherty, Gayle Helane

    2012-02-01

    Nitric oxide has been investigated widely both during neurodevelopment and in neurological diseases. However, whilst it has been established that nitric oxide-producing enzymes of nitric oxide synthase family are expressed in cerebellar Purkinje neurons, the effects of nitric oxide on the viability and morphology of these neurons remain unknown. Here, we have demonstrated that the activity of neuronal nitric oxide synthase, but not the inducible or endothelial forms of this enzyme, is required to support the survival of a proportion of cerebellar Purkinje neurons in vitro. We discovered that donation of high concentrations of exogenous nitric oxide reduces Purkinje neuron survival in culture and that peroxynitrite is also toxic to these cells. Finally, we demonstrated that exogenous nitric oxide and peroxynitrite reduce both the magnitude and the complexity of the neurite arbour extended by cerebellar Purkinje neurons. Taken together, these findings reveal that whilst a low level of endogenous nitric oxide, released by the activity of neuronal nitric oxide synthase, is beneficial to cerebellar Purkinje neurons in vitro, high levels of exogenous nitric oxide and peroxynitrite are detrimental to both the survival of these neurons and to their ability to extend processes and form functional neural networks. PMID:21728061

  13. L-citrulline immunostaining identifies nitric oxide production sites within neurons

    NASA Technical Reports Server (NTRS)

    Martinelli, G. P. T.; Friedrich, V. L. Jr; Holstein, G. R.

    2002-01-01

    The cellular and subcellular localization of L-citrulline was analyzed in the adult rat brain and compared with that of traditional markers for the presence of nitric oxide synthase. Light, transmission electron, and confocal laser scanning microscopy were used to study tissue sections processed for immunocytochemistry employing a monoclonal antibody against L-citrulline or polyclonal anti-neuronal nitric oxide synthase sera, and double immunofluorescence to detect neuronal nitric oxide synthase and L-citrulline co-localization. The results demonstrate that the same CNS regions and cell types are labeled by neuronal nitric oxide synthase polyclonal antisera and L-citrulline monoclonal antibodies, using both immunocytochemistry and immunofluorescence. Short-term pretreatment with a nitric oxide synthase inhibitor reduces L-citrulline immunostaining, but does not affect neuronal nitric oxide synthase immunoreactivity. In the vestibular brainstem, double immunofluorescence studies show that many, but not all, neuronal nitric oxide synthase-positive cells co-express L-citrulline, and that local intracellular patches of intense L-citrulline accumulation are present in some neurons. Conversely, all L-citrulline-labeled neurons co-express neuronal nitric oxide synthase. Cells expressing neuronal nitric oxide synthase alone are interpreted as neurons with the potential to produce nitric oxide under other stimulus conditions, and the subcellular foci of enhanced L-citrulline staining are viewed as intracellular sites of nitric oxide production. This interpretation is supported by ultrastructural observations of subcellular foci with enhanced L-citrulline and/or neuronal nitric oxide synthase staining that are located primarily at postsynaptic densities and portions of the endoplasmic reticulum. We conclude that nitric oxide is produced and released at focal sites within neurons that are identifiable using L-citrulline as a marker. Copyright 2002 IBRO.

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

    SciTech Connect

    Zhu, Wenzhen; Yang, Bingwu; Fu, Huiling; Ma, Long; Liu, Tingting; Chai, Rongfei; Zheng, Zhaodi; Zhang, Qunye; Li, Guorong

    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. Nitric-phosphoric acid oxidation of organic waste materials

    SciTech Connect

    Pierce, R.A.; Smith, J.R.

    1995-11-01

    A wet chemical oxidation technology has been developed to address issues facing defense-related facilities, private industry, and small-volume generators such as university and medical laboratories. Initially tested to destroy and decontaminate a heterogenous mixture of radioactive-contaminated solid waste, the technology can also remediate other hazardous waste forms. The process, unique to Savannah River, offers a valuable alternative to incineration and other high-temperature or high-pressure oxidation processes. The process uses nitric acid in phosphoric acid; phosphoric acid allows nitric acid to be retained in solution well above its normal boiling point. The reaction converts organics to carbon dioxide and water, and generates NO{sub x} vapors which can be recycled using air and water. Oxidation is complete in one to three hours. In previous studies, many organic compounds were completely oxidized, within experimental error, at atmospheric pressure below 180{degrees}C; more stable compounds were decomposed at 200{degrees}C and 170 kPa. Recent studies have evaluated processing parameters and potential throughputs for three primary compounds: EDTA, polyethylene, and cellulose. The study of polyvinylchloride oxidation is incomplete at this time.

  16. Choosing the right chondrocyte cell line: Focus on nitric oxide.

    PubMed

    Santoro, Anna; Conde, Javier; Scotece, Morena; Abella, Vanessa; López, Verónica; Pino, Jesús; Gómez, Rodolfo; Gómez-Reino, Juan Jesús; Gualillo, Oreste

    2015-12-01

    Nitric oxide (NO) has been considered a catabolic factor that contributes to OA pathology by inducing chondrocytes apoptosis, matrix metalloproteinases synthesis, and pro-inflammatory cytokines expression. Thus, the research on NO regulation in chondrocytes represents a relevant field which needs to be explored in depth. However, to date, only the murine ATDC-5 cell line and primary chondrocytes are well-established cells to study NO production in cartilage tissues. The goal of this study is to determine whether two commonly used human chondrocytic cell lines: SW-1353 and T/C-28a2 cell lines are good models to examine lipopolysaccharide and/or pro-inflammatory cytokine-driven NO release and iNOS expression. To this aim, we carefully examined NO production and iNOS protein expression in human T/C-28a2 and SW-1353 chondrocytes stimulated with LPS and interleukin (IL)-1 alone or in combination. We also use ATDC-5 cells as a positive control for NO production. NO accumulation has been determined by colorimetric Griess reaction, whereas NOS type II expression was determined by Western Blot analysis. Our results clearly demonstrated that neither human T/C-28a2 nor SW-1353 chondrocytes showed a detectable increase in NO production or iNOS expression after bacterial endotoxin or cytokines challenge with IL-1. Our study demonstrated that T/C-28a2 and SW-1353 human cell lines are not suitable for studying NO release and iNOS expression confirming that ATDC5 and human primary cultured chondrocytes are the best in vitro cell system to study the actions derived from this mediator. PMID:26016689

  17. Nitric oxide reduces sickle hemoglobin polymerization: Potential role of nitric oxide-induced charge alteration in depolymerization

    PubMed Central

    Ikuta, Tohru; Thatte, Hemant S.; Tang, Jay X.; Mukerji, Ishita; Knee, Kelly; Bridges, Kenneth R.; Wang, Sabina; Montero-Huerta, Pedro; Joshi, Ratan Mani; Head, C. Alvin

    2013-01-01

    We previously demonstrated that inhaling nitric oxide (NO) increases the oxygen affinity of sickle red blood cells (RBCs) in patients with sickle cell disease (SCD). Our recent studies found that NO lowered the P50 values of sickle hemoglobin (HbS) hemolysates but did not increase methemoglobin (metHb) levels, supporting the role of NO, but not metHb, in the oxygen affinity of HbS. Here we examine the mechanism by which NO increases HbS oxygen affinity. Because anti-sickling agents increase sickle RBC oxygen affinity, we first determined whether NO exhibits anti-sickling properties. The viscosity of HbS hemolysates, measured by falling ball assays, increased upon deoxygenation; NO treatment reduced the increment. Multiphoton microscopic analyses showed smaller HbS polymers in deoxygenated sickle RBCs and HbS hemolysates exposed to NO. These results suggest that NO inhibits HbS polymer formation and has anti-sickling properties. Furthermore, we found that HbS treated with NO exhibits an isoelectric point similar to that of HbA, suggesting that NO alters the electric charge of HbS. NOHbS adducts had the same elution time as HbA upon high performance liquid chromatography analysis. This study demonstrates that NO may disrupt HbS polymers by abolishing the excess positive charge of HbS, resulting in increased oxygen affinity. PMID:21457702

  18. Oxidation of quercetin by salivary components. Quercetin-dependent reduction of salivary nitrite under acidic conditions producing nitric oxide.

    PubMed

    Takahama, Umeo; Oniki, Takayuki; Hirota, Sachiko

    2002-07-17

    Under acidic conditions, nitrite is protonated to nitrous acid (pK(a) = 3.2-3.4) that can be transformed into nitric oxide by self-decomposition and reduction. When sodium nitrite was mixed with quercetin at pH 1-2, quercetin was oxidized producing nitric oxide. In addition to quercetin, kaempferol and quercetin 4'-glucoside were also oxidized by nitrous acid, but oxidation of apigenin, luteolin, and rutin was slow compared to oxidation of the above flavonols. These results suggested that flavonols, which have a free hydroxyl group at carbon position 3, can readily reduce nitrous acid to nitric oxide. When the pH of saliva was decreased to 1-2, formation of nitric oxide was observed. The nitric oxide formation was enhanced by quercetin, and during this process quercetin was oxidized. These results indicate that there is a possibility of reactions between phenolics and nitrous acid derived from salivary nitrite in the stomach. PMID:12105964

  19. Gene variations of nitric oxide synthase regulate the effects of a saturated fat rich meal on endothelial function

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective: Endothelial nitric oxide synthase gene variations have been linked to a higher risk for cardiovascular diseases by unknown mechanisms. Our aim was to determine if two SNPs located in NOS3 (E298D and i19342) interfere with microvascular endothelial function (MEF) and/or oxidative stress du...

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

    PubMed Central

    De Luca, Chiara; Gugliandolo, Agnese; Calabrò, Carlo; Currò, Monica; Ientile, Riccardo; Raskovic, Desanka; Korkina, Ludmila; Caccamo, Daniela

    2015-01-01

    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 (CCTTT)n 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 (CCTTT)11 allele represents a genetic determinant for FM/CFS, and the (CCTTT)16 allele discriminates MCS from SMCS patients. Instead, the (CCTTT)8 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 (CCTTT)n polymorphism may be useful for differential diagnosis of various IEI. PMID:25878398

  1. Inhibitor Bound Crystal Structures of Bacterial Nitric Oxide Synthase.

    PubMed

    Holden, Jeffrey K; Dejam, Dillon; Lewis, Matthew C; Huang, He; Kang, Soosung; Jing, Qing; Xue, Fengtian; Silverman, Richard B; Poulos, Thomas L

    2015-07-01

    Nitric oxide generated by bacterial nitric oxide synthase (NOS) increases the susceptibility of Gram-positive pathogens Staphylococcus aureus and Bacillus anthracis to oxidative stress, including antibiotic-induced oxidative stress. Not surprisingly, NOS inhibitors also improve the effectiveness of antimicrobials. Development of potent and selective bacterial NOS inhibitors is complicated by the high active site sequence and structural conservation shared with the mammalian NOS isoforms. To exploit bacterial NOS for the development of new therapeutics, recognition of alternative NOS surfaces and pharmacophores suitable for drug binding is required. Here, we report on a wide number of inhibitor-bound bacterial NOS crystal structures to identify several compounds that interact with surfaces unique to the bacterial NOS. Although binding studies indicate that these inhibitors weakly interact with the NOS active site, many of the inhibitors reported here provide a revised structural framework for the development of new antimicrobials that target bacterial NOS. In addition, mutagenesis studies reveal several key residues that unlock access to bacterial NOS surfaces that could provide the selectivity required to develop potent bacterial NOS inhibitors. PMID:26062720

  2. Modulation of nitric oxide synthase activity in macrophages

    PubMed Central

    Jorens, P. G.; Matthys, K. E.

    1995-01-01

    L-Arginine is converted to the highly reactive and unstable nitric oxide (NO) and L-citrulline by an enzyme named nitric oxide synthase (NOS). NO decomposes into other nitrogen oxides such as nitrite (NO2-) and nitrate (NO2-), and in the presence of superoxide anion to the potent oxidizing agent peroxynitrite (ONOO−). Activated rodent macrophages are capable of expressing an inducible form of this enzyme (iNOS) in response to appropriate stimuli, i.e., lipopolysaccharide (LPS) and interferon-γ (IFNγ). Other cytokines can modulate the induction of NO biosynthesis in macrophages. NO is a major effector molecule of the anti-microbial and cytotoxic activity of rodent macrophages against certain micro-organisms and tumour cells, respectively. The NO synthesizing pathway has been demonstrated in human monocytes and other cells, but its role in host defence seems to be accessory. A delicate functional balance between microbial stimuli, host-derived cytokines and hormones in the microenvironment regulates iNOS expression. This review will focus mainly on the known and proposed mechanisms of the regulation of iNOS induction, and on agents that can modulate NO release once the active enzyme has been expressed in the macrophage. PMID:18475620

  3. Increased brain nitric oxide levels following ethanol administration.

    PubMed

    Finnerty, Niall; O'Riordan, Saidhbhe L; Klamer, Daniel; Lowry, John; Pålsson, Erik

    2015-05-01

    Nitric oxide is a ubiquitous messenger molecule, which at elevated concentrations has been implicated in the pathogenesis of several neurological disorders. Its role in oxidative stress, attributed in particular to the formation of peroxynitrite, proceeds through its high affinity for the superoxide radical. Alcoholism has recently been associated with the induction of oxidative stress, which is generally defined as a shift in equilibrium between pro-oxidant and anti-oxidant species in the direction of the former. Furthermore, its primary metabolite acetaldehyde, has been extensively associated with oxidative damage related toxic effects following alcohol ingestion. The principal objective of this study was the application of long term in vivo electrochemistry (LIVE) to investigate the effect of ethanol (0.125, 0.5 and 2.0 g kg(-1)) and acetaldehyde (12.5, 50 and 200 mg kg(-1)) on NO levels in the nucleus accumbens of freely moving rats. Systemic administrations of ethanol and acetaldehyde resulted in a dose-dependent increases in NO levels, albeit with very differing time courses. Subsequent to this the effect on accumbal NO levels, of subjecting the animal to different drug combinations, was also elucidated. The nitric oxide synthase inhibitor L-NAME (20 mg kg(-1)) and acetaldehyde sequestering agent D-penicillamine (50 mg kg(-1)) both attenuated the increase in NO levels following ethanol (1 g kg(-1)) administration. Conversely, the alcohol dehydrogenase inhibitor 4-methylpyrazole (25 mg kg(-1)) and catalase inhibitor sodium azide (10 mg kg(-1)) potentiated the increase in NO levels following ethanol administration. Finally, dual inhibition of aldehyde dehydrogenase and catalase by cyanamide (25 mg kg(-1)) caused an attenuation of ethanol effects on NO levels. Taken together these data highlight a robust increase in brain NO levels following systemic alcohol administration which is dependent on NO synthase activity and may involve both alcohol- and acetaldehyde-dependent mechanisms. PMID:25819134

  4. Use of a solid mixture containing diethylenetriamine/nitric oxide (DETANO) to liberate nitric oxide gas in the presence of horticultural produce to extend postharvest life.

    PubMed

    Wills, R B H; Soegiarto, L; Bowyer, M C

    2007-08-01

    Postharvest treatment of fruit and vegetables with a low concentration of nitric oxide gas can extend postharvest life but application of nitric oxide by release from a gas cylinder is not feasible for many horticultural situations. This paper reports on development of a solid mixture to generate nitric oxide gas in the presence of horticultural produce. The solid NO-donor compound, diethylenetriamine/nitric oxide (DETANO) was found to quantitatively liberate nitric oxide in the presence of a range of acidic substances including citric acid. A solid mixture of DETANO and citric acid with wheat starch added as a filler and moisture absorbent in the ratio of 1:10:20 was found to be stable for at least six months when stored in dry air. However, in humid air, absorption of moisture from the atmosphere led to reaction of DETANO with citric acid and the evolution of nitric oxide gas. When the dry mixture was placed in a container with strawberry and mushroom, the moisture given off by produce activated the mixture and resulted in a similar extension in postharvest life as achieved by direct fumigation with nitric oxide gas. Commercial use of such a solid mixture could be through tablets or sachets which are more manageable in a farm or packing house than gas fumigation. PMID:17604663

  5. Apigenin attenuates diabetes-associated cognitive decline in rats via suppressing oxidative stress and nitric oxide synthase pathway.

    PubMed

    Mao, Xiao-Yuan; Yu, Jing; Liu, Zhao-Qian; Zhou, Hong-Hao

    2015-01-01

    Our present investigation aimed to determine the neuroprotection of apigenin (API) against diabetes-associated cognitive decline (DACD) a diabetic rat model and exploring its potential mechanism. Diabetic rat model was induced by intraperitoneal injection of streptozotocin. All experiment animals treated with vehicle or API by doses of 10, 20 and 40 mg/kg for seven weeks. Firstly, the body weight and blood glucose levels were detected. We used Morris water maze test to evaluate learning and memory function. The oxidative indicators (malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH)), cNOS, iNOS, caspase-3 and caspase-9 were measured in cerebral cortex and hippocampus using corresponding commercial kits. API can increase body weight, reduce the blood glucose levels, and improve the cognitive function in rats induced by diabetes. API decrease the MDA content, and increase SOD activity and GSH level of diabetic animals in the cerebral cortex and hippocampus of diabetic rats. Meanwhile, constitutive nitric oxide synthase (cNOS), inducible nitric oxide synthase (iNOS), caspase-3/9 were markedly exhibited in the cerebral cortex and hippocampus of diabetic rats. In summary, our current work discloses that API attenuates DACD in rats via suppressing oxidative stress, nitric oxide and apoptotic cascades synthase pathway. PMID:26629041

  6. Apigenin attenuates diabetes-associated cognitive decline in rats via suppressing oxidative stress and nitric oxide synthase pathway

    PubMed Central

    Mao, Xiao-Yuan; Yu, Jing; Liu, Zhao-Qian; Zhou, Hong-Hao

    2015-01-01

    Our present investigation aimed to determine the neuroprotection of apigenin (API) against diabetes-associated cognitive decline (DACD) a diabetic rat model and exploring its potential mechanism. Diabetic rat model was induced by intraperitoneal injection of streptozotocin. All experiment animals treated with vehicle or API by doses of 10, 20 and 40 mg/kg for seven weeks. Firstly, the body weight and blood glucose levels were detected. We used Morris water maze test to evaluate learning and memory function. The oxidative indicators (malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH)), cNOS, iNOS, caspase-3 and caspase-9 were measured in cerebral cortex and hippocampus using corresponding commercial kits. API can increase body weight, reduce the blood glucose levels, and improve the cognitive function in rats induced by diabetes. API decrease the MDA content, and increase SOD activity and GSH level of diabetic animals in the cerebral cortex and hippocampus of diabetic rats. Meanwhile, constitutive nitric oxide synthase (cNOS), inducible nitric oxide synthase (iNOS), caspase-3/9 were markedly exhibited in the cerebral cortex and hippocampus of diabetic rats. In summary, our current work discloses that API attenuates DACD in rats via suppressing oxidative stress, nitric oxide and apoptotic cascades synthase pathway. PMID:26629041

  7. Interaction and reactivity of nitric oxide and carbon monoxide on ruthenium surfaces

    SciTech Connect

    Quick, E.E.

    1980-03-01

    A multifaceted investigation of the reduction of nitric oxide by carbon monoxide using a ruthenium (102) single crystal catalyst in the pressure range 10/sup -3/ to 10 Torr and temperature range of 300 to 475/sup 0/C has been undertaken. Kinetic and isotopic results indicate that the reaction products CO/sub 2/ and N/sub 2/ were produced via two reaction mechanisms. Using a reducing gas mixture (low P/sub NO//P/sub CO/ ratio) a two site mechanism was operative involving NO dissociation. The carbon monoxide kinetic order varied from +1 to -3 and the nitric oxide order varied from +1 to 0. The catalyst under these conditions was determined to be metallic ruthenium with oxygen bonded within the first surface layer. The oxygen was unreactive and formed a (1 x 3)-0 LEED pattern. Under oxidizing conditions (high P/sub NO//P/sub CO/ ratio) the catalyst was ruthenium dioxide and the functional mechanism under these reaction conditions yielded a nitric oxide order of +2 to -4. Inclusion of a site poisoning mechanism under reducing conditions and an RuO/sub 2/ growth mechanism involving ruthenium cation transfer under oxidizing conditions into the kinetic rate laws led to an overall rate law which could be fit to the carbon monoxide and nitric oxide order plots. Using isotopically oxygen labelled reactants, it was observed that the three possible isotopes of carbon dioxide were produced. A ..gamma..-CO surface species is postulated as an intermediate in the exchange process. The reaction was observed to be initially surface structure insensitive and the reaction kinetics were derived using a Langmuir-Hinshelwood formalism.

  8. The role of nitric oxide in low level light therapy

    NASA Astrophysics Data System (ADS)

    Hamblin, Michael R.

    2008-02-01

    The use of low levels of visible or near infrared light for reducing pain, inflammation and edema, promoting healing of wounds, deeper tissues and nerves, and preventing tissue damage by reducing cellular apoptosis has been known for almost forty years since the invention of lasers. Despite many reports of positive findings from experiments conducted in vitro, in animal models and in randomized controlled clinical trials, LLLT remains controversial. Firstly the biochemical mechanisms underlying the positive effects are incompletely understood, and secondly the complexity of choosing amongst a large number of illumination parameters has led to the publication of a number of negative studies as well as many positive ones. This review will focus on the role of nitric oxide in the cellular and tissue effects of LLLT. Red and near-IR light is primarily absorbed by cytochrome c oxidase (unit four in the mitochondrial respiratory chain). Nitric oxide produced in the mitochondria can inhibit respiration by binding to cytochrome c oxidase and competitively displacing oxygen, especially in stressed or hypoxic cells. If light absorption displaced the nitric oxide and thus allowed the cytochrome c oxidase to recover and cellular respiration to resume, this would explain many of the observations made in LLLT. Why the effect is only seen in hypoxic, stressed or damaged cells or tissues? How the effects can keep working for some time (hours or days) postillumination? Why increased NO concentrations are sometimes measured in cell culture or in animals? How blood flow can be increased? Why angiogenesis is sometimes increased after LLLT in vivo?

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

    SciTech Connect

    Grimes, Travis Shane; Mincher, Bruce Jay; Schmitt, Nicholas C

    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.

  10. Nitric oxide production increases during Toxoplasma gondii encephalitis in mice.

    PubMed

    Dincel, Gungor Cagdas; Atmaca, Hasan Tarik

    2015-09-01

    Toxoplasma gondii is an intracellular parasite with the potential of causing severe encephalitis among immunocompromised human and animals. The aim of this experimental study was to investigate the immunomodulatory and immunopathological role of nitric oxide (NO) in central nervous systems and to identify any correlation between toxoplasmosis neuropathology and investigate the consequences of the cellular responses protect against T. gondii. Mice were infected with ME49 strain T. gondii and levels of endothelial, neuronal and inducible nitric oxide synthase (eNOS, nNOS, iNOS), glial fibrillary acidic protein (GFAP) and neurofilament (NF) were examined in brain tissues by immunohistochemistry, during the development and establishment of a chronic infection at 10 30 and 60 days post infection. Results of the study revealed that the levels of eNOS (p<0.05), nNOS (p<0.05), iNOS (p<0.005), GFAP (p<0.005) and NF (p<0.005) were remarkably higher in T. gondii-infected mice than in uninfected control. The most prominent finding from our study was 10 and 30 days after inoculation data indicating that increased levels of NO not only a potential neuroprotective role for immunoregulatory and immunopathological but also might be a molecular trigger of bradyzoite development. Furthermore, this findings were shown that high expressed NO origin was not only inducible nitric oxide synthase but also endothelial and neuronal. We demonstrated that activation of astrocytes and microglia/macrophages is a significant event in toxoplasma encephalitis (TE). The results also clearly indicated that increased levels of NO might contribute to neuropathology related with TE. Furthermore, expression of NF might gives an idea of the progress and critical for diagnostic significance of this disease. PMID:26115941

  11. Reduced upper airway nitric oxide in cystic fibrosis.

    PubMed Central

    Balfour-Lynn, I M; Laverty, A; Dinwiddie, R

    1996-01-01

    Nitric oxide (NO) produced within the respiratory tract is detectable in exhaled and nasal air. Its synthesis may be induced by inflammatory cytokines and reduced by glucocorticoids. Increased concentrations have been found in asthma and bronchiectasis. In this study, NO concentrations were determined in 63 children with cystic fibrosis, of whom 13 were on inhaled steroids (mean age 13.3 years) and 50 were not (mean age 12.3 years); 57 normal children (mean age 12.2 years) were also studied. NO was measured by chemiluminescence analyser, exhaled NO following a relaxed vital capacity manoeuvre, and nasal NO with the breath held following a full inspiration. Mean concentration of exhaled NO in cystic fibrosis patients (no steroids) was 4.7 parts per billion (ppb) (95% confidence interval (CI) 4.0 to 5.3); this did not differ from values in normal children (mean 4.8 ppb, 95% CI 3.8 to 5.8) or in cystic fibrosis patients on inhaled steroids (mean 3.6 ppb, 95% CI 2.5 to 4.8). Nasal concentrations were significantly lower in cystic fibrosis patients, with or without inhaled steroids, than in normal children (cystic fibrosis, no inhaled steroids: 460 ppb, 95% CI 399 to 520; cystic fibrosis, inhaled steroids: 522 ppb, 95% CI 313 to 730, v normal children: 1024 ppb, 95% CI 896 to 1152, p < 0.0001). Considering the inflammatory nature of cystic fibrosis, it is surprising exhaled NO levels were not increased, but this may have been due to alteration in NO diffusion through thick mucus. The low nasal NO concentrations, which are probably the result of impaired flow from the paranasal sinuses, may contribute to the recurrent respiratory infections typical of cystic fibrosis. PMID:8984918

  12. Nitric oxide produced during murine listeriosis is protective.

    PubMed Central

    Boockvar, K S; Granger, D L; Poston, R M; Maybodi, M; Washington, M K; Hibbs, J B; Kurlander, R L

    1994-01-01

    Nitric oxide (NO) has been shown to be important for intracellular microbiostasis in vitro. To determine the role of NO in immune function in vivo, groups of C57BL/6 mice were given a sublethal intravenous inoculum of Listeria monocytogenes EGD, and their urine was monitored daily for nitrate, the mammalian end product of NO metabolism. Urinary nitrate levels peaked at 5 to 10 times the basal level on days 5 to 6, when spleen and liver Listeria counts declined most steeply, and decreased thereafter, when spleens and livers were nearly sterile. Peritoneal macrophages explanted from Listeria-infected mice produced nitrite spontaneously, whereas macrophages from uninfected mice did not. The inducible NO synthase mRNA was detectable in the spleens of infected mice on days 1 to 4 of infection. When Listeria-infected mice were treated orally throughout the infection with NG-monomethyl-L-arginine (NMMA), a specific NO synthase inhibitor they showed no detectable rise in urinary nitrate excretion. Mean Listeria counts in the livers and spleens NMMA-treated mice were 1 to 3 orders of magnitude greater than counts in control mice on days 4 through 8 of infection. Compared with control mice, NMMA-treated mice also showed worse clinical signs of infection, namely, weight loss, hypothermia, decreased food and water intake, and decreased urine output. Histologically NMMA-treated mice had many more inflammatory foci in their livers and spleens than control mice. The histologic observation that mononuclear cells are present at sites of infection suggests that inhibiting NO production did not block the flux of macrophages into infected viscera. As controls for possible drug toxicity, a group of uninfected mice given NMMA orally showed no detrimental effects on weight, temperature, and food and water intake. These experiments demonstrate that inhibition of NO production in Listeria-infected mice results in an exacerbated infection and thus that NO synthesis is important for immune defense against Listeria infection in mice. Images PMID:7509315

  13. Evidence for the participation of nitric oxide in pemphigus.

    PubMed

    Siebra, M X; Santos, M A; Almeida, T L P; Leite, A C R M; Cunha, F Q; Rocha, F A C

    2006-05-01

    Pemphigus is an inflammatory autoimmune disorder of the skin. Nitric oxide (NO) is an inflammatory mediator linked to a variety of physiological and pathophysiological phenomena that include skin tumors, psoriasis, urticaria, and atopic dermatitis. Inflammatory cells present in pemphigus lesions are important sources of NO production. We investigated whether NO is involved in pemphigus. A prospective cohort study was conducted at the Dermatology Service of the Hospital Universitário Walter Cantídio of the Federal University of Ceará. All patients seen at the outpatient clinic between August 2000 and July 2001, with a clinically and histologically confirmed diagnosis of pemphigus were included. The median age was 42.5 years (range: 12-69 years) with a male to female ratio of 3:2. Total serum nitrite levels, used as a marker for NO production, were determined by the Griess reaction. Skin biopsies from pemphigus and breast surgery (control) patients were used for the detection of the inducible NO synthase (iNOS) by immunohistochemistry. Twenty-two (22) patients with pemphigus and eight (8) controls who did not differ in demographic characteristics were included. Total serum nitrite levels were significantly higher (>7 micromol/L) in pemphigus patients compared to controls (<6 micromol/L), regardless of the severity of the clinical activity of pemphigus (P < 0.0001). All pemphigus biopsies presented increased immunostaining for iNOS that was not detected in normal skin samples. These data are the first to demonstrate that pemphigus patients display increased serum NO levels that are associated with increased iNOS expression in the affected skin. PMID:16648905

  14. Xiaokening stimulates endothelial nitric oxide release in diabetic rats

    PubMed Central

    Liu, Hong; Liu, Lei; Wei, Qunli; Cui, Jie; Yan, Changdong; Wang, Xin; Wu, Yongping

    2015-01-01

    INTRODUCTION Diabetes mellitus induces microangiopathic changes that lead to endothelial dysfunction. This study investigated the effect of Xiaokening, a type of Chinese compound medicine, on the mesenteric arteriolar endothelial cell function of diabetic rats and its underlying mechanism. METHODS Diabetes mellitus was induced in rat models via intraperitoneal injection of 60 mg/kg streptozotocin and observed over three weeks. Mesenteric arterioles, which were isolated in a cannulated and pressurised state, were incubated with intravascular injections of 1, 3 or 5 g/L Xiaokening for 24, 48 or 72 hours. The effects of Xiaokening on the release of nitric oxide (NO) on the mesenteric arterioles were detected under shear stress of 1, 10 and 20 dyn/cm2. Biochemical methods were used to determine the activities of superoxide dismutase (SOD) and xanthine oxidase (XO). The expressions of endothelial NO synthase (eNOS), SOD and XO in the mesenteric arterioles were assessed using Western blot. RESULTS Compared to normal rat arterioles, less NO was released in the mesenteric arterioles of diabetic rats. Xiaokening was found to have a concentration- and time-dependent effect on NO release; when the shear stress was increased, there was a gradual increase in the release of NO. Compared to normal arterioles, the expression of eNOS in the mesenteric arterioles of diabetic rats was lower. Incubation with Xiaokening increased SOD activity and expression, and decreased XO activity and expression in the mesenteric arterioles of the diabetic rats. CONCLUSION Xiaokening was able to significantly increase NO release and improve the endothelial function of mesenteric arterioles through antioxidative mechanisms. PMID:26243977

  15. Elucidating nitric oxide synthase domain interactions by molecular dynamics.

    PubMed

    Hollingsworth, Scott A; Holden, Jeffrey K; Li, Huiying; Poulos, Thomas L

    2016-02-01

    Nitric oxide synthase (NOS) is a multidomain enzyme that catalyzes the production of nitric oxide (NO) by oxidizing l-Arg to NO and L-citrulline. NO production requires multiple interdomain electron transfer steps between the flavin mononucleotide (FMN) and heme domain. Specifically, NADPH-derived electrons are transferred to the heme-containing oxygenase domain via the flavin adenine dinucleotide (FAD) and FMN containing reductase domains. While crystal structures are available for both the reductase and oxygenase domains of NOS, to date there is no atomic level structural information on domain interactions required for the final FMN-to-heme electron transfer step. Here, we evaluate a model of this final electron transfer step for the heme-FMN-calmodulin NOS complex based on the recent biophysical studies using a 105-ns molecular dynamics trajectory. The resulting equilibrated complex structure is very stable and provides a detailed prediction of interdomain contacts required for stabilizing the NOS output state. The resulting equilibrated complex model agrees well with previous experimental work and provides a detailed working model of the final NOS electron transfer step required for NO biosynthesis. PMID:26448477

  16. Pterins inhibit nitric oxide synthase activity in rat alveolar macrophages.

    PubMed Central

    Jorens, P. G.; van Overveld, F. J.; Bult, H.; Vermeire, P. A.; Herman, A. G.

    1992-01-01

    1. The synthesis of nitrite and citrulline from L-arginine by immune-stimulated rat alveolar macrophages and the modulation of this synthesis were studied. 2,4-Diamino-6-hydroxypyrimidine (DAHP), 6R-5,6,7,8-tetrahydro-L-biopterin (BH4) and L-sepiapterin were potent inhibitors of the recombinant interferon-gamma induced production of nitrogen oxides in intact cultured cells with I50 values for BH4 and L-sepiapterin of approximately 10 microM. They were equally effective in inhibiting the induced production of citrulline. This inhibitory effect was concentration-dependent for all three modulators investigated. 2. The inhibitory effects were not dependent on incubation times of either 24 or 48 h, on the immune-stimulus used (lipopolysaccharide, interferon-gamma), or whether these stimuli were added during or after the induction period. 3. Pterin-6-carboxylic acid (PCA), which cannot be converted into BH4, and methotrexate (MTX), which inhibits dihydrofolatereductase but not de novo biosynthesis of BH4, did not change the production of nitrite. 4. The data indicate that DAHP, an inhibitor of the de novo biosynthesis of the co-factor BH4, blocks the nitric oxide synthase activity in intact cells. Since the pterins BH4 and L-sepiapterin blocked the L-arginine dependent production of nitrite and citrulline, the activity of nitric oxide synthase in phagocytic cells may be regulated by metabolic endproducts of the de novo biosynthesis of BH4. PMID:1281717

  17. Interactions between nitric oxide and plant hormones in aluminum tolerance

    PubMed Central

    He, Huyi; He, Longfei; Gu, Minghua

    2012-01-01

    Nitric oxide (NO) is involved, together with plant hormones, in the adaptation to Al stress in plants. However, the mechanism by which NO and plant hormones interplay to improve Al tolerance are still unclear. We have recently shown that patterns of plant hormones alteration differ between rye and wheat under Al stress. NO may enhance Al tolerance by regulating hormonal equilibrium in plants, as a regulator of plant hormones signaling. In this paper, some unsolved issues are discussed based on recent studies and the complex network of NO and plant hormones in inducing Al tolerance of plants are proposed. PMID:22499184

  18. The measurement of nitric oxide production by cultured endothelial cells.

    PubMed

    Hart, C Michael; Kleinhenz, Dean J; Dikalov, Sergey I; Boulden, Beth M; Dudley, Samuel C

    2005-01-01

    Nitric oxide (NO) produced by vascular endothelial cells (ECs) plays a critical role in normal vascular physiology. Important insights into mechanisms regulating the production of endothelial NO have been derived from in vitro studies employing cultured ECs. Although many techniques for the detection of NO have been described, many of these methods lack adequate sensitivity to detect the small amount of NO produced by cultured ECs. In this chapter, we describe three protocols that employ chemiluminescence, electron spin resonance, or electrochemical techniques to permit the reliable detection of EC NO production. PMID:16291257

  19. H2S regulation of nitric oxide metabolism

    PubMed Central

    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

  20. Production of nitric oxide in host-virus interaction

    PubMed Central

    Sarkar, Tuhin Subhra; Majumdar, Uddalak; Roy, Anirban; Maiti, Debasis; Goswamy, Achintya Mohan; Bhattacharjee, Arindam; Ghosh, Subrata Kumar

    2010-01-01

    Nitric oxide (NO) plays a key role in plant diseases resistance. Here we have first time demonstrated that begomovirus infection in susceptible H. cannabinus plants, results in elevated NO and reactive nitrogen species production during early infection stage not only in infected leaf but also in root and shoot. Production of NO was further confirmed by oxyhemoglobin assay. Furthermore, we used Phenyl alanine ammonia lyase as marker of pathogenesis related enzyme. In addition evidence for protein tyrosine nitration during the early stage of viral infection clearly showed the involvement of nitrosative stress. PMID:20215875

  1. Application of nitric oxide measurements in clinical conditions beyond asthma

    PubMed Central

    Malinovschi, Andrei; Ludviksdottir, Dora; Tufvesson, Ellen; Rolla, Giovanni; Bjermer, Leif; Alving, Kjell; Diamant, Zuzana

    2015-01-01

    Fractional exhaled nitric oxide (FeNO) is a convenient, non-invasive method for the assessment of active, mainly Th2-driven, airway inflammation, which is sensitive to treatment with standard anti-inflammatory therapy. Consequently, FeNO serves as a valued tool to aid diagnosis and monitoring in several asthma phenotypes. More recently, FeNO has been evaluated in several other respiratory, infectious, and/or immunological conditions. In this short review, we provide an overview of several clinical studies and discuss the status of potential applications of NO measurements in clinical conditions beyond asthma. PMID:26672962

  2. Direct Reaction of Amides with Nitric Oxide To Form Diazeniumdiolates

    PubMed Central

    2015-01-01

    We report the apparently unprecedented direct reaction of nitric oxide (NO) with amides to generate ions of structure R(C=O)NH–N(O)=NO–, with examples including R = Me (1a) or 3-pyridyl (1b). The sodium salts of both released NO in pH 7.4 buffer, with 37 °C half-lives of 1–3 min. As NO-releasing drug candidates, diazeniumdiolated amides would have the advantage of generating only 1 equiv of base on hydrolyzing exhaustively to NO, in contrast to their amine counterparts, which generate 2 equiv of base. PMID:25210948

  3. Nitric Oxide--Some Old and New Perspectives

    NASA Astrophysics Data System (ADS)

    Ainscough, Eric W.; Brodie, Andrew M.

    1995-08-01

    The discovery and early use of NO is recalled followed by some of its chemical reactions to give useful products such as nitric acid and fertilizers. However NO produced from the internal combustion engine results in photochemical smog production and ozone depletion. A rebirth of interest in NO has occurred because of its unexpected roles in physiology and neurobiology. Its production can lead to biological responses such as vasodilation, cell adhesion, neurotransmission and immune regulation. Finally the ways denitrifying bacteria convert NO and other oxides of nitrogen to dinitrogen are discussed.

  4. Relative rates of nitric oxide and nitrous oxide production by nitrifiers, denitrifiers, and nitrate respirers

    NASA Technical Reports Server (NTRS)

    Anderson, I. C.; Levine, J. S.

    1986-01-01

    An account is given of the atmospheric chemical and photochemical effects of biogenic nitric and nitrous oxide emissions. The magnitude of the biogenic emission of NO is noted to remain uncertain. Possible soil sources of NO and N2O encompass nitrification by autotropic and heterotropic nitrifiers, denitrification by nitrifiers and denitrifiers, nitrate respiration by fermenters, and chemodenitrification. Oxygen availability is the primary determinant of these organisms' relative rates of activity. The characteristics of this major influence are presently investigated in light of the effect of oxygen partial pressure on NO and N2O production by a wide variety of common soil-nitrifying, denitrifying, and nitrate-respiring bacteria under laboratory conditions. The results obtained indicate that aerobic soils are primary sources only when there is sufficient moisture to furnish anaerobic microsites for denitrification.

  5. Association of inducible nitric oxide synthase with asthma severity, total serum immunoglobulin E and blood eosinophil levels

    PubMed Central

    Batra, Jyotsna; Singh, Tej Pratap; Mabalirajan, Ulanganathan; Sinha, Aditi; Prasad, Rajendra; Ghosh, Balaram

    2007-01-01

    Background Nitric oxide is released by immune, epithelial and endothelial cells, and plays an important part in the pathophysiology of asthma. Objective To investigate the association of inducible nitric oxide synthases (iNOS) gene repeat polymorphisms with asthma. Methods 230 families with asthma (842 individuals) were recruited to identify and establish the genetic association of iNOS repeats with asthma and associated phenotypes. Serum nitric oxide levels in selected individuals were measured and correlated with specific genotypes. Multiple logistic regression analysis was performed to determine the effect of age and sex. Results A total of four repeats—a (CCTTT)n promoter repeat, a novel intron 2 (GT)n repeat (BV680047), an intron 4 (GT)n repeat (AFM311ZB1) and an intron 5 (CA)n repeat (D17S1878)—were identified and genotyped. A significant transmission distortion to the probands with asthma was seen for allele 3 of the AFM311ZB1 gene (p = 0.006). This allele was also found to be significantly associated with percentage blood eosinophils (p<0.001) and asthma severity (p = 0.04). Moreover, it was functionally correlated with high serum nitric oxide levels (p = 0.006). Similarly, the promoter repeat was found to be associated with serum total immunoglobulin (Ig)E (p = 0.028). Individuals carrying allele 4 of this repeat have high serum IgE (p<0.001) and nitric oxide levels (p = 0.03). Conclusion This is the first study to identify the repeat polymorphisms in the iNOS gene that are associated with severity of asthma and eosinophils. The functional relevance of the associated alleles with serum nitric oxide levels was also shown. Therefore, these results could be valuable in elucidating the role of nitric oxide in asthma pathogenesis. PMID:17189532

  6. Methods to Detect Nitric Oxide in Plants: Are DAFs Really Measuring NO?

    PubMed

    Ruemer, Stefan; Krischke, Markus; Fekete, Agnes; Lesch, Maria; Mueller, Marin J; Kaiser, Werner M

    2016-01-01

    Nitric oxide, a gaseous radical molecule, appears involved in many reactions in all living organisms. Fluorescent dyes like DAF-2 and related compounds are still widely used to monitor NO production inside or outside cells, although doubts about their specificity have recently been raised. We present evidence that DAF dyes do not only react with nitric oxide but also with peroxidase enzyme and hydrogen peroxide. Both are secreted in the case of elicitation of tobacco suspension cells with cryptogein, with a fluorescence increase mimicking NO release from cells. However, HPLC separation shows that fluorescence outside cells does not at all originate from DAF-2T, the product of DAF-2 and NO, but from other yet unidentified compounds. Inside cells, other DAF molecules are formed but only a minor part is DAF-2T. The chemical nature of the novel DAF derivatives still needs to be determined. PMID:27094411

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

    NASA Astrophysics Data System (ADS)

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

    2011-06-01

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

  8. Nitric oxide synthase inhibition reduces muscle inflammation and necrosis in modified muscle use

    NASA Technical Reports Server (NTRS)

    Pizza, F. X.; Hernandez, I. J.; Tidball, J. G.

    1998-01-01

    The objective of this study was to determine the role of nitric oxide in muscle inflammation, fiber necrosis, and apoptosis of inflammatory cells in vivo. The effects of nitric oxide synthase (NOS) inhibition on the concentrations of neutrophils, ED1+ and ED2+ macrophages, apoptotic inflammatory cells, and necrotic muscle fibers in rats subjected to 10 days of hindlimb unloading and 2 days of reloading were determined. Administration of NOS inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) significantly reduced the concentrations of neutrophils, ED1+ and ED2+ macrophages, and necrotic fibers in soleus muscle relative to water-treated controls. The concentration of apoptotic inflammatory cells was also significantly lower for L-NAME-treated animals compared with water-treated controls. However, the proportion of the inflammatory cell population that was apoptotic did not differ between L-NAME-treated and control animals, suggesting that L-NAME treatment did not decrease inflammatory cell populations by increasing the frequency of apoptosis. Thus, nitric oxide or one of its intermediates promotes muscle inflammation and fiber necrosis during modified muscle use and plays no more than a minor role in the resolution of muscle inflammation by inducing apoptosis of inflammatory cells.

  9. Chronic Ethanol Ingestion Increases Aortic Endothelial Nitric Oxide Synthase Expression and Nitric Oxide Production in the Rat

    PubMed Central

    Kleinhenz, Dean J.; Sutliff, Roy L.; Polikandriotis, John A.; Walp, Erik R.; Dikalov, Sergey I.; Guidot, David M.; Hart, C. Michael

    2011-01-01

    Background Chronic alcohol consumption perturbs cellular function in a variety of organ systems. Previous studies have suggested that moderate alcohol consumption reduces vascular disease, whereas heavier alcohol consumption may worsen it. The mechanisms for these vascular effects of chronic alcohol ingestion continue to be defined and constitute the focus of this study. Methods Male Sprague Dawley rats were fed an isocaloric, Lieber-Decarli liquid diet containing either ethanol (36% calories) or MaltoseDextrin (substituted for ethanol) for 6 weeks. Telemetric blood pressure measurements were taken before and after ethanol feeding. After the rats were killed, the aortas were analyzed for endothelial nitric oxide (NO) synthase expression and NO production. Results Chronic ethanol ingestion decreased mean arterial pressure and increased aortic NO production as demonstrated by direct ex vivo measurements using iron diethyldithio-carbamic acid as well as analysis of nitrosyl-hemoglobin (NO-Hb) levels. Consistent with these assays of vascular NO production, endothelium-dependent relaxation responses to acetycholine (Ach) were enhanced in ethanol-fed animals. Aortic endothelial nitric oxide synthase expression was also increased by chronic ethanol ingestion. Conclusions These findings demonstrate that a regimen of chronic alcohol ingestion in the rat produced generally salutary effects in the systemic vasculature following a 6-week treatment regimen. These findings extend previous in vitro studies to demonstrate that alcohol has potent effects on vascular endothelial nitric oxide synthase expression, NO production, and vascular function. Consistent with previous reports, these findings confirm that alcohol-induced alterations in the production of reactive nitrogen species play an important role in the pathogenesis of alcohol-mediated tissue effects. PMID:18028525

  10. Dual inhibition of nitric oxide and prostaglandin production contributes to the antiinflammatory properties of nitric oxide synthase inhibitors.

    PubMed Central

    Salvemini, D; Manning, P T; Zweifel, B S; Seibert, K; Connor, J; Currie, M G; Needleman, P; Masferrer, J L

    1995-01-01

    We have recently put forward the hypothesis that the dual inhibition of proinflammatory nitric oxide (NO) and prostaglandins (PG) may contribute to the antiinflammatory properties of nitric oxide synthase (NOS) inhibitors. This hypothesis was tested in the present study. A rapid inflammatory response characterized by edema, high levels of nitrites (NO2-, a breakdown product of NO), PG, and cellular infiltration into a fluid exudate was induced by the administration of carrageenan into the subcutaneous rat air pouch. The time course of the induction of inducible nitric oxide synthase (iNOS) protein in the pouch tissue was found to coincide with the production of NO2-. Dexamethasone inhibited both iNOS protein expression and NO2- synthesis in the fluid exudate (IC50 = 0.16 mg/kg). Oral administration of N-iminoethyl-L-lysine (L-NIL) or NG-nitro-L-arginine methyl ester (NO2Arg) not only blocked nitrite accumulation in the pouch fluid in a dose-dependent fashion but also attenuated the elevated release of PG. Finally, carrageenan administration produced a time-dependent increase in cellular infiltration into the pouch exudate that was inhibited by dexamethasone and NOS inhibitors. At early times, i.e., 6 h, the cellular infiltrate is composed primarily of neutrophils (98%). Pretreatment with colchicine reduced both neutrophil infiltration and leukotriene B4 accumulation in the air pouch by 98% but did not affect either NO2- or PG levels. In conclusion, the major findings of this paper are that (a) selective inhibitors of iNOS are clearly antiinflammatory agents by inhibiting not only NO but also PG and cellular infiltration and (b) that neutrophils are not responsible for high levels of NO and PG produced. Images PMID:7542281

  11. Genetic and Epigenetic Variations in Inducible Nitric Oxide Synthase Promoter, Particulate Pollution and Exhaled Nitric Oxide in Children

    PubMed Central

    Salam, Muhammad T.; Byun, Hyang-Min; Lurmann, Fred; Breton, Carrie V.; Wang, Xinhui; Eckel, Sandrah P.; Gilliland, Frank D.

    2012-01-01

    Background Inducible nitric oxide synthase (iNOS, encoded by NOS2) is the major enzyme for nitric oxide synthesis in airways. As such, measurement of exhaled nitric oxide (FeNO) provides an in vivo assessment of iNOS activity. Short-term exposure to air pollution, haplotypes and DNA methylation in NOS2 promoter have been associated independently with iNOS expression and/or FeNO. Objective We aimed to examine the effects of ambient air pollutants, NOS2 promoter haplotypes and NOS2 promoter methylation on FeNO level in children. Methods We selected 940 participants in the Children’s Health Study who provided buccal samples and had undergone FeNO measurement on the same day. DNA methylation was measured using a bisulfite-polymerase chain reaction Pyrosequencing assay. Seven single nucleotide polymorphisms captured the haplotype diversity in the NOS2 promoter. Average particulate matter with aerodynamic diameter ≤2.5μm and ≤10μm (PM2.5 and PM10), ozone and nitrogen dioxide levels 7 days before FeNO measurement were estimated based on air pollution data obtained at central monitoring sites. Results We found interrelated effects of PM2.5, NOS2 promoter haplotypes and iNOS methylation on FeNO. Elevated 7-day average PM2.5 exposure was associated with lower iNOS methylation (P=.01). NOS2 promoter haplotypes were globally associated with NOS2 promoter methylation (P=6.2 × 10−8). There was interaction among one common promoter haplotype, iNOS methylation level and PM2.5 exposure on FeNO (Pinteraction=.00007). Conclusion Promoter variants in NOS2 and short term PM2.5 exposure affect iNOS methylation. This is one of the first studies showing contributions of genetic and epigenetic variations in air pollution mediated phenotype expression. PMID:22055874

  12. Role of Nitric Oxide in the Regulation of Renin and Vasopressin Secretion

    NASA Technical Reports Server (NTRS)

    Reid, Ian A.

    1994-01-01

    Research during recent years has established nitric oxide as a unique signaling molecule that plays important roles in the regulation of the cardiovascular, nervous, immune, and other systems. Nitric oxide has also been implicated in the control of the secretion of hormones by the pancreas, hypothalamus, and anterior pituitary gland, and evidence is accumulating that it contributes to the regulation of the secretion of renin and vasopressin, hormones that play key roles in the control of sodium and water balance. Several lines of evidence have implicated nitric oxide in the control of renin secretion. The enzyme nitric oxide synthase is present in vascular and tubular elements of the kidney, particularly in cells of the macula densa, a structure that plays an important role in the control of renin secretion. Guanylyl cyclase, a major target for nitric oxide, is also present in the kidney. Drugs that inhibit nitric oxide synthesis generally suppress renin release in vivo and in vitro, suggesting a stimulatory role for the L-arginine/nitric oxide pathway in the control of renin secretion. Under some conditions, however, blockade of nitric oxide synthesis increases renin secretion. Recent studies indicate that nitric oxide not only contributes to the regulation of basal renin secretion, but also participates in the renin secretory responses to activation of the renal baroreceptor, macula densa, and beta adrenoceptor mechanisms that regulate renin secretion. Histochemical and immunocytochemical studies have revealed the presence of nitric oxide synthase in the supraoptic and paraventricular nuclei of the hypothalamus and in the posterior pituitary gland. Colocalization of nitric oxide synthase and vasopressin has been demonstrated in some hypothalamic neurons. Nitric oxide synthase activity in the hypothalamus and pituitary is increased by maneuvers known to stimulate vasopressin secretion, including salt loading and dehydration, Administration of L-arginine and nitric oxide donors in vitro and in vivo has variable effects on vasopressin secretion, but the most common one is inhibition. Blockade of nitric oxide synthesis has been reported to increase vasopressin secretion, but again variable results have been obtained. An attractive working hypothesis is that nitric oxide serves a neuromodulatory role as an inhibitor of vasopressin secretion.

  13. Applications of plasma sources for nitric oxide medicine

    NASA Astrophysics Data System (ADS)

    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.

  14. Nitric Oxide-Mediated Posttranslational Modifications: Impacts at the Synapse.

    PubMed

    Bradley, Sophie A; Steinert, Joern R

    2016-01-01

    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. PMID:26635909

  15. The role of nitric oxide in tendon healing.

    PubMed

    Bokhari, Ali R; Murrell, George A C

    2012-02-01

    Nitric oxide (NO) is a small free radical that is generated by a family of enzymes called the nitric oxide synthases (NOS). There are 3 isoforms of NOS: endothelial NOS (eNOS), brain or neuronal NOS (bNOS), and inducible NOS (iNOS). In experiments performed during the last 20 years, we have shown that NO is induced by all 3 isoforms of NOS after tendon injury and that NOS activity is upregulated in tendinopathy. In normal uninjured tendons, there is very little NOS activity. In injured rat and human tendons, NOS activity was found in healing fibroblasts in a temporal fashion. In animal models, competitive inhibition of NOS resulted in reduced tendon healing, whereas the addition of NO resulted in enhanced tendon healing. In cultured human cells, the addition of NO via chemical means and adenovirus transfection resulted in enhanced collagen synthesis. We performed 3 randomized, double-blinded clinical trials that demonstrated a significant positive beneficial effect of NO treatment on clinical symptoms and function in patients with Achilles tendinopathy, tennis elbow, and supraspinatus tendonitis. NO was delivered via glyceryl trinitrate (GTN) patches. We also conducted a 3-year prospective follow-up that demonstrated significant long-term efficacy of GTN patches in treating noninsertional Achilles tendinopathy. In a 5-year prospective comparison treating lateral epicondylitis, we found no additional benefits of GTN vs placebo at 5 years. The use of a new GTN patch, OrthoDerm, demonstrated no evidence for efficacy in treating chronic lateral epicondylitis. PMID:22244067

  16. Diurnal variation of nitric oxide in the upper stratosphere

    NASA Technical Reports Server (NTRS)

    Kondo, Y.; Aimedieu, P.; Pirre, M.; Ramaroson, R.; Matthews, W. A.

    1990-01-01

    Two recent measurements of the temporal variation of nitric oxide at constant altitude near 40 km are reported. The observations were made at float altitude with a balloon-borne chemiluminescence detector together with in situ ozone measurements. The first measurement was made at 44 N on September 17, 1987, at an altitude of 40 km from before sunrise until 1000 LT. The second observation was made at the same latitude on June 18, 1988, at 39 km from 0800 to 1230 LT. At an altitude of 40 km, nitric oxide was observed to start increasing very rapidly at sunrise when the solar zenith angle reached about 95 deg. After the rapid initial buildup, the rate of NO increase stabilized for 3 hours at about 1.2 ppbv/hour. Near 1100 LT at 39 km in summer, the NO mixing ratio was observed to become nearly constant. These features of the diurnal variation of NO are in accord with the temporal variation expected from a time-dependent zero-dimensional photochemical model.

  17. Nitric oxide synthase derangements and hypertension in kidney disease

    PubMed Central

    Baylis, Chris

    2012-01-01

    Purpose of Review Nitric oxide (NO) deficiency occurs by multiple mechanisms and contributes to the pathogenesis of progression of chronic kidney disease (CKD) and its cardiovascular complications. This article concentrates on recent developments on the regulation of the endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA) in chronic kidney disease and on the importance of the NO synthases in kidney disease progression, particularly in diabetic nephropathy. Recent Findings The increased plasma ADMA seen in renal disease is generally predictive of severity of CKD progression and cardiovascular risk. However, some assumptions about the control of ADMA have been challenged; the primacy of the kidney as a metabolic organ for plasma ADMA regulation coming under scrutiny and the relative importance of the 2 isoforms of the ADMA-metabolizing enzymes dimethylarginine dimethylaminohydrolases (DDAHs) is being reevaluated. Alterations in nitric oxide synthases also contribute to CKD progression with the endothelial isoform playing a major role in diabetic nephropathy. Summary Improving our understanding of ADMA regulation is important since pharmacologic targeting of DDAH is underway. The major role of eNOS-derived NO in diabetic nephropathy should lead to novel therapies. The beneficial actions of dietary nitrate supplementation on blood pressure and kidney disease are of considerable clinical relevance. PMID:22048724

  18. Role of nitric oxide in inflammation-mediated neurodegeneration.

    PubMed

    Liu, Bin; Gao, Hui-Ming; Wang, Jiz-Yuh; Jeohn, Gwang-Ho; Cooper, Cynthia L; Hong, Jau-Shyong

    2002-05-01

    Increasing evidence has suggested that inflammation in the brain is closely associated with the pathogenesis of several degenerative neurologic disorders, including Parkinson's disease, Alzheimer's diseases, multiple sclerosis, amyotrophic lateral sclerosis, and AIDS dementia. The hallmark of brain inflammation is the activation of glial cells, especially that of microglia that produce a variety of proinflammatory and neurotoxic factors, including cytokines, fatty acid metabolites, free radicals--such as nitric oxide (NO) and superoxide. Excessive production of NO, as a consequence of nitric oxide synthase induction in activated glia, has been attributed to participate in neurodegeneration. Using primary mixed neuron-glia cultures and glia-enriched cultures prepared from embryonic rodent brain tissues, we have systemically studied the relationship between the production of NO and neurodegeneration in response to stimulation by the inflammagen lipopolysaccharide. This review summarizes our recent findings on the kinetics of NO generation, the relative contribution of microglia and astrocytes to NO accumulation, the relationship between NO production and neurodegeneration, and points of intervention along the pathways associated with NO generation to achieve neuroprotection. We also describe our results relating to the effect of several opioid-related agents on microglial activation and neuroprotection. Among these agents, the opioid receptor antagonist naloxone, especially its non-opioid enantiomer (+)-naloxone, promises to be of potential therapeutic value for the treatment of inflammation-related diseases. PMID:12076984

  19. Nitric oxide and peroxynitrite production in ocular inflammation.

    PubMed Central

    Allen, J B; Keng, T; Privalle, C

    1998-01-01

    Recent studies have implicated nitric oxide and peroxynitrite in the pathogenesis of many diseases, such as septic shock, arthritis, lung disease, and atherosclerosis. Nitric oxide (.NO) exerts many diverse effects on vascular tone, affecting neurotransmission and cellular cytotoxicity/communication. Our laboratory and others have documented a proinflammatory role for .NO in ocular inflammation. Uveitis, which is an inflammation of the highly vascular uveal tract in the eye, is a debilitating condition that can lead to visual impairment and blindness. It is characterized by acute, recurrent, or persistent inflammation with disruption of the blood-aqueous barrier and is accompanied by protein leakage and leukocyte infiltration into the aqueous humor and anterior chamber. Systemic injection of endotoxin into mice and rats, or intraocular injection of endotoxin into mice, rats, and rabbits induces acute uveitis, which clinically and histologically resembles acute anterior uveitis in humans. These models facilitate the study of pathogenic mechanisms that contribute to ocular inflammation. In addition to .NO, superoxide anion radicals (O2.-), and peroxynitrite (ONOO-), the products of the reaction between .NO and O2.-, are also implicated in uveitis. The role of peroxynitrite in ocular inflammation is still largely unknown. Characterization of the roles of these important uveitic mediators in the ocular inflammatory response will provide information critical to the understanding of the pathogenesis of intraocular inflammation so that more effective therapeutic intervention(s) can be developed. PMID:9788889

  20. Nitric oxide-modulating agents for gastrointestinal disorders.

    PubMed

    Whittle, Brendan J R

    2005-11-01

    Almost 20 years after the identification of the biological role of nitric oxide (NO), the full therapeutic potential of novel agents that mimic the activity of NO or interfere with its synthesis has yet to be realised for utilities involving the gastrointestinal tract. New utilities for classical NO donors, which were used as vasodilators for decades, in the treatment of motility disorders have been explored and a product for treating anal fissure was recently launched. New classes of compounds incorporating a NO-donating moiety into standard non-steroidal anti-inflammatory drugs, the NO-non-steroidal anti-inflammatory drugs (NO-NSAIDs) or COX-inhibiting nitric oxide donors (CINODs) have also been developed. These have been shown to exhibit reduced gastrointestinal injury in experimental models, and reports on their efficacy and safety in Phase I and II studies are now available. Modulation of the inducible NO synthase isoform that generates excessive NO that can lead to subsequent cytotoxic moieties, such as peroxynitrite, may have therapeutic possibilities in a range of inflammatory diseases of the gut. Likewise, agents that promote the decomposition of peroxynitrite or removal of its other component, superoxide, may also prove to be of use. Further targets for pharmaceutical exploitation are likely to come from both genomic and molecular insights into the processes that regulate the NO system. PMID:16255675

  1. Environmental effects on fractional exhaled nitric oxide in allergic children.

    PubMed

    La Grutta, Stefania; Ferrante, Giuliana; Malizia, Velia; Cibella, Fabio; Viegi, Giovanni

    2012-01-01

    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 (PM(2.5) and PM(10)), nitrogen dioxide (NO(2)), and sulfur dioxide (SO(2))-as well as formaldehyde and electric baseboard heating have been shown to increase FeNO, whilst ozone (O(3)) 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. PMID:22162708

  2. Effects of nitric oxide on stem cell therapy.

    PubMed

    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. PMID:26394194

  3. Nitric Oxide Signaling in Hypergravity-Induced Neuronal Plasticity

    NASA Technical Reports Server (NTRS)

    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.

  4. Implications of glial nitric oxide in neurodegenerative diseases

    PubMed Central

    Yuste, Jose Enrique; Tarragon, Ernesto; Campuzano, Carmen María; Ros-Bernal, Francisco

    2015-01-01

    Nitric oxide (NO) is a pleiotropic janus-faced molecule synthesized by nitric oxide synthases (NOS) which plays a critical role in a number of physiological and pathological processes in humans. The physiological roles of NO depend on its local concentrations, as well as its availability and the nature of downstream target molecules. Its double-edged sword action has been linked to neurodegenerative disorders. Excessive NO production, as the evoked by inflammatory signals, has been identified as one of the major causative reasons for the pathogenesis of several neurodegenerative diseases. Moreover, excessive NO synthesis under neuroinflammation leads to the formation of reactive nitrogen species and neuronal cell death. There is an intimate relation between microglial activation, NO and neuroinflammation in the human brain. The role of NO in neuroinflammation has been defined in animal models where this neurotransmitter can modulate the inflammatory process acting on key regulatory pathways, such as those associated with excitotoxicity processes induced by glutamate accumulation and microglial activation. Activated glia express inducible NOS and produce NO that triggers calcium mobilization from the endoplasmic reticulum, activating the release of vesicular glutamate from astroglial cells resulting in neuronal death. This change in microglia potentially contributes to the increased age-associated susceptibility and neurodegeneration. In the current review, information is provided about the role of NO, glial activation and age-related processes in the central nervous system (CNS) that may be helpful in the isolation of new therapeutic targets for aging and neurodegenerative diseases. PMID:26347610

  5. Salmonella typhimurium mutants that downregulate phagocyte nitric oxide production.

    PubMed

    Eriksson, S; Björkman, J; Borg, S; Syk, A; Pettersson, S; Andersson, D I; Rhen, M

    2000-06-01

    To examine the potential and strategies of the facultative intracellular pathogen Salmonella typhimurium to increase its fitness in host cells, we applied a selection that enriches for mutants with increased bacterial growth yields in murine J774-A.1 macrophage-like cells. The selection, which was based on intracellular growth competition, rapidly yielded isolates that out-competed the wild-type strain during intracellular growth. J774-A.1 cells responded to challenge with S. typhimurium by mounting an inducible nitric oxide synthase (iNOS) mRNA and protein expression and a concomitant nitric oxide (NO) production. Inhibition of NO production with the use of the competitive inhibitor N-monomethyl-L-arginine (NMMA) resulted in a 20-fold increase in bacterial growth yield, suggesting that the NO response prevented bacterial intracellular growth. In accordance with this observation, five out of the nine growth advantage mutants isolated inhibited production of NO from J774-A.1 cells, despite an induction of iNOS mRNA and iNOS protein. Accompanying bacterial phenotypes included alterations in lipopolysaccharide structure and in the profiles of proteins secreted by invasion-competent bacteria. The results indicate that S. typhimurium has the ability to mutate in several different ways to increase its host fitness and that inhibition of iNOS activity may be a major adaptation. PMID:11207580

  6. The flavonoid luteolin induces nitric oxide production and arterial relaxation

    PubMed Central

    Si, Hongwei; Wyeth, Richard P.; Liu, Dongmin

    2013-01-01

    Purpose Luteolin, a flavone present in many foods and medicinal plants, may have beneficial effects on various human chronic diseases. In the present study, we investigated the hypothesis that luteolin can directly act on vascular endothelial cells (ECs), leading to nitric oxide (NO) production and subsequent vascular relaxation. Methods Rat aortic rings were mounted in organ bath. Luteolin was added cumulatively and vessel relaxation of rat aortic rings precontracted with phenylephrine (PE) or potassium was recorded. Endothelial nitric oxide synthase (eNOS) phosphorylation at Ser1177 and NO production from aortic rings and primary human aortic endothelial cells (HAECs) exposed to luteolin were measured by using Western blot and fluorometric assay, respectively. Results Luteolin dose-dependently (10-100 μmol/L) elicited relaxation of PE- or potassium-contracted aortic rings. The vasorelaxation effect of luteolin was attenuated by the eNOS inhibitor, N-nitro-L-arginine methyl ester, suggesting that this luteolin action is at least partially mediated by activating eNOS activity. We further found that luteolin dose-dependently (10-100 μmol/L) increased eNOS phosphorylation at Ser1177 (up to 1.9 fold) in isolated rat rings. Consistently, exposure of HAECs to luteolin also increased eNOS phosphorylation and NO production. Conclusion Luteolin may be a vascular protective agent by directly acting on vascular ECs to stimulate NO-dependent vascular dilatation. PMID:23604495

  7. Nitric oxide heme interactions in nitrophorin from Cimex lectularius

    NASA Astrophysics Data System (ADS)

    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.

  8. Effect of nitrate and L-arginine therapy on nitric oxide levels in serum, heart, and aorta of fetal hypothyroid rats.

    PubMed

    Ghasemi, Asghar; Mehrazin, Fatemeh; Zahediasl, Saleh

    2013-12-01

    Reduced nitric oxide availability and a heterogeneous pattern of nitric oxide synthase activity in some tissues have been reported in hypothyroidism. This study aimed at determining the effects of oral nitrate and L-arginine administration on serum, heart, and aorta nitric oxide metabolite concentrations in fetal hypothyroid rats. In an experimental study, pregnant Wistar rats were administrated tap water or 0.02 % of 6-propyl-2-thiouracil in drinking water during pregnancy and their male pups were followed (n = 8/group). In adult progeny, serum, heart, and aorta nitric oxide metabolite concentrations were measured by the Griess method after 1-week administration of sodium nitrate (500 mg/L) or L-arginine (2 %) in drinking water. Serum thyroid hormone and thyroid-stimulating hormone levels were also measured. Compared to controls, fetal hypothyroid progeny had significantly lower nitric oxide metabolite concentrations in heart (0.32 ± 0.07 vs. 0.90 ± 0.14 nmol/mg protein, p = 0.004) and aorta (2.98±0.56 vs. 6.15±0.74 nmol/mg protein, p = 0.011) tissues. Nitrate therapy restored heart nitric oxide metabolite levels decreased by fetal hypothyroidism, while L-arginine administration further decreased aorta nitric oxide metabolite levels. Sodium nitrate increased and L-arginine decreased serum nitric oxide metabolite levels in both control and fetal hypothyroid animals. In conclusion, nitrate therapy restores decreased heart nitric oxide metabolite levels, whereas L-arginine decreases aorta nitric oxide metabolite levels even further in fetal hypothyroid rats, findings relevant to the cardiovascular consequences of congenital hypothyroidism in adulthood. PMID:23568620

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

    PubMed Central

    Menaka, K. B.; Ramesh, Amitha; Thomas, Biju; Kumari, N. Suchetha

    2009-01-01

    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. PMID:20407654

  10. The potential of nitric oxide releasing therapies as antimicrobial agents

    PubMed Central

    Schairer, David O.; Chouake, Jason S.; Nosanchuk, Joshua D.; Friedman, Adam J.

    2012-01-01

    Nitric oxide (NO) is a short-lived, diatomic, lipophilic gas that plays an integral role in defending against pathogens. Among its many functions are involvement in immune cell signaling and in the biochemical reactions by which immune cells defend against bacteria, fungi, viruses and parasites. NO signaling directs a broad spectrum of processes, including the differentiation, proliferation, and apoptosis of immune cells. When secreted by activated immune cells, NO diffuses across cellular membranes and exacts nitrosative and oxidative damage on invading pathogens. These observations led to the development of NO delivery systems that can harness the antimicrobial properties of this evanescent gas. The innate microbicidal properties of NO, as well as the antimicrobial activity of the various NO delivery systems, are reviewed. PMID:22546899

  11. SAMPLING AND DETERMINATION OF GAS-PHASE HYDROGEN PEROXIDE FOLLOWING REMOVAL OF OZONE BY GAS-PHASE REACTION WITH NITRIC OXIDE

    EPA Science Inventory

    A method for determination of hydrogen peroxide in the ambient atmosphere is described, using impinger or diffusion scrubber collection of hydrogen peroxide with aqueous-phase analysis by an enzyme-catalyzed fluorescence technique. Interference from ozone at ambient levels is rem...

  12. Chronic Ethanol Ingestion Increases Nitric Oxide Production in the Lung

    PubMed Central

    Polikandriotis, John A.; Rupnow, Heidi L.; Brown, Lou Ann; Hart, C. Michael

    2007-01-01

    Purpose: Chronic ethanol (EtOH) ingestion increases the incidence of the Acute Respiratory Distress Syndrome (ARDS). The mechanisms underlying EtOH-induced susceptibility to lung injury continue to be defined. This study examines the hypothesis that EtOH increases endothelial nitric oxide synthase (eNOS) expression and activity in the lungs of a rat model of chronic EtOH ingestion. Methods: Male Sprague Dawley rats were fed liquid diets containing EtOH (36% of calories) or Maltose-dextrin as an isocaloric substitution for EtOH (Control) for 6 weeks. Selected animals were also treated with the angiotensin converting enzyme (ACE) inhibitor, lisinopril (3 mg/L in diet) for 6 weeks. At study completion, animals were sacrificed, and lung tissue was collected for assays of nitric oxide (NO) metabolism or pulmonary microvascular endothelial cells (MVEC) were isolated for analysis of NO release. Results: Compared to the Control diet, chronic EtOH ingestion increased lung H2O2 production, eNOS expression and activity, lung cGMP content and levels of protein nitration and oxidation. MVEC from animals with chronic EtOH ingestion released greater amounts of NO. EtOH-induced increases in lung H2O2 production, eNOS expression and activity, cGMP content, protein nitration and oxidation, and MVEC NO production were all attenuated by treatment with lisinopril. Conclusions: Chronic EtOH ingestion stimulates ACE-dependent increases in NO production in the lung. These novel findings indicate that chronic EtOH ingestion increases reactive species production in the lung parenchyma and provide new insights into mechanisms by which EtOH causes phenotypic alterations in the lung and its response to inflammatory stimuli. PMID:17889307

  13. Comparison of Nitric Oxide Concentrations in μs- and ns-Atmospheric Pressure Plasmas by UV Absorption Spectroscopy

    NASA Astrophysics Data System (ADS)

    Peters, F.; Hirschberg, J.; Mertens, N.; Wieneke, S.; Viöl, W.

    2016-04-01

    In this paper, an absorption spectroscopy measurement method was applied on two atmospheric pressure plasma sources to determine their production of nitric oxide. The concentrations are essential for evaluating the plasma sources based on the principle of the Dielectric Barrier Discharge (DBD) for applications in plasma medicine. The described method is based on a setup with an electrodeless discharge lamp filled with a mixture of oxygen and nitrogen. One of the emitted wavelengths is an important resonance wavelength of nitric oxide (λ = 226.2 nm). By comparing the absorption behaviour at the minimum and maximum of the spectral absorption cross section of nitric oxide around that wavelength, and measuring the change in intensity by the absorbing plasma, the concentration of nitric oxide inside the plasma can be calculated. The produced nitric oxide concentrations depend on the pulse duration and are in the range of 180 ppm to 1400 ppm, so that a distance of about 10cm to the respiratory tract is enough to conform to the VDI Guideline 2310.

  14. Arginine supplementation does not enhance serum nitric oxide levels in elderly nursing home residents with pressure ulcers.

    PubMed

    Stechmiller, Joyce K; Langkamp-Henken, Bobbi; Childress, Beverly; Herrlinger-Garcia, Kelli A; Hudgens, Jan; Tian, Lili; Percival, Susan S; Steele, Ruby

    2005-04-01

    The purpose of this study was to determine whether arginine supplementation enhances in vitro (neutrophil burst and mitogen-induced lymphocyte proliferation) and in vivo (delayed-type hypersensitivity [DTH] and serum nitric oxide) measures of immune function in nursing home elders with pressure ulcers. Twenty-six elders, 65 years of age or older, with one or more pressure ulcers, were randomized to receive 8.5 g of arginine or an isonitrogenous supplement for 4 weeks. Immune function studies and serum arginine, ornithine, citrulline, and nitric oxide were measured at baseline, 4 weeks postsupplementation (Week 4) and after a 6-week washout (Week 10). At Week 4, serum ornithine increased (p = .01) and arginine trended to increase (p = .055), but there was no increase in citrulline or nitric oxide with arginine supplementation. There were no differences in neutrophil burst or DTH responses between groups. Whole blood mitogen-induced proliferation decreased significantly at Week 10 in the isonitrogenous but not in the arginine-supplemented group. There is mounting concern that arginine supplementation during an inflammatory state could be detrimental due to overwhelming nitric oxide production. A key finding of this study is that arginine supplementation did not increase serum nitric oxide levels over that observed in elders with pressure ulcers given an isonitrogenous supplement. PMID:15788738

  15. Hemoglobin Effects on Nitric Oxide Mediated Hypoxic Vasodilation.

    PubMed

    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 optimum fit of the threshold phenomenon by the model. Our revised model suggests, but does not prove, that changes in NO concentration can be the primary cause of the relationship between pO2 and cerebral blood flow. PMID:26782203

  16. Nitric-oxide supplementation for treatment of long-term complications in argininosuccinic aciduria

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Argininosuccinate lyase (ASL) is required for the synthesis and channeling of L-arginine to nitric oxide synthase (NOS) for nitric oxide (NO) production. Congenital ASL deficiency causes argininosuccinic aciduria (ASA), the second most common urea cycle disorder, and leads to deficiency of both urea...

  17. Effect of soy isoflavone supplementation on nitric oxide metabolism and blood pressure in menopausal women

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Isoflavones, having chemical structures similar to estrogens, are believed to stimulate nitric oxide production and thus lower blood pressure. The efficacy of soy isoflavone supplementation to stimulate nitric oxide production and lower blood pressure in menopausal women with high normal blood press...

  18. SALICYLIC ACID- AND NITRIC OXIDE-MEDIATED SIGNAL TRANSDUCTION IN DISEASE RESISTANCE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Current advances in plant defense signaling is discussed, with emphasis on the role of nitric oxide and salicylic acid in the development of disease resistance. Nitric Oxide has recently been shown to have an important role in plant disease resistance. We show an increase in NOS-like activity in TMV...

  19. Nitric oxide-releasing mesalamine: potential utility for treatment of inflammatory bowel disease.

    PubMed

    Wallace, J L

    2003-05-01

    Nitric oxide can accelerate ulcer healing and exert anti-inflammatory effects. Addition of a nitric oxide-releasing moiety to mesalamine significantly boosts its anti-inflammatory activity. NO-releasing mesalamine suppresses inflammatory cytokine production and reduces leukocyte infiltration. PMID:12846442

  20. Levels of selected minerals, nitric oxide, and vitamins in aborted Sakis sheep raised under semitropical conditions

    PubMed Central

    Aypak, Serap Unubol

    2010-01-01

    The serum levels of calcium, phosphorus, magnesium, copper, zinc and iron and of nitric oxide, retinol, and β-carotene were determined in Sakiz ewes that had experienced an abortion and in healthy controls. Ten healthy and 25 aborted Sakiz sheep were selected from Afyon zone in western Turkey. Their ages ranged between 2 and 4 years weighing between 40 and 60 kg at the time of experiment. All of the abortions occurred in October. The concentrations of retinol, β-carotene, phosphorus, and zinc were significantly lower and those of calcium and nitric oxide were increased in aborted ewes relative to healthy controls. The serum levels of iron, copper, and magnesium were not significantly different among the two groups. In conclusion, abortion is an important problem in commercially important species of ruminants in many regions in the tropics including of western Turkey. Deficiencies of retinol, β-carotene, phosphorus and zinc, and the increase of calcium and nitric oxide concentration may play an important role in the etiology of abortion in ewes. Prophylactic measures such as vitamin and mineral supplementation may be of help to prevent or reduce the incidence of abortion in sheep. PMID:21076941

  1. New neolignans from the seeds of Myristica fragrans that inhibit nitric oxide production.

    PubMed

    Cao, Gui-Yun; Xu, Wei; Yang, Xiu-Wei; Gonzalez, Frank J; Li, Fei

    2015-04-15

    Five new 8-O-4' type neolignans, named myrifralignan A-E (1-5), together with five known analogues (6-10), were isolated from the seeds of Myristica fragrans Houtt. Their chemical structures were determined using several spectroscopic methods. Compounds 3-10 exhibited potent inhibitory activity against the production of nitric oxide (NO) in the RAW264.7 cell line stimulated by lipopolysaccaride. Myrislignan (7) and machilin D (10) were the most potent inhibitors of NO production amongst these compounds. The IC50 values of myrislignan and machilin D were 21.2 and 18.5 μM. And, their inhibitory activity was more than L-N(6)-(1-iminoethyl)-lysine, a selective inhibitor of inducible nitric oxide synthase (IC50=27.1 μM). Furthermore, real-time PCR analysis revealed that these neolignans could significantly suppress the expression of inducible nitric oxide synthase mRNA. These results demonstrated that the 8-O-4' type neolignans are promising candidates as anti-inflammatory agents. PMID:25466017

  2. Insights into the nitric oxide reductase mechanism of flavodiiron proteins from a flavin-free enzyme

    PubMed Central

    Hayashi, Takahiro; Caranto, Jonathan D.; Wampler, David A.; Kurtz, Donald M.; Monne-Loccoz, Pierre

    2010-01-01

    Flavodiiron proteins (FDPs) catalyze reductive scavenging of dioxygen and nitric oxide in air sensitive microorganisms. FDPs contain a distinctive non-heme diiron/flavin mononucleotide (FMN) active site. Alternative mechanisms for the nitric oxide reductase (NOR) activity have been proposed consisting of either protonation of a diiron-bridging hyponitrite or super-reduction of a diferrous-dinitrosyl by the proximal FMNH2 in the rate-determining step. In order to test these alternative mechanisms, we examined a deflavinated FDP (deflavo-FDP) from Thermotoga maritima. The deflavo-FDP retains an intact diiron site but does not show multi-turnover NOR or O2 reductase (O2R) activity. Reactions of the reduced (diferrous) deflavo-FDP with nitric oxide were examined by UV-vis absorption, EPR, resonance Raman, and FTIR spectroscopies. Anaerobic addition of nitric oxide up to 1 NO:diferrous deflavo-FDP results in formation of a diiron-mononitrosyl complex characterized by a broad S = 1/2 EPR signal arising from antiferromagnetic coupling of an S = 3/2 {FeNO}7 with an S = 2 Fe(II). Further addition of NO results in two reaction pathways, one of which produces N2O and the diferric site and the other of which produces a stable diiron-dinitrosyl complex. Both NO-treated and as-isolated deflavo-FDPs regain full NOR and O2R activities upon simple addition of FMN. The production of N2O upon addition of NO to the mononitrosyl deflavo-FDP supports the hyponitrite mechanism, but the concomitant formation of a stable diiron-dinitrosyl complex in the deflavo-FDP is consistent with a super-reduction pathway in the flavinated enzyme. We conclude that a diiron-mononitrosyl complex is an intermediate in the NOR catalytic cycle of FDPs. PMID:20669924

  3. Effect of Myocardial Reperfusion on the Release of Nitric Oxide after Regional Ischemia

    PubMed Central

    Nakamura, Koki; Al-Ruzzeh, Sharif; Gray, Caroline; Yacoub, Magdi; Amrani, Mohamed

    2006-01-01

    Off-pump coronary artery bypass surgery is increasing in popularity worldwide. However, very little is known about the effect of regional myocardial ischemia-reperfusion on nitric oxide release. In an animal model mimicking off-pump bypass, male Sprague-Dawley rats (350–450 g) were mechanically ventilated under general anesthesia. After left lateral thoracotomy, the animals underwent occlusion of either the left anterior descending artery (for 3, 5, 7.5, 10, 12.5, 15, or 20 minutes) or the circumflex artery (for 5, 10, or 15 minutes). Twenty-four hours after reperfusion, heart tissue was stained for determination of the area at risk and the infarcted area. Blood samples obtained before ischemia, 10 minutes after reperfusion, and 24 hours after reperfusion were analyzed for plasma concentrations of nitric oxide. After occlusion of the left anterior descending artery, the size of the infarcted area increased dramatically as the duration of occlusion increased, and was significantly larger after 12.5, 15, or 20 minutes of occlusion than after 3 minutes. After occlusion of the circumflex artery, the size of the infarcted area increased steadily and was significantly larger after 15 minutes of occlusion than after 5 minutes. There was no significant correlation between the duration of coronary occlusion and the plasma concentration of nitric oxide: 10 minutes after reperfusion, this concentration was significantly lower than that before ischemia, but it was twice the baseline level 24 hours after reperfusion. We concluded that the duration of regional ischemia did not affect the plasma concentration of nitric oxide in the systemic circulation. PMID:16572867

  4. Estriol-induced fibrinolysis due to the activation of plasminogen to plasmin by nitric oxide synthesis in platelets.

    PubMed

    Jana, Pradipta; Maiti, Smarajit; Kahn, Nighat N; Sinha, Asru K

    2015-04-01

    Estriol, an oestrogen, at 0.6 nmol/l was reported to inhibit ADP-induced platelet aggregation through nitric oxide synthesis. As nitric oxide has been reported to cause fibrinolysis due to the activation of plasminogen to plasmin, the role of estriol as a fibrinolytic agent was investigated. Also, the mechanism of estriol-induced nitric oxide synthesis in anucleated platelets was investigated. The estriol-induced lysis of platelet-rich plasma (PRP) clot was determined by photography of the clot lysis and by the assay of fibrin degradation products in the lysate and was obtained by SDS-PAGE. Nitric oxide was determined by methemoglobin method. The platelet membrane protein was isolated from the platelets by using Triton X-100 (0.05% v/v). The binding of estriol to the protein was determined by Scatchard plot by using an ELISA for estriol. Estriol at 0.6 nmol/l was found to lyse the clotted PRP due to fibrinolysis that produced fibrin degradation products in the lysate. The amino acid analysis of the platelet membrane protein, which resembles with nitric oxide synthase (NOS) activity, was activated nearly 10-fold over the control in the presence of estriol and was identified to be a human serum albumin precursor (Mr. 69 kDa) that binds to estriol with Kd1 of 6.0 × 10 mol/l and 39 ± 2 molecules of estriol bound the NOS molecule. The estriol-induced nitric oxide is capable of inducing fibrinolysis of the clotted PRP. The binding of estriol to platelet membrane NOS activated the enzyme in the absence of DNA in the platelet. PMID:24695088

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

    PubMed

    Zhu, Wenzhen; Yang, Bingwu; Fu, Huiling; Ma, Long; Liu, Tingting; Chai, Rongfei; Zheng, Zhaodi; Zhang, Qunye; Li, Guorong

    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. PMID:25680459

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

    PubMed

    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. PMID:26024545

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

    PubMed

    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]. PMID:26909371

  8. [Thrombosis and coronary disease: neutrophils, nitric oxide and aspirin].

    PubMed

    López-Farré, A; Farré, J; Sánchez de Miguel, L; Romero, J; Gómez, J; Rico, L; Casado, S

    1998-03-01

    In recent years, relevant changes have occurred in the knowledge of the cellular mechanisms regulating platelet aggregation and adhesion to the endothelial surface. In particular, major aspects of the interactions between platelets and endothelial cells and neutrophils have been clarified. These interactions involve not only thrombosis-promoting or thrombosis-inhibiting properties but also several aspects of the regulation of vascular function. A new concept has progressively emerged showing thrombosis as a multicellular event in which cell-to cell interactions between platelets, neutrophils, and endothelium regulate the size of a growing thrombus. In brief, there is consistent evidence showing that two vasodilating mediators produced by endothelial cells and neutrophils (nitric oxide and prostacyclin) have antiaggregating platelet effects. Platelet activation is particularly relevant in myocardial ischemia, and several pharmacological strategies have been devised to prevent intravascular platelet activation. Aspirin remains a keystone of these preventive and damage-limiting strategies. Current knowledge maintains that low doses of aspirin decrease in vivo platelet aggregation by a selective inhibitory effect on thromboxane A2 production by platelets with maintenance of prostacyclin production by the endothelium. We have recently focussed our research on the basis that the antiaggregating effect of aspirin could be explained not only by the above-mentioned effects on thromboxane A2 synthesis, but also through its action on neutrophils. Our in vitro and ex vivo studies have demonstrated that neutrophils enhance the antiaggregating effects of acetylsalicilic acid on platelets. We have shown that acetylsalicilic acid stimulates nitric oxide production on neutrophils inhibiting the aggregating effects of thrombin, ADP or epinephrine on platelets. the role of the neutrophils in ischemic events enhancing the tissue damage through the release of several proteases, reactive oxygen species and tumor necrosis factor-alpha has been extensively demonstrated. In an experimental model of acute ischemia/reperfusion in rabbits, we have shown that acetylsalicilic acid is able to enhance the nitric oxide production by neutrophils providing a potential mechanism for the beneficial action of aspirin in the myocardial infarction. Further research is needed to assess the mechanisms of the action of aspirin during the thrombotic phenomena and its effects on the different types of cells that compound the microvascular environment. PMID:9577162

  9. Nitric oxide- and nitric oxide donors-induced relaxation and its modulation by oxidative stress in piglet pulmonary arteries

    PubMed Central

    López-López, José Gustavo; Pérez-Vizcaíno, Francisco; Cogolludo, Angel L; Ibarra, Manuel; Zaragozá-Arnáez, Francisco; Tamargo, Juan

    2001-01-01

    Inhaled nitric oxide (iNO) is widely used in the treatment of pulmonary hypertension while inhaled NO donors have been suggested as an alternative therapy. The differential susceptibility to inactivation by oxidative stress and oxyhaemoglobin of NO and two NO donors, sodium nitroprusside (SNP) and S-nitroso-N-acetyl-penicillamine (SNAP) were analysed in isolated endothelium-denuded pulmonary arteries from 2-week-old piglets stimulated with U46619. NO, SNAP and SNP relaxed the arteries (pIC30=7.73±0.12, 7.26±0.17 and 6.43±0.13, respectively) but NO was not detected electrochemically in the bath after the addition of SNP and only at concentrations at which SNAP produced more than 50% relaxation. The sGC inhibitor ODQ (10−6 M) or the sarcoplasmic Ca2+-ATPase thapsigargin (2×10−6 M) markedly inhibited the relaxation induced by NO, SNAP and SNP. Addition of oxyhaemoglobin (3×10−7 M) or diethyldithiocarbamate (1 mM) markedly inhibited NO- (pIC30=6.88±0.07 and 6.92±0.18, respectively), weakly inhibited SNAP- and had no effect on SNP-induced relaxation. Xanthine oxidase (5 mu ml−1) plus hypoxanthine (10−4 M) markedly inhibited NO- (pIC30=6.96±0.12) but not SNAP- or SNP-induced relaxation. Superoxide dismutase (SOD), MnCl2, diphenileneiodonium and exposing the luminal surface of the rings outwards (inversion) potentiated the relaxant responses of NO (pIC30=8.52±0.16, 8.23±0.11, 8.01±0.11 and 8.20±0.10, respectively). However, SOD did not modify the NO detected by the electrode and had no effect on SNAP- or SNP-induced relaxation. Therefore, the kinetics and local distribution of NO release of NO donors influence the susceptibility to the scavenging effects of oxyhaemoglobin and superoxide. PMID:11429384

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

    PubMed

    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 risk mitral surgery. This will require new collaboration between the pharmaceutical companies, national grant agencies and the clinical community. Until these trials are realized we should gather multi-institutional experience from large retrospective studies and prospective data from a new international registry. We must step up international efforts if we wish to maintain the iNO modality in the armamentarium of hemodynamic tools for the perioperative management of our high risk cardiac surgical patients. PMID:26186889

  11. Nitric Oxide, Oxidative Stress, and p66Shc Interplay in Diabetic Endothelial Dysfunction

    PubMed Central

    Greco, Simona; Capogrossi, Maurizio C.; Gaetano, Carlo

    2014-01-01

    Increased oxidative stress and reduced nitric oxide (NO) bioavailability play a causal role in endothelial cell dysfunction occurring in the vasculature of diabetic patients. In this review, we summarized the molecular mechanisms underpinning diabetic endothelial and vascular dysfunction. In particular, we focused our attention on the complex interplay existing among NO, reactive oxygen species (ROS), and one crucial regulator of intracellular ROS production, p66Shc protein. PMID:24734227

  12. Transcriptomic Response to Nitric Oxide Treatment in Larix olgensis Henry

    PubMed Central

    Hu, Xiaoqing; Yang, Jingli; Li, Chenghao

    2015-01-01

    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. PMID:26633380

  13. Nitric oxide in the middle to upper thermosphere

    NASA Technical Reports Server (NTRS)

    Siskind, David E.; Rusch, David W.

    1992-01-01

    The results of six rocket observations of thermospheric nitric oxide are reviewed and reconciled with the available laboratory photochemical data. The impact of the recently revised recommendation for the N (S-4) + O2 rate coefficient on photochemical models is assessed. Use of the new rate coefficient leads to significantly enhanced production of NO, particularly at F-region altitudes during solar maximum conditions. A comparison of photochemical calculations with the rocket profiles indicates that the new rate coefficient introduces a significant discrepancy which can be resolved if the recombination reaction of N + NO is temperature dependent. Calculations using the preposed rate coefficient predict the NO solar cycle variation at 180 km to be less than at 140 km, which is also in agreement with the observations.

  14. The actions and interactions of nitric oxide in solid tumours.

    PubMed

    Brennan, P A

    2000-08-01

    The small molecule nitric oxide (NO) has undergone an image change since its identification as a biological messenger in 1987. It is a free radical, with a diverse range of actions in both physiological and pathological processes. Whilst over 30000 research papers have been written to date on NO, its role in tumour biology remains incompletely understood and research in this field is still in its infancy. NO would appear to have both tumour promoting and inhibiting effects which are presumed to be dependent on its local concentration within the tumour. Recently the relationships of NO to the tumour suppressor gene p53 have been experimentally elucidated, demonstrating how mutations of p53 may adversely affect the host by enhancing NO production. This review summarizes the brief history of this molecule, outlines its roles in the common solid tumours and suggests areas for future research. PMID:11016461

  15. Exhaled Nitric Oxide: Sources of Error in Offline Measurement

    PubMed Central

    LINN, WILLIAM S.; AVILA, MARISELA; GONG, HENRY

    2007-01-01

    Delayed offline measurement of exhaled nitric oxide (eNO), although useful in environmental and clinical research, is limited by the instability of stored breath samples. The authors characterized sources of instability with the goal of minimizing them. Breath and other air samples were stored under various conditions, and NO levels were measured repeatedly over 1–7 d. Concentration change rates varied positively with temperature and negatively with initial NO level, thus “stable” levels reflected a balance of NO-adding and NO-removing processes. Storage under refrigeration for a standardized period of time can optimize offline eNO measurement, although samples at room temperature are effectively stable for several hours. PMID:16268114

  16. Deciphering Nitric Oxide Stress in Bacteria with Quantitative Modeling

    PubMed Central

    Robinson, Jonathan L.; Adolfsen, Kristin J.; Brynildsen, Mark P.

    2014-01-01

    Many pathogens depend on nitric oxide (NO•) detoxification and repair to establish an infection, and inhibitors of these systems are under investigation as next-generation antibiotics. Due to the broad reactivity of NO• and its derivatives with biomolecules, a deep understanding of how pathogens sense and respond to NO•, as an integrated system, has been elusive. Quantitative kinetic modeling has been proposed as a method to enhance analysis and understanding of NO• stress at the systems-level. Here we review the motivation for, current state of, and future prospects of quantitative modeling of NO• stress in bacteria, and suggest that such mathematical approaches would prove equally useful in the study of other broadly reactive antimicrobials, such as hydrogen peroxide (H2O2). PMID:24983704

  17. Working with nitric oxide and hydrogen sulfide in biological systems

    PubMed Central

    Yuan, Shuai; Kevil, Christopher G.

    2014-01-01

    Nitric oxide (NO) and hydrogen sulfide (H2S) are gasotransmitter molecules important in numerous physiological and pathological processes. Although these molecules were first known as environmental toxicants, it is now evident that that they are intricately involved in diverse cellular functions with impact on numerous physiological and pathogenic processes. NO and H2S share some common characteristics but also have unique chemical properties that suggest potential complementary interactions between the two in affecting cellular biochemistry and metabolism. Central among these is the interactions between NO, H2S, and thiols that constitute new ways to regulate protein function, signaling, and cellular responses. In this review, we discuss fundamental biochemical principals, molecular functions, measurement methods, and the pathophysiological relevance of NO and H2S. PMID:25550314

  18. Effects of nitric oxide on neuroendocrine function and behavior.

    PubMed

    Nelson, R J; Kriegsfeld, L J; Dawson, V L; Dawson, T M

    1997-10-01

    Nitric oxide (NO) is an unusual chemical messenger. NO mediates blood vessel relaxation when produced by endothelial cells. When produced by macrophages, NO contributes to the cytotoxic function of these immune cells. NO also functions as a neurotransmitter and neuromodulator in the central and peripheral nervous systems. The effects on blood vessel tone and neuronal function form the basis for an important role of NO on neuroendocrine function and behavior. NO mediates hypothalamic portal blood flow and, thus, affects oxytocin and vasopression secretion; furthermore, NO mediates neuroendocrine function in the hypothalamic-pituitary-gonadal and hypothalamic-pituitary-adrenal axes. NO influences several motivated behaviors including sexual, aggressive, and ingestive behaviors. Learning and memory are also influenced by NO. Taken together, NO is emerging as an important chemical mediator of neuroendocrine function and behavior. PMID:9344634

  19. Nitric Oxide Regulates Neurogenesis in the Hippocampus following Seizures

    PubMed Central

    Carreira, Bruno P.; Santos, Daniela F.; Santos, Ana I.; Carvalho, Caetana M.; Arajo, Ins M.

    2015-01-01

    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. PMID:26587180

  20. Regulation of Injury-Induced Neurogenesis by Nitric Oxide

    PubMed Central

    Carreira, Bruno P.; Carvalho, Caetana M.; Araújo, Inês M.

    2012-01-01

    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. PMID:22997523

  1. Calmodulin-induced structural changes in endothelial nitric oxide synthase.

    PubMed

    Persechini, Anthony; Tran, Quang-Kim; Black, D J; Gogol, Edward P

    2013-01-31

    We have derived structures of intact calmodulin (CaM)-free and CaM-bound endothelial nitric oxide synthase (eNOS) by reconstruction from cryo-electron micrographs. The CaM-free reconstruction is well fitted by the oxygenase domain dimer, but the reductase domains are not visible, suggesting they are mobile and thus delocalized. Additional protein is visible in the CaM-bound reconstruction, concentrated in volumes near two basic patches on each oxygenase domain. One of these corresponds with a presumptive docking site for the reductase domain FMN-binding module. The other is proposed to correspond with a docking site for CaM. A model is suggested in which CaM binding and docking position the reductase domains near the oxygenase domains and promote docking of the FMN-binding modules required for electron transfer. PMID:23266515

  2. Influence of nitric oxide in the improvement of muscle power

    PubMed Central

    Bernardo, Daniela Navarro D'Almeida; Bryk, Flávio Fernandes; Fucs, Patrícia Maria de Moraes Barros

    2015-01-01

    ABSTRACT OBJECTIVE To evaluate whether nitric oxide (NO) supplementa-tion is directly related to increased muscle power in response to strength exercise training METHODS The study included 36 individuals who underwent training for eight weeks (three times per week) with weights, who were randomly divided into two groups, both receiving the same training protocol, but one group used 3g of arginine, as a precursor of NO, and the other received placebo RESULTS There was no significant difference between groups, only a significant difference for both groups between moments: before and after the training protocol CONCLUSION Oral administration of arginine asso-ciated with a training program did not increase the muscular power of individuals. Level of Evidence I, Study Type: Highquality randomized trial with statistically significant diffe-rence or no statistically significant difference but narrow confidence intervals. PMID:27057140

  3. microRNA and human inducible nitric oxide synthase.

    PubMed

    Guo, Zhong; Geller, David A

    2014-01-01

    Regulation of human inducible nitric oxide synthase (iNOS) expression involves both transcriptional and posttranscriptional mechanisms. Human iNOS gene transcription is controlled in a cell type-specific manner by extracellular cytokines. Transcriptional regulation of human iNOS gene involves transcription factors NF-κB, Stat-1, AP-1, C/EBPβ, KLF6, Oct 1, and NRF. Important posttranscriptional mechanisms also regulate human iNOS mRNA stability through RNA binding proteins HuR, TTP, KSRP, and PABP. Recently, there are several miRNAs that were validated to regulate human and rodent iNOS gene expression. Among them, miR-939 and miR-26a were identified to bind with the human iNOS 3'-UTR and exert a translational blockade of human iNOS protein synthesis. PMID:25189382

  4. Reaction between nitric oxide and ozone in solid nitrogen

    NASA Technical Reports Server (NTRS)

    Lucas, D.; Pimentel, G. C.

    1979-01-01

    Nitrogen dioxide, NO2, is produced when nitric oxide, NO, and ozone, O3, are suspended in a nitrogen matrix at 11-20 K. The NO2 is formed with first-order kinetics, a 12 K rate constant of (1.4 + or - 0.2) x 0.00001/sec, and an apparent activation energy of 106 + or - 10 cal/mol. Isotopic labeling, variation of concentrations, and cold shield experiments show that the growth of NO2 is due to reaction between ozone molecules and NO monomers, and that the reaction is neither infrared-induced nor does it seem to be a heavy atom tunneling process. Reaction is attributed to nearest-neighbor NO.O3 pairs probably held in a specific orientational relationship that affects the kinetic behavior. When the temperature is raised, more such reactive pairs are generated, presumably by local diffusion. Possible mechanisms are discussed.

  5. Transcriptomic Response to Nitric Oxide Treatment in Larix olgensis Henry.

    PubMed

    Hu, Xiaoqing; Yang, Jingli; Li, Chenghao

    2015-01-01

    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. PMID:26633380

  6. Cocoa flavanols: effects on vascular nitric oxide and blood pressure.

    PubMed

    Fraga, César G; Litterio, María C; Prince, Paula D; Calabró, Valeria; Piotrkowski, Bárbara; Galleano, Mónica

    2011-01-01

    Diets rich in fruits and vegetables have been associated with benefits for human health. Those effects have been partially ascribed to their content in flavonoids, compounds that are present in many edible plants and its derived foods. In humans, a significant number of studies has been developed analyzing the effect of foods and beverages rich in flavonoids on the presence and progression of risk factors associated to cardiovascular diseases, including hypertension. Cocoa derived products, rich in flavanols, have been thoroughly studied and demonstrated to be efficient improving endothelial function and decreasing blood pressure in humans and animals. However, the final chemical species and the mechanism/s responsible for these effects have not been completely defined. In this paper we present data supporting the hypothesis that flavanols could define superoxide anion production and then, establish optimal nitric oxide levels and blood pressure. PMID:21297914

  7. Nitric oxide regulates synaptic transmission between spiny projection neurons

    PubMed Central

    Sagi, Yotam; Heiman, Myriam; Peterson, Jayms D.; Musatov, Sergei; Scarduzio, Mariangela; Logan, Stephen M.; Kaplitt, Michael G.; Surmeier, Dalton J.; Heintz, Nathaniel; Greengard, Paul

    2014-01-01

    Recurrent axon collaterals are a major means of communication between spiny projection neurons (SPNs) in the striatum and profoundly affect the function of the basal ganglia. However, little is known about the molecular and cellular mechanisms that underlie this communication. We show that intrastriatal nitric oxide (NO) signaling elevates the expression of the vesicular GABA transporter (VGAT) within recurrent collaterals of SPNs. Down-regulation of striatal NO signaling resulted in an attenuation of GABAergic signaling in SPN local collaterals, down-regulation of VGAT expression in local processes of SPNs, and impaired motor behavior. PKG1 and cAMP response element-binding protein are involved in the signal transduction that transcriptionally regulates VGAT by NO. These data suggest that transcriptional control of the vesicular GABA transporter by NO regulates GABA transmission and action selection. PMID:25413364

  8. Fabrication of nitric oxide-releasing polyurethane glucose sensor membranes

    PubMed Central

    Koh, Ahyeon; Riccio, Daniel A.; Sun, Bin; Carpenter, Alexis W.; Nichols, Scott P.; Schoenfisch, Mark H.

    2011-01-01

    Despite clear evidence that polymeric nitric oxide (NO) release coatings reduce the foreign body response (FBR) and may thus improve the analytical performance of in vivo continuous glucose monitoring devices when used as sensor membranes, the compatibility of the NO release chemistry with that required for enzymatic glucose sensing remains unclear. Herein, we describe the fabrication and characterization of NO-releasing polyurethane sensor membranes using NO donor-modified silica vehicles embedded within the polymer. In addition to demonstrating tunable NO release as a function of the NO donor silica scaffold and polymer compositions and concentrations, we describe the impact of the NO release vehicle and its release kinetics on glucose sensor performance. PMID:21795038

  9. Expression of inducible nitric oxide synthase and formation of nitric oxide by alveolar macrophages: an interspecies comparison.

    PubMed Central

    Jesch, N K; Dörger, M; Enders, G; Rieder, G; Vogelmeier, C; Messmer, K; Krombach, F

    1997-01-01

    Nitric oxide (NO) is suggested to play a role in mediating pulmonary injury. However, interspecies differences appear to exist in the ability of alveolar macrophages (AM) to express the inducible nitric oxide synthase (iNOS) and to generate NO. The purpose of this study was to compare iNOS expression and NO production by rat, hamster, monkey, and human AM using the identical experimental conditions in vitro. As AM donors, CD rats, Syrian golden hamsters, cynomolgus monkeys, and nonsmoking, healthy human volunteers were used. The AM were obtained by bronchoalveolar lavage and stimulated in vitro with various concentrations and combinations of lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma). The oxidation product of NO, nitrite, was measured in the AM supernatant by the Griess reaction. The expression of iNOS in AM was detected using immunocytochemistry and immunoblotting. The expression of iNOS mRNA was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR). Rat AM, stimulated with either LPS or IFN-gamma, produced nitrite in a time- and dose-dependent manner. Combination of LPS and IFN-gamma resulted in a significantly enhanced nitrite formation. However, none of the treatments was able to induce hamster, monkey, or human AM to release measurable amounts of nitrite. Whereas expression of iNOS protein was only detected in stimulated rat AM, expression of iNOS mRNA was found in unstimulated and stimulated rat AM, slightly in stimulated hamster AM, but not in monkey and human AM. In conclusion, our findings point to distinct regulatory mechanisms of the NO pathway in AM from these four different species. PMID:9400741

  10. Nitric oxide-mediated modulation of the murine locomotor network

    PubMed Central

    Foster, Joshua D.; Dunford, Catherine; Sillar, Keith T.

    2013-01-01

    Spinal motor control networks are regulated by neuromodulatory systems to allow adaptability of movements. The present study aimed to elucidate the role of nitric oxide (NO) in the modulation of mammalian spinal locomotor networks. This was investigated with isolated spinal cord preparations from neonatal mice in which rhythmic locomotor-related activity was induced pharmacologically. Bath application of the NO donor diethylamine NONOate (DEA/NO) decreased the frequency and modulated the amplitude of locomotor-related activity recorded from ventral roots. Removal of endogenous NO with coapplication of a NO scavenger (PTIO) and a nitric oxide synthase (NOS) blocker [nitro-l-arginine methyl ester (l-NAME)] increased the frequency and decreased the amplitude of locomotor-related activity. This demonstrates that endogenously derived NO can modulate both the timing and intensity of locomotor-related activity. The effects of DEA/NO were mimicked by the cGMP analog 8-bromo-cGMP. In addition, the soluble guanylyl cyclase (sGC) inhibitor ODQ blocked the effects of DEA/NO on burst amplitude and frequency, although the frequency effect was only blocked at low concentrations of DEA/NO. This suggests that NO-mediated modulation involves cGMP-dependent pathways. Sources of NO were studied within the lumbar spinal cord during postnatal development (postnatal days 1–12) with NADPH-diaphorase staining. NOS-positive cells in the ventral horn exhibited a rostrocaudal gradient, with more cells in rostral segments. The number of NOS-positive cells was also found to increase during postnatal development. In summary, we have shown that NO, derived from sources within the mammalian spinal cord, modulates the output of spinal motor networks and is therefore likely to contribute to the fine-tuning of locomotor behavior. PMID:24259545

  11. Purification, characterisation and distribution of ovine neuronal nitric oxide synthase.

    PubMed

    Crack, P J; Tetaz, T; Smith, A I

    1998-08-01

    Nitric oxide (NO) is an ubiquitous intercellular messenger molecule synthesised from the amino acid L-arginine by the enzyme nitric oxide synthase (NOS). A number of NOS iso-enzymes have been identified, varying in molecular size, tissue distribution and possible biological role. To further understand the role of NO in the regulation of neuroendocrine function in the sheep, we have purified and characterised ovine neuronal NOS (nNOS) using anion exchange, affinity and size-exclusion chromatography. SDS-PAGE reveals that ovine nNOS has an apparent denatured molecular weight of 150 kDa which correlates well with the other purified nNOS forms such as rat, bovine and porcine. The native molecular weight predicted by size-exclusion chromatography was 200 kD which is in close agreement with that found for porcine and rat nNOS. Internal amino acid sequences generated from tryptic digests of the purified ovine nNOS are highly homologous to rat nNOS. There was no significant difference in the cofactor dependence and kinetic characteristics of ovine nNOS when compared to rat and bovine nNOS, (K(m) for L-arginine 2.8, 2.0 and 2.3 microM respectively). A polyclonal anti-peptide antibody directed toward the C-terminal end of the rat nNOS sequence showed full cross-reactivity with the purified ovine nNOS. Immunohistochemical and Western analysis using this antiserum demonstrate the expression of nNOS in the cortex, cerebellum, hypothalamus and pituitary of the sheep. The lack of staining in the neural and anterior lobes of the pituitary seems to suggest that NOS plays a varied role in the control of endocrine systems between species. PMID:9854819

  12. Elevation in Exhaled Nitric Oxide Predicts for Radiation Pneumonitis

    SciTech Connect

    Guerrero, Thomas; Martinez, Josue; McCurdy, Matthew R.; Wolski, Michael; McAleer, Mary Francis

    2012-02-01

    Purpose: Radiation pneumonitis is a major toxicity after thoracic radiotherapy (RT), with no method available to accurately predict the individual risk. This was a prospective study to evaluate exhaled nitric oxide as a predictive biomarker for radiation pneumonitis in esophageal cancer patients. Patients and Methods: A total of 34 patients prescribed neoadjuvant chemoradiotherapy for esophageal cancer were enrolled in the present trial. Each patient underwent respiratory surveys and exhaled nitric oxide (NO) measurements before, at the end of, and 1 to 2 months after completing RT. Pneumonitis toxicity was scored using the Common Terminology Criteria for Adverse Events, version 4.0. The demographics, dosimetric factors, and exhaled NO levels were evaluated for correlation with symptomatic patients (scores {>=}2). Results: Of the 34 patients, 28 were evaluable. All had received 50.4 Gy RT with concurrent chemotherapy. The pneumonitis toxicity score was Grade 3 for 1, Grade 2 for 3, Grade 1 for 7, and Grade 0 for 17. The dosimetric factors were not predictive of symptoms. The mean exhaled NO level measured before, at completion, and at restaging was 17.3 {+-} 8.5 (range, 5.5-36.7), 16.0 {+-} 14.2 (range, 5.8-67.7), and 14.7 {+-} 6.2 (range, 5.5-28.0) parts per billion, respectively. The ratio of exhaled NO at the end of RT vs. before treatment was 3.4 (range, 1.7-6.7) for the symptomatic and 0.8 (range, 0.3-1.3) for the asymptomatic (p = .0017) patients. The elevation in exhaled NO preceded the peak symptoms by 33 days (range, 21-50). The interval to peak symptoms was inversely related to the exhaled NO elevation. Conclusions: Elevations in exhaled NO at the end of RT was found to predict for radiation pneumonitis symptoms.

  13. Nitric oxide regulated two-component signaling in Pseudoalteromonas atlantica.

    PubMed

    Arora, Dhruv P; Boon, Elizabeth M

    2012-05-11

    Bacteria employ two-component signaling to detect and respond to environmental stimuli. In essence, two-component signaling relies on a protein called a response regulator that can elicit a change in gene expression or protein function in response to phosphoryl transfer from a histidine kinase. Phosphorylation of the associated histidine kinase is regulated by detection of an environmental signal, thus linking sensing to cellular response. Recently, it has been suggested that H-NOX (Heme-nitric oxide/oxygen binding) proteins may act as nitric oxide (NO) sensors in two-component signaling systems. NO/H-NOX regulated histidine kinases have been reported, but their cognate response regulators have yet to be identified. In this work we provide biochemical characterization of a complete NO/H-NOX-regulated two-component signaling pathway in the biofilm-dwelling marine bacterium, Pseudoalteromonas atlantica. In P. atlantica, as is typical for bacteria that code for H-NOX, an hnoX gene is found in the same operon as a gene coding for a two-component signaling histidine kinase (H-NOX-associated histidine kinase; HahK). We find that HahK is capable of autophosphorylation in vitro and that NO-bound H-NOX inhibits HahK activity, implicating H-NOX as a selective NO sensor. The cognate response regulator, a protein annotated as a cyclic-di-GMP processing enzyme that we have named HarR (H-NOX-associated response regulator), was identified using bioinformatics tools. Phosphoryl transfer from HahK to HarR has been established. This report reveals the first biochemical characterization of an H-NOX-associated response regulator and contributes to a deeper understanding of NO/H-NOX signaling in bacteria. PMID:22521885

  14. Nitrated lipids decompose to nitric oxide and lipid radicals and cause vasorelaxation.

    PubMed

    Lima, Emersom S; Bonini, Marcelo G; Augusto, Ohara; Barbeiro, Hermes V; Souza, Heraldo P; Abdalla, Dulcineia S P

    2005-08-15

    Nitric oxide-derived oxidants such as nitrogen dioxide and peroxynitrite have been receiving increasing attention as mediators of nitric oxide toxicity. Indeed, nitrated and nitrosated compounds have been detected in biological fluids and tissues of healthy subjects and in higher yields in patients under inflammatory or infectious conditions as a consequence of nitric oxide overproduction. Among them, nitrated lipids have been detected in vivo. Here, we confirmed and extended previous studies by demonstrating that nitrolinoleate, chlolesteryl nitrolinoleate, and nitrohydroxylinoleate induce vasorelaxation in a concentration-dependent manner while releasing nitric oxide that was characterized by chemiluminescence-and EPR-based methodologies. As we first show here, diffusible nitric oxide production is likely to occur by isomerization of the nitrated lipids to the corresponding nitrite derivatives that decay through homolysis and/or metal ion/ascorbate-assisted reduction. The homolytic mechanism was supported by EPR spin-trapping studies with 3,5-dibromo-4-nitrosobenzenesulfonic acid that trapped a lipid-derived radical during nitrolinoleate decomposition. In addition to provide a mechanism to explain nitric oxide production from nitrated lipids, the results support their role as endogenous sources of nitric oxide that may play a role in endothelium-independent vasorelaxation. PMID:16043024

  15. Nitric Oxide and Peroxynitrite in Health and Disease

    PubMed Central

    PACHER, PÁL; BECKMAN, JOSEPH S.; LIAUDET, LUCAS

    2008-01-01

    The discovery that mammalian cells have the ability to synthesize the free radical nitric oxide (NO) has stimulated an extraordinary impetus for scientific research in all the fields of biology and medicine. Since its early description as an endothelial-derived relaxing factor, NO has emerged as a fundamental signaling device regulating virtually every critical cellular function, as well as a potent mediator of cellular damage in a wide range of conditions. Recent evidence indicates that most of the cytotoxicity attributed to NO is rather due to peroxynitrite, produced from the diffusion-controlled reaction between NO and another free radical, the superoxide anion. Peroxynitrite interacts with lipids, DNA, and proteins via direct oxidative reactions or via indirect, radical-mediated mechanisms. These reactions trigger cellular responses ranging from subtle modulations of cell signaling to overwhelming oxidative injury, committing cells to necrosis or apoptosis. In vivo, peroxynitrite generation represents a crucial pathogenic mechanism in conditions such as stroke, myocardial infarction, chronic heart failure, diabetes, circulatory shock, chronic inflammatory diseases, cancer, and neurodegenerative disorders. Hence, novel pharmacological strategies aimed at removing peroxynitrite might represent powerful therapeutic tools in the future. Evidence supporting these novel roles of NO and peroxynitrite is presented in detail in this review. PMID:17237348

  16. Nitric Oxide Participation in the Fungicidal Mechanism of Gamma Interferon-Activated Murine Macrophages against Paracoccidioides brasiliensis Conidia

    PubMed Central

    Gonzalez, Angel; de Gregori, Waldemar; Velez, Diana; Restrepo, Angela; Cano, Luz E.

    2000-01-01

    Paracoccidioidomycosis, a systemic mycosis restricted to Latin America and produced by the dimorphic fungus Paracoccidioides brasiliensis, is probably acquired by inhalation of conidia produced by the mycelial form. The macrophage (Mφ) represents the major cell defense against this pathogen; when activated with gamma interferon (IFN-γ), murine Mφs kill the fungus by an oxygen-independent mechanism. Our goal was to determine the role of nitric oxide in the fungicidal effect of Mφs on P. brasiliensis conidia. The results revealed that IFN-γ-activated murine Mφs inhibited the conidium-to-yeast transformation process in a dose-dependent manner; maximal inhibition was observed in Mφs activated with 50 U/ml and incubated for 96 h at 37°C. When Mφs were activated with 150 to 200 U of cytokine per ml, the number of CFU was 70% lower than in nonactivated controls, indicating that there was a fungicidal effect. The inhibitory effect was reversed by the addition of anti-IFN-γ monoclonal antibodies. Activation by IFN-γ also enhanced Mφ nitric oxide production, as revealed by increasing NO2 values (8 ± 3 μM in nonactivated Mφs versus 43 ± 13 μM in activated Mφs). The neutralization of IFN-γ also reversed nitric oxide production at basal levels (8 ± 5 μM). Additionally, we found that there was a significant inverse correlation (r = −0.8975) between NO2− concentration and transformation of P. brasiliensis conidia. Additionally, treatment with any of the three different nitric oxide inhibitors used (arginase, NG-monomethyl-l-arginine, and aminoguanidine), reverted the inhibition of the transformation process with 40 to 70% of intracellular yeast and significantly reduced nitric oxide production. These results show that IFN-γ-activated murine Mφs kill P. brasiliensis conidia through the l-arginine–nitric oxide pathway. PMID:10768942

  17. Nitric oxide contributes to substance P-induced increases in lung rapidly adapting receptor activity in guinea-pigs.

    PubMed Central

    Joad, J P; Kott, K S; Bonham, A C

    1997-01-01

    1. Substance P induces fluid flux via nitric oxide, and fluid flux stimulates lung rapidly adapting receptors (RARs). We therefore proposed that nitric oxide contributes to substance P-evoked increases in RAR activity. Since substance P decreases dynamic compliance (Cdyn), which can stimulate RARs, we also determined whether nitric oxide contributed to substance P-induced effects on pulmonary function. 2. In anaesthetized guinea-pigs, the effects of substance P on RAR activity, Cdyn, pulmonary resistance (RL), and arterial blood pressure were measured before and after i.v. infusion of NG-methyl-L-arginine (L-NMMA; a nitric oxide synthase inhibitor), or L-NMMA followed by L-arginine (a nitric oxide precursor which reverses the effects of L-NMMA). 3. Substance P-evoked increases in RAR activity were blunted by L-NMMA (P = 0.006) but not by L-NMMA-L-arginine (P = 0.42). 4. Substance P-evoked decreases in Cdyn were slightly inhibited by L-NMMA (P = 0.02) and slightly enhanced by L-NMMA-L-arginine (P = 0.004). However, at the time at which L-NMMA maximally reduced substance P-induced RAR stimulation (the first 30 s), it did not change substance P-induced decreases in Cdyn. 5. Substance P-evoked increases in RL were not changed by L-NMMA (P = 0.10) and were enhanced by L-NMMA-L-arginine (P = 0.03). 6. L-NMMA-evoked increases in mean arterial blood pressure were reversed by L-arginine. Substance P-evoked decreases in mean arterial blood pressure were not changed by L-NMMA or by L-NMMA-L-arginine. 7. We conclude that nitric oxide contributes to substance P-evoked increases in RAR activity and that the increases are most probably independent of decreases in Cdyn. PMID:9379417

  18. Protective effects of three smoke flavouring phenols on oxidative damage and nitric oxide production.

    PubMed

    Huang, Ming-Hsing; Chang, Lee-Wen; Sung, Wen-Chieh; Vong, Wen-Jong; Wang, Bor-Sen

    2011-06-15

    In this study, the effects of three smoke flavouring phenols, including 4-methoxyphenol (4-MP), 4-ethyl-2-methoxyphenol (EMP), and 4-propenyl-2-methoxyphenol (isoeugenol), on oxidative damage and nitric oxide production, were examined. In the range 5-20μM, EMP displayed the highest inhibitory effects on radical production and biomolecule oxidation in the acellular systems of the three smoke flavouring phenols. In addition, 4-MP, EMP and isoeugenol, in the range 5-20μM, protected liver cells against tert-butyl hydroperoxide (t-BHP)-induced cytotoxicity, correlating with protection against intracellular glutathione depletion. Meanwhile, the inhibitory effects of the three smoke flavouring phenols on nitric oxide (NO) generation, in lipopolysaccharide (LPS)-stimulated macrophages, increased with increasing concentrations. The decrease in NO production was attributed to the reduced inducible nitric oxide synthase (iNOS) expression in macrophages. These data suggested that the three smoke flavouring phenols, particularly EMP, show biological activities that contribute to antioxidation as well as anti-inflammation. PMID:25213941

  19. Influence of nitric oxide on histamine and carbachol-induced gastric Acid secretion in the common african toad - bufo regularis.

    PubMed

    Alada, A R A; Salahdeen, H M; Akande, O O; Idolor, G O

    2005-01-01

    The study aimed to determine the influence of nitric oxide (NO) on the action of histamine and carbachol on acid secretion in the common African toad - Bufo regularis. Gastric acidity was determined by titration method. The acid secretion was determined when nitric oxide was absent following administration of NO synthase inhibitor; N-nitro-L-arginine methyl ester (L-NAME) and when nitric oxide was in excess by administration of exogenous NO donor, sodium nitroprusside (SNP). Histamine or carbachol increased acid secretion in the toad. Acid output increased from 0.32 +/- 0.04 mEq/15min to 0.56 +/- 0.08 and 0.61 +/- 0.05 mEq/15min for histamine and carbachol respectively [P < 0.05]. Pretreatment of the toad with L-NAME produced further increases in histamine (0.62 +/- 0.06 mEq/15min) or carbachol (0.74 +/- 0.06 mEq/15min) induced acid secretion respectively. SNP however, completely abolished the acid secretion stimulated by either histamine or carbachol. It was therefore concluded that nitric oxide has a negative influence on the histamine or carbachol-stimulated acid secretion in the toad - Bufo regularis. PMID:17220932

  20. Nitric oxide synthase and NADPH-diaphorase after acute hypobaric hypoxia in the rat caudate putamen.

    PubMed

    Encinas, Juan Manuel; Fernández, Ana Patricia; Salas, Eduardo; Castro-Blanco, Susana; Muñoz, Priscila; Rodrigo, José; Serrano, Julia

    2004-03-01

    Changes in the production system of nitric oxide (NO), a multifunctional biological messenger known to participate in blood-flow regulation, neuromodulation, and neuroprotection or neurotoxicity, were investigated in the caudate putamen of adult rats submitted to hypobaric hypoxia. Employing immunohistochemistry, Western blotting, enzymatic assay, and NADPH-diaphorase staining, we demonstrate that neuronal nitric oxide synthase (nNOS) expression and constitutive nitric oxide synthase (cNOS) activity were transiently activated by 7 h of exposure to a simulated altitude of 8325 m (27,000 ft). In addition, endothelial nitric oxide synthase (eNOS) immunoreactivity and blood vessel NADPH-diaphorase staining peaked immediately after the hypoxic stimulus, whereas inducible nitric oxide synthase (iNOS) expression and activity remained unaltered. Nitrotyrosine formation, a marker of protein nitration, was evaluated by immunohistochemistry and Western blotting, and was found to increase parallel to nitric oxide synthesis. We conclude that the nitric oxide system undergoes significant transient alterations in the caudate putamen of adult rats submitted to acute hypobaric hypoxia. PMID:14980808

  1. Effect of soy isoflavone supplementation on nitric oxide metabolism and blood pressure in menopausal women1234

    PubMed Central

    Taylor, Addison A; Smith, E O'Brian; Barnes, Stephen; Hachey, David L

    2012-01-01

    Background: Isoflavones, having chemical structures similar to estrogens, are believed to stimulate nitric oxide production and thus lower blood pressure. The efficacy of soy isoflavone supplementation to stimulate nitric oxide production and lower blood pressure in menopausal women with high normal blood pressure remains unknown. Objective: The objective was to test the effect of soy isoflavone supplementation on nitric oxide production and blood pressure in menopausal women with high normal blood pressure. Design: A randomized, double-blind, parallel, placebo-controlled 6-wk trial was conducted to assess the effects of daily supplementation with 80 mg soy hypocotyl isoflavones (in aglycone units) on nitric oxide metabolism and blood pressure in 24 menopausal women with 12 women per group. Changes in nitric oxide metabolism were assessed via a primed, constant-infusion protocol with [15N]arginine and [13C]- and [2H]citrulline. Changes in blood pressure and associated vascular hemodynamics were assessed via office and 24-h ambulatory blood pressure monitoring, forearm blood flow, and indexes of arterial compliance. Results: When compared with placebo and after control for pretreatment values, soy isoflavone supplementation had no effect on arginine flux, citrulline flux, nitric oxide synthesis, blood pressure, forearm blood flow, or estimates of arterial stiffness. Conclusion: Daily supplementation with 80 mg soy hypocotyl isoflavones over a 6-wk period had no effect on nitric oxide metabolism or blood pressure and associated vascular hemodynamics in menopausal women with high normal blood pressure. PMID:22552034

  2. Indium Tin Oxide Resistor-Based Nitric Oxide Microsensors

    NASA Technical Reports Server (NTRS)

    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.

  3. Controlled release of nitric oxide chemotherapy using a nano-sized biodegradable multi-arm polymer

    PubMed Central

    Duan, Shaofeng; Cai, Shuang; Yang, Qiuhong; Forrest, M. Laird

    2013-01-01

    Nitric oxide is a cell signaling molecule that can be a potent inducer of cell death in cancers at elevated concentrations. Nitric oxide molecules are short-lived in vivo; therefore, NO-donating prodrugs have been developed that can deliver NO to tissues at micromolar concentrations. However, NO is also toxic to normal tissues and chronic exposure at low levels can induce tumor growth. We have designed a polymeric carrier system to deliver nitric oxide locoregionally to tumorigenic tissues. A highly water solubility and biodegradable 4-arm polymer nanocarrier, sugar poly-(6-O-methacryloyl-D-galactose), was synthesized using MADIX/RAFT polymerization, and utilized to deliver high concentrations of nitric oxide to xenografts of human head and neck squamous cell carcinoma (HNSCC). The in vitro release of the newly synthesized nitric oxide donor, O2-(2,4-dinitrophenyl) 1-[4-(2-hydroxy)ethyl]-3-methylpiperazin-1-yl]diazen-1-ium-1,2-diolate and its corresponding multi-arm polymer-based nanoconjugate demonstrated a 1- and 2.3-fold increase in half-life, respectively, compared to the release half-life of the nitric oxide -donor prodrug JS-K. When administered to tumor-bearing nude mice, the subcutaneously injected multi-arm polymer nitric oxide nanoparticles resulted in 50% tumor inhibition and a 7-week extension of the average survival time, compared to intravenous JS-K therapy (nitric oxide nanoparticles: CR=25%, PR=37.5%, PD=37.5%; JS-K: PD=100%). In summary, we have developed an effective nitric oxide anti-cancer chemotherapy that could be administered regionally to provide the local disease control, improving prognosis for head and neck cancers. PMID:22281420

  4. Respiratory detoxification of nitric oxide by the cytochrome c nitrite reductase of Escherichia coli.

    PubMed

    Poock, Susannah R; Leach, Emily R; Moir, James W B; Cole, Jeffrey A; Richardson, David J

    2002-06-28

    Nitric oxide is a key element in host defense against invasive pathogens. The periplasmic cytochrome c nitrite reductase (NrfA) of Escherichia coli catalyzes the respiratory reduction of nitrite, but in vitro studies have shown that it can also reduce nitric oxide. The physiological significance of the latter reaction in vivo has never been assessed. In this study the reduction of nitric oxide by Escherichia coli was measured in strains active or deficient in periplasmic nitrite reduction. Nrf(+) cells, harvested from cultures grown anaerobically, possessed a nitric-oxide reductase activity with physiological electron donation of 60 nmol min(-1) x mg dry wt(-1), and an in vivo turnover number of NrfA of 390 NO* s(-1) was calculated. Nitric-oxide reductase activity could not be detected in Nrf(-) strains. Comparison of the anaerobic growth of Nrf(+) and Nrf(-) strains revealed a higher sensitivity to nitric oxide in the NrfA(-) strains. A higher sensitivity to the nitrosating agent S-nitroso-N-acetyl penicillamine (SNAP) was also observed in agar plate disk-diffusion assays. Oxygen respiration by E. coli was also more sensitive to nitric oxide in the Nrf(-) strains compared with the Nrf(+) parent strain. The results demonstrate that active periplasmic cytochrome c nitrite reductase can confer the capacity for nitric oxide reduction and detoxification on E. coli. Genomic analysis of many pathogenic enteric bacteria reveals the presence of nrf genes. The present study raises the possibility that this reflects an important role for the cytochrome c nitrite reductase in nitric oxide management in oxygen-limited environments. PMID:11960983

  5. Nitric oxide adsorption and nitric oxide-carbon monoxide interaction on Ru/ZnO catalyst

    SciTech Connect

    Guglielminotti, E.; Boccuzzi, F. )

    1993-06-01

    The adsorption of NO and the interaction of NO-CO mixtures on Ru/ZnO has been studied by FTIR and mass spectroscopic experiments. NO is adsorbed initially on Ru[sup 0] and Ru[sup 2-] surface sites present on the reduced catalyst; however, a slow NO dissociation process leads to NO species adsorbed on more oxidized Ru[sup 3+] sites and to NO[sub 2][sup -] species adsorbed on the support. CO reacts at 423-573 K with the NO species dissociated on the Ru sites giving isocyanate and carbonate species spilled over to the support and resistant to decomposition up to 573 K, whereas CO is adsorbed on Ru[sup 0] and Ru[sup 2+] sites. The formation of large amounts of CO[sub 2] and N[sub 2] has been shown by mass spectroscopic experiments to occur only at T [ge] 473 K. The opposite reaction of NO interacting with preadsorbed CO leads to CO displacement producing NO and CO species on oxidized Ru and carboxylates or carbonates on the ZnO phase. In this case, with NO predominating in the NO-CO mixture, higher quantities of N[sub 2]O, N[sub 2], and CO[sub 2] are formed already at room temperature, whereas isocyanate species are formed in small quantities also at higher temperatures. The mass spectral and FTIR results confirm previous literature data showing that the isocyanates compete with the production of N[sub 2] and CO[sub 2] during the NO-CO reaction on supported metal catalysts. 19 refs., 3 figs.

  6. Investigation of iron oxide-chromia-alumina aerogels for the selective catalytic reduction of nitric oxide by ammonia

    SciTech Connect

    Willey, R.J.; Lai, H.; Peri, J.B. )

    1991-08-01

    The selective catalytic reduction of nitric oxide by ammonia over iron oxide-chromia-alumina aerogels was studied over the temperature range of 423 to 750 K. The highest activities were observed for Fe/Cr/Al materials with a 60% conversion at 720 K for a reactor flow velocity of 1,008 m{sup 3}/h-kg. Oxygen significantly enhanced the reaction rate as explained by a redox mechanism. Infrared characterization showed weak adsorption of nitric oxide on the preoxidized materials and quite strong adsorption on the reduced material; ammonia adsorption was strong on both oxidized and reduced materials. Observation of interaction between adsorbed nitric oxide and ammonia (when ammonia was added to reduced catalysts which held preadsorbed nitric oxide) provided insight into the reaction mechanism.

  7. The Biological Chemistry of Nitric Oxide as It Pertains to the Extrapulmonary Effects of Inhaled Nitric Oxide

    PubMed Central

    Gow, Andrew J.

    2006-01-01

    The chemical properties of nitric oxide (NO) have been studied for over 200 years. However, it is only within the last 20 years that the biological implications of this chemistry have been considered. The classical model of NO action within the vasculature centers on production in the endothelium, diffusion to the smooth muscle, and subsequent activation of guanylate cyclase via binding to its heme iron. In the context of this model, it is difficult to conceptualize extrapulmonary effects of inhaled NO. However, NO possesses complex redox chemistry and is capable of forming a range of nitrogen oxide species and is therefore capable of interacting with a variety of biomolecules. Of particular interest is its reaction with reduced cysteine to form an S-nitrosothiol (SNO). SNOs are formed throughout NO biology and are a post-translational modification that has been shown to regulate many proteins under physiologic conditions. Hemoglobin, which was considered to be solely a consumer of NO, can form SNO in a conformationally dependent manner, which allows for the transport of inhaled NO beyond the realm of the lung. Higher oxides of nitrogen are capable of modifying proteins via nitration of tyrosines, which has been shown to occur under pathologic conditions. By virtue of its redox reactivity, one can appreciate that inhaled NO has a variety of routes by which it can act and that these routes may lead to extrapulmonary effects. PMID:16565423

  8. Nitric Oxide Levels in Patients with Chronic Renal Disease

    PubMed Central

    Meenakshi, S. R.; Agarwal, Rajni

    2013-01-01

    Background and Objectives: Nitric Oxide (NO), the L-arginine derivative, is tonically synthesised by the endothelium within the kidney and it plays a crucial role in the regulation of the blood pressure and the renal blood flow. NO regulates the renal function through the modulation of the vascular tone and sodium handling. With the progressive development of the renal insufficiency, it remains unclear whether the endogenous NO production is increased or decreased in the kidney. This study was carried out to determine whether there were any changes in the levels of NO and teir correlation with the routine parameters of the renal dysfunction in the patients of Chronic Renal Failure (CRF), as the disease progresses in conjunction with poor renal functions. Methods: Thirty patients with chronic renal disease which was caused by chronic glomerulonephritis and hypertension, who were on Maintenance Haemodialysis (MHD) with serum creatinine levels of > 2.5 mg/dl, were included in this study. Thirty healthy voluntary blood donors were taken as the controls. NO was estimated by a spectrophotometric method by using cadmium reduction. The routine renal function tests, BUN and Creatinine were performed by the standard clinical chemistry procedures. Results: The serum NO levels were found to be significantly increased (p < 0.01) in the CRF on MHD (98.77 ± 35.40 μmol/l) as compared to the controls (22.03 ± 7.23 μmol/l). The NO output correlated with the serum creatinine (r = 0.8123, p < 0.01) and the urea concentration (r = 0.5166, p = <0.01) in the CRF group. Conclusion: The NO levels were markedly enhanced in the CRF patients who were on MHD. This was due to the dialysis procedure itself, which led to the stimulation of cytokine induced NO synthase and also due to the platelets which generated more NO due to uraemia. At high concentrations, NO is a cytotoxic molecule which is responsible for the complications of dialysis and it results in Nitrosative Stress in these patients, as it is a highly reactive free radical. Since the no output correlated with the serum creatinine and urea concentrations, a higher no production probably indicated insufficient blood purification, due to the common effect on their elimination pathways via the renal tract. Therefore, the alterations of the renal function, that are reflected in the changes of the creatinine concentration, will be accompanied by the changes in the serum NO. Thus, the determination of the NO levels in the peripheral blood may be useful in the assessment of the dialysis and they can also be used as markers in the follow up and the prognosis in these type of patients. PMID:23998047

  9. Nitric oxide synthase: role as a transmitter/mediator in the brain and endocrine system.

    PubMed

    Dawson, T M; Dawson, V L

    1996-01-01

    Nitric oxide is a unique biological messenger molecule. It is produced by endothelial cells to mediate blood vessel relaxation; it mediates, in part, the immune functions of activated macrophages; and in the central and peripheral nervous system it serves as a neurotransmitter. In the nervous system, nitric oxide may regulate neurotransmitter release, it may play a key role in synaptic plasticity and morphogenesis, and it may regulate sexual and aggressive behavior. Under conditions of excessive formation, nitric oxide is emerging as an important neurotoxin. PMID:8712777

  10. Fractional exhaled nitric oxide measurement with a handheld device.

    PubMed

    Magori, Erhard; Hiltawsky, Karsten; Fleischer, Maximilian; Simon, Elfriede; Pohle, Roland; von Sicard, Oliver; Tawil, Angelika

    2011-06-01

    A sensing system for fractional exhaled nitric oxide (FeNO) measurement is presented, which is characterized by a compact setup and a cost potential to be made available for the patient at home. The sensing is based on the work function measurement of a phthalocyanine-type sensing material, which is shown to be sufficiently sensitive for NO(2) in the ppb range. The transducer used to measure the work function is a field effect transistor with a suspended gate electrode. Selectivity is given with respect to other breath components including typically metabolic by-products. The measurement system includes breath treatments in a simple setup, which essentially are dehumidification and a quantitative conversion of NO to NO(2) with a conversion rate of approx. 95%, using a disposable oxidation catalyst. The accomplishment of the correct exhalation maneuver and feeding of the suited portion of exhaled air to the sensor is provided by breath sampling means. The sensor is not gas consuming. This allows us to fill the measurement chamber once, instead of establishing a gas flow for the measurement. This feature simplifies the device architecture. In this paper, we report on sensor characteristics, system architecture and measurement with artificial breath-gas as well as with human breath with the device. PMID:21646688

  11. Hydrogen sulfide and endothelial dysfunction: relationship with nitric oxide.

    PubMed

    Altaany, Zaid; Moccia, Francesco; Munaron, Luca; Mancardi, Daniele; Wang, Rui

    2014-01-01

    The endothelium is a cellular monolayer that lines the inner surface of blood vessels and plays a central role in the maintenance of cardiovascular homeostasis by controlling platelet aggregation, vascular tone, blood fluidity and fibrinolysis, adhesion and transmigration of inflammatory cells, and angiogenesis. Endothelial dysfunctions are associated with various cardiovascular diseases, including atherosclerosis, hypertension, myocardial infarction, and cardiovascular complications of diabetes. Numerous studies have established the anti-inflammatory, anti-apoptotic, and anti-oxidant effects of hydrogen sulfide (H2S), the latest member to join the gasotransmitter family along with nitric oxide and carbon monoxide, on vascular endothelium. In addition, H2S may prime endothelial cells (ECs) toward angiogenesis and contribute to wound healing, besides to its well-known ability to relax vascular smooth muscle cells (VSMCs), and thereby reducing blood pressure. Finally, H2S may inhibit VSMC proliferation and platelet aggregation. Consistently, a deficit in H2S homeostasis is involved in the pathogenesis of atherosclerosis and of hyperglycaemic endothelial injury. Therefore, the application of H2S-releasing drugs or using gene therapy to increase endogenous H2S level may help restore endothelial function and antagonize the progression of cardiovascular diseases. The present article reviews recent studies on the role of H2S in endothelial homeostasis, under both physiological and pathological conditions, and its putative therapeutic applications. PMID:25005182

  12. Effect of nitric oxide on the growth of Chlamydophila pneumoniae.

    PubMed

    Carratelli, Caterina Romano; Rizzo, Antonietta; Paolillo, Rossella; Catania, Maria Rosaria; Catalanotti, Piergiorgio; Rossano, Fabio

    2005-11-01

    Chlamydophila pneumoniae is an important human intracellular pathogen; however, the pathogenesis of C. pneumoniae infection is poorly understood and the immune control mechanism versus host cells is not completely known. The role of the nitric oxide (NO) synthase pathway in inhibiting the ability of C. pneumoniae to infect macrophage J774 cells and the ability of NO to damage isolated C. pneumoniae were investigated. Exposure of infected cultures to recombinant murine gamma interferon (MurIFN-gamma) resulted in increased production of NO and reduced viability. Addition of 2-(N,N-diethylamino)-diazenolase-2-oxide before infection of J774 cells or during chlamydial cultivation released NO, both resulting in a reduction in the viability of C. pneumoniae in a dose-dependent way. These results indicate that immune control of chlamydial growth in murine macrophage cells may trigger a mechanism that includes NO release with effects on the multiplication of the microorganism, thus suggesting that NO may play a role in preventing the systemic spread of Chlamydia. PMID:16333333

  13. Release of nitric oxide from building stones into the atmosphere

    NASA Astrophysics Data System (ADS)

    Baumgärtner, M.; Remde, A.; Bock, E.; Conrad, R.

    Stone material from the corroding surface of buildings generally released nitric oxide with rates of 0.42-4.2 ng NON h -1 g -1 d.w. despite their large range of moisture, pH and content of ammonium, nitrite and nitrate. The net release rates of NO were independent of the NO mixing ratio of the atmosphere up to 1 ppmv NO. Whereas NO 2 was taken up by all stones tested, uptake of NO was only observed in one out of five types of stone. NO release rates were highest at the stone surface and rapidly decreased in depth lower than 1 cm. NO release persisted for up to >3 months after the stone sample was removed from the building. NO was mainly produced during the biogenic oxidation of ammonium to nitrate at the stone surface which was probably due to endolithic nitrifying bacteria. Chemical decomposition of nitrite to NO and NO 2 was only observed under acidic conditions.

  14. Organelle-Specific Nitric Oxide Detection in Living Cells via HaloTag Protein Labeling

    PubMed Central

    Zhu, Qian; Du, Zengmin; Hu, Aiguo; Yang, Yi

    2015-01-01

    Nitric oxide (NO) is a membrane-permeable signaling molecule that is constantly produced, transferred, and consumed in vivo. NO participates and plays important roles in multiple biological processes. However, spatiotemporal imaging of NO in living cells is challenging. To fill the gap in currently used techniques, we exploited the versatility of HaloTag technology and synthesized a novel organelle-targetable fluorescent probe called HTDAF-2DA. We demonstrate the utility of the probe by monitoring subcellular NO dynamics. The developed strategy enables precise determination of local NO function. PMID:25923693

  15. Flow-Tagging Velocimetry for Hypersonic Flows Using Fluorescence of Nitric Oxide

    NASA Technical Reports Server (NTRS)

    Danehy, P. M.; OByrne, S.; Houwing, A. F. P.

    2001-01-01

    We investigate a new type of flow-tagging velocimetry technique for hypersonic flows. The technique involves exciting a thin line of nitric oxide molecules with a laser beam and then, after some delay, acquiring an image of the displaced line. One component of velocity is determined from the time of flight. This method is applied to measure the velocity profile in a Mach 8.5 laminar, hypersonic boundary layer in the Australian National Universities T2 free-piston shock tunnel. The velocity is measured with an uncertainty of approximately 2%. Comparison with a CFD simulation of the flow shows reasonable agreement.

  16. Diterpenoids from the Roots of Euphorbia fischeriana with Inhibitory Effects on Nitric Oxide Production.

    PubMed

    Lee, Jin Woo; Lee, Chul; Jin, Qinghao; Jang, Hari; Lee, Dongho; Lee, Ha-Jin; Shin, Jong Won; Han, Sang Bae; Hong, Jin Tae; Kim, Youngsoo; Lee, Mi Kyeong; Hwang, Bang Yeon

    2016-01-22

    Bioactivity-guided isolation of a methanolic extract of Euphorbia fischeriana led to the isolation of four new abietane-type diterpenoids, fischeriolides A-D (1-4), together with 11 known diterpenoids. Their structures were elucidated based on the interpretation of 1D and 2D NMR spectroscopic and HRESIMS data. The absolute configuration of compound 3 was determined by single-crystal X-ray diffraction analysis and electronic circular dichroism methods. Compounds 5-9 exhibited inhibitory effects on LPS-induced nitric oxide production in RAW 264.7 macrophages with IC50 values in the range 4.9-12.6 μM. PMID:26702644

  17. Humulene derivatives from Zingiber zerumbet with the inhibitory effects on lipopolysaccharide-induced nitric oxide production.

    PubMed

    Jang, Dae Sik; Min, Hye-Young; Kim, Moon-Sun; Han, Ah-Reum; Windono, Tri; Jeohn, Gwang-Ho; Kang, Sam Sik; Lee, Sang Kook; Seo, Eun-Kyoung

    2005-07-01

    A new humulene sesquiterpene, 5-hydroxyzerumbone (5-hydroxy-2E,6E,9E-humulatrien-8-one) (1) and a known compound, zerumboneoxide (2) were isolated from the rhizomes of Zingiber zerumbet (Zingiberaceae), and found to inhibit lipopolysaccharide-induced nitric oxide production in murine macrophage RAW 264.7 cells with IC50 values of 14.1 and 23.5 microM, respectively, by bioassay-guided fractionation (positive control: N(omega)-monomethyl-L-arginine, IC50=21.3 microM). The structure of 1 was determined by spectroscopic methods including 1D and 2D-NMR. PMID:15997145

  18. The transport of nitric oxide in the upper atmosphere by planetary waves and the zonal mean circulation

    NASA Technical Reports Server (NTRS)

    Jones, G. A.; Avery, S. K.

    1982-01-01

    A time-dependent numerical model was developed and used to study the interaction between planetary waves, the zonal mean circulation, and the trace constituent nitric oxide in the region between 55 km and 120 km. The factors which contribute to the structure of the nitric oxide distribution were examined, and the sensitivity of the distribution to changes in planetary wave amplitude was investigated. Wave-induced changes in the mean nitric oxide concentration were examined as a possible mechanism for the observed winter anomaly. Results indicate that vertically-propagating planetary waves induce a wave-like structure in the nitric oxide distribution and that at certain levels, transports of nitric oxide by planetary waves could significantly affect the mean nitric oxide distribution. The magnitude and direction of these transports at a given level was found to depend not only on the amplitude of the planetary wave, but also on the loss rate of nitric oxide at that level.

  19. Nitric oxide as a regulator of B. anthracis pathogenicity

    PubMed Central

    Popova, Taissia G.; Teunis, Allison; Vaseghi, Haley; Zhou, Weidong; Espina, Virginia; Liotta, Lance A.; Popov, Serguei G.

    2015-01-01

    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 Bacillus 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 lymphatic system. PMID:26388860

  20. Cardiovascular Consequences When Nitric Oxide and Lipid Signaling Converge

    PubMed Central

    Rudolph, Volker; Freeman, Bruce A.

    2009-01-01

    The identification of nitric oxide (•NO) as an endogenously produced free radical mediator of endothelial-dependent relaxation and host defense has fundamentally changed concepts of cell signal transduction. Ligand-receptor oriented paradigms of cell signaling were originally centered on the concept of a high affinity and specific interaction between a ligand and its receptor, resulting in the activation of secondary signaling events such as gene expression or modulation of catalytic protein function. While •NO ligation of the heme iron of soluble guanylate cyclase is consistent with this perspective, the readily diffusible and broadly reactive •NO is increasingly appreciated to react with a vast array of target molecules that mediate paracrine vasodilator actions, inhibition of thrombosis and neointimal proliferation and both pro- and anti-inflammatory signaling reactions that are not affected by inhibitors of soluble guanylate cyclase. There is an expanding array of functionally significant “off target” collateral reactions mediated by •NO that are guanylate cyclase-independent and rather are dictated by anatomic distribution and the formation of secondary •NO-derived species. These reactions are a critical element of redox-regulated signaling and are addressed herein in the context of the oxidation of unsaturated fatty acids to vascular and inflammatory signaling mediators. Because of their abundance and the intrinsic reactivity of unsaturated lipid intermediates and eicosanoid metabolism enzymes with •NO and other oxides of nitrogen, lipid signaling mechanisms are a significant target for regulation by •NO in the vascular compartment. This convergence of •NO and lipid signaling pathways thus adds another level of regulation to physiological responses such as vasodilation, thrombosis and inflammation. Herein, interactions between •NO and lipid signaling events are placed in the context of cardiovascular regulation. PMID:19745170

  1. Isolation and characterization of nitric oxide reductase from Paracoccus halodenitrificans.

    PubMed

    Sakurai, N; Sakurai, T

    1997-11-11

    Nitric oxide reductase was isolated from the membrane fraction of a denitrifying bacterium, Paracoccus halodenitrificans, in the presence of n-dodecyl beta-D-maltoside. A relatively simple and effective procedure to purify NO reductase using DEAE-Toyopearl and hydroxyapatite (ceramic) chromatographies has been developed. The enzyme consisted of two subunits with molecular masses of 20 and 42 kDa associated with the c-type heme and two b-type hemes, respectively. The optical and magnetic circular dichroism (MCD) spectra of the oxidized (as isolated) and reduced enzymes indicated that the heme c is in the low-spin state and the hemes b are in the high- and low-spin states. The EPR spectrum also showed the presence of the split high-spin component (g perpendicular = 6.6, 6.0) and two low spin components (gz,y,x = 2.96, 2.26, 1.46, gz = 3.59). Although the presence of an extra iron was suggested from atomic absorption spectroscopy, a non-heme iron could not be detected by colorimetric titrations using ferene and 2-(5-nitro-2-pyridylazo)- 5-(N-propyl-N-sulfopropylamino)phenolate (PAPS). One of the extra signals at g = 4.3 and 2.00 might come from a non-heme iron, while they may originate from an adventitious iron and a certain nonmetallic radical, respectively. When CO acted on the reduced enzyme, both of the low-spin hemes were not affected, and when NO acted on the reduced enzyme, the optical and MCD spectra were of a mixture of the oxidized and reduced enzymes. Consequently, the reduction of NO was supposed to take place at the high-spin heme b. The heme c and the low-spin heme b centers were considered to function as electron mediators during the intermolecular and intramolecular processes. PMID:9374857

  2. Nitric oxide emissions from soils amended with municipal waste biosolids

    NASA Astrophysics Data System (ADS)

    Roelle, Paul A.; Aneja, Viney P.

    Land spreading nitrogen-rich municipal waste biosolids (NO 3--N<256 mg N kg -1 dry weight, NH 3-N˜23,080 mg N kg -1 dry weight, Total Kjeldahl N˜41,700 mg N kg -1 dry weight) to human food and non-food chain land is a practice followed throughout the US. This practice may lead to the recovery and utilization of the nitrogen by vegetation, but it may also lead to emissions of biogenic nitric oxide (NO), which may enhance ozone pollution in the lower levels of the troposphere. Recent global estimates of biogenic NO emissions from soils are cited in the literature, which are based on field measurements of NO emissions from various agricultural and non-agricultural fields. However, biogenic emissions of NO from soils amended with biosolids are lacking. Utilizing a state-of-the-art mobile laboratory and a dynamic flow-through chamber system, in-situ concentrations of nitric oxide (NO) were measured during the spring/summer of 1999 and winter/spring of 2000 from an agricultural soil which is routinely amended with municipal waste biosolids. The average NO flux for the late spring/summer time period (10 June 1999-5 August 1999) was 69.4±34.9 ng N m -2 s -1. Biosolids were applied during September 1999 and the field site was sampled again during winter/spring 2000 (28 February 2000-9 March 2000), during which the average flux was 3.6±1.7 ng N m -2 s -1. The same field site was sampled again in late spring (2-9 June 2000) and the average flux was 64.8±41.0 ng N m -2 s -1. An observationally based model, developed as part of this study, found that summer accounted for 60% of the yearly emission while fall, winter and spring accounted for 20%, 4% and 16% respectively. Field experiments were conducted which indicated that the application of biosolids increases the emissions of NO and that techniques to estimate biogenic NO emissions would, on a yearly average, underestimate the NO flux from this field by a factor of 26. Soil temperature and % water filled pore space (%WFPS) were observed to be significant variables for predicting NO emissions, however %WFPS was found to be most significant during high soil temperature conditions. In the range of pH values found at this site (5.8±0.3), pH was not observed to be a significant parameter in predicting NO emissions.

  3. Association of expired nitric oxide with occupational particulate exposure.

    PubMed

    Kim, Jee Young; Wand, Matthew P; Hauser, Russ; Mukherjee, Sutapa; Herrick, Robert F; Christiani, David C

    2003-05-01

    Particulate air pollution has been associated with adverse respiratory health effects. This study assessed the utility of expired nitric oxide to detect acute airway responses to metal-containing fine particulates. Using a repeated-measures study design, we investigated the association between the fractional concentration of expired nitric oxide (F(E)NO) and exposure to particulate matter with an aerodynamic mass median diameter of less than or equal to 2.5 micro m (PM(2.5)) in boilermakers exposed to residual oil fly ash and metal fumes. Subjects were monitored for 5 days during boiler repair overhauls in 1999 (n = 20) or 2000 (n = 14). The Wilcoxon median baseline F(E)NO was 10.6 ppb [95% confidence interval (CI): 9.1, 12.7] in 1999 and 7.4 ppb (95% CI: 6.7, 8.0) in 2000. The Wilcoxon median PM(2.5) 8-hr time-weighted average was 0.56 mg/m(3) (95% CI: 0.37, 0.93) in 1999 and 0.86 mg/m(3) (95% CI: 0.65, 1.07) in 2000. F(E)NO levels during the work week were significantly lower than baseline F(E)NO in 1999 (p < 0.001). A significant inverse exposure-response relationship between log-transformed F(E)NO and the previous workday's PM(2.5) concentration was found in 1999, after adjusting for smoking status, age, and sampling year. With each 1 mg/m(3) incremental increase in PM(2.5) exposure, log F(E)NO decreased by 0.24 (95% CI: -0.38, -0.10) in 1999. The lack of an exposure-response relationship between PM(2.5) exposure and F(E)NO in 2000 could be attributable to exposure misclassification resulting from the use of respirators. In conclusion, occupational exposure to metal-containing fine particulates was associated with significant decreases in F(E)NO in a survey of workers with limited respirator usage. PMID:12727593

  4. Pharmacology and potential therapeutic applications of nitric oxide-releasing non-steroidal anti-inflammatory and related nitric oxide-donating drugs

    PubMed Central

    Keeble, J E; Moore, P K

    2002-01-01

    This review examines the biological significance, therapeutic potential and mechanism(s) of action of a range of nitric oxide-releasing non-steroidal anti-inflammatory drugs (NO-NSAID) and related nitric oxide-releasing donating drugs (NODD). The slow release of nitric oxide (NO) from these compounds leads to subtle changes in the profile of pharmacological activity of the parent, non-steroidal anti-inflammatory drugs (NSAID). For example, compared with NSAID, NO-NSAID cause markedly diminished gastrointestinal toxicity and improved anti-inflammatory and anti-nociceptive efficacy. In addition, nitroparacetamol exhibits hepatoprotection as opposed to the hepatotoxic activity of paracetamol. The possibility that NO-NSAID or NODD may be of therapeutic benefit in a wide variety of disease states including pain and inflammation, thrombosis and restenosis, neurodegenerative diseases of the central nervous system, colitis, cancer, urinary incontinence, liver disease, impotence, bronchial asthma and osteoporosis is discussed. PMID:12237248

  5. Endothelial Nitric-oxide Synthase Activation Generates an Inducible Nitric-oxide Synthase-like Output of Nitric Oxide in Inflamed Endothelium*

    PubMed Central

    Lowry, Jessica L.; Brovkovych, Viktor; Zhang, Yongkang; Skidgel, Randal A.

    2013-01-01

    High levels of NO generated in the vasculature under inflammatory conditions are usually attributed to inducible nitric-oxide synthase (iNOS), but the role of the constitutively expressed endothelial NOS (eNOS) is unclear. In normal human lung microvascular endothelial cells (HLMVEC), bradykinin (BK) activates kinin B2 receptor (B2R) signaling that results in Ca2+-dependent activation of eNOS and transient NO. In inflamed HLMVEC (pretreated with interleukin-1β and interferon-γ), we found enhanced binding of eNOS to calcium-calmodulin at basal Ca2+ levels, thereby increasing its basal activity that was dependent on extracellular l-Arg. Furthermore, B2R stimulation generated prolonged high output eNOS-derived NO that is independent of increased intracellular Ca2+ and is mediated by a novel Gαi-, MEK1/2-, and JNK1/2-dependent pathway. This high output NO stimulated with BK was blocked with a B2R antagonist, eNOS siRNA, or eNOS inhibitor but not iNOS inhibitor. Moreover, B2R-mediated NO production and JNK phosphorylation were inhibited with MEK1/2 and JNK inhibitors or MEK1/2 and JNK1/2 siRNA but not with ERK1/2 inhibitor. BK induced Ca2+-dependent eNOS phosphorylation at Ser1177, Thr495, and Ser114 in cytokine-treated HLMVEC, but these modifications were not dependent on JNK1/2 activation and were not responsible for prolonged NO output. Cytokine treatment did not alter the expression of B2R, Gαq/11, Gαi1,2, JNK, or eNOS. B2R activation in control endothelial cells enhanced migration, but in cytokine-treated HLMVEC it reduced migration. Both responses were NO-dependent. Understanding how JNK regulates prolonged eNOS-derived NO may provide new therapeutic targets for the treatment of disorders involving vascular inflammation. PMID:23255592

  6. The red-vine-leaf extract AS195 increases nitric oxide synthase-dependent nitric oxide generation and decreases oxidative stress in endothelial and red blood cells.

    PubMed

    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. PMID:26977302

  7. Disruption of endothelial peroxisome proliferator-activated receptor-? reduces vascular nitric oxide production

    PubMed Central

    Kleinhenz, Jennifer M.; Kleinhenz, Dean J.; You, Shaojin; Ritzenthaler, Jeffrey D.; Hansen, Jason M.; Archer, David R.; Sutliff, Roy L.

    2009-01-01

    Vascular endothelial cells express the ligand-activated transcription factor, peroxisome proliferator-activated receptor-? (PPAR?), which participates in the regulation of metabolism, cell proliferation, and inflammation. PPAR? ligands attenuate, whereas the loss of function mutations in PPAR? stimulate, endothelial dysfunction, suggesting that PPAR? may regulate vascular endothelial nitric oxide production. To explore the role of endothelial PPAR? in the regulation of vascular nitric oxide production in vivo, mice expressing Cre recombinase driven by an endothelial-specific promoter were crossed with mice carrying a floxed PPAR? gene to produce endothelial PPAR? null mice (ePPAR??/?). When compared with littermate controls, ePPAR??/? animals were hypertensive at baseline and demonstrated comparable increases in systolic blood pressure in response to angiotensin II infusion. When compared with those of control animals, aortic ring relaxation responses to acetylcholine were impaired, whereas relaxation responses to sodium nitroprusside were unaffected in ePPAR??/? mice. Similarly, intact aortic segments from ePPAR??/? mice released less nitric oxide than those from controls, whereas endothelial nitric oxide synthase expression was similar in control and ePPAR??/? aortas. Reduced nitric oxide production in ePPAR??/? aortas was associated with an increase in the parameters of oxidative stress in the blood and the activation of nuclear factor-?B in aortic homogenates. These findings demonstrate that endothelial PPAR? regulates vascular nitric oxide production and that the disruption of endothelial PPAR? contributes to endothelial dysfunction in vivo. PMID:19666848

  8. Disruption of endothelial peroxisome proliferator-activated receptor-gamma reduces vascular nitric oxide production.

    PubMed

    Kleinhenz, Jennifer M; Kleinhenz, Dean J; You, Shaojin; Ritzenthaler, Jeffrey D; Hansen, Jason M; Archer, David R; Sutliff, Roy L; Hart, C Michael

    2009-11-01

    Vascular endothelial cells express the ligand-activated transcription factor, peroxisome proliferator-activated receptor-gamma (PPARgamma), which participates in the regulation of metabolism, cell proliferation, and inflammation. PPARgamma ligands attenuate, whereas the loss of function mutations in PPARgamma stimulate, endothelial dysfunction, suggesting that PPARgamma may regulate vascular endothelial nitric oxide production. To explore the role of endothelial PPARgamma in the regulation of vascular nitric oxide production in vivo, mice expressing Cre recombinase driven by an endothelial-specific promoter were crossed with mice carrying a floxed PPARgamma gene to produce endothelial PPARgamma null mice (ePPARgamma(-/-)). When compared with littermate controls, ePPARgamma(-/-) animals were hypertensive at baseline and demonstrated comparable increases in systolic blood pressure in response to angiotensin II infusion. When compared with those of control animals, aortic ring relaxation responses to acetylcholine were impaired, whereas relaxation responses to sodium nitroprusside were unaffected in ePPARgamma(-/-) mice. Similarly, intact aortic segments from ePPARgamma(-/-) mice released less nitric oxide than those from controls, whereas endothelial nitric oxide synthase expression was similar in control and ePPARgamma(-/-) aortas. Reduced nitric oxide production in ePPARgamma(-/-) aortas was associated with an increase in the parameters of oxidative stress in the blood and the activation of nuclear factor-kappaB in aortic homogenates. These findings demonstrate that endothelial PPARgamma regulates vascular nitric oxide production and that the disruption of endothelial PPARgamma contributes to endothelial dysfunction in vivo. PMID:19666848

  9. The effect of nitric oxide on the growth of marine phytoplankton

    NASA Astrophysics Data System (ADS)

    Zhengbin, Zhang; Cai, Lin; Chunying, Liu; Mingyi, Sun; Haibing, Ding

    2003-10-01

    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 growth 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.

  10. Inhibition of nitric oxide synthase does not alter ocular dominance shifts in kitten visual cortex.

    PubMed Central

    Reid, S N; Daw, N W; Czepita, D; Flavin, H J; Sessa, W C

    1996-01-01

    1. Since nitric oxide has been proposed as a feedback factor in plasticity in the hippocampus, we tested whether it might also be a feedback factor in sensory-dependent plasticity in the cat visual cortex. 2. The effects of monocular deprivation were compared between eight hemispheres with infusion of a nitric oxide synthase inhibitor, and eight control hemispheres with either infusion of the inactive isomer, or no infusion. Although nitric oxide synthase activity was reduced significantly, the ocular dominance histograms were not substantially different in the two groups of animals. We conclude that the feedback factor for sensory-dependent plasticity in the visual cortex is likely to be some factor other than nitric oxide. Images Figure 1 Figure 2 PMID:8842008

  11. Activation of CFTR chloride current by nitric oxide in human T lymphocytes.

    PubMed Central

    Dong, Y J; Chao, A C; Kouyama, K; Hsu, Y P; Bocian, R C; Moss, R B; Gardner, P

    1995-01-01

    Nitric oxide, which is produced by cytokine-activated mononuclear cells, is thought to play an important role in inflammation and immunity. While the function of nitric oxide as a direct cytotoxic effector molecule is well established, its function as a transducer molecule in immune cells is not. By use of whole-cell patch clamp recordings, we show that nitric oxide activates cystic fibrosis transmembrane conductance regulator CI- currents in normal human cloned T cells by a cGMP-dependent mechanism. This pathway is defective in cystic fibrosis-derived human cloned T cells. These findings not only delineate a novel transduction mechanism for nitric oxide but also support the hypothesis that an intrinsic immune defect may exist in cystic fibrosis. PMID:7540975

  12. EXAMINING THE TEMPORAL VARIABILITY OF AMMONIA AND NITRIC OXIDE EMISSIONS FROM AGRICULTURAL PROCESSES

    EPA Science Inventory

    This paper examines the temporal variability of airborne emissions of ammonia from livestock operations and fertilizer application and nitric oxide from soils. In the United States, the livestock operations and fertilizer categories comprise the majority of the ammonia emissions...

  13. Thalidomide ameliorates portal hypertension via nitric oxide synthase independent reduced systolic blood pressure

    PubMed Central

    Theodorakis, Nicholas G; Wang, Yining N; Korshunov, Vyacheslav A; Maluccio, Mary A; Skill, Nicholas J

    2015-01-01

    AIM: Portal hypertension is a common complication of liver cirrhosis and significantly increases mortality and morbidity. Previous reports have suggested that the compound thalidomide attenuates portal hypertension (PHT). However, the mechanism for this action is not fully elucidated. One hypothesis is that thalidomide destabilizes tumor necrosis factor α (TNFα) mRNA and therefore diminishes TNFα induction of nitric oxide synthase (NOS) and the production of nitric oxide (NO). To examine this hypothesis, we utilized the murine partial portal vein ligation (PVL) PHT model in combination with endothelial or inducible NOS isoform gene knockout mice. METHODS: Wild type, inducible nitric oxide synthase (iNOS)-/- and endothelial nitric oxide synthase (eNOS)-/- mice received either PVL or sham surgery and were given either thalidomide or vehicle. Serum nitrate (total nitrate, NOx) was measured daily for 7 d as a surrogate of NO synthesis. Serum TNFα level was quantified by enzyme-linked immunosorbent assay. TNFα mRNA was quantified in liver and aorta tissue by reverse transcription-polymerase chain reaction. PHT was determined by recording splenic pulp pressure (SPP) and abdominal aortic flow after 0-7 d. Response to thalidomide was determined by measurement of SPP and mean arterial pressure (MAP). RESULTS: SPP, abdominal aortic flow (Qao) and plasma NOx were increased in wild type and iNOS-/- PVL mice when compared to sham operated control mice. In contrast, SPP, Qao and plasma NOx were not increased in eNOS-/- PVL mice when compared to sham controls. Serum TNFα level in both sham and PVL mice was below the detection limit of the commercial ELISA used. Therefore, the effect of thalidomide on serum TNFα levels was undetermined in wild type, eNOS-/- or iNOS-/- mice. Thalidomide acutely increased plasma NOx in wild type and eNOS-/- mice but not iNOS-/- mice. Moreover, thalidomide temporarily (0-90 min) decreased mean arterial pressure, SPP and Qao in wild type, eNOS-/- and iNOS-/- PVL mice, after which time levels returned to the respective baseline. CONCLUSION: Thalidomide does not reduce portal pressure in the murine PVL model by modulation of NO biosynthesis. Rather, thalidomide reduces PHT by decreasing MAP by an undetermined mechanism. PMID:25892862

  14. Fructose diphosphate attenuates the acetaminophen-induced liver injury in the rat evidence for involvement of nitric oxide.

    PubMed

    Mihas, Anastasios A; Kanji, Vijaya K; Mihas, Thanos A; Joseph, Roy M; Markov, Angel K; Heuman, Douglas M

    2003-01-01

    We have previously shown that fructose-1,6-diphosphate (FDP) stimulates the synthesis of nitric oxide probably by stimulating the hepatic inducible nitric oxide synthase (iNOS). The aim of the present study was to evaluate the hepatoprotective role of FDP in acetaminophen-induced liver injury and whether this hepatoprotective effect is mediated by nitric oxide. Liver injury was induced in adult Sprague-Dawley rats by the administration of acetaminophen (1.6 g/kg by gavage) 10 min prior to the intraperitoneal injection of either FDP or normal saline. Liver injury was assessed by alanine aminotransferase (ALT) activity in the serum. iNOS and malondialdehyde (MDA) levels were determined in liver homogenates. Acetaminophen produced striking elevations of serum ALT, high MDA levels and a profound decrease in the liver iNOS. Administration of FDP attenuated the ALT and MDA elevations and prevented the liver iNOS depletion caused by acetaminophen. Pretreatment of the animals with the iNOS inhibitor L-NAME abolished this hepatoprotection. These findings suggest that FDP protects against acetaminophen-induced liver injury, at least partly, by stimulating production of nitric oxide. PMID:15686124

  15. Oxygen Effects on Thermophilic Microbial Populations in Biofilters Treating Nitric Oxide Containing Off-Gas Streams

    SciTech Connect

    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.

  16. Matrix metalloproteinases in atherosclerosis: role of nitric oxide, hydrogen sulfide, homocysteine, and polymorphisms

    PubMed Central

    Vacek, Thomas P; Rehman, Shahnaz; Neamtu, Diana; Yu, Shipeng; Givimani, Srikanth; Tyagi, Suresh C

    2015-01-01

    Atherosclerosis is an inflammatory process that involves activation of matrix metalloproteinases (MMPs); MMPs degrade collagen and allow for smooth-muscle cell migration within a vessel. Moreover, this begets an accumulation of other cellular material, resulting in occlusion of the vessel and ischemic events to tissues in need of nutrients. Homocysteine has been shown to activate MMPs via an increase in oxidative stress and acting as a signaling molecule on receptors like the peroxisome proliferator activated receptor-γ and N-methyl-D-aspartate receptor. Nitric oxide has been shown to be beneficial in some cases of deactivating MMPs. However, in other cases, it has been shown to be harmful. Further studies are warranted on the scenarios that are beneficial versus destructive. Hydrogen sulfide (H2S) has been shown to decrease MMP activities in all cases in the literature by acting as an antioxidant and vasodilator. Various MMP-knockout and gene-silencing models have been used to determine the function of the many different MMPs. This has allowed us to discern the role that each MMP has in promoting or alleviating pathological conditions. Furthermore, there has been some study into the MMP polymorphisms that exist in the population. The purpose of this review is to examine the role of MMPs and their polymorphisms on the development of atherosclerosis, with emphasis placed on pathways that involve nitric oxide, hydrogen sulfide, and homocysteine. PMID:25767394

  17. Is there a relationship between endothelial nitric oxide synthase gene polymorphisms and ankylosing spondylitis?

    PubMed Central

    Sari, Ismail; Igci, Yusuf Ziya; Can, Gercek; Taylan, Ali; Solmaz, Dilek; Gogebakan, Bulent; Akar, Servet; Eslik, Zeynep; Bozkaya, Giray; Akkoc, Nurullah

    2013-01-01

    OBJECTIVE: Nitric oxide is produced by endothelial nitric oxide synthase, and its production can be influenced by polymorphisms of the endothelial nitric oxide synthase gene. Because candidate genes responsible for susceptibility to ankylosing spondylitis are mostly unknown and available data suggest that there may be problems related to the nitric oxide pathway, such as endothelial dysfunction and increased asymmetric dimethylarginine, this study aimed to assess the association of common endothelial nitric oxide synthase gene polymorphisms with ankylosing spondylitis. METHODS: One hundred ninety-four unrelated Turkish ankylosing spondylitis patients and 113 healthy without apparent cardiovascular disease, hypertension or diabetes mellitus were included. All individuals were genotyped by PCR-RFLP for two single-nucleotide polymorphisms, namely 786T>C (rs2070744, promoter region) and 786 Glu298Asp (rs1799983, exon 7). Variable numbers of tandem repeat polymorphisms in intron 4 were also studied and investigated by direct electrophoresis on agarose gel following polymerase chain reaction analysis. The Bath ankylosing spondylitis metrology index of the patients was calculated, and human leukocyte antigen B27 was studied. RESULTS: All studied polymorphisms satisfied Hardy-Weinberg equilibrium. Sex distributions were similar between the patient and control groups. No significant differences were found in the distributions of allele and genotype frequencies of the studied endothelial nitric oxide synthase polymorphisms between patients and controls. There were no correlations between endothelial nitric oxide synthase polymorphisms, disease duration, Bath ankylosing spondylitis metrology index or human leukocyte antigen B27. CONCLUSION: The results presented in this study do not support a major role of common endothelial nitric oxide synthase polymorphisms in Turkish ankylosing spondylitis patients. PMID:23644848

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

    PubMed Central

    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

  19. Nitrite inhibition of Clostridium botulinum: electron spin resonance detection of iron-nitric oxide complexes.

    PubMed

    Reddy, D; Lancaster, J R; Cornforth, D P

    1983-08-19

    Vegetative cells of Clostridium botulinum were shown to contain iron-sulfur proteins that react with added nitrite to form iron-nitric oxide complexes, with resultant destruction of the iron-sulfur cluster. Inactivation of iron-sulfur enzymes (especially ferredoxin) by binding of nitric oxide would almost certainly inhibit growth, and thus is probably the mechanism of botulinal inhibition by nitrite in foods. PMID:6308761

  20. The reaction of hydrogen peroxide with nitrogen dioxide and nitric oxide.

    NASA Technical Reports Server (NTRS)

    Gray, D.; Lissi, E.; Heicklen, J.

    1972-01-01

    The reactions were studied with the aid of a mass spectrometer. A pinhole bleed system provided continuous sampling of the gas mixture in the cell during the reaction. It was found that the homogeneous reactions of nitric oxide and nitrogen dioxide with hydrogen peroxide are too slow to be of any significance in the upper atmosphere. However, the heterogeneous reactions may be important in the conversion of nitric oxide to nitrogen dioxide in the case of polluted urban atmospheres.

  1. Structure-based design of bacterial nitric oxide synthase inhibitors.

    PubMed

    Holden, Jeffrey K; Kang, Soosung; Hollingsworth, Scott A; Li, Huiying; Lim, Nathan; Chen, Steven; Huang, He; Xue, Fengtian; Tang, Wei; Silverman, Richard B; Poulos, Thomas L

    2015-01-22

    Inhibition of bacterial nitric oxide synthase (bNOS) has the potential to improve the efficacy of antimicrobials used to treat infections by Gram-positive pathogens Staphylococcus aureus and Bacillus anthracis. However, inhibitor specificity toward bNOS over the mammalian NOS (mNOS) isoforms remains a challenge because of the near identical NOS active sites. One key structural difference between the NOS isoforms is the amino acid composition of the pterin cofactor binding site that is adjacent to the NOS active site. Previously, we demonstrated that a NOS inhibitor targeting both the active and pterin sites was potent and functioned as an antimicrobial ( Holden , , Proc. Natl. Acad. Sci. U.S.A. 2013 , 110 , 18127 ). Here we present additional crystal structures, binding analyses, and bacterial killing studies of inhibitors that target both the active and pterin sites of a bNOS and function as antimicrobials. Together, these data provide a framework for continued development of bNOS inhibitors, as each molecule represents an excellent chemical scaffold for the design of isoform selective bNOS inhibitors. PMID:25522110

  2. Asenapine modulates nitric oxide release and calcium movements in cardiomyoblasts

    PubMed Central

    Grossini, Elena; Gramaglia, Carla; Farruggio, Serena; Camillo, Lara; Mary, David; Vacca, Giovanni; Zeppegno, Patrizia

    2016-01-01

    Objective: To examine the effects of asenapine on nitric oxide (NO) release and Ca2+ transients in H9C2 cell line, which were either subjected to peroxidation or not. Materials and Methods: H9C2 were treated with asenapine alone or in presence of intracellular kinase blockers, serotoninergic and dopaminergic antagonists, and voltage Ca2+ channels inhibitors. Experiments were also performed in H9C2 treated with hydrogen peroxide. NO release and intracellular Ca2+ were measured through specific probes. Results: In H9C2, asenapine differently modulated NO release and Ca2+ movements depending on peroxidative condition. The Ca2+ pool mobilized by asenapine mainly originated from the extracellular space and was slightly affected by thapsigargin. Moreover, the effects of asenapine were reduced or prevented by kinases blockers, dopaminergic and serotoninergic receptors inhibitors, and voltage Ca2+ channels blockers. Conclusions: On the basis of our findings, we can conclude that asenapine by interacting with its specific receptors, exerts dual effects on NO release and Ca2+ homeostasis in H9C2; this would be of particular clinical relevance when considering their role in cardiac function modulation.

  3. Local-time Variation of Nitric Oxide: Modeling and Observations

    NASA Astrophysics Data System (ADS)

    Lin, C. Y. T.; Bailey, S. M.; Yonker, J. D.; Venkataramani, K.; Deng, Y.

    2014-12-01

    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. Solar soft X-ray energy between 0.1 and 7 nm is absorbed mostly in the lower thermosphere between 100 and 150 km. Photoelectrons are created and initiate chains of photochemical reactions which leads to the production of nitric oxide (NO). On the other hand, solar irradiance longer than 150 nm destroys NO. In this study, observation of the local-time variation of NO abundance in the lower thermosphere is derived from the Remote Atmospheric and Ionospheric Detection System (RAIDS) measurements in summer 2010. Soft X-ray and EUV irradiance from the Extreme ultraviolet Variability Experiment (EVE) on the Solar Dynamic Observatory (SDO) is used to drive the NOx1D model during the same period of time. By comparing variation of NO abundance at local sunlit hours, the effects of solar irradiance on thermospheric NO photochemistry in the model are examined.

  4. Why is nitric oxide important for our brain?

    PubMed Central

    Džoljić, Eleonora; Grabatinić, Ivan; Kostić, Vladimir

    2015-01-01

    Summary The freely diffusible gaseous compound nitric oxide (NO) has been shown to be an important messenger in many organ systems throughout the body, and particularly in the central nervous system (CNS). The importance of NO as an intermediary in cell communication in the brain is highlighted by the fact that the excitatory amino acid glutamate, the most abundant CNS neurotransmitter, is an initiator of the reaction that forms NO. Because of its numerous physiological and pathophysiological roles, the impact of NO on clinical medicine is developing. NO can act as a “double-edged sword” and it has been demonstrated that clarification of the dual effect of NO might have implications for clinical medicine, and could lead to the emergence of therapeutic opportunities. Accordingly, NO was proclaimed “Mole cule of the Year” in 1992 by the journal Science, while discovery of the pathways and roles of NO was acknowledged with the Nobel Prize in 1998. Additionally, the ubiquity of NO in the CNS implies that drugs designed to modify the biological activity of NO may have distinct effects. Thus, further clinical applications of NO, of its analogs or of newly developed NOS inhibitors are forthcoming. The therapeutic challenge would be to succeed in manipulating the NO pathways selectively. PMID:26910176

  5. High correlations between temperature and nitric oxide in the thermosphere

    NASA Astrophysics Data System (ADS)

    Weimer, D. R.; Mlynczak, M. G.; Hunt, L. A.; Tobiska, W. Kent

    2015-07-01

    Obtaining accurate predictions of the neutral density in the thermosphere has been a long-standing problem. During geomagnetic storms the auroral heating in the polar ionospheres quickly raises the temperature of the thermosphere, resulting in higher neutral densities that exert a greater drag force on objects in low Earth orbit. Rapid increases and decreases in the temperature and density may occur within a couple days. A key parameter in the thermosphere is the total amount of nitric oxide (NO). The production of NO is accelerated by the auroral heating, and since NO is an efficient radiator of thermal energy, higher concentrations of this molecule accelerate the rate at which the thermosphere cools. This paper describes an improved technique that calculates changes in the global temperature of the thermosphere. Starting from an empirical model of the Poynting flux into the ionosphere, a set of differential equations derives the minimum, global value of the exospheric temperature, which can be used in a neutral density model to calculate the global values. The relative variations in NO content are used to obtain more accurate cooling rates. Comparisons with the global rate of NO emissions that are measured with the Sounding of the Atmosphere using Broadband Emission Radiometry instrument show that there is very good agreement with the predicted values. The NO emissions correlate highly with the total auroral heating that has been integrated over time. We also show that the NO emissions are highly correlated with thermospheric temperature, as well as indices of solar extreme ultraviolet radiation.

  6. Combination of complex adsorption and anammox for nitric oxide removal.

    PubMed

    Wang, Xiaojing; Xu, Xiaochen; Liu, Sitong; Zhang, Yun; Zhao, Chuanqi; Yang, Fenglin

    2016-07-15

    High-efficiency Fe(II)EDTA (approximately 80%) was selected to remove nitric oxide (NO) in a complex adsorption process; subsequently, this Fe(II)EDTA was combined with the anammox process to eliminate the NO in flue gas. The Fe(II)EDTA-NO solution negatively affected the conventional nitrite-dependent anammox bacteria when the solution concentration exceeded 0.5mM. Fe(II)EDTA-NO-cultivated anammox bacteria removed the ammonium coupled to complex NO reduction (≤3.5mM). The batch test results demonstrated that NH4(+) was eliminated through Fe(II)EDTA-NO reduction via anammox. The removal of complex NO and NH4(+) exhibited high relativity relevance, and the Fe(II)EDTA-NO/NH4(+) molar ratio was approximately 0.97. The complex NO-dependent process generates lesser nitrate than that generated by conventional anammox. Moreover, Candidatus Kuenenia stuttgartiensitiensis became the dominant anammox bacterial community when the biomass is cultivated using the inoculated bacteria, and the proportion of the former increased to 90% from the initial 38% for ribosomal intergenic spacer analysis and library construction. PMID:27037471

  7. Cloricromene inhibits the induction of nitric oxide synthase.

    PubMed

    Zingarelli, B; Carnuccio, R; Di Rosa, M

    1993-10-19

    The effect of cloricromene, a coumarin derivative, was investigated on the lipopolysaccharide-stimulated nitric oxide (NO) synthase induction in intact aortas from endotoxin shocked rats and in the murine macrophage cell line J774. Rings of thoracic aortas from lipopolysaccharide (4 mg/kg, i.v.)-shocked rats, contracted with phenylephrine, showed a progressive decrease in tone, that was of a greater magnitude than that of aortas from naive rats. Moreover, a decreased response to the constrictor effect of phenylephrine was observed in aortas from shocked rats. In vivo treatment with cloricromene (2 mg/kg, i.v.) 30 min before lipopolysaccharide administration partially prevented the loss in tone of aortic rings and improved their reactivity to phenylephrine. Murine J774 macrophages activated with lipopolysaccharide (100 ng/ml) produced significant amounts of nitrites (NO2-; 28.2 +/- 3.5 nmol/10(6) cells per 24 h). Cloricromene (2, 20 or 200 microM) added to the cells concomitantly with lipopolysaccharide inhibited NO2- production in a concentration-dependent manner. Maximum inhibition (84.0 +/- 8.0%) was observed when cloricromene (200 microM) was added to the cells 6 h before lipopolysaccharide, whereas it was ineffective when given 6 h after endotoxin. These results demonstrate that cloricromene inhibits the expression but not the activity of the inducible NO synthase. PMID:7506214

  8. Nitric oxide in the middle to upper thermosphere

    SciTech Connect

    Siskind, D.E. ); Rusch, D.W. )

    1992-03-01

    The authors review the results of six rocket of thermospheric nitric oxide and attempt to reconcile them with the available laboratory photochemical data. Specifically, they assess the impact of the recently revised recommendation for the N({sup S}) + O{sub 2} rate coefficient on photochemical models. Use of the new rate coefficient lead to a significantly enhanced production of NO, particularly at F region altitudes during solar maximum conditions. A comparison of photochemical calculations with the rocket profiles indicates that the new rate coefficient introduces a significant discrepancy which can be resolved if the recombination reaction of N + NO is temperature dependent. The best fit value for the N + NO rate coefficient at thermospheric temperatures is 1.6 {times} 10{sup {minus}10} exp ({minus}(460 {plus minus} 60)T). The temperature dependence of this rate coefficient disagrees with the current recommendation from the Jet Propulsion Laboratory, but it is in better agreement with another, earlier laboratory measurement. Calculations using the proposed rate coefficient predict the NO solar cycle variation at 180 m to be less than at 140 km which is also in agreement with the observations. It is likely that the use of these new rate coefficients will affect calculations of the thermal budget of the upper atmosphere as well as the downward transport of NO into the middle atmosphere.

  9. Origin and Impact of Nitric Oxide in Pseudomonas aeruginosa Biofilms.

    PubMed

    Cutruzzolà, Francesca; Frankenberg-Dinkel, Nicole

    2016-01-01

    The formation of the organized bacterial community called biofilm is a crucial event in bacterial physiology. Given that biofilms are often refractory to antibiotics and disinfectants to which planktonic bacteria are susceptible, their formation is also an industrially and medically relevant issue. Pseudomonas aeruginosa, a well-known human pathogen causing acute and chronic infections, is considered a model organism to study biofilms. A large number of environmental cues control biofilm dynamics in bacterial cells. In particular, the dispersal of individual cells from the biofilm requires metabolic and morphological reprogramming in which the second messenger bis-(3′-5′)-cyclic dimeric GMP (c-di-GMP) plays a central role. The diatomic gas nitric oxide (NO), a well-known signaling molecule in both prokaryotes and eukaryotes, is able to induce the dispersal of P. aeruginosa and other bacterial biofilms by lowering c-di-GMP levels. In this review, we summarize the current knowledge on the molecular mechanisms connecting NO sensing to the activation of c-di-GMP-specific phosphodiesterases in P. aeruginosa, ultimately leading to c-di-GMP decrease and biofilm dispersal. PMID:26260455

  10. EXHALED NITRIC OXIDE IN THE DIAGNOSIS AND MANAGEMENT OF ASTHMA

    PubMed Central

    Rodway, George W.; Choi, JiYeon; Hoffman, Leslie A.; Sethi, Jigme M.

    2009-01-01

    Exhaled nitric oxide (eNO) utilized as an aid to the diagnosis and management of lung disease is receiving attention from pulmonary researchers and clinicians alike because it offers a noninvasive means to directly monitor airway inflammation. Research evidence suggests that eNO levels significantly increase in individuals with asthma prior to diagnosis, decrease with inhaled corticosteroid administration, and correlate with the number of eosinophils in induced sputum. These observations have been used to support an association between eNO levels and airway inflammation. This review presents an update on current opportunities regarding use of eNO in patient care, and more specifically, on its potential usage for asthma diagnosis and monitoring. The review will also discuss factors that may complicate use of eNO as a diagnostic tool, including changes in disease severity, symptom response, and technical measurement issues. Regardless of the rapid, convenient, and noninvasive nature of this test, additional well-designed, long-term longitudinal studies are necessary to fully evaluate the clinical utility of eNO in asthma management. PMID:19176709

  11. Role of wheat trHb in nitric oxide scavenging.

    PubMed

    Kim, Dae Yeon; Hong, Min Jeong; Seo, Yong Weon

    2014-09-01

    We examined the role of wheat truncated-hemoglobin (TatrHb) in nitric oxide (NO) scavenging in transgenic Arabidopsis plants by assessing the response to an NO donor/scavenger and salt stress. The degree of increase in Na(+) and decrease in K(+) levels in the transgenic plants were more than those in the wild-type plants, and the ratio of Na(+) to K(+) increased in the transgenic plants under salt stress. Endogenous NO increased dramatically in the salt-treated wild-type plants but not in the transgenic plants. Additionally, the maximum photosystem II quantum ratio of variable to maximum fluorescence (Fv/Fm) in transgenic plants decreased more significantly than that in the wild-type plants, indicating that the transgenic plants suffered more severe photosynthetic damage because of salt stress than that by the wild type. Similar results were observed in germination experiments by using Murashige and Skoog media containing 100 mM sodium chloride. The Fv/Fm decreased in the leaves of salt-treated transgenic plants, indicating that transgenic seeds were more sensitive to salt stress than that by the wild-type seeds. In addition, the negative effect on seed germination was more severe in transgenic plants than in the wild types under NaCl treatment conditions. The results support the hypothesis that plant trHb shares NO scavenging functions and characteristics with bacterial trHb. PMID:24981925

  12. Nitric oxide: a multitasked signaling gas in plants.

    PubMed

    Domingos, Patricia; Prado, Ana Margarida; Wong, Aloysius; Gehring, Christoph; Feijo, Jose A

    2015-04-01

    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 Ca(2+) 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. PMID:25680232

  13. Measurement of nitric oxide in human exhaled breath

    SciTech Connect

    Gordon, S.M.; Spicer, C.W.; Ollison, W.M.

    1997-12-31

    This project was initiated to confirm the reliability of nitric oxide (NO) measurement in the breath matrix, using two different analytical techniques - ozone and luminol chemiluminescence - and to corroborate literature reports of elevated breath NO values. To measure peak oral and nasal NO levels, subjects performed slow vital capacity and breath holding maneuvers directly into the monitors through the mouth and the nose, respectively. Additional measurements were made using normal breathing techniques. Initial interferent tests indicate that measured NO signals are real and are not confounded by measurement artifacts. Similar results were obtained using the two independent analytical methods in dry or humid air. The NO signal was unaffected by maximum concentrations of potential breath interferents, such as sulfur compounds and alkenes. The measured breath NO concentrations were greater than typical room air levels and differed significantly with the breathing technique used. During these tests room air averaged 4-5 ppb NO. Peak oral NO levels were 4.3 {+-} 1.5 ppb during a slow vital capacity maneuver and 8.0 {+-} 5.0 ppb during a breath holding maneuver. By contrast, higher peak nasal NO levels were measured for both slow vital capacity (17.8 {+-} 7.8 ppb) and breath holding maneuvers (45.4 {+-} 29.5 ppb).

  14. Gender Bias in Gastroparesis: Is Nitric Oxide the Answer?

    PubMed Central

    Sekhar, K. R.; Mukhopadhyay, S.

    2011-01-01

    Accumulating evidence suggests that gender-related differences are prominent in gastric motility functions in both health and disease. Women are more susceptible to gastroparesis than men. Though the mechanism(s) involved are not fully understood, impairment of the nitrergic system is one of the main factors responsible for the disease. Uncoupling of neuronal nitric oxide synthase (nNOS) causes a decreased synthesis of NO leading to a reduction in smooth muscle relaxation. Tetrahydrobiopterin (BH4) (an essential cofactor for nNOS) is a key regulator of nNOS activity for stomach dysfunction and gastroparesis. In addition, BH4 has been shown to be a potent antioxidant and anti-inflammatory agent. Well established by results from our laboratory, a diminished intracellular (BH4:total biopterin) ratio in diabetic female rats significantly impairs nNOS activity and function. Recent research has been focused on BH4 biosynthesis and gastroparesis because reduced BH4 cofactor levels can alter the production of NO by nNOS. Researchers are now paying more attention to the possibility of using BH4 as a therapeutic strategy in gastroparesis. The purpose of this review is to provide an overview of the regulation and function of nNOS by sex hormones and BH4 and its potential role in the treatment of gastroparesis. PMID:21559738

  15. Estimation of salivary nitric oxide in oral precancer patients.

    PubMed

    Metgud, R; Anandani, C; Singh, K

    2015-05-01

    The role of nitric oxide (NO) in the initiation, promotion and progression of cancer has been the subject of speculation and conflicting reports in the literature. The high incidence of oral cancer and precancer has been linked to tobacco chewing and smoking habits; NO is considered an indicator of tobacco-related diseases. We compared salivary NO levels in oral precancer and normal patients. Unstimulated whole saliva was collected from 15 patients with oral precancer (group 1) and 15 healthy age and sex matched subjects (group 2). Salivary nitrite levels were estimated using a colorimetric method and a spectrophotometer. The salivary nitrite concentration of group 2 (median = 4.21 ?g/ml) was significantly less than for group 1 (median = 12.91 ?g/ml). We have added evidence concerning involvement of NO in the pathogenesis of oral cancer, but whether it is a potentially carcinogenic agent at the concentration at which it is present in oral precancer patients requires further evaluation. PMID:25831210

  16. Nitric oxide cycle in mammals and the cyclicity principle.

    PubMed

    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. PMID:11970729

  17. Exhaled nitric oxide concentration upon acute exposure to moderate altitude.

    PubMed

    Caspersen, C; Stang, J; Thorsen, E; Stensrud, T

    2013-03-01

    The purpose of this study was to assess immediate changes in the partial pressure of nitric oxide (NO) in exhaled gas (PE NO ) in healthy trained subjects who were acutely exposed to moderate altitude. One group of nine and another group of 20 healthy subjects were exposed to an ambient pressure of 728 hPa (546 mmHg) corresponding to an altitude of 2800 m for 5 and 90 min, respectively, in an altitude chamber. PE NO was measured offline by sampling exhaled gas in tight metal foil bags at 5, 30, 60, and 90 min. A correction for increased expiratory flow rate due to gas density effects at altitude was performed (PE NO corr). PE NO was significantly decreased by 13-16%, while the fraction of NO in exhaled gas (FE NO) was increased by 16-19% compared to sea level. There was no significant change in PE NO corr after exposure to altitude for 5, 30, 60, and 90 min. We conclude that there was no change in PENO upon arrival at altitude after correcting for gas density effects on expiratory flow rate. Corrections for altitude effects must be done before comparing measurements performed at different altitudes when using measurements of FENO to monitor athletes who have asthma during training at altitude. PMID:23157566

  18. REGULATION OF OBESITY AND INSULIN RESISTANCE BY NITRIC OXIDE

    PubMed Central

    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

  19. Regulation of oxygen distribution in tissues by endothelial nitric oxide.

    PubMed

    Victor, Victor M; Nuez, Cristina; D'Ocn, Pilar; Taylor, Cormac T; Esplugues, Juan V; Moncada, Salvador

    2009-05-22

    Nitric oxide (NO) decreases cellular oxygen (O(2)) consumption by competitively inhibiting cytochrome c oxidase. Here, we show that endogenously released endothelial NO, either basal or stimulated, can modulate O(2) consumption both throughout the thickness of conductance vessels and in the microcirculation. Furthermore, we have shown that such modulation regulates O(2) distribution to the surrounding tissues. We have demonstrated these effects by measuring O(2) consumption in blood vessels in a hypoxic chamber and O(2) distribution in the microcirculation using the fluorescent oxygen-probe Ru(phen)(3)(2+). Removal of NO by physical or pharmacological means, or in eNOS(-/-) mice, abolishes this regulatory mechanism. Our results indicate that, in addition to its well-known effect on the regulation of vascular tone, endothelial NO plays a major role in facilitating the distribution of O(2), an action which is crucial for the adaptation of tissues, including the vessel wall itself, to hypoxia. It is possible that changes in the distribution of O(2) throughout the vessel wall may be implicated in the origin of vascular pathologies such as atherosclerosis. PMID:19407240

  20. Electrospun nitric oxide releasing bandage with enhanced wound healing.

    PubMed

    Lowe, A; Bills, J; Verma, R; Lavery, L; Davis, K; Balkus, K J

    2015-02-01

    Research has shown that nitric oxide (NO) enhances wound healing. The incorporation of NO into polymers for medical materials and surgical devices has potential benefits for many wound healing applications. In this work, acrylonitrile (AN)-based terpolymers were electrospun to form non-woven sheets of bandage or wound dressing type materials. NO is bound to the polymer backbone via the formation of a diazeniumdiolate group. In a 14 day NO release study, the dressings released 79 μmol NO g(-1) polymer. The NO-loaded dressings were tested for NO release in vivo, which demonstrate upregulation of NO-inducible genes with dressing application compared to empty dressings. Studies were also conducted to evaluate healing progression in wounds with dressing application performed weekly and daily. In two separate studies, excisional wounds were created on the dorsa of 10 mice. Dressings with NO loaded on the fibers or empty controls were applied to the wounds and measurements of the wound area were taken at each dressing change. The data show significantly enhanced healing progression in the wounds with weekly NO application, which is more dramatic with daily application. Further, the application of daily NO bandages results in improved wound vascularity. These data demonstrate the potential for this novel NO-releasing dressing as a valid wound healing therapy. PMID:25463501

  1. Effect of Electrode Configuration on Nitric Oxide Gas Sensor Behavior

    PubMed Central

    Cui, Ling; Murray, Erica P.

    2015-01-01

    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. PMID:26404312

  2. Nitric oxide in follicle development and oocyte competence.

    PubMed

    Basini, Giuseppina; Grasselli, Francesca

    2015-07-01

    Apart from its well-known role in regulating endothelial function, in mammals, nitric oxide (NO) is an important signaling molecule involved in many processes, regulating different biological functions. It has been demonstrated that NO plays a role in the physiology of the reproductive system, where it acts in controlling the activity of reproductive organs in both sexes. In the female of several animal species, experimental data suggest the presence of an intraovarian NO-generating system, which could be involved in the control of follicular development. The role of NO in regulating follicular atresia by apoptosis is still controversial, as a dual action depending mostly on its concentration has been documented. NO also displays positive effects on follicle development and selection related to angiogenic events and it could also play a modulatory role in steroidogenesis in ovarian cells. Both in monovulatory and poliovulatory species, the increase in PGE2 production induced by NO via a stimulatory effect on COX-2 activity appears to be a common ovulatory mechanism. Considerable evidence also exists to support an involvement of the NO/NO synthase system in the control of meiotic maturation of cumulus-oocyte complexes. PMID:25792567

  3. Sodium nitrite: the "cure" for nitric oxide insufficiency.

    PubMed

    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. PMID:22464105

  4. Development of nitric oxide neurons in the chick embryo retina.

    PubMed

    Ríos, H; López-Costa, J J; Fosser, N S; Brusco, A; Saavedra, J P

    2000-03-15

    Nitric oxide (NO) is a gas involved in neurotransmission in the central nervous system (CNS) and in vertebrate retinas. This paper describes five types of nitrergic neurons in developing and adult chick retina using the nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) reaction. Three of them, nitrergic types 1, 2 and 3, were observed in the inner nuclear layer, while nitrergic type 4 was observed in the ganglion cell layer; nitrergic type 5 were the retinal photoreceptors. Cell processes formed four nitrergic networks, which could be observed in the inner plexiform layer (IPL), at sublayers 1, 3a, 3b and 4. Another nitrergic network was observed in the outer plexiform layer (OPL). From hatching, the dendritic branches were completely developed in the IPL and in the OPL, forming the mentioned networks. Current evidence suggests that NO is coexpressed with other neurotransmitters in neurons of the CNS. Double-staining procedures, using NADPHd and 5HT immunohistochemistry in chicken retina, in a sequential or in an alternative manner, did not reveal the coexistence of these two neurotransmitters in the same neurons, but their networks matched in sublayers 1 and 4 of the IPL. PMID:10727726

  5. Nitric Oxide-Dependent Posttranslational Modification in Plants: An Update

    PubMed Central

    Astier, Jeremy; Lindermayr, Christian

    2012-01-01

    Nitric oxide (NO) has been demonstrated as an essential regulator of several physiological processes in plants. The understanding of the molecular mechanism underlying its critical role constitutes a major field of research. NO can exert its biological function through different ways, such as the modulation of gene expression, the mobilization of second messengers, or interplays with protein kinases. Besides this signaling events, NO can be responsible of the posttranslational modifications (PTM) of target proteins. Several modifications have been identified so far, whereas metal nitrosylation, the tyrosine nitration and the S-nitrosylation can be considered as the main ones. Recent data demonstrate that these PTM are involved in the control of a wide range of physiological processes in plants, such as the plant immune system. However, a great deal of effort is still necessary to pinpoint the role of each PTM in plant physiology. Taken together, these new advances in proteomic research provide a better comprehension of the role of NO in plant signaling. PMID:23203119

  6. Role of nitric oxide in subventricular zone neurogenesis.

    PubMed

    Matarredona, Esperanza R; Murillo-Carretero, Maribel; Moreno-López, Bernardo; Estrada, Carmen

    2005-09-01

    A possible role of nitric oxide (NO) in adult neurogenesis has been suggested based on anatomical findings showing that subventricular zone (SVZ) neuroblasts are located close to NO-producing cells, and on the known antiproliferative actions of NO in many cell types. Experiments have been performed in rodents with systemic and intracerebroventricular administrations of the NO synthase (NOS) inhibitor L-NAME. NOS inhibition leads to significant increases in the number of proliferating cells in the SVZ and olfactory bulb (OB). NO exerts its cytostatic action preferentially on the cell population expressing nestin but not betaIII-tubulin, which may correspond to the type C cells described in the SVZ. The negative effect of NO on SVZ cell proliferation has also been confirmed in SVZ primary cultures. An inhibition of the tyrosine kinase activity of the epidermal growth factor receptor (EGFR) is described as one of the molecular mechanisms responsible for the antiproliferative effect of NO in SVZ cells. Biochemical data supporting this conclusion has been obtained using the neuroblastoma cell line NB69, which endogenously expresses the EGFR. In these cells, the antimitotic action of NO occurs upon inhibition of the EGFR tyrosine phosphorylation, probably by a direct S-nitrosylation of the receptor. The latest published reports on NO and neurogenesis indicate that NO physiologically participates in the control of adult neurogenesis by modulating the proliferation and fate of the SVZ progenitor cells. These effects might be partially due to a direct inhibition of the EGFR by S-nitrosylation. PMID:16111562

  7. Nitric Oxide-Releasing Chitosan Oligosaccharides as Antibacterial Agents

    PubMed Central

    Lu, Yuan; Slomberg, Danielle L.; Schoenfisch, Mark H.

    2014-01-01

    Secondary amine-functionalized chitosan oligosaccharides of different molecular weights (i.e., ~2500, 5000, 10000) were synthesized by grafting 2-methyl aziridine from the primary amines on chitosan oligosaccharides, followed by reaction with nitric oxide (NO) gas under basic conditions to yield N-diazeniumdiolate NO donors. The total NO storage, maximum NO flux, and half-life of the resulting NO-releasing chitosan oligosaccharides were controlled by the molar ratio of 2-methyl aziridine to primary amines (e.g., 1:1, 2:1) and the functional group surrounding the N-diazeniumdiolates (e.g., polyethylene glycol (PEG) chains), respectively. The secondary amine-modified chitosan oligosaccharides greatly increased the NO payload over existing biodegradable macromolecular NO donors. In addition, the water-solubility of the chitosan oligosaccharides enabled their penetration across the extracellular polysaccharides matrix of Pseudomonas aeruginosa biofilms and association with embedded bacteria. The effectiveness of these chitosan oligosaccharides at biofilm eradication was shown to depend on both the molecular weight and ionic characteristics. Low molecular weight and cationic chitosan oligosaccharides exhibited rapid association with bacteria throughout the entire biofilm, leading to enhanced biofilm killing. At concentrations resulting in 5-log killing of bacteria in Pseudomonas aeruginosa biofilms, the NO-releasing and control chitosan oligosaccharides elicited no significant cytotoxicity to mouse fibroblast L929 cells in vitro. PMID:24268196

  8. Nitric oxide enhances Th9 cell differentiation and airway inflammation

    PubMed Central

    Niedbala, Wanda; Besnard, Anne-Gaelle; Nascimento, Daniele Carvalho; Donate, Paula Barbim; Sonego, Fabiane; Yip, Edwin; Guabiraba, Rodrigo; Chang, Hyun-Dong; Fukada, Sandra Y.; Salmond, Robert J.; Schmitt, Edgar; Bopp, Tobias; Ryffel, Bernhard; Liew, Foo Y.

    2014-01-01

    Th9 cells protect hosts against helminthic infection but also mediate allergic disease. Here we show that nitric oxide (NO) promotes Th9 cell polarization of murine and human CD4+ T cells. NO de-represses the tumor suppressor gene p53 via nitrosylation of Mdm2. NO also increases p53-mediated IL-2 production, STAT5 phosphorylation and IRF4 expression, all essential for Th9 polarization. NO also increases the expression of TGFβR and IL-4R, pivotal to Th9 polarization. OVA-sensitized mice treated with an NO donor developed more severe airway inflammation. Transferred Th9 cells induced airway inflammation, which was exacerbated by NO and blocked by anti-IL-9 antibody. Nos2−/− mice had less Th9 cells and developed attenuated eosinophilia during OVA-induced airway inflammation compared to wild-type mice. Our data demonstrate that NO is an important endogenous inducer of Th9 cells and provide a hitherto unrecognized mechanism for NO-mediated airway inflammation via the expansion of Th9 cells. PMID:25099390

  9. Phototherapeutic Release of Nitric Oxide with Engineered Nanoconstructs.

    PubMed

    Fraix, Aurore; Marino, Nino; Sortino, Salvatore

    2016-01-01

    The multiple role nitric oxide (NO) plays in a number of physiological and pathophysiological processes has, over the last few years, stimulated a massive interest in the development of new strategies and methods for generating NO in a controlled way, with the exciting prospect of tackling important diseases. Photochemical precursors of NO are particularly suited to this end because light triggering permits an exquisite control of location and timing of NO delivery. Integration of NO photodonors within the structure of appropriate materials represents a key step in the fabrication of functional devices for phototherapeutic applications. It also offers the advantage of concentrating a large number of chromophores in a restricted area with the result of significantly increasing the NO reservoir and the light harvesting properties. We present here an overview of the most significant advances made in the last 5 years in the fabrication of engineered nanoconstructs able to delivery NO under the exclusive control of light inputs, highlighting the logical design and their potential applications in battling cancer and bacterial infections. PMID:26589511

  10. Coordination of nitric oxide by heme-hemopexin.

    PubMed

    Shipulina, N; Hunt, R C; Shaklai, N; Smith, A

    1998-04-01

    Hemopexin, which acts as an antioxidant by binding heme (Kd < 1 pM), is synthesized by hepatic parenchymal cells, by neurons of the central and peripheral nervous systems, and by human retinal ganglia. Two key regulatory molecules, nitric oxide (.NO) and carbon monoxide (CO), both bind to heme proteins and since ferroheme-hemopexin binds CO, the possible role of heme-hemopexin in binding .NO was investigated. .NO binds rapidly to hemopexin-bound ferroheme as shown by characteristic changes in the Soret and visible-region absorbance spectra. Circular dichroism spectra of .NO-ferroheme-hemopexin in the Soret region exhibit an unusual bisignate feature with a zero crossover at the absorbance wavelength maximum, showing that exciton coupling is occurring. Notably, the .NO complex of ferroheme-hemopexin is sufficiently avid and stable to allow hemopexin to bind this molecule in vivo and, thus, hemopexin may protect against NO-mediated toxicity especially in conditions of trauma and hemolysis. PMID:9588949

  11. [Nitric Oxide in Modulation of Crystallogenic Propeties of Biological Fluid].

    PubMed

    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. PMID:27192838

  12. Molecular dynamics simulation of nitric oxide in myoglobin

    USGS Publications Warehouse

    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.

  13. Morphine stimulates nitric oxide release in human mitochondria.

    PubMed

    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. PMID:26350413

  14. Nitric Oxide-Releasing S-Nitrosothiol-Modified Xerogels

    PubMed Central

    Riccio, Daniel A.; Dobmeier, Kevin P.; Hetrick, Evan M.; Privett, Benjamin J.; Paul, Heather S.; Schoenfisch, Mark H.

    2009-01-01

    The synthesis, material characterization, and in vitro biocompatibility of S-nitrosothiol (RSNO)-modified xerogels is described. Thiol-functionalized xerogel films were formed by hydrolysis and co-condensation of 3-mercaptopropyltrimethoxysilane (MPTMS) and methyltrimethoxysilane (MTMOS) sol-gel precursors at varying concentrations. Subsequent thiol nitrosation via acidified nitrite produced RSNO-modified xerogels capable of generating nitric oxide (NO) for up to 2 weeks under physiological conditions. Xerogels also exhibited NO generation upon irradiation with broad-spectrum light or exposure to copper, with NO fluxes proportional to wattage and concentration, respectively. Xerogels were capable of storing up to ∼1.31 µmol NO mg−1, and displayed negligible fragmentation over a 2 week period. Platelet and bacterial adhesion to nitrosated films was reduced compared to non-nitrosated controls, confirming the antithrombotic and antibacterial properties of the NO-releasing materials. Fibroblast cell viability was maintained on the xerogel surfaces illustrating the promise of RSNO-modified xerogels as biomedical device coatings. PMID:19501904

  15. A Novel Protocol for Detection of Nitric Oxide in Plants.

    PubMed

    Jain, Prachi; David, Anisha; Bhatla, Satish C

    2016-01-01

    Detection of nitric oxide (NO) in plant cells is mostly undertaken using diaminofluorescein (DAF) dyes. Serious drawbacks and limitations have been identified in methods using DAF as a probe for NO detection. The present work reporting an alternative fluorescent probe for NO detection is thus proposed for varied applications in plant systems for physiological investigations. This method involves a simple, two-step synthesis, characterization, and application of MNIP-Cu {Copper derivative of [4-methoxy-2-(1H-napthol[2,3-d]imidazol-2-yl)phenol]} for specific and rapid binding with NO, leading to its detection in plant cells by epifluorescence microscopy and confocal laser scanning microscopy (CLSM). Using sunflower (Helianthus annuus L.) whole seedlings, hypocotyl segments, stigmas from capitulum, protoplasts, and isolated oil bodies, present investigations demonstrate the versatile nature of MNIP-Cu in applications for NO localization studies. MNIP-Cu can detect NO in vivo without any time lag (ex. 330-385 nm; em. 420-500 nm). It exhibits fluorescence both under anoxic and oxygen-rich conditions. This probe is specific to NO, which enhances its fluorescence due to MNIP-Cu complexing with NO and treatment with PTIO leads to quenching of fluorescence. It is relatively nontoxic when used at a concentration of up to 50 μM. PMID:27094412

  16. Structure-Based Design of Bacterial Nitric Oxide Synthase Inhibitors

    PubMed Central

    2015-01-01

    Inhibition of bacterial nitric oxide synthase (bNOS) has the potential to improve the efficacy of antimicrobials used to treat infections by Gram-positive pathogens Staphylococcus aureus and Bacillus anthracis. However, inhibitor specificity toward bNOS over the mammalian NOS (mNOS) isoforms remains a challenge because of the near identical NOS active sites. One key structural difference between the NOS isoforms is the amino acid composition of the pterin cofactor binding site that is adjacent to the NOS active site. Previously, we demonstrated that a NOS inhibitor targeting both the active and pterin sites was potent and functioned as an antimicrobial (Holden, , Proc. Natl. Acad. Sci. U.S.A.2013, 110, 1812724145412). Here we present additional crystal structures, binding analyses, and bacterial killing studies of inhibitors that target both the active and pterin sites of a bNOS and function as antimicrobials. Together, these data provide a framework for continued development of bNOS inhibitors, as each molecule represents an excellent chemical scaffold for the design of isoform selective bNOS inhibitors. PMID:25522110

  17. Differential Modulation of Nitric Oxide Synthases in Aging: Therapeutic Opportunities

    PubMed Central

    Cau, Stefany B. A.; Carneiro, Fernando S.; Tostes, Rita C.

    2012-01-01

    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. PMID:22737132

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

    PubMed

    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. PMID:12296866

  19. Role of nitric oxide in the gastrointestinal tract

    PubMed Central

    Lanas, Angel

    2008-01-01

    Worldwide osteoarthritis (OA) affects more than 9.6% of men and 18% of women older that 60 years. Treatment for OA often requires chronic use of selective or nonselective nonsteroidal anti-inflammatory drugs (NSAIDs), which have been associated with gastrointestinal and cardiovascular complications. An increased risk for upper gastrointestinal bleeding with NSAIDs alone and when combined with low-dose aspirin has been described in numerous studies. Although cyclo-oxygenase-2 inhibitors have been shown to carry a lower risk for gastrointestinal injury than nonselective NSAIDs, research continues to identify new treatments that not only are effective but also provide an improved benefit/risk profile, including better gastrointestinal tolerability. Nitric oxide (NO) is known to have a protective effect on the gastrointestinal tract. In preclinical studies NO was shown to help maintain gastric mucosal integrity, to inhibit leukocyte adherence to the endothelium, and to repair NSAID-induced damage. In addition, epidemiologic studies have shown that the use of NO-donating agents with NSAIDs or aspirin resulted in reduced risk for gastrointestinal bleeding. Recent studies have shown that cyclo-oxygenase inhibiting NO-donating drugs (CINODs), in which a NO molecule is chemically linked to an NSAID, are effective anti-inflammatory agents and may result in less gastrointestinal damage than is associated with NSAID use. Therefore, these agents provide a potential therapeutic option for patients with arthritis who require long-term NSAID therapy. PMID:19007429

  20. Pharmacologic strategies in neonatal pulmonary hypertension other than nitric oxide.

    PubMed

    Lakshminrusimha, Satyan; Mathew, Bobby; Leach, Corinne L

    2016-04-01

    Inhaled nitric oxide (iNO) is approved for use in persistent pulmonary hypertension of the newborn (PPHN) but does not lead to sustained improvement in oxygenation in one-third of patients with PPHN. Inhaled NO is less effective in the management of PPHN secondary to congenital diaphragmatic hernia (CDH), extreme prematurity, and bronchopulmonary dysplasia (BPD). Intravenous pulmonary vasodilators such as prostacyclin, alprostadil, sildenafil, and milrinone have been successfully used in PPHN resistant to iNO. Oral pulmonary vasodilators such as endothelin receptor antagonist bosentan and phosphodiesterase-5 inhibitors such as sildenafil and tadalafil are used both during acute and chronic phases of PPHN. In the absence of infection, glucocorticoids may also be effective in PPHN. Many of these pharmacologic agents are not approved for use in PPHN and our knowledge is based on case reports and small trials. Large multicenter randomized controlled trials with long-term follow-up are required to evaluate alternate pharmacologic strategies in PPHN. PMID:26778236

  1. Pulmonary vasodilation by inhaled nitric oxide after endothelial injury

    SciTech Connect

    Rimar, S.; Gillis, C.N. )

    1992-11-01

    Inhaled nitric oxide gas (NO) has recently been shown to reverse experimentally induced pulmonary vasoconstriction. To examine the effect of free radical injury and methylene blue exposure on inhaled NO-induced pulmonary vasodilation the authors studied ventilated rabbit lungs perfused with Krebs solution containing 3% dextran and indomethacin. When NO gas (120 ppm) was added to the inhaled mixture for 3 min, the elevated pulmonary arterial perfusion pressure (Ppa) induced by the thromboxane analogue U-46619 was significantly reduced [8 [+-] 2 (SE) mmHg]. Acetylcholine similarly reduced Ppa (9 [+-] 1 mmHg). After free radical injury and methylene blue exposure, inhaled NO again produced significant vasodilation (5 [+-] 1 and 9 [+-] 2 mmHg, respectively), but acetylcholine resulted in an increase in Ppa ([minus]9 [+-] 3 and [minus]4 [+-] 1 mmHg, respectively). These data demonstrate that pulmonary vasodilation produced by inhaled NO is unaffected by free radical injury or methylene blue in the intact lung despite concomitant reversal of acetylcholine-induced vasodilation. 21 refs., 4 figs.

  2. Nitric oxide synthase activity in the molluscan CNS.

    PubMed

    Moroz, L L; Chen, D; Gillette, M U; Gillette, R

    1996-02-01

    Putative nitric oxide synthase (NOS) activity was assayed in molluscan CNS through histochemical localization of NADPH-diaphorase and through measurement of L-arginine/L-citrulline conversion. Several hundreds of NADPH-dependent diaphorase-positive neurons stained consistently darkly in the nervous system of the predatory opisthobranch Pleurobranchaea californica, whereas stained neurons were relatively sparse and/or light in the other opisthobranchs (Philine, Aplysia, Tritonia, Flabellina, Cadina, Armina, Coriphella, and Doriopsilla sp.) and cephalopods (Sepia and Rossia sp.). L-Arginine/L-citrulline conversion was beta-NADPH dependent, insensitive to removal of Ca2+, inhibited by the calmodulin blocker trifluoperazine, and inhibited by the competitive NOS inhibitor N-nitro-L-arginine methyl ester (L-NAME) but not D-NAME. Inhibitors of arginase [L-valine and (+)-S-2-amino-5-iodoacetamidopentanoic acid)] did not affect L-citrulline production in the CNS. NOS activity was largely associated with the particulate fraction and appeared to be a novel, constitutive Ca(2+)-independent isoform. Enzymatic conversion of L-arginine/L-citrulline in Pleurobranchaea and Aplysia CNS was 4.0 and 9.8%, respectively, of that of rat cerebellum, L-Citrulline formation in gill and muscle of Pleurobranchaea was not significant. The localization of relatively high NOS activity in neuron somata in the CNS of Pleurobranchaea is markedly different from the other opisthobranchs, all of which are grazers. Potentially, this is related to the animal's opportunistic predatory lifestyle. PMID:8592165

  3. GAPDH regulates cellular heme insertion into inducible nitric oxide synthase

    PubMed Central

    Chakravarti, Ritu; Aulak, Kulwant S.; Fox, Paul L.; Stuehr, Dennis J.

    2010-01-01

    Heme proteins play essential roles in biology, but little is known about heme transport inside mammalian cells or how heme is inserted into soluble proteins. We recently found that nitric oxide (NO) blocks cells from inserting heme into several proteins, including cytochrome P450s, hemoglobin, NO synthases, and catalase. This finding led us to explore the basis for NO inhibition and to identify cytosolic proteins that may be involved, using inducible NO synthase (iNOS) as a model target. Surprisingly, we found that GAPDH plays a key role. GAPDH was associated with iNOS in cells. Pure GAPDH bound tightly to heme or to iNOS in an NO-sensitive manner. GAPDH knockdown inhibited heme insertion into iNOS and a GAPDH mutant with defective heme binding acted as a dominant negative inhibitor of iNOS heme insertion. Exposing cells to NO either from a chemical donor or by iNOS induction caused GAPDH to become S-nitrosylated at Cys152. Expressing a GAPDH C152S mutant in cells or providing a drug to selectively block GAPDH S-nitrosylation both made heme insertion into iNOS resistant to the NO inhibition. We propose that GAPDH delivers heme to iNOS through a process that is regulated by its S-nitrosylation. Our findings may uncover a fundamental step in intracellular heme trafficking, and reveal a mechanism whereby NO can govern the process. PMID:20921417

  4. Nitric oxide measurements in the Arctic winter stratosphere

    SciTech Connect

    Fahey, D.W. ); Kawa, S.R. Univ. of Colorado, Boulder ); Chan, K.R. )

    1990-03-01

    Measurements of nitric oxide (NO) from five flights of the NASA ER-2 aircraft during the Airborne Arctic Stratospheric Expedition (AASE) are presented. The NO values and vertical gradient near 60{degree}N latitude are similar to previous measurements near 50{degree}N in winter (Ridley et al., 1984; 1987). The NO latitudinal gradient is distinctly negative outside of the polar vortex, approaching zero at the boundary of the vortex, and remaining below the 20 pptv detection limit inside the vortex. The low NO values in the vortex occur at solar zenith angles as low as 82{degree} indicating that NO{sub 2} values in the vortex are also low. Steady state NO{sub 2} and NO{sub x} (NO+NO{sub 2}) are calculated from measured NO, O{sub 3}, and ClO, and modeled photodissociation rates. NO{sub x} outside the vortex shows a negative dependence on latitude and solar zenith angle. The average ratio of NO{sub x} to NO{sub y} (at the same relative latitudes from different flight days) shows a strong latitude gradient with values near 0.08 at 12{degree} equatorward of the vortex edge, decreasing to less than 0.02 at the vortex boundary. Low NO{sub x} and NO{sub x}/NO{sub y} inside and near the vortex boundary may be indications of heterogeneous removal of ClONO{sub 2} and N{sub 2}O{sub 5}.

  5. Characterization of a Fluorescent Probe for Imaging Nitric Oxide

    PubMed Central

    Ghebremariam, Yohannes T; Huang, Ngan F; Kambhampati, Swetha; Volz, Katharina S; Joshi, Gururaj G; Anslyn, Eric V; Cooke, John P

    2014-01-01

    Background Nitric Oxide (NO), a potent vasodilator and anti-atherogenic molecule, is synthesized in various cell types including vascular endothelial cells (ECs). The biological importance of NO enforces the need to develop and characterize specific and sensitive probes. To date, several fluorophores, chromophores and colorimetric techniques have been developed to detect NO or its metabolites (NO2 and NO3) in biological fluids, viable cells or cell lysates. Methods Recently, a novel probe (NO550) has been developed and reported to detect NO in solution and in primary astrocytes and neuronal cells with a fluorescence signal arising from a non-fluorescent background. Results Here, we report further characterization of this probe by optimizing conditions for the detection and imaging of NO products in primary vascular endothelial cells, fibroblasts, embryonic stem cell (ESC)- and induced pluripotent stem cell (iPSC)- derived endothelial cells (ESC-ECs. and iPSC-ECs respectively) in the absence and presence of pharmacological agents that modulate NO levels. In addition, we studied the stability of this probe in cells over time and evaluated its compartmentalization in reference to organelle-labeling dyes. Finally, we synthesized an inherently fluorescent diazo ring compound (AZO550) that is expected to form when the non-fluorescent NO550 reacts with cellular NO and compared its cellular distribution with that of NO550. Conclusion NO550 is a promising agent for imaging NO at baseline and in response to pharmacological agents that modulate its levels. PMID:24335468

  6. Nitric Oxide (NO) Measurements in Stomatal Guard Cells.

    PubMed

    Agurla, Srinivas; Gayatri, Gunja; Raghavendra, Agepati S

    2016-01-01

    The quantitative measurement of nitric oxide (NO) in plant cells acquired great importance, in view of the multifaceted function and involvement of NO as a signal in various plant processes. Monitoring of NO in guard cells is quite simple because of the large size of guard cells and ease of observing the detached epidermis under microscope. Stomatal guard cells therefore provide an excellent model system to study the components of signal transduction. The levels and functions of NO in relation to stomatal closure can be monitored, with the help of an inverted fluorescence or confocal microscope. We can measure the NO in guard cells by using flouroprobes like 4,5-diamino fluorescein diacetate (DAF-2DA). This fluorescent dye, DAF-2DA, is cell permeable and after entry into the cell, the diacetate group is removed by the cellular esterases. The resulting DAF-2 form is membrane impermeable and reacts with NO to generate the highly fluorescent triazole (DAF-2T), with excitation and emission wavelengths of 488 and 530 nm, respectively. If time-course measurements are needed, the epidermis can be adhered to a cover-glass or glass slide and left in a small petri dishes. Fluorescence can then be monitored at required time intervals; with a precaution that excitation is done minimally, only when a fluorescent image is acquired. The present method description is for the epidermis of Arabidopsis thaliana and Pisum sativum and should work with most of the other dicotyledonous plants. PMID:27094410

  7. Effect of Electrode Configuration on Nitric Oxide Gas Sensor Behavior.

    PubMed

    Cui, Ling; Murray, Erica P

    2015-01-01

    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. PMID:26404312

  8. Photo-crosslinked Biodegradable Elastomers for Controlled Nitric Oxide Delivery

    PubMed Central

    Wang, Ying; Kibbe, Melina R.; Ameer, Guillermo A.

    2013-01-01

    The delivery of nitric oxide (NO) has important applications in medicine, especially for procedures that involve the vasculature. We report photo-curable biodegradable poly(diol citrate) elastomers capable of slow release of NO. A methacrylated poly(diol citrate) macromonomer was prepared by polycondensation of citric acid with 1, 8-octanediol or 1, 12-dodecanediol followed by functionalization with 2-aminoethyl methacrylate. A miscible NO donor, diazeniumdiolated N, N-diethyldiethylenetriamine, was synthesized and incorporated into the polymer matrix. An elastomeric network was obtained via photo-polymerization of macromonomers upon UV irradiation within three minutes. Films and tubes of the NO-releasing crosslinked macromonomers exhibited strong tensile strength and radial compressive strength, respectively. They also exhibited cell compatibility and biodegradability in vitro. Sustained NO release under physiological conditions was achieved for at least one week. NO release enhanced the proliferation of human umbilical vein endothelial cells but inhibited the proliferation of human aortic smooth muscle cells. Photo-polymerizable NO-releasing materials provide a new approach for the localized and sustained delivery of NO to treat thrombosis and restenosis in the vasculature. PMID:24707352

  9. Nitric oxide synthase deficiency and the pathophysiology of muscular dystrophy

    PubMed Central

    Tidball, James G; Wehling-Henricks, Michelle

    2014-01-01

    The secondary loss of neuronal nitric oxide synthase (nNOS) that occurs in dystrophic muscle is the basis of numerous, complex and interacting features of the dystrophic pathology that affect not only muscle itself, but also influence the interaction of muscle with other tissues. Many mechanisms through which nNOS deficiency contributes to misregulation of muscle development, blood flow, fatigue, inflammation and fibrosis in dystrophic muscle have been identified, suggesting that normalization in NO production could greatly attenuate diverse aspects of the pathology of muscular dystrophy through multiple regulatory pathways. However, the relative importance of the loss of nNOS from the sarcolemma versus the importance of loss of total nNOS from dystrophic muscle remains unknown. Although most current evidence indicates that nNOS localization at the sarcolemma is not required to achieve NO-mediated reductions of pathology in muscular dystrophy, the question remains open concerning whether membrane localization would provide a more efficient rescue from features of the dystrophic phenotype. PMID:25194047

  10. Concepts of neural nitric oxide-mediated transmission

    PubMed Central

    Garthwaite, John

    2008-01-01

    As a chemical transmitter in the mammalian central nervous system, nitric oxide (NO) is still thought a bit of an oddity, yet this role extends back to the beginnings of the evolution of the nervous system, predating many of the more familiar neurotransmitters. During the 20 years since it became known, evidence has accumulated for NO subserving an increasing number of functions in the mammalian central nervous system, as anticipated from the wide distribution of its synthetic and signal transduction machinery within it. This review attempts to probe beneath those functions and consider the cellular and molecular mechanisms through which NO evokes short- and long-term modifications in neural performance. With any transmitter, understanding its receptors is vital for decoding the language of communication. The receptor proteins specialised to detect NO are coupled to cGMP formation and provide an astonishing degree of amplification of even brief, low amplitude NO signals. Emphasis is given to the diverse ways in which NO receptor activation initiates changes in neuronal excitability and synaptic strength by acting at pre- and/or postsynaptic locations. Signalling to non-neuronal cells and an unexpected line of communication between endothelial cells and brain cells are also covered. Viewed from a mechanistic perspective, NO conforms to many of the rules governing more conventional neurotransmission, particularly of the metabotropic type, but stands out as being more economical and versatile, attributes that presumably account for its spectacular evolutionary success. PMID:18588525

  11. Enhanced biogenic emissions of nitric oxide and nitrous oxide following surface biomass burning

    NASA Technical Reports Server (NTRS)

    Anderson, Iris C.; Levine, Joel S.; Poth, Mark A.; Riggan, Philip J.

    1988-01-01

    Recent measurements indicate significantly enhanced biogenic soil emissions of both nitric oxide (NO) and nitrous oxide (N2O) following surface burning. These enhanced fluxes persisted for at least six months following the burn. Simultaneous measurements indicate enhanced levels of exchangeable ammonium in the soil following the burn. Biomass burning is known to be an instantaneous source of NO and N2O resulting from high-temperature combustion. Now it is found that biomass burning also results in significantly enhanced biogenic emissions of these gases, which persist for months following the burn.

  12. Photocontrol of nitric oxide production in cell culture using a caged isoform selective inhibitor.

    PubMed

    Perdicakis, Basil; Montgomery, Heather J; Abbott, Glenn L; Fishlock, Dan; Lajoie, Gilles A; Guillemette, J Guy; Jervis, Eric

    2005-01-01

    Over the past decade, multiphoton microscopy has progressed from a photonic novelty to a technique whose application is currently experiencing exponential growth in the biological sciences. A novel application of this technology with significant therapeutic potential is the control of drug activity by multiphoton photolysis of caged therapeutics. As an initial case study, the potent isoform selective inhibitor N-(3-(aminomethyl)benzyl) acetamidine (1400W) of inducible nitric oxide synthase (iNOS) has been conjugated to a caging molecule 6-bromo-7-hydroxy-4-hydroxyquinoline-2-ylmethyl acetyl ester (Bhc). Here we present the first report of a bulk therapeutic effect, inhibition of nitric oxide production, in mammalian cell culture by multiphoton photolysis of a caged drug, Bhc-1400W. Mouse macrophage RAW 264.7 cells induced with bacterial lipopolysaccharides to express iNOS were used to assess the therapeutic value of the conjugated inhibitor. Both 1400W and Bhc-1400W are stable in metabolically active cells and an optimal time interval for the photorelease of the inhibitor was determined. The ratios of the IC(50) values of Bhc-1400W over 1400W calculated in the presence of iNOS enzyme and in RAW 264.7 cell culture are 19 and 100, respectively, indicating that a broad therapeutic range exists in cell culture. Multiphoton uncaging protocols and therapeutic doses of inhibitors were not cytotoxic. Photocontrol of LPS induced nitric oxide production was achieved in mammalian cell culture using a single laser focal volume. This technology has the potential to control active drug concentrations in vivo, a lack of which is one of the main problems currently associated with systemic drug administration. PMID:15582451

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

    PubMed Central

    Rao, Minxi; Smith, Brian C.

    2015-01-01

    ABSTRACT Nitric oxide (NO) plays an important signaling role in all domains of life. Many bacteria contain a heme-nitric oxide/oxygen binding (H-NOX) protein that selectively binds NO. These H-NOX proteins often act as sensors that regulate histidine kinase (HK) activity, forming part of a bacterial two-component signaling system that also involves one or more response regulators. In several organisms, NO binding to the H-NOX protein governs bacterial biofilm formation; however, the source of NO exposure for these bacteria is unknown. In mammals, NO is generated by the enzyme nitric oxide synthase (NOS) and signals through binding the H-NOX domain of soluble guanylate cyclase. Recently, several bacterial NOS proteins have also been reported, but the corresponding bacteria do not also encode an H-NOX protein. Here, we report the first characterization of a bacterium that encodes both a NOS and H-NOX, thus resembling the mammalian system capable of both synthesizing and sensing NO. We characterized the NO signaling pathway of the marine alphaproteobacterium Silicibacter sp. strain TrichCH4B, determining that the NOS is activated by an algal symbiont, Trichodesmium erythraeum. NO signaling through a histidine kinase-response regulator two-component signaling pathway results in increased concentrations of cyclic diguanosine monophosphate, a key bacterial second messenger molecule that controls cellular adhesion and biofilm formation. Silicibacter sp. TrichCH4B biofilm formation, activated by T. erythraeum, may be an important mechanism for symbiosis between the two organisms, revealing that NO plays a previously unknown key role in bacterial communication and symbiosis. PMID:25944856

  14. Ethanol Metabolism and Effects: Nitric Oxide and its Interaction

    PubMed Central

    Deng, Xin-sheng; Deitrich, Richard A.

    2008-01-01

    Ethanol (EtOH) in alcoholic beverages is consumed by a large number of individuals and its elimination is primarily by oxidation. The role of nitric oxide (NO) in ethanol’s effects is important since NO is one of the most prominent biological factors in mammals. NO is constantly formed endogenously from L-arginine. Dose and length of EtOH exposure, and cell type are the main factors affecting EtOH effects on NO production. Either acute or chronic EtOH ingestion affects inducible NO synthase (iNOS) activity. However it seems that EtOH suppresses induced-NO production by inhibition of iNOS in different cells. On the other hand, it is clear that acute low doses of EtOH increase both the release of NO and endothelial NOS (eNOS) expression, and augment endothelium-mediated vasodilatation, whereas higher doses impair endothelial functions. EtOH selectively affects neuronal NOS (nNOS) activity in different brain cells, which may relate to various behavioral interactions. Therefore, there is an excellent chance for EtOH and NO to react with each other. Effects of EtOH on NO production and NOS activity may be important to ethanol modification of cell or organ function. Nitrosated compounds (alkyl nitrites) are often found as the interaction products, which might be one of the minor pathways of EtOH metabolism. NO also inhibits EtOH metabolizing enzymes. Furthermore, NO is involved in EtOH induced liver damage and has a role in fetal development during ethanol exposure in pregnancy. The mechanisms underlying these effects are only partially understood. Hence, the current discussion of the interaction of ethanol and NO is presented. PMID:18690862

  15. Alpha-Tocopherol and endothelial nitric oxide synthesis.

    PubMed

    Heller, Regine; Werner-Felmayer, Gabriele; Werner, Ernst R

    2004-12-01

    Nitric oxide (NO), a central regulator of vascular tone and homeostasis, is generated upon activation of endothelial NO synthase (eNOS), which is mediated by an increase of intracellular calcium and/or by eNOS phosphorylation. A reduction of NO bioavailability leads to endothelial dysfunction that has been shown to be improved by alpha-tocopherol in certain conditions. The underlying mechanisms, however, are not completely clarified. The present study was performed to investigate whether alpha-tocopherol is able to affect endothelial NO synthesis. The formation of NO was measured in human umbilical vein endothelial cells using citrulline (coproduct) and cGMP (product of the NO-activated soluble guanylate cyclase) as indicator molecules. alpha-Tocopherol (10-200 microM, 24 hr) increased ionomycin-induced citrulline and cGMP formation in intact cells in a concentration-dependent manner. In parallel, ionomycin-stimulated phosphorylation of eNOS at serine 1177, known to support enzyme activation, was increased by alpha-tocopherol, suggesting that this was the mechanism responsible for enhanced NO formation. The effect of alpha-tocopherol was dependent on its hydrophobic structure because it was mimicked by gamma-tocopherol but not by trolox, a hydrophilic derivative of alpha-tocopherol. Coincubation with ascorbic acid (100 microM, 24 hr) amplified the effects of alpha-tocopherol on eNOS phosphorylation and NO formation, which is possibly related to the regeneration of oxidized alpha-tocopherol by ascorbate. Our data suggest that vasoprotective effects of alpha-tocopherol in vivo may be related to an increase of NO formation. The effect of alpha-tocopherol seems to be dependent on tissue saturation with ascorbic acid, and both vitamins may act synergistically to provide optimal conditions for endothelial NO formation. PMID:15753135

  16. Microarray analysis of nitric oxide responsive transcripts in Arabidopsis.

    PubMed

    Parani, Madasamy; Rudrabhatla, Sairam; Myers, Rachel; Weirich, Heatherbea; Smith, Bruce; Leaman, Douglas W; Goldman, Stephen L

    2004-07-01

    Nitric oxide (NO) is emerging as an important signalling molecule with diverse physiological functions in plants. In the current study, changes in gene expression in response to 0.1 mm and 1.0 mm sodium nitroprusside (SNP), a donor of NO, were studied in Arabidopsis using the whole genome ATH1 microarray, representing over 24,000 genes. We observed 342 up-regulated and 80 down-regulated genes in response to NO treatments. These included 126 novel genes with unknown functions. Most of these changes were specific to NO treatment, as we observed a reverse trend when the plants were treated with NO scavenger, 2-[4-carboxyphenyl]-4,4,5,5-tetramethylimidazoline-1-oxy-3-oxide (c-PTIO). Hierarchical clustering revealed 162 genes showing a dose-dependent increase in signal from 0.1 mm SNP to 1.0 mm SNP treatment. We observed the up-regulation of several genes encoding disease-resistance proteins, WRKY proteins, transcription factors, zinc finger proteins, glutathione S-transferases, ABC transporters, kinases and biosynthetic genes of ethylene, jasmonic acid, lignin and alkaloids. This report provides an insight into the molecular basis for the seemingly diverse biological functions of NO in plants. Interestingly, about 2.0% of the genes in Arabidopsis responded to NO treatment, about 10% of which were transcription factors. NO may also influence the plant's signal transduction network as indicated by the transcriptional activation of several protein kinases, including a mitogen-activated protein (MAP) kinase. We identified many genes previously not shown to be associated with NO responses in plants, and this is the first report of NO responsive genes based on a whole genome microarray. PMID:17134397

  17. Rational Design of a Structural and Functional Nitric Oxide Reductase

    SciTech Connect

    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.

  18. Effects of Erythrocyte Aging on Nitric Oxide and Nitrite Metabolism

    PubMed Central

    Owusu, Benjamin Y.; Stapley, Ryan; Honavar, Jaideep

    2013-01-01

    Abstract Aims: Recent studies have suggested that in addition to oxygen transport, red blood cells (RBC) are key regulators of vascular function by both inhibiting and promoting nitric oxide (NO)-mediated vasodilation. Most studies assume that RBC are homogenous, but, in fact, they comprise cells of differing morphology and biochemical composition which are dependent on their age, parameters that control NO reactions. We tested the hypothesis that distinct RBC populations will have differential effects on NO signaling. Results: Young and old RBC were separated by density gradient centrifugation. Consistent with previous reports, old RBC had decreased levels of surface N-acetyl neuraminic acid and increased oxygen binding affinities. Competition kinetic experiments showed that older RBCs scavenged NO∼2-fold faster compared with younger RBC, which translated to a more potent inhibition of both acetylcholine and NO-donor dependent vasodilation of isolated aortic rings. Moreover, nitrite oxidation kinetics was faster with older RBC compared with younger RBC; whereas no differences in nitrite-reduction kinetics were observed. This translated to increased inhibitory effect of older RBC to nitrite-dependent vasodilation under oxygenated and deoxygenated conditions. Finally, leukodepleted RBC storage also resulted in more dense RBC, which may contribute to the greater NO-inhibitory potential of stored RBC. Innovation: These results suggest that a key element in vascular NO-homeostasis mechanisms is the distribution of RBC ages across the physiological spectrum (0–120 days) and suggest a novel mechanism for inhibited NO bioavailability in diseases which are characterized by a shift to an older RBC phenotype. Conclusion: Older RBC inhibit NO bioavailability by increasing NO- and nitrite scavenging. Antioxid. Redox Signal. 19, 1198–1208. PMID:23311696

  19. (-)-Epicatechin-induced recovery of mitochondria from simulated diabetes: Potential role of endothelial nitric oxide synthase.

    PubMed

    Ramírez-Sánchez, Israel; Rodríguez, Alonso; Moreno-Ulloa, Aldo; Ceballos, Guillermo; Villarreal, Francisco

    2016-05-01

    (-)-Epicatechin increases indicators associated with mitochondrial biogenesis in endothelial cells and myocardium. We investigated endothelial nitric oxide synthase involvement on (-)-epicatechin-induced increases in indicators associated with mitochondrial biogenesis in human coronary artery endothelial cells cultured in normal-glucose and high-glucose media, as well as to restore indicators of cardiac mitochondria from the effects of simulated diabetes. Here, we demonstrate the role of endothelial nitric oxide synthase on (-)-epicatechin-induced increases in mitochondrial proteins, transcription factors and sirtuin 1 under normal-glucose conditions. In simulated diabetes endothelial nitric oxide synthase function, mitochondrial function-associated and biogenesis-associated indicators were adversely impacted by high glucose, effects that were reverted by (-)-epicatechin. As an animal model of type 2 diabetes, 2-month old C57BL/6 mice were fed a high-fat diet for 16 weeks. Fasting and fed blood glucose levels were increased and NO plasma levels decreased. High-fat-diet-fed mice myocardium revealed endothelial nitric oxide synthase dysfunction, reduced mitochondrial activity and markers of mitochondrial biogenesis. The administration of 1 mg/kg (-)-epicatechin for 15 days by oral gavage shifted these endpoints towards control mice values. Results suggest that endothelial nitric oxide synthase mediates (-)-epicatechin-induced increases of indicators associated with mitochondrial biogenesis in endothelial cells. (-)-Epicatechin also counteracts the negative effects that high glucose or simulated type 2 diabetes has on endothelial nitric oxide synthase function. PMID:26993496

  20. Laser absorption of nitric oxide for thermometry in high-enthalpy air

    NASA Astrophysics Data System (ADS)

    Spearrin, R. M.; Schultz, I. A.; Jeffries, J. B.; Hanson, R. K.

    2014-12-01

    The design and demonstration of a laser absorption sensor for thermometry in high-enthalpy air is presented. The sensor exploits the highly temperature-sensitive and largely pressure-independent concentration of nitric oxide in air at chemical equilibrium. Temperature is thus inferred from an in situ measurement of nascent nitric oxide. The strategy is developed by utilizing a quantum cascade laser source for access to the strong fundamental absorption band in the mid-infrared spectrum of nitric oxide. Room temperature measurements in a high-pressure static cell validate the suitability of the Voigt lineshape model to the nitric oxide spectra at high gas densities. Shock-tube experiments enable calibration of a collision-broadening model for temperatures between 1200-3000 K. Finally, sensor performance is demonstrated in a high-pressure shock tube by measuring temperature behind reflected shock waves for both fixed-chemistry experiments where nitric oxide is seeded, and for experiments involving nitric oxide formation in shock-heated mixtures of N2 and O2. Results show excellent performance of the sensor across a wide range of operating conditions from 1100-2950 K and at pressures up to 140 atm.

  1. Effect of nitric oxide compounds on monkey ciliary muscle in vitro

    PubMed Central

    Gabelt, B’Ann T.; Kaufman, Paul L.; Rasmussen, Carol A.

    2012-01-01

    The effects of various nitric oxide compounds and their inhibitors on monkey ciliary muscle contraction in vitro were investigated in both the longitudinal and circular vectors. The responses to nitric oxide compounds in carbachol precontracted ciliary muscle consisted of an initial relaxation often followed by recovery to near carbachol precontracted levels while the compound was still present. Sodium nitroprusside produced the greatest relaxation responses (nearly 100% relaxation in both vectors at 10−3 M). The highest concentrations of isosorbide dinitrate (10−4 M) and L-arginine (10−3 M) produced relaxation responses of approximately 50% in both vectors. 8-Bromo cyclic GMP produced the smallest relaxation responses (25–35%). Nitric oxide synthase inhibition enhanced carbachol contraction up to 20% in the longitudinal but not the circular vector. Phosphodiesterase inhibition did not further enhance the relaxation response to L-arginine. Guanylate cyclase inhibition partially attenuated the relaxation response to sodium nitroprusside. Nitric oxide generating compounds were effective in relaxing precontracted monkey ciliary muscle in vitro. Endogenous production of nitric oxide is likely involved in the regulation of the contractile response in monkey ciliary muscle. Nitric oxide generating compounds may have potential value in therapeutic areas where modulation of ciliary muscle tension is desirable. PMID:21147103

  2. Effects of simulated microgravity on arterial nitric oxide synthase and nitrate and nitrite content

    NASA Technical Reports Server (NTRS)

    Ma, Jin; Kahwaji, Chadi I.; Ni, Zhenmin; Vaziri, Nosratola D.; Purdy, Ralph E.

    2003-01-01

    The aim of the present work was to investigate the alterations in nitric oxide synthase (NOS) expression and nitrate and nitrite (NOx) content of different arteries from simulated microgravity rats. Male Wistar rats were randomly assigned to either a control group or simulated microgravity group. For simulating microgravity, animals were subjected to hindlimb unweighting (HU) for 20 days. Different arterial tissues were removed for determination of NOS expression and NOx. Western blotting was used to measure endothelial NOS (eNOS) and inducible NOS (iNOS) protein content. Total concentrations of NOx, stable metabolites of nitric oxide, were determined by the chemiluminescence method. Compared with controls, isolated vessels from simulated microgravity rats showed a significant increase in both eNOS and iNOS expression in carotid arteries and thoracic aorta and a significant decrease in eNOS and iNOS expression of mesenteric arteries. The eNOS and iNOS content of cerebral arteries, as well as that of femoral arteries, showed no differences between the two groups. Concerning NOx, vessels from HU rats showed an increase in cerebral arteries, a decrease in mesenteric arteries, and no change in carotid artery, femoral artery and thoracic aorta. These data indicated that there were differential alterations in NOS expression and NOx of different arteries after hindlimb unweighting. We suggest that these changes might represent both localized adaptations to differential body fluid redistribution and other factors independent of hemodynamic shifts during simulated microgravity.

  3. The role of pre-ischaemic application of the nitric oxide donor spermine/nitric oxide complex in enhancing flap survival in a rat model.

    PubMed

    Küntscher, M V; Juran, S; Menke, H; Gebhard, M M; Erdmann, D; Germann, G

    2002-07-01

    Spermine/nitric oxide complex (Sper/NO) is a new nitric oxide (NO) donor with a long half-life providing controlled biological release of NO in vivo. The purpose of this study was to determine whether flap survival could be improved by pre-ischaemic or post-ischaemic intravenous administration of Sper/NO. We divided 37 male Wistar rats into four experimental groups. An extended epigastric adipocutaneous flap was raised in each animal. The mean area of flap necrosis was assessed for all groups on the fifth postoperative day, using planimetry software. The average area of flap necrosis was mean +/- s.d. = 68.2%+/-18.1% in the control group, and 29.7% +/- 13.3% in the non-ischaemic controls. The group with pre-ischaemic application of Sper/NO demonstrated an average flap necrosis of mean+/-s.d. = 11.2%+/-5.9%, whereas this increased to 59.2%+/-14.4% in the group receiving Sper/NO 5 min prior to reperfusion. The group with pre-ischaemic application of Sper/NO showed a significantly lower area of flap necrosis than either of the control groups or the group receiving Sper/NO just prior to reperfusion (P < 0.05). The group receiving Sper/NO just prior to reperfusion demonstrated a significantly higher mean area of flap necrosis than the non-ischaemic controls (P < 0.05), but did not differ significantly from the control group. Our data show that pharmacological preconditioning and enhancement of flap survival can be achieved by intravenous administration of Sper/NO. The application of Sper/NO at the end of the ischaemia period or in the early reperfusion period provides no protection against ischaemia-reperfusion injury. PMID:12372374

  4. Studies on the oxidation of hexamethylbenzene 1: Oxidation of hexamethylbenzene with nitric acid

    NASA Technical Reports Server (NTRS)

    Chiba, K.; Tomura, S.; Mizuno, T.

    1986-01-01

    The oxidative reaction of hexamethylbenzene (HMB) with nitric acid was studied, and the hitherto unknown polymethylbenzenepolycarboxylic acids were isolated: tetramethylphthalic anhydride, tetramethylisophthalic acid, 1,3,5-, 1,2,4- and 1,2,3-trimethylbenzenetricarboxylic acids. When HMB was warmed with 50% nitric acid at about 80 C, tetramethylphthalic anhydride and tetramethylisophthalic acid were initially produced. The continued reaction led to the production of trimethylbenzenetricarboxylic acids, but only slight amounts of dimethylbenzenetetracarboxylic acids were detected in the reaction mixture. Whereas tetramethylphthalic anydride and tetramethylisophthalic acid were obtained, pentamethylbenzoic acid, a possible precursor of them, was scarcely produced. On the other hand, a yellow material extracted with ether from the initial reaction mixture contained bis-(nitromethyl)prehnitene (CH3)4C6(CH2NO2)2, which was easily converted into the phthalic anhydride.

  5. NO to cancer: The complex and multifaceted role of nitric oxide and the epigenetic nitric oxide donor, RRx-001☆

    PubMed Central

    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

  6. Nitric oxide and chemically induced hepatotoxicity: beneficial effects of the liver-selective nitric oxide donor, V-PYRRO/NO.

    PubMed

    Liu, Jie; Waalkes, Michael P

    2005-03-15

    Nitric oxide (NO) is endogenously produced by the enzyme NO synthase in the cell or pharmacologically delivered to tissues as NO prodrugs. This simple molecule is a potent biological mediator in a myriad of physiological and pathological events. The liver plays a central role in metabolism and immune processes, and is a major target organ influenced by NO. NO production in the liver is usually increased in response to acute insult with hepatotoxicants, and may be decreased during chronic liver diseases. The induction of NO production could be envisioned as an early adaptive response, which may become a mediator of tissue damage when in excess. In this regard, inhibition of endogenous NO synthase has been shown to be beneficial in some cases and detrimental in others. The creation of eNOS and iNOS knockout animals has advanced our understanding of NO function in hepatic response to toxic insults. Knocking endogenous NO production can be beneficial in response to certain toxicants; however, in general it weakens the body's defense mechanisms against toxic insults. A variety of pharmacological NO prodrugs have been developed, and, when used appropriately, most of them have demonstrated beneficial effects in the liver in a variety of pathological settings. In this review, we discuss the relationship between NO and hepatotoxicity, and the beneficial effects of NO donors on the liver, using the liver-selective NO donor, V-PYRRO/NO, as an example to demonstrate that pharmacologically delivered NO could have therapeutic benefits for liver disorders. PMID:15691592

  7. Is endothelial-nitric-oxide-synthase-derived nitric oxide involved in cardiac hypoxia/reoxygenation-related damage?

    PubMed

    Rus, A; Peinado, M A; Blanco, S; Del Moral, M L

    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 LNIO would not be useful in alleviating the adverse effects of cardiac H/R. PMID:21451249

  8. Indoor-outdoor nitric oxide and nitrogen dioxide concentrations at three sites in Riyadh, Saudi Arabia

    SciTech Connect

    Rowe, D.R. ); Al-Dhowalia, K.H.; Mansour, M.E. )

    1991-08-01

    The objective of this study was to evaluate the nitric oxide and nitrogen oxide concentrations indoors and outdoors at three sites in Riyadh, Saudi Arabia. Results show that the outdoor and indoor concentrations for NO were at least 270 and 16 times the reported average worldwide NO concentrations, respectively. The NO(sub 2) concentrations were about 14 times reported outdoor worldwide levels; however, NO(sub 2) concentrations indoors were generally below those reported in the literature. The data presented, in combination with information presented in previous articles, will provide a valuable background database for use in dispersion models to determine the effect of the Kuwaiti oil well fires on the air quality of Riyadh.

  9. Nitric Oxide in the Offensive Strategy of Fungal and Oomycete Plant Pathogens

    PubMed Central

    Arasimowicz-Jelonek, Magdalena; Floryszak-Wieczorek, Jolanta

    2016-01-01

    In the course of evolutionary changes pathogens have developed many invasion strategies, to which the host organisms responded with a broad range of defense reactions involving endogenous signaling molecules, such as nitric oxide (NO). There is evidence that pathogenic microorganisms, including two most important groups of eukaryotic plant pathogens, also acquired the ability to synthesize NO via non-unequivocally defined oxidative and/or reductive routes. Although the both kingdoms Chromista and Fungi are remarkably diverse, the experimental data clearly indicate that pathogen-derived NO is an important regulatory molecule controlling not only developmental processes, but also pathogen virulence and its survival in the host. An active control of mitigation or aggravation of nitrosative stress within host cells seems to be a key determinant for the successful invasion of plant pathogens representing different lifestyles and an effective mode of dispersion in various environmental niches. PMID:26973690

  10. Nitric Oxide in the Offensive Strategy of Fungal and Oomycete Plant Pathogens.

    PubMed

    Arasimowicz-Jelonek, Magdalena; Floryszak-Wieczorek, Jolanta

    2016-01-01

    In the course of evolutionary changes pathogens have developed many invasion strategies, to which the host organisms responded with a broad range of defense reactions involving endogenous signaling molecules, such as nitric oxide (NO). There is evidence that pathogenic microorganisms, including two most important groups of eukaryotic plant pathogens, also acquired the ability to synthesize NO via non-unequivocally defined oxidative and/or reductive routes. Although the both kingdoms Chromista and Fungi are remarkably diverse, the experimental data clearly indicate that pathogen-derived NO is an important regulatory molecule controlling not only developmental processes, but also pathogen virulence and its survival in the host. An active control of mitigation or aggravation of nitrosative stress within host cells seems to be a key determinant for the successful invasion of plant pathogens representing different lifestyles and an effective mode of dispersion in various environmental niches. PMID:26973690

  11. Influence of nitric oxide synthase inhibition, nitric oxide and hydroperoxide on insulin release induced by various secretagogues.

    PubMed Central

    Panagiotidis, G; Akesson, B; Rydell, E L; Lundquist, I

    1995-01-01

    1. Recent studies have suggested that the generation of nitric oxide (NO) and hydrogen peroxide (H2O2) by islet NO synthase and monoamine oxidase, respectively, may have a regulatory influence on insulin secretory processes. We have investigated the pattern of insulin release from isolated islets of Langerhans in the presence of various pharmacological agents known to perturb the intracellular levels of NO and the oxidation state of SH-groups. 2. The NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) dose-dependently increased L-arginine-induced insulin release. D-Arginine did not influence L-arginine-induced insulin secretion. However, D-NAME which reportedly has no inhibitory action on NO synthase, modestly increased L-arginine-induced insulin release, but was less effective than L-NAME. High concentrations (10 mM) of D-arginine as well as L-NAME and D-NAME could enhance basal insulin release. 3. The intracellular NO donor, hydroxylamine, dose-dependently inhibited insulin secretion induced by L-arginine and L-arginine+L-NAME. 4. Glucose-induced insulin release was increased by NO synthase inhibition (L-NAME) and inhibited by the intracellular NO donor, hydroxylamine. Sydnonimine-1 (SIN-1), an extracellular donor of NO and superoxide, induced a modest suppression of glucose-stimulated insulin release. SIN-1 did not influence insulin secretion induced by L-arginine or the adenylate cyclase activator, forskolin. 5. The intracellular 'hydroperoxide donor' tert-butylhydroperoxide in the concentration range of 0.03-3 mM inhibited insulin release stimulated by the nutrient secretagogues glucose and L-arginine. Low concentrations (0.03-30 microM) of tert-butylhydroperoxide, however enhanced insulin secretion induced by the phosphodiesterase inhibitor isobutylmethylxanthine (IBMX).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7533613

  12. Mamao Pomace Extract Alleviates Hypertension and Oxidative Stress in Nitric Oxide Deficient Rats

    PubMed Central

    Kukongviriyapan, Upa; Kukongviriyapan, Veerapol; Pannangpetch, Patchareewan; Donpunha, Wanida; Sripui, Jintana; Sae-Eaw, Amporn; Boonla, Orachorn

    2015-01-01

    Reactive oxygen species (ROS)-induced oxidative stress plays a major role in pathogenesis of hypertension. Antidesma thwaitesianum (local name: Mamao) is a tropical plant distributed in the tropical/subtropical areas of the world, including Thailand. Mamao pomace (MP), a by-product generated from Mamao fruits, contains large amounts of antioxidant polyphenolic compounds. The aim of this study was to investigate the antihypertensive and antioxidative effects of MP using hypertensive rats. For this purpose, male Sprague-Dawley rats were given Nω-nitro-l-arginine methyl ester (l-NAME), an inhibitor of endothelial nitric oxide synthase (eNOS), in drinking water (50 mg/kg) for three weeks. MP extract was orally administered daily at doses of 100 and 300 mg/kg. l-NAME administration induced marked increase in blood pressure, peripheral vascular resistance, and oxidative stress. MP treatment significantly prevented the increase in blood pressure, hindlimb blood flow and hindlimb vascular resistance of l-NAME treated hypertensive rats (p < 0.05). The antihypertensive effect of MP treatment was associated with suppression of superoxide production from carotid strips and also with an increase in eNOS protein expression and nitric oxide bioavailability. The present results provide evidence for the antihypertensive effect of MP and suggest that MP might be useful as a dietary supplement against hypertension. PMID:26225998

  13. Manganese-induced oxidative stress in two ontogenetic stages of chamomile and amelioration by nitric oxide.

    PubMed

    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. PMID:24388509

  14. Laser-fluorescence measurements of nitric oxide in low-pressure H2/O2/NO flames

    NASA Technical Reports Server (NTRS)

    Cattolica, R. J.; Mataga, T. G.; Cavolowsky, J. A.

    1989-01-01

    The concentration profiles of NO in low-pressure (76 Torr) H2/O2/Ar flames to which nitric oxide is added are measured by pulsed laser-induced fluorescence. Temporally resolved fluorescence measurements are used to determine the collisional deexcitation rates needed to convert time-integrated fluorescence signal into oxide concentration. Five flames are studied with H2/O2 equivalence ratios of 0.88, 0.98, 1.22, 1.37, and 1.50. In these flames the collisional deexcitation rate decreases rapidly above the burner surface as the density decreases with increasing temperature. A 20 percent decrease is observed for the lean flames, and a 30 percent decrease for the rich flames. Within the precision of the measurement technique (+ or - 10 percent), no significant removal of nitric oxide is observed in these flames.

  15. Solubilization and Resolution of the Membrane-Bound Nitrite Reductase from Paracoccus Halodenitrificans into Nitrite and Nitric Oxide Reductases

    NASA Technical Reports Server (NTRS)

    Grant, Michael A.; Cronin, Sonja E.; Hochstein, Lawrence I.

    1984-01-01

    Membranes prepared from Paracoccus halodenitrificans reduced nitrite or nitric oxide to nitrous oxide. Extraction of these membranes with the detergent CHAPSO [3-(3-Chlolamidoporopyldimethylammonio)-1-(2- hydroxy-1-propanesulfonate)], followed by ammonium sulfate fractionation of the solubilized proteins, resulted in the separation of nitrite and nitric oxide reductase activities. The fraction containing nitrite reductase activity spectrally resembled a cd-type cytochrome. Several cytochromes were detected in the nitric oxide reductase fraction. Which, if any, of these cytochromes is associated with the reduction of nitric oxide is not clear at this time.

  16. Oleic acid-dependent modulation of Nitric oxide associated 1 protein levels regulates nitric oxide-mediated defense signaling in Arabidopsis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  17. Nitric oxide and salicylic acid signaling in plant defense

    PubMed Central

    Klessig, Daniel F.; Durner, Jörg; Noad, Robert; Navarre, Duroy A.; Wendehenne, David; Kumar, Dhirendra; Zhou, Jun Ma; Shah, Jyoti; Zhang, Shuqun; Kachroo, Pradeep; Trifa, Youssef; Pontier, Dominique; Lam, Eric; Silva, Herman

    2000-01-01

    Salicylic acid (SA) plays a critical signaling role in the activation of plant defense responses after pathogen attack. We have identified several potential components of the SA signaling pathway, including (i) the H2O2-scavenging enzymes catalase and ascorbate peroxidase, (ii) a high affinity SA-binding protein (SABP2), (iii) a SA-inducible protein kinase (SIPK), (iv) NPR1, an ankyrin repeat-containing protein that exhibits limited homology to IκBα and is required for SA signaling, and (v) members of the TGA/OBF family of bZIP transcription factors. These bZIP factors physically interact with NPR1 and bind the SA-responsive element in promoters of several defense genes, such as the pathogenesis-related 1 gene (PR-1). Recent studies have demonstrated that nitric oxide (NO) is another signal that activates defense responses after pathogen attack. NO has been shown to play a critical role in the activation of innate immune and inflammatory responses in animals. Increases in NO synthase (NOS)-like activity occurred in resistant but not susceptible tobacco after infection with tobacco mosaic virus. Here we demonstrate that this increase in activity participates in PR-1 gene induction. Two signaling molecules, cGMP and cyclic ADP ribose (cADPR), which function downstream of NO in animals, also appear to mediate plant defense gene activation (e.g., PR-1). Additionally, NO may activate PR-1 expression via an NO-dependent, cADPR-independent pathway. Several targets of NO in animals, including guanylate cyclase, aconitase, and mitogen-activated protein kinases (e.g., SIPK), are also modulated by NO in plants. Thus, at least portions of NO signaling pathways appear to be shared between plants and animals. PMID:10922045

  18. The formation of nitric oxide donors from peroxynitrite.

    PubMed Central

    Moro, M. A.; Darley-Usmar, V. M.; Lizasoain, I.; Su, Y.; Knowles, R. G.; Radomski, M. W.; Moncada, S.

    1995-01-01

    1. Administration of peroxynitrite (ONOO-, 30-300 microM) caused relaxation of rabbit aortic strips superfused in series in a cascade. The compound responsible for this effect had a half-life greater than 20 s and could not therefore be either nitric oxide (NO) or ONOO- which have half-lives in the order of 1-2 s under these conditions. However the relaxation was inhibited by oxyhaemoglobin, suggesting the compound could be converted to NO in the vascular tissues or in the superfusate. 2. The products of the reactions between ONOO- and Krebs buffer containing 11 mM glucose, but not glucose-free Krebs buffer, caused relaxation of the bioassay tissues. These data suggest that stable NO donor(s) were formed from the reaction of ONOO- with glucose. We therefore prepared these NO donor(s) by the reaction of glucose solutions with ONOO- in order to characterize their ability to release NO. 3. These reaction product(s) caused relaxation in the cascade and inhibition of platelet aggregation. Both effects were dependent on the concentration of D-glucose, were equally effective if L-glucose was used as a reactant and were reversed by oxyhaemoglobin. 3. The products of the reaction between ONOO- and glucose or other biological molecules containing an alcohol functional group, such as fructose, glycerol, or glyceraldehyde, released NO in the presence of Cu2+and L-cysteine. 5. These results indicate that ONOO- reacts with sugars or other compounds containing an alcohol functional group(s) to form NO donors with the characteristics of organic nitrate/nitrites. This may represent a further detoxification pathway for ONOO- in vivo. PMID:8640338

  19. Nitric oxide targets oligodendrocytes and promotes their morphological differentiation.

    PubMed

    Garthwaite, Giti; Hampden-Smith, Kathryn; Wilson, Gary W; Goodwin, David A; Garthwaite, John

    2015-03-01

    In the central nervous system, nitric oxide (NO) transmits signals from one neurone to another, or from neurones to astrocytes or blood vessels, but the possibility of oligodendrocytes being physiological NO targets has been largely ignored. By exploiting immunocytochemistry for cGMP, the second messenger generated on activation of NO receptors, oligodendrocytes were found to respond to both exogenous and endogenous NO in cerebellar slices from rats aged 8 days to adulthood. Atrial natriuretic peptide, which acts on membrane-associated guanylyl cyclase-coupled receptors, also raised oligodendrocyte cGMP in cerebellar slices. The main endogenous source of NO accessing oligodendrocytes appeared to be the neuronal NO synthase isoform, which was active even under basal conditions and in a manner that was independent of glutamate receptors. Oligodendrocytes in brainstem slices were also shown to be potential NO targets. In contrast, in the optic nerve, oligodendrocyte cGMP was raised by natriuretic peptides but not NO. When cultures of cerebral cortex were continuously exposed to low NO concentrations (estimated as 40-90 pM), oligodendrocytes responded with a striking increase in arborization. This stimulation of oligodendrocyte growth could be replicated by low concentrations of 8-bromo-cGMP (maximum effect at 1 µM). It is concluded that oligodendrocytes are probably widespread targets for physiological NO (or natriuretic peptide) signals, with the resulting rise in cGMP serving to enhance their growth and maturation. NO might help coordinate the myelination of axons to the ongoing level of neuronal activity during development and could potentially contribute to adaptive changes in myelination in the adult. PMID:25327839

  20. From synaptically localized to volume transmission by nitric oxide.

    PubMed

    Garthwaite, John

    2016-01-01

    Nitric oxide (NO) functions widely as a transmitter/diffusible second messenger in the central nervous system, exerting physiological effects in target cells by binding to specialized guanylyl cyclase-coupled receptors, resulting in cGMP generation. Despite having many context-dependent physiological roles and being implicated in numerous disease states, there has been a lack of clarity about the ways that NO operates at the cellular and subcellular levels. Recently, several approaches have been used to try to gain a more concrete, quantitative understanding of this unique signalling pathway. These approaches have included analysing the kinetics of NO receptor function, real-time imaging of cellular NO signal transduction in target cells, and the use of ultrasensitive detector cells to record NO as it is being generated from native sources in brain tissue. The current picture is that, when formed in a synapse, NO is likely to act only very locally, probably mostly within the confines of that synapse, and to exist only in picomolar concentrations. Nevertheless, closely neighbouring synapses may also be within reach, raising the possibility of synaptic crosstalk. By engaging its enzyme-coupled receptors, the low NO concentrations are able to stimulate physiological (submicromolar) increases in cGMP concentration in an activity-dependent manner. When many NO-emitting neurones or synapses are active simultaneously in a tissue region, NO can act more like a volume transmitter to influence, and perhaps coordinate, the behaviour of cells within that region, irrespective of their identity and anatomical connectivity. PMID:26486504

  1. Energy Landscapes and Catalysis in Nitric-oxide Synthase*

    PubMed Central

    Sobolewska-Stawiarz, Anna; Leferink, Nicole G. H.; Fisher, Karl; Heyes, Derren J.; Hay, Sam; Rigby, Stephen E. J.; Scrutton, Nigel S.

    2014-01-01

    Nitric oxide (NO) plays diverse roles in mammalian physiology. It is involved in blood pressure regulation, neurotransmission, and immune response, and is generated through complex electron transfer reactions catalyzed by NO synthases (NOS). In neuronal NOS (nNOS), protein domain dynamics and calmodulin binding are implicated in regulating electron flow from NADPH, through the FAD and FMN cofactors, to the heme oxygenase domain, the site of NO generation. Simple models based on crystal structures of nNOS reductase have invoked a role for large scale motions of the FMN-binding domain in shuttling electrons from the FAD-binding domain to the heme oxygenase domain. However, molecular level insight of the dynamic structural transitions in NOS enzymes during enzyme catalysis is lacking. We use pulsed electron-electron double resonance spectroscopy to derive inter-domain distance relationships in multiple conformational states of nNOS. These distance relationships are correlated with enzymatic activity through variable pressure kinetic studies of electron transfer and turnover. The binding of NADPH and calmodulin are shown to influence interdomain distance relationships as well as reaction chemistry. An important effect of calmodulin binding is to suppress adventitious electron transfer from nNOS to molecular oxygen and thereby preventing accumulation of reactive oxygen species. A complex landscape of conformations is required for nNOS catalysis beyond the simple models derived from static crystal structures of nNOS reductase. Detailed understanding of this landscape advances our understanding of nNOS catalysis/electron transfer, and could provide new opportunities for the discovery of small molecule inhibitors that bind at dynamic protein interfaces of this multidimensional energy landscape. PMID:24610812

  2. Biogenic nitric oxide emissions upscaling: An approach for Zimbabwe

    NASA Astrophysics Data System (ADS)

    Kirkman, G. A.; Yang, W. X.; Meixner, F. X.

    2001-12-01

    A mechanistic upscaling scheme was developed to estimate temporal nitric oxide [NO] emissions from soils for three distinct land use classes by spatial extrapolation of laboratory measurements for Zimbabwe (383,667 km2). Laboratory measurements on miombo woodland, grassland, and agricultural Zimbabwean soils were used to derive moisture- and temperature-dependent NO emission algorithms. By combining monthly fields of modeled soil moisture and temperature (based on climate means, vegetation indices, soil, and terrain elevation data) a mean monthly soil NO flux, including rainfall-induced elevated flux events (pulsing), was obtained. Countrywide emission rates ranged from 0.1-0.4 ng N m-2 s-1 for the dry season to wet season mean fluxes of 3.7-9.4 ng N m-2 s-1 for miombo, 4.4-7.0 ng N m-2 s-1 for grassland, and 4.6-10.9 ng N m-2 s-1 for agriculture. Annual net soil NO emissions (less canopy reduction) for Zimbabwe were 32.9 Gg N yr-1, with miombo woodlands (66% of Zimbabwe) contributing 63% to the regional NO budget. Rainfall-induced NO pulsing contributed an additional 14% to countrywide annual bulk NO emissions. The majority of these pulses occurred during the first half of the rainy season (November-December), with agricultural soils contributing the most and grassland soils contributing the least to pulsing. The upscaling approach provided a first countrywide estimate of spatiotemporal soil NO emissions for a hitherto largely unresolved source: the soil-moisture-limited African subtropical savannas.

  3. Production of Nitric Oxide within the Aplysia californica Nervous System

    PubMed Central

    2009-01-01

    Nitric oxide (NO), an intercellular signaling molecule, helps coordinate neuronal network activity. Here we examine NO generation in the Aplysia californica central nervous system using 4,5-diaminofluorescein diacetate (DAF-2 DA), a fluorescent reagent that forms 4,5-diaminofluorescein triazole (DAF-2T) upon reaction with NO. Recognizing that other fluorescence products are formed within the biochemically complex intracellular environment, we validate the observed fluorescence as being from DAF-2T; using both capillary electrophoresis and mass spectrometry we confirm that DAF-2T is formed from tissues and cells exposed to DAF-2 DA. We observe three distinct subcellular distributions of fluorescence in neurons exposed to DAF-2 DA. The first shows uniform fluorescence inside the cell, with these cells being among previously confirmed NO synthase (NOS)-positive regions in the Aplysia cerebral ganglion. The second, seen inside buccal neurons, exhibits point sources of fluorescence, 1.5 ± 0.7 μm in diameter. Interestingly, the number of fluorescence puncta increases when the tissue is preincubated with the NOS substrate l-arginine, and they disappear when cells are preexposed to the NOS inhibitor l-nitro-arginine methyl ester (l-NAME), demonstrating that the fluorescence is connected to NOS-dependent NO production. The third distribution type, seen in the R2 neuron, also exhibits fluorescent puncta but only on the cell surface. Fluorescence is also observed in the terminals of cultured bag cell neurons loaded with DAF-2 DA. Surprisingly, fluorescence at the R2 surface and bag cell neuron terminals is not modulated by l-arginine or l-NAME, suggesting that it has a source distinct from the buccal and cerebral ganglion DAF 2T-positive tissues. PMID:20532188

  4. Fluorinated Xerogel-Derived Microelectrodes for Amperometric Nitric Oxide Sensing

    PubMed Central

    Shin, Jae Ho; Privett, Benjamin J.; Kita, Justin M.; Wightman, R. Mark; Schoenfisch, Mark H.

    2009-01-01

    An amperometric fluorinated xerogel-derived nitric oxide (NO) microelectrode is described. A range of fluorine-modified xerogel polymers were synthesized via the co-hydrolysis and condensation of alkylalkoxy- and fluoroalkoxysilanes. Such polymers were evaluated as NO sensor membranes to identify the optimum composition for maximizing NO permeability while providing sufficient selectivity for NO in the presence of common interfering species. By taking advantage of both the versatility of sol–gel chemistry and the “poly(tetrafluoroethylene) (PTFE)-like” high NO permselective properties of the xerogels, the performance of the fluorinated xerogel-derived sensors was excellent, surpassing all miniaturized NO sensors reported to date. In contrast to previous electrochemical NO sensor designs, xerogel-based NO microsensors were fabricated using a simple, reliable dip-coating procedure. An optimal permselective membrane was achieved by synthesizing xerogels of methyltrimethoxysilane (MTMOS) and 20% (heptadecafluoro-1,1,2,2-tetrahydrodecyl)trimethoxysilane (17FTMS, balance MTMOS) under acid-catalyzed conditions. The resulting NO microelectrode had a conical tip of ~20 μm in diameter and ~55 mm in length, and exhibited sensitivities of 7.91 pA·nM−1 from 0.2 to 3.0 nM (R2 = 0.9947) and 7.60 nA·mM−1 from 0.5 to 4.0 μM (R2 = 0.9999), detection limit of 83 pM (S/N = 3), response time (t95%) of <3 sec, and selectivity (logKNO,jamp) of −5.74, <−6, <−6, <−6, <−6, −5.84, and −1.33 for j = nitrite, ascorbic acid, uric acid, acetaminophen, dopamine, ammonia/ammonium, and carbon monoxide. In addition, the sensor proved functional up to 20 d, maintaining ≥90% of the sensor's initial sensitivity without serious deterioration in selectivity. PMID:18714964

  5. DISSECTING STRUCTURAL AND ELECTRONIC EFFECTS IN INDUCIBLE NITRIC OXIDE SYNTHASE

    PubMed Central

    Hannibal, Luciana; Page, Richard C.; Haque, Mohammad Mahfuzul; Bolisetty, Karthik; Yu, Zhihao; Misra, Saurav; Stuehr, Dennis J.

    2015-01-01

    Nitric oxide synthases (NOS) are haem-thiolate enzymes that catalyse the conversion of L-Arginine (LArg) 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 an H-bond for oxygen activation (O-O scission). We present a comparative study of native iNOS versus 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 their native counterparts. Single turnover reactions catalysed by iNOSoxy with LArg (first reaction step) or N-hydroxyarginine (second reaction step) showed that mesohaem substitution triggered faster rates of FeIIO2 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 to 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 toward 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. PMID:25608846

  6. Nitric oxide signaling in oxytocin-mediated cardiomyogenesis.

    PubMed

    Danalache, Bogdan A; Paquin, Joanne; Donghao, Wang; Grygorczyk, Ryszard; Moore, Jennifer C; Mummery, Christine L; Gutkowska, Jolanta; Jankowski, Marek

    2007-03-01

    Oxytocin (OT), a hormone recently identified in the heart, induces embryonic and cardiac somatic stem cells to differentiate into cardiomyocytes (CM), possibly through nitric oxide (NO). We verified this hypothesis using P19 cells and P19 Clone 6 derivatives expressing a green fluorescent protein (GFP) reporter linked to cardiac myosin light chain-2v promoter. OT treatment of these cells induced beating cell colonies that were fully inhibited by N,G-nitro-L-arginine-methyl-ester (L-NAME), an inhibitor of NO synthases (NOS), partially reduced by 1400W, an inhibitor of inducible NOS, and ODQ, an inhibitor of NO-sensitive guanylyl cyclases. The NO generator S-nitroso-N-acetylpenicillamine (SNAP) reversed the L-NAME inhibition of cell beating and GFP expression. In OT-induced cells, L-NAME significantly decreased transcripts of the cardiac markers Nkx2.5, MEF2c, alpha-myosin heavy chain, and less, GATA4, endothelial NOS, and atrial natriuretic peptide, as well as the skeletal myocyte (SM) marker myogenin. Image analysis of OT-induced P19Cl6-GFP cells revealed ventricular CM coexpressing sarcomeric alpha-actinin and GFP, with some cells exclusively expressing alpha-actinin, most likely of the SM phenotype. The OT-mediated production of CM, but not SM, was diminished by L-NAME. In P19 cells, exogenously added OT stimulated the expression of its own transcript, which was reduced in the presence of L-NAME. Surprisingly, L-NAME alone decreased the expression of anti-stage specific embryonic antigen-1 marker of the undifferentiated state and induced some beating colonies as well as GFP in P19Cl6-GFP cells. Collectively, our data suggest that the pleiotropic action of NO is involved in the initiation of CM differentiation of P19 cells and maintenance of their undifferentiated state. PMID:17138963

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

    PubMed Central

    Freschi, Luciano

    2013-01-01

    Nitric oxide (NO) is currently considered a ubiquitous signal in plant systems, playing significant roles in a wide range of 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. PMID:24130567

  8. Nitric oxide in inflammation and pain associated with osteoarthritis

    PubMed Central

    Abramson, Steven B

    2008-01-01

    Osteoarthritis (OA) is a degenerative disease involving chondrocytes, cartilage and other joint tissues, and has a number of underlying causes, including both biochemical and mechanical factors. Although proinflammatory factors including nitric oxide (NO) are associated with OA, there is recent evidence suggesting that NO and its redox derivatives may also play protective roles in the joint. However, the mechanisms that underlie the development and progression of OA are not completely understood. Experiments have demonstrated that NO plays a catabolic role in the development of OA and mediates the inflammatory response, is involved in the degradation of matrix metalloproteinases, inhibits the synthesis of both collagen and proteoglycans, and helps to mediate apoptosis. However, there is also evidence that in cultured chondrocytes the addition of exogenous NO may inhibit proinflammatory activation by preventing the nuclear localization of the transcription factor nuclear factor-κB, whereas the presence of peroxynitrite – a redox derivative of NO – appears to enhance the inflammatory response by sustaining the nuclear localization of nuclear factor-κB. In addition, under some conditions exogenous NO can stimulate collagen synthesis in cultured rat fibroblasts and human tendon cells. The protective roles of NO in multiple cell types, along with the opposing activities in cultured chondrocytes, suggest that NO may play additional protective roles in chondrocyte function. NO and its derivatives have a similarly complicated involvement in nociception and pain, which may contribute to the functional disability of OA. Further research may help to elucidate a potential role for NO-donating agents in the management of OA. PMID:19007427

  9. Inhaled nitric oxide in acute pulmonary embolism: a systematic review.

    PubMed

    Bhat, Tariq; Neuman, Adi; Tantary, Mohmad; Bhat, Hilal; Glass, Daniel; Mannino, William; Akhtar, Muhammad; Bhat, Alina; Teli, Sumaya; Lafferty, James

    2015-01-01

    Acute pulmonary embolism (PE) is usually a complication secondary to migration of a deep venous clot or thrombi to lungs, but other significant etiologies include air, amniotic fluid, fat, and bone marrow. Regardless of the underlying etiology, little progress has been made in finding an effective pharmacologic intervention for this serious complication. Among the wide spectrum of PE, massive PE is associated with considerable morbidity and mortality, primarily due to severely elevated pulmonary vascular resistance leading to right ventricular failure, hypoxemia, and cardiogenic shock. We currently have limited therapeutic options at our disposal. Inhaled nitric oxide (iNO) has been proposed as a potential therapeutic agent in cases of acute PE in which hemodynamic compromise secondary to increased pulmonary vascular resistance is present, based on iNO's selective dilation of the pulmonary vasculature and antiplatelet activity. A systematic search of studies using the PubMed database was undertaken in order to assess the available literature. Although there are currently no published randomized controlled trials on the subject, except a recently publish phase I trial involving eight patients, several case reports and case series describe and document the use of iNO in acute PE. The majority of published reports have documented improvements in oxygenation and hemodynamic variables, often within minutes of administration of iNO. These reports, when taken together, raise the possibility that iNO may be a potential therapeutic agent in acute PE. However, based on the current literature, it is not possible to conclude definitively whether iNO is safe and effective. These case reports underscore the need for randomized controlled trials to establish the safety and efficacy of iNO in the treatment of massive acute PE. The purpose of this article is to review the current literature in the use of iNO in the setting of PE given how acute PE causes acute onset of pulmonary hypertension. PMID:25813791

  10. Research progress on neurobiology of neuronal nitric oxide synthase.

    PubMed

    Luo, Chun-Xia; Zhu, Dong-Ya

    2011-02-01

    Neuronal nitric oxide synthase (nNOS) is mainly expressed in neurons, to some extent in astrocytes and neuronal stem cells. The alternative splicing of nNOS mRNA generates 5 isoforms of nNOS, including nNOS-α, nNOS-β, nNOS-µ, nNOS-γ and nNOS-2. Monomer of nNOS is inactive, and dimer is the active form. Dimerization requires tetrahydrobiopterin (BH4), heme and L-arginine binding. Regulation of nNOS expression relies largely on cAMP response element-binding protein (CREB) activity, and nNOS activity is regulated by heat shock protein 90 (HSP90)/HSP70, calmodulin (CaM), phosphorylation and dephosphorylation at Ser847 and Ser1412, and the protein inhibitor of nNOS (PIN). There are primarily 9 nNOS-interacting proteins, including post-synaptic density protein 95 (PSD95), clathrin assembly lymphoid leukemia (CALM), calcium/calmodulin-dependent protein kinase II alpha (CAMKIIA), Disks large homolog 4 (DLG4), DLG2, 6-phosphofructokinase, muscle type (PFK-M), carboxy-terminal PDZ ligand of nNOS (CAPON) protein, syntrophin and dynein light chain (LC). Among them, PSD95, CAPON and PFK-M are important nNOS adapter proteins in neurons. The interaction of PSD95 with nNOS controls synapse formation and is implicated in N-methyl-D-aspartic acid-induced neuronal death. nNOS-derived NO is implicated in synapse loss-mediated early cognitive/motor deficits in several neuropathological states, and negatively regulates neurogenesis under physiological and pathological conditions. PMID:21270901

  11. Altered Nitric Oxide System in Cardiovascular and Renal Diseases

    PubMed Central

    Bae, Eun Hui; Ma, Seong Kwon; Kim, Soo Wan

    2016-01-01

    Nitric oxide (NO) is synthesized by a family of NO synthases (NOS), including neuronal, inducible, and endothelial NOS (n/i/eNOS). NO-mediated effects can be beneficial or harmful depending on the specific risk factors affecting the disease. In hypertension, the vascular relaxation response to acetylcholine is blunted, and that to direct NO donors is maintained. A reduction in the activity of eNOS is mainly responsible for the elevation of blood pressure, and an abnormal expression of iNOS is likely to be related to the progression of vascular dysfunction. While eNOS/nNOS-derived NO is protective against the development of atherosclerosis, iNOS-derived NO may be proatherogenic. eNOS-derived NO may prevent the progression of myocardial infarction. Myocardial ischemia/reperfusion injury is significantly enhanced in eNOS-deficient animals. An important component of heart failure is the loss of coronary vascular eNOS activity. A pressure-overload may cause severer left ventricular hypertrophy and dysfunction in eNOS null mice than in wild-type mice. iNOS-derived NO has detrimental effects on the myocardium. NO plays an important role in regulating the angiogenesis and slowing the interstitial fibrosis of the obstructed kidney. In unilateral ureteral obstruction, the expression of eNOS was decreased in the affected kidney. In triply n/i/eNOS null mice, nephrogenic diabetes insipidus developed along with reduced aquaporin-2 abundance. In chronic kidney disease model of subtotal-nephrectomized rats, treatment with NOS inhibitors decreased systemic NO production and induced left ventricular systolic dysfunction (renocardiac syndrome). PMID:27231671

  12. The clinical use of exhaled nitric oxide in wheezing children.

    PubMed

    Martins, Pedro; Caires, Iolanda; Rosado Pinto, José; Lopes da Mata, Pedro; Torres, Simões; Valente, Joana; Borrego, Carlos; Neuparth, Nuno

    2008-01-01

    The body of published work on the role of exhaled nitric oxide (FENO) in the study of bronchial inflammation allows it to be classed as a simple, non-invasive measurement that is very useful in evaluating asthmatic patients. During a prospective study into the effects of air pollution on the health of the population of Viseu (Saud'AR Project), children with a clinical history of wheezing were identified through using the International Study of Asthma and Allergy in Childhood (ISAAC) questionnaire. Children later filled in a new standardised questionnaire and underwent skin-prick-tests, spirometry and FENO measurement. Their mean age was 7.8+/-1.1 years. Comparing those who wheezed in the 6 months before evaluation (n=27) with those who didn't, statistical differences for DeltaFEV1 (8% median versus 4.5%, p=0.0399) and for FENO (23 ppb median versus 12 ppb, p=0.0195, respectively) were observed. Concerning children who needed a bronchodilator in the six previous months (n=19) and those who didn't, there was also a statistically significant difference in FENO: 27 ppb median versus 11 ppb median, respectively; p<0.0001. When comparing children who needed an unscheduled medical appointment in the six months previous to the evaluation (n=9) and those who didn't, there was also significant differences for FE NO: 28 ppb median versus 13 ppb median, p=0.0029. In conclusion, the existence of symptoms seems to be better related to FE NO than spirometry. PMID:18363018

  13. Emission of nitric oxide from soil: laboratory vs. micrometeorological techniques

    NASA Astrophysics Data System (ADS)

    Meixner, F. X.; Mayer, J.-C.; Bargsten, A.; Andreae, M. O.

    2009-04-01

    High quality field measurements of the surface exchange of nitric oxide (NO) between soils and the atmosphere usually demand complex instrumentation and considerable power supplies. The latter often impedes such flux measurements at remote sites. However, soil samples could be taken everywhere, and consecutive parameterization of NO emission rates (derived from laboratory incubation of these soil samples) and up-scaling through independent data of soil properties (e.g. soil moisture, soil temperature, soil texture) is an effective alternative to quantify NO emission from soils, particularly from (very) remote sites. These laboratory derived NO emission rates have quite frequently verified through field measurements by the dynamic chamber technique. Here, we will present the first intercomparison between the laboratory and a micrometeorological (gradient) technique. In August 2006, the field experiment LIBRETTO (LIndenBerg REacTive Trace gas prOfiles) was carried out in cooperation with the German Meteorological Service (DWD) at the field site of the Richard Aßmann Observatory in Lindenberg. At 0.15 m and 2.0 m, concentrations of the trace gases O3, NO and NO2 were measured. Applying the modified Bowen ration technique to the measured concentration differences and the directly measured sensible heat flux (eddy covariance data from DWD) yielded the field surface fluxes of the trace gases (corrected for their flux divergence due to fast photochemical reactions during the vertical turbulent transport). Soil humidity and temperature in the top soil were measured at a separate plot at the field site. Mixed soil samples were taken in May 2008 at the LIBRETTO field site, air-dried, sieved (

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

    PubMed Central

    Groß, Felicitas; Durner, Jörg; Gaupels, Frank

    2013-01-01

    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-signaling. In chemical reactions between NO and ROS reactive nitrogen species (RNS) 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 catalyzing 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 (PCD). PMID:24198820

  15. Nitric oxide targets oligodendrocytes and promotes their morphological differentiation

    PubMed Central

    Garthwaite, Giti; Hampden-Smith, Kathryn; Wilson, Gary W; Goodwin, David A; Garthwaite, John

    2015-01-01

    In the central nervous system, nitric oxide (NO) transmits signals from one neurone to another, or from neurones to astrocytes or blood vessels, but the possibility of oligodendrocytes being physiological NO targets has been largely ignored. By exploiting immunocytochemistry for cGMP, the second messenger generated on activation of NO receptors, oligodendrocytes were found to respond to both exogenous and endogenous NO in cerebellar slices from rats aged 8 days to adulthood. Atrial natriuretic peptide, which acts on membrane-associated guanylyl cyclase-coupled receptors, also raised oligodendrocyte cGMP in cerebellar slices. The main endogenous source of NO accessing oligodendrocytes appeared to be the neuronal NO synthase isoform, which was active even under basal conditions and in a manner that was independent of glutamate receptors. Oligodendrocytes in brainstem slices were also shown to be potential NO targets. In contrast, in the optic nerve, oligodendrocyte cGMP was raised by natriuretic peptides but not NO. When cultures of cerebral cortex were continuously exposed to low NO concentrations (estimated as 4090 pM), oligodendrocytes responded with a striking increase in arborization. This stimulation of oligodendrocyte growth could be replicated by low concentrations of 8-bromo-cGMP (maximum effect at 1 M). It is concluded that oligodendrocytes are probably widespread targets for physiological NO (or natriuretic peptide) signals, with the resulting rise in cGMP serving to enhance their growth and maturation. NO might help coordinate the myelination of axons to the ongoing level of neuronal activity during development and could potentially contribute to adaptive changes in myelination in the adult. PMID:25327839

  16. The role of nuclear endothelial nitric oxide synthase in the endothelial and prostate microenvironments.

    PubMed

    Nanni, Simona; Grasselli, Annalisa; Benvenuti, Valentina; Aiello, Aurora; Pantisano, Valentina; Re, Agnese; Gaetano, Carlo; Capogrossi, Maurizio C; Bacchetti, Silvia; Pontecorvi, Alfredo; Farsetti, Antonella

    2011-03-01

    This review is based on novel observations from our laboratory on the nuclear translocation and functional role of endothelial nitric oxide synthase (eNOS) in endothelial and prostate cancer (PCa) epithelial cells. Nitric oxide (NO), the product of eNOS, is a free radical involved in the physiology and pathophysiology of living organisms and in a variety of biological processes including the maintenance of vascular homeostasis. Of relevance in this context is the role that estrogens play in the apoptotic process and the migration of endothelial cells through the regulation of target genes such as eNOS itself. It has been shown that both estrogen and NO signaling, mediated respectively by the estrogen receptors (ERs) and eNOS, can strongly counteract endothelial senescence through a common effector, the catalytic subunit of human telomerase. Therefore, this protein has been identified as a key molecule in the aging process which, intriguingly, is considered the only risk factor in the development of PCa and one of the major determinants of cardiovascular diseases. Indeed, in both these contexts we have defined a molecular mechanism involving activation of eNOS and hypoxia-inducible factors in association with ERβ that characterizes the most aggressive form of PCa or influences endothelial cell differentiation. Altogether these data led us to postulate that activation of eNOS is a crucial requirement for the delaying of endothelial senescence as well as for the acquisition of androgen-independence and for tumor progression in the prostate microenvironment. PMID:25961244

  17. Photo-control of nitric oxide synthase activity using a caged isoform specific inhibitor.

    PubMed

    Montgomery, Heather J; Perdicakis, Basil; Fishlock, Dan; Lajoie, Gilles A; Jervis, Eric; Guy Guillemette, J

    2002-06-01

    Nitric oxide (NO) plays a critical role in a number of physiological processes and is produced in mammalian cells by nitric oxide synthase (NOS) isozymes. Because of the diverse functions of NO, pharmaceutical interventions which seek to abrogate adverse effects of excess NOS activity must not interfere with the normal regulation of NO levels in the body. A method has been developed for the control of NOS enzyme activity using the localized photochemical release of a caged isoform-specific NOS inhibitor. The caged form of an iNOS inhibitor has been synthesized and tested for photosensitivity and potency. UV and multiphoton uncaging were verified using a hemoglobin-based assay. IC(50) values were determined for the inhibitor (70+/-11 nM), the caged inhibitor (1098+/-172 nM), the UV uncaged inhibitor (67+/-26 nM) and the multiphoton uncaged inhibitor (73+/-11 nM). UV irradiation of the caged inhibitor resulted in a 86% reduction in iNOS activity after 5 min. Multiphoton uncaging had an apparent first order time constant of 0.007+/-0.001 min(-1). A therapeutic range exists, with molar excess of inhibitor to enzyme from 3- to 7-fold, over which the full dynamic range of the inhibition can be exploited. PMID:11937350

  18. Generation of a Conditional Allele for the Mouse Endothelial Nitric Oxide Synthase Gene

    PubMed Central

    Jiang, Rosie; Wang, Suwan; Takahashi, Keiko; Fujita, Hiroki; Fruci, Christopher R.; Breyer, Matthew D.; Harris, Raymond C; Takahashi, Takamune

    2012-01-01

    Mice with endothelial nitric oxide synthase (eNOS) deletions have defined the crucial role of eNOS in vascular development, homeostasis, and pathology. However, cell specific eNOS function has not been determined, although an important role of eNOS has been suggested in multiple cell types. Here we have generated a floxed eNOS allele in which exons 9–12, encoding the sites essential to eNOS activity, are flanked with loxP sites. Mice homozygous for the floxed allele showed normal eNOS protein levels and no overt phenotype. Conversely, homozygous mice with Cre-deleted alleles displayed truncated eNOS protein, lack of vascular nitric oxide production, and exhibited similar phenotype to eNOS knockout mice, including hypertension, low heart rate, and focal renal scar. These findings demonstrate that the floxed allele is normal and it can be converted to a non-functional eNOS allele through Cre recombination. This mouse will allow time and cell specific eNOS deletion. PMID:22467476

  19. Borna disease virus P protein inhibits nitric oxide synthase gene expression in astrocytes

    SciTech Connect

    Peng Guiqing; Zhang Fengmin; Zhang Qi; Wu Kailang; Zhu Fan; Wu Jianguo

    2007-09-30

    Borna disease virus (BDV) is one of the potential infectious agents involved in the development of central nervous system (CNS) diseases. Neurons and astrocytes are the main targets of BDV infection, but little is known about the roles of BDV infection in the biological effects of astrocytes. Here we reported that BDV inhibits the activation of inducible nitric oxide synthase (iNOS) in murine astrocytes induced by bacterial LPS and PMA. To determine which protein of BDV is responsible for the regulation of iNOS expression, we co-transfected murine astrocytes with reporter plasmid iNOS-luciferase and plasmid expressing individual BDV proteins. Results from analyses of reporter activities revealed that only the phosphoprotein (P) of BDV had an inhibitory effect on the activation of iNOS. In addition, P protein inhibits nitric oxide production through regulating iNOS expression. We also reported that the nuclear factor kappa B (NF-{kappa}B) binding element, AP-1 recognition site, and interferon-stimulated response element (ISRE) on the iNOS promoter were involved in the repression of iNOS gene expression regulated by the P protein. Functional analysis indicated that sequences from amino acids 134 to 174 of the P protein are necessary for the regulation of iNOS. These data suggested that BDV may suppress signal transduction pathways, which resulted in the inhibition of iNOS activation in astrocytes.

  20. Nitrous oxide-antinociception is mediated by opioid receptors and nitric oxide in the periaqueductal gray region of the midbrain

    PubMed Central

    Emmanouil, Dimitris E.; Dickens, Andrea S.; Heckert, Rick W.; Ohgami, Yusuke; Chung, Eunhee; Han, Shujie; Quock, Raymond M.

    2008-01-01

    Previous studies have shown that nitrous oxide (N2O)-induced antinociception is sensitive to antagonism by blockade of opioid receptors and also by inhibition of nitric oxide (NO) production. The present study was conducted to determine whether these occur within the same brain site. Mice were stereotaxically implanted with microinjection cannulae in the periaqueductal gray (PAG) area of the midbrain. In saline-pretreated mice, exposure to 70% N2O resulted in a concentration-dependent antinociceptive effect in the mouse abdominal constriction test. Pretreatment with an opioid antagonist in the PAG significantly antagonized the antinociceptive effect. Pretreatment with an inhibitor of NO production in the PAG also significantly antagonized the antinociceptive effect. These findings suggest that N2O acts in the PAG via an NO-dependent, opioid receptor-mediated mechanism to induce antinociception. PMID:17683915

  1. Characteristics and function of cardiac mitochondrial nitric oxide synthase.

    PubMed

    Dedkova, Elena N; Blatter, Lothar A

    2009-02-15

    We used laser scanning confocal microscopy in combination with the nitric oxide (NO)-sensitive fluorescent dye DAF-2 and the reactive oxygen species (ROS)-sensitive dyes CM-H(2)DCF and MitoSOX Red to characterize NO and ROS production by mitochondrial NO synthase (mtNOS) in permeabilized cat ventricular myocytes. Stimulation of mitochondrial Ca(2+) uptake by exposure to different cytoplasmic Ca(2+) concentrations ([Ca(2+)](i) = 1, 2 and 5 microm) resulted in a dose-dependent increase of NO production by mitochondria when L-arginine, a substrate for mtNOS, was present. Collapsing the mitochondrial membrane potential with the protonophore FCCP or blocking the mitochondrial Ca(2+) uniporter with Ru360 as well as blocking the respiratory chain with rotenone or antimycin A in combination with oligomycin inhibited mitochondrial NO production. In the absence of L-arginine, mitochondrial NO production during stimulation of Ca(2+) uptake was significantly decreased, but accompanied by increase in mitochondrial ROS production. Inhibition of mitochondrial arginase to limit L-arginine availability resulted in 50% inhibition of Ca(2+)-induced ROS production. Both mitochondrial NO and ROS production were blocked by the nNOS inhibitor (4S)-N-(4-amino-5[aminoethyl]aminopentyl)-N'-nitroguanidine and the calmodulin antagonist W-7, while the eNOS inhibitor L-N(5)-(1-iminoethyl)ornithine (L-NIO) or iNOS inhibitor N-(3-aminomethyl)benzylacetamidine, 2HCl (1400W) had no effect. The superoxide dismutase mimetic and peroxynitrite scavenger MnTBAP abolished Ca(2+)-induced ROS generation and increased NO production threefold, suggesting that in the absence of MnTBAP either formation of superoxide radicals suppressed NO production or part of the formed NO was transformed quickly to peroxynitrite. In the absence of L-arginine, mitochondrial Ca(2+) uptake induced opening of the mitochondrial permeability transition pore (PTP), which was blocked by the PTP inhibitor cyclosporin A and MnTBAP, and reversed by L-arginine supplementation. In the presence of the mtNOS cofactor (6R)-5,6,7,8,-tetrahydrobiopterin (BH(4); 100 microm) mitochondrial ROS generation and PTP opening decreased while mitochondrial NO generation slightly increased. These data demonstrate that mitochondrial Ca(2+) uptake activates mtNOS and leads to NO-mediated protection against opening of the mitochondrial PTP, provided sufficient availability of l-arginine and BH(4). In conclusion, our data show the importance of L-arginine and BH(4) for cardioprotection via regulation of mitochondrial oxidative stress and modulation of PTP opening by mtNOS. PMID:19103678

  2. Effects of chemical ischemia in cerebral cortex slices. Focus on nitric oxide.

    PubMed

    Cavallini, S; Marti, M; Marino, S; Selvatici, R; Beani, L; Bianchi, C; Siniscalchi, A

    2005-12-01

    Superfused rat cerebral cortex slices were submitted to a continuous electrical (5 Hz) stimulation and treated with sodium azide (1-10 mM) in the presence of 2 mM 2-deoxyglucose ("chemical ischemia"). Presynaptic cholinergic activity, evaluated as acetylcholine release, was inhibited depending on the sodium azide concentrations and on the length of application (5-30 min). Following a 5-min treatment with 10 mM sodium azide, acetylcholine release was reduced to 45+/-2.3%; simultaneously, there was a 15- and 10-fold increase in glutamate and nitric oxide effluxes, respectively. After restoring normal superfusion conditions, acetylcholine release recovered to 70+/-3.1% of the controls; the N-methyl-D-aspartate receptor antagonist MK-801 (10 microM) as well as the nitric oxide scavengers, haemoglobin (20 microM) and 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-l-oxyl-3-oxide (150 microM), improved the recovery in presynaptic activity, showing that both glutamate and nitric oxide play detrimental roles in chemical ischemia. On the other hand, the post-ischemic recovery was worsened by the guanylylcyclase inhibitor 1H-[l,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (10 microM), suggesting that the activation of such a pathway plays a neuroprotective role and that the nitric oxide-induced harmful effects depend on different mechanisms. Chemical ischemia-evoked nitric oxide efflux partly derived from its calcium-dependent endogenous synthesis, since both the intracellular calcium chelator, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (1 mM), and the nitric oxide synthase inhibitor, N(omega)-nitro-L-arginine methyl ester (100 microM), substantially prevented sodium azide effects. Nitric oxide efflux was only weakly reduced by MK-801 and was not modified by either the L-type calcium channel blocker, nifedipine (10 microM) or the N-type calcium channel blocker omega-conotoxin (0.5 microM), thus suggesting a prevailing intracellular calcium-dependence of nitric oxide production, although a partial extracellular calcium source cannot be ruled out. These findings show that sodium azide plus 2-deoxyglucose treatment is a useful protocol to induce brain ischemia in vitro and underline the involvement of nitric oxide in the complex events following the ischemic insult. PMID:16135390

  3. Proliferation of macrophages due to the inhibition of inducible nitric oxide synthesis by oxidized low-density lipoproteins

    PubMed Central

    Brunner, Monika; Gruber, Miriam; Schmid, Diethart; Baran, Halina; Moeslinger, Thomas

    2015-01-01

    Oxidized low-density lipoprotein (ox-LDL) is assumed to be a major causal agent in hypercholesteraemia-induced atherosclerosis. Because the proliferation of lipid-loaden macrophages within atherosclerotic lesions has been described, we investigated the dependence of macrophage proliferation on the inhibition of inducible nitric oxide synthase (iNOS) by hypochlorite oxidized LDL. Ox-LDL induces a dose dependent inhibition of inducible nitric oxide synthesis in lipopolysaccharide-interferon stimulated mouse macrophages (J774.A1) with concomitant macrophage proliferation as assayed by cell counting, tritiated-thymidine incorporation and measurement of cell protein. Native LDL did not influence macrophage proliferation and inducible nitric oxide synthesis. iNOS protein and mRNA was reduced by HOCl-oxidized LDL (0-40 µg/ml) as revealed by immunoblotting and competitive semiquantitative PCR. Macrophage proliferation was increased by the addition of the iNOS inhibitor L-NAME. The addition of ox-LDL to L-NAME containing incubations induced no further statistically significant increase in cell number. Nitric oxide donors decreased ox-LDL induced macrophage proliferation and nitric oxide scavengers restored macrophage proliferation to the initial values achieved by ox-LDL. The decrease of cytosolic DNA fragments in stimulated macrophages incubated with ox-LDL demonstrates that the proliferative actions of ox-LDL are associated with a decrease of NO-induced apoptosis. Our data show that inhibition of iNOS dependent nitric oxide production caused by hypochlorite oxidized LDL enhances macrophage proliferation. This might be a key event in the pathogenesis of atherosclerotic lesions. PMID:26600745

  4. Traumatic Brain Injury Disrupts Cerebrovascular Tone Through Endothelial Inducible Nitric Oxide Synthase Expression and Nitric Oxide Gain of Function

    PubMed Central

    Villalba, Nuria; Sonkusare, Swapnil K.; Longden, Thomas A.; Tran, Tram L.; Sackheim, Adrian M.; Nelson, Mark T.; Wellman, George C.; Freeman, Kalev

    2014-01-01

    Background Traumatic brain injury (TBI) has been reported to increase the concentration of nitric oxide (NO) in the brain and can lead to loss of cerebrovascular tone; however, the sources, amounts, and consequences of excess NO on the cerebral vasculature are unknown. Our objective was to elucidate the mechanism of decreased cerebral artery tone after TBI. Methods and Results Cerebral arteries were isolated from rats 24 hours after moderate fluid‐percussion TBI. Pressure‐induced increases in vasoconstriction (myogenic tone) and smooth muscle Ca2+ were severely blunted in cerebral arteries after TBI. However, myogenic tone and smooth muscle Ca2+ were restored by inhibition of NO synthesis or endothelium removal, suggesting that TBI increased endothelial NO levels. Live native cell NO, indexed by 4,5‐diaminofluorescein (DAF‐2 DA) fluorescence, was increased in endothelium and smooth muscle of cerebral arteries after TBI. Clamped concentrations of 20 to 30 nmol/L NO were required to simulate the loss of myogenic tone and increased (DAF‐2T) fluorescence observed following TBI. In comparison, basal NO in control arteries was estimated as 0.4 nmol/L. Consistent with TBI causing enhanced NO‐mediated vasodilation, inhibitors of guanylyl cyclase, protein kinase G, and large‐conductance Ca2+‐activated potassium (BK) channel restored function of arteries from animals with TBI. Expression of the inducible isoform of NO synthase was upregulated in cerebral arteries isolated from animals with TBI, and the inducible isoform of NO synthase inhibitor 1400W restored myogenic responses following TBI. Conclusions The mechanism of profound cerebral artery vasodilation after TBI is a gain of function in vascular NO production by 60‐fold over controls, resulting from upregulation of the inducible isoform of NO synthase in the endothelium. PMID:25527626

  5. Nitric oxide and cardiovascular effects: new insights in the role of nitric oxide for the management of osteoarthritis

    PubMed Central

    Mackenzie, Isla S; Rutherford, Daniel; MacDonald, Thomas M

    2008-01-01

    Nitric oxide (NO) is an important mediator in both health and disease. In addition to its effects on vascular tone and platelet function, it plays roles in inflammation and pain perception that may be of relevance in osteoarthritis. Many patients with osteoarthritis take nonsteroidal anti-inflammatory drugs (NSAIDs) long term for pain control. Over recent years concern has been raised about the possible cardiovascular side effects of NSAIDs. The reasons for this possible increased cardiovascular risk with NSAIDs are not yet entirely clear, although changes in blood pressure, renal salt handling and platelet function may contribute. Recently, drugs that chemically link a NSAID with a NO donating moiety (cyclo-oxygenase-inhibiting NO-donating drugs [CINODs]) were developed. NO is an important mediator of endothelial function, acting as a vasodilator and an inhibitor of platelet aggregation, and having anti-inflammatory properties. The potential benefits of CINODs include the combination of effective analgesic and anti-inflammatory actions with NO release, which might counterbalance any adverse cardiovascular effects of NSAIDs. Effects of CINODs in animal studies include inhibition of vasopressor responses, blood pressure reduction in hypertensive rats and inhibition of platelet aggregation. CINODs may also reduce ischemic damage to compromised myocardial tissue. In addition, endothelial dysfunction is a recognized feature of inflammatory arthritides, and therefore a drug that might provide slow release of NO to the vasculature while treating pain is an attractive prospect in these conditions. Further studies of the effects of CINODs in humans are required, but these agents represent a potential exciting advance in the management of osteoarthritis. PMID:19007428

  6. Are nitric oxide donors a valuable tool to study the functional role of nitric oxide in plant metabolism?

    PubMed

    Arasimowicz-Jelonek, M; Floryszak-Wieczorek, J; Kosmala, A

    2011-09-01

    In the present work, we tested known nitric oxide (NO) modulators generating the NO+ (sodium nitroprusside, SNP) and NO˙ forms (S-nitroso-N-acetyl-D-penicillamine, SNAP and nitrosoglutathione, GSNO). This allowed us to compare downstream NO-related physiological effects on proteins found in leaves of pelargonium (Pelargonium peltatum L.). Protein modification via NO donors generally affects plant metabolism in a distinct manner, manifested by a lower thiobarbituric acid reactive substance (TBARS) content and lipoxygenase (LOX) activity in response to SNAP and GSNO. This is in contrast to the response observed for SNP treatment. Most changes in enzyme activity (GR, glutathione reductase; GST, glutathione-S-transferase; GPX, glutathione peroxidase) are most spectacular and repeatable during the first 8 h of incubation, which is explained by the half-life of the applied donors. In particular, a close dependence was found between the time-course of NO emission from the applied donors and the temporary inhibition of antioxidant enzymes, such as catalase (CAT) and ascorbate peroxidase (APX). The observed changes were accompanied by time-dependent alterations in protein accumulation as analysed by two-dimensional gel electrophoresis (2-DE) in pelargonium leaves treated with NO donors (SNP, SNAP and GSNO). Using proteomics, different proteins were found to be down- and up-regulated. However, no new protein spots characteristic of all three donors were found. These results indicate that the form of NO emitted from the donor structure plays a key role in switching on appropriate metabolic modifications. It has been noted that several NO-affected metabolomic changes induced by the used donors were not comparable, which confirms the need to maintain caution when interpreting results obtained using the pharmacological approach with different NO modulator compounds. PMID:21815979

  7. Proteasomal control of cytokinin synthesis protects Mycobacterium tuberculosis against nitric oxide

    PubMed Central

    Samanovic, Marie I.; Tu, Shengjiang; Novák, Ondřej; Iyer, Lakshminarayan M.; McAllister, Fiona E.; Aravind, L.; Gygi, Steven P.; Hubbard, Stevan R.; Strnad, Miroslav; Darwin, K. Heran

    2015-01-01

    Summary One of several roles of the Mycobacterium tuberculosis proteasome is to defend against host-produced nitric oxide (NO), a free radical that can damage numerous biological macromolecules. Mutations that inactivate proteasomal degradation in Mycobacterium tuberculosis result in bacteria that are hypersensitive to NO and attenuated for growth in vivo, but it was not known why. To elucidate the link between proteasome function, NO-resistance, and pathogenesis, we screened for suppressors of NO hypersensitivity in a mycobacterial proteasome ATPase mutant and identified mutations in Rv1205. We determined that Rv1205 encodes a pupylated proteasome substrate. Rv1205 is a homologue of the plant enzyme LONELY GUY, which catalyzes the production of hormones called cytokinins. Remarkably, we report for the first time that an obligate human pathogen secretes several cytokinins. Finally, we determined that the Rv1205-dependent accumulation of cytokinin breakdown products is likely responsible for the sensitization of Mycobacterium tuberculosis proteasome-associated mutants to NO. PMID:25728768

  8. Short polymers of arginine rapidly translocate into vascular cells: effects on nitric oxide synthesis.

    PubMed

    Uemura, Shiro; Rothbard, Jonathan B; Matsushita, Hidetsugu; Tsao, Philip S; Fathman, C Garrison; Cooke, John P

    2002-12-01

    The present study was designed to determine the efficiency of translocation of short polymers of arginine into vascular smooth muscle cells (VSMC) and to determine their effect on nitric oxide (NO) synthesis. Immunostaining revealed that heptamers of L-arginine (R7) rapidly translocated into the VSMC. This rapid transport was not observed with shorter polymers of L-arginine (R5) nor heptamers of lysine (K7). Translocation of R7 was not inhibited by the addition of free L-arginine into the media. When cells were transiently pretreated with R7 or a nonamer of arginine (R9), NO(2) production from cytokine stimulated VSMC was significantly increased, whereas incubation with R5 and K7 had no effect. Short polymers of arginine not only have a unique ability of rapid VSMC translocation but once internalized enhance NO production. Heptamers (or larger polypeptides) of arginine may be useful in therapy to enhance NO production in the vascular system. PMID:12499624

  9. Aerobic Oxidation of an Osmium(III) N-Hydroxyguanidine Complex To Give Nitric Oxide.

    PubMed

    Xiang, Jing; Wang, Qian; Yiu, Shek-Man; Man, Wai-Lun; Kwong, Hoi-Ki; Lau, Tai-Chu

    2016-05-16

    The aerobic oxidation of the N-hydroxyguanidinum moiety of N-hydroxyarginine to NO is a key step in the biosynthesis of NO by the enzyme nitric oxide synthase (NOS). So far, there is no chemical system that can efficiently carry out similar aerobic oxidation to give NO. We report here the synthesis and X-ray crystal structure of an osmium(III) N-hydroxyguanidine complex, mer-[Os(III){NH═C(NH2)(NHOH)}(L)(CN)3](-) (OsGOH, HL = 2-(2-hydroxyphenyl)benzoxazole), which to the best of our knowledge is the first example of a transition metal N-hydroxyguanidine complex. More significantly, this complex readily undergoes aerobic oxidation at ambient conditions to generate NO. The oxidation is pH-dependent; at pH 6.8, fac-[Os(NO)(L)(CN)3](-) is formed in which the NO produced is bound to the osmium center. On the other hand, at pH 12, aerobic oxidation of OsGOH results in the formation of the ureato complex [Os(III)(NHCONH2)(L)(CN)3](2-) and free NO. Mechanisms for this aerobic oxidation at different pH values are proposed. PMID:27135258

  10. Superior catalysts for selective catalytic reduction of nitric oxide. Quarterly technical progress report, April 1, 1995--June 30, 1995

    SciTech Connect

    Li, W.B.; Yang, R.T.

    1995-12-01

    Efforts continued towards the synthesis of new pillared clay catalysts for the selective catalytic reduction of nitric oxide by ammonia. The possibility of utilizing hydrocarbons was also investigated.

  11. Role of oxidative stress, inflammation, nitric oxide and transforming growth factor-beta in the protective effect of diosgenin in monocrotaline-induced pulmonary hypertension in rats.

    PubMed

    Ahmed, Lamiaa A; Obaid, Al Arqam Z; Zaki, Hala F; Agha, Azza M

    2014-10-01

    Pulmonary hypertension is a progressive disease of various origins that is associated with right ventricular dysfunction. In the present study, the protective effect of diosgenin was investigated in monocrotaline-induced pulmonary hypertension in rats. Pulmonary hypertension was induced by a single subcutaneous injection of monocrotaline (60 mg/kg). Diosgenin (100 mg/kg) was given by oral administration once daily for 3 weeks. At the end of the experiment, mean arterial blood pressure, electrocardiography and echocardiography were recorded. Rats were then sacrificed and serum was separated for determination of total nitrate/nitrite level. Right ventricles and lungs were isolated for estimation of oxidative stress markers, tumor necrosis factor-alpha, total nitrate/nitrite and transforming growth factor-beta contents. Myeloperoxidase and caspase-3 activities in addition to endothelial and inducible nitric oxide synthase protein expression were also determined. Moreover, histological analysis of pulmonary arteries and cardiomyocyte cross-sectional area was performed. Diosgenin treatment provided a significant improvement toward preserving hemodynamic changes and alleviating oxidative stress, inflammatory and apoptotic markers induced by monocrotaline in rats. Furthermore, diosgenin therapy prevented monocrotaline-induced changes in nitric oxide production, endothelial and inducible nitric oxide synthase protein expression as well as histological analysis. These findings support the beneficial effect of diosgenin in pulmonary hypertension induced by monocrotaline in rats. PMID:25062790

  12. Remote sensing of nitric oxide emissions from planes, trains and automobiles

    NASA Astrophysics Data System (ADS)

    Popp, Peter John

    Remote sensing has been proven as an effective method for measuring in-use mobile source emissions. This document describes the development of a remote sensor for mobile source nitric oxide, based on an instrument previously developed at the University of Denver for measuring carbon monoxide and hydrocarbon emissions. The new remote sensor makes use of a high-speed ultraviolet spectrometer to quantify nitric oxide by absorption spectroscopy at 226 nm in the ultraviolet region. The high-speed spectrometer is coupled to an existing FEAT remote sensor, for the simultaneous measurement of CO, CO2 and hydrocarbons by non-dispersive infrared absorption spectroscopy. The utility of the instrument was demonstrated in the measurement of nitric oxide emissions from automobiles, commercial aircraft, and railroad locomotives. The remote sensor was used to measure nitric oxide emissions from motor vehicles in Chicago in 1997 and 1998, as part of a five-year study to characterize motor vehicle emissions and deterioration in that city. Emissions data were collected for over 19,000 vehicles in 1997 and almost 23,000 vehicles in 1998. All of these records contained valid measurements for carbon monoxide and hydrocarbons, in addition to nitric oxide. In September of 1997, a study was conducted with the cooperation of British Airways and the British Airports Authority to demonstrate the capability of the remote sensor in measuring nitric oxide emissions from in-use commercial aircraft. In two days of sampling at London Heathrow Airport, a total of 122 measurements were made of 90 different aircraft, ranging in size from Gulfstream executive jets to Boeing 747-400s. The measured nitric oxide emission indices were not inconsistent with commercial aircraft emission indices published by the International Civil Aviation Organization. The utility of the remote sensor in measuring nitric oxide emissions from railroad locomotives was demonstrated in January of 1999, in a study conducted with the cooperation of the Burlington Northern Santa Fe Railway. Nitric oxide emissions measured from freight locomotives in a controlled test at a switchyard agreed with previously published values. Measurements of in-use locomotives hauling coal trains revealed higher NO emissions than those measured from similar locomotives in the controlled test.

  13. Nitrate, nitrite and nitric oxide reductases: from the last universal common ancestor to modern bacterial pathogens.

    PubMed

    Vázquez-Torres, Andrés; Bäumler, Andreas J

    2016-02-01

    The electrochemical gradient that ensues from the enzymatic activity of cytochromes such as nitrate reductase, nitric oxide reductase, and quinol oxidase contributes to the bioenergetics of the bacterial cell. Reduction of nitrogen oxides by bacterial