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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. 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

  3. Nitric Oxide Nanoparticle Technology

    PubMed Central

    Englander, Laura

    2010-01-01

    Staphylococcus aureus infections account for the majority of skin and soft tissue infections in the United States. Staphylococcus aureus is rapidly evolving resistance to contemporary topical as well as systemic antibiotics. Alternatives to current treatment options for skin and soft tissue infections are needed for more effective treatment now and in the future. Nitric oxide's proven roles in both wound repair and as an antimicrobial agent make it an excellent candidate for the treatment of skin infections. Recent attempts at novel nitric oxide therapies, in the form of nitric oxide donors, have shown limited potential in treating cutaneous infection. However, more recent developments in nitric oxide delivery, using nitric oxide nanoparticle technology, demonstrate substantial promise in the promotion of wound repair and eradication of skin and soft tissue infections. PMID:20725551

  4. 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.

  5. [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

  6. 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

  7. Determination of nitric oxide with ultramicrosensors based on electropolymerized films of metal tetraaminophthalocyanines.

    PubMed

    Jin, J; Miwa, T; Mao, L; Tu, H; Jin, L

    1999-05-01

    Preparation and electrochemical responses to nitric oxide (NO) of the electropolymerized films of metal tetraaminophthalocyanines (MTAPc, M=Co, Ni, Cu) are studied to test them as molecular devices for design and construction of amperometric ultramicrosensors for selective and sensitive determination of NO. The ultramicrosensors based on electropolymerized films of MTAPc and Nafion, are found to show a low detection limit, high selectivity and sensitivity to NO determination. The potential interference from some endogenous electroactive substances in biological tissues, such as catecholamines and their metabolites, ascorbic acid (AA), uric acid (UA), and nitrite (NO(2)(-)), the metabolite of NO at the concentrations higher than those in biological systems could be eliminated by using a technique of DPV or DPA and further coating the modified ultramicrosensors with a layer of Nafion. PMID:18967543

  8. 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.

    2015-06-01

    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 was 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. Our method is fast and comparably easy to handle thus it opens the door for deciphering the distribution of NO in the ocean and it facilitates laboratory studies on NO pathways.

  9. 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.

  10. Constitutive eNOS-derived nitric oxide is a determinant of endothelial junctional integrity.

    PubMed

    Predescu, Dan; Predescu, Sanda; Shimizu, Jun; Miyawaki-Shimizu, Kayo; Malik, Asrar B

    2005-09-01

    Basal vascular endothelial permeability is normally kept low in part by the restrictiveness of interendothelial junctions (IEJs). We investigated the possible role of nitric oxide (NO) in controlling IEJ integrity and thereby regulating basal vascular permeability. We determined the permeability of continuous endothelia in multiple murine vascular beds, including lung vasculature, of wild-type mice, endothelial nitric oxide synthase (eNOS) null mice, and mice treated with NOS inhibitor N-nitro-L-arginine methyl ester (L-NAME). Light and electron microscopic studies revealed that L-NAME treatment resulted in IEJs opening within a few minutes with a widespread response within 30 min. We observed a 35% increase in transendothelial transport of albumin, using as tracer dinitrophenylated albumin in mouse lungs and other organs studied. To rule out the involvement of blood cells in the mechanism of increased endothelial permeability, vascular beds were flushed free of blood, treated with L-NAME, and perfused with the tracer. The open IEJs observed in these studies indicated a direct role for NO in preserving the normal structure of endothelial junctions. We also used the electron-opaque tracer lanthanum chloride to assess vascular permeability. Lanthanum chloride was presented by perfusion to various vascular beds of mice lacking NO. Open IEJs were seen only in capillary and venular endothelial segments of mice lacking NO, and there was a concomitant increase in vascular permeability to the tracer. Together, these data demonstrate that constitutive eNOS-derived NO is a crucial determinant of IEJ integrity and thus serves to maintain the low basal permeability of continuous endothelia. PMID:16093363

  11. Tropospheric nitric oxide measurements

    NASA Technical Reports Server (NTRS)

    Torres, A. L.

    1988-01-01

    Nitric oxide (NO) plays a key role in tropospheric photo-chemistry. The photochemical oxidation of hydrocarbons, for example, can serve as either a source or a sink for ozone, depending on the local abundance of NO. Nitric oxide also helps govern atmospheric concentrations of the hydroxyl (OH) radical. The OH radical is the single most important player in photochemical transformations because it controls the atmospheric lifetimes of so many chemical species. Although NO serves as a very effective catalyst in many important chemical processes, its concentration is low enough to normally be expressed in units of parts per trillion by volume (pptv). Consequently, commercially available detectors for NO (with detection limits of about one part per billion) have proven to be unsuitable for use anywhere except in urban areas and near other local pollution sources. Under the sponsorship of NASA's Global Tropospheric Experiment (GTE), Wallops has developed an extremely sensitive detector with a detection limit of a few pptv. The system was specifically designed for aircraft use, with the objective of applying it in global aircraft studies of tropospheric chemistry. Studies with the detector are examined.

  12. Determination of in vivo nitric oxide levels in animal tissues using a novel spin trapping technology.

    PubMed

    Vanin, Anatoly F; Timoshin, Alexander A

    2011-01-01

    It has been established that microdialysis ensured by the passage of aqueous solutions of Fe(3+) complexes with N-methyl-D: -glucamine dithiocarbamate (MGDMGD ) through fine dialysis fibers permeable for compounds with molecular weights below 5 kDa. These fibers can be implanted into heart, liver, and kidney tissues, enabling effective binding of Fe(3+)-MGD complexes to nitric oxide generated in interstitial fluids of narcotized rats in vivo. Subsequent treatment of dialyzate samples (60 μL) with sodium dithionite favors conversion of newly formed diamagnetic NO-Fe(3+)-MGD complexes into electron paramagnetic resonance-detectable NO-Fe(2+)-MGD complexes. The basal levels of NO determined from the concentrations of the complexes in the respective tissues are similar (1 μМ). The microdialysis data suggest that treatment of rats with a water-soluble analogue of nitroglycerine or a dinitrosyl iron complex with thiosulfate induces a long-lasting (>1 h) increase in the steady-state level of NO in animal tissues. This novel technology can be used for comparative analyses of production rates of NO and reactive oxygen species when using iron-dithiocarbamate complexes and spin traps for reactive oxygen species, respectively. PMID:21161635

  13. Demystified … Nitric oxide

    PubMed Central

    Stuart-Smith, K

    2002-01-01

    The discovery of nitric oxide (NO) demonstrated that cells could communicate via the manufacture and local diffusion of an unstable lipid soluble molecule. Since the original demonstration of the vascular relaxant properties of endothelium derived NO, this fascinating molecule has been shown to have multiple, complex roles within many biological systems. This review cannot hope to cover all of the recent advances in NO biology, but seeks to place the discovery of NO in its historical context, and show how far our understanding has come in the past 20 years. The role of NO in mitochondrial respiration, and consequently in oxidative stress, is described in detail because these processes probably underline the importance of NO in the development of disease. PMID:12456772

  14. Direct determination of the activation energy for the reaction of nitric oxide with ozone

    SciTech Connect

    Borders, R.A.

    1981-01-01

    The activation energy for the reaction of nitric oxide with ozone has been directly measured as a function of temperature. The instrument constructed for this study consisted of two flow tubes that are connected together at each end, where the reaction zone temperature of each flow tube was controlled independently. The reaction of nitric oxide and ozone was pseudo-first order ((NO)/(O/sub 3/) greater than or equal to 250) and studied by following the reduction of the chemiluminescence of one of the products (NO/sup *//sub 2/(/sup 2/B/sub 1,2/)) of the reaction. The chemiluminescence was measured using a microcomputer-controlled photon counter designed for these studies. The activation energy has been found to vary with temperature. The activation energy varies from 2390 +/- 10 calories at 216 K to 2970 +/- 60 calories at 333 K. The variation over the complete temperature range studied (204-353 K) is large enough (650 calories) that the errors associated with the method cannot account for all of the variation. There are other pathways for this reaction other than ground state reactants going to ground state products, and their contribution to the activation energy (approx.500 calories) has been found to be sufficient to account for the observed variation with temperature when added to the variation predicted by either transition state (180 calories) or collision (150 calories) theory.

  15. Biotransformation of nitric oxide.

    PubMed Central

    Yoshida, K; Kasama, K

    1987-01-01

    Previous investigations into the health effects of nitrogen oxides (NOx) have mostly been conducted with special reference to nitrogen dioxide (NO2) and its direct effects on the respiratory system, while the study of nitric oxide (NO) has been disregarded. We carried out a study on NO by exposing rats and mice to 15NO or administering 15N-nitrite and 15N-nitrate to these animals by IP injection in order to elucidate the metabolic fate of NO. The results of our study and previous findings led us to assume that the major metabolic path of inhaled NO is as follows: inhaled NO reacts with hemoglobin, forming nitrosyl-hemoglobin (NOHb), and from NOHb, nitrite (NO2-) and nitrate (NO3-) are generated. Major quantities of NO3- are discharged into the urine and a certain amount is discharged into the oral cavity through the salivary glands and transformed to NO2-. Part of this NO2- is converted to N2 gas in the stomach. Nitrate in the intestine is partly reduced to ammonia (NH3) through NO2-, reabsorbed into the body, and converted to urea. Most of the metabolites of inhaled NO are excreted rapidly from the body within 48 hr. PMID:3665863

  16. Study of Atmospheric Nitric Oxide

    NASA Technical Reports Server (NTRS)

    Dalgarno, A.

    1998-01-01

    We investigated the contribution of energetic nitrogen atoms to the production of nitric oxide in the thermosphere and their influence on the infrared emission spectrum. The nitric oxide molecules are important contributors to the cooling of the atmosphere. We first pointed out that in determining the energy distribution of the nitrogen atoms, it is important to take into account the thermal motion of the atmospheric gases. It had been ignored in all earlier studies. The source spectra are broadened considerably by the center of mass motion of the reactants. We worked out the consequences for the production of nitric oxide at night, using as sources of energetic N atoms, NO(+) + e yield N + O, N(D-2) + O yield N + O. The high energy tail is enhanced by orders of magnitude. We had earlier suggested (Sharma et al. 1993) that the reaction of energetic nitrogen atoms with O2 was responsible for the rotationally enhanced NO identified in the infrared spectrum. Our calculations provided quantitative confirmation of the suggestion. We proceeded to explore the validity of another approximation used in earlier analyses, the hard sphere approximation for the energy loss in elastic collisions. We carried out precise quantum mechanical calculations of the elastic 2 differential scattering of nitrogen atoms in collisions with oxygen atoms and showed that although the hard sphere approximation was nowhere of high precision, reasonable results could be obtained with an effective cross section of 6 x 10(exp 15)sq cm. We also initiated a program to include inelastic energy loss processes in the determination of the energy distribution function. We began a calculation of the rotation and vibrational excitation cross sections of molecular nitrogen and nitrogen atoms and developed a method for including inelastic energy loss as a function of scattering angle in the Boltzmann equation. A procedure for obtaining the solution of the Boltzman equation was worked out.

  17. Chemiluminescence of nitric oxide

    NASA Technical Reports Server (NTRS)

    Sharp, W. E.; Rusch, D. W.

    1981-01-01

    Measurements of the intensities of the delta and gamma bands of nitric oxide in the nighttime terrestrial thermosphere are presented and used to infer the rate coefficient for the transition from the C 2 Pi to the A 2 Sigma + states. The nightglow spectrum was observed between 1900 and 2300 A at a resolution of 15 A by a rocket-borne scanning 1/4-m spectrometer pointing north at an apogee of 150 km. Progressions of the delta, gamma and epsilon bands are identified on the spectra by the construction of synthetic spectra, and the contributions of resonance fluorescence to the total band intensities are calculated. Finally, the ratio of the sum of the gamma bands for v-prime = 0 to the sum of the delta bands for v-prime = 0 is used to derive a branching ratio of 0.21 + or - 0.04 to the A 2 Sigma + state, which yields a probability for the C-A transition of 5.6 + or - 1.5 x to the 6th/sec.

  18. 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

  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. 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 transcription–polymerase 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 oxide–producing 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.

  1. 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.

  2. 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 ...

  3. Electron-impact excitation of nitric oxide.

    NASA Technical Reports Server (NTRS)

    Stone, E. J.; Zipf, E. C.

    1972-01-01

    The absolute cross sections for the excitation of the nitrosyl cation Baer-Miescher bands, two nitric oxide bands, and several atomic nitrogen multiplets in the vacuum UV by electron impact on NO have been measured over an energy range extending from threshold to 300 eV. The variation of the dipole transition moment for the nitrosyl cation band system was also determined.

  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. Spectrofluorimetric determination of nitric oxide at trace levels with 5,6-diamino-1,3-naphthalene disulfonic acid.

    PubMed

    Zhang, Xian; Wang, Hong; Liang, Shu-Cai; Zhang, Hua-Shan

    2002-03-01

    Based on the selective reaction that 5,6-diamino-1,3-naphthalene disulfonic acid (DANDS) traps nitric oxide (NO) in the presence of dioxygen to yield the highly fluorescent form, 1-[H]-naphthotriazole-6,8-disulfonic acid in moderately alkaline medium, a new spectrofluorimetric method for the determination of NO has been reported. The method offered the advantage of specificity, sensitivity and a simple protocol for the direct detection of NO in aqueous solution. The linear calibration range for NO was 0.04-1.44 mumoll(-1) with a 3sigma detection limit of 0.6 nmoll(-1). The proposed method has been used to monitor the release of NO from S-nitrosocysteine, a NO-releasing agent. PMID:18968522

  6. An electrogenic nitric oxide reductase.

    PubMed

    Al-Attar, Sinan; de Vries, Simon

    2015-07-22

    Nitric oxide reductases (Nors) are members of the heme-copper oxidase superfamily that reduce nitric oxide (NO) to nitrous oxide (N₂O). In contrast to the proton-pumping cytochrome oxidases, Nors studied so far have neither been implicated in proton pumping nor have they been experimentally established as electrogenic. The copper-A-dependent Nor from Bacillus azotoformans uses cytochrome c₅₅₁ as electron donor but lacks menaquinol activity, in contrast to our earlier report (Suharti et al., 2001). Employing reduced phenazine ethosulfate (PESH) as electron donor, the main NO reduction pathway catalyzed by Cu(A)Nor reconstituted in liposomes involves transmembrane cycling of the PES radical. We show that Cu(A)Nor reconstituted in liposomes generates a proton electrochemical gradient across the membrane similar in magnitude to cytochrome aa₃, highlighting that bacilli using Cu(A)Nor can exploit NO reduction for increased cellular ATP production compared to organisms using cNor. PMID:26149211

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

    PubMed Central

    Gokay, Nevzat Selim; Yilmaz, Ibrahim; Demiroz, Ahu Senem; Gokce, Alper; Dervisoglu, Sergülen; Gokay, Banu Vural

    2016-01-01

    The objective of this study was to investigate the effects of selective inducible nitric oxide synthase and neuronal nitric oxide synthase inhibitors on cartilage regeneration. The study involved 27 Wistar rats that were divided into five groups. On Day 1, both knees of 3 rats were resected and placed in a formalin solution as a control group. The remaining 24 rats were separated into 4 groups, and their right knees were surgically damaged. Depending on the groups, the rats were injected with intra-articular normal saline solution, neuronal nitric oxide synthase inhibitor 7-nitroindazole (50 mg/kg), inducible nitric oxide synthase inhibitor amino-guanidine (30 mg/kg), or nitric oxide precursor L-arginine (200 mg/kg). After 21 days, the right and left knees of the rats were resected and placed in formalin solution. The samples were histopathologically examined by a blinded evaluator and scored on 8 parameters. Although selective neuronal nitric oxide synthase inhibition exhibited significant (P = 0.044) positive effects on cartilage regeneration following cartilage damage, it was determined that inducible nitric oxide synthase inhibition had no statistically significant effect on cartilage regeneration. It was observed that the nitric oxide synthase activation triggered advanced arthrosis symptoms, such as osteophyte formation. The fact that selective neuronal nitric oxide synthase inhibitors were observed to have mitigating effects on the severity of the damage may, in the future, influence the development of new agents to be used in the treatment of cartilage disorders. PMID:27382570

  11. Inducible nitric oxide synthase and inflammation.

    PubMed

    Salvemini, D; Marino, M H

    1998-01-01

    Nitric oxide (NO), derived from L-arginine (L-Arg) by the enzyme nitric oxide synthase (NOS), is involved in acute and chronic inflammatory events. In view of the complexity associated with the inflammatory response, the dissection of possible mechanisms by which NO modulates this response will be profitable in designing novel and more efficacious NOS inhibitors. In this review we describe the consequences associated with the induction of inducible nitric oxide synthase (iNOS) and its therapeutic implications. PMID:15991919

  12. Nitric oxide and nitric oxide synthase in Huntington's disease.

    PubMed

    Deckel, A W

    2001-04-15

    Nitric oxide (NO) is a biologically active inorganic molecule produced when the semiessential amino acid l-arginine is converted to l-citrulline and NO via the enzyme nitric oxide synthase (NOS). NO is known to be involved in the regulation of many physiological processes, such as control of blood flow, platelet adhesion, endocrine function, neurotransmission, neuromodulation, and inflammation, to name only a few. During neuropathological conditions, the production of NO can be either protective or toxic, dependent on the stage of the disease, the isoforms of NOS involved, and the initial pathological event. This paper reviews the properties of NO and NOS and the pathophysiology of Huntington's disease (HD). It discusses ways in which NO and NOS may interact with the protein product of HD and reviews data implicating NOS in the neuropathology of HD. This is followed by a synthesis of current information regarding how NO/NOS may contribute to HD-related pathology and identification of areas for potential future research. PMID:11288139

  13. Novel effects of nitric oxide

    NASA Technical Reports Server (NTRS)

    Davis, K. L.; Martin, E.; Turko, I. V.; Murad, F.

    2001-01-01

    Nitric oxide (NO), a simple free radical gas, elicits a surprisingly wide range of physiological and pathophysiological effects. NO interacts with soluble guanylate cyclase to evoke many of these effects. However, NO can also interact with molecular oxygen and superoxide radicals to produce reactive nitrogen species that can modify a number of macromolecules including proteins, lipids, and nucleic acids. NO can also interact directly with transition metals. Here, we have reviewed the non--3',5'-cyclic-guanosine-monophosphate-mediated effects of NO including modifications of proteins, lipids, and nucleic acids.

  14. 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

  15. 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.

  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. 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

  18. Whole body nitric oxide synthesis in healthy men determined from [15N] arginine-to-[15N]citrulline labeling.

    PubMed Central

    Castillo, L; Beaumier, L; Ajami, A M; Young, V R

    1996-01-01

    The rates of whole body nitric oxide (NO) synthesis, plasma arginine flux, and de novo arginine synthesis and their relationships to urea production, were examined in a total of seven healthy adults receiving an L-amino acid diet for 6 days. NO synthesis was estimated by the rate of conversion of the [15N] guanidino nitrogen of arginine to plasma [15N] ureido citrulline and compared with that based on urinary nitrite (NO2-)/nitrate (NO3-) excretion. Six subjects received on dietary day 7, a 24-hr (12-hr fed/12-hr fasted) primed, constant, intravenous infusion of L-[guanidino-15N2]arginine and [13C]urea. A similar investigation was repeated with three of these subjects, plus an additional subject, in which they received L-[ureido-13C]citrulline, to determine plasma citrulline fluxes. The estimated rates (mean +/- SD) of NO synthesis over a period of 24 hr averaged 0.96 +/- 0.1 mumol .kg-1.hr-1 and 0.95 +/- 0.1 mumol.kg-1.hr-1, for the [15N]citrulline and the nitrite/nitrate methods, respectively. About 15% of the plasma arginine turnover was associated with urea formation and 1.2% with NO formation. De novo arginine synthesis averaged 9.2 +/- 1.4 mumol. kg-1.hr-1, indicating that approximately 11% of the plasma arginine flux originates via conversion of plasma citrulline to arginine. Thus, the fraction of the plasma arginine flux associated with NO and also urea synthesis in healthy humans is small, although the plasma arginine compartment serves as a significant precursor pool (54%) for whole body NO formation. This tracer model should be useful for exploring these metabolic relationships in vivo, under specific pathophysiologic states where the L-arginine-NO pathway might be altered. Images Fig. 4 PMID:8876157

  19. 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

  20. 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

  1. Nitric oxide in liver diseases.

    PubMed

    Iwakiri, Yasuko; Kim, Moon Young

    2015-08-01

    Nitric oxide (NO) and its derivatives play important roles in the physiology and pathophysiology of the liver. Despite its diverse and complicated roles, certain patterns of the effect of NO on the pathogenesis and progression of liver diseases are observed. In general, NO derived from endothelial NO synthase (eNOS) in liver sinusoidal endothelial cells (LSECs) is protective against disease development, while inducible NOS (iNOS)-derived NO contributes to pathological processes. This review addresses the roles of NO in the development of various liver diseases with a focus on recently published articles. We present here two recent advances in understanding NO-mediated signaling - nitrated fatty acids (NO2-FAs) and S-guanylation - and conclude with suggestions for future directions in NO-related studies on the liver. PMID:26027855

  2. Airway nitric oxide in microgravity

    NASA Astrophysics Data System (ADS)

    Linnarsson, D.; Gustafsson, L.; Hemmingsson, Tryggve; Frostell, C.; Paiva, M.

    2005-10-01

    Nitric Oxide (NO), a molecule with a wide range of biological effects, is found in exhaled gas. Elevation of expired NO is an early sign of airway inflammation in asthma and dust inhalation. Animal experiments have demonstrated a marked increase of expired NO after venous gas emboli (bubbles, VGE), which may occur after decompression in conjunction with extravehicular activity (EVA). For this MAP project, astronauts will perform a simple inhalation-exhalation procedure weekly during their flights, and before and after EVA. Furthermore, the microgravity environment offers a possibility to gain new insights into how and where NO is formed in the lungs and what local effects NO may have there. The planned experiments have been made possible by recent developments of new techniques by the team's industrial partners; Aerocrine has developed a highly compact and accurate NO analyser, and Linde Gas Theapeutics has developed a highly compact device for NO administration in the inhaled air.

  3. UV Induced Oxidation of Nitric Oxide

    NASA Technical Reports Server (NTRS)

    Parrish, Clyde, F. (Inventor); Luecke, Dale E. (Inventor)

    2007-01-01

    Nitric oxide in a gaseous stream is converted to nitrogen dioxide using oxidizing species generated at least in part using in situ UV radiation sources. The sources of the oxidizing species include oxygen and/or hydrogen peroxide. The oxygen may be a component of the gaseous stream or added to the gaseous stream, preferably near a UV radiation source, and is converted to ozone by the UV irradiation. The hydrogen peroxide is decomposed through a combination of vaporization and UV irradiation. The hydrogen peroxide is preferably stored at stable concentration levels, i.e., approximately 50% by volume and increased in concentration in a continuous process preceding vaporization within the flow channel of the gaseous stream and in the presence of the UV radiation sources.

  4. Comparison of a thermospheric photochemical model with Student Nitric Oxide Explorer (SNOE) observations of nitric oxide

    NASA Astrophysics Data System (ADS)

    Barth, C. A.; Bailey, S. M.

    2004-03-01

    A time-dependent thermospheric model has been used to calculate the nitric oxide density in the lower thermosphere for a 935-day period, 11 March 1998 to 30 September 2000. This model uses daily values of the observed solar soft X-ray irradiance (2-7 nm) as an energy input parameter. The model does not include an energy input from auroral electron precipitation. The results of the model calculation of nitric oxide density at 110 km were compared with observations of nitric oxide density made with the Student Nitric Oxide Explorer (SNOE) for the 935-day period. At the equator the model calculations and the observations agree very well with a linear correlation coefficient of 0.876. The correlation coefficient remains high for the altitude region 107-117 km, the region where solar soft X-rays (2-7 nm) are the major source of nitric oxide production. The comparison of the model calculations with the observations as a function of latitude show that there is excess nitric oxide poleward of 30°N and S latitude particularly during the fall-winter season. We believe that the source of this excess nitric oxide is the nitric oxide that is produced in the auroral region (65°-75°N and S geomagnetic latitude) by precipitating auroral electrons. We believe that aurorally produced nitric oxide is transported equatorward by horizontal winds. At midlatitudes the excess nitric oxide decays to about half of its initial value in one day. At times of large geomagnetic storms we believe that aurorally produced nitric oxide is transported all the way to the equator by horizontal winds. The excellent correlation of the model calculations and the SNOE observations of nitric oxide at 110 km between 30°S and 30°N support the hypothesis that solar soft X-rays are the source of the variability of nitric oxide in the thermosphere at low latitudes.

  5. 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.-

  6. 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.

  7. Nitric oxide scavenging by cell-free hemoglobin may be a primary factor determining hypertension in polycythemic patients.

    PubMed

    Rusak, T; Misztal, T; Piszcz, J; Tomasiak, M

    2014-02-01

    We tested the hypothesis that hypertension associated with polycythemia vera (PV) may be related to hemoglobin released from erythrocytes (cell-free hemoglobin, fHb). We assessed hematocrit, mean arterial pressure (MAP), blood viscosity, and the level of fHb and nitrite/nitrate (NOx) in the plasma of 73 PV patients and 38 healthy controls. The effect of isovolemic erythrocytapheresis (ECP) on the considered parameters was also studied. From the whole group of PV patients a subset of subjects with normal (normotensive patients, n = 16) and elevated MAP (hypertensive patients, n = 57) can be subtracted. It was found that in comparison with healthy controls, PV patients have significantly (p ≤ 0.01) elevated Hct (0.567 vs. 0.422), blood viscosity (5.45 vs. 3.56 cP), MAP (106.8 vs. 93.8 mmHg), plasma fHb (9.7 vs. 2.8 mg/dL), and NOx levels (34.1 vs. 27.5 μM). Compared with normotensive patients, hypertensive PV patients demonstrated a higher rise in fHb (10.2 vs. 8.0) and plasma NOx levels (35.8 vs. 31.0). In PV patients, fHb positively correlates with MAP (r = 0.489), NOx levels (r = 0.461), hematocrit (r = 0.428), and viscosity (r = 0.393). Blood viscosity positively correlated with hematocrit (r = 0.894), but not with other considered parameters. In PV patients MAP poorly correlated with hematocrit, whereas the correlation between MAP and NOx altered from - 0.325 (healthy control) to + 0.268 (PV patients). ECP procedure was associated with a significant (p < 0.01) reduction of hematocrit, fHb, blood viscosity, and MAP. In the normotensive subgroup of PV patients the ECP procedure did not affect MAP. It can be concluded that accelerated scavenging of nitric oxide by fHb rather than high Hct may be a key factor determining the development of hypertension in PV patients. PMID:24180690

  8. 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...

  9. 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...

  10. Reversibility of heme-nitric oxide reactions for use in an inhaled nitric oxide sensor

    NASA Astrophysics Data System (ADS)

    Parikh, Bhairavi R.; Soller, Babs R.; Rencus, Tal

    1997-06-01

    Nitric Oxide is a simple gaseous compound which serves as a regulatory molecule in a number of physiological processes. Due to its biological role as a potent local vasodilator,there has been widespread interest in the therapeutic use of gaseous nitric oxide a selective pulmonary vasodilator. Our goal is the development of a sensor for the direct and continuous measurement of inhaled nitric oxide concentrations. This study evaluated the reversibility of potential sensing compounds upon reaction with nitric oxide. Previously, absorption spectroscopy was used to study the sensitivity of the Fe II, Fe III and oxygenated forms of three biologically active hemes known to rapidly react with NO: hemoglobin, myoglobin, and cytochrome-c. This study focused on the photo-reversibility of the hem's reaction with nitric oxide. Hemoglobin, myoglobin and cytochrome-c in the Fe III state reversibly reacted with nitric oxide. Hemoglobin and myoglobin in the Fe II state non-reversibly reacted with nitric oxide to form an unstable product. Cytochrome-c (FeII) does not react with nitric oxide. The oxy forms of hemoglobin and myoglobin react with nitric oxide to form their respective met forms, unreversible via photolysis. For all reversible reactions, photolysis was gradual and complete within five minutes.

  11. Nitric oxide synthase in ferret brain: localization and characterization.

    PubMed Central

    Matsumoto, T.; Mitchell, J. A.; Schmidt, H. H.; Kohlhaas, K. L.; Warner, T. D.; Förstermann, U.; Murad, F.

    1992-01-01

    1. In the present study, we have investigated the distribution of nitric oxide synthase in the ferret brain. Nitric oxide synthase was determined biochemically and immunochemically. 2. In the rat brain, the highest nitric oxide synthase activity has been detected in the cerebellum. However, in the ferret brain, the highest activity was found in the striatum and the lowest in the cerebellum and cerebral cortex. The enzymatic activity was localized predominantly in the cytosolic fractions, it was dependent on NADPH and Ca2+, and inhibited by NG-nitro-L-arginine or NG-methyl-L-arginine. 3. Western blot analysis revealed that all regions of the ferret brain contained a 160 kD protein crossreacting with an antibody to nitric oxide synthase purified from the rat cerebellum, and the levels of relative intensity of staining by the antibody correlated with the distribution of nitric oxide synthase activity. 4. These results indicate that the ferret brain contains a nitric oxide synthase similar to the rat brain, but the distribution of enzymatic activity in the ferret brain differs markedly from the rat brain. Images Figure 1 PMID:1282076

  12. 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

  13. 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.

  14. 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

  15. 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.

  16. 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

  17. [Exhaled nitric oxide in pediatric asthma].

    PubMed

    Alvarez Caro, Francisco; Pérez Guirado, Alejandro; Ruiz Del Árbol Sánchez, Paloma; de Miguel Mallén, Angeles; Alvarez Berciano, Francisco

    2010-12-01

    Exhaled nitric oxide has become a new diagnostic tool in pediatric daily practice. It provides valuable information on the nature of the underlying inflammation, being useful to establish the diagnosis and to differentiate which patients could benefit more from the anti-inflammatory treatment. As well, it can be useful in predicting asthmatic exacerbations and be used as a guide to make therapeutic modifications. Taking everything to account, the pediatrician has to know its interpretation and its applications. This manuscript reviews the main applications of exhaled nitric oxide in pediatric asthma. PMID:21132252

  18. Nitric oxide regulates blastocyst hatching in mice

    PubMed Central

    Pan, Xiaoyan; Wang, Xuenan; Wang, Xiyan; Sun, Zhanxuan; Zhang, Xue; Liang, Xuanxuan; Li, Zhixin; Dou, Zhaohua

    2015-01-01

    Objective: This study is to determine the regulatory role of nitric oxide in mouse blastocyst hatching. Methods: Kunming female mice were superovulated and then mated with mature male mice. On day 2.5 of their pregnancy, the pregnant mice were killed and morulae were flushed from their uterine horns with culture media. Morulae were cultured in media with different concentrations of N-nitro-L arginine methyl ester (L-NAME), sodium nitroprusside (SNP), 8-Br-3’-5’-cyclic guanosine monophosphate (8-Br-cGMP) or the combination of L-NAME with SNP or 8-Br-cGMP for 48 h. The hatched blastocysts were examined on day 5 and the expressions of epithelial nitric oxide synthase (eNOS) and active cysteinyl aspartate specific proteinase 3 (caspase 3) were observed under confocal laser scanning microscope. Results: L-NAME significantly reduced the expression of eNOS in blastocyst cells. With the increase of the concentrations of L-NAME, SNP or 8-Br-cGMP, blastocyst hatching rate was significantly lowered. In addition, 5 mM L-NAME, 2 μM SNP and 2 μM 8-Br-cGMP completely inhibited blastocyst hatching. Low concentrations of SNP or 8-Br-cGMP in culture media containing 5 mM L-NAME significantly reversed the inhibition of blastocyst hatching and promoted hatching development. Moreover, 5 mM L-NAME and 2 μM 8-Br-cGMP had no significant influence on the expression of active caspase 3 in blastocyst cells. SNP (> 500 nM) significantly increased the expression of active caspase 3 in blastocyst cells. Conclusions: NO/cGMP pathway plays an important role in mouse blastocyst hatching. Excessive or depleted NO can interrupt blastocyst hatching. Excessive NO leads to apoptosis of blastocyst cells. PMID:26221236

  19. 49 CFR 173.337 - Nitric oxide.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Nitric oxide. 173.337 Section 173.337 Transportation Other Regulations Relating to Transportation PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION HAZARDOUS MATERIALS REGULATIONS SHIPPERS-GENERAL REQUIREMENTS FOR SHIPMENTS AND PACKAGINGS Gases; Preparation...

  20. 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...

  1. Nitric oxide. Novel biology with clinical relevance.

    PubMed Central

    Billiar, T R

    1995-01-01

    OBJECTIVE: The author provides the reader with a view of the regulation and function of nitric oxide (NO), based on the three distinct enzyme isoforms that synthesize NO. SUMMARY BACKGROUND DATA: Nitric oxide is a short-lived molecule exhibiting functions as diverse as neurotransmission and microbial killing. Recent advances in the characterization of the enzymes responsible for NO synthesis and in the understanding of how NO interacts with targets have led to new insights into the many facets of this diverse molecule. METHODS: Nitric oxide is produced by one of three enzyme isoforms of NO synthesis. These enzymes vary considerably in their distribution, regulation, and function. Accordingly, the NO synthesis or lack of NO production will have consequences unique to that isoform. Therefore, this review summarizes the regulation and function of NO generated by each of the three isoforms. RESULTS: Nitric oxide exhibits many unique characteristics that allow this molecule to perform so many functions. The amount, duration, and location of the NO synthesis will depend on the isoform of NO synthase expressed. For each isoform, there probably are disease processes in which deficiency states exist. For induced NO synthesis, states of overexpression exist. CONCLUSIONS: Understanding the regulation and function of the enzymes that produce NO and the unique characteristics of each enzyme isoform is likely to lead to therapeutic approaches to prevent or treat a number of diseases. PMID:7537035

  2. 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...

  3. Determination of nitric oxide metabolites, nitrate and nitrite, in Anopheles culicifacies mosquito midgut and haemolymph by anion exchange high-performance liquid chromatography: plausible mechanism of refractoriness

    PubMed Central

    Sharma, Arun; Raghavendra, Kamaraju; Adak, Tridibesh; Dash, Aditya P

    2008-01-01

    Background The diverse physiological and pathological role of nitric oxide in innate immune defenses against many intra and extracellular pathogens, have led to the development of various methods for determining nitric oxide (NO) synthesis. NO metabolites, nitrite (NO2-) and nitrate (NO3-) are produced by the action of an inducible Anopheles culicifacies NO synthase (AcNOS) in mosquito mid-guts and may be central to anti-parasitic arsenal of these mosquitoes. Method While exploring a plausible mechanism of refractoriness based on nitric oxide synthase physiology among the sibling species of An. culicifacies, a sensitive, specific and cost effective high performance liquid chromatography (HPLC) method was developed, which is not influenced by the presence of biogenic amines, for the determination of NO2- and NO3- from mosquito mid-guts and haemolymph. Results This method is based on extraction, efficiency, assay reproducibility and contaminant minimization. It entails de-proteinization by centrifugal ultra filtration through ultracel 3 K filter and analysis by high performance anion exchange liquid chromatography (Sphereclone, 5 μ SAX column) with UV detection at 214 nm. The lower detection limit of the assay procedure is 50 pmoles in all midgut and haemolymph samples. Retention times for NO2- and NO3- in standards and in mid-gut samples were 3.42 and 4.53 min. respectively. Assay linearity for standards ranged between 50 nM and 1 mM. Recoveries of NO2- and NO3- from spiked samples (1–100 μM) and from the extracted standards (1–100 μM) were calculated to be 100%. Intra-assay and inter assay variations and relative standard deviations (RSDs) for NO2- and NO3- in spiked and un-spiked midgut samples were 5.7% or less. Increased levels NO2- and NO3- in midguts and haemolymph of An. culicifacies sibling species B in comparison to species A reflect towards a mechanism of refractoriness based on AcNOS physiology. Conclusion HPLC is a sensitive and accurate technique

  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. 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.

  7. Global observations of nitric oxide in the thermosphere

    NASA Astrophysics Data System (ADS)

    Barth, C. A.; Mankoff, K. D.; Bailey, S. M.; Solomon, S. C.

    2003-01-01

    Nitric oxide density in the lower thermosphere (97-150 km) has been measured from the polar-orbiting Student Nitric Oxide Explorer (SNOE) satellite as a function of latitude, longitude, and altitude for the 2 1/2 year period from 11 March 1998 until 30 September 2000. The observations show that the maximum density occurs near 106-110 km and that the density is highly variable. The nitric oxide density at low latitudes correlates well with the solar soft X-ray irradiance (2-7 nm), indicating that it is the solar X-rays that produce thermospheric nitric oxide at low and midlatitudes. Nitric oxide is produced at auroral latitudes (60°-70° geomagnetic) by the precipitation of electrons (1-10 keV) into the thermosphere. During high geomagnetic activity, increased nitric oxide may be present at midlatitudes as the result of meridional winds that carry the nitric oxide equatorward.

  8. A selective nanosensing probe for nitric oxide

    NASA Astrophysics Data System (ADS)

    Gouma, P. I.; Kalyanasundaram, K.

    2008-12-01

    Measurement of NO gas in exhaled human breath may be used to monitor oxidative stress and pulmonary diseases. Until now, only bulk, expensive, chemiluminescence-based NO monitors have been available to medicine. A nanosensing probe based on WO3 selectively detecting minute nitric oxide gas concentrations in the presence of interfering volatile compounds is presented. This is possible due to the chemical affinity of rhenium trioxide based phases to oxidizing gases. The NO nanoprobe is expected to lead to portable and affordable, noninvasive, single breath sampling, NO diagnostics.

  9. 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.

  10. Endothelial nitric oxide synthase in the microcirculation.

    PubMed

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

    2015-12-01

    Endothelial nitric oxide synthase (eNOS, NOS3) is responsible for producing nitric oxide (NO)--a key molecule that can directly (or indirectly) act as a vasodilator and anti-inflammatory mediator. In this review, we examine the structural effects of regulation of the eNOS enzyme, including post-translational modifications and subcellular localization. After production, NO diffuses to surrounding cells with a variety of effects. We focus on the physiological role of NO and NO-derived molecules, including microvascular effects on vessel tone and immune response. Regulation of eNOS and NO action is complicated; we address endogenous and exogenous mechanisms of NO regulation with a discussion of pharmacological agents used in clinical and laboratory settings and a proposed role for eNOS in circulating red blood cells. PMID:26390975

  11. Dexmedetomidine inhibits vasoconstriction via activation of endothelial nitric oxide synthase.

    PubMed

    Nong, Lidan; Ma, Jue; Zhang, Guangyan; Deng, Chunyu; Mao, Songsong; Li, Haifeng; Cui, Jianxiu

    2016-09-01

    Despite the complex vascular effects of dexmedetomidine (DEX), its actions on human pulmonary resistance arteries remain unknown. The present study tested the hypothesis that DEX inhibits vascular tension in human pulmonary arteries through the endothelial nitric oxide synthase (eNOS) mediated production of nitric oxide (NO). Pulmonary artery segments were obtained from 62 patients who underwent lung resection. The direct effects of DEX on human pulmonary artery tension and changes in vascular tension were determined by isometric force measurements recorded on a myograph. Arterial contractions caused by increasing concentrations of serotonin with DEX in the presence or absence of L-NAME (endothelial nitric oxide synthase inhibitor), yohimbine (α2-adrenoceptor antagonist) and indomethacin (cyclooxygenase inhibitor) as antagonists were also measured. DEX had no effect on endothelium-intact pulmonary arteries, whereas at concentrations of 10(-8)~10(-6) mol/L, it elicited contractions in endothelium-denuded pulmonary arteries. DEX (0.3, 1, or 3×10(-9) mmol/L) inhibited serotonin-induced contraction in arteries with intact endothelium in a dose-dependent manner. L-NAME and yohimbine abolished DEX-induced inhibition, whereas indomethacin had no effect. No inhibitory effect was observed in endothelium-denuded pulmonary arteries. DEX-induced inhibition of vasoconstriction in human pulmonary arteries is mediated by NO production induced by the activation of endothelial α2-adrenoceptor and nitric oxide synthase. PMID:27610030

  12. Dexmedetomidine inhibits vasoconstriction via activation of endothelial nitric oxide synthase

    PubMed Central

    Nong, Lidan; Ma, Jue; Zhang, Guangyan; Deng, Chunyu; Mao, Songsong; Li, Haifeng

    2016-01-01

    Despite the complex vascular effects of dexmedetomidine (DEX), its actions on human pulmonary resistance arteries remain unknown. The present study tested the hypothesis that DEX inhibits vascular tension in human pulmonary arteries through the endothelial nitric oxide synthase (eNOS) mediated production of nitric oxide (NO). Pulmonary artery segments were obtained from 62 patients who underwent lung resection. The direct effects of DEX on human pulmonary artery tension and changes in vascular tension were determined by isometric force measurements recorded on a myograph. Arterial contractions caused by increasing concentrations of serotonin with DEX in the presence or absence of L-NAME (endothelial nitric oxide synthase inhibitor), yohimbine (α2-adrenoceptor antagonist) and indomethacin (cyclooxygenase inhibitor) as antagonists were also measured. DEX had no effect on endothelium-intact pulmonary arteries, whereas at concentrations of 10–8~10–6 mol/L, it elicited contractions in endothelium-denuded pulmonary arteries. DEX (0.3, 1, or 3×10–9 mmol/L) inhibited serotonin-induced contraction in arteries with intact endothelium in a dose-dependent manner. L-NAME and yohimbine abolished DEX-induced inhibition, whereas indomethacin had no effect. No inhibitory effect was observed in endothelium-denuded pulmonary arteries. DEX-induced inhibition of vasoconstriction in human pulmonary arteries is mediated by NO production induced by the activation of endothelial α2-adrenoceptor and nitric oxide synthase. PMID:27610030

  13. Rate of Nitric Oxide Scavenging by hemoglobin bound to haptoglobin

    PubMed Central

    Azarov, Ivan; He, Xiaojun; Jeffers, Anne; Basu, Swati; Ucer, Burak; Hantgan, Roy R.; Levy, Andrew; Kim-Shapiro, Daniel B.

    2008-01-01

    Cell-free hemoglobin, released from the red cell, may play a major role in regulating the bioavailability of nitric oxide. The abundant serum protein haptoglobin, rapidly binds to free hemoglobin forming a stable complex accelerating its clearance. The haptoglobin gene is polymorphic with two classes of alleles denoted 1 and 2. We have previously demonstrated that the haptoglobin 1 protein-hemoglobin complex is cleared twice as fast as the haptoglobin 2 protein-hemoglobin complex. In this report we explored whether haptoglobin binding to hemoglobin reduces the rate of nitric oxide scavenging using time-resolved absorption spectroscopy. We found that both the haptoglobin 1 and haptoglobin 2 protein complexes react with nitric oxide at the same rate as unbound cell-free hemoglobin. To confirm these results we developed a novel assay where free hemoglobin and hemoglobin bound to haptoglobin competed in the reaction with NO. The relative rate of the NO reaction was then determined by examining the amount of reacted species using analytical ultracentrifugation. Since complexation of hemoglobin with haptoglobin does not reduce NO scavenging, we propose that the haptoglobin genotype may influence nitric oxide bioavailability by determining the clearance rate of the haptoglobin-hemoglobin complex. We provide computer simulations showing that a two-fold difference in the rate of uptake of the haptoglobin hemoglobin complex by macrophages significantly affects nitric oxide bioavailability thereby providing a plausible explanation for why there is more vasospasm after subarachnoid hemorrhage in individuals and transgenic mice homozygous for the Hp 2 allele. PMID:18364244

  14. Nitric oxide-induced calcium release

    PubMed Central

    Kakizawa, Sho; Yamazawa, Toshiko; Iino, Masamitsu

    2013-01-01

    Ryanodine receptors (RyRs), located in the sarcoplasmic/endoplasmic reticulum (SR/ER) membrane, are required for intracellular Ca2+ release that is involved in a wide range of cellular functions. In addition to Ca2+-induced Ca2+ release in cardiac cells and voltage-induced Ca2+ release in skeletal muscle cells, we recently identified another mode of intracellular Ca2+ mobilization mediated by RyR, i.e., nitric oxide-induced Ca2+ release (NICR), in cerebellar Purkinje cells. NICR is evoked by neuronal activity, is dependent on S-nitrosylation of type 1 RyR (RyR1) and is involved in the induction of long-term potentiation (LTP) of cerebellar synapses. In this addendum, we examined whether peroxynitrite, which is produced by the reaction of nitric oxide with superoxide, may also have an effect on the Ca2+ release via RyR1 and the cerebellar LTP. We found that scavengers of peroxynitrite have no significant effect either on the Ca2+ release via RyR1 or on the cerebellar LTP. We also found that an application of a high concentration of peroxynitrite does not reproduce neuronal activity-dependent Ca2+ release in Purkinje cells. These results support that NICR is induced by endogenous nitric oxide produced by neuronal activity through S-nitrosylation of RyR1. PMID:23247505

  15. Nitric oxide releasing material adsorbs more fibrinogen.

    PubMed

    Lantvit, Sarah M; Barrett, Brittany J; Reynolds, Melissa M

    2013-11-01

    One mechanism of the failure of blood-contacting devices is clotting. Nitric oxide (NO) releasing materials are seen as a viable solution to the mediation of surface clotting by preventing platelet activation; however, NO's involvement in preventing clot formation extends beyond controlling platelet function. In this study, we evaluate NO's effect on factor XII (fibrinogen) adsorption and activation, which causes the initiation of the intrinsic arm of the coagulation cascade. This is done by utilizing a model plasticized poly(vinyl) chloride (PVC), N-diazeniumdiolate system and looking at the adsorption of fibrinogen, an important clotting protein, to these surfaces. The materials have been prepared in such a way to eliminate changes in surface properties between the control (plasticized PVC) and composite (NO-releasing) materials. This allows us to isolate NO release and determine the effect on the adsorption of fibrinogen, to the material surface. Surprisingly, it was found that an NO releasing material with a surface flux of 17.4 ± 0.5 × 10(-10) mol NO cm(-2) min(-1) showed a significant increase in the amount of fibrinogen adsorbed to the material surface compared to one with a flux of 13.0 ± 1.6 × 10(-10) mol NO cm(-2) min(-1) and the control (2334 ± 496, 226 ± 99, and 103 ±31% fibrinogen adsorbed of control, respectively). This study suggests that NO's role in controlling clotting is extended beyond platelet activation. PMID:23554300

  16. Modulation of nitric oxide bioavailability by erythrocytes

    NASA Astrophysics Data System (ADS)

    Huang, Kuang-Tse; Han, Tae H.; Hyduke, Daniel R.; Vaughn, Mark W.; van Herle, Helga; Hein, Travis W.; Zhang, Cuihua; Kuo, Lih; Liao, James C.

    2001-09-01

    Nitric oxide (NO) activates soluble guanylyl cyclase in smooth muscle cells to induce vasodilation in the vasculature. However, as hemoglobin (Hb) is an effective scavenger of NO and is present in high concentrations inside the red blood cell (RBC), the bioavailability of NO would be too low to elicit soluble guanylyl cyclase activation in the presence of blood. Therefore, NO bioactivity must be preserved. Here we present evidence suggesting that the RBC participates in the preservation of NO bioactivity by reducing NO influx. The NO uptake by RBCs was increased and decreased by altering the degree of band 3 binding to the cytoskeleton. Methemoglobin and denatured hemoglobin binding to the RBC membrane or cytoskeleton also were shown to contribute to reducing the NO uptake rate of the RBC. These alterations in NO uptake by the RBC, hence the NO bioavailability, were determined to correlate with the vasodilation of isolated blood vessels. Our observations suggest that RBC membrane and cytoskeleton associated NO-inert proteins provide a barrier for NO diffusion and thus account for the reduction in the NO uptake rate of RBCs.

  17. 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

  18. 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.

  19. Detection of hydrazine compounds in gaseous samples by their conversion to nitric oxide-yielding derivatives

    SciTech Connect

    Rounbehler, D.P.

    1988-10-04

    This patent describes a method of detecting the presence of hydrazine, monomethylhydrazine, and unsymmetrical dimethylhydrazine in a gaseous sample, essentially in real time. The method consists of the steps of: (a) contacting a gaseous sample with aldehyde or ketone vapors to convert hydrazine, monomethylhydrazine, and unsymmetrical dimethylhydrazine in the sample to hydrazine derivatives; (b) heating the sample in the presence of an oxidant to decompose derivatives produced in steps (a) to produce nitric oxide gas; and (c) determining the amount of nitric oxide gas produced in step (b), wherein any nitric oxide gas determined is indicative of the presence of hydrazine, monomethylhydrazine, and unsymmetrical dimethylhydrazine in the gaseous sample.

  20. [Nitric oxide and the kidneys].

    PubMed

    Dzúrik, R; Spustová, V

    2001-02-01

    Nitrogen oxide (NO) is one of the crucial modulators of the vascular tonus. Apart from its effect on the cardiovascular system it exerts an effect also on other types of cells and ensures their functions.Specially comprehensive is its synthesis and action in the kidneys: NO is formed in the endothelial cells due to the activity of constitutional endothelial synthase (eNOS), in mesangial cells of inductive synthase (iNOS), in smooth muscle cells (vsmNOS), in tubular cells neuronal NOS (nNOS) and iNOS and in the macula densa nNOS. By modulation of the v.afferens it influences the blood flow through the glomeruli and filtration pressure in the glomeruli. It participates in the tubuloglomerular feedback: the cells of the macula densa produce NO via nNOS, the genetic transcription and translation of which as well as the kationic translation system ensure the transport of the L-arginine precursor and regulate very sensitively NO formation. The latter diffuses via the extraglomerular mesangium into the iuxtaglomerular apparatus where renin is forned.NO reduces proteinuria and renal proliferation. During renal insufficiency NO production is inhibited and in diabetes NO production is increased. Diabetic hyperfiltration and hypertrophy are ascribed to produced NO. Experimental studies contributed substantially to the knowledge of renal effects of NO. At present intensive clinical research has been started which, no doubt, will influence medical practice. PMID:15635855

  1. 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

  2. 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.

  3. Processes regulating nitric oxide emissions from soils.

    PubMed

    Pilegaard, Kim

    2013-07-01

    Nitric oxide (NO) is a reactive gas that plays an important role in atmospheric chemistry by influencing the production and destruction of ozone and thereby the oxidizing capacity of the atmosphere. NO also contributes by its oxidation products to the formation of acid rain. The major sources of NO in the atmosphere are anthropogenic emissions (from combustion of fossil fuels) and biogenic emission from soils. NO is both produced and consumed in soils as a result of biotic and abiotic processes. The main processes involved are microbial nitrification and denitrification, and chemodenitrification. Thus, the net result is complex and dependent on several factors such as nitrogen availability, organic matter content, oxygen status, soil moisture, pH and temperature. This paper reviews recent knowledge on processes forming NO in soils and the factors controlling its emission to the atmosphere. Schemes for simulating these processes are described, and the results are discussed with the purpose of scaling up to global emission. PMID:23713124

  4. Nitric oxide and asthma: a review.

    PubMed

    Ashutosh, K

    2000-01-01

    Nitric oxide (NO) is synthesized from the amino acid arginine by enzymes called nitric oxide synthases. NO has an important physiologic role in the regulation of vascular tone, response to vascular injury, and hemostasis. It also acts as a neurotransmitter for the nonadrenergic noncholinergic nerves and has important antimicrobial, immunologic, and proinflammatory activities. The lung is rich in nitric oxide synthases, and NO is normally present in the exhaled air. Use of NO in the treatment of asthma has not withstood the test of time and is not recommended. With the advent of analyzers capable of measuring NO rapidly and reliably, however, the analysis of NO in exhaled air is being increasingly recognized as a potential noninvasive test for the evaluation of the inflammatory component of the pathology of patients with asthma. An increase in the exhaled NO has been shown to accompany eosinophilic inflammation and to correlate with other indices of inflammation in asthma. Exhaled NO increases during exacerbation and decreases with recovery in patients with asthma. As exhaled NO is not increased during bronchospasm in the absence of coexisting inflammation, it could serve to differentiate between the inflammatory and bronchospastic components in asthma, thereby guiding therapy with steroids and other anti-inflammatory medications. Levels of NO also can be increased in certain other conditions, for example, allergic rhinitis and adult respiratory distress syndrome, but these can be clinically differentiated from asthma and do not lessen the diagnostic value of exhaled NO. Measurements of exhaled NO are influenced by several physiologic and technical variables, which results in a wide variation in the levels reported from the different laboratories. Standardization of technique, a better understanding of the confounding effects of physiologic and environmental variables, and establishment of the normal range and variability of exhaled NO are needed before its

  5. Nitric oxide regulates vascular adaptive mitochondrial dynamics.

    PubMed

    Miller, Matthew W; Knaub, Leslie A; Olivera-Fragoso, Luis F; Keller, Amy C; Balasubramaniam, Vivek; Watson, Peter A; Reusch, Jane E B

    2013-06-15

    Cardiovascular disease risk factors, such as diabetes, hypertension, dyslipidemia, obesity, and physical inactivity, are all correlated with impaired endothelial nitric oxide synthase (eNOS) function and decreased nitric oxide (NO) production. NO-mediated regulation of mitochondrial biogenesis has been established in many tissues, yet the role of eNOS in vascular mitochondrial biogenesis and dynamics is unclear. We hypothesized that genetic eNOS deletion and 3-day nitric oxide synthase (NOS) inhibition in rodents would result in impaired mitochondrial biogenesis and defunct fission/fusion and autophagy profiles within the aorta. We observed a significant, eNOS expression-dependent decrease in mitochondrial electron transport chain (ETC) protein subunits from complexes I, II, III, and V in eNOS heterozygotes and eNOS null mice compared with age-matched controls. In response to NOS inhibition with NG-nitro-L-arginine methyl ester (L-NAME) treatment in Sprague Dawley rats, significant decreases were observed in ETC protein subunits from complexes I, III, and IV as well as voltage-dependent anion channel 1. Decreased protein content of upstream regulators of mitochondrial biogenesis, cAMP response element-binding protein and peroxisome proliferator-activated receptor-γ coactivator-1α, were observed in response to 3-day L-NAME treatment. Both genetic eNOS deletion and NOS inhibition resulted in decreased manganese superoxide dismutase protein. L-NAME treatment resulted in significant changes to mitochondrial dynamic protein profiles with decreased fusion, increased fission, and minimally perturbed autophagy. In addition, L-NAME treatment blocked mitochondrial adaptation to an exercise intervention in the aorta. These results suggest that eNOS/NO play a role in basal and adaptive mitochondrial biogenesis in the vasculature and regulation of mitochondrial turnover. PMID:23585138

  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. 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

  8. 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

  9. 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

  10. 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.

  11. 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…

  12. 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...

  13. 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...

  14. 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....

  15. 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....

  16. 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...

  17. 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....

  18. 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....

  19. 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....

  20. 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.

  1. 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

  2. Reduction of nitric oxide emissions from a combustor

    NASA Technical Reports Server (NTRS)

    Craig, R. A.; Pritchard, H. O. (Inventor)

    1980-01-01

    A turbojet combustor and method for controlling nitric oxide emissions by employing successive combustion zones is described. After combustion of an initial portion of the fuel in a primary combustion zone, the combustion products of the primary zone are combined with the remaining portion of fuel and additional plenum air and burned in a secondary combustion zone under conditions that result in low nitric oxide emissions. Low nitric oxide emissions are achieved by a novel turbojet combustor arrangement which provides flame stability by allowing stable combustion to be accompanied by low nitric oxide emissions resulting from controlled fuel-lean combustion (ignited by the emission products from the primary zone) in a secondary combustion zone at a lower combustion temperature resulting in low emission of nitric oxide.

  3. Nitric oxide protects endothelium from cadmium mediated leakiness.

    PubMed

    Nagarajan, Shunmugam; Rajendran, Saranya; Saran, Uttara; Priya, M Krishna; Swaminathan, Akila; Siamwala, Jamila H; Sinha, Swaraj; Veeriah, Vimal; Sonar, Punam; Jadhav, Vivek; Jaffar Ali, B M; Chatterjee, Suvro

    2013-05-01

    Cadmium targets the vascular endothelium causing endothelial dysfunction and leakiness of endothelial barrier. Nitric oxide plays a major role in mediating endothelial functions including angiogenesis, migration and permeability. The present study investigates the nitric oxide effects on cadmium induced endothelial leakiness. Results of ex vivo and in vitro permeability assays showed that even a sub-lethal dose of cadmium chloride (1 µM) was sufficient to induce leakiness of endothelial cells. Cadmium drastically altered the actin polymerisation pattern and membrane tension of these cells compared to controls. Addition of nitric oxide donor Spermine NONOate (SP) significantly blunted cadmium-mediated effects and recover endothelial cells integrity. Cadmium-induced cytoskeletal rearrangements and membrane leakiness are associated with the low nitric oxide availability and high reactive oxygen species generation. In brief, we show the protective role of nitric oxide against cadmium-mediated endothelial leakiness. PMID:23404577

  4. Nitric oxide modulators: an emerging class of medicinal agents.

    PubMed

    Deshpande, S R; Satyanarayana, K; Rao, M N A; Pai, K V

    2012-11-01

    Nitric oxide, a unique messenger in biological system, is ubiquitously present virtually in all tissues revealing its versatile nature of being involved in diverse physiological functions such as vascular tone, inhibition of platelet aggregation, cell adhesion, neurotransmission and enzyme and immune regulation. The tremendous advancements made in the past few decades in this area suggests that the nitric oxide modulation either by its exogenous release through nitric oxide donors or inhibition of its synthesis by nitric oxide synthase inhibitors in physiological milieu may provide newer clinical strategies for the treatment of some diseases. In this review, an attempt is made to document and understand the biological chemistry of different classes of nitric oxide modulators that would prove to be a fruitful area in the years to come. PMID:23798773

  5. Nitric oxide scavengers as a therapeutic approach to nitric oxide mediated disease.

    PubMed

    Fricker, S P

    1999-08-01

    The essential role of nitric oxide (NO) in normal physiology and its involvement in the pathophysiology of a variety of diseases render the compound an attractive therapeutic target. NO donor drugs are used in the treatment of hypotension and angina where abnormalities in the L-arginine-nitric oxide pathway have been implicated. Overproduction of NO has been associated with a number of disease states including septic shock, inflammatory diseases, diabetes, ischaemia-reperfusion injury, adult respiratory distress syndrome, neurodegenerative diseases and allograft rejection. NO is produced by a group of enzymes, the nitric oxide synthases. Selective inhibition of the inducible isoform is one approach to the treatment of diseases where there is an overproduction of NO; an alternative approach is to scavenge or remove excess NO. A number of NO scavenger molecules have demonstrated pharmacological activity in disease models, particularly models of septic shock. These include organic molecules such as PTIO (2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide), haemoglobin derivatives such as the pyridoxalated haemoglobin polyoxyethylene conjugate (PHP), low molecular weight iron compounds of diethylenetriaminepentaacetic acid and diethyldithiocarbamate and ruthenium polyaminocarboxylate complexes. The data suggest a potential role for NO scavengers in the treatment of NO mediated disease. PMID:15992146

  6. Nitric oxide and platelet energy metabolism.

    PubMed

    Tomasiak, Marian; Stelmach, Halina; Rusak, Tomasz; Wysocka, Jolanta

    2004-01-01

    This study was undertaken to determine whether nitric oxide (NO) can affect platelet responses through the inhibition of energy production. It was found that NO donors: S-nitroso-N-acetylpenicyllamine, SNAP, (5-50 microM) and sodium nitroprusside, SNP, (5-100 microM) inhibited collagen- and ADP-induced aggregation of porcine platelets. The corresponding IC50 values for SNAP and SNP varied from 5 to 30 microM and from 9 to 75 microM, respectively. Collagen- and thrombin-induced platelet secretion was inhibited by SNAP (IC50 = 50 microM) and by SNP (IC50 = 100 microM). SNAP (20-100 microM), SNP (10-200 microM) and collagen (20 microg/ml) stimulated glycolysis in intact platelets. The degree of glycolysis stimulation exerted by NO donors was similar to that produced by respiratory chain inhibitors (cyanide and antimycin A) or uncouplers (2,4-dinitrophenol). Neither the NO donors nor the respiratory chain blockers affected glycolysis in platelet homogenate. SNAP (20-100 microM) and SNP (50-200 microM) inhibited oxygen consumption by platelets. The effect of SNP and SNAP on glycolysis and respiration was not reduced by 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one, a selective inhibitor of NO-stimulated guanylate cyclase. SNAP (5-100 microM) and SNP (10-300 microM) inhibited the activity of platelet cytochrome oxidase and had no effect on NADH:ubiquinone oxidoreductase and succinate dehydrogenase. Blocking of the mitochondrial energy production by antimycin A slightly affected collagen-evoked aggregation and strongly inhibited platelet secretion. The results indicate that: 1) in porcine platelets NO is able to diminish mitochondrial energy production through the inhibition of cytochrome oxidase, 2) the inhibitory effect of NO on platelet secretion (but not aggregation) can be attributed to the reduction of mitochondrial energy production. PMID:15448739

  7. 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...

  8. Nitric oxide-mediated blood flow regulation as affected by smoking and nicotine.

    PubMed

    Toda, Noboru; Toda, Hiroshi

    2010-12-15

    Cigarette smoking is a major risk factor for atherosclerosis, cerebral and coronary vascular diseases, hypertension, and diabetes mellitus. Chronic smoking impairs endothelial function by decreasing the formation of nitric oxide and increasing the degradation of nitric oxide via generation of oxygen free radicals. Nitric oxide liberated from efferent nitrergic nerves is also involved in vasodilatation, increased regional blood flow, and hypotension that are impaired through nitric oxide sequestering by smoking-induced factors. Influence of smoking on nitric oxide-induced blood flow regulation is not necessarily the same in all organs and tissues. However, human studies are limited mainly to the forearm blood flow measurement that assesses endothelial function under basal and stimulated conditions and also determination of penile tumescence and erection in response to endothelial and neuronal nitric oxide. Therefore, information about blood flow regulation in other organs, such as the brain and placenta, has been provided mainly from studies on experimental animals. Nicotine, a major constituent of cigarette smoke, acutely dilates cerebral arteries and arterioles through nitric oxide liberated from nitrergic neurons, but chronically interferes with endothelial function in various vasculatures, both being noted in studies on experimental animals. Cigarette smoke constituents other than nicotine also have some vascular actions. Not only active but also passive smoking is undoubtedly harmful for both the smokers themselves and their neighbors, who should bear in mind that they can face serious diseases in the future, which may result in lengthy hospitalization, and a shortened lifespan. PMID:20868673

  9. 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

  10. 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

  11. An intercomparison of nitric oxide measurement techniques

    NASA Technical Reports Server (NTRS)

    Hoell, J. M., Jr.; Gregory, G. L.; Mcdougal, D. S.; Carroll, M. A.; Mcfarland, M.; Ridley, B. A.; Davis, D. D.; Bradshaw, J.; Rodgers, M. O.; Torres, A. L.

    1985-01-01

    Results from an intercomparison of techniques to measure tropospheric levels of nitric oxide (NO) are discussed. The intercomparison was part of the National Aeronautics and Space Administration's Global Tropospheric Experiment and was conducted at Wallops Island, VA, in July 1983. Instruments intercompared included a laser-induced fluorescence system and two chemiluminescence instruments. The intercomparisons were performed with ambient air at NO mixing ratios ranging from 10 to 60 pptv and NO-enriched ambient air at mixing ratios from 20 to 170 pptv. All instruments sampled from a common manifold. The techniques exhibited a high degree of correlation among themselves and with changes in the NO mixing ratio. Agreement among the three techniques was placed at approximately + or - 30 percent. Within this level of agreement, no artifacts or species interferences were identified.

  12. The emerging multifaceted roles of nitric oxide.

    PubMed Central

    Kuo, P C; Schroeder, R A

    1995-01-01

    Nitric oxide (NO) is a highly reactive free radical with a multitude of organ specific regulatory functions. Since 1985, NO has been the subject of numerous research efforts and as a result, has been found to play a major role in the cardiovascular, pulmonary, gastrointestinal, immune, and central nervous systems. In addition, deranged NO synthesis is the basis for a number of pathophysiologic states, such as atherosclerosis, pulmonary hypertension, pyloric stenosis, and the hypertension associated with renal failure. Traditional NO donors such as sodium nitroprusside and new pharmacologic NO adducts such as S-nitrosothiols may serve as exogenous sources of NO for the treatment of NO-deficient pathologic states. This review is an attempt to acquaint the surgical community with the fundamentals of NO biochemistry and physiology. Increased knowledge of its functions in normal homeostasis and pathologic states will enable physicians to better understand these disease processes and utilize new pharmacologic therapies. PMID:7717775

  13. 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

  14. Nitric Oxide and Respiratory Helminthic Diseases

    PubMed Central

    Muro, Antonio; Pérez-Arellano, José-Luís

    2010-01-01

    Nitric oxide (NO) is a very simple molecule that displays very important functions both in helminths (mainly those involved in respiratory pathology) and in mammalian hosts. In this paper we review four issues related to interaction of NO and lung helminthic diseases. Firstly, we evaluated data available on the NO synthesis and release by helminths and their biological role. Next, we summarized the effect of antigens obtained from different phases of the biological cycle on NO production by host mammalian cells (mainly from human sources). Thirdly, we revised the evaluation of NO on the biological activities and/or the viability of respiratory helminths. Lastly, the deleterious consequences of increased production of NO during helminthic human infection are detailed. PMID:20169170

  15. 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

  16. Nitric oxide flow tagging in unseeded air.

    PubMed

    Dam, N; Klein-Douwel, R J; Sijtsema, N M; Meulen, J J

    2001-01-01

    A scheme for molecular tagging velocimetry is presented that can be used in air flows without any kind of seeding. The method is based on the local and instantaneous creation of nitric oxide (NO) molecules from N(2) and O(2) in the waist region of a focused ArF excimer laser beam. This NO distribution is advected by the flow and can be visualized any time later by laser-induced fluorescence in the gamma bands. The creation of NO is confirmed by use of an excitation spectrum. Two examples of the application of the new scheme for air-flow velocimetry are given in which single laser pulses are used for creation and visualization of NO. PMID:18033499

  17. 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.

  18. 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

  19. 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

  20. Nitric oxide, stomatal closure, and abiotic stress.

    PubMed

    Neill, Steven; Barros, Raimundo; Bright, Jo; Desikan, Radhika; Hancock, John; Harrison, Judith; Morris, Peter; Ribeiro, Dimas; Wilson, Ian

    2008-01-01

    Various data indicate that nitric oxide (NO) is an endogenous signal in plants that mediates responses to several stimuli. Experimental evidence in support of such signalling roles for NO has been obtained via the application of NO, usually in the form of NO donors, via the measurement of endogenous NO, and through the manipulation of endogenous NO content by chemical and genetic means. Stomatal closure, initiated by abscisic acid (ABA), is effected through a complex symphony of intracellular signalling in which NO appears to be one component. Exogenous NO induces stomatal closure, ABA triggers NO generation, removal of NO by scavengers inhibits stomatal closure in response to ABA, and ABA-induced stomatal closure is reduced in mutants that are impaired in NO generation. The data indicate that ABA-induced guard cell NO generation requires both nitric oxide synthase-like activity and, in Arabidopsis, the NIA1 isoform of nitrate reductase (NR). NO stimulates mitogen-activated protein kinase (MAPK) activity and cGMP production. Both these NO-stimulated events are required for ABA-induced stomatal closure. ABA also stimulates the generation of H2O2 in guard cells, and pharmacological and genetic data demonstrate that NO accumulation in these cells is dependent on such production. Recent data have extended this model to maize mesophyll cells where the induction of antioxidant defences by water stress and ABA required the generation of H2O2 and NO and the activation of a MAPK. Published data suggest that drought and salinity induce NO generation which activates cellular processes that afford some protection against the oxidative stress associated with these conditions. Exogenous NO can also protect cells against oxidative stress. Thus, the data suggest an emerging model of stress responses in which ABA has several ameliorative functions. These include the rapid induction of stomatal closure to reduce transpirational water loss and the activation of antioxidant defences

  1. Nitric Oxide Signaling and Neural Stem Cell Differentiation in Peripheral Nerve Regeneration

    PubMed Central

    Tao Li, Jessica; Somasundaram, Chandra; Bian, Ka; Xiong, Weijun; Mahmooduddin, Faiz; Nath, Rahul K.; Murad, Ferid

    2010-01-01

    Objective: The objective was to examine whether nitric oxide signaling plays a role in human embryonic stem cell differentiation into neural cells. This article reviews current literature on nitric oxide signaling and neural stem cell differentiation for potential therapeutic application to peripheral nerve regeneration. Methods: Human embryonic H9-stem cells were grown, maintained on mitomycin C–treated mouse embryonic fibroblast feeder layer, cultured on Matrigel to be feeder-free, and used for all the experiments. Fluorescent dual-immunolabeling and confocal image analysis were used to detect the presence of the neural precursor cell markers nestin and nitric oxide synthase-1. Fluorescence-activated cell sorting analysis was used to determine the percentage of expression. Results: We have shown the confocal image of stage 1 human embryonic stem cells coexpressing nestin and nitric oxide synthase-1. Fluorescence-activated cell sorting analysis indicated 24.3% positive labeling of nitric oxide synthase-1. Adding retinoic acid (10−6 M) to the culture medium increased the percent of nitric oxide synthase-1 positive cells to 33.9%. Combining retinoic acid (10−6 M) with 8-brom cyclic guanosine monophosphate (10−5 M), the fluorescence-activated cell sorting analysis demonstrated a further increase of nitric oxide synthase-1 positive cells to 45.4%. Our current results demonstrate a prodifferentiation potency of nitric oxide synthase-1, stimulated by retinoic acid with and without cyclic guanosine monophosphate. Conclusion: We demonstrated for the first time how nitric oxide/cyclic guanosine monophosphate signaling contributes to the development of neural precursors derived from human embryonic stem cells and enhances the differentiation of precursors toward functional neurons for peripheral nerve regeneration. PMID:20563304

  2. Surface plasmon resonance biochip based on ZnO thin film for nitric oxide sensing.

    PubMed

    Feng, Wei-Yi; Chiu, Nan-Fu; Lu, Hui-Hsin; Shih, Hsueh-Ching; Yang, Dongfang; Lin, Chii-Wann

    2008-01-01

    In this study, the design of a novel optical sensor that comprises surface plasmon resonance sensing chip and zinc oxide nano-film was proposed for the detection of nitric oxide gas. The electrical and optical properties of zinc oxide film vary in the presence of nitric oxide. This effect was utilized to prepare biochemical sensors with transduction based on surface plasmon resonance. Due to the refractive index of the transparent zinc oxide film that was deposited on the gold film, however, changes will be observed in the surface plasmon resonance spectra. For this reason, the thickness of zinc oxide film will be investigated and determined in this study. The interaction of nitric oxide with a 20 nm zinc oxide layer on gold leads to the shift of the resonance angle. The analysis on the reflectance intensity of light demonstrates that such effect is caused by the variation of conductivity and permittivity of zinc oxide film. Finally, a shift in surface plasmon resonance angle was measured in 25 ppm nitric oxide at 180 C and a calibration curve of nitride oxide concentration versus response intensity was successfully obtained in the range of 250 to 1000 ppm nitric oxide at lower temperature of 150 C. Moreover, these effects are quasi-reversible. PMID:19164025

  3. Horseradish peroxidase catalyzed nitric oxide formation from hydroxyurea.

    PubMed

    Huang, Jinming; Sommers, Erin M; Kim-Shapiro, Daniel B; King, S Bruce

    2002-04-01

    Hydroxyurea represents an approved treatment for sickle cell anemia and a number of cancers. Chemiluminescence and electron paramagnetic resonance spectroscopic studies show horseradish peroxidase catalyzes the formation of nitric oxide from hydroxyurea in the presence of hydrogen peroxide. Gas chromatographic headspace analysis and infrared spectroscopy also reveal the production of nitrous oxide in this reaction, which provides evidence for nitroxyl, the one-electron reduced form of nitric oxide. These reactions also generate carbon dioxide, ammonia, nitrite, and nitrate. None of these products form within 1 h in the absence of hydrogen peroxide or horseradish peroxidase. Electron paramagnetic resonance spectroscopy and trapping studies show the intermediacy of a nitroxide radical and a C-nitroso species during this reaction. Absorption spectroscopy indicates that both compounds I and II of horseradish peroxidase act as one-electron oxidants of hydroxyurea. Nitroxyl, generated from Angeli's salt, reacts with ferric horseradish peroxidase to produce a ferrous horseradish peroxidase-nitric oxide complex. Electron paramagnetic resonance experiments with a nitric oxide specific trap reveal that horseradish peroxidase is capable of oxidizing nitroxyl to nitric oxide. A mechanistic model that includes the observed nitroxide radical and C-nitroso compound intermediates has been forwarded to explain the observed product distribution. These studies suggest that direct nitric oxide producing reactions of hydroxyurea and peroxidases may contribute to the overall pharmacological properties of this drug. PMID:11916434

  4. 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

  5. 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

  6. 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

  7. Nitric Oxide Loaded Echogenic Liposomes for Nitric Oxide Delivery and Inhibition of Intimal Hyperplasia

    PubMed Central

    Huang, Shao-Ling; Kee, Patrick H.; Kim, Hyunggun; Moody, Melanie R.; Chrzanowski, Stephen M.; MacDonald, Robert C.; McPherson, David D.

    2011-01-01

    Objective To develop a new bioactive gas delivery method using echogenic liposomes (ELIP) as the gas carrier. Background Nitric oxide (NO) is a bioactive gas with potent therapeutic effects. Bioavailability of NO by systemic delivery is low with potential systemic effects. Methods Liposomes containing phospholipids and cholesterol were prepared using a new freezing under pressure method. The encapsulation and release profile of NO from NO containing-ELIP (NO-ELIP) or a mixture of NO/Argon (NO/Ar-ELIP was studied. Uptake of NO from NO-ELIP by cultured vascular smooth muscle cells (VSMC) both in the absence and presence of hemoglobin was determined. The effect of NO-ELIP delivery to attenuate intimal hyperplasia in a balloon-injured artery was determined. Results Coencapsulation of NO with argon (Ar) enabled the adjustment the amount of encapsulated NO. A total of 10 µl of gas can be encapsulated into 1 mg liposomes. The release profile of NO from NO-ELIP demonstrated an initial rapid release followed by a slower release over 8 hours. Sixty-eight percent of cells remained viable when incubated with 80 µg/ml of NO/Ar-ELIP for 4 hours. NO delivery to VSMC using NO/Ar-ELIP was 7-fold higher than unencapsulated NO. NO/Ar-ELIP remained effective NO delivery to VSMC even in the presence of hemoglobin. Local NO-ELIP administration to balloon-injured carotid arteries attenuated the development of intimal hyperplasia and reduced arterial wall thickening by 41±9%. Conclusions Liposomes can protect and deliver a bioactive gas to target tissues with the potential for both visualization of gas delivery and controlled therapeutic gas release. PMID:19660697

  8. Protein kinase Cδ regulates endothelial nitric oxide synthase expression via Akt activation and nitric oxide generation

    PubMed Central

    Sud, Neetu; Wedgwood, Stephen; Black, Stephen M.

    2008-01-01

    In this study, we explore the roles of the delta isoform of PKC (PKCδ) in the regulation of endothelial nitric oxide synthase (eNOS) activity in pulmonary arterial endothelial cells isolated from fetal lambs (FPAECs). Pharmacological inhibition of PKCδ with either rottlerin or with the peptide, δV1-1, acutely attenuated NO production, and this was associated with a decrease in phosphorylation of eNOS at Ser1177 (S1177). The chronic effects of PKCδ inhibition using either rottlerin or the overexpression of a dominant negative PKCδ mutant included the downregulation of eNOS gene expression that was manifested by a decrease in both eNOS promoter activity and protein expression after 24 h of treatment. We also found that PKCδ inhibition blunted Akt activation as observed by a reduction in phosphorylated Akt at position Ser473. Thus, we conclude that PKCδ is actively involved in the activation of Akt. To determine the effect of Akt on eNOS signaling, we overexpressed a dominant negative mutant of Akt and determined its effect of NO generation, eNOS expression, and phosphorylation of eNOS at S1177. Our results demonstrated that Akt inhibition was associated with decreased NO production that correlated with reduced phosphorylation of eNOS at S1177, and decreased eNOS promoter activity. We next evaluated the effect of endogenously produced NO on eNOS expression by incubating FPAECs with the eNOS inhibitor 2-ethyl-2-thiopseudourea (ETU). ETU significantly inhibited NO production, eNOS promoter activity, and eNOS protein levels. Together, our data indicate involvement of PKCδ-mediated Akt activation and NO generation in maintaining eNOS expression. PMID:18192589

  9. 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.

  10. L-arginine inhibits isoproterenol-induced cardiac hypertrophy through nitric oxide and polyamine pathways.

    PubMed

    Lin, Yan; Wang, Li-Na; Xi, Yu-Hui; Li, Hong-Zhu; Xiao, Feng-Gang; Zhao, Ya-Jun; Tian, Ye; Yang, Bao-Feng; Xu, Chang-Qing

    2008-08-01

    Polyamines (putrescine, spermidine and spermine) are essential for cell growth and differentiation. Nitric oxide exhibits antihypertrophic functions and inhibits cardiac remodelling. However, the metabolism of polyamines and the potential interactions with nitric oxide in cardiac hypertrophy remain unclear. We randomly divided Wistar rats into four treatment groups: controls, isoproterenol (ISO), ISO and L-arginine, and L-arginine. Isoproterenol (5 mg/kg/day, subcutaneously) and/or L-arginine (800 mg/kg/day, intraperitoneally) was administered once daily for 7 days. The expression of atrial natriuretic peptide mRNA was determined by reverse transcription-polymerase chain reaction, and fibrogenesis of heart was assessed by Van Gieson staining. Polyamines were measured with high-performance liquid chromatography, and plasma nitric oxide content and lactate dehydrogenase (LDH) activity were determined with a spectrophotometer. The expression levels of ornithine decarboxylase, spermidine/spermine N1-acetyltransferase (SSAT), endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) were analysed by Western blot. Heart-to-body weight ratio, left ventricle-to-body weight ratio, atrial natriuretic peptide mRNA expression, collagen fibres and LDH activity were elevated, both ornithine decarboxylase and SSAT proteins were up-regulated, and total polyamines were increased in the group treated with ISO. Additionally, the expression of iNOS was up-regulated, eNOS was down-regulated, and nitric oxide levels were low. Notably, cotreatment with L-arginine reversed most of these changes except for SSAT expression,which was further up-regulated. We propose that increased polyamines and decreased nitric oxide are involved in cardiac hypertrophy induced by ISO and suggest that L-arginine pre-treatment can attenuate cardiac hypertrophy through the regulation of key enzymes of the polyamine and nitric oxide pathways. PMID:18816294

  11. Investigation on binding of nitric oxide to horseradish peroxidase by absorption spectrometry

    NASA Astrophysics Data System (ADS)

    Qiang, Li; Zhu, Shuhua; Ma, Hongmei; Zhou, Jie

    2010-01-01

    Binding of nitric oxide to horseradish peroxidase (HRP) has been investigated by absorption spectrometry in 0.2 M anaerobic phosphate buffer solution (pH 7.4). Based on this binding equilibrium, a model equation for evaluating the binding constant of nitric oxide to HRP is developed and the binding constant is calculated to be (1.55 ± 0.06) × 10 4 M -1, indicating that HRP can form a stable complex with nitric oxide. The type of inhibition by nitric oxide is validated on the basis of studying initial reaction rates of HRP-catalyzed oxidation of guaiacol in the presence of hydrogen peroxide and nitric oxide. The inhibition mechanism is found to follow an apparent non-competitive inhibition by Lineweaver-Burk method. Based on this kinetic mechanism, the binding constant is also calculated to be (5.22 ± 0.06) × 10 4 M -1. The values of the binding constant determined by the two methods are almost identical. The non-competitive inhibition model is also applicable to studying the effect of nitric oxide on other metalloenzymes, which catalyze the two-substrate reaction with the "ping-pong" mechanism.

  12. 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...

  13. 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...

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

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 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, 2011 CFR

    2011-04-01

    ... 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, 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...

  17. 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...

  18. Role of inducible nitric oxide synthase-derived nitric oxide in lipopolysaccharide plus interferon-gamma-induced pulmonary inflammation.

    PubMed

    Zeidler, Patti C; Millecchia, Lyndell M; Castranova, Vincent

    2004-02-15

    Exposure of mice to lipopolysaccharide (LPS) plus interferon-gamma (IFN-gamma) increases nitric oxide (NO) production, which is proposed to play a role in the resulting pulmonary damage and inflammation. To determine the role of inducible nitric oxide synthase (iNOS)-induced NO in this lung reaction, the responses of inducible nitric oxide synthase knockout (iNOS KO) versus C57BL/6J wild-type (WT) mice to aspirated LPS + IFN-gamma were compared. Male mice (8-10 weeks) were exposed to LPS (1.2 mg/kg) + IFN-gamma (5000 U/mouse) or saline. At 24 or 72 h postexposure, lungs were lavaged with saline and the acellular fluid from the first bronchoalveolar lavage (BAL) was analyzed for total antioxidant capacity (TAC), lactate dehydrogenase (LDH) activity, albumin, tumor necrosis factor-alpha (TNF-alpha), and macrophage inflammatory protein-2 (MIP-2). The cellular fraction of the total BAL was used to determine alveolar macrophage (AM) and polymorphonuclear leukocyte (PMN) counts, and AM zymosan-stimulated chemiluminescence (AM-CL). Pulmonary responses 24 h postexposure to LPS + IFN-gamma were characterized by significantly decreased TAC, increased BAL AMs and PMNs, LDH, albumin, TNF-alpha, and MIP-2, and enhanced AM-CL to the same extent in both WT and iNOS KO mice. Responses 72 h postexposure were similar; however, significant differences were found between WT and iNOS KO mice. iNOS KO mice demonstrated a greater decline in total antioxidant capacity, greater BAL PMNs, LDH, albumin, TNF-alpha, and MIP-2, and an enhanced AM-CL compared to the WT. These data suggest that the role of iNOS-derived NO in the pulmonary response to LPS + IFN-gamma is anti-inflammatory, and this becomes evident over time. PMID:14962504

  19. Treatment of severe status asthmaticus with nitric oxide.

    PubMed

    Rishani, R; El-Khatib, M; Mroueh, S

    1999-12-01

    The paper reports on a 13-year-old girl with chronic asthma who presented in acute respiratory failure following an exacerbation of her disease. Nitric oxide was added to the ventilator circuit at 7 ppm and then 15 ppm after the patient failed to respond to bronchodilators and steroids. This was followed by rapid improvement in respiratory mechanics and blood gases with no adverse effects. Nitric oxide appears to have a direct relaxing effect on the bronchial smooth muscle. PMID:10587422

  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. Nitric Oxide Inhibits Coxiella burnetii Replication and Parasitophorous Vacuole Maturation

    PubMed Central

    Howe, Dale; Barrows, Lorraine F.; Lindstrom, Nicole M.; Heinzen, Robert A.

    2002-01-01

    Nitric oxide is a recognized cytotoxic effector against facultative and obligate intracellular bacteria. This study examined the effect of nitric oxide produced by inducible nitric oxide synthase (iNOS) up-regulated in response to cytokine stimulation, or by a synthetic nitric oxide donor, on replication of obligately intracellular Coxiella burnetii in murine L-929 cells. Immunoblotting and nitrite assays revealed that C. burnetii infection of L-929 cells augments expression of iNOS up-regulated in response to gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α). Infection in the absence of cytokine stimulation did not result in demonstrable up-regulation of iNOS expression or in increased nitrite production. Nitrite production by cytokine-treated cells was significantly inhibited by the iNOS inhibitor S-methylisothiourea (SMT). Treatment of infected cells with IFN-γ and TNF-α or the synthetic nitric oxide donor 2,2′-(hydroxynitrosohydrazino)bis-ethanamine (DETA/NONOate) had a bacteriostatic effect on C. burnetii replication. Inhibition of replication was reversed upon addition of SMT to the culture medium of cytokine-treated cells. Microscopic analysis of infected cells revealed that nitric oxide (either cytokine induced or donor derived) inhibited formation of the mature (large) parasitophorous vacuole that is characteristic of C. burnetii infection of host cells. Instead, exposure of infected cells to nitric oxide resulted in the formation of multiple small, acidic vacuoles usually containing one C. burnetii cell. Removal of nitrosative stress resulted in the coalescence of small vacuoles to form a large vacuole harboring multiple C. burnetii cells. These experiments demonstrate that nitric oxide reversibly inhibits replication of C. burnetii and formation of the parasitophorous vacuole. PMID:12183564

  2. [Inhaled nitric oxide: one modality in the treatment of ARDS].

    PubMed

    Carrillo-Esper, R; Ramírez-Hernández, J M; Gargallo-Hernández, J J; Hernández-Vásquez, R; Domínguez-Rodríguez, M I; Alemán-Alarcón, C E; Gallegos-Rodríguez, G

    1999-01-01

    We describe a patient with acute respiratory distress syndrome (ARDS), refractory to treatment with conventional mechanical ventilation. The hemodynamic parameters showed severe pulmonary hypertension with increased intrapulmonary shunt. Inhaled nitric oxide was administered and we observed a diminishing in pulmonary hypertension and intrapulmonary shunt with an important increase of oxygen exchange. We reviewed the literature and make a suggestion concerning use of inhaled nitric oxide in patients with ARDS. PMID:10491897

  3. Tapentadol and nitric oxide synthase systems.

    PubMed

    Bujalska-Zadrożny, Magdalena; Wolińska, Renata; Gąsińska, Emilia; Nagraba, Łukasz

    2015-04-01

    Tapentadol, a new analgesic drug with a dual mechanism of action (μ-opioid receptor agonism and norepinephrine reuptake inhibition), is indicated for the treatment of moderate to severe acute and chronic pain. In this paper, the possible additional involvement of the nitric oxide synthase (NOS) system in the antinociceptive activity of tapentadol was investigated using an unspecific inhibitor of NOS, L-NOArg, a relatively specific inhibitor of neuronal NOS, 7-NI, a relatively selective inhibitor of inducible NOS, L-NIL, and a potent inhibitor of endothelial NOS, L-NIO. Tapentadol (1-10 mg/kg, intraperitoneal) increased the threshold for mechanical (Randall-Selitto test) and thermal (tail-flick test) nociceptive stimuli in a dose-dependent manner. All four NOS inhibitors, administered intraperitoneally in the dose range 0.1-10 mg/kg, potentiated the analgesic action of tapentadol at a low dose of 2 mg/kg in both models of pain. We conclude that NOS systems participate in tapentadol analgesia. PMID:25485639

  4. Airborne intercomparison of nitric oxide measurement techniques

    NASA Technical Reports Server (NTRS)

    Hoell, James M., Jr.; Gregory, Gerald L.; Mcdougal, David S.; Torres, Arnold L.; Davis, Douglas D.

    1987-01-01

    Results from an airborne intercomparison of techniques to measure tropospheric levels of nitric oxide (NO) are discussed. The intercomparison was part of the National Aeronautics and Space Administration's Global Tropospheric Experiment and was conducted during missions flown in the fall of 1983 and spring of 1984. Instruments intercompared included a laser-induced fluorescence (LIF) system and two chemiluminescence instruments (CL). NO mixing ratios from below 5 pptv (parts per trillion by volume) to greater than 100 pptv were reported, with the majority less than 20 pptv. Good correlation was observed between the measurements reported by the CL and LIF techniques. The general level of agreement observed for the ensemble of measurements obtained during the two missions provides the basis from which one can conclude that equally 'valid' measurements of background levels of NO can be expected from either CL or LIF instruments. At the same time the periods of disagreement that were observed between the CL and LIF instruments as well as between the two CL instruments highlight the difficulty of obtaining reliable measurements with NO mixing ratios in the 5-20 pptv range and emphasize the vigilance that should be maintained in future NO measurements.

  5. 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

  6. 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

  7. 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.

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

    PubMed

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

    2016-09-01

    Emerging evidence strongly suggests that dietary nitrate, derived in the diet primarily from vegetables, could contribute to cardiovascular health via effects on nitric oxide (NO) status. NO plays an essential role in cardiovascular health. It is produced via the classical L-arginine-NO-synthase pathway and the recently discovered enterosalivary nitrate-nitrite-NO pathway. The discovery of this alternate pathway has highlighted dietary nitrate as a candidate for the cardioprotective effect of a diet rich in fruit and vegetables. Clinical trials with dietary nitrate have observed improvements in blood pressure, endothelial function, ischemia-reperfusion injury, arterial stiffness, platelet function, and exercise performance with a concomitant augmentation of markers of NO status. While these results are indicative of cardiovascular benefits with dietary nitrate intake, there is still a lingering concern about nitrate in relation to methemoglobinemia, cancer, and cardiovascular disease. It is the purpose of this review to present an overview of NO and its critical role in cardiovascular health; to detail the observed vascular benefits of dietary nitrate intake through effects on NO status as well as to discuss the controversy surrounding the possible toxic effects of nitrate. PMID:25976309

  9. Nitric oxide and cancer: a review

    PubMed Central

    2013-01-01

    Nitric oxide (NO), is a ubiquitous, water soluble, free radical gas, which plays key role in various physiological as well as pathological processes. Over past decades, NO has emerged as a molecule of interest in carcinogenesis and tumor growth progression. However, there is considerable controversy and confusion in understanding its role in cancer biology. It is said to have both tumoricidal as well as tumor promoting effects which depend on its timing, location, and concentration. NO has been suggested to modulate different cancer-related events including angiogenesis, apoptosis, cell cycle, invasion, and metastasis. On the other hand, it is also emerging as a potential anti-oncogenic agent. Strategies for manipulating in vivo production and exogenous delivery of this molecule for therapeutic gain are being investigated. However, further validation and experimental/clinical trials are required for development of novel strategies based on NO for cancer treatment and prevention. This review discusses the range of actions of NO in cancer by performing an online MEDLINE search using relevant search terms and a review of the literature. Various mechanisms by which NO acts in different cancers such as breast, cervical, gastric,colorectal, and head and neck cancers are addressed. It also offers an insight into the dichotomous nature of NO and discusses its novel therapeutic applications for cancer prevention and treatment. PMID:23718886

  10. [Inhalation of nitric oxide - dependence: case report

    PubMed

    Carvalho, W B; Matsumoto, T; Horita, S M; Almeida, N M; Martins, F R

    2000-01-01

    OBJECTIVE: Describe the hemodynamic response with rebound of pulmonary hypertension after withdrawal of inhaled nitric oxide (NO) in a pediatric patient with acute respiratory distress syndrome (ARDS). METHODS: Case report of a child with ARDS and pulmonary hypertension evaluated through ecocardiografic with dopller, receiving inhaled NO for a period of 21 days. RESULTS: There was a decrease of the pulmonary artery pressure (PAP) from 52 mmHg to 44 mmHg after the initial titulation of NO inhalation dose. After the withdrawal of inhaled NO an elevation of PAP was observed (55 mmHg). It was necessary to reinstall the inhaled NO to obtain a more appropriate value (34 mmHg). A new attempt of interruption of the inhaled NO after prolonged inhalation (20 days) resulted in a new clinic worsening and increase of PAP, with the indication to reinstall the inhaled NO. In the 24th day of permanence in the intensive care unit the patient died due to multiple organ dysfunction. CONCLUSIONS: The possibility of pulmonary hypertension rebound after withdrawal of inhaled NO is a complication that may have important clinical implications for patients who need a prolonged treatment with NO. This case report emphasizes these implications. PMID:14647690

  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

  12. 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

  13. Observations of Lower Thermospheric Nitric Oxide from the Student Nitric Oxide Explorer

    NASA Astrophysics Data System (ADS)

    Bailey, S. M.

    2004-12-01

    The production of nitric oxide is a key response of the upper atmosphere to solar energy deposition. NO plays a strong role in the thermospheric energy balance as it emits efficiently in the infrared, it is the terminal ion in the lower ionosphere, and if transported to lower altitudes will catalytically destroy ozone. NO is primarily produced through the reaction of excited atomic nitrogen with molecular oxygen. One of the primary loss mechanisms of NO is photodissociation by solar ultraviolet irradiance. In order to produce the excited atomic nitrogen atom, the strong N2 molecular bond must be broken. At low latitudes, solar soft X-ray irradiance is the energy source that leads to NO. At high latitudes, auroral electrons and the energetic secondary electrons provide the source of energy that leads to the large amounts of NO observed there. Coupling between latitude regions may occur as high latitude NO is transported by winds to lower latitude. In this talk we describe observations of NO from the Student Nitric Oxide Explorer (SNOE). SNOE observed fluorescently scattered sunlight by NO at 215 and 237 nm to obtain global concentrations of NO in the lower thermosphere daily from February 1998 through December 2003. We will present case studies of the observed response to large auroral storms. In particular, the effects of the large storms of April 2002 and November 2003 will be presented. The SNOE observations show that auroral energy deposition produces a significant global effect on the upper atmosphere.

  14. 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.

  15. 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

  16. 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...

  17. Inhaled nitric oxide to prevent bronchopulmonary dysplasia in preterm neonates.

    PubMed

    Mercier, Jean-Christophe; Olivier, Paul; Loron, Gauthier; Fontaine, Romain; Maury, Laure; Baud, Olivier

    2009-02-01

    Bronchopulmonary dysplasia is a chronic lung disease that affects premature infants and contributes to their morbidity and mortality. With the advent of prenatal steroids and postnatal exogenous surfactant and less aggressive respiratory support, premature infants can develop chronic oxygen dependency without even acute respiratory distress. This 'new bronchopulmonary dysplasia' could be the result of impaired postnatal growth. Several experimental studies have suggested a possible role of the vascular endothelial growth factor/nitric oxide (VEGF/NO) pathway in restoring pulmonary angiogenesis and enhancing distal lung growth. The results of the clinical studies are, however, inconclusive, and it is currently unclear which subsets of premature infants might benefit from inhaled nitric oxide. Besides, severe intracranial haemorrhage and/or cystic periventricular leucomalacia may affect the most immature babies, many of whom are spared from severe initial respiratory disease. Recently, inhaled nitric oxide was shown to significantly decrease the incidence of these neurological events, and to improve the long-term outcome in a few clinical trials. At times neuroprotective, at times neurotoxic, nitric oxide is capable of divergent effects depending upon the extent of cerebral damage, the redox state of the cell, and the experimental model used. Recently, our group found that inhaled nitric oxide had remote effects including angiogenesis and maturation on the developing brain in rodent pups. Thus, we await the results of the recently completed randomised clinical trial of inhaled nitric oxide to prevent bronchopulmonary dysplasia (the European Nitric Oxide or 'EUNO' trial) where, besides the primary endpoint of chronic oxygen dependency reduction at 36 weeks' postconceptional age, long-term lung and brain will be followed-up until 7 years of age. PMID:18986855

  18. Racial Differences in Nitric Oxide-Dependent Vasorelaxation

    PubMed Central

    Mata-Greenwood, Eugenia; Chen, Dong-Bao

    2008-01-01

    Along with the growing heterogeneity of the American population, ethnic/racial disparity is becoming a clear health issue in the United States. The awareness of ethnic/racial disparities has been growing because of considerable data gathered from recent clinical and epidemiological studies. These studies have highlighted the importance of addressing these differences in the diagnosis and treatment of various diseases potentially according to race. It is becoming particularly clear that there is a 2- to 3-fold racial difference in certain cardiovascular diseases (eg, preeclampsia) associated with dysfunctional nitric oxide–mediated vasodilation. In this review, the authors summarize the current literature on racial disparities in nitric oxide–mediated vasodilation in relation to cardiovascular health with an emphasis on vascular nitric oxide bioavailability as a balance between production via endothelial nitric oxide synthase and degradation through reactive oxygen species. The major hypotheses postulated on the biological basis of these differences are also highlighted. PMID:18212350

  19. Mitochondrial nitric oxide synthase participates in septic shock myocardial depression by nitric oxide overproduction and mitochondrial permeability transition pore opening.

    PubMed

    Xu, Ce; Yi, Chenju; Wang, Huiping; Bruce, Iain C; Xia, Qiang

    2012-01-01

    The aim of this study was to determine whether mitochondrial nitric oxide (NO) synthase (NOS) is involved in septic shock myocardial depression. The cecal ligation and puncture (CLP) method was used to induce septic shock. There was a significant depression of hemodynamic parameters recorded in the septic shock stage. After using nonselective NOS inhibitor N-nitro-L-arginine methyl ester (L-NAME), inducible NOS inhibitor aminoguanidine (AMG), and neuronal NOS inhibitor 7-nitroindazole (7-NI), depression of the parameters was partly attenuated. Nitric oxide production in isolated cardiac mitochondria increased obviously in the CLP-septic shock stage, L-NAME and 7-NI both decreased NO production significantly. Nitrite/nitrate (NOx) production in the septic shock stage was much greater than those in the corresponding sham groups, and NOx production in the cytosol by inducible NOS was greater. Treatment with AMG suppressed NOx production in the cytosol by iNOS, whereas treatment with 7-NI decreased NOx production in the mitochondria. Mitochondrial NOS expression increased significantly in the septic shock stage, and its overexpression was attenuated using 7-NI. There was no significant decrease in the mitochondrial permeability transition pore measurement in the CLP-septic shock group, whereas a significant decrease was observed in those treated with L-NAME or 7-NI. These results indicate that overexpression of mitochondrial NOS is involved in myocardial depression. PMID:21993446

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

    NASA Astrophysics Data System (ADS)

    Barker, Susan Lynn Ritenour

    1999-11-01

    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.

  1. 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)

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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.

  8. 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

  9. 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

  10. 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

  11. 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

  12. Parameters controlling nitric oxide emissions from gas turbine combustors

    NASA Technical Reports Server (NTRS)

    Heywood, J. B.; Mikus, T.

    1973-01-01

    Nitric oxide forms in the primary zone of gas turbine combustors where the burnt gas composition is close to stoichiometric and gas temperatures are highest. It was found that combustor air inlet conditions, mean primary zone fuel-air ratio, residence time, and the uniformity of the primary zone are the most important variables affecting nitric oxide emissions. Relatively simple models of the flow in a gas turbine combustor, coupled with a rate equation for nitric oxide formation via the Zeldovich mechanism are shown to correlate the variation in measured NOx emissions. Data from a number of different combustor concepts are analyzed and shown to be in reasonable agreement with predictions. The NOx formation model is used to assess the extent to which an advanced combustor concept, the NASA swirl can, has produced a lean well-mixed primary zone generally believed to be the best low NOx emissions burner type.

  13. 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

  14. [Level of nitric oxide in the kidneys during apoptosis activation].

    PubMed

    Komarievtseva, I O; Orlova, O A; Blahodarenko, Ie A

    2002-01-01

    The content of nitric oxide stable metabolites in a tissue of kidneys of rats in conditions of activation of apoptosis was investigated. Research was carried out in two models: acute renal failure and a hypertrophy of a unique kidney after a unilateral nephrectomy. Detection of apoptosis was carried out by definition of DNA fragmentation. Substantial increase of the nitric oxide stable metabolites contents is revealed at activation of apoptosis in both models. Change of a ratio of the contents of nitrite--anions in relation to the general contents of NO2- + NO3- is revealed, indicating the role of peroxide processes in effect of nitric oxide and its metabolites on the cell. PMID:14964872

  15. 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. PMID:27247597

  16. Kinetics of the reaction of nitric oxide with hydrogen

    NASA Technical Reports Server (NTRS)

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

    1974-01-01

    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 reaction kinetics were studied in the temperature range 2400-4500 K using a shock-tube technique. The decomposition of nitric oxide behind the shock was found to be modeled well by a fifteen-reaction system. A principle result of the study was the determination of the rate constant 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 k sub 1 were obtained for each test through comparisons of measured and numerically predicted NO profiles.

  17. [Study on the altered nitric oxide metabolism in experimental diabetes].

    PubMed

    Tábi, Tamási; Soltész, Zsuzsa; Magyar, Kálmán; Szöko, Eva

    2006-01-01

    Decreased biological action of nitric oxide (NO) and increased oxidative stress are established to be involved in the development of endothelium dysfunction, early sign of diabetic angiopathy. In the present study, increased nitric oxide synthase (NOS) enzyme activity in the aorta and decreased activity in the kidney tissue of streptozotocin-induced diabetic rats has been found in the early phase of the disease. Augmentation of oxidative transformation of NO in the kidney and heart of the diabetic animals has been demonstrated by the measurement of the stable end-products of NO and other reactive nitrogen species. Insulin treatment was found effective to reduce the intensified oxidative metabolism of NO without increasing its production. Reduced biological effects of NO observed in endothelial dysfunction, is thus probably the consequence of its increased oxidative inactivation. PMID:17094672

  18. Nitric oxide synthase in macula densa regulates glomerular capillary pressure.

    PubMed Central

    Wilcox, C S; Welch, W J; Murad, F; Gross, S S; Taylor, G; Levi, R; Schmidt, H H

    1992-01-01

    Tubular-fluid reabsorption by specialized cells of the nephron at the junction of the ascending limb of the loop of Henle and the distal convoluted tubule, termed the macula densa, releases compounds causing vasoconstriction of the adjacent afferent arteriole. Activation of this tubuloglomerular feedback response reduces glomerular capillary pressure of the nephron and, hence, the glomerular filtration rate. The tubuloglomerular feedback response functions in a negative-feedback mode to relate glomerular capillary pressure to tubular-fluid delivery and reabsorption. This system has been implicated in renal autoregulation, renin release, and longterm body fluid and blood-pressure homeostasis. Here we report that arginine-derived nitric oxide, generated in the macula densa, is an additional intercellular signaling molecule that is released during tubular-fluid reabsorption and counters the vasoconstriction of the afferent arteriole. Antibody to rat cerebellar constitutive nitric oxide synthase stained rat macula densa cells specifically. Microperfusion of the macula densa segment of single nephrons with N omega-methyl-L-arginine (an inhibitor of nitric oxide synthase) or with pyocyanin (a lipid-soluble inhibitor of endothelium-derived relaxation factor) showed that generation of nitric oxide can vasodilate the afferent arteriole and increase glomerular capillary pressure; this effect was blocked by drugs that prevent tubular-fluid reabsorption. We conclude that nitric oxide synthase in macula densa cells is activated by tubular-fluid reabsorption and mediates a vasodilating component to the tubuloglomerular feedback response. These findings imply a role for arginine-derived nitric oxide in body fluid-volume and blood-pressure homeostasis, in addition to its established roles in modulation of vascular tone by the endothelium and in neurotransmission. Images PMID:1281548

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

    PubMed

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

    2016-08-01

    This study aimed to investigate whether nitric oxide participates in the cardiovascular function and haemodynamic adaptation to acute haemorrhage in animals with thyroid disorders. Sprague-Dawley rats aged 2months old treated with T3 (hyper, 20μg/100g body weight) or 0.02% methimazole (hypo, w/v) during 28days were pre-treated with N(G) nitro-l-arginine methyl ester (L-NAME) and submitted to 20% blood loss. Heart function was evaluated by echocardiography. Measurements of arterial blood pressure, heart rate, nitric oxide synthase activity and protein levels were performed. We found that hypo decreased fractional shortening and ejection fraction and increased left ventricle internal diameter. Hyper decreased ventricle diameter and no changes in cardiac contractility. Haemorrhage elicited a hypotension of similar magnitude within 10min. Then, this parameter was stabilized at about 30-40min and maintained until finalized, 120min. L-NAME rats showed that the immediate hypotension would be independent of nitric oxide. Nitric oxide synthase inhibition blunted the changes of heart rate induced by blood loss. Hyper and hypo had lower atrial enzyme activity associated with a decreased enzyme isoform in hypo. In ventricle, hyper and hypo had a higher enzyme activity, which was not correlated with changes in protein levels. Haemorrhage induced an increased heart nitric oxide production. We concluded that thyroid disorders were associated with hypertrophic remodelling which impacted differently on cardiac function and its adaptation to a hypovolemia. Hypovolemia triggered a nitric oxide synthase activation modulating the heart function to maintain haemodynamic homeostasis. This involvement depends on a specific enzyme isoform, cardiac chamber and thyroid state. PMID:27270898

  20. Novel antileukemic agents derived from tamibarotene and nitric oxide donors.

    PubMed

    Bian, Haiyong; Feng, Jinhong; Li, Minyong; Xu, Wenfang

    2011-12-01

    A series of novel nitric oxide-releasing tamibarotene derivatives were synthesized by coupling nitric oxide (NO) donors with tamibarotene via various spacers, and were evaluated for their antiproliferative activities against human leukemic HL-60, NB4 and K562 cell lines in vitro. The test results showed that three compounds (7g, 9a and 9e) exhibited more potent antileukemic activity than the control tamibarotene. Furthermore, the preliminary structure-activity analysis revealed that amino acids serving as spacers could bring about significantly improved biological activities of NO donor hybrids. These interesting results could provide new insights into the development of NO-based antileukemic agents. PMID:22014829

  1. Nitroaromatic amino acids as inhibitors of neuronal nitric oxide synthase.

    PubMed

    Cowart, M; Kowaluk, E A; Daanen, J F; Kohlhaas, K L; Alexander, K M; Wagenaar, F L; Kerwin, J F

    1998-07-01

    Nitric oxide (NO.) is an important biomodulator of many physiological processes. The inhibition of inappropriate production of NO. by the isoforms of nitric oxide synthase (NOS) has been proposed as a therapeutic approach for the treatment of stroke, inflammation, and other processes. In this study, certain 2-nitroaryl-substituted amino acid analogues were discovered to inhibit NOS. Analogues bearing a 5-methyl substituent on the aromatic ring demonstrated maximal inhibitory potency. For two selected inhibitors, investigation of the kinetics of the enzyme showed the inhibition to be competitive with l-arginine. Additionally, functional NOS inhibition in tissue preparations was demonstrated. PMID:9651169

  2. Nitric oxide and biopterin in depression and stress.

    PubMed

    van Amsterdam, J G; Opperhuizen, A

    1999-01-18

    Depression has been hypothesized to be related to the reduced biosynthesis of neurotransmitters such as serotonin, noradrenalin and dopamine. Much past research has also been devoted to dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in depression. The present article reviews the evidence linking tetrahydrobiopterin, a co-factor in the biosynthesis of neurotransmitters, and nitric oxide, an apparent neuroendocrine modulator of the HPA axis, to the immune system and to neuronal control within affective disorder and stress. On the basis of this review, it is suggested that future psychoneuroimmunological research should more fully explore the possible role of tetrahydrobiopterin and nitric oxide in depressive disorders. PMID:10195314

  3. Inhibitors of nitric oxide synthase in inflammatory arthritis.

    PubMed

    Boughton-Smith, N K; Tinker, A C

    1998-07-01

    There is considerable evidence that excessive nitric oxide (NO) synthesized from L-arginine by inducible nitric oxide synthase (iNOS) plays an important pathological role in inflammatory arthritis. Since NO synthesized by constitutive isoforms of NOS has a physiological role, a great deal of activity has been directed at identifying inhibitors of NOS that are selective for the induced isoform. The major chemical areas that have been described so far in the search for such selective iNOS inhibitors and the activity of some of these compounds in animal models of arthritis are reviewed. PMID:18465556

  4. Diffusion of nitric oxide into low density lipoprotein.

    PubMed

    Denicola, Ana; Batthyány, Carlos; Lissi, Eduardo; Freeman, Bruce A; Rubbo, Homero; Radi, Rafael

    2002-01-11

    A key early event in the development of atherosclerosis is the oxidation of low density lipoprotein (LDL) via different mechanisms including free radical reactions with both protein and lipid components. Nitric oxide (( small middle dot)NO) is capable of inhibiting LDL oxidation by scavenging radical species involved in oxidative chain propagation reactions. Herein, the diffusion of ( small middle dot)NO into LDL is studied by fluorescence quenching of pyrene derivatives. Selected probes 1-(pyrenyl)methyltrimethylammonium (PMTMA) and 1-(pyrenyl)-methyl-3-(9-octadecenoyloxy)-22,23-bisnor-5-cholenate (PMChO) were chosen so that they could be incorporated at different depths of the LDL particle. Indeed, PMTMA and PMChO were located in the surface and core of LDL, respectively, as indicated by changes in fluorescence spectra, fluorescence quenching studies with water-soluble quenchers and the lifetime values (tau(o)) of the excited probes. The apparent second order rate quenching constants of ( small middle dot)NO (k(NO)) for both probes were 2.6-3.8 x 10(10) m(-1) s(-1) and 1.2 x 10(10) m(-1) s(-1) in solution and native LDL, respectively, indicating that there is no significant barrier to the diffusion of ( small middle dot)NO to the surface and core of LDL. Nitric oxide was also capable of diffusing through oxidized LDL. Considering the preferential partitioning of ( small middle dot)NO in apolar milieu (6-8 for n-octanol:water) and therefore a larger ( small middle dot)NO concentration in LDL with respect to the aqueous phase, a corrected k(NO) value of approximately 0.2 x 10(10) m(-1) s(-1) can be determined, which still is sufficiently large and consistent with a facile diffusion of ( small middle dot)NO through LDL. Applying the Einstein-Smoluchowsky treatment, the apparent diffusion coefficient (D(')NO) of ( small middle dot)NO in native LDL is on average 2 x 10(-5) cm(2) s(-1), six times larger than that previously reported for erythrocyte plasma membrane

  5. [Nitric oxide and anti-protozoan chemotherapy].

    PubMed

    Gradoni, L; Ascenzi, P

    2004-06-01

    Constitutive nitric oxide (NO) is generated by constitutively expressed types of NO-synthase enzymes (NOS-I and -III), being involved in physiological processes such as nervous transmission and vasodilatation. Inducible NO, synthesized by the NO-synthase isoform NOS-II, is an anti-pathogen and tumoricidal agent. However, inducible NO production requires a tight control because of cytotoxic and immune-modulation activity. NO produced by human and canine macrophages has long been demonstrated to be involved in the intracellular killing of Leishmania. Mechanisms of parasite survival and persistence in the host have been throughly investigated, and include suppression of NOS-II and the parasite entry into NOS-II negative cells. Both intracellular and extracellular morphotypes of Trypanosoma cruzi are killed by NO in vitro and in vivo, although a role of NO in the pathogenesis of heart disease has been reported. Killing of extracellular protozoa such as Trichomonas vaginalis and Naegleria fowleri by activated macrophages is also mediated by NO. The main control of Plasmodium spp infection in human and murine hepatocytes, and in human monocytes is achieved by NO-mediated mechanisms. Protection from severe malaria in African children has been found associated with polymorphisms of the NOS-II promoter; however, a pathogenic role of endogenous NO has been documented in cerebral malaria. Although several macromolecules are putative NO targets, recent experimental work has shown that NO-releasing compounds inhibit cysteine proteases (CP) of P. falciparum, T. cruzi and L. infantum in a dose-dependent manner. CPs are present in a wide range of parasitic protozoa and appear to be relevant in several aspects of the life cycle and of the parasite-host relationships. Comparative analysis of 3-D amino acid sequence models of CPs from a broad range of living organisms, from viruses to mammals, suggests that the Sy atom of the Cys catalytic residue undergoes NO-dependent chemical

  6. Cadmium attenuates bradykinin-driven nitric oxide production by interplaying with the localization pattern of endothelial nitric oxide synthase.

    PubMed

    Majumder, Syamantak; Gupta, Ravi; Reddy, Himabindu; Sinha, Swaraj; Muley, Ajit; Kolluru, Gopi Krishna; Chatterjee, Suvro

    2009-08-01

    Cadmium, a ubiquitous heavy metal, interferes with endothelial functions and angiogenesis. Bradykinin is a Ca-mobilizing soluble peptide that acts via nitric oxide to promote vasodilation and capillary permeability. The objective of the present study was to explore the Cd implications in bradykinin-dependent endothelial functions. An egg yolk angiogenesis model was employed to evaluate the effect of Cd on bradykinin-induced angiogenesis. The results demonstrate that 100 nmol/L Cd attenuated bradykinin-dependent angiogenesis. The results of the in vitro wound healing and tube formation assays by using EAhy 926, a transformed endothelial cell line, suggest that Cd blocked bradykinin-mediated endothelial migration and tube formation by 38% and 67%, respectively, while nitric oxide supplementation could reverse the effect of Cd on bradykinin-induced endothelial migration by 94%. The detection of nitric oxide by using a DAF-2DA fluorescent probe, Griess assay, and ultrasensitive electrode suggests that Cd blocked bradykinin-induced nitric oxide production. Fluorescence imaging of eNOS-GFP transfected endothelial cells, immunofluorescence, and Western blot studies of Cd and bradykinin-treated cells show that Cd interfered with the localization pattern of eNOS, which possibly attenuates nitric oxide production in part. Additionally, Ca imaging of Cd- and bradykinin-treated cells suggests that Cd blocked bradykinin-dependent Ca influx into the cells, thus partially blocking Ca-dependent nitric oxide production in endothelial cells. The results of this study conclude that Cd blunted the effect of bradykinin by interfering with the Ca-associated NOS activity specifically by impeding subcellular trafficking of eNOS. PMID:19767824

  7. The energy-conserving nitric-oxide-reductase system in Paracoccus denitrificans. Distinction from the nitrite reductase that catalyses synthesis of nitric oxide and evidence from trapping experiments for nitric oxide as a free intermediate during denitrification.

    PubMed

    Carr, G J; Page, M D; Ferguson, S J

    1989-02-15

    1. A Clark-type electrode that responds to nitric oxide has been used to show that cytoplasmic membrane vesicles of Paracoccus denitrificans have a nitric-oxide reductase activity. Nitrous oxide is the reaction product. NADH, succinate or isoascorbate plus 2,3,5,6-tetramethyl-1,4-phenylene diamine can act as reductants. The NADH-dependent activity is resistant to freezing of the vesicles and thus the NADH:nitric-oxide oxidoreductase activity of stored frozen vesicles provides a method for calibrating the electrode by titration of dissolved nitric oxide with NADH. The periplasmic nitrite reductase and nitrous-oxide reductase enzymes are absent from the vesicles which indicates that nitric-oxide reductase is a discrete enzyme associated with the denitrification process. This conclusion was supported by the finding that nitric-oxide reductase activity was absent from both membranes prepared from aerobically grown P. denitrificans and bovine heart submitochondrial particles. 2. The NADH: nitric-oxide oxidoreductase activity was inhibited by concentrations of antimycin or myxothiazol that were just sufficient to inhibit the cytochrome bc1 complex of the ubiquinol--cytochrome-c oxidoreductase. The activity was deduced to be proton translocating by the observations of: (a) up to 3.5-fold stimulation upon addition of an uncoupler; and (b) ATP synthesis with a P:2e ratio of 0.75. 3. Nitrite reductase of cytochrome cd1 type was highly purified from P. denitrificans in a new, high-yield, rapid two- or three-step procedure. This enzyme catalysed stoichiometric synthesis of nitric oxide. This observation, taken together with the finding that the maximum rate of NADH:nitric-oxide oxidoreductase activity catalysed by the vesicles was comparable with that of NADH:nitrate-oxidoreductase, is consistent with a role for nitric-oxide reductase in the physiological conversion of nitrate or nitrite to dinitrogen gas. 4. Intact cells of P. denitrificans also reduced nitric oxide in an

  8. 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.

  9. Satellite ultraviolet measurements of nitric oxide fluorescence with a diffusive transport model.

    NASA Technical Reports Server (NTRS)

    Rusch, D. W.

    1973-01-01

    Twilight measurements of fluorescence in the (1, 0) gamma band of nitric oxide were made from June 1967 to January 1969 by an ultraviolet scanning spectrometer on board the polar orbiting satellite Ogo 4. Nitric oxide vertical column emission rates were measured between solar zenith angles of 93 and 98 deg. Seasonal and latitudinal variations were found to be less than a factor of 1.3, the scatter and uncertainty in the data prohibiting more precise determinations from being made. Time independent chemical diffusion models for the vertical distribution of nitric oxide agree well with profiles measured from sounding rockets. The column emission rates calculated from the theoretical models are larger than the satellite measurements by a factor of 3.

  10. Decoding the Substrate Supply to Human Neuronal Nitric Oxide Synthase

    PubMed Central

    Habermeier, Alice; Closs, Ellen I.

    2013-01-01

    Nitric oxide, produced by the neuronal nitric oxide synthase (nNOS) from L-arginine is an important second messenger molecule in the central nervous system: It influences the synthesis and release of neurotransmitters and plays an important role in long-term potentiation, long-term depression and neuroendocrine secretion. However, under certain pathological conditions such as Alzheimer’s or Parkinson’s disease, stroke and multiple sclerosis, excessive NO production can lead to tissue damage. It is thus desirable to control NO production in these situations. So far, little is known about the substrate supply to human nNOS as a determinant of its activity. Measuring bioactive NO via cGMP formation in reporter cells, we demonstrate here that nNOS in both, human A673 neuroepithelioma and TGW-nu-I neuroblastoma cells can be fast and efficiently nourished by extracellular arginine that enters the cells via membrane transporters (pool I that is freely exchangeable with the extracellular space). When this pool was depleted, NO synthesis was partially sustained by intracellular arginine sources not freely exchangeable with the extracellular space (pool II). Protein breakdown made up by far the largest part of pool II in both cell types. In contrast, citrulline to arginine conversion maintained NO synthesis only in TGW-nu-I neuroblastoma, but not A673 neuroepithelioma cells. Histidine mimicked the effect of protease inhibitors causing an almost complete nNOS inhibition in cells incubated additionally in lysine that depletes the exchangeable arginine pool. Our results identify new ways to modulate nNOS activity by modifying its substrate supply. PMID:23874440

  11. Endothelial cell nitric oxide production in acute chest syndrome.

    PubMed

    Hammerman, S I; Klings, E S; Hendra, K P; Upchurch, G R; Rishikof, D C; Loscalzo, J; Farber, H W

    1999-10-01

    Acute chest syndrome (ACS) is the most common form of acute pulmonary disease associated with sickle cell disease. To investigate the possibility that alterations in endothelial cell (EC) production and metabolism of nitric oxide (NO) products might be contributory, we measured NO products from cultured pulmonary EC exposed to red blood cells and/or plasma from sickle cell patients during crisis. Exposure to plasma from patients with ACS caused a 5- to 10-fold increase in S-nitrosothiol (RSNO) and a 7- to 14-fold increase in total nitrogen oxide (NO(x)) production by both pulmonary arterial and microvascular EC. Increases occurred within 2 h of exposure to plasma in a concentration-dependent manner and were associated with increases in endothelial nitric oxide synthase (eNOS) protein and eNOS enzymatic activity, but not with changes in nitric oxide synthase (NOS) III or NOS II transcripts, inducible NOS (iNOS) protein nor iNOS enzymatic activity. RSNO and NO(x) increased whether plasma was obtained from patients with ACS or other forms of vasoocclusive crisis. Furthermore, an oxidative state occurred and oxidative metabolites of NO, particularly peroxynitrite, were produced. These findings suggest that altered NO production and metabolism to damaging oxidative molecules contribute to the pathogenesis of ACS. PMID:10516198

  12. 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...

  13. 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.

  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. Nitric oxide inhibition sustains vasopressin-induced vasoconstriction.

    PubMed Central

    Dworkin, M. J.; Carnochan, P.; Allen-Mersh, T. G.

    1995-01-01

    Hepatic parenchymal vasoconstriction increases cytotoxic drug uptake into hepatic metastases by increasing the tumour to liver blood flow ratio. Prolonged infusion of the vasoconstrictor vasopressin does not result in sustained vasoconstriction, and this may limit the benefit of vasopressin in infusional chemotherapy. We have assessed whether loss of vasopressin-induced vasoconstriction is mediated by nitric oxide. Hepatic and tumour blood flow were continuously monitored, in an animal hepatic tumour model, by laser Doppler flowmetry. The response to regionally infused vasopressin and the nitric oxide inhibitor N-nitro-L-arginine methyl ester (L-NAME) were assessed over a 30 min infusion period. The vasopressin-induced vasoconstrictor effect diminished after 15 min despite continued infusion. Vasoconstriction was significantly prolonged when L-NAME was infused in addition to vasopressin. The increase in tumour to normal blood flow ratio was greater over the infusion period when L-NAME was co-administered with vasopressin. Our results suggest that the loss of vasopressin-induced vasoconstriction seen in liver parenchyma after regional infusion is prevented by the nitric oxide synthase inhibitor L-name and may be mediated by nitric oxide. PMID:7734317

  16. 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...

  17. Apple fruit responses following exposure to nitric oxide

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  18. Absorptivity of nitric oxide in the fundamental vibrational band

    NASA Astrophysics Data System (ADS)

    Holland, R. F.; Vasquez, M. C.; Beattie, W. H.; McDowell, R. S.

    1983-05-01

    From observations of the spectral absorbance of mixtures of nitric oxide in nitrogen at room temperature, an integrated absorptivity for the NO fundamental band of 137.3 + or - 4.6 per(sq cm atm) at 0 C is derived. The indicated uncertainty is the estimated maximum error.

  19. Nitric oxide and almitrine: the definitive answer for hypoxemia.

    PubMed

    Payen, D M; Muret, J

    1999-02-01

    Hypoxia-induced by acute lung injury results from abnormal ventilation/perfusion ratio distribution towards shunt or low ventilation/perfusion zones. Pharmacological modification of pulmonary blood flow distribution improving ventilation/perfusion ratio should correct hypoxia. The development of inhaled nitric oxide therapy had confirmed this concept, but with a relatively high proportion of 'non responders'. Then development of other drugs used alone or in association with nitric oxide may reinforce the benefit of nitric oxide. This has been tested with almitrine bismesylate, a lipophilic drug that reinforce hypoxic pulmonary vasoconstriction. Using inhaled nitric oxide in combination with almitrine, several studies in adult respiratory distress syndrome or acute lung injury patients have shown spectacular results in term of PaO2 and pulmonary shunt reduction. Moreover, the proportion of responders to this combination seems largely great than those observed for each drug alone. In conclusion, pulmonary blood flow manipulation improving ventilation/perfusion mismatching is one of the major strategies to correct severe hypoxia. PMID:17013295

  20. Oscillations of nitric oxide concentration in the perturbed denitrification pathway of Paracoccus denitrificans.

    PubMed Central

    Kucera, I

    1992-01-01

    The metabolism of nitric oxide in Paracoccus denitrificans has been studied using a Clark-type electrode. The uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP) and the SH reagent N-ethylmaleimide, both of which released nitric oxide from cells respiring nitrite, were found to be efficient inhibitors of nitric oxide reductase activity. Control experiments with another uncoupler, pentachlorophenol, showed that the inhibitory effect of CCCP was not the result of a decrease in membrane potential. The denitrification pathway in cells with partly inhibited nitric oxide reductase, or in a reconstituted system containing purified nitric reductase and membrane vesicles, exhibited marked sustained oscillations of nitric oxide concentration. The occurrence of the oscillations was strictly dependent on the initial concentration of nitrite. The observed oscillatory kinetics is considered to reflect two regulatory signals destabilizing the denitrification pathway, namely the inhibition of nitric oxide reductase by nitric oxide and/or by nitrite. PMID:1325776

  1. 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.

  2. Nitric oxide and the autonomic regulation of cardiac excitability. The G.L. Brown Prize Lecture.

    PubMed

    Paterson, D

    2001-01-01

    Cardiac sympathetic imbalance and arrhythmia; Nitric oxide-cGMP pathway and the cholinergic modulation of cardiac excitability; Nitric oxide-cGMP pathway and the sympathetic modulation of cardiac excitability; Functional significance of nitric oxide in the autonomic regulation of cardiac excitability; Summary; References. Experimental Physiology (2001) 86.1, 1-12. PMID:11429613

  3. 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...

  4. Air contamination with nitric oxide: effect on exhaled nitric oxide response.

    PubMed

    Therminarias, A; Flore, P; Favre-Juvin, A; Oddou, M F; Delaire, M; Grimbert, F

    1998-03-01

    This study examines the response of exhaled nitric oxide (NO) concentration (ECNO) and quantity of exhaled NO over time (EVNO) in 10 healthy subjects breathing into five polyethylene bags, one in which synthetic air was free of NO and four in which NO was diluted to concentrations of 20 +/- 0.6, 49 +/- 0.8, 98 +/- 2, and 148 +/- 2 ppb, respectively. Each subject was connected to each bag for 10 min at random. Minute ventilation and ECNO were measured continuously, and EVNO was calculated continuously. ECNO and EVNO values were significantly higher for an inhaled NO concentration of 20 ppb than for NO-free air. Above 20 ppb, ECNO and EVNO increased linearly with inhaled NO concentration. It is reasonable to assume that a share of the quantity of inspired NO over time (InspVNO) because of air contamination by pollution is rejected by the ventilatory pathway. Insofar as InspVNO does not affect endogenous production or the metabolic fate of NO in the airway, this share may be estimated as being approximately one third of InspVNO, the remainder being taken by the endogenous pathway. Thus, air contamination by the NO resulting from pollution greatly increases the NO response in exhaled air. PMID:9517592

  5. Nitric oxide synthesis and biological functions of nitric oxide released from ruthenium compounds.

    PubMed

    Pereira, A C; Paulo, M; Araújo, A V; Rodrigues, G J; Bendhack, L M

    2011-09-01

    During three decades, an enormous number of studies have demonstrated the critical role of nitric oxide (NO) as a second messenger engaged in the activation of many systems including vascular smooth muscle relaxation. The underlying cellular mechanisms involved in vasodilatation are essentially due to soluble guanylyl-cyclase (sGC) modulation in the cytoplasm of vascular smooth cells. sGC activation culminates in cyclic GMP (cGMP) production, which in turn leads to protein kinase G (PKG) activation. NO binds to the sGC heme moiety, thereby activating this enzyme. Activation of the NO-sGC-cGMP-PKG pathway entails Ca(2+) signaling reduction and vasodilatation. Endothelium dysfunction leads to decreased production or bioavailability of endogenous NO that could contribute to vascular diseases. Nitrosyl ruthenium complexes have been studied as a new class of NO donors with potential therapeutic use in order to supply the NO deficiency. In this context, this article shall provide a brief review of the effects exerted by the NO that is enzymatically produced via endothelial NO-synthase (eNOS) activation and by the NO released from NO donor compounds in the vascular smooth muscle cells on both conduit and resistance arteries, as well as veins. In addition, the involvement of the nitrite molecule as an endogenous NO reservoir engaged in vasodilatation will be described. PMID:21755266

  6. NOSTRIN: A protein modulating nitric oxide release and subcellular distribution of endothelial nitric oxide synthase

    PubMed Central

    Zimmermann, Kirstin; Opitz, Nils; Dedio, Jürgen; Renné, Christoph; Müller-Esterl, Werner; Oess, Stefanie

    2002-01-01

    Activity and localization of endothelial nitric oxide synthase (eNOS) is regulated in a remarkably complex fashion, yet the complex molecular machinery mastering stimulus-induced eNOS translocation and trafficking is poorly understood. In a search by the yeast two-hybrid system using the eNOS oxygenase domain as bait, we have identified a previously uncharacterized eNOS-interacting protein, dubbed NOSTRIN (for eNOS traffic inducer). NOSTRIN contains a single polypeptide chain of 506-aa residues of 58 kDa with an N-terminal cdc15 domain and a C-terminal SH3 domain. NOSTRIN mRNA is abundant in highly vascularized tissues such as placenta, kidney, lung, and heart, and NOSTRIN protein is expressed in vascular endothelial cells. Coimmunoprecipitation experiments demonstrated the eNOS–NOSTRIN interaction in vitro and in vivo, and NOSTRIN's SH3 domain was essential and sufficient for eNOS binding. NOSTRIN colocalized extensively with eNOS at the plasma membrane of confluent human umbilical venous endothelial cells and in punctate cytosolic structures of CHO-eNOS cells. NOSTRIN overexpression induced a profound redistribution of eNOS from the plasma membrane to vesicle-like structures matching the NOSTRIN pattern and at the same time led to a significant inhibition of NO release. We conclude that NOSTRIN contributes to the intricate protein network controlling activity, trafficking, and targeting of eNOS. PMID:12446846

  7. Nitric oxide control of cardiac function: is neuronal nitric oxide synthase a key component?

    PubMed Central

    Sears, Claire E; Ashley, Euan A; Casadei, Barbara

    2004-01-01

    Nitric oxide (NO) has been shown to regulate cardiac function, both in physiological conditions and in disease states. However, several aspects of NO signalling in the myocardium remain poorly understood. It is becoming increasingly apparent that the disparate functions ascribed to NO result from its generation by different isoforms of the NO synthase (NOS) enzyme, the varying subcellular localization and regulation of NOS isoforms and their effector proteins. Some apparently contrasting findings may have arisen from the use of non-isoform-specific inhibitors of NOS, and from the assumption that NO donors may be able to mimic the actions of endogenously produced NO. In recent years an at least partial explanation for some of the disagreements, although by no means all, may be found from studies that have focused on the role of the neuronal NOS (nNOS) isoform. These data have shown a key role for nNOS in the control of basal and adrenergically stimulated cardiac contractility and in the autonomic control of heart rate. Whether or not the role of nNOS carries implications for cardiovascular disease remains an intriguing possibility requiring future study. PMID:15306414

  8. 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

  9. 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

  10. Modulation of parathion toxicity by glucose feeding: Is nitric oxide involved?

    SciTech Connect

    Liu Jing . E-mail: jing.pope@okstate.edu; Gupta, Ramesh C.; Goad, John T.; Karanth, Subramanya; Pope, Carey

    2007-03-15

    Glucose feeding can markedly exacerbate the toxicity of the anticholinesterase insecticide, parathion. We determined the effects of parathion on brain nitric oxide and its possible role in potentiation of toxicity by glucose feeding. Adult rats were given water or 15% glucose in water for 3 days and challenged with vehicle or parathion (18 mg/kg, s.c.) on day 4. Functional signs, plasma glucose and brain cholinesterase, citrulline (an indicator of nitric oxide production) and high-energy phosphates (HEPs) were measured 1-3 days after parathion. Glucose feeding exacerbated cholinergic toxicity. Parathion increased plasma glucose (15-33%) and decreased cortical cholinesterase activity (81-90%), with no significant differences between water and glucose treatment groups. In contrast, parathion increased brain regional citrulline (40-47%) and decreased HEPs (18-40%) in rats drinking water, with significantly greater changes in glucose-fed rats (248-363% increase and 31-61% decrease, respectively). We then studied the effects of inhibiting neuronal nitric oxide synthase (nNOS) by 7-nitroindazole (7NI, 30 mg/kg, i.p. x4) on parathion toxicity and its modulation by glucose feeding. Co-exposure to parathion and 7NI led to a marked increase in cholinergic signs of toxicity and lethality, regardless of glucose intake. Thus, glucose feeding enhanced the accumulation of brain nitric oxide following parathion exposure, but inhibition of nitric oxide synthesis was ineffective at counteracting increased parathion toxicity associated with glucose feeding. Evidence is therefore presented to suggest that nitric oxide may play both toxic and protective roles in cholinergic toxicity, and its precise contribution to modulation by glucose feeding requires further investigation.

  11. 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

  12. Subclinical mastitis causes alterations in nitric oxide, total oxidant and antioxidant capacity in cow milk.

    PubMed

    Atakisi, Onur; Oral, Hasan; Atakisi, Emine; Merhan, Oguz; Metin Pancarci, S; Ozcan, Ayla; Marasli, Saban; Polat, Bulent; Colak, Armagan; Kaya, Semra

    2010-08-01

    The aim of this study was to investigate total antioxidant (TAC), and oxidant capacity (TOC) and nitric oxide (NO) levels in milk of cows with subclinical mastitis. Brown Swiss and Holstein breed cows were screened with California Mastitis Test (CMT) to determine mammary glands with subclinical mastitis. Moreover, somatic cell counts (SCC) were determined electronically in all milk samples. Mammary quarters were classified as healthy (n=25) or subclinical mastitis (n=35) based on CMT scores and somatic cell count (SCC: < or =200,000/ml or >200,000/ml) in milk. Nitric oxide, TOC and SCC levels were significantly higher (p<0.001, p<0.005 and p<0.001, respectively) in milk from mammary quarters with subclinical mastitis compared to those from healthy mammary quarters. In conclusion, subclinical mastitis results in higher NO concentrations, TOC and SCC, and NO and TOC were positively correlated with SCC. Moreover, alterations in NO levels and TOC in milk could be used as an alternative diagnostic tool to screen for subclinical mastitis. PMID:20132956

  13. 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.

  14. 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

  15. 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.

  16. 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

  17. Fine Particulate Matter Constituents, Nitric Oxide Synthase DNA Methylation and Exhaled Nitric Oxide.

    PubMed

    Chen, Renjie; Qiao, Liping; Li, Huichu; Zhao, Yan; Zhang, Yunhui; Xu, Wenxi; Wang, Cuicui; Wang, Hongli; Zhao, Zhuohui; Xu, Xiaohui; Hu, Hui; Kan, Haidong

    2015-10-01

    It remains unknown how fine particulate matter (PM2.5) constituents affect differently the fractional concentration of exhaled nitric oxide (FeNO, a biomarker of airway inflammation) and the DNA methylation of its encoding gene (NOS2A). We aimed to investigate the short-term effects of PM2.5 constituents on NOS2A methylation and FeNO. We designed a longitudinal study among chronic obstructive pulmonary disease (COPD) patients with six repeated health measurements in Shanghai, China. We applied linear mixed-effect models to evaluate the associations. We observed that the inverse association between PM2.5 and methylation at position 1 was limited within 24 h, and the positive association between PM2.5 and FeNO was the strongest at lag 1 day. Organic carbon, element carbon, NO3(-) and NH4(+) were robustly and significantly associated with decreased methylation and elevated FeNO. An interquartile range increase in total PM2.5 and the four constituents was associated with decreases of 1.19, 1.63, 1.62, 1.17, and 1.14 in percent methylation of NOS2A, respectively, and increases of 13.30%,16.93%, 8.97%, 18.26%, and 11.42% in FeNO, respectively. Our results indicated that organic carbon, element carbon, NO3(-) and NH4(+) might be mainly responsible for the effects of PM2.5 on the decreased NOS2A DNA methylation and elevated FeNO in COPD patients. PMID:26372312

  18. Interleukin-12 gene-expression of macrophages is regulated by nitric oxide.

    PubMed

    Rothe, H; Hartmann, B; Geerlings, P; Kolb, H

    1996-07-01

    Interleukin-12 is a heterodimeric cytokine, mainly produced by macrophages. In our present study we demonstrate that interleukin-12 expression is regulated by nitric oxide. Incubation of the macrophage cell line IC 21 with interferon-gamma gave rise to both interleukin-12 p40 mRNA and nitric oxide production. The concurrent addition of the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine inhibited nitrite production and in parallel completely suppressed interleukin-12 p40 mRNA formation. This indicated that endogenous nitric oxide synthase activity was required for IL-12 p40 gene expression. Exposure of the cells towards the nitric oxide generating compounds nitroprusside or S-nitroso-N-acetyl-penicillamine induced interleukin-12 p40 mRNA. Maximal mRNA levels were induced with nitric oxide donors at 1 microM concentration. We conclude that nitric oxide may exert an autoregulatory and paracrine control of interleukin-12 gene expression. PMID:8694804

  19. Exhaled nitric oxide in children after accidental exposure to chlorine gas.

    PubMed

    Grasemann, Hartmut; Tschiedel, Eva; Groch, Manuela; Klepper, Jörg; Ratjen, Felix

    2007-08-01

    Chronic exposure to chlorine gas has been shown to cause occupational asthma. Acute inhalation of chlorine is known to cause airway inflammation and induce airway nitric oxide formation. Exhaled nitric oxide may therefore be a marker of airway damage after chlorine gas exposure. After accidental chlorine gas exposure in a swimming pool, exhaled nitric oxide and pulmonary function were repeatedly measured in 18 children over a 1-mo period. Symptomatic children with impaired pulmonary function had higher nitric oxide levels on the day after the exposure compared to day 8 and day 28. Differences in exhaled nitric oxide were more pronounced at a higher exhalation flow compared to lower flow, suggesting peripheral rather than central airway damage. This was in accordance with the observed changes in pulmonary function. No changes in exhaled nitric oxide were seen in asymptomatic children. These data suggest that acute chlorine gas exposure results in a mild increase of exhaled nitric oxide in symptomatic children. PMID:17687720

  20. The Achievements of the Student Nitric Oxide Explorer

    NASA Astrophysics Data System (ADS)

    Bailey, S. M.

    2005-12-01

    The Student Nitric Oxide Explorer (SNOE) completed nearly six years of continuous observation before it reentered the Earth's atmosphere on December 13, 2003. The primary goals of SNOE were to determine the magnitude and variability of nitric oxide in the lower thermosphere and to determine the relationship between NO and the energetic inputs to the atmosphere that create it. SNOE observations confirmed previously held suspicions that the solar soft X-ray irradiance was stronger than the prior sparsely available data and empirical models suggested. SNOE demonstrated that solar soft X-ray irradiance and auroral energy deposition control the abundance of NO over the globe, but provided the very surprising results that wintertime midlatitude NO is controlled by auroral energy while summertime polar NO is controlled by solar irradiance. The morphology of NO is also providing clues to the processes in the magnetospheric which lead to the auroral energy deposition. Serendipitous observations of polar mesospheric clouds by SNOE have provided an excellent database for climatological studies of these clouds, showing that there is a strong hemispheric asymmetry in their distribution and that they are strongly influenced by local dynamics. Many students contributed greatly toward SNOE's design, development, testing, launch, operations, and data analysis. SNOE was managed for NASA by the Universities Space Research Association (USRA) under the Student Explorers Demonstration Initiative (STEDI). The goal of STEDI was to show that small relevant research satellite missions could be developed at low cost and with high educational benefit by giving students a large involvement. SNOE was developed and operated through its primary mission for under five million dollars (excluding only launch vehicle costs). The SNOE development team consisted primarily of students working closely with a small number of experienced professionals. Students had significant responsibilities in all areas

  1. 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

  2. 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.

  3. 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.

  4. Existence of nitric oxide synthase in rat hippocampal pyramidal cells.

    PubMed Central

    Wendland, B; Schweizer, F E; Ryan, T A; Nakane, M; Murad, F; Scheller, R H; Tsien, R W

    1994-01-01

    It has been proposed that nitric oxide (NO) serves as a key retrograde messenger during long-term potentiation at hippocampal synapses, linking induction of long-term potentiation in postsynaptic CA1 pyramidal cells to expression of long-term potentiation in presynaptic nerve terminals. However, nitric oxide synthase (NOS), the proposed NO-generating enzyme, has not yet been detected in the appropriate postsynaptic cells. We here demonstrate specific NOS immunoreactivity in the CA1 region of hippocampal sections by using an antibody specific for NOS type I and relatively gentle methods of fixation. NOS immunoreactivity was found in dendrites and cell bodies of CA1 pyramidal neurons. Cultured hippocampal pyramidal cells also displayed specific immunostaining. Control experiments showed no staining with preimmune serum or immune serum that was blocked with purified NOS. These results demonstrate that CA1 pyramidal cells contain NOS, as required were NO involved in retrograde signaling during hippocampal synaptic plasticity. Images PMID:7510887

  5. 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.

  6. 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

  7. Nitric Oxide Scavenging by Hemoglobin in Health, Disease, and Therapeutics

    NASA Astrophysics Data System (ADS)

    Kim-Shapiro, Daniel

    2007-11-01

    Nitric oxide (NO) is the endothelium-derived relaxing factor (EDRF). It is made in endothelial cells lining blood vessels and diffuses to smooth muscle cells where it leads to muscle relaxation, vessel dilatation, and increased blood flow and also plays a large role in controlling platelet aggregation and inflammation. Hemoglobin (Hb), the oxygen carrying molecule in the blood, reacts at nearly diffusion limited rates with nitric oxide to (in some reactions) form nitrate ands thereby destroy NO activity. The presence of such large amounts of such a potent NO scavenger in the blood challenges the idea that NO is indeed the EDRF. Encapsulation in red blood cells in healthy individuals limits NO scavenging by Hb. Biophysical experiments will be described exploring and evaluating these mechanisms. Other studies will be described discussing how red cells break open (lyse) in pathological situations and the cell-free Hb reduces NO bioavailability. Finally, methods to restore NO bioavailability through therapeutics will be discussed.

  8. Nitric oxide: a regulator of eukaryotic initiation factor 2 kinases.

    PubMed

    Tong, Lingying; Heim, Rachel A; Wu, Shiyong

    2011-06-15

    Generation of nitric oxide (NO(•)) can upstream induce and downstream mediate the kinases that phosphorylate the α subunit of eukaryotic initiation factor 2 (eIF2α), which plays a critical role in regulating gene expression. There are four known eIF2α kinases (EIF2AKs), and NO(•) affects each one uniquely. Whereas NO(•) directly activates EIF2AK1 (HRI), it indirectly activates EIF2AK3 (PERK). EIF2AK4 (GCN2) is activated by depletion of l-arginine, which is used by nitric oxide synthase (NOS) during the production of NO(•). Finally EIF2AK2 (PKR), which can mediate inducible NOS expression and therefore NO(•) production, can also be activated by NO(•). The production of NO(•) and activation of EIF2AKs coordinately regulate physiological and pathological events such as innate immune response and cell apoptosis. PMID:21463677

  9. Effect of fuel/air nonuniformity on nitric oxide emissions

    NASA Technical Reports Server (NTRS)

    Lyons, V. J.

    1979-01-01

    A flame tube combustor holding jet A fuel was used in experiments performed at a pressure of .3 Mpa and a reference velocity of 25 meters/second for three inlet air temperatures of 600, 700, and 800 K. The gas sample measurements were taken at locations 18 cm and 48 cm downstream of the perforated plate flameholder. Nonuniform fuel/air profiles were produced using a fuel injector by separately fueling the inner five fuel tubes and the outer ring of twelve fuel tubes. Six fuel/air profiles were produced for nominal overall equivalence ratios of .5 and .6. An example of three of three of these profiles and their resultant nitric oxide NOx emissions are presented. The uniform fuel/air profile cases produced uniform and relatively low profile levels. When the profiles were either center-peaked or edge-peaked, the overall mass-weighted nitric oxide levels increased.

  10. 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

  11. 49 CFR 173.337 - Nitric oxide.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... oxide in a DOT 3AL is cylinder is authorized only by highway and rail. (2) UN cylinder. In a UN cylinder... UN tubes and MEGCs is not authorized. (3) Valves. Cylinders must be equipped with a stainless steel... be equipped with pressure relief devices of any type. (b) Each UN cylinder must be cleaned...

  12. 49 CFR 173.337 - Nitric oxide.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... oxide in a DOT 3AL is cylinder is authorized only by highway and rail. (2) UN cylinder. In a UN cylinder... UN tubes and MEGCs is not authorized. (3) Valves. Cylinders must be equipped with a stainless steel... be equipped with pressure relief devices of any type. (b) Each UN cylinder must be cleaned...

  13. 49 CFR 173.337 - Nitric oxide.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... oxide in a DOT 3AL is cylinder is authorized only by highway and rail. (2) UN cylinder. In a UN cylinder... UN tubes and MEGCs is not authorized. (3) Valves. Cylinders must be equipped with a stainless steel... be equipped with pressure relief devices of any type. (b) Each UN cylinder must be cleaned...

  14. 49 CFR 173.337 - Nitric oxide.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... oxide in a DOT 3AL is cylinder is authorized only by highway and rail. (2) UN cylinder. In a UN cylinder... UN tubes and MEGCs is not authorized. (3) Valves. Cylinders must be equipped with a stainless steel... be equipped with pressure relief devices of any type. (b) Each UN cylinder must be cleaned...

  15. 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...

  16. 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

  17. 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

  18. 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.

  19. A Dirofilaria immitis Polyprotein Up-Regulates Nitric Oxide Production

    PubMed Central

    Tezuka, Hiroyuki; Imai, Shinjiro; Tsukidate, Setsuko; Fujita, Koichiro

    2002-01-01

    We investigated the effect of recombinant Dirofilaria immitis polyprotein (rDiAg) on nitric oxide (NO) production by peritoneal macrophages. rDiAg induced NO production by macrophages from wild-type and lipopolysaccharide-hyporesponsive C3H/HeJ, but not CD40−/−, mice. These results suggest that CD40 is involved in rDiAg-driven NO production by murine macrophages. PMID:12183583

  20. Evidence for nitric oxide-mediated sympathetic forearm vasodiolatation in humans.

    PubMed Central

    Dietz, N M; Engelke, K A; Samuel, T T; Fix, R T; Joyner, M J

    1997-01-01

    1. Our aim was to determine if sympathetic vasodilatation occurs in the human forearm, and if the vasodilating substance nitric oxide contributes to this dilatation. We also sought to determine if the nitric oxide might be released as a result of cholinergic stimulation of the vascular endothelium. 2. Blood flow was measured in the resting non-dominant forearm with venous occlusion plethysmography. To increase sympathetic traffic to the resting forearm, rhythmic handgrip exercise to fatigue followed by post-exercise ischaemia was performed by the dominant forearm. A brachial artery catheter in the non-dominant arm was used to selectively infuse drugs. 3. During control conditions, there was mild vasodilatation in the resting forearm during exercise followed by constriction during post-exercise ischaemia. When exercise was performed after brachial artery administration of bretylium (to block noradrenaline release) and phentolamine (an alpha-adrenergic antagonist), profound vasodilatation was seen in the resting forearm during both exercise and post-exercise ischaemia. 4. When the nitric oxide synthase blocker NG-monomethyl-L-arginine (L-NMMA) was administered in the presence of bretylium and phentolamine prior to another bout of handgripping, little or no vasodilatation was seen either during exercise or post-exercise ischaemia. Atropine also blunted the vasodilator responses to exercise and post-exercise ischaemia after bretylium and phentolamine. 5. These results support the existence of active sympathetic vasodilatation in the human forearm and the involvement of nitric oxide in this phenomenon. They also suggest nitric oxide might be released as a result of cholinergic stimulation of the vascular endothelium. PMID:9032700

  1. Sensor materials for an intravascular fiber optic nitric oxide sensor

    NASA Astrophysics Data System (ADS)

    Soller, Babs R.; Parikh, Bhairavi R.; Stahl, Russell F.

    1996-04-01

    Nitric oxide (NO) is an important regulatory molecule in physiological processes including neurotransmission and the control of blood pressure. It is produced in excess during septic shock, the profound hypotensive state which accompanies severe infections. In-vivo measurement of NO would enhance the understanding of its varied biological roles. Our goal is the development of an intravascular fiber-optic sensor for the continuous measurement of NO. This study evaluated nitric oxide sensitive compounds as potential sensing materials in the presence and absence of oxygen. Using absorption spectroscopy we studied both the Fe II and Fe III forms of three biologically active hemes known to rapidly react with NO: hemoglobin, myoglobin, and cytochrome-c. The Fe II forms of hemoglobin and myoglobin and the Fe III form of cytochrome-c were found to have the highest sensitivity to NO. Cytochrome c (Fe III) is selective for NO even at high oxygen levels, while myoglobin is selective only under normal oxygen levels. NO concentrations as low as 1 (mu) M can be detected with our fiber-optic spectrometer using cytochrome c, and as low as 300 nM using myoglobin. Either of these materials would be adequate to monitor the increase in nitric oxide production during the onset of septic shock.

  2. 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.

  3. The Role of Nitric Oxide Synthase Uncoupling in Tumor Progression

    PubMed Central

    Rabender, Christopher S.; Alam, Asim; Sundaresan, Gobalakrishnan; Cardnell, Robert J.; Yakovlev, Vasily A.; Mukhopadhyay, Nitai D.; Graves, Paul; Zweit, Jamal; Mikkelsen, Ross B.

    2015-01-01

    Here evidence suggests that nitric oxide synthases (NOS) of tumor cells, in contrast to normal tissues, synthesize predominantly superoxide and peroxynitrite. Based on HPLC analysis, the underlying mechanism for this uncoupling is a reduced tetrahydrobiopterin: dihydrobiopterin ratio (BH4:BH2) found in breast, colorectal, epidermoid and head and neck tumors compared to normal tissues. Increasing BH4:BH2 and reconstitution of coupled NOS activity in breast cancer cells with the BH4 salvage pathway precursor, sepiapterin, causes significant shifts in downstream signaling including increased cGMP-dependent protein kinase (PKG) activity, decreased β-catenin expression and TCF4 promoter activity, and reduced NF-κB promoter activity. Sepiapterin inhibited breast tumor cell growth in vitro and in vivo as measured by clonogenic assay, Ki67 staining and 18F-deoxyglucose positron emission tomography (FDG-PET). In summary, using diverse tumor types, it is demonstrated that the BH4:BH2 ratio is lower in tumor tissues and as a consequence nitric oxide synthase activity generates more peroxynitrite and superoxide anion than nitric oxide resulting in important tumor growth promoting and anti-apoptotic signaling properties. Implications The synthetic BH4, Kuvan®, is used to elevate BH4:BH2 in some phenylketonuria patients and to treat diseases associated with endothelial dysfunction suggesting a novel, testable approach for correcting an abnormality of tumor metabolism to control tumor growth. PMID:25724429

  4. Nitric oxide in atherosclerosis: vascular protector or villain?

    PubMed

    Dusting, G J; Fennessy, P; Yin, Z L; Gurevich, V

    1998-11-01

    1. Nitric oxide (NO) has important roles in physiological vasodilatation, cytotoxicity and vascular disease. Nitric oxide and prostacyclin (PGI2), both released from the endothelium, act synergistically to inhibit platelet aggregation and adhesion. These autacoids also inhibit the adhesion and migration of leucocytes and, in some arteries, they synergize in terms of vasodilation. 2. The development of atherosclerosis and hyperlipaemia per se is accompanied by impairment of endothelium-dependent vasodilation. 3. Atherosclerosis is associated with marked changes in the activity of isoforms of NO synthase (NOS) in the artery wall, including increased expression of the NOS2 (inducible) isoform in complex human lesions as well as in the neointima of experimental animal models. 4. Failure of NO release from the endothelium with normal physiological stimuli, which has been attributed to a defect in the operation of the endothelial NOS (NOS3), provides conditions propitious for leucocyte adhesion, vasospasm, thrombosis and, in addition, may promote increased proliferation of intimal cells. 5. Nitric oxide and superoxide anions generated by inflammatory cells in atherosclerosis react to form cytodestructive peroxynitrite radicals, potentially causing injury to the endothelium and myocytes, and this may be a factor in apoptosis of cells leading to plaque rupture. 6. We have been able to reverse these NO defects with therapeutic agents, including angiotensin-converting enzyme inhibitors, antagonists of platelet-activating factor and NO donor compounds, all offering promise in protecting against some manifestations of vascular disease. PMID:9809190

  5. Nitric oxide induces caspase activity in boar spermatozoa.

    PubMed

    Moran, J M; Madejón, L; Ortega Ferrusola, C; Peña, F J

    2008-07-01

    Nitric oxide (NO) is a highly reactive free radical that plays a key role in intra- and intercellular signaling. Production of radical oxygen species and an apoptotic-like phenomenon have recently been implicated in cryodamage during sperm cryopreservation. The objective of the present study was to evaluate the effect of sodium nitroprusside (SNP), an NO donor, on boar sperm viability. Semen samples were pooled from four boars that were routinely used for artificial insemination. Flow cytometry was used to compare semen incubated with SNP to control semen. Specifically, NO production was measured using the NO indicator dye diaminofluorescein diacetate, and caspase activity was determined using the permeable pan-caspase inhibitor Z-VAD linked to FITC. SNP induced a significant increase in the percentage of sperm cells showing caspase activity, from 9.3% in control samples to 76.2% in SNP-incubated samples (P<0.01). This study suggests that NO is a major free radical involved in boar sperm damage. PMID:18433854

  6. Increased amount of nitric oxide in exhaled air of asthmatics.

    PubMed

    Alving, K; Weitzberg, E; Lundberg, J M

    1993-10-01

    The presence of nitric oxide (NO) in the exhaled air of humans has recently been described. We wanted to assess at what level exhaled NO originates in normal airways, and to determine whether airway inflammation induces changes in the levels of exhaled NO. Exhaled NO was continuously measured by chemiluminescence technique during normal tidal breathing through the nose or mouth, with a detection limit of 1 part per billion (ppb). Twelve control subjects were compared to eight patients with mild atopic asthma and rhinitis caused by occupational allergen. In control subjects, the major part of NO in exhaled air (up to 30 ppb) seemed to originate in the nasal airways, with only minor contribution from the lower airways and the oral cavity. However, in mild asthmatics, the level of exhaled NO during oral breathing, indicating the involvement of the lower airways, was increased 2-3 fold. Since increased production of NO in the lower airways may involve activated macrophages or neutrophils, we suggest that exhaled NO may be used to instantly monitor ongoing bronchial inflammation, at least when involving inducible NO synthase. PMID:7507065

  7. Role of nitric oxide in cardiovascular adaptation to intermittent hypoxia.

    PubMed

    Manukhina, Eugenia B; Downey, H Fred; Mallet, Robert T

    2006-04-01

    Hypoxia is one of the most frequently encountered stresses in health and disease. The duration, frequency, and severity of hypoxic episodes are critical factors determining whether hypoxia is beneficial or harmful. Adaptation to intermittent hypoxia has been demonstrated to confer cardiovascular protection against more severe and sustained hypoxia, and, moreover, to protect against other stresses, including ischemia. Thus, the direct and cross protective effects of adaptation to intermittent hypoxia have been used for treatment and prevention of a variety of diseases and to increase efficiency of exercise training. Evidence is mounting that nitric oxide (NO) plays a central role in these adaptive mechanisms. NO-dependent protective mechanisms activated by intermittent hypoxia include stimulation of NO synthesis as well as restriction of NO overproduction. In addition, alternative, nonenzymic sources of NO and negative feedback of NO synthesis are important factors in optimizing NO concentrations. The adaptive enhancement of NO synthesis and/or availability activates or increases expression of other protective factors, including heat shock proteins, antioxidants and prostaglandins, making the protection more robust and sustained. Understanding the role of NO in mechanisms of adaptation to hypoxia will support development of therapies to prevent and treat hypoxic or ischemic damage to organs and cells and to increase adaptive capabilities of the organism. PMID:16565431

  8. Decoding Nitric Oxide Release Rates of Amine-Based Diazeniumdiolates

    PubMed Central

    Wang, Yan-Ni; Collins, Jack; Holland, Ryan J.; Keefer, Larry K.; Ivanic, Joseph

    2013-01-01

    Amine-based diazeniumdiolates (NONOates) have garnered widespread use as nitric oxide (NO) donors and their potential for nitroxyl (HNO) release has more recently been realized. While NO release rates can vary significantly with the type of amine, half-lives of seconds to days under physiological conditions, there is as yet no way to determine a priori the NO or HNO production rates of a given species and no discernible trends have manifested other than that secondary amines produce only NO (i.e., no HNO). As a step to understanding these complex systems, here we describe a procedure for modeling amine-based NONOates in water solvent that provides an excellent correlation (R2 = 0.94) between experimentally measured dissociation rates of seven secondary amine species and their computed NO release activation energies. The significant difference in behavior of NONOates in the gas and solvent phases is also rigorously demonstrated via explicit additions of quantum mechanical water molecules. The presented results suggest that the as-yet unsynthesized simplest amine-based NONOate, the diazeniumdiolated ammonia anion [H2N-N(O)=NO−], could serve as an unperturbed HNO donor. These results provide a step forward toward the accurate modeling of general NO and/or HNO donors as well as for the identification of tailored prodrug candidates. PMID:23834533

  9. Nitric Oxide Diffusion Rate is Reduced in the Aortic Wall☆

    PubMed Central

    Liu, Xiaoping; Srinivasan, Parthasarathy; Collard, Eric; Grajdeanu, Paula; Zweier, Jay L.; Friedman, Avner

    2008-01-01

    Endogenous nitric oxide (NO) plays important physiological roles in the body. As a small diatomic molecule, NO has been assumed to freely diffuse in tissues with a diffusion rate similar to that in water. However, this assumption has not been tested experimentally. In this study, a modified Clark-type NO electrode attached with a customized aorta holder was used to directly measure the flux of NO diffusion across the aortic wall at 37°C. Experiments were carefully designed for accurate measurements of the apparent NO diffusion coefficient D and the partition coefficient α in the aortic wall. A mathematical model was presented for analyzing experimental data. It was determined that α = 1.15 ± 0.11 and D = 848 ± 45 μm2/s (n = 12). The NO diffusion coefficient in the aortic wall is nearly fourfold smaller than the reported diffusion coefficient in solution at 37°C, indicating that NO diffusion in the vascular wall is no longer free, but markedly dependent on the environment in the tissue where these NO molecules are. These results imply that the NO diffusion rate in the vascular wall may be upregulated and downregulated by certain physiological and/or pathophysiological processes affecting the composition of tissues. PMID:18032554

  10. Dual effects of nitric oxide on cat carotid body chemoreception.

    PubMed

    Iturriaga, R; Villanueva, S; Mosqueira, M

    2000-09-01

    We studied the effects of nitric oxide (NO) released by NO donors on cat carotid body (CB) chemosensory activity during normoxia and hypoxia. CBs excised from pentobarbital sodium-anaesthetized cats were perfused with Tyrode at 38 degrees C and pH 7.40. The frequency of chemosensory discharges (f(x)) was recorded from the carotid sinus nerve, and changes of NO concentration were measured by a chronoamperometric technique, with NO-selective carbon-fiber microelectrodes inserted in the CB. During steady chemosensory excitation induced by hypoxia, bolus injections of NO (DeltaNO = 0. 5-12 microM), released by S-nitroso-N-acetylpenicillamine (SNAP) and 6-(2-hydroxy-1-methyl-nitrosohydrazino)-N-methyl-1-hexanamine++ + (NOC-9), transiently reduced f(x) in a dose-dependent manner. However, during normoxia, the same concentration of NO (DeltaNO = 0. 5-13 microM) released by the NO donors increased f(x) in a dose-dependent manner. The present results show a dual effect of NO on CB chemoreception that is dependent on the PO(2) levels. During hypoxia, NO is predominantly an inhibitor of chemoreception, whereas, in normoxia, NO increased f(x). The mechanisms by which NO produces chemosensory excitation during normoxia remain to be determined. PMID:10956344

  11. 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.

  12. 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

  13. 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.

  14. Nitric oxide reacts with intracellular glutathione and activates the hexose monophosphate shunt in human neutrophils: evidence for S-nitrosoglutathione as a bioactive intermediary.

    PubMed Central

    Clancy, R M; Levartovsky, D; Leszczynska-Piziak, J; Yegudin, J; Abramson, S B

    1994-01-01

    We performed experiments to determine whether nitric oxide promoted the formation of intracellular S-nitrosothiol adducts in human neutrophils. At concentrations sufficient to inhibit chemoattractant-induced superoxide anion production, nitric oxide caused a depletion of measurable intracellular glutathione as determined by both the monobromobimane HPLC method and the glutathione reductase recycling assay. The depletion of glutathione could be shown to be due to the formation of intracellular S-nitrosoglutathione as indicated by the ability of sodium borohydride treatment of cytosol to result in the complete recovery of measurable glutathione. The formation of intracellular S-nitrosylated compounds was confirmed by the capacity of cytosol derived from nitric oxide-treated cells to ADP-ribosylate glyceraldehyde-3-phosphate dehydrogenase. Depletion of intracellular glutathione was accompanied by a rapid and concomitant activation of the hexose monophosphate shunt (HMPS) following exposure to nitric oxide. Kinetic studies demonstrated that nitric oxide-dependent activation of the HMPS was reversible and paralleled nitric oxide-induced glutathione depletion. Synthetic preparations of S-nitrosoglutathione shared with nitric oxide the capacity to inhibit superoxide anion production and activate the HMPS. These data suggest that nitric oxide may regulate cellular functions via the formation of intracellular S-nitrosothiol adducts and the activation of the HMPS. Images PMID:8170969

  15. 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

  16. Role of exhaled nitric oxide as a predictor of atopy

    PubMed Central

    2013-01-01

    Background The fractional exhaled nitric oxide (FeNO) is a quantitative, noninvasive and safe measure of airways inflammation that may complement the assessment of asthma. Elevations of FeNO have recently been found to correlate with allergic sensitization. Therefore, FeNO may be a useful predictor of atopy in the general population. We sought to determine the diagnostic accuracy of FeNO in predicting atopy in a population-based study. Methods We conducted a cross-sectional study in an age- and sex- stratified random sample of 13 to 15 year-olds in two communities in Peru. We asked participants about asthma symptoms, environmental exposures and sociodemographics, and underwent spirometry, assessment of FeNO and an allergy skin test. We used multivariable logistic regression to model the odds of atopy as a function of FeNO, and calculated area-under-the-curves (AUC) to determine the diagnostic accuracy of FeNO as a predictor of atopy. Results Of 1441 recruited participants, 1119 (83%) completed all evaluations. Mean FeNO was 17.6 ppb (SD=0.6) in atopics and 11.6 ppb (SD=0.8) in non-atopics (p<0.001). In multivariable analyses, a FeNO>20 ppb was associated with an increase in the odds of atopy in non-asthmatics (OR=5.3, 95% CI 3.3 to 8.5) and asthmatics (OR=16.2, 95% CI 3.4 to 77.5). A FeNO>20 ppb was the best predictor for atopy with an AUC of 68% (95% CI 64% to 69%). Stratified by asthma, the AUC was 65% (95% CI 61% to 69%) in non-asthmatics and 82% (95% CI 71% to 91%) in asthmatics. Conclusions FeNO had limited accuracy to identify atopy among the general population; however, it may be a useful indicator of atopic phenotype among asthmatics. PMID:23639047

  17. Solar-terrestrial coupling: Solar soft X-rays and thermospheric nitric oxide

    NASA Astrophysics Data System (ADS)

    Barth, Charles A.; Bailey, Scott M.; Solomon, Stanley C.

    Simultaneous measurements were made of the solar soft x-ray irradiances and the thermospheric nitric oxide density in the tropics from the Student Nitric Oxide Explorer (SNOE) satellite. The analysis of these observations for 44 days of low geomagnetic activity in the spring of 1998 show that there is a correlation between the solar soft x-ray irradiances and thermospheric nitric oxide densities in the tropics. Photochemical model calculations that used the measured solar soft x-ray irradiances as input parameters adequately reproduce the magnitude of the time-varying component of the thermospheric nitric oxide in the tropics. An additional amount of nitric oxide is present in the tropics that does not vary with the time period of the solar rotation. The conclusion of this analysis is that solar soft x-rays are the primary cause of the variation in the thermospheric nitric oxide densities in the tropics during times of low geomagnetic activity.

  18. 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

  19. Histochemical study of the nitric oxide synthase activity in experimental trichinellosis.

    PubMed

    Hadaś, E; Gustowska, L; Boczoń, K; Janczewska, D

    1999-01-01

    Nitric oxide plays a critical role in a variety of biological activities. It has been nicknamed a "killer" and "mediator" due to its toxic and signalling properties. Apart from its regular physiological function, nitric oxide indirectly participates in infectious diseases. Our report seems to be the first presentation of the nitric oxide synthase participation in the host biochemical defence mechanisms and in morphological transformation of muscle cells in trichinellosis. PMID:16883715

  20. 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

  1. 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

  2. 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

  3. 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.

  4. Nitric Oxide Suppresses β-Cell Apoptosis by Inhibiting the DNA Damage Response.

    PubMed

    Oleson, Bryndon J; Broniowska, Katarzyna A; Naatz, Aaron; Hogg, Neil; Tarakanova, Vera L; Corbett, John A

    2016-08-01

    Nitric oxide, produced in pancreatic β cells in response to proinflammatory cytokines, plays a dual role in the regulation of β-cell fate. While nitric oxide induces cellular damage and impairs β-cell function, it also promotes β-cell survival through activation of protective pathways that promote β-cell recovery. In this study, we identify a novel mechanism in which nitric oxide prevents β-cell apoptosis by attenuating the DNA damage response (DDR). Nitric oxide suppresses activation of the DDR (as measured by γH2AX formation and the phosphorylation of KAP1 and p53) in response to multiple genotoxic agents, including camptothecin, H2O2, and nitric oxide itself, despite the presence of DNA damage. While camptothecin and H2O2 both induce DDR activation, nitric oxide suppresses only camptothecin-induced apoptosis and not H2O2-induced necrosis. The ability of nitric oxide to suppress the DDR appears to be selective for pancreatic β cells, as nitric oxide fails to inhibit DDR signaling in macrophages, hepatocytes, and fibroblasts, three additional cell types examined. While originally described as the damaging agent responsible for cytokine-induced β-cell death, these studies identify a novel role for nitric oxide as a protective molecule that promotes β-cell survival by suppressing DDR signaling and attenuating DNA damage-induced apoptosis. PMID:27185882

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

    PubMed

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

    2011-01-01

    Only recently we can link thermogenesis, mitochondria, nitric oxide, and redox regulation in biochemical terms. Currently, we are discussing these processes from the aspect of fundamental principles of molecular physiology. Thus, the present article highlights both cell physiology and the principles of the maintenance of energy homeostasis in organisms. Energy homeostasis means much more than simple combustion; adipose tissues at this point of evolution development are related to a broad spectrum of metabolic disturbances and all aspects of cellular remodeling (i.e. structural, metabolic and endocrine changes). Therefore, this paper addresses not only thermogenesis but also energy homeostasis, oxidative phosphorylation and ATP production, proliferation and differentiation of brown adipocytes, their life and death, mitochondriogenesis and angiogenesis. These processes will be united by molecular players of oxidation/reduction reactions, thus creating the principles based on the redox regulation. PMID:21622264

  6. Macrophage oxidation of L-arginine to nitrite and nitrate: nitric oxide is an intermediate

    SciTech Connect

    Marletta, M.A.; Yoon, P.S.; Iyengar, R.; Leaf, C.D.; Wishnok, J.S.

    1988-11-29

    Previous studies have shown that murine macrophages immunostimulated with interferon ..gamma.. and Escherichia coli lipopolysaccharide synthesize NO/sub 2//sup -/, NO/sub 3//sup -/, and citrulline from L-arginine by oxidation of one of the two chemically equivalent guanido nitrogens. The enzymatic activity for this very unusual reaction was found in the 100,000g supernatant isolated from activated RAW 264.7 cells and was totally absent in unstimulated cells. This activity requires NADPH and L-arginine and is enhanced by Mg/sup 2 +/. When the subcellular fraction containing the enzyme activity was incubated with L-arginine, NADPH, and Mg/sup 2 +/, the formation of nitric oxide was observed. Nitric oxide formation was dependent on the presence of L-arginine and NADPH and was inhibited by the NO/sub 2//sup -//NO/sub 3//sup -/ synthesis inhibitor N/sup G/-monomethyl-L-arginine. Furthermore, when incubated with L-(guanido-/sup 15/N/sub 2/)arginine, the nitric oxide was /sup 15/N-labeled. The results show that nitric oxide is an intermediate in the L-arginine to NO/sub 2//sup -/, NO/sub 3//sup -/, and citrulline pathway. L-Arginine is required for the activation of macrophages to the bactericidal/tumoricidal state and suggests that nitric oxide is serving as an intracellular signal for this activation process in a manner similar to that very recently observed in endothelial cells, where nitric oxide leads to vascular smooth muscle relaxation.

  7. 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.

  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. 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

  10. Endothelial nitric oxide synthase mediates lymphangiogenesis and lymphatic metastasis

    PubMed Central

    Lahdenranta, Johanna; Hagendoorn, Jeroen; Padera, Timothy P.; Hoshida, Tohru; Nelson, Gregory; Kashiwagi, Satoshi; Jain, Rakesh K.; Fukumura, Dai

    2009-01-01

    Lymphatic metastasis is a critical determinant of cancer prognosis. Recently, several lymphangiogenic molecules such as vafscular endothelial growth factor (VEGF)-C and -D were identified. However, the mechanistic understanding of lymphatic metastasis is still in infancy. Nitric oxide (NO) plays a crucial role in regulating blood vessel growth and function as well as lymphatic vessel function. NOS expression correlates with lymphatic metastasis. However, causal relationship between NOS and lymphatic metastasis has not been documented. To this end, we first show that both VEGF receptor-2 and -3 stimulation activate eNOS in lymphatic endothelial cells and that NO donors induce proliferation and/or survival of cultured lymphatic endothelial cells in a dose dependent manner. We find that an NOS inhibitor L-NMMA blocked regeneration of lymphatic vessels. Using intravital microscopy that allows us to visualize the steps of lymphatic metastasis, we show that genetic deletion of eNOS as well as NOS blockade attenuates peritumor lymphatic hyperplasia of VEGF-C-overexpressing T241 fibrosarcomas and decreases the delivery of metastatic tumor cells to the draining lymph nodes. Genetic deletion of eNOS in the host also leads to a decrease in T241 tumor cell dissemination to the lymph nodes and macroscopic lymph node metastasis of B16F10 melanoma. These findings indicate that eNOS mediates VEGF-C induced lymphangiogenesis and, consequently, plays a critical role in lymphatic metastasis. Our findings explain the correlation between NOS and lymphatic metastasis seen in a number of human tumors and open the door for potential therapies exploiting NO signaling to treat diseases of the lymphatic system. PMID:19318557

  11. Phylogenesis of constitutively formed nitric oxide in non-mammals.

    PubMed

    Toda, N; Ayajiki, K

    2006-01-01

    It is widely recognized that nitric oxide (NO) in mammalian tissues is produced from L-arginine via catalysis by NO synthase (NOS) isoforms such as neuronal NOS (nNOS) and endothelial NOS (eNOS) that are constitutively expressed mainly in the central and peripheral nervous system and vascular endothelial cells, respectively. This review concentrates only on these constitutive NOS (cNOS) isoforms while excluding information about iNOS, which is induced mainly in macrophages upon stimulation by cytokines and polysaccharides. The NO signaling pathway plays a crucial role in the functional regulation of mammalian tissues and organs. Evidence has also been accumulated for the role of NO in invertebrates and non-mammalian vertebrates. Expression of nNOS in the brain and peripheral nervous system is widely determined by staining with NADPH (reduced nicotinamide adenine dinucleotide phosphate) diaphorase or NOS immunoreactivity, and functional roles of NO formed by nNOS are evidenced in the early phylogenetic stages (invertebrates and fishes). On the other hand, the endothelium mainly produces vasodilating prostanoids rather than NO or does not liberate endothelium-derived relaxing factor (EDRF) (fishes), and the ability of endothelial cells to liberate NO is observed later in phylogenetic stages (amphibians). This review article summarizes various types of interesting information obtained from lower organisms (invertebrates, fishes, amphibians, reptiles, and birds) about the properties and distribution of nNOS and eNOS and also the roles of NO produced by the cNOS as an important intercellular signaling molecule. PMID:17236649

  12. The shaping of nitric oxide signals by a cellular sink

    PubMed Central

    Griffiths, Charmaine; Garthwaite, John

    2001-01-01

    The functioning of nitric oxide (NO) as a biological messenger necessitates that there be an inactivation mechanism. Cell suspensions from a rat brain region rich in the NO signalling pathway (cerebellum) were used to investigate the existence of such a mechanism and to determine its properties.The cells consumed NO in a manner that could not be explained by reaction with O2, superoxide ions or contaminating red blood cells. Functionally, the mechanism was able to convert constant rates of NO formation into low steady-state NO concentrations. For example, with NO produced at 90 nm min−1, the cells (20 × 106 ml−1) held NO at 20 nm. Various other cell types behaved similarly.The influence of NO inactivation on the ability of NO to access its receptor, soluble guanylyl cyclase, was explored by measuring cGMP accumulation in response to the clamped NO concentrations. The extrapolated steady-state EC50 for NO was 2 nm, a concentration readily achieved by low NO release rates, despite inactivation.When confronted by higher NO release rates for several minutes, the clamping mechanism failed, resulting in a progressive rise in NO concentration. While the clamp was maintained, cellular respiration was unaffected but, as it failed, respiration became inhibited by NO. The IC50 was measured to be 120 nm (at 100–140 μm O2).It is concluded that cerebellar (and other) cells possess a powerful NO inactivation mechanism that, extrapolated to the whole tissue, would impose on NO a half-life of around 100 ms. This and other properties of the device appear ideal for shaping low-level NO signals for activating its receptor, soluble guanylyl cyclase, whilst avoiding adverse effects on mitochondrial function. The exhaustibility of the mechanism provides a scenario for NO to become toxic. PMID:11691877

  13. Dexamethasone, tetrahydrobiopterin and uncoupling of endothelial nitric oxide synthase

    PubMed Central

    Tobias, Silke; Habermeier, Alice; Siuda, Daniel; Reifenberg, Gisela; Xia, Ning; Closs, Ellen I; Förstermann, Ulrich; Li, Huige

    2015-01-01

    Objective To find out whether dexamethasone induces an uncoupling of the endothelial nitric oxide synthase (eNOS). Methods & Results A major cause of eNOS uncoupling is a deficiency of its cofactor tetrahydrobiopterin (BH4). Treatment of human EA.hy 926 endothelial cells with dexamethasone decreased mRNA and protein expression of both BH4-synthesizing enzymes: GTP cyclohydrolase I and dihydrofolate reductase. Consistently, a concentration- and time-dependent reduction of BH4, dihydrobiopterin (BH2) as well as BH4: BH2 ratio was observed in dexamethasone-treated cells. Surprisingly, no evidence for eNOS uncoupling was found. We then analyzed the expression and phosphorylation of the eNOS enzyme. Dexamethasone treatment led to a down-regulation of eNOS protein and a reduction of eNOS phosphorylation at serine 1177. A reduction of eNOS expression may lead to a relatively normal BH4: eNOS molar ratio in dexamethasone-treated cells. Because the BH4-eNOS stoichiometry rather than the absolute BH4 amount is the key determinant of eNOS functionality (i.e., coupled or uncoupled), the down-regulation of eNOS may represent an explanation for the absence of eNOS uncoupling. Phosphorylation of eNOS at serine 1177 is needed for both the NO-producing activity of the coupled eNOS and the superoxide-producing activity of the uncoupled eNOS. Thus, a reduction of serine 1177 phosphorylation may render a potentially uncoupled eNOS hardly detectable. Conclusions Although dexamethasone reduces BH4 levels in endothelial cells, eNOS uncoupling is not evident. The reduction of NO production in dexamethasone-treated endothelial cells is mainly attributable to reduced eNOS expression and decreased eNOS phosphorylation at serine 1177. PMID:26512245

  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. 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

  16. 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

  17. 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

  18. Natural nitric oxide (NO) inhibitors from Chloranthus japonicus.

    PubMed

    Guo, Yan-Qiong; Zhao, Jing-Jun; Li, Zhen-Zhen; Tang, Gui-Hua; Zhao, Zhi-Min; Yin, Sheng

    2016-07-01

    Eight new lindenane sesquiterpenoid dimers, chlojapolides A-H (1-8), along with 11 known analogues were isolated from the whole plant of Chloranthus japonicus. Their structures including absolute configurations were elucidated by spectral and chemical methods. All the compounds were examined for their inhibitory effects on the nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW 264.7 macrophages, and compounds 1, 11, 13, and 17 exhibited pronounced inhibition with IC50 values in the range of 6.91-15.75μM, being more active than the positive control, quercetin (IC50=15.90μM). PMID:27177824

  19. Flavanols, the Kuna, Cocoa Consumption, and Nitric Oxide

    PubMed Central

    Hollenberg, Norman K.; Fisher, Naomi D.L.; McCullough, Marjorie L.

    2013-01-01

    The Kuna Indians who reside in an archipelago on the Caribbean Coast of Panama have very low blood pressure levels, live longer than other Panamanians, and have a reduced frequency of myocardial infarction, stroke, diabetes mellitus, and cancer -- at least on their death certificates. One outstanding feature of their diet includes a very high intake of flavanol-rich cocoa. Flavonoids in cocoa activate nitric oxide synthesis in healthy humans. The possibility that the high flavanol intake protects the Kuna against high blood pressure, ischemic heart disease, stroke, diabetes mellitus, and cancer is sufficiently intriguing and sufficiently important that large, randomized controlled clinical trials should be pursued. PMID:20409950

  20. Fractional exhaled nitric oxide-measuring devices: technology update

    PubMed Central

    Maniscalco, Mauro; Vitale, Carolina; Vatrella, Alessandro; Molino, Antonio; Bianco, Andrea; Mazzarella, Gennaro

    2016-01-01

    The measurement of exhaled nitric oxide (NO) has been employed in the diagnosis of specific types of airway inflammation, guiding treatment monitoring by predicting and assessing response to anti-inflammatory therapy and monitoring for compliance and detecting relapse. Various techniques are currently used to analyze exhaled NO concentrations under a range of conditions for both health and disease. These include chemiluminescence and electrochemical sensor devices. The cost effectiveness and ability to achieve adequate flexibility in sensitivity and selectivity of NO measurement for these methods are evaluated alongside the potential for use of laser-based technology. This review explores the technologies involved in the measurement of exhaled NO. PMID:27382340

  1. 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.

  2. Nitric oxide-oxygen radicals interactions in atherosclerosis.

    PubMed

    Rubbo, H; Batthyany, C; Radi, R

    2000-01-01

    Atherosclerosis is one of the most common diseases and the principal cause of death in western civilization. The pathogenesis of this disease can be explained on the basis of the 'oxidative-modification hypothesis,' which proposes that low-density lipoprotein (LDL) oxidation represents a key early event. Nitric oxide (*NO) regulates critical lipid membrane and lipoprotein oxidation events by a) contributing to the formation of more potent secondary oxidants from superoxide (i.e.: peroxynitrite), and b) its antioxidant properties through termination reactions with lipid radicals to possibly less reactive secondary nitrogen-containing products (LONO, LOONO). Relative rates of production and steady state concentrations of superoxide and *NO and cellular sites of production will profoundly influence the expression of differential oxidant injury-enhancing and protective effects of *NO. Full understanding of the physiological roles of *NO, coupled with detailed insight into *NO regulation of oxygen radical-dependent reactions, will yield a more rational basis for intervention strategies directed toward oxidant-dependent atherogenic processes. PMID:15693284

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

    PubMed

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

    2006-05-01

    Fibromyalgia (FM) is a common chronic pain syndrome with an unknown etiology. Recent years added new information to our understanding of FM pathophysiology. Researches on genetics, biogenic amines, neurotransmitters, hypothalamic-pituitary-adrenal axis hormones, oxidative stress, and mechanisms of pain modulation, central sensitization, and autonomic functions in FM revealed various abnormalities indicating that multiple factors and mechanisms are involved in the pathogenesis of FM. Oxidative stress and nitric oxide may play an important role in FM pathophysiology, however it is still not clear whether oxidative stress abnormalities documented in FM are the cause or the effect. This should encourage further researches evaluating the potential role of oxidative stress and nitric oxide in the pathophysiology of FM and the efficacy of antioxidant treatments (omega-3 and -6 fatty acids, vitamins and others) in double blind and placebo controlled trials. These future researches will enhance our understanding of the complex pathophysiology of this disorder. PMID:16328420

  4. 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

  5. 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 μm. The laser source is a continuous-wave, room temperature external cavity quantum cascade laser. An acousto-optic modulator is used to abruptly turn off the optical power incident on the cavity when the laser and cavity pass through resonance.

  6. Relevance of Chemical Kinetics for Medicine: The Case of Nitric Oxide

    NASA Astrophysics Data System (ADS)

    Balaban, Alexandru T.; Seitz, William

    2003-06-01

    Nitric oxide, NO, is central to many physiological processes including regulation of blood pressure and nerve signal transmission. Enzymes in endothelial cells and in the brain of mammals continuously synthesize it—generally in low and carefully regulated concentrations. The well known reaction of NO with oxygen to produce toxic nitrogen dioxide, NO2, has a rate which is bimolecular in NO. High concentrations of NO, as are found often in industrial plants or cigarettes, react rapidly with oxygen to produce toxic NO2. However, the half-life of NO at low NO concentrations as found in solutions and gases occurring in blood vessels, brains, and lungs is sufficiently long for biochemical purposes. Kinetics, then, determines the harmful versus helpful aspects of nitric oxide. At concentrations below 80 ppm NO is used in hospitals for lung vasodilation of preterm newborns and patients with pulmonary distress.

  7. 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.

  8. 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

  9. 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...

  10. The role of nitric oxide in ocular surface cells.

    PubMed

    Kim, Jae Chan; Park, Gun Sic; Kim, Jin Kook; Kim, Young Myeong

    2002-06-01

    The role of nitric oxide (NO) in the ocular surface remains unknown. We investigated the conditions leading to an increase of NO generation in tear and the main sources of NO in ocular surface tissue. We evaluated the dual action (cell survival or cell death) of NO depending on its amount. We measured the concentration of nitrite plus nitrate in the tears of ocular surface diseases and examined the main source of nitric oxide synthase (NOS). When cultured human corneal fibroblast were treated with NO producing donor with or without serum, the viabilities of cells was studied. We found that the main sources of NO in ocular surface tissue were corneal epithelium, fibroblast, endothelium, and inflammatory cells. Three forms of NOS (eNOS, bNOS, and iNOS) were expressed in experimentally induced inflammation. In the fibroblast culture system, the NO donor (SNAP, S-nitroso-N-acetyl-D, L-penicillamine) prevented the death of corneal fibroblast cells caused by serum deprivation in a dose dependent manner up to 500 micrometer SNAP, but a higher dose decreased cell viability. This study suggested that NO might act as a double-edged sword in ocular surface diseases depending on the degree of inflammation related with NO concentration. PMID:12068145

  11. Interaction of Nitric Oxide with Catalase: Structural and Kinetic Analysis

    PubMed Central

    2011-01-01

    We present the structures of bovine catalase in its native form and complexed with ammonia and nitric oxide, obtained by X-ray crystallography. Using the NO generator 1-(N,N-diethylamino)diazen-1-ium-1,2-diolate, we were able to generate sufficiently high NO concentrations within the catalase crystals that substantial occupation was observed despite a high dissociation rate. Nitric oxide seems to be slightly bent from the heme normal that may indicate some iron(II) character in the formally ferric catalase. Microspectrophotometric investigations inline with the synchrotron X-ray beam reveal photoreduction of the central heme iron. In the cases of the native and ammonia-complexed catalase, reduction is accompanied by a relaxation phase. This is likely not the case for the catalase NO complex. The kinetics of binding of NO to catalase were investigated using NO photolyzed from N,N′-bis(carboxymethyl)-N,N′-dinitroso-p-phenylenediamine using an assay that combines catalase with myoglobin binding kinetics. The off rate is 1.5 s–1. Implications for catalase function are discussed. PMID:21524057

  12. 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

  13. 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.

  14. Neuronal Nitric Oxide Synthase in Vascular Physiology and Diseases

    PubMed Central

    Costa, Eduardo D.; Rezende, Bruno A.; Cortes, Steyner F.; Lemos, Virginia S.

    2016-01-01

    The family of nitric oxide synthases (NOS) has significant importance in various physiological mechanisms and is also involved in many pathological processes. Three NOS isoforms have been identified: neuronal NOS (nNOS or NOS 1), endothelial NOS (eNOS or NOS 3), and an inducible NOS (iNOS or NOS 2). Both nNOS and eNOS are constitutively expressed. Classically, eNOS is considered the main isoform involved in the control of the vascular function. However, more recent studies have shown that nNOS is present in the vascular endothelium and importantly contributes to the maintenance of the homeostasis of the cardiovascular system. In physiological conditions, besides nitric oxide (NO), nNOS also produces hydrogen peroxide (H2O2) and superoxide (O2•-) considered as key mediators in non-neuronal cells signaling. This mini-review highlights recent scientific releases on the role of nNOS in vascular homeostasis and cardiovascular disorders such as hypertension and atherosclerosis. PMID:27313545

  15. 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.

  16. 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

  17. Cytokinins can act as suppressors of nitric oxide in Arabidopsis

    PubMed Central

    Liu, Wei-Zhong; Kong, Dong-Dong; Gu, Xue-Xin; Gao, Hong-Bo; Wang, Jin-Zheng; Xia, Min; Gao, Qian; Tian, Li-Li; Xu, Zhang-Hong; Bao, Fang; Hu, Yong; Ye, Neng-Sheng; Pei, Zhen-Ming; He, Yi-Kun

    2013-01-01

    Maintaining nitric oxide (NO) homeostasis is essential for normal plant physiological processes. However, very little is known about the mechanisms of NO modulation in plants. Here, we report a unique mechanism for the catabolism of NO based on the reaction with the plant hormone cytokinin. We screened for NO-insensitive mutants in Arabidopsis and isolated two allelic lines, cnu1-1 and 1–2 (continuous NO-unstressed 1), that were identified as the previously reported altered meristem program 1 (amp1) and as having elevated levels of cytokinins. A double mutant of cnu1-2 and nitric oxide overexpression 1 (nox1) reduced the severity of the phenotypes ascribed to excess NO levels as did treating the nox1 line with trans-zeatin, the predominant form of cytokinin in Arabidopsis. We further showed that peroxinitrite, an active NO derivative, can react with zeatin in vitro, which together with the results in vivo suggests that cytokinins suppress the action of NO most likely through direct interaction between them, leading to the reduction of endogenous NO levels. These results provide insights into NO signaling and regulation of its bioactivity in plants. PMID:23319631

  18. A protective role for endothelial nitric oxide synthase in glomerulonephritis.

    PubMed

    Heeringa, Peter; Steenbergen, Eric; van Goor, Harry

    2002-03-01

    In acute glomerulonephritis (GN), increased nitric oxide (NO) production occurs, suggesting a pathophysiological role for NO in the disease process. Although NO potentially could have both toxic as well as protective effects, its exact role in the pathophysiology of GN is unclear and may depend on the NOS isoform generating NO. The protective effects of NO such as prevention of leukocyte and platelet activation and adhesion have been attributed to NO generated by endothelial nitric oxide synthase (eNOS). Evidence for a beneficial role for eNOS includes the demonstration of reduced eNOS expression in experimental models of GN as well as human biopsy specimens that is mostly likely due to endothelial cell necrosis. Reduced NO production in GN also may occur through reaction of NO with superoxide anions or the myeloperoxidase (MPO)/hypochlorous acid (HOCL) system. Further evidence has been provided by the observation that in several experimental models of GN, glomerular injury is exacerbated following treatment with non-selective NO inhibitors. Finally, the development of GN is severely aggravated in mice lacking a functional gene for eNOS as compared to wild-type mice, providing direct support for a protective role of eNOS-derived NO in acute GN. PMID:11849432

  19. 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.

  20. 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

  1. 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

  2. Tipping off endothelial tubes: nitric oxide drives tip cells.

    PubMed

    Priya, Mani Krishna; Sahu, Giriraj; Soto-Pantoja, David R; Goldy, Naga; Sundaresan, Abaya Meenakshi; Jadhav, Vivek; Barathkumar, T R; Saran, Uttara; Jaffar Ali, B M; Roberts, David D; Bera, Amal Kanti; Chatterjee, Suvro

    2015-04-01

    Angiogenesis, the formation of new blood vessels from pre-existing vessels, is a complex process that warrants cell migration, proliferation, tip cell formation, ring formation, and finally tube formation. Angiogenesis is initiated by a single leader endothelial cell called "tip cell," followed by vessel elongation by "stalk cells." Tip cells are characterized by their long filopodial extensions and expression of vascular endothelial growth factor receptor-2 and endocan. Although nitric oxide (NO) is an important modulator of angiogenesis, its role in angiogenic sprouting and specifically in tip cell formation is poorly understood. The present study tested the role of endothelial nitric oxide synthase (eNOS)/NO/cyclic GMP (cGMP) signaling in tip cell formation. In primary endothelial cell culture, about 40% of the tip cells showed characteristic sub-cellular localization of eNOS toward the anterior progressive end of the tip cells, and eNOS became phosphorylated at serine 1177. Loss of eNOS suppressed tip cell formation. Live cell NO imaging demonstrated approximately 35% more NO in tip cells compared with stalk cells. Tip cells showed increased level of cGMP relative to stalk cells. Further, the dissection of NO downstream signaling using pharmacological inhibitors and inducers indicates that NO uses the sGC/cGMP pathway in tip cells to lead angiogenesis. Taken together, the present study confirms that eNOS/NO/cGMP signaling defines the direction of tip cell migration and thereby initiates new blood vessel formation. PMID:25510468

  3. Endostatin induces acute endothelial nitric oxide and prostacyclin release

    SciTech Connect

    Li Chunying; Harris, M. Brennan; Venema, Virginia J.; Venema, Richard C. . E-mail: rvenema@mcg.edu

    2005-04-15

    Chronic exposure to endostatin (ES) blocks endothelial cell (EC) proliferation, and migration and induces EC apoptosis thereby inhibiting angiogenesis. Nitric oxide (NO) and prostacyclin (PGI{sub 2}), in contrast, play important roles in promoting angiogenesis. In this study, we examined the acute effects of ES on endothelial NO and PGI{sub 2} production. Unexpectedly, a cGMP reporter cell assay showed that ES-induced acute endothelial NO release in cultured bovine aortic endothelial cells (BAECs). Enzyme immunoassay showed that ES also induced an acute increase in PGI{sub 2} production in BAECs. These results were confirmed by ex vivo vascular ring studies that showed vascular relaxation in response to ES. Immunoblot analysis showed that ES stimulated acute phosphorylation of endothelial nitric oxide synthase (eNOS) at Ser116, Ser617, Ser635, and Ser1179, and dephosphorylation at Thr497 in BAECs, events associated with eNOS activation. Short-term exposure of EC to ES, therefore, unlike long-term exposure which is anti-angiogenic, may be pro-angiogenic.

  4. Shear-Induced Nitric Oxide Production by Endothelial Cells.

    PubMed

    Sriram, Krishna; Laughlin, Justin G; Rangamani, Padmini; Tartakovsky, Daniel M

    2016-07-12

    We present a biochemical model of the wall shear stress-induced activation of endothelial nitric oxide synthase (eNOS) in an endothelial cell. The model includes three key mechanotransducers: mechanosensing ion channels, integrins, and G protein-coupled receptors. The reaction cascade consists of two interconnected parts. The first is rapid activation of calcium, which results in formation of calcium-calmodulin complexes, followed by recruitment of eNOS from caveolae. The second is phosphorylation of eNOS by protein kinases PKC and AKT. The model also includes a negative feedback loop due to inhibition of calcium influx into the cell by cyclic guanosine monophosphate (cGMP). In this feedback, increased nitric oxide (NO) levels cause an increase in cGMP levels, so that cGMP inhibition of calcium influx can limit NO production. The model was used to predict the dynamics of NO production by an endothelial cell subjected to a step increase of wall shear stress from zero to a finite physiologically relevant value. Among several experimentally observed features, the model predicts a highly nonlinear, biphasic transient behavior of eNOS activation and NO production: a rapid initial activation due to the very rapid influx of calcium into the cytosol (occurring within 1-5 min) is followed by a sustained period of activation due to protein kinases. PMID:27410748

  5. 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

  6. 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.

  7. 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

  8. Endothelial nitric oxide synthase (NOS) deficiency affects energy metabolism pattern in murine oxidative skeletal muscle.

    PubMed Central

    Momken, Iman; Fortin, Dominique; Serrurier, Bernard; Bigard, Xavier; Ventura-Clapier, Renée; Veksler, Vladimir

    2002-01-01

    Oxidative capacity of muscles correlates with capillary density and with microcirculation, which in turn depend on various regulatory factors, including NO generated by endothelial nitric oxide synthase (eNOS). To determine the role of eNOS in patterns of regulation of energy metabolism in various muscles, we studied mitochondrial respiration in situ in saponin-permeabilized fibres as well as the energy metabolism enzyme profile in the cardiac, soleus (oxidative) and gastrocnemius (glycolytic) muscles isolated from mice lacking eNOS (eNOS(-/-)). In soleus muscle, the absence of eNOS induced a marked decrease in both basal mitochondrial respiration without ADP (-32%; P <0.05) and maximal respiration in the presence of ADP (-29%; P <0.05). Furthermore, the eNOS(-/-) soleus muscle showed a decrease in total creatine kinase (-29%; P <0.05), citrate synthase (-31%; P <0.01), adenylate kinase (-27%; P <0.05), glyceraldehyde-3-phosphate dehydrogenase (-43%; P <0.01) and pyruvate kinase (-26%; P <0.05) activities. The percentage of myosin heavy chains I (slow isoform) was significantly increased from 24.3+/-1.5% in control to 30.1+/-1.1% in eNOS(-/-) soleus muscle ( P <0.05) at the expense of a slight non-significant decrease in the three other (fast) isoforms. Besides, eNOS(-/-) soleus showed a 28% loss of weight. Interestingly, we did not find differences in any parameters in cardiac and gastrocnemius muscles compared with respective controls. These results show that eNOS knockout has an important effect on muscle oxidative capacity as well on the activities of energy metabolism enzymes in oxidative (soleus) muscle. The absence of such effects in cardiac and glycolytic (gastrocnemius) muscle suggests a specific role for eNOS-produced NO in oxidative skeletal muscle. PMID:12123418

  9. Furoxan-Bearing Micelles for Nitric Oxide Delivery.

    PubMed

    Hasegawa, Urara; Wang, Tengjiao; Chen, Jerry J Y; Uyama, Hiroshi; van der Vlies, André J

    2016-07-01

    Furoxans, or 1,2,5-oxadiazole-N-oxides, are a class of nitric oxide (NO)-donating compounds that release NO in response to thiol-containing molecules. In this study, polymeric micelles bearing furoxan moieties are prepared from an amphiphilic block copolymer consisting of a hydrophobic furoxan-bearing block and a hydrophilic poly(N-acryloylmorpholine) block. The block copolymer is prepared using a combination of the reversible addition-fragmentation chain transfer polymerization and the copper-catalyzed Huisgen cycloaddition techniques. The block copolymers form spherical micelles with a diameter of 50 nm by self-assembly in water. The micelles release NO in response to cysteine and show improved stability against hydrolytic decomposition. Furthermore, the micelles show a synergistic anti-proliferative effect with ibuprofen in human colon cancer cells. PMID:26953715

  10. 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

  11. Nitric Oxide-Releasing Dendrimers as Antibacterial Agents

    PubMed Central

    Sun, Bin; Slomberg, Danielle L.; Chudasama, Shalini L.; Lu, Yuan

    2012-01-01

    The antibacterial activity of a series of nitric oxide (NO)-releasing poly(propylene imine) (PPI) dendrimers was evaluated against both Gram-positive and Gram-negative pathogenic bacteria, including methicillin-resistant Staphylococcus aureus. A direct comparison of the bactericidal efficacy between NO-releasing and control PPI dendrimers (i.e., non-NO-releasing) revealed both enhanced biocidal action of NO-releasing dendrimers and reduced toxicity against mammalian fibroblast cells. Antibacterial activity for the NO donor-functionalized PPI dendrimers was shown to be a function of both dendrimer size (molecular weight) and exterior functionality. In addition to minimal toxicity against fibroblasts, NO-releasing PPI dendrimers modified with styrene oxide exhibited the greatest biocidal activity (≥9.999% killing) against all bacterial strains tested. The N-diazeniumdiolate NO donor-functionalized PPI dendrimers presented in this study hold promise as effective NO-based therapeutics for combating bacterial infections. PMID:23013537

  12. Enhancement of nitric oxide generation by low frequency electromagnetic field.

    PubMed

    Yoshikawa; Tanigawa; Tanigawa; Imai; Hongo; Kondo

    2000-07-01

    Oxidative stress is implicated in the intracellular signal transduction pathways for nitric oxide synthase (NOS) induction. The electromagnetic field (EMF) is believed to increase the free radical lifespan [S. Roy, Y. Noda, V. Eckert, M.G. Traber, A. Mori, R. Liburdy, L. Packer, The phorbol 12-myristate 13-acetate (PMA)-induced oxidative burst in rat peritoneal neutrophils is increased by a 0.1 mT (60 Hz) magnetic field, FEBS Lett. 376 (1995) 164-6; F.S. Prato, M. Kavaliers, J.J. Carson, Behavioural evidence that magnetic field effects in the land snail, Cepaea nemoralis, might not depend on magnetite or induced electric currents, Bioelectromagnetics 17 (1996) 123-30; A.L. Hulbert, J. Metcalfe, R. Hesketh, Biological response to electromagnetic fields, FASEB 12 (1998) 395-420]. We tested the effects of EMF on endotoxin induced nitric oxide (NO) generation in vivo. Male BALB/C mice were injected with lipopolysaccharide (LPS) intraperitoneously (i.p.), followed by the exposure to EMF (0.1 mT, 60 Hz). Five hours and 30 min after the LPS administration, mice were administered with a NO spin trap, ferrous N-methyl-D-glucaminedithiocarbamate (MGD-Fe). Thirty minutes later, mice were sacrificed, and their livers were removed. The results were compared to three control groups: group A (LPS (-) EMF(-)); group B (LPS(-) EMF(+)); group C (LPS(+) EMF(-)). The ESR spectra of obtained livers were examined at room temperature. Three-line spectra of NO adducts were observed in the livers of all groups. In groups A and B very weak signals were observed, but in groups C and D strong spectra were observed. The signal intensity of the NO adducts in Group D was also significantly stronger than that in Group C. EMF itself did not induce NO generation, however, it enhanced LPS induced NO generation in vivo. PMID:10927193

  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. Interaction of caveolin-1, nitric oxide, and nitric oxide synthases in hypoxic human SK-N-MC neuroblastoma cells.

    PubMed

    Shen, Jiangang; Lee, Waisin; Li, Yue; Lau, Chi Fai; Ng, Kwong Man; Fung, Man Lung; Liu, Ke Jian

    2008-10-01

    Neuroblastoma cells are capable of hypoxic adaptation, but the mechanisms involved are not fully understood. We hypothesized that caveolin-1 (cav-1), a plasma membrane signal molecule, might play a role in protecting neuroblastoma cells from oxidative injury by modulating nitric oxide (NO) production. We investigated the alterations of cav-1, cav-2, nitric oxide synthases (NOS), and NO levels in human SK-N-MC neuroblastoma cells exposed to hypoxia with 2% [O2]. The major discoveries include: (i) cav-1 but not cav-2 was up-regulated in the cells exposed to 15 h of hypoxia; (ii) NO donor 1-[N, N-di-(2-aminoethyl) amino] diazen-1-ium-1, 2-diolate up-regulated the expression of cav-1, whereas the non-selective NOS inhibitor N(G)-nitro-L-arginine methyl ester and inducible NOS (iNOS) inhibitor 1400W each abolished the increase in cav-1 expression in the hypoxic SK-N-MC cells. These results suggest that iNOS-induced NO production contributes to the up-regulation of cav-1 in the hypoxic SK-N-MC cells. Furthermore, we studied the roles played by cav-1 in regulating NO, NOS, and apoptotic cell death in the SK-N-MC cells subjected to 15 h of hypoxic treatment. Both cav-1 transfection and cav-1 scaffolding domain peptide abolished the induction of iNOS, reduced the production of NO, and reduced the rates of apoptotic cell death in the hypoxic SK-N-MC cells. These results suggest that increased expression of cav-1 in response to hypoxic stimulation could prevent oxidative injury induced by reactive oxygen species. The interactions of cav-1, NO, and NOS could be an important signal pathway in protecting the neuroblastoma cells from oxidative injury, contributing to the hypoxic tolerance of neuroblastoma cells. PMID:18717816

  15. Lipopolysaccharide induces nitric oxide synthase expression and platelet-activating factor increases nitric oxide production in human fetal membranes in culture

    PubMed Central

    Seyffarth, Gunter; Nelson, Paul N; Dunmore, Simon J; Rodrigo, Nalinda; Murphy, Damian J; Carson, Ray J

    2004-01-01

    Background Platelet-activating factor and nitric oxide may be involved in the initiation of human labour as inflammatory mediators. The aim of this study was to test whether platelet-activating factor and lipopolysaccharide were able to induce nitric oxide synthase expression and stimulate the production of nitric oxide in human fetal membrane explants in culture. Methods Fetal membranes were collected from Caesarean sections at term. RNA was extracted from membranes and subjected to a qualitative RT-PCR to assess the baseline expression of iNOS. Discs of fetal membranes were cultured for 24 hours in the presence of platelet-activating factor at a dose range of 0.1 nanomolar – 1 micomolar or 1 microgram/ml lipopolysaccharide. Nitric oxide production was measured via nitrite ions in the culture medium and mRNA for iNOS was detected by RT-PCR. Results Culturing the membrane discs in medium containing serum induced nitric oxide synthase expression and platelet-activating factor significantly stimulated the production of nitric oxide under these conditions. When cultured without serum inducible nitric oxide synthase expression was induced by lipopolysaccharide, but not by platelet-activating factor. Conclusion Platelet-activating factor may have a role in the initiation of labour, at term or preterm, via the increased local production of nitric oxide as an inflammatory mediator. In this model of intrauterine infection, lipopolysaccharide was found to induce iNOS expression by fetal membranes, and this mechanism could be involved in preterm labour. PMID:15191613

  16. 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

  17. 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

  18. Serum nitric oxide concentrations in patients with multiple sclerosis and patients with epilepsy.

    PubMed

    Ibragic, Saida; Sofic, Emin; Suljic, Enra; Avdagic, Nesina; Bajraktarevic, Azra; Tahirovic, Ismet

    2012-01-01

    Nitric oxide (NO), a neurotransmitter and a free radical, has been purported to be involved in numerous neurological diseases. We investigated the serum nitric oxide concentration in 30 patients with multiple sclerosis (MS), in 30 patients with epilepsy and in 30 control subjects. The aim was also to determine whether a statistically significant difference in serum NO concentrations exists between the groups of interest. The total serum nitric oxide concentration was measured using the Griess reaction after reducing nitrates to nitrites with elemental zinc. In the group multiple sclerosis, the mean NO concentrations were X ± SEM = 31.02 ± 1.79 μmol/l, in the control group X ± SEM = 25.31 ± 1.44 μmol/l and in the group epilepsy X ± SEM = 22.51 ± 1.28 μmol/l. Student's t test showed a statistically significant difference between subjects with multiple sclerosis and the control group (p = 0.013), as well as between the groups multiple sclerosis and epilepsy (p = 0.0002). This data confirms that NO may play an important role in the pathogenesis of multiple sclerosis, whereas its role in epilepsy still remains unclear. PMID:21779769

  19. 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...

  20. 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...

  1. 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

    ... week of pregnancy) with respiratory failure. Inhaled nitric oxide therapy is typically administered in...-term infants, use of this therapy may shorten the length of time respiratory support is required... receive respiratory support? Are there short-term risks of inhaled nitric oxide therapy among...

  2. 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...

  3. Nitric Oxide Mediates the Stress Response Induced by Diatom Aldehydes in the Sea Urchin Paracentrotus lividus

    PubMed Central

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

    2011-01-01

    Diatoms are ubiquitous and abundant primary producers that have been traditionally considered as a beneficial food source for grazers and for the transfer of carbon through marine food webs. However, many diatom species produce polyunsaturated aldehydes that disrupt development in the offspring of grazers that feed on these unicellular algae. Here we provide evidence that production of the physiological messenger nitric oxide increases after treatment with the polyunsaturated aldehyde decadienal in embryos of the sea urchin Paracentrotus lividus. At high decadienal concentrations, nitric oxide mediates initial apoptotic events leading to loss of mitochondrial functionality through the generation of peroxynitrite. At low decadienal concentrations, nitric oxide contributes to the activation of hsp70 gene expression thereby protecting embryos against the toxic effects of this aldehyde. When nitric oxide levels were lowered by inhibiting nitric oxide synthase activity, the expression of hsp70 in swimming blastula decreased and the proportion of abnormal plutei increased. However, in later pluteus stages nitric oxide was no longer able to exert this protective function: hsp70 and nitric oxide synthase expression decreased with a consequent increase in the expression of caspase-8. Our findings that nitric oxide production increases rapidly in response to a toxic exogenous stimulus opens new perspectives on the possible role of this gas as an important messenger to environmental stress in sea urchins and for understanding the cellular mechanisms underlying toxicity during diatom blooms. PMID:22022485

  4. 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

  5. The inflammatory and cytotoxic effects of a nitric oxide releasing cream on normal skin.

    PubMed

    Ormerod, A D; Copeland, P; Hay, I; Husain, A; Ewen, S W

    1999-09-01

    We describe the pro-inflammatory and cytotoxic effects of nitric oxide in vivo in human skin. Nitrite and ascorbic acid were mixed on the skin of 12 normal volunteers, three times daily, to release nitric oxide. Exposure to nitric oxide was varied by randomizing the concentration of nitrite and duration of application. Nitric oxide treated skin showed significant increases in cells expressing CD3, CD4, CD8, CD68, neutrophil elastase, ICAM-1, VCAM-1, nitrosotyrosine, p53, and apoptotic cells compared with skin treated with ascorbic acid alone. There was no significant increase in mast cells. Following application of nitric oxide there were significantly fewer CD1a positive Langerhans cells in the epidermis. These appeared to lose dendritic morphology and migrate from the epidermis. There was no significant difference in staining for Ki-67, a marker related to proliferating cell nuclear antigen, between active and control skin but staining was greater after exposure to higher dose nitric oxide than the low dose. Apoptosis, cytotoxicity, and p53 staining were relatively greater after 48 h exposure than after 24 h. These results suggest that nitric oxide is pro-inflammatory and is toxic to DNA, leading to the accumulation of p53 and subsequent apoptosis. High-dose nitric oxide paradoxically led to a smaller increase in macrophages and T cells than low dose suggesting an immunosuppressive effect of higher levels. PMID:10469339

  6. Effects of inhaled nitric oxide 10 ppm in spontaneously breathing horses anaesthetized with halothane.

    PubMed

    Young, L E; Marlin, D J; McMurphy, R M; Walsh, K; Dixon, P M

    1999-08-01

    Inhaled nitric oxide, a selective pulmonary vasodilator, is known to improve arterial oxygenation after cardiopulmonary bypass and during acute respiratory distress syndrome in humans. During general anaesthesia with spontaneous ventilation, healthy adult horses develop large alveolar-arterial oxygen tension differences. In this study, we have determined the effects of inhaled nitric oxide (10 parts per million (ppm)) on venous admixture and pulmonary haemodynamics in horses anaesthetized with halothane. Seven adult horses were studied twice in random sequence. After premedication with romifidine 100 micrograms kg-1, anaesthesia was induced with ketamine 2.2 mg kg-1 and maintained with 1.1 MAC (0.95%) of halothane in oxygen. Horses breathed spontaneously. After 65 min, each horse had nitric oxide 10 ppm added to the inspired gas for 20 min (procedure HA + NO) or anaesthesia was continued with halothane in oxygen (procedure HA). Cardiac output, minute ventilation, arterial and mixed venous oxygen and carbon dioxide tensions, and mean pulmonary and carotid arterial pressures were measured for 100 min. Shunt fraction and pulmonary and systemic vascular resistances were calculated. Shunt fraction (SF) and mean pulmonary artery pressure (PPA mean) were not different between the two groups after 65 min of general anaesthesia (HA: SF 0.20 (SD 0.06), PPA mean 45 (8) mm Hg; HA + NO: SF 0.21 (0.04), PPA mean 44 (7) mm Hg) or after 85 min (HA: SF 0.22 (0.07), PPA mean 45 (8) mm Hg; HA + NO: SF 0.20 (0.03), PPA mean 43 (7) mm Hg). There were no significant effects of time or nitric oxide inhalation on any other variable. There was a significant correlation (r = 0.80, P < 0.05) between calculated shunt fraction 65 min after induction of anaesthesia and body weight. PMID:10618949

  7. Compensatory Feto-Placental Upregulation of the Nitric Oxide System during Fetal Growth Restriction

    PubMed Central

    Pisaneschi, Silvia; Strigini, Francesca A. L.; Sanchez, Angel M.; Begliuomini, Silvia; Casarosa, Elena; Ripoli, Andrea; Ghirri, Paolo; Boldrini, Antonio; Fink, Bruno; Genazzani, Andrea R.; Coceani, Flavio; Simoncini, Tommaso

    2012-01-01

    Background Fetal Growth Restriction is often associated with a feto-placental vascular dysfunction conceivably involving endothelial cells. Our study aimed to verify this pathogenic role for feto-placental endothelial cells and, coincidentally, demonstrate any abnormality in the nitric oxide system. Methods Prenatal assessment of feto-placental vascular function was combined with measurement of nitric oxide (in the form of S-nitrosohemoglobin) and its nitrite byproduct, and of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine. Umbilical vein endothelial cells were also harvested to determine their gene profile. The study comprised term pregnancies with normal (n = 40) or small-for-gestational-age (n = 20) newborns, small-for-gestational-age preterm pregnancies (n = 15), and bi-chorial, bi-amniotic twin pregnancies with discordant fetal growth (n = 12). Results Umbilical blood nitrite (p<0.001) and S-nitrosohemoglobin (p = 0.02) rose with fetal growth restriction while asymmetric dimethylarginine decreased (p = 0.003). Nitrite rise coincided with an abnormal Doppler profile from umbilical arteries. Fetal growth restriction umbilical vein endothelial cells produced more nitrite and also exhibited reciprocal changes in vasodilator (upwards) and vasoconstrictor (downwards) transcripts. Elevation in blood nitrite and S-nitrosohemoglobin persisted postnatally in the fetal growth restriction offspring. Conclusion Fetal growth restriction is typified by increased nitric oxide production during pregnancy and after birth. This response is viewed as an adaptative event to sustain placental blood flow. However, its occurrence may modify the endothelial phenotype and may ultimately represent an element of risk for cardiovascular disease in adult life. PMID:23028913

  8. Behavioral impairments and changes of nitric oxide and inducible nitric oxide synthase in the brains of molarless KM mice.

    PubMed

    Pang, Qian; Hu, Xingxue; Li, Xinya; Zhang, Jianjun; Jiang, Qingsong

    2015-02-01

    More studies showed that as a common disorder in senior population, loss of teeth could adversely affect human cognitive function, and nitric oxide (NO) might play an important role in the cognitive function. However, the underlying mechanism has not yet been well-established. The objectives of this study are to evaluate behavior changes of KM mice after loss of molars, and levels of NO and inducible nitric oxide synthase (iNOS) in the brain in molarless condition. It is hypothesized that loss of molars of the mice tested results in the cognitive impairments and that the process is mediated by NO in the brain through the signaling pathways. Morris water maze is used to test the behavioral changes after 8 weeks of the surgery. The changes of NO and iNOS are evaluated by using Griess assay, western blot, and immunohistochemistry method. The results show that 8 weeks after loss of molars, the spatial learning and memory of KM mice impair and the levels of NO and iNOS in mice hippocampus increase. These findings suggest that molar extraction is associated with the behavioral impairment, and that the changes of NO and iNOS in the hippocampus may be involved in the behavioral changes in the molarless condition. PMID:25447296

  9. 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

  10. Nitric oxide generated from isoniazid activation by KatG: source of nitric oxide and activity against Mycobacterium tuberculosis.

    PubMed

    Timmins, Graham S; Master, Sharon; Rusnak, Frank; Deretic, Vojo

    2004-08-01

    Isonicotinic acid hydrazide (INH) is a frontline antituberculosis agent. Once taken up by Mycobacterium tuberculosis, INH requires activation by the catalase-peroxidase KatG, converting INH from its prodrug form into a range of bactericidal reactive species. Here we used 15N-labeled INH together with electron paramagnetic resonance spin trapping techniques to demonstrate that nitric oxide (NO*) is generated from oxidation at the hydrazide nitrogens during the activation of INH by M. tuberculosis KatG. We also observed that a specific scavenger of NO* provided protection against the antimycobacterial activity of INH in bacterial culture. No significant increases in mycobacterial protein nitration were detected, suggesting that NOdot; and not peroxynitrite, a nitrating metabolite of NO*, is involved in antimycobacterial action. In conclusion, INH-derived NO* has biological activity, which directly contributes to the antimycobacterial action of INH. PMID:15273113

  11. Truncating mutation in the nitric oxide synthase 1 gene is associated with infantile achalasia.

    PubMed

    Shteyer, Eyal; Edvardson, Simon; Wynia-Smith, Sarah L; Pierri, Ciro Leonardo; Zangen, Tzili; Hashavya, Saar; Begin, Michal; Yaacov, Barak; Cinamon, Yuval; Koplewitz, Benjamin Z; Vromen, Amos; Elpeleg, Orly; Smith, Brian C

    2015-03-01

    Nitric oxide is thought to have a role in the pathogenesis of achalasia. We performed a genetic analysis of 2 siblings with infant-onset achalasia. Exome analysis revealed that they were homozygous for a premature stop codon in the gene encoding nitric oxide synthase 1. Kinetic analyses and molecular modeling showed that the truncated protein product has defects in folding, nitric oxide production, and binding of cofactors. Heller myotomy had no effect in these patients, but sildenafil therapy increased their ability to drink. The finding recapitulates the previously reported phenotype of nitric oxide synthase 1-deficient mice, which have achalasia. Nitric oxide signaling appears to be involved in the pathogenesis of achalasia in humans. PMID:25479138

  12. Engineering nitric oxide synthase chimeras to function as NO dioxygenases.

    PubMed

    Wang, Zhi-Qiang; Haque, Mohammad Mahfuzul; Binder, Katherine; Sharma, Manisha; Wei, Chin-Chuan; Stuehr, Dennis J

    2016-05-01

    Nitric oxide synthases (NOSs) catalyze a two-step oxidation of l-arginine to form nitric oxide (NO) and l-citrulline. NOS contains a N-terminal oxygenase domain (NOSoxy) that is the site of NO synthesis, and a C-terminal reductase domain (NOSred) that binds nicotinamide adenine dinucleotide phosphate (NADPH), flavin adenine dinucleotide (FAD), and flavin mononucleotide (FMN) and provides electrons to the NOSoxy heme during catalysis. The three NOS isoforms in mammals inducible NOS (iNOS), neuronal NOS (nNOS), and endothelial NOS (eNOS) share high structural similarity but differ in NO release rates and catalytic properties due to differences in enzyme kinetic parameters. These parameters must be balanced for NOS enzymes to release NO, rather than consume it in a competing, inherent NO dioxygenase reaction. To improve understanding, we drew on a global catalytic model and previous findings to design three NOS chimeras that may predominantly function as NO dioxygenases: iNOSoxy/nNOSred (Wild type (WT) chimera), V346I iNOSoxy/nNOSred (V346I chimera) and iNOSoxy/S1412D nNOSred (S1412D chimera). The WT and S1412D chimeras had higher NO release than the parent iNOS, while the V346I chimera exhibited much lower NO release, consistent with expectations. Measurements indicated that a greater NO dioxygenase activity was achieved, particularly in the V346I chimera, which dioxygenated an estimated two to four NO per NO that it released, while the other chimeras had nearly equivalent NO dioxygenase and NO release activities. Computer simulations of the global catalytic model using the measured kinetic parameters produced results that mimicked the measured outcomes, and this provided further insights on the catalytic behaviors of the chimeras and basis of their increased NO dioxygenase activities. PMID:27013266

  13. Modeling nitric oxide emissions from biosolid amended soils

    NASA Astrophysics Data System (ADS)

    Roelle, Paul A.; Aneja, Viney P.; Mathur, Rohit; Vukovich, Jeff; Peirce, Jeffrey

    Utilizing a state-of-the-art mobile laboratory in conjunction with a dynamic flow-through chamber system, nitric oxide concentrations [NO] were measured and NO fluxes were calculated during the summer, winter and spring of 1999/2000. The field site where these measurements were conducted was an agricultural soil amended with biosolids from a municipal wastewater treatment facility. These NO flux values were then used to assess the impact of including biosolid amended soils as a land-use class in an air quality model. The average NO flux from this biosolid amended soil was found to be exponentially dependent on soil temperature [NO Flux ( ng N m-2 s-1)=1.07 exp(0.14 T soil) ; R2=0.81—NO Flux=71.3 ng N m -2 s-1 at 30°C]. Comparing this relationship to results of the widely applied biogenic emissions inventory system (BEIS2) model revealed that for this field site, if the BEIS2 model was used, the NO emissions would have been underestimated by a factor of 26. Using this newly developed NO flux algorithm, combined with North Carolina Division of Water Quality statistics on how many biosolid amended acres are permitted per county, county-based NO inventories from these biosolid amended soils were calculated. Results from this study indicate that county-level biogenic NO emissions can increase by as much as 18% when biosolid amended soils are included as a land-use class. The multiscale air quality simulation platform (MAQSIP) was then used to determine differences in ozone (O 3) and odd-reactive nitrogen compounds (NO y) between models run with and without the biosolid amended acreages included in the inventory. Results showed that during the daytime, when atmospheric mixing heights are typically at their greatest, any increase in O 3 or NO y concentrations predicted by the model were small (<3%). In some locations during late evening/early morning hours, ozone was found to be consumed by as much as 11%.

  14. Febrigenic signaling to the brain does not involve nitric oxide

    PubMed Central

    Steiner, Alexandre A; Rudaya, Alla Y; Ivanov, Andrei I; Romanovsky, Andrej A

    2004-01-01

    The involvement of peripheral nitric oxide (NO) in febrigenic signaling to the brain has been proposed because peripherally administered NO synthase (NOS) inhibitors attenuate lipopolysaccharide (LPS)-induced fever in rodents. However, how the unstable molecule of NO can reach the brain to trigger fever is unclear. It is also unclear whether NOS inhibitors attenuate fever by blocking febrigenic signaling or, alternatively, by suppressing thermogenesis in brown fat. Male Wistar rats were chronically implanted with jugular catheters; their colonic and tail skin temperatures (Tc and Tsk) were monitored. Study 1 was designed to determine whether the relatively stable, physiologically relevant forms of NO, that is, S-nitrosoalbumin (SNA) and S-nitrosoglutathione (SNG), are pyrogenic and whether they enhance LPS fever. At a neutral ambient temperature (Ta) of 31°C, afebrile or LPS (1 μg kg−1, i.v.)-treated rats were infused i.v. with SNA (0.34 or 4.1 μmol kg−1; the controls received NaNO2 and albumin) or SNG (10 or 60 μmol kg−1; the controls received glutathione). Tc of SNA- or SNG-treated rats never exceeded that of the controls. In Study 2, we tested whether the known fever-attenuating effect of the NOS inhibitor Nω-nitro-L-arginine methyl ester (L-NAME) at a subneutral Ta (when fever is brought about by thermogenesis) also occurs at a neutral Ta (when fever is brought about by skin vasoconstriction). At a subneutral Ta of 24°C, L-NAME (2.5 mg kg−1, i.v.) attenuated LPS (10 μg kg−1, i.v.) fever, presumably by inhibiting thermogenesis. At 31°C, L-NAME enhanced LPS fever by augmenting skin vasoconstriction (Tsk fall). In summary, both SNA and SNG had no pyrogenic effect of their own and failed to enhance LPS fever; peripheral L-NAME attenuated only fever brought about by increased thermogenesis. It is concluded that NO is uninvolved in febrigenic signaling to the brain. PMID:15006900

  15. 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

  16. Arginase activity and nitric oxide levels in patients with obstructive sleep apnea syndrome

    PubMed Central

    Yüksel, Meral; Okur, Hacer Kuzu; Pelin, Zerrin; Öğünç, Ayliz Velioğlu; Öztürk, Levent

    2014-01-01

    OBJECTIVE: Obstructive sleep apnea syndrome is characterized by repetitive obstruction of the upper airways, and it is a risk factor for cardiovascular diseases. There have been several studies demonstrating low levels of nitric oxide in patients with obstructive sleep apnea syndrome compared with healthy controls. In this study, we hypothesized that reduced nitric oxide levels would result in high arginase activity. Arginase reacts with L-arginine and produces urea and L-ornithine, whereas L-arginine is a substrate for nitric oxide synthase, which produces nitric oxide. METHODS: The study group consisted of 51 obstructive sleep apnea syndrome patients (M/F: 43/8; mean age 49±10 years of age) and 15 healthy control subjects (M/F: 13/3; mean age 46±14 years of age). Obstructive sleep apnea syndrome patients were divided into two subgroups based on the presence or absence of cardiovascular disease. Nitric oxide levels and arginase activity were measured via an enzyme-linked immunosorbent assay of serum samples. RESULTS: Serum nitric oxide levels in the control subjects were higher than in the obstructive sleep apnea patients with and without cardiovascular diseases (p<0.05). Arginase activity was significantly higher (p<0.01) in obstructive sleep apnea syndrome patients without cardiovascular diseases compared with the control group. Obstructive sleep apnea syndrome patients with cardiovascular diseases had higher arginase activity than the controls (p<0.001) and the obstructive sleep apnea syndrome patients without cardiovascular diseases (p<0.05). CONCLUSION: Low nitric oxide levels are associated with high arginase activity. The mechanism of nitric oxide depletion in sleep apnea patients suggests that increased arginase activity might reduce the substrate availability of nitric oxide synthase and thus could reduce nitric oxide levels. PMID:24714832

  17. Role of Nitric Oxide and Flavohemoglobin Homolog Genes in Aspergillus nidulans Sexual Development and Mycotoxin Production ▿ †

    PubMed Central

    Baidya, Sachin; Cary, Jeffrey W.; Grayburn, W. Scott; Calvo, A. M.

    2011-01-01

    Flavohemoglobins are widely distributed in both prokaryotes and eukaryotes. These proteins are involved in reducing nitric oxide levels. Deletion of the Aspergillus nidulans flavohemoglobin gene fhbA induced sexual development and decreased sterigmatocystin production. Supplementation with a nitric oxide-releasing compound promoted cleistothecial formation and increased nsdD and steA expression, indicating that nitric oxide induces sexual development. This is the first study on the effect of nitric oxide on morphogenesis and secondary metabolism in fungi. PMID:21642398

  18. 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

  19. Nitric Oxide Regulates Neurogenesis in the Hippocampus following Seizures

    PubMed Central

    Carreira, Bruno P.; Santos, Daniela F.; Santos, Ana I.; Carvalho, Caetana M.; Araújo, Inês 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. Anti-obesogenic role of endothelial nitric oxide synthase

    PubMed Central

    Sansbury, Brian E.; Hill, Bradford G.

    2015-01-01

    The prevalence of obesity has increased remarkably in the past four decades. Because obesity can promote the development of type 2 diabetes and cardiovascular disease, understanding the mechanisms that engender weight gain and discovering safe anti-obesity therapies are of critical importance. In particular, the gaseous signaling molecule, nitric oxide (NO), appears to be a central factor regulating adiposity and systemic metabolism. Obese and diabetic states are characterized by a deficit in bioavailable NO, with such decreases commonly attributed to downregulation of endothelial NO synthase (eNOS), loss of eNOS activity, or quenching of NO by its reaction with oxygen radicals. Gain-of-function studies, in which vascular-derived NO has been increased pharmacologically or genetically, reveal remarkable actions of NO on body composition and systemic metabolism. This review addresses the metabolic actions of eNOS and the potential therapeutic utility of harnessing its anti-obesogenic effects. PMID:25189393

  1. 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

  2. The metabolites of nitric oxide in sickle-cell disease.

    PubMed

    Rees, D C; Cervi, P; Grimwade, D; O'Driscoll, A; Hamilton, M; Parker, N E; Porter, J B

    1995-12-01

    Plasma NOx concentrations were raised in 22 acute painful crises in SCD. We have measured blood concentrations of nitric oxide metabolites (NOx) in sickle-cell disease (SCD), and shown that they are increased compared with healthy controls (P = 0.002), and haemoglobin E/beta-thalassaemic controls (P = 0.05). Concentrations in steady-state SCD were also higher than in healthy controls (P = 0.04) but not significantly different from the concentrations at the beginning of painful crises (P = 0.34). Importantly, in 12 regularly exchanged sicklers, the mean pre-transfusion NOx concentration did not differ significantly from the control population (P = 0.52), suggesting that the changes in NO metabolism can be reversed. It is unlikely that the increased concentrations of NOx in SCD result from anaemia or haemolysis as the untransfused haemoglobin E/beta-thalassaemics did not show increased levels. PMID:8547126

  3. Nitric oxide-cyclic GMP signaling in stem cell differentiation

    PubMed Central

    Mujoo, Kalpana; Krumenacker, Joshua S.; Murad, Ferid

    2011-01-01

    The nitric oxide-cyclic GMP (NO-cGMP) pathway mediates important physiological functions associated with various integrative body systems including the cardiovascular and nervous systems. Furthermore, NO regulates cell growth, survival, apoptosis, proliferation and differentiation at the cellular level. To understand the significance of the NO-cGMP pathway in development and differentiation, studies have been conducted both in developing embryos and stem cells. Manipulation of the NO-cGMP pathway by employing activators and inhibitors as pharmacological probes and/or genetic manipulation of NO signaling components has implicated the involvement of this pathway in regulation of stem cell differentiation. This review will focus on some of the work pertaining to the role of NO-cGMP in differentiation of stem cells into cells of various lineages particularly into myocardial cells and stem cell based therapy. PMID:22019632

  4. 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

  5. Erythropoietin and cerebral vascular protection: role of nitric oxide.

    PubMed

    Santhanam, Anantha Vijay R; Katusic, Zvonimir S

    2006-11-01

    Cerebral vasospasm after subarachnoid hemorrhage (SAH) is a major clinical problem causing cerebral ischemia and infarction. The pathogenesis of vasospasm is related to a number of pathological processes including endothelial damage and alterations in vasomotor function leading to narrowing of arterial diameter and a subsequent decrease in cerebral blood flow. Discovery of the tissue protective effects of erythropoietin (EPO) stimulated the search for therapeutic application of EPO for the prevention and treatment of cerebrovascular disease. Recent studies have identified the role of EPO in vascular protection mediated by the preservation of endothelial cell integrity and stimulation of angiogenesis. In this review, we discuss the EPO-induced activation of endothelial nitric oxide (NO) synthase and its contribution to the prevention of cerebral vasospasm. PMID:17049112

  6. 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

  7. Hydrogen peroxide and nitric oxide as signalling molecules in plants.

    PubMed

    Neill, Steven J; Desikan, Radhika; Clarke, Andrew; Hurst, Roger D; Hancock, John T

    2002-05-01

    It is now clear that hydrogen peroxide (H(2)O(2)) and nitric oxide (NO) function as signalling molecules in plants. A wide range of abiotic and biotic stresses results in H(2)O(2) generation, from a variety of sources. H(2)O(2) is removed from cells via a number of antioxidant mechanisms, both enzymatic and non-enzymatic. Both biotic and abiotic stresses can induce NO synthesis, but the biosynthetic origins of NO in plants have not yet been resolved. Cellular responses to H(2)O(2) and NO are complex, with considerable cross-talk between responses to several stimuli. In this review the potential roles of H(2)O(2) and NO during various stresses and the signalling pathways they activate are discussed. Key signalling components that might provide targets for enhancing crop production are also identified. PMID:11997372

  8. Differential regulation of cytokine production by nitric oxide.

    PubMed Central

    Marcinkiewicz, J; Chain, B M

    1993-01-01

    Nitric oxide (NO) has recently been identified as a potent and pleiotropic intracellular mediator produced by and acting on many cells of the body. Although considerable attention has been devoted to the regulation of NO by inflammatory cytokines, and also to the role of NO as an important effector molecule in immune function, there is very little information on the role of this mediator in modulating T-cell-dependent cytokine production. In this study we show that physiological levels of NO (either produced by activated macrophages or by the addition of exogenous NO donors) can selectively down-regulate interleukin-3 (IL-3) production by spleen cells from contact-sensitized mice, while leaving IL-2 activity unaffected. Thus NO may have an important role as an immunomodulatory as well as effector molecule in the immune system. PMID:8244457

  9. Solar cycle variation of thermospheric nitric oxide at solstice

    NASA Technical Reports Server (NTRS)

    Gerard, J.-C.; Fesen, C. G.; Rusch, D. W.

    1990-01-01

    A coupled, two-dimensional, chemical-diffusive model of the thermosphere is used to study the role of solar activity in the global distribution of nitric oxide. The model calculates self-consistently the zonally averaged temperature, circulation, and composition for solstice under solar maximum and solar minimum conditions. A decrease of the NO density by a factor of three to four in the E region is predicted from solar maximum to solar minimum. It is found that the main features of the overall morphology and the changes induced by the solar cycle are well reproduced in the model, although some details are not satisfactorily predicted. The sensitivity of the NO distribution to eddy transport and to the quenching of metastable N(2D) atoms by atomic oxygen is also described.

  10. 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

  11. 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

  12. Nitric oxide inhibits falcipain, the Plasmodium falciparum trophozoite cysteine protease.

    PubMed

    Venturini, G; Colasanti, M; Salvati, L; Gradoni, L; Ascenzi, P

    2000-01-01

    Nitric oxide (NO) is a pluripotent regulatory molecule possessing, among others, an antiparasitic activity. In the present study, the inhibitory effect of NO on the catalytic activity of falcipain, the papain-like cysteine protease involved in Plasmodium falciparum trophozoite hemoglobin degradation, is reported. In particular, NO donors S-nitrosoglutathione (GSNO), (+/-)-(E)-p6ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenami de (NOR-3), 3-morpholinosydnonimine (SIN-1), and sodium nitroprusside (SNP) inhibit dose-dependently the falcipain activity present in the P. falciparum trophozoite extract, this effect likely attributable to S-nitrosylation of the Cys25 catalytic residue. The results represent a new insight into the modulation mechanism of falcipain activity, thereby being relevant in developing new strategies for inhibition of the P. falciparum life cycle. PMID:10623597

  13. 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.

  14. Natural Product Nitric Oxide Chemistry: New Activity of Old Medicines

    PubMed Central

    Jiang, Hong; Torregrossa, Ashley C.; Parthasarathy, Deepa K.; Bryan, Nathan S.

    2012-01-01

    The use of complementary and alternative medicine (CAM) as a therapy and preventative care measure for cardiovascular diseases (CVD) may prove to be beneficial when used in conjunction with or in place of conventional medicine. However, the lack of understanding of a mechanism of action of many CAMs limits their use and acceptance in western medicine. We have recently recognized and characterized specific nitric oxide (NO) activity of select alternative and herbal medicines that may account for many of their reported health benefits. The ability of certain CAM to restore NO homeostasis both through enhancing endothelial production of NO and by providing a system for reducing nitrate and nitrite to NO as a compensatory pathway for repleting NO bioavailability may prove to be a safe and cost-effective strategy for combating CVD. We will review the current state of science behind NO activity of herbal medicines and their effects on CVD. PMID:22548122

  15. 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

  16. Voltametric assessment of brain nitric oxide during heatstroke in rats.

    PubMed

    Canini, F; Bourdon, L; Cespuglio, R; Buguet, A

    1997-08-01

    Anesthetized rats exposed to a high ambient temperature develop heatstroke with brain ischemia. Since nitric oxide (NO) plays an important role during normothermic ischemia, its cortical and cerebellar production were continuously assessed in pentobarbital anesthetized rats exposed to heat by using differential pulsed voltammetry. After 60 min at thermoneutrality, the rats were submitted to an ambient temperature of 40 degrees C until death. After 60 min in the heat, the rats were injected intraperitoneally with saline, MK801 (1 mg.kg(-1)), an antagonist of N-methyl-D-aspartate (NMDA) receptors, or L-arginine p-nitroanilide (L-ANA; 100 mg.kg(-1)), an inhibitor of NO synthase. Just before death, a 70% increase in NO production was observed in both the cerebellum and the cortex of saline-treated rats. The cortical increase in NO was not modified by MK801 while the NO signal was suppressed by L-ANA. PMID:9291142

  17. Nitric oxide evoked p53-accumulation and apoptosis.

    PubMed

    Brüne, Bernhard; Schneiderhan, Nicole

    2003-04-01

    The tumor suppressor p53 accumulates under conditions of cellular stress and affects cell cycle progression and/or apoptosis. This has been exemplified for endogenously produced or exogenously supplied nitric oxide (NO) and thus accounts at least in part for cell destructive signaling qualities of this bioactive molecule and/or derived reactive nitrogen species. However, detailed mechanisms of toxicity and pathways of cell demise remain to be elucidated. Establishing that NO-treatment left the ubiquitination and the p53-Mdm2 interaction intact may point to an impaired nuclear-cytoplasmic shuttling to account for p53 stabilization. This was verified by heterokaryon analysis. We conclude that attenuated nuclear export contributes to stabilization and activation of p53 under the influence of NO. PMID:12628747

  18. Nitric oxide inhibitory constituents from the barks of Cinnamomum cassia.

    PubMed

    He, Shan; Zeng, Ke-Wu; Jiang, Yong; Tu, Peng-Fei

    2016-07-01

    Six new compounds including one γ-butyrolactone, cinncassin A (1), two tetrahydrofuran derivatives, cinncassins B and C (2, 3), two lignans, cinncassins D and E (4, 5), and one phenylpropanol glucoside, cinnacassoside D (6), together with 14 known lignans (7-20) were isolated from the barks of Cinnamomum cassia. The structures of 1-6 were elucidated by extensive 1D and 2D NMR spectroscopic data analysis as well as chemical methods, and the absolute configurations were established by experimental and calculated ECD data. The anti-inflammatory activities of the isolates were evaluated on nitric oxide (NO) production in lipopolysaccharide (LPS)-induced BV-2 microglial cells. Compounds 5, 7, 8, and 15 showed potent inhibition activities with IC50 values of 17.6, 17.7, 18.7, and 17.5μM, respectively. PMID:27223848

  19. Production of nitric oxide by lightning on Venus

    NASA Technical Reports Server (NTRS)

    Levine, J. S.; Gregory, G. L.; Harvey, G. A.; Howell, W. E.; Borucki, W. J.; Orville, R. E.

    1982-01-01

    The first measurements of the production of nitric oxide (NO) by a laboratory discharge in a simulated Venus atmosphere are presented. The average NO yield over a range of energies was found to be 3.7 + or - 0.7 x 10 to the 15th molecules/joule. Simultaneous measurements of carbon monoxide (CO) resulting from the lightning-induced dissociation of carbon dioxide (CO2) indicated a CO yield of about 4 x 10 to the 17th molecules/joule. These measurements suggest that at and below cloud level, a region where solar ultraviolet radiation cannot penetrate, the dissociation of CO2 by lightning may be a significant source of oxygen atoms. Depending on the assumed value for the total energy dissipated by lightning on Venus, the production of NO by lightning may be a significant sink of atmospheric nitrogen over the history of Venus.

  20. A multifaceted molecule, nitric oxide in oral and periodontal diseases.

    PubMed

    Uğar-Cankal, Dilek; Ozmeric, Nurdan

    2006-04-01

    Nitric oxide (NO) is a molecule with multiple effects on different tissues. NO takes important roles in vasodilatation, bacterial challenge and cytokine stimulation, regulation of mineralized tissue function, neurotransmission, and platelet aggregation, etc. However, under pathological conditions, NO has damaging effects. NO is synthesized by NO synthases (NOS) and inducible isoform of NOS (iNOS) is closely related to the pathophysiological characteristics of inflammatory diseases such as periodontal diseases. The expression of iNOS has been investigated in salivary gland-related diseases, temporomandibular joint disorders and oral cancer as well. The beneficial and damaging effects of NO in diseases related with periodontal, dental and maxillofacial area are discussed in this review. The biological pathways involved with NO and NO inhibitors may be good drug targets to have a role in the future management of patients with diseases in orofacial region. PMID:16387291

  1. Metallo Protoporphyrin Functionalized Microelectrodes for Electrocatalytic Sensing of Nitric Oxide

    PubMed Central

    Li, Chen-Zhong; Alwarappan, Subbiah; Zhang, Wenbo; Scafa, Nikki; Zhang, Xueji

    2010-01-01

    Nitric oxide (NO) has been considered as an important bio-regulatory molecule in the physiological process. All the existing methods often employed for NO measurement are mainly indirect and not suitable for in vivo conditions. In this paper, we report a systematic study of electrocatalytic NO reduction by comparing the redox properties of NO at carbon microelectrodes functionalized by Fe, Mn and Co protoporphyrins. The mechanisms of electrocatalytic reduction of NO by different metalloporphyrins have been proposed and compared. In addition, by varying the metallic cores of the metalloporphyrins, NO exhibits voltammograms in which the cathodic peak current occur at different potential. A comparative study on the electrochemical behavior of each of these metalloporphyrin (as a result of varying the metallic core) has been performed and a possible mechanism for the observed behavior is proposed. The results confirmed the potential applicability of using metalloporphyrins modified electrodes for voltammetric NO detection. PMID:20526418

  2. 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

  3. 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

  4. Antibacterial Efficacy of Exogenous Nitric Oxide on Periodontal Pathogens

    PubMed Central

    Backlund, C.J.; Sergesketter, A.R.; Offenbacher, S.; Schoenfisch, M.H.

    2014-01-01

    Current treatments for periodontitis (e.g., scaling/root planing and chlorhexidine) have limited efficacy since they fail to suppress microbial biofilms satisfactorily over time, and the use of adjunctive antimicrobials can promote the emergence of antibiotic-resistant organisms. Herein, we report the novel application of nitric oxide (NO)-releasing scaffolds (i.e., dendrimers and silica particles) as anti-periodontopathogenic agents. The effectiveness of macromolecular NO release was demonstrated by a 3-log reduction in periodontopathogenic Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis viability. In contrast, Streptococcus mutans and Streptococcus sanguinis, caries-associated organisms, were substantially less sensitive to NO treatment. Both dendrimer- and silica-based NO release exhibited substantially less toxicity to human gingival fibroblasts at concentrations necessary to eradicate periodontopathogens than did clinical concentrations of chlorhexidine. These results suggest the potential utility of macromolecular NO-release scaffolds as a novel platform for the development of periodontal disease therapeutics. PMID:25139363

  5. Modulation of endothelial nitric oxide by plant-derived products.

    PubMed

    Schmitt, Christoph A; Dirsch, Verena M

    2009-09-01

    Nitric oxide (NO), produced by endothelial nitric oxide synthase (eNOS), is recognised as a central anti-inflammatory and anti-atherogenic principle in the vasculature. Decreased availability of NO in the vasculature promotes the progression of cardiovascular diseases. Epidemiological and clinical studies have demonstrated that a growing list of natural products, as components of the daily diet or phytomedical preparations, may improve vascular function by enhancing NO bioavailability. In this article we first outline common pathways modulating endothelial NO production or bioavailability to provide a basis for subsequent mechanistic discussions. Then we comprehensively review natural products and plant extracts known to positively influence eNOS activity and/or endothelial function in vitro or in vivo. We will discuss red wine, highlighting polyphenols, oligomeric procyanidins (OPC) and resveratrol as modulators of endothelial NO production. Other dietary products and their active components known to activate eNOS include cocoa (OPC and its monomer (-)-epicatechin), pomegranates (polyphenols), black and green tea (flavanoids, especially epigallocatechin gallate), olive oil (oleic acid and polyphenols), soy (genistein), and quercetin, one of the most abundant flavonoids in plants. In addition, phytomedical preparations made from ginkgo, hawthorn and ginseng, as well as formulations used in traditional Chinese Medicine, have been shown to affect endothelial NO production. Recurring phytochemical patterns among active fractions and purified compounds are discussed. In summary, there is increasing evidence that several single natural products and plant extracts influence endothelial NO production. Identification of such compounds and characterisation of their cellular actions may increase our knowledge of the regulation of endothelial NO production and could provide valuable clues for the prevention or treatment of cardiovascular diseases. PMID:19497380

  6. Nitric oxide alters metabolism in isolated alveolar type II cells.

    PubMed

    Miles, P R; Bowman, L; Huffman, L

    1996-07-01

    Alveolar type II cells may be exposed to nitric oxide (.NO) from external sources, and these cells can also generate .NO. Therefore we studied the effects of altering .NO levels on various type II cell metabolic processes. Incubation of cells with the .NO generator, S-nitroso-N-acetylpenicillamine (SNAP; 1 mM), leads to reductions of 60-70% in the synthesis of disaturated phosphatidylcholines (DSPC) and cell ATP levels. Cellular oxygen consumption, an indirect measure of cell ATP synthesis, is also reduced by SNAP. There is no direct effect of SNAP on lung mitochondrial ATP synthesis, suggesting that .NO does not directly inhibit this process. On the other hand, incubation of cells with NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase (NOS), the enzyme responsible for .NO synthesis, results in increases in DSPC synthesis, cell ATP content, and cellular oxygen consumption. The L-NAME effects are reversed by addition of L-arginine, the substrate for NOS. Production of .NO by type II cells is inhibited by L-NAME, a better inhibitor of constitutive NOS (cNOS) than inducible NOS (iNOS), and is reduced in the absence of external calcium. Aminoguanidine, a specific inhibitor of iNOS, has no effect on cell ATP content or on .NO production. These results indicate that alveolar type II cell lipid and energy metabolism can be affected by .NO and suggest that there may be cNOS activity in these cells. PMID:8760128

  7. Endothelial nitric oxide synthase regulates microvascular hyperpermeability in vivo

    PubMed Central

    Hatakeyama, Takuya; Pappas, Peter J; Hobson, Robert W; Boric, Mauricio P; Sessa, William C; Durán, Walter N

    2006-01-01

    Nitric oxide (NO) is an important regulator of blood flow, but its role in permeability is still challenged. We tested in vivo the hypotheses that: (a) endothelial nitric oxide synthase (eNOS) is not essential for regulation of baseline permeability; (b) eNOS is essential for hyperpermeability responses in inflammation; and (c) molecular inhibition of eNOS with caveolin-1 scaffolding domain (AP-Cav) reduces eNOS-regulated hyperpermeability. We used eNOS-deficient (eNOS−/−) mice and their wild-type control as experimental animals, platelet-activating factor (PAF) at 10−7 m as the test pro-inflammatory agent, and integrated optical intensity (IOI) as an index of microvascular permeability. PAF increased permeability in wild-type cremaster muscle from a baseline of 2.4 ± 2.2 to a peak net value of 84.4 ± 2.7 units, while the corresponding values in cremaster muscle of eNOS−/− mice were 1.0 ± 0.3 and 15.6 ± 7.7 units (P < 0.05). Similarly, PAF increased IOI in the mesentery of wild-type mice but much less in the mesentery of eNOS−/− mice. PAF increased IOI to comparable values in the mesenteries of wild-type mice and those lacking the gene for inducible NOS (iNOS). Administration of AP-Cav blocked the microvascular hyperpermeability responses to 10−7 m PAF. We conclude that: (1) baseline permeability does not depend on eNOS; (2) eNOS and NO are integral elements of the signalling pathway for the hyperpermeability response to PAF; (3) iNOS does not affect either baseline permeability or hyperpermeability responses to PAF; and (4) caveolin-1 inhibits eNOS regulation of microvascular permeability in vivo. Our results establish eNOS as an important regulator of microvascular permeability in inflammation. PMID:16675496

  8. Muscular nitric oxide synthase (muNOS) and utrophin.

    PubMed

    Chaubourt, Emmanuel; Voisin, Vincent; Fossier, Philippe; Baux, Gérard; Israël, Maurice; De La Porte, Sabine

    2002-01-01

    Duchenne muscular dystrophy (DMD), the severe X-linked recessive disorder which results in progressive muscle degeneration, is due to a lack of dystrophin, a membrane cytoskeletal protein. Three types of treatment are envisaged: pharmacological (glucocorticoid), myoblast transplantation, and gene therapy. An alternative to the pharmacological approach is to compensate for dystrophin loss by the upregulation of another cytoskeletal protein, utrophin. Utrophin and dystrophin are part of a complex of proteins and glycoproteins, which links the basal lamina to the cytoskeleton, thus ensuring the stability of the muscle membrane. One protein of the complex, syntrophin, is associated with a muscular isoform of the neuronal nitric oxide synthase (nNOS). We have demonstrated an overexpression of utrophin, visualised by immunofluorescence and quantified by Western blotting, in normal myotubes and in mdx (the animal model of DMD) myotubes, as in normal (C57) and mdx mice, both treated with nitric oxide (NO) donor or L-arginine, the NOS substrate. There is evidence that utrophin may be capable of performing the same cellular functions as dystrophin and may functionally compensate for its lack. Thus, we propose to use NO donors, as palliative treatment of Duchenne and Becker muscular dystrophies, pending, or in combination with, gene and/or cellular therapy. Discussion has focussed on the various isoforms of NOS that could be implicated in the regeneration process. Dystrophic and healthy muscles respond to treatment, suggesting that although NOS is delocalised in the cytoplasm in the case of DMD, it conserves substantial activity. eNOS present in mitochondria and iNOS present in cytoplasm and the neuromuscular junction could also be activated. Lastly, production of NO by endothelial NOS of the capillaries would also be beneficial through increased supply of metabolites and oxygen to the muscles. PMID:11755782

  9. Thromboresistance Characterization of Extruded Nitric Oxide-Releasing Silicone Catheters

    PubMed Central

    Amoako, Kagya A.; Archangeli, Christopher; Handa, Hitesh; Major, Terry; Meyerhoff, Mark E.; Annich, Gail M.; Bartlett, Robert H.

    2013-01-01

    Intravascular catheters used in clinical practice can activate platelets, leading to thrombus formation and stagnation of blood flow. Nitric oxide (NO)-releasing polymers have been shown previously to reduce clot formation on a number of blood contacting devices. In this work, trilaminar NO-releasing silicone catheters were fabricated and tested for their thrombogenicity. All catheters had specifications of L = 6 cm, inner diameter = 21 gauge (0.0723 cm), outer diameter = 12 gauge (0.2052 cm), and NO-releasing layer thickness = 200 ± 11 μm. Control and NO-releasing catheters were characterized in vitro for their NO flux and NO release duration by gas phase chemiluminescence measurements. The catheters were then implanted in the right and left internal jugular veins of (N = 6 and average weight = 3 kg) adult male rabbits for 4 hours thrombogenicity testing. Platelet counts and function, methemoglobin (metHb), hemoglobin (Hb), and white cell counts and functional time (defined as patency time of catheter) were monitored as measured outcomes. Nitric oxide-releasing catheters (N = 6) maintained an average flux above (2 ± 0.5) × 10−10 mol/min/cm2 for more than 24 hours, whereas controls showed no NO release. Methemoglobin, Hb, white cell, and platelet counts and platelet function at 4 hours were not significantly different from baseline (α = 0.05). However, clots on controls were visibly larger and prevented blood draws at a significantly (p < 0.05) earlier time (2.3 ± 0.7 hours) into the experiment, whereas all NO-releasing catheters survived the entire 4 hours test period. Results indicate that catheter NO flux levels attenuated thrombus formation in a short-term animal model. PMID:22395119

  10. 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.

  11. Superoxide reacts with nitric oxide to nitrate tyrosine at physiological pH via peroxynitrite.

    PubMed

    Reiter, C D; Teng, R J; Beckman, J S

    2000-10-20

    Tyrosine nitration is a widely used marker of peroxynitrite (ONOO(-)) produced from the reaction of nitric oxide with superoxide. Pfeiffer and Mayer (Pfeiffer, S., and Mayer, B. (1998) J. Biol. Chem. 273, 27280-27285) reported that superoxide produced from hypoxanthine plus xanthine oxidase in combination with nitric oxide produced from spermine NONOate did not nitrate tyrosine at neutral pH. They suggested that nitric oxide and superoxide at neutral pH form a less reactive intermediate distinct from preformed alkaline peroxynitrite that does not nitrate tyrosine. Using a stopped-flow spectrophotometer to rapidly mix potassium superoxide with nitric oxide at pH 7.4, we report that an intermediate spectrally and kinetically identical to preformed alkaline cis-peroxynitrite was formed in 100% yield. Furthermore, this intermediate nitrated tyrosine in the same yield and at the same rate as preformed peroxynitrite. Equivalent concentrations of nitric oxide under aerobic conditions in the absence of superoxide did not produce detectable concentrations of nitrotyrosine. Carbon dioxide increased the efficiency of nitration by nitric oxide plus superoxide to the same extent as peroxynitrite. In experiments using xanthine oxidase as a source of superoxide, tyrosine nitration was substantially inhibited by urate formed from hypoxanthine oxidation, which was sufficient to account for the lack of tyrosine nitration previously reported. We conclude that peroxynitrite formed from the reaction of nitric oxide with superoxide at physiological pH remains an important species responsible for tyrosine nitration in vivo. PMID:10906340

  12. New nitric oxide donors based on ruthenium complexes.

    PubMed

    Lunardi, C N; da Silva, R S; Bendhack, L M

    2009-01-01

    Nitric oxide (NO) donors produce NO-related activity when applied to biological systems. Among its diverse functions, NO has been implicated in vascular smooth muscle relaxation. Despite the great importance of NO in biological systems, its pharmacological and physiological studies have been limited due to its high reactivity and short half-life. In this review we will focus on our recent investigations of nitrosyl ruthenium complexes as NO-delivery agents and their effects on vascular smooth muscle cell relaxation. The high affinity of ruthenium for NO is a marked feature of its chemistry. The main signaling pathway responsible for the vascular relaxation induced by NO involves the activation of soluble guanylyl-cyclase, with subsequent accumulation of cGMP and activation of cGMP-dependent protein kinase. This in turn can activate several proteins such as K+ channels as well as induce vasodilatation by a decrease in cytosolic Ca2+. Oxidative stress and associated oxidative damage are mediators of vascular damage in several cardiovascular diseases, including hypertension. The increased production of the superoxide anion (O2-) by the vascular wall has been observed in different animal models of hypertension. Vascular relaxation to the endogenous NO-related response or to NO released from NO deliverers is impaired in vessels from renal hypertensive (2K-1C) rats. A growing amount of evidence supports the possibility that increased NO inactivation by excess O2- may account for the decreased NO bioavailability and vascular dysfunction in hypertension. PMID:19219301

  13. Nitric Oxide Regulation of Mitochondrial Processes: Commonality in Medical Disorders.

    PubMed

    Stefano, George B; Kream, Richard M

    2015-01-01

    The vital status of diverse classes of eukaryotic mitochondria is reflected by the high degree of evolutionary modification functionally linked to ongoing multifaceted organelle development. From this teleological perspective, a logistical enhancement of eukaryotic cellular energy requirements indicates a convergence of metabolic processes within the mitochondrial matrix for optimal synthesis of ATP from ADP and inorganic phosphate and necessitates an evolutionarily driven retrofit of the primordial endosymbiont bacterial plasma membrane into the inner mitochondrial membrane. The biochemical complexity of eukaryotic inner membrane electron transport complexes linked to temporally-defined, state-dependent, fluctuations in mitochondrial oxygen utilization is capable of generating deleterious reactive oxygen species. Within this functional context, an extensive neurochemical literature supports the role of the free radical gas nitric oxide (NO) as a key signaling molecule involved in the regulation of multiple aspects of mitochondrial respiration/oxidative phosphorylation. Importantly, the unique chemical properties of NO underlie its rapid metabolism in vivo within a mechanistic spectrum of small oxidative molecules, free and protein-bound thiol adducts, and reversible binding to ferrous heme iron centers. Recent compelling work has identified a medically relevant dual regulation pathway for mitochondrial NO expression mediated by traditionally characterized NO synthases (NOS) and by enzymatic reduction of available cellular nitrite pools by a diverse class of cytosolic and mitochondrial nitrite reductases. Accordingly, our short review presents selected medically-based discussion topics relating to multi-faceted NO regulation of mitochondrial functions in human health and disease states. PMID:26177568

  14. 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

  15. 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

  16. The influence of organic peroxides on platelet aggregation and sensitivity to nitric oxide.

    PubMed

    Naseem, K M; Bruckdorfer, K R

    1999-01-01

    The effects of oxidative stress, induced by water-soluble and lipid peroxides, on platelet reactivity and platelet sensitivity to nitric oxide were investigated. Hydrogen peroxide and cumene hydroperoxide potentiated thrombin-induced platelet aggregation. In contrast, 15(S)-hydroperoxyeicosatetraenoic acid had no such effect, while 12(S)-hydroperoxyeicosatetraenoic acid inhibited platelet reactivity. All of the peroxides tested were found to decrease platelet sensitivity to nitric oxide, although the mechanisms by which the various peroxides altered platelet sensitivity to nitric oxide were different. The water-soluble peroxides opposed the actions of nitric oxide without affecting cyclic GMP levels, while 15(S)-hydroperoxyeicosatetraenoic acid caused a significant reduction in the concentration of cyclic GMP formed in response to NO. The data from this study demonstrate that water-soluble and lipid peroxides both affect platelet reactivity and regulation, but by different mechanisms. Thus, caution should be exercised when selecting peroxides to be used as models of oxidative stress. PMID:16801085

  17. Mechanistic studies of nitrations and oxidations in solutions of dinitrogen pentaoxide in nitric acid

    SciTech Connect

    Willmer, R.F.

    1992-01-01

    Mechanisms of nitrations in solutions of dinitrogen pentaoxide in nitric acid of 1,2,4-trichloro-5-nitrobenzene and 1,2-dichloro-4-nitrobenzene have been proposed. The kinetics and products of the nitration, in the title medium, of substantially deactivated benzoic acids and benzaldehydes have been investigated. Kinetics of nitration of some substituted benzoic acids in nitric acid solutions containing dinitrogen pentaoxide or nitronium trifluoro-methanesulphonate (nitronium triflate) have been compared. Rate coefficients for reactions in dinitrogen pentaoxide solutions were generally similar to those from nitronium triflate solutions of the same estimated nitronium ion concentration. Yields of aromatic products of nitration of some benzoic acid derivatives in the nitric acid solutions have been determined. Nitrodecarboxylation of 4-fluorobenzoic acid occurs as a result of nitronium ion attach at C(1). The competition between oxidation to the corresponding benzoic acid and nitration in the aromatic ring of some substituted benzaldehydes has been probed by kinetic and product studies. 4-Carboxybenzaldehyde is nitrated but more deactivated substrates are predominantly oxidized. Rapid reversible gem-dinitrate formation occurs in concentrated dinitrogen pentaoxide solutions. The equilibrium extent of formation of [alpha]-deuterio-(4-nitropheny)-dinitratomethane from [alpha]-deuterio-4-nitrobenzaldehyde is reported. 4-nitrobenzaldehyde and the gem-dinitrate are oxidized in processes in which [alpha]-hydrogen loss is at least partially rate determining. The relative rates of oxidation in nitronium triflate solutions suggest that the [alpha]-hydrogen is removed as a hydride ion in that medium. There is evidence for the intrusion of a radical mechanism of nitration in concentrated solutions of dinitrogen pentaoxide. (4-Nitrophenyl)dinitratomethane was produced on the addition of 4-nitrobenzaldehyde to a solution of dinitrogen pentaoxide in dichloromethane.

  18. 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.

  19. Increasing nitric oxide content in Arabidopsis thaliana by expressing rat neuronal nitric oxide synthase resulted in enhanced stress tolerance.

    PubMed

    Shi, Hai-Tao; Li, Rong-Jun; Cai, Wei; Liu, Wen; Wang, Chao-Lun; Lu, Ying-Tang

    2012-02-01

    Nitric oxide (NO) plays essential roles in many physiological and developmental processes in plants, including biotic and abiotic stresses, which have adverse effects on agricultural production. However, due to the lack of findings regarding nitric oxide synthase (NOS), many difficulties arise in investigating the physiological roles of NO in vivo and thus its utilization for genetic engineering. Here, to explore the possibility of manipulating the endogenous NO level, rat neuronal NOS (nNOS) was expressed in Arabidopsis thaliana. The 35S::nNOS plants showed higher NOS activity and accumulation of NO using the fluorescent probe 3-amino, 4-aminomethyl-2', 7'-difluorescein, diacetate (DAF-FM DA) assay and the hemoglobin assay. Compared with the wild type, the 35S::nNOS plants displayed improved salt and drought tolerance, which was further confirmed by changes in physiological parameters including reduced water loss rate, reduced stomatal aperture, and altered proline and malondialdehyde content. Quantitative real-time PCR analyses revealed that the expression of several stress-regulated genes was up-regulated in the transgenic lines. Furthermore, the transgenic lines also showed enhanced disease resistance against Pseudomonas syringae pv. tomato (Pst) DC3000 by activating the expression of defense-related genes. In addition, we found that the 35S::nNOS lines flowered late by regulating the expression of CO, FLC and LFY genes. Together, these results demonstrated that it is a useful strategy to exploit the roles of plant NO in various processes by the expression of rat nNOS. The approach may also be useful for genetic engineering of crops with increased environmental adaptations. PMID:22186181

  20. The production of nitric oxide by marine ammonia-oxidizing archaea and inhibition of archaeal ammonia oxidation by a nitric oxide scavenger.

    PubMed

    Martens-Habbena, Willm; Qin, Wei; Horak, Rachel E A; Urakawa, Hidetoshi; Schauer, Andrew J; Moffett, James W; Armbrust, E Virginia; Ingalls, Anitra E; Devol, Allan H; Stahl, David A

    2015-07-01

    Nitrification is a critical process for the balance of reduced and oxidized nitrogen pools in nature, linking mineralization to the nitrogen loss processes of denitrification and anammox. Recent studies indicate a significant contribution of ammonia-oxidizing archaea (AOA) to nitrification. However, quantification of the relative contributions of AOA and ammonia-oxidizing bacteria (AOB) to in situ ammonia oxidation remains challenging. We show here the production of nitric oxide (NO) by Nitrosopumilus maritimus SCM1. Activity of SCM1 was always associated with the release of NO with quasi-steady state concentrations between 0.05 and 0.08 μM. NO production and metabolic activity were inhibited by the nitrogen free radical scavenger 2-phenyl-4,4,5,5,-tetramethylimidazoline-1-oxyl-3-oxide (PTIO). Comparison of marine and terrestrial AOB strains with SCM1 and the recently isolated marine AOA strain HCA1 demonstrated a differential sensitivity of AOB and AOA to PTIO and allylthiourea (ATU). Similar to the investigated AOA strains, bulk water column nitrification at coastal and open ocean sites with sub-micromolar ammonia/ammonium concentrations was inhibited by PTIO and insensitive to ATU. These experiments support predictions from kinetic, molecular and biogeochemical studies, indicating that marine nitrification at low ammonia/ammonium concentrations is largely driven by archaea and suggest an important role of NO in the archaeal metabolism. PMID:25420929

  1. 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

  2. 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

  3. 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

  4. A hypothesis about cellular signaling with nitric oxide in the earliest life forms in evolution.

    PubMed

    Murad, Ferid; Barber, Roger

    2009-11-01

    We propose that nitric oxide participated as an extracellular and intracellular messenger in the early evolution of life. From a toxic and noxious substance it evolved into an important material for cellular communication and regulation with unique chemistry and properties. The presence of some nitric oxide complexes in extraterrestrial samples may support evidence for life forms in the past or present. Although nitric oxide probably participated in the evolution and maintenance of life, if pollution continues at an ever-increasing rate, it could also end life on the planet as we know it today. PMID:19439177

  5. Correlation of urinary nitric oxide concentrations with the development of hip dysplasia in Labrador retrievers.

    PubMed

    Morich, K; Ohlerth, S; Reist, M; Lang, J; Riitano, M; Schawalder, P; Spreng, D

    2003-10-01

    Urinary nitric oxide was determined in terms of the ratio of the concentrations of total urinary nitrite and nitrate:creatinine in 40 juvenile labrador retrievers, and radiographic signs of hip dysplasia and distraction indices were investigated in the same dogs in later life. The ratio was correlated significantly with the Norberg angle and with subchondral sclerosis in both hips, and with the grade of dysplasia in each hip and the dogs' overall grade of hip dysplasia. No correlations were observed between the ratio and the distraction indices or other radiographic criteria for hip dysplasia. PMID:14582731

  6. 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

  7. 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

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

    PubMed

    Wang, Jianhua; Zhao, Yuzheng; Wang, Chao; 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

  9. 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.

  10. Nitro-linolenic acid is a nitric oxide donor.

    PubMed

    Mata-Pérez, Capilla; Sánchez-Calvo, Beatriz; Begara-Morales, Juan C; Carreras, Alfonso; Padilla, María N; Melguizo, Manuel; Valderrama, Raquel; Corpas, Francisco J; Barroso, Juan B

    2016-07-01

    Nitro-fatty acids (NO2-FAs), which are the result of the interaction between reactive nitrogen species (RNS) and non-saturated fatty acids, constitute a new research area in plant systems, and their study has significantly increased. Very recently, the endogenous presence of nitro-linolenic acid (NO2-Ln) has been reported in the model plant Arabidopsis thaliana. In this regard, the signaling role of this molecule has been shown to be key in setting up a defense mechanism by inducing the chaperone network in plants. Here, we report on the ability of NO2-Ln to release nitric oxide (NO) in an aqueous medium with several approaches, such as by a spectrofluorometric probe with DAF-2, the oxyhemoglobin oxidation method, ozone chemiluminescence, and also by confocal laser scanning microscopy in Arabidopsis cell cultures. Jointly, this ability gives NO2-Ln the potential to act as a signaling molecule by the direct release of NO, due to its capacity to induce different changes mediated by NO or NO-related molecules such as nitration and S-nitrosylation or by the electrophilic capacity of these molecules through a nitroalkylation mechanism. PMID:27164295

  11. Endothelial cell expression of haemoglobin α regulates nitric oxide signalling.

    PubMed

    Straub, Adam C; Lohman, Alexander W; Billaud, Marie; Johnstone, Scott R; Dwyer, Scott T; Lee, Monica Y; Bortz, Pamela Schoppee; Best, Angela K; Columbus, Linda; Gaston, Benjamin; Isakson, Brant E

    2012-11-15

    Models of unregulated nitric oxide (NO) diffusion do not consistently account for the biochemistry of NO synthase (NOS)-dependent signalling in many cell systems. For example, endothelial NOS controls blood pressure, blood flow and oxygen delivery through its effect on vascular smooth muscle tone, but the regulation of these processes is not adequately explained by simple NO diffusion from endothelium to smooth muscle. Here we report a new model for the regulation of NO signalling by demonstrating that haemoglobin (Hb) α (encoded by the HBA1 and HBA2 genes in humans) is expressed in human and mouse arterial endothelial cells and enriched at the myoendothelial junction, where it regulates the effects of NO on vascular reactivity. Notably, this function is unique to Hb α and is abrogated by its genetic depletion. Mechanistically, endothelial Hb α haem iron in the Fe(3+) state permits NO signalling, and this signalling is shut off when Hb α is reduced to the Fe(2+) state by endothelial cytochrome b5 reductase 3 (CYB5R3, also known as diaphorase 1). Genetic and pharmacological inhibition of CYB5R3 increases NO bioactivity in small arteries. These data reveal a new mechanism by which the regulation of the intracellular Hb α oxidation state controls NOS signalling in non-erythroid cells. This model may be relevant to haem-containing globins in a broad range of NOS-containing somatic cells. PMID:23123858

  12. An introduction to nitric oxide sensing and response in bacteria.

    PubMed

    Stern, Andrew M; Zhu, Jun

    2014-01-01

    Nitric oxide (NO) is a radical gas that has been intensively studied for its role as a bacteriostatic agent. NO reacts in complex ways with biological molecules, especially metal centers and other radicals, to generate other bioactive compounds that inhibit enzymes, oxidize macromolecules, and arrest bacterial growth. Bacteria encounter not only NO derived from the host during infection but also NO derived from other bacteria and inorganic sources. The transcriptional responses used by bacteria to respond to NO are diverse but usually involve an iron-containing transcription factor that binds NO and alters its affinity for either DNA or factors involved in transcription, leading to the production of enzymatic tolerance systems. Some of these systems, such as flavohemoglobin and flavorubredoxin, directly remove NO. Some do not but are still important for NO tolerance through other mechanisms. The targets of NO that are protected by these systems include many metabolic pathways such as the tricarboxylic acid cycle and branched chain amino acid synthesis. This chapter discusses these topics and others and serves as a general introduction to microbial NO biology. PMID:24581392

  13. [Pathophysiological and therapeutic implications of nitric oxide in hepatology].

    PubMed

    Battista, S; Bar, F; Pollet, C; Mengozzi, G; Molino, G

    2002-12-01

    The L-arginine/nitric oxide (NO) pathway has been recognized as a main regulator of several cell functions. Accordingly, there is an increasing number of pathophysiological conditions in which a precise knowledge of NO status could prove helpful in understanding the mechanisms involved in disease development, prevention and treatment. These include several hepatic disorders, such as liver cirrhosis and associated hyperdynamic circulation with portal hypertension, ischaemia-reperfusion injury occurring during liver transplantation, and chronic cholestatic conditions. Overall, NO seems to exert a dual role in the pathobiology of liver diseases: one mostly beneficial, due to its vasoactive effects; and one mostly negative, due to its local toxic effects. Protective actions are primarily mediated via vasodilation, antithrombosis, inhibition of neutrophil adhesion and inhibition of apoptosis. Deleterious effects are dependent upon the formation of highly reactive substances during oxidative stress. In this review aspects related to NO implications in the homeostasis of liver functions as well as in the pathogenesis of some relevant hepatic clinical syndromes will be discussed in view of possible therapeutic options. PMID:16491056

  14. 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

  15. 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

  16. Antihypertensive effects of fargesin in vitro and in vivo via attenuating oxidative stress and promoting nitric oxide release.

    PubMed

    Sha, Sha; Xu, Dandan; Wang, Yanwei; Zhao, Weifang; Li, Xiaoni

    2016-08-01

    Fargesin, a bioactive neolignan isolated from magnolia plants, is widely used in the treatment of managing rhinitis, inflammation, histamine, sinusitis, and headache. To provide more biological information about fargesin, we investigated the effects of fargesin on rat aortic rings and 2-kidney, 1-clip (2K1C) hypertensive rats. In vitro, fargesin caused concentration-dependent vasorelaxation in rat isolated aortic rings induced by KCl and norepinephrine. The effect was weakened by endothelium denudation and nitric oxide (NO) synthesis inhibition. In vivo, the evolution of systolic blood pressure (SBP) was followed by weekly measurements. Angiotensin II (Ang II) and endothelin (ET) levels, NO and nitric oxide synthase (NOS), and plasma and liver oxidative stress markers were determined at the end of the experimental period. After 5 weeks of fargesin treatment, we found that fargesin treatment reduced SBP, cardiac hypertrophy, and Ang II and ET levels of hypertensive rats. Increased NOS activity and NO level were observed in fargesin-treated rats. Normalisation of plasma MDA concentrations and improvement of the antioxidant defence system in plasma and liver accompanied the antihypertensive effect of fargesin. Taken together, these results provided substantial evidences that fargesin has antihypertensive effect in 2K1C hypertensive rats via inhibiting oxidative stress and promoting NO release. PMID:27409158

  17. 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.

  18. Measurement of nitric oxide in single cells and tissue using a porphyrinic microsensor.

    PubMed

    Malinski, T; Huk, I

    2001-05-01

    This unit describes the preparation and applications of porphyrinic sensors for quantitative measurement of nitric oxide (NO) in single cells and in tissues. The determination of NO is based on the electrochemical oxidation of NO on a carbon fiber electrode covered with a thin layer of a conducting polymeric metalloporphyrin catalyst, overlaid with another thin film of Nafion, a cation exchange material. The electric current generated during NO oxidation on the surface of the polymeric porphyrin is linearly proportional to the concentration of NO, so this current is used as an analytical signal which can be measured in either the amperometric or the voltammetric mode. Both methods provide a quantitative signal. This unit describes the electrochemical setup for measurement of NO in single cells and tissue. Support protocols describe porphyrin synthesis, sensor preparation, and sensor calibration. PMID:18428525

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

    PubMed

    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

  20. Production and Consumption of Nitric Oxide by Three Methanotrophic Bacteria

    PubMed Central

    Ren, Tie; Roy, Réal; Knowles, Roger

    2000-01-01

    We studied nitrogen oxide production and consumption by methanotrophs Methylobacter luteus (group I), Methylosinus trichosporium OB3b (group II), and an isolate from a hardwood swamp soil, here identified by 16S ribosomal DNA sequencing as Methylobacter sp. strain T20 (group I). All could consume nitric oxide (nitrogen monoxide, NO), and produce small amounts of nitrous oxide (N2O). Only Methylobacter strain T20 produced large amounts of NO (>250 parts per million by volume [ppmv] in the headspace) at specific activities of up to 2.0 × 10−17 mol of NO cell−1 day−1, mostly after a culture became O2 limited. Production of NO by strain T20 occurred mostly in nitrate-containing medium under anaerobic or nearly anaerobic conditions, was inhibited by chlorate, tungstate, and O2, and required CH4. Denitrification (methanol-supported N2O production from nitrate in the presence of acetylene) could not be detected and thus did not appear to be involved in the production of NO. Furthermore, cd1 and Cu nitrite reductases, NO reductase, and N2O reductase could not be detected by PCR amplification of the nirS, nirK, norB, and nosZ genes, respectively. M. luteus and M. trichosporium produced some NO in ammonium-containing medium under aerobic conditions, likely as a result of methanotrophic nitrification and chemical decomposition of nitrite. For Methylobacter strain T20, arginine did not stimulate NO production under aerobiosis, suggesting that NO synthase was not involved. We conclude that strain T20 causes assimilatory reduction of nitrate to nitrite, which then decomposes chemically to NO. The production of NO by methanotrophs such as Methylobacter strain T20 could be of ecological significance in habitats near aerobic-anaerobic interfaces where fluctuating O2 and nitrate availability occur. PMID:10966405

  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 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

  3. Nitric Oxide Improves Internal Iron Availability in Plants1

    PubMed Central

    Graziano, Magdalena; Beligni, María Verónica; Lamattina, Lorenzo

    2002-01-01

    Iron deficiency impairs chlorophyll biosynthesis and chloroplast development. In leaves, most of the iron must cross several biological membranes to reach the chloroplast. The components involved in the complex internal iron transport are largely unknown. Nitric oxide (NO), a bioactive free radical, can react with transition metals to form metal-nitrosyl complexes. Sodium nitroprusside, an NO donor, completely prevented leaf interveinal chlorosis in maize (Zea mays) plants growing with an iron concentration as low as 10 μm Fe-EDTA in the nutrient solution. S-Nitroso-N-acetylpenicillamine, another NO donor, as well as gaseous NO supply in a translucent chamber were also able to revert the iron deficiency symptoms. A specific NO scavenger, 2-(4-carboxy-phenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, blocked the effect of the NO donors. The effect of NO treatment on the photosynthetic apparatus of iron-deficient plants was also studied. Electron micrographs of mesophyll cells from iron-deficient maize plants revealed plastids with few photosynthetic lamellae and rudimentary grana. In contrast, in NO-treated maize plants, mesophyll chloroplast appeared completely developed. NO treatment did not increase iron content in plant organs, when expressed in a fresh matter basis, suggesting that root iron uptake was not enhanced. NO scavengers 2-(4-carboxy-phenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide and methylene blue promoted interveinal chlorosis in iron-replete maize plants (growing in 250 μm Fe-EDTA). Even though results support a role for endogenous NO in iron nutrition, experiments did not establish an essential role. NO was also able to revert the chlorotic phenotype of the iron-inefficient maize mutants yellow stripe1 and yellow stripe3, both impaired in the iron uptake mechanisms. All together, these results support a biological action of NO on the availability and/or delivery of metabolically active iron within the plant. PMID:12481068

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

    PubMed Central

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

    2003-01-01

    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

  5. Nitric oxide delivery by ultrasonic cracking: some limitations.

    PubMed

    Postema, Michiel; Bouakaz, Ayache; ten Cate, Folkert J; Schmitz, Georg; de Jong, Nico; van Wamel, Annemieke

    2006-12-22

    Nitric oxide (NO) has been implicated in smooth muscle relaxation. Its use has been widespread in cardiology. Due to the effective scavenging of NO by hemoglobin, however, the drug has to be applied locally or in large quantities, to have the effect desired. We propose the use of encapsulated microbubbles that act as a vehicle to carry the gas to a region of interest. By applying a burst of high-amplitude ultrasound, the shell encapsulating the gas can be cracked. Consequently, the gas is released upon which its dissolution and diffusion begins. This process is generally referred to as (ultra)sonic cracking. To test if the quantities of released gas are high enough to allow for NO-delivery in small vessels (ø<200 microm), we analyzed high-speed optical recordings of insonified stiff-shelled microbubbles. These microbubbles were subjected to ultrasonic cracking using 0.5 or 1.7 MHz ultrasound with mechanical index MI>0.6. The mean quantity released from a single microbubble is 1.7 fmol. This is already more than the NO production of a 1mm long vessel with a 50 microm diameter during 100 ms. However, we simulated that the dissolution time of typical released NO microbubbles is equal to the half-life time of NO in whole blood due to scavenging by hemoglobin (1.8 ms), but much smaller than the extravascular half-life time of NO (>90 ms). We conclude that ultrasonic cracking can only be a successful means for nitric oxide delivery, if the gas is released in or near the red blood cell-free plasma next to the endothelium. A complicating factor in the in vivo situation is the variation in blood pressure. Although our simulations and acoustic measurements demonstrate that the dissolution speed of free gas increases with the hydrostatic pressure, the in vitro acoustic amplitudes suggest that the number of released microbubbles decreases at higher hydrostatic pressures. This indicates that ultrasonic cracking mostly occurs during the expansion phase. PMID:16889810

  6. 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

  7. Vanillic acid prevents the deregulation of lipid metabolism, endothelin 1 and up regulation of endothelial nitric oxide synthase in nitric oxide deficient hypertensive rats.

    PubMed

    Kumar, Subramanian; Prahalathan, Pichavaram; Saravanakumar, Murugesan; Raja, Boobalan

    2014-11-15

    Hypertension is one of the main factors causing cardiovascular diseases. The present study was designed to evaluate the protective effect of vanillic acid against nitric oxide deficient rats. Hypertension was induced in adult male albino rats of Wistar strain, weighing 180-220g, by oral administration of N(ω)-nitro-l arginine methyl ester (l-NAME) 40mg/kg in drinking water for 4 weeks. Vanillic acid was administered orally at a dose of 50mg/kg b.w. Nitric oxide deficient rats showed increased levels of mean arterial pressure (MAP), heart rate (HR) and decreased heart nitric oxide metabolites (NOx). A significant increase in the levels of plasma cholesterol, low density lipoprotein-cholesterol (LDL-C), very low density lipoprotein-cholesterol (VLDL-C), triglycerides (TG), free fatty acids (FFA), phospholipids (PL), 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase in the plasma, liver and kidney and decreased level of high density lipoprotein-cholesterol (HDL-C) are observed, whereas there is a decrease in the activities of plasma lipoprotein lipase (LPL) and lecithin cholesterol acyl transferase (LCAT) in nitric oxide deficient rats. l-NAME rats also showed an increase in TC, TG, FFA and PL levels in the liver and kidney tissues. Vanillic acid treatment brought the above parameters towards near normal level. Moreover the down regulated endothelial nitric oxide synthase (eNOS) and up regulated expression of endothelin 1 (ET1) components was also attenuated by vanillic acid treatment. All the above outcomes were confirmed by the histopathological examination. These results suggest that vanillic acid has enough potential to attenuate hypertension, dyslipidemia and hepatic and renal damage in nitric oxide deficient rats. PMID:25239071

  8. 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...

  9. Nitric Oxide Plasma Sources for Bio-Decontamination and Plasma Therapy

    NASA Astrophysics Data System (ADS)

    Vasilets, Victor N.; Shekhter, Anatoly B.

    One of the main products generated in atmospheric plasma sources is nitric oxide. The nitric oxide molecule is known as anti-bacterial agent on one hand and the molecule providing signaling and regulation biological functions on the other hand. Human body produces NO to kill invading pathogens. At the same time nitric oxide works as a primary vasoregulator and anti-hypertensive agent. NO also ­regulates: inflammation, collagen production, angiogenesis and apoptosis. Exogenous NO generated by plasma devices could enhance bio-activity of NO-assisted ­processes in human organism. Some applications of nitric oxide for bio-decontamination and plasma therapy will be illustrated and discussed in the paper.

  10. Nitric oxide mediates glutamate-linked enhancement of cGMP levels in the cerebellum

    SciTech Connect

    Bredt, D.S.; Snyder, S.H. )

    1989-11-01

    Nitric oxide, which mediates influences of numerous neurotransmitters and modulators on vascular smooth muscle and leukocytes, can be formed in the brain from arginine by an enzymatic activity that stoichiometrically generates citrulline. The authors show that glutamate and related amino acids, such as N-methyl-D-aspartate, markedly stimulate arginine-citrulline transformation in cerebellar slices stoichiometrically with enhancement of cGMP levels. N{sup {omega}}-monomethyl-L-arginine blocks the augmentation both of citrulline and cGMP with identical potencies. Arginine competitively reverses both effects of N{sup {omega}}-monomethyl-L-arginine with the same potencies. Hemoglobin, which complexes nitric oxide, prevents the stimulation by N-methyl-D-aspartate of cGMP levels, and superoxide dismutase, which elevates nitric oxide levels, increases cGMP formation. These data establish that nitric oxide mediates the stimulation by glutamate of cGMP formation.

  11. 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.

  12. Inducible nitric-oxide synthase attenuates vasopressin-dependent Ca2+ signaling in rat hepatocytes.

    PubMed

    Patel, Sandip; Gaspers, Lawrence D; Boucherie, Sylviane; Memin, Elisabeth; Stellato, Kerri Anne; Guillon, Gilles; Combettes, Laurent; Thomas, Andrew P

    2002-09-13

    Increases in both Ca(2+) and nitric oxide levels are vital for a variety of cellular processes; however, the interaction between these two crucial messengers is not fully understood. Here, we demonstrate that expression of inducible nitric-oxide synthase in hepatocytes, in response to inflammatory mediators, dramatically attenuates Ca(2+) signaling by the inositol 1,4,5-trisphosphate-forming hormone, vasopressin. The inhibitory effects of induction were reversed by nitric oxide inhibitors and mimicked by prolonged cyclic GMP elevation. Induction was without effect on Ca(2+) signals in response to AlF(4)(-) or inositol 1,4,5-trisphosphate, indicating that phospholipase C activation and release of Ca(2+) from inositol 1,4,5-trisphosphate-sensitive Ca(2+) stores were not targets for nitric oxide inhibition. Vasopressin receptor levels, however, were dramatically reduced in induced cultures. Our data provide a possible mechanism for hepatocyte dysfunction during chronic inflammation. PMID:12097323

  13. 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

  14. Nitric Oxide Mediates Glutamate-Linked Enhancement of cGMP Levels in the Cerebellum

    NASA Astrophysics Data System (ADS)

    Bredt, David S.; Snyder, Solomon H.

    1989-11-01

    Nitric oxide, which mediates influences of numerous neurotransmitters and modulators on vascular smooth muscle and leukocytes, can be formed in the brain from arginine by an enzymatic activity that stoichiometrically generates citrulline. We show that glutamate and related amino acids, such as N-methyl-D-aspartate, markedly stimulate arginine-citrulline transformation in cerebellar slices stoichiometrically with enhancement of cGMP levels. Nω-monomethyl-L-arginine blocks the augmentation both of citrulline and cGMP with identical potencies. Arginine competitively reverses both effects of Nω-monomethyl-L-arginine with the same potencies. Hemoglobin, which complexes nitric oxide, prevents the stimulation by N-methyl-D-aspartate of cGMP levels, and superoxide dismutase, which elevates nitric oxide levels, increases cGMP formation. These data establish that nitric oxide mediates the stimulation by glutamate of cGMP formation.

  15. Nitric oxide synthase in the peripheral nervous system of the goldfish, Carassius auratus.

    PubMed

    Brüning, G; Hattwig, K; Mayer, B

    1996-04-01

    Neuronal nitric oxide synthase was located in various organs of the goldfish by NADPH-diaphorase histochemistry and immunohistochemistry. Positive cells were detected throughout the digestive tract. A particularly dense plexus of nitric-oxide-synthase-containing fibers was present at the opening of the pneumatic duct into the esophagus and at the intestinal sphincter separating the esophagus and the intestinal bulb. The nitroxergic innervation was mainly confined to the muscularis. The muscular layer of the swim bladder and of the pneumatic duct was densely equipped with stained neurons and fibers. In the heart, the majority of small neurons located at the sinu-atrial junction was found to be positive for nitric oxide synthase. The muscularis of the urinary duct was supplied by fibers originating from many intramural ganglia harboring intensely stained neurons. These results suggest that nitric oxide represents a widespread transmitter in the peripheral nervous system of teleost species. PMID:8601299

  16. Effect of acute lithium administration on penile erection: involvement of nitric oxide system

    PubMed Central

    Sandoughdaran, Saleh; Sadeghipour, Hamed; Sadeghipour, Hamid Reza

    2016-01-01

    Background: Lithium has been the treatment of choice for bipolar disorder (BD) for many years. Although erectile dysfunction is a known adverse effect of this drug, the mechanism of action by which lithium affects erectile function is still unknown. Objective: The aim was to investigate the possible involvement of nitric oxide (NO) in modulatory effect of lithium on penile erection (PE). We further evaluated the possible role of Sildenafil in treatment of lithium-induced erectile dysfunction. Materials and Methods: Erectile function was determined using rat model of apomorphine-induced erections. For evaluating the effect of lithium on penile erection, rats received intraperitoneal injection of graded doses of lithium chloride 30 mins before subcutaneous injection of apomorphine. To determine the possible role of NO pathway, sub-effective dose of N (G)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor, was administered 15 min before administration of sub-effective dose of lithium chloride. In other separate experimental groups, sub- effective dose of the nitric oxide precursor, L-arginine, or Sildenafil was injected into the animals 15 min before administration of a potent dose of lithium. 30 min after administration of lithium chloride, animals were assessed in apomorphine test. Serum lithium levels were measured 30 min after administration of effective dose of lithium. Results: Lithium at 50 and 100 mg/kg significantly decreased number of PE (p<0.001), whereas at lower doses (5, 10 and 30 mg/kg) had no effect on apomorphine induced PE. The serum Li+ level of rats receiving 50 mg/kg lithium was 1±0.15 mmol/L which is in therapeutic range of lithium. The inhibitory effect of Lithium was blocked by administration of sub-effective dose of nitric oxide precursor L-arginine (100 mg/kg) (p<0.001) and sildenafil (3.5 mg/kg) (p<0.001) whereas pretreatment with a low and sub-effective dose of L-NAME (10mg/kg) potentiated sub-effective dose of

  17. 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.

  18. 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

  19. 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.

  20. 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

  1. Effect of nitric oxide on the transport and release of oxygen in fetal blood.

    PubMed

    Clementi, Maria Elisabetta; Orsini, Federica; Schininà, Maria Eugenia; Noia, Giuseppe; Giardina, Bruno

    2003-03-14

    It is well known that nitric oxide (NO), the most important vasodilator agent, plays an important role in lowering vascular resistance in the human umbilical-placental circulation and that its deficiency is related to the pathogenesis of pre-eclamptic disorder. Besides it has recently been demonstrated that human hemoglobin (HbA) is able to transport nitric oxide, as S-nitrosohemoglobin (SNO-Hb), from the arterial to the venous blood. In the present study we examine the functional properties of the adult and fetal nitrosated hemoglobins to see if the double transport of oxygen and NO may influence the fetal oxygenation and the relation between maternal and fetal blood. Our results show that S-nitrosation significantly increases the oxygen affinity of the adult Hb (HbA) with respect to native protein (no-nitrosated) while the functional properties of HbF are less influenced. The oxygen affinity modification, found for SNO-HbA, was ascribed to the nitrosation of cysteine beta 93: really, the same residue is also present in the gamma chains of fetal hemoglobin, while the increase of affinity is less evidenced; hence, it is probable that the 39 aminoacidic substitutions between beta and gamma chains allay the effects of S-nitrosation. As regards the physiological modulators (protons, chloride ions, 2,3-diphosphoglyceric acid, and temperature), they influence the oxygen affinity of the two hemoglobins S-nitrosated, in equal mode with respect to the native forms determining the same variation on the oxygen affinity. Hence, our results evidence the fact that the NO release by SNO-HbA "in vivo" would be limited to regions of extremely low oxygen tension (such as hypoxic regions), while in fetus, SNO-HbF would unload nitric oxide and oxygen at pressure values close to normal. PMID:12615064

  2. Cloned and expressed nitric oxide synthase structurally resembles cytochrome P-450 reductase

    NASA Astrophysics Data System (ADS)

    Bredt, David S.; Hwang, Paul M.; Glatt, Charles E.; Lowenstein, Charles; Reed, Randall R.; Snyder, Solomon H.

    1991-06-01

    Nitric oxide is a messenger molecule, mediating the effect of endothelium-derived relaxing factor in blood vessels and the cytotoxic actions of macrophages, and playing a part in neuronal communication in the brain. Cloning of a complementary DNA for brain nitric oxide synthase reveals recognition sites for NADPH, FAD, flavin mononucleotide and calmodulin as well as phosphorylation sites, indicating that the synthase is regulated by many different factors. The only known mammalian enzyme with close homology is cytochrome P-450 reductase.

  3. 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

  4. 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.

  5. Comparison of a Thermospheric Photochemical Model with SNOE Observations of Nitric Oxide

    NASA Astrophysics Data System (ADS)

    Barth, C. A.; Bailey, S. M.; Mankoff, K. D.

    2002-12-01

    A time-dependent, photochemical model has been used to calculate nitric oxide density in the lower thermosphere for 935 days (March 11, 1998 - September 30, 2000) as a function of latitude. The model data has been compared with observations made by the Student Nitric Oxide Explorer (SNOE). The energy inputs to the model are solar soft x-rays, solar extreme ultraviolet radiation, and auroral electrons. The solar soft x-rays in the 2-7 nm wavelength band have been measured by the SNOE solar x-ray photometer. The atmospheric structure is calculated using the MSIS model with the 10.7 cm radio flux and the geomagnetic index Ap as inputs. The model calculation has been performed for latitudes between 0 and 80 degrees N in steps of 5 degrees. A model calculation for the two and a half years using only solar soft x-rays (no auroral electrons) shows strong seasonal behavior in the nitric oxide density particularly in the regions of polar night. The correlation of the calculated nitric oxide density at the equator with SNOE observations shows excellent agreement and a high correlation coefficient. A model calculation with both solar soft x-rays and auroral electron precipitation shows large and varying nitric oxide density in the auroral region between 60 and 70 degrees geomagnetic latitude. When the model calculation is subtracted from the SNOE observations, excess nitric oxide is found equatorward of the auroral region. Since the only source of odd nitrogen in the region between 0 and 55 degrees N is the solar soft x-ray source and that is accounted for in the model, this excess nitric oxide is attributed to nitric oxide that has been transported out of the auroral region by meridional winds.

  6. Inhaled aerosolized prostacyclin and nitric oxide as selective pulmonary vasodilators in ARDS--a pilot study.

    PubMed

    Van Heerden, P V; Blythe, D; Webb, S A

    1996-10-01

    Nitric oxide 10 ppm and inhaled aerosolized prostacyclin 50 ng/kg/min were compared as selective pulmonary vasodilators in five patients with hypoxaemia secondary to acute respiratory distress syndrome. Neither agent resulted in systemic haemodynamic changes, indicating true pulmonary selectivity. Inhaled aerolized prostacyclin improved oxygenation to a degree comparable to nitric oxide, as measured by the arterial alveolar oxygen partial pressure gradient and shunt fraction. PMID:8909667

  7. Conversion of nitrite to nitric oxide at zinc via S-nitrosothiols.

    PubMed

    Cardenas, Allan Jay P; Abelman, Rebecca; Warren, Timothy H

    2014-01-01

    Nitrite is an important reservoir of nitric oxide activity in the plasma and cells. Using a biomimetic model, we demonstrate the conversion of zinc-bound nitrite in the tris(pyrazolyl)borate complex (iPr2)TpZn(NO2) to the corresponding S-nitrosothiol RSNO and zinc thiolate (iPr2)TpZn-SR via reaction with thiols H-SR. Decomposition of the S-nitrosothiol formed releases nitric oxide gas. PMID:24217415

  8. 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 μg/ml) was significantly less than for group 1 (median = 12.91 μg/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

  9. Subcellular targeting and trafficking of nitric oxide synthases

    PubMed Central

    Oess, Stefanie; Icking, Ann; Fulton, David; Govers, Roland; Müller-Esterl, Werner

    2006-01-01

    Unlike most other endogenous messengers that are deposited in vesicles, processed on demand and/or secreted in a regulated fashion, NO (nitric oxide) is a highly active molecule that readily diffuses through cell membranes and thus cannot be stored inside the producing cell. Rather, its signalling capacity must be controlled at the levels of biosynthesis and local availability. The importance of temporal and spatial control of NO production is highlighted by the finding that differential localization of NO synthases in cardiomyocytes translates into distinct effects of NO in the heart. Thus NO synthases belong to the most tightly controlled enzymes, being regulated at transcriptional and translational levels, through co- and post-translational modifications, by substrate availability and not least via specific sorting to subcellular compartments, where they are in close proximity to their target proteins. Considerable efforts have been made to elucidate the molecular mechanisms that underlie the intracellular targeting and trafficking of NO synthases, to ultimately understand the cellular pathways controlling the formation and function of this powerful signalling molecule. In the present review, we discuss the mechanisms and triggers for subcellular routing and dynamic redistribution of NO synthases and the ensuing consequences for NO production and action. PMID:16722822

  10. 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

  11. 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

  12. 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

  13. 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

  14. Nitric oxide destabilizes Pias3 and regulates sumoylation.

    PubMed

    Qu, Jing; Liu, Guang-Hui; Wu, Kaiyuan; Han, Peiwei; Wang, Peng; Li, Jiangmei; Zhang, Xu; Chen, Chang

    2007-01-01

    Small ubiquitin-related protein modifiers (SUMO) modification is an important mechanism for posttranslational regulation of protein function. However, it is largely unknown how the sumoylation pathway is regulated. Here, we report that nitric oxide (NO) causes global hyposumoylation in mammalian cells. Both SUMO E2 conjugating enzyme Ubc9 and E3 ligase protein inhibitor of activated STAT3 (Pias3) were targets for S-nitrosation. S-nitrosation did not interfere with the SUMO conjugating activity of Ubc9, but promoted Pias3 degradation by facilitating its interaction with tripartite motif-containing 32 (Trim32), a ubiquitin E3 ligase. On the one hand, NO promoted Trim32-mediated Pias3 ubiquitination. On the other hand, NO enhanced the stimulatory effect of Pias3 on Trim32 autoubiquitination. The residue Cys459 of Pias3 was identified as a target site for S-nitrosation. Mutation of Cys459 abolished the stimulatory effect of NO on the Pias3-Trim32 interaction, indicating a requirement of S-nitrosation at Cys459 for positive regulation of the Pias3-Trim32 interplay. This study reveals a novel crosstalk between S-nitrosation, ubiquitination, and sumoylation, which may be crucial for NO-related physiological and pathological processes. PMID:17987106

  15. [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

  16. 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

  17. Nitric oxide and cyclic guanosine monophosphate signaling in the eye.

    PubMed

    Murad, Ferid

    2008-06-01

    This brief review describes the components and pathways utilized in nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) signaling. Since the discovery of the effects of NO and cGMP on smooth muscle relaxation about 30 years ago, the field has expanded in many directions such that many, but not all, biochemical and biological effects seem to be regulated by these unique signaling molecules. While many of the effects of NO are due to activation of soluble guanylyl cyclase (sGC) that can be considered the receptor for NO, cGMP, in turn, can activate a cGMP-dependent protein kinase (PKG) to phosphorylate an array of proteins. Some of the effects of cGMP can be independent of PKG and are due to effects on ion channels or cyclic nucleotide phosphodiesterases. Also, some of the effects of NO can be independent of sGC activation. The isoenzymes and macromolecules that participate in these signaling pathways can serve as molecular targets to identify compounds that increase or decrease their activation and thus serve as chemical leads for discovering novel drugs for a variety of diseases. Some examples are given. However, with about 90,000 publications in the field since our first reports in 1977, this brief review can only give the readers a sample of the excitement and opportunities we have found in this cell signaling system. PMID:18443613

  18. Vascular system: role of nitric oxide in cardiovascular diseases.

    PubMed

    Bian, Ka; Doursout, Marie-Françoise; Murad, Ferid

    2008-04-01

    In contrast with the short research history of the enzymatic synthesis of nitric oxide (NO), the introduction of nitrate-containing compounds for medicinal purposes marked its 150th anniversary in 1997. Glyceryl trinitrate (nitroglycerin) is the first compound of this category. On October 12, 1998, the Nobel Assembly awarded the Nobel Prize in Medicine or Physiology to scientists Robert Furchgott, Louis Ignarro, and Ferid Murad for their discoveries concerning NO as a signaling molecule in the cardiovascular system. NO-mediated signaling is a recognized component in various physiologic processes (eg, smooth muscle relaxation, inhibition of platelet and leukocyte aggregation, attenuation of vascular smooth muscle cell proliferation, neurotransmission, and immune defense), to name only a few. NO has also been implicated in the pathology of many inflammatory diseases, including arthritis, myocarditis, colitis, and nephritis and a large number of pathologic conditions such as amyotrophic lateral sclerosis, cancer, diabetes, and neurodegenerative diseases. Some of these processes (eg, smooth muscle relaxation, platelet aggregation, and neurotransmission) require only a brief production of NO at low nanomolar concentrations and are dependent on the recruitment of cyclic guanosine monophosphate (cGMP)-dependent signaling. Other processes are associated with direct interaction of NO or reactive nitrogen species derived from it with target proteins and requires a more sustained production of NO at higher concentrations but do not involve the cGMP pathway. PMID:18401228

  19. Nitric oxide removal by wastewater bacteria in a biotrickling filter.

    PubMed

    Niu, Hejingying; Leung, Dennis Y C; Wong, Chifat; Zhang, Tong; Chan, Mayngor; Leung, Fred C C

    2014-03-01

    Nitric oxide (NO) is one of the most important air pollutants in atmosphere mainly emitted from combustion source. A biotrickling filter was designed and operated to remove NO from an air stream using bacteria extracted from the sewage sludge of a municipal sewage treatment plant. To obtain the best operation conditions for the biotrickling filter, orthogonal experiments (L9(3(4))) were designed. Inlet oxygen concentration was found to be the most significant factor of the biotrickling filter and has a significant negative effect on the system. The optimal conditions of the biotrickling filter occurred at a temperature of 40°C, a pH of 8.0 and a chemical oxygen demand of 165 mg/L in the recycled water with no oxygen in the system. The bacteria sample was detected by DNA sequencing technology and showed 93%-98% similarity to Pseudomonas mendocina. Moreover, a full gene sequencing results indicated the bacterium was a brand new strain and named as P. mendocina DLHK. This strain can transfer nitrate to organic nitrogen. The result suggested the assimilation nitrogen process in this system. Through the isotope experimental analysis, two intermediate products ((15)NO and (15)N2O) were found. The results indicated the denitrification function and capability of the biotrickling filter in removing NO. PMID:25079268

  20. 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.

  1. 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

  2. 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

  3. 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

  4. 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

  5. A motif for reversible nitric oxide interactions in metalloenzymes.

    PubMed

    Zhang, Shiyu; Melzer, Marie M; Sen, S Nermin; Çelebi-Ölçüm, Nihan; Warren, Timothy H

    2016-07-01

    Nitric oxide (NO) participates in numerous biological processes, such as signalling in the respiratory system and vasodilation in the cardiovascular system. Many metal-mediated processes involve direct reaction of NO to form a metal-nitrosyl (M-NO), as occurs at the Fe(2+) centres of soluble guanylate cyclase or cytochrome c oxidase. However, some copper electron-transfer proteins that bear a type 1 Cu site (His2Cu-Cys) reversibly bind NO by an unknown motif. Here, we use model complexes of type 1 Cu sites based on tris(pyrazolyl)borate copper thiolates [Cu(II)]-SR to unravel the factors involved in NO reactivity. Addition of NO provides the fully characterized S-nitrosothiol adduct [Cu(I)](κ(1)-N(O)SR), which reversibly loses NO on purging with an inert gas. Computational analysis outlines a low-barrier pathway for the capture and release of NO. These findings suggest a new motif for reversible binding of NO at bioinorganic metal centres that can interconvert NO and RSNO molecular signals at copper sites. PMID:27325092

  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. 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. PMID:27127388

  8. 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).

  9. 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

  10. Heparin modulation on hepatic nitric oxide synthase in experimental steatohepatitis

    PubMed Central

    HASSANIN, AMAL; MALEK, HALA ABDEL; SALEH, DALIA

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) is considered to be a hepatic manifestation of metabolic syndrome, and has been etiologically associated with insulin resistance (IR). The histopathology of NAFLD ranges between simple steatosis and nonalcoholic steatohepatitis (NASH), with or without fibrosis. The aim of the present study was to examine the effect of heparin on steatohepatitis and hepatic-induced nitric oxide synthase (iNOS) expression in mice. Male mice were divided into four groups, which included the normal basal diet (control), high fat (HF) diet, HF diet + heparin (treatment group) and heparin control groups. After eight weeks from the initiation of the experiment, blood was collected and livers were harvested for biochemical analysis and histological studies. Serum levels of aspartate aminotransferase, alanine aminotransferase, hepatic triglyceride (TG) and hydroxyproline, as well as the IR, superoxide anion generation and mRNA expression of the hepatic iNOS enzyme were evaluated. Liver specimens were processed for histopathological and immunohistopathological evaluation. Heparin administration decreased the levels of the liver enzymes, IR, superoxide generation, hepatic TG, hydroxyproline and iNOS expression when compared with the HF diet group. These changes were associated with an improvement in inflammation and fibrosis observed via histopathological examination. Therefore, heparin treatment attenuates hepatic injury in steatohepatitis. PMID:25289058

  11. 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.

  12. 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

  13. 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

  14. Nitrosative stress in Escherichia coli: reduction of nitric oxide.

    PubMed

    Vine, Claire E; Cole, Jeffrey A

    2011-01-01

    The ability of enteric bacteria to protect themselves against reactive nitrogen species generated by their own metabolism, or as part of the innate immune response, is critical to their survival. One important defence mechanism is their ability to reduce NO (nitric oxide) to harmless products. The highest rates of NO reduction by Escherichia coli K-12 were detected after anaerobic growth in the presence of nitrate. Four proteins have been implicated as catalysts of NO reduction: the cytoplasmic sirohaem-containing nitrite reductase, NirB; the periplasmic cytochrome c nitrite reductase, NrfA; the flavorubredoxin NorV and its associated oxidoreductase, NorW; and the flavohaemoglobin, Hmp. Single mutants defective in any one of these proteins and even the mutant defective in all four proteins reduced NO at the same rate as the parent. Clearly, therefore, there are mechanisms of NO reduction by enteric bacteria that remain to be characterized. Far from being minor pathways, the currently unknown pathways are adequate to sustain almost optimal rates of NO reduction, and hence potentially provide significant protection against nitrosative stress. PMID:21265775

  15. 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

  16. Nasal nitric oxide in children with recurrent acute otitis media.

    PubMed

    Torretta, S; Marchisio, P; Capaccio, P; Pignataro, L

    2016-01-01

    Recently, reduced Nasal nitric oxide (nNO) nNO levels have been reported in children with adenoidal hypertrophy predisposing to chronic nasosinusal inflammation. Given the strict anatomic and physiopathologic link between the nasopharyngeal and middle ear compartments, and considering the high prevalence of otitis prone children among those affected with chronic adenoiditis, we designed a study aimed to test any possible difference in nNO levels between non-allergic children with and without recurrent acute otitis media (RAOM) associated with chronic adenoiditis. The study involved 54 children with RAOM (44.4% males; mean age= 7.5±3.5 years) and 51 children without RAOM (47.4% males; mean age= 7.0±3.8 years). nNO levels were significantly reduced in children with RAOM compared to children without RAOM (676.9±250.7 ppb vs 831.8±320.4 ppb, respectively; p= 0.02). Our results could be related to reduced NO production by the ciliated paranasal, nasopharyngeal and middle ear epithelium and the impaired sinusal ostial and Eustachian tube patency due to chronic inflammation, and seem to confirm the involvement of NO pathway in recurrent upper airway infections related to impaired ciliated respiratory mucosa. PMID:27049104

  17. 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

  18. 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

  19. 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

  20. 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.

  1. 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

  2. Inaccuracies of nitric oxide measurement methods in biological media

    PubMed Central

    Hunter, Rebecca A.; Storm, Wesley L.; Coneski, Peter N.

    2013-01-01

    Despite growing reports on the biological action of nitric oxide (NO) as a function of NO payload, the validity of such work is often questionable due to the manner in which NO is measured and/or the solution composition in which NO is quantified. To highlight the importance of measurement technique for a given sample type, NO produced from a small molecule NO donor (N-diazeniumdiolated l-proline, PROLI/NO) and a NO-releasing xerogel film were quantified in a number of physiological buffers and fluids, cell culture media, and bacterial broth using the Griess assay, a chemiluminescence analyzer, and an amperometric NO sensor. Despite widespread use, the Griess assay proved to be inaccurate for measuring NO in many of the media tested. In contrast, the chemiluminescence analyzer provided superb kinetic information in most buffers, but was impractical for NO analysis in proteinaceous media. The electrochemical NO sensor enabled greater flexibility across the various media with potential for spatial resolution, albeit at lower than expected NO totals versus either the Griess assay or chemiluminescence. The results of this study highlight the importance of measurement strategy for accurate NO analysis and reporting NO-based biological activity. PMID:23286383

  3. Origin and Impact of Nitric Oxide in Pseudomonas aeruginosa Biofilms

    PubMed Central

    2015-01-01

    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

  4. Starved Escherichia coli preserve reducing power under nitric oxide stress.

    PubMed

    Gowers, Glen-Oliver F; Robinson, Jonathan L; Brynildsen, Mark P

    2016-07-15

    Nitric oxide (NO) detoxification enzymes, such as NO dioxygenase (NOD) and NO reductase (NOR), are important to the virulence of numerous bacteria. Pathogens use these defense systems to ward off immune-generated NO, and they do so in environments that contain additional stressors, such as reactive oxygen species, nutrient deprivation, and acid stress. NOD and NOR both use reducing equivalents to metabolically deactivate NO, which suggests that nutrient deprivation could negatively impact their functionality. To explore the relationship between NO detoxification and nutrient deprivation, we examined the ability of Escherichia coli to detoxify NO under different levels of carbon source availability in aerobic cultures. We observed failure of NO detoxification under both carbon source limitation and starvation, and those failures could have arisen from inabilities to synthesize Hmp (NOD of E. coli) and/or supply it with sufficient NADH (preferred electron donor). We found that when limited quantities of carbon source were provided, NO detoxification failed due to insufficient NADH, whereas starvation prevented Hmp synthesis, which enabled cells to maintain their NADH levels. This maintenance of NADH levels under starvation was confirmed to be dependent on the absence of Hmp. Intriguingly, these data show that under NO stress, carbon-starved E. coli are better positioned with regard to reducing power to cope with other stresses than cells that had consumed an exhaustible amount of carbon. PMID:27207837

  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. Porins facilitate nitric oxide-mediated killing of mycobacteria.

    PubMed

    Fabrino, Daniela Leite; Bleck, Christopher K E; Anes, Elsa; Hasilik, Andrej; Melo, Rossana C N; Niederweis, Michael; Griffiths, Gareth; Gutierrez, Maximiliano Gabriel

    2009-09-01

    Non-pathogenic mycobacteria such us Mycobacterium smegmatis reside in macrophages within phagosomes that fuse with late endocytic/lysosomal compartments. This sequential fusion process is required for the killing of non-pathogenic mycobacteria by macrophages. Porins are proteins that allow the influx of hydrophilic molecules across the mycobacterial outer membrane. Deletion of the porins MspA, MspC and MspD significantly increased survival of M. smegmatis in J774 macrophages. However, the mechanism underlying this observation is unknown. Internalization of wild-type M. smegmatis (SMR5) and the porin triple mutant (ML16) by macrophages was identical indicating that the viability of the porin mutant in vivo was enhanced. This was not due to effects on phagosome trafficking since fusion of phagosomes containing the mutant with late endocytic compartments was unaffected. Moreover, in ML16-infected macrophages, the generation of nitric oxide (NO) was similar to the wild type-infected cells. However, ML16 was significantly more resistant to the effects of NO in vitro compared to SMR5. Our data provide evidence that porins render mycobacteria vulnerable to killing by reactive nitrogen intermediates within phagosomes probably by facilitating uptake of NO across the mycobacterial outer membrane. PMID:19460455

  7. Biosynthesis of nitric oxide activates iron regulatory factor in macrophages.

    PubMed Central

    Drapier, J C; Hirling, H; Wietzerbin, J; Kaldy, P; Kühn, L C

    1993-01-01

    Biosynthesis of nitric oxide (NO) from L-arginine modulates activity of iron-dependent enzymes, including mitochondrial acontiase, an [Fe-S] protein. We examined the effect of NO on the activity of iron regulatory factor (IRF), a cytoplasmic protein which modulates both ferritin mRNA translation and transferrin receptor mRNA stability by binding to specific mRNA sequences called iron responsive elements (IREs). Murine macrophages were activated with interferon-gamma and lipopolysaccharide to induce NO synthase activity and cultured in the presence or absence of NG-substituted analogues of L-arginine which served as selective inhibitors of NO synthesis. Measurement of the nitrite concentration in the culture medium was taken as an index of NO production. Mitochondria-free cytosols were then prepared and aconitase activity as well as IRE binding activity and induction of IRE binding activity were correlated and depended on NO synthesis after IFN-gamma and/or LPS stimulation. Authentic NO gas as well as the NO-generating compound 3-morpholinosydnonimine (SIN-1) also conversely modulated aconitase and IRE binding activities of purified recombinant IRF. These results provide evidence that endogenously produced NO may modulate the post-transcriptional regulation of genes involved in iron homeostasis and support the hypothesis that the [Fe-S] cluster of IRF mediates iron-dependent regulation. Images PMID:7504626

  8. Diode-laser-based ultraviolet absorption sensor for nitric oxide

    NASA Astrophysics Data System (ADS)

    Hanna, S. F.; Barron-Jimenez, R.; Anderson, T. N.; Lucht, R. P.; Caton, J. A.; Walther, T.

    2002-07-01

    An all-solid-state continuous-wave laser system for ultraviolet absorption measurements of the nitric oxide (NO) molecule has been developed and demonstrated. The single-mode, tunable output of a 10-mW, 395-nm external-cavity diode laser (ECDL) is sum-frequency-mixed with the output of a 115-mW, frequency-doubled, diode-pumped Nd:YAG laser in a beta-barium-borate crystal to produce 40 nW of tunable radiation at 226.8 nm. The wavelength of the 395-nm ECDL is then scanned over NO absorption lines to produce fully resolved absorption spectra. Initial results from mixtures of NO in nitrogen in a room-temperature gas cell are discussed. The estimated NO detection limit of the system for a demonstrated absorption sensitivity of 2×10-3 is 0.2 ppm per meter of path length for 300 K gas. The estimated accuracy of the measurements is ±10%.

  9. Nitric oxide-releasing NSAIDs: GI-safe antithrombotics.

    PubMed

    Wallace, J L; Del Soldato, P; Cirino, G; Muscará, M N

    1999-04-01

    Aspirin is increasingly being used for long-term prophylaxis of myocardial infarction and stroke, but its use is limited by toxicity in the gastrointestinal tract. Even very low doses of aspirin can markedly increase the risk of gastrointestinal bleeding and ulceration. While proven effective in prophylaxis of stroke and myocardial infarction, the efficacy of aspirin is limited. Addition of a nitric oxide-releasing moiety to several non-steroidal anti-inflammatory drugs results in a profound reduction in their toxicity in the gastrointestinal tract and kidney. A similar derivatization of aspirin has recently been shown to result in a more potent, gastrointestinal-sparing antithrombotic drug. Two such compounds (NCX-4215 and NCX-4016; NicOx SA) have undergone detailed evaluation thus far. In each case, the NO-aspirin has shown improved anti-aggregatory activity while not inducing detectable gastric damage. The compounds have also been shown to exert protective effects in the gastrointestinal tract exposed to other injurious agents. The NO-aspirin derivatives significantly inhibit leukocyte adherence to the vascular endothelium, which may contribute to their anti-thrombotic activity. NO-releasing derivatives of aspirin and naproxen also exhibit beneficial effects in experimental hypertension, which would also contribute to improved anti-thrombotic activity. NO-releasing derivatives of NSAIDs offer great potential as gastrointestinal-sparing anti-thrombotic drugs. PMID:16158351

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

    PubMed Central

    CEDERGREN, J; FORSLUND 2, T; SUNDQVIST 2, T; SKOGH 1, T

    2002-01-01

    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 µmol/l, P = 0·008), whereas a slight increase in l-citrulline (33 ± 11 versus 26 ± 9 µmol/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 µmol/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

  11. 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}.

  12. 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

  13. 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

  14. Partitioned Exhaled Nitric Oxide to Non-Invasively Assess Asthma

    PubMed Central

    Puckett, James L.; George, Steven C.

    2008-01-01

    Asthma is a chronic inflammatory disease of the lungs, characterized by airway hyperresponsiveness. Chronic repetitive bouts of acute inflammation lead to airway wall remodeling and possibly the sequelae of fixed airflow obstruction. Nitric oxide (NO) is a reactive molecule synthesized by NO synthases (NOS). NOS are expressed by cells within the airway wall and functionally, two NOS isoforms exist: constitutive and inducible. In asthma, the inducible isoform is over expressed, leading to increased production of NO, which diffuses into the airway lumen, where it can be detected in the exhaled breath. The exhaled NO signal can be partitioned into airway and alveolar components by measuring exhaled NO at multiple flows and applying mathematical models of pulmonary NO dynamics. The airway NO flux and alveolar NO concentration can be elevated in adults and children with asthma and have been correlated with markers of airway inflammation and airflow obstruction in cross-sectional studies. Longitudinal studies which specifically address the clinical potential of partitioning exhaled NO for diagnosis, managing therapy, and predicting exacerbation are needed. PMID:18718562

  15. Kinetic-dependent Killing of Oral Pathogens with Nitric Oxide

    PubMed Central

    Backlund, C.J.; Worley, B.V.; Sergesketter, A.R.

    2015-01-01

    Nitric oxide (NO)–releasing silica nanoparticles were synthesized via the co-condensation of tetramethyl orthosilicate with aminosilanes and subsequent conversion of secondary amines to N-diazeniumdiolate NO donors. A series of ~150 nm NO-releasing particles with different NO totals and release kinetics (i.e., half-lives) were achieved by altering both the identity and mol% composition of the aminosilane precursors. Independent of identical 2 h NO-release totals, enhanced antibacterial action was observed against the periodontopathogens Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis with extended NO-release kinetics at pH 7.4. Negligible bactericidal effect was observed against cariogenic Streptococcus mutans at pH 7.4, even when using NO-releasing silica particles with greater NO-release totals. However, antibacterial activity was observed against S. mutans at lower pH (6.4). This result was attributed to more rapid proton-initiated decomposition of the N-diazeniumdiolate NO donors and greater NO-release payloads. The data suggest a differential sensitivity to NO between cariogenic and periodontopathogenic bacteria with implications for the future development of NO-releasing oral care therapeutics. PMID:26078424

  16. A topical nitric oxide-generating therapy for cutaneous leishmaniasis.

    PubMed

    Davidson, R N; Yardley, V; Croft, S L; Konecny, P; Benjamin, N

    2000-01-01

    Nitric oxide (NO) synthesized by macrophages is cidal to Leishmania. Since NO diffuses into tissues, we reasoned that NO-generating creams applied topically to lesions might be an effective and inexpensive treatment for cutaneous leishmaniasis (CL). NO was generated non-enzymatically by the acidification of nitrite (KNO2) by ascorbic acid (ASC) or salicylic acid (SAL). Experiments in vitro showed that the combinations of KNO2 and SAL, ASC, or KC1 all killed promastigotes and amastigotes of L. major in a dose- and time-dependent manner, but were toxic to macrophages at higher concentrations. Experiments in vivo showed modest efficacy of the combinations applied topically to L. major CL lesions of BALB/c mice. Forty patients with parasitologically proven L. tropica CL from Aleppo, Syria, were treated for 4 weeks with KNO2 in aqueous cream combined with KC1, ASC, or SAL. Only 11 (28%) of 40 patients showed improvement and only 5 (12%) of 40 were cured at 2 months. Further development of NO-generating creams is warranted. PMID:10975011

  17. Nitric oxide synthases are associated with bronchial dysplasia.

    PubMed

    Puhakka, Airi R A; Harju, Terttu H; Pääkkö, Paavo K; Soini, Ylermi M; Kinnula, Vuokko L

    2006-03-01

    Recent studies suggest that reactive oxygen (ROS) and nitrogen species (RNS) are highly associated with the pathogenesis of cigarette smoke related lung diseases but their role in the malignant conversion of bronchial epithelium is unclear. The immunohistochemical expression of inducible, endothelial and neuronal nitric oxide synthases (iNOS, eNOS and nNOS) and nitrotyrosine as a biomarker of oxidative/nitrosative stress was evaluated in 79 cases including 13 non-smokers, 20 smokers without chronic obstructive pulmonary disease (COPD), 22 with COPD and 24 with metaplasia-dysplasia-sequence of the bronchial epithelium. Normal lung of non-smokers was mainly negative for nitrotyrosine, while it was higher in the alveolar macrophages of cigarette smokers and COPD than in non-smokers (p=0.025, p<0.001), and in the alveolar epithelium of smokers and COPD than in non-smokers (p=0.049). There were no major differences in the nitrotyrosine immunoreactivity between the metaplastic/dysplastic lesions and bronchial epithelium of cigarette smokers. Inducible NOS and nNOS were mainly non-detectable or weak in the normal looking bronchial epithelium of smokers and COPD, whereas metaplasia and dysplasia showed positivity for iNOS (22/24) and nNOS (14/24) in the majority of cases. Strong immunoreactivity for iNOS and nNOS was also found more often in dysplastic than metaplastic (p=0.011 and p=0.049, respectively) specimens. Thus, smoking can cause protein nitration also in normal lung. Prominent iNOS and nNOS immunoreactivity in the metaplasia-dysplasia-lesions suggests a divergent role of NOSs in lung carcinogenesis. PMID:16420964

  18. 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

  19. Real-time electrical detection of nitric oxide in biological systems with sub-nanomolar sensitivity

    NASA Astrophysics Data System (ADS)

    Jiang, Shan; Cheng, Rui; Wang, Xiang; Xue, Teng; Liu, Yuan; Nel, Andre; Huang, Yu; Duan, Xiangfeng

    2013-07-01

    Real-time monitoring of nitric oxide concentrations is of central importance for probing the diverse roles of nitric oxide in neurotransmission, cardiovascular systems and immune responses. Here we report a new design of nitric oxide sensors based on hemin-functionalized graphene field-effect transistors. With its single atom thickness and the highest carrier mobility among all materials, graphene holds the promise for unprecedented sensitivity for molecular sensing. The non-covalent functionalization through π-π stacking interaction allows reliable immobilization of hemin molecules on graphene without damaging the graphene lattice to ensure the highly sensitive and specific detection of nitric oxide. Our studies demonstrate that the graphene-hemin sensors can respond rapidly to nitric oxide in physiological environments with a sub-nanomolar sensitivity. Furthermore, in vitro studies show that the graphene-hemin sensors can be used for the detection of nitric oxide released from macrophage cells and endothelial cells, demonstrating their practical functionality in complex biological systems.

  20. Are exhaled nitric oxide measurements using the portable NIOX MINO repeatable?

    PubMed Central

    2010-01-01

    Background Exhaled nitric oxide is a non-invasive marker of airway inflammation and a portable analyser, the NIOX MINO (Aerocrine AB, Solna, Sweden), is now available. This study aimed to assess the reproducibility of the NIOX MINO measurements across age, sex and lung function for both absolute and categorical exhaled nitric oxide values in two distinct groups of children and teenagers. Methods Paired exhaled nitric oxide readings were obtained from 494 teenagers, aged 16-18 years, enrolled in an unselected birth cohort and 65 young people, aged 6-17 years, with asthma enrolled in an interventional asthma management study. Results The birth cohort participants showed a high degree of variability between first and second exhaled nitric oxide readings (mean intra-participant difference 1.37 ppb, 95% limits of agreement -7.61 to 10.34 ppb), although there was very close agreement when values were categorised as low, normal, intermediate or high (kappa = 0.907, p < 0.001). Similar findings were seen in subgroup analyses by sex, lung function and asthma status. Similar findings were seen in the interventional study participants. Conclusions The reproducibility of exhaled nitric oxide is poor for absolute values but acceptable when values are categorised as low, normal, intermediate or high in children and teenagers. One measurement is therefore sufficient when using categorical exhaled nitric oxide values to direct asthma management but a mean of at least two measurements is required for absolute values. PMID:20416092

  1. (-)-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

  2. Potential neurogenic and vascular roles of nitric oxide in migraine headache and aura.

    PubMed

    Myers, D E

    1999-02-01

    It has long been known that nitrate and nitrite medications consistently cause significant headache as a side effect. Classical research has shown that cerebral vasodilation accompanies the use of these medications. More modern studies suggest that these vasodilators exert their action on blood vessels via nitric oxide and its second messenger, cyclic guanosine monophosphate. This paper reviews research studies and theoretical articles which address the concept that nitric oxide plays a major role in the vasodilation associated with the headache phase of migraine with aura. A brief discussion of nitric oxide biochemistry and pharmacology follows. In addition, there is a review of evidence examining the possible contributions of nitric oxide to the neurogenic and vascular events associated with spreading cortical depression, an animal model of migraine aura. The paradoxical hypotheses that nitric oxide may contribute to both the propagation of spreading cortical depression and its limitation are presented. Finally, a rationale for the experimental use of nitric oxide agonists and antagonists in the abortion of migraine aura is introduced. PMID:15613204

  3. 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.

  4. Inhibitory effects of indole α-lipoic acid derivatives on nitric oxide production in LPS/IFNγ activated RAW 264.7 macrophages.

    PubMed

    Karabay, Arzu Zeynep; Koc, Aslı; Gurkan-Alp, A Selen; Buyukbingol, Zeliha; Buyukbingol, Erdem

    2015-04-01

    Alpha-lipoic acid (α-lipoic acid) is a potent antioxidant compound that has been shown to possess anti-inflammatory effects. RAW 264.7 macrophages produce various inflammatory mediators such as nitric oxide, IL-1β, IL-6 and TNF-alpha upon activation with LPS (Lipopolysaccharide) and IFNγ (interferon gamma). In this study, the effect of 12 synthetic indole α-lipoic acid derivatives on nitric oxide production and iNOS (inducible nitric oxide synthase) protein expression in LPS/IFNγ activated RAW 264.7 macrophages was determined. Cell proliferation, nitric oxide levels and iNOS protein expression were examined with thiazolyl blue tetrazolium blue test, griess assay and western blot, respectively. Our results showed that all of the indole α-lipoic acid derivatives showed significant inhibitory effects on nitric oxide production and iNOS protein levels (p < 0.05). The most active compounds were identified as compound I-4b, I-4e and II-3b. In conclusion, these indole α-lipoic acid derivatives may have the potential for treatment of inflammatory conditions related with high nitric oxide production. PMID:25727912

  5. 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

  6. 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.

  7. Nitric oxide metabolite concentrations in maternal plasma decrease during parturition: possible transient down-regulation of nitric oxide synthesis.

    PubMed

    Nanno, H; Sagawa, N; Itoh, H; Matsumoto, T; Terakawa, K; Mori, T; Itoh, H; Nakao, K

    1998-06-01

    To elucidate the possible involvement of nitric oxide (NO) in parturition, we measured the maternal plasma concentrations of the NO metabolites, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and guanosine 3',5'-cyclic phosphate (cGMP) in pregnant women at various gestational ages including those at vaginal and elective Caesarean deliveries. The plasma cGMP and NO metabolite concentrations at vaginal delivery were significantly lower than those of the pregnant women in the third trimester of pregnancy. These concentrations remained low until 4 h after delivery but returned 24 h after delivery to values similar to those of the non-pregnant women. Such suppressions of plasma cGMP and NO metabolite concentrations were not observed in the women who underwent elective Caesarean section before the onset of labour. Moreover, no significant changes were observed in the plasma ANP and BNP concentrations at the time of vaginal and Caesarean deliveries, except that a slight but significant elevation of the plasma ANP concentration was observed 1 h after Caesarean delivery. In conclusion, the plasma concentrations of cGMP and NO metabolites significantly decreased at vaginal delivery but not at Caesarean delivery. These changes were independent of the plasma ANP and BNP concentrations, suggesting the possible down-regulation of maternal NO synthesis during parturition. PMID:9665345

  8. NO to cancer: The complex and multifaceted role of nitric oxide and the epigenetic nitric oxide donor, RRx-001.

    PubMed

    Scicinski, Jan; Oronsky, Bryan; Ning, Shoucheng; Knox, Susan; Peehl, Donna; Kim, Michelle M; Langecker, Peter; Fanger, Gary

    2015-12-01

    The endogenous mediator of vasodilation, nitric oxide (NO), has been shown to be a potent radiosensitizer. However, the underlying mode of action for its role as a radiosensitizer - while not entirely understood - is believed to arise from increased tumor blood flow, effects on cellular respiration, on cell signaling, and on the production of reactive oxygen and nitrogen species (RONS), that can act as radiosensitizers in their own right. NO activity is surprisingly long-lived and more potent in comparison to oxygen. Reports of the effects of NO with radiation have often been contradictory leading to confusion about the true radiosensitizing nature of NO. Whether increasing or decreasing tumor blood flow, acting as radiosensitizer or radioprotector, the effects of NO have been controversial. Key to understanding the role of NO as a radiosensitizer is to recognize the importance of biological context. With a very short half-life and potent activity, the local effects of NO need to be carefully considered and understood when using NO as a radiosensitizer. The systemic effects of NO donors can cause extensive side effects, and also affect the local tumor microenvironment, both directly and indirectly. To minimize systemic effects and maximize effects on tumors, agents that deliver NO on demand selectively to tumors using hypoxia as a trigger may be of greater interest as radiosensitizers. Herein we discuss the multiple effects of NO and focus on the clinical molecule RRx-001, a hypoxia-activated NO donor currently being investigated as a radiosensitizer in the clinic. PMID:26164533

  9. 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

  10. 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.

  11. Nitric Oxide Is a Signal for NNR-Mediated Transcription Activation in Paracoccus denitrificans

    PubMed Central

    Van Spanning, Rob J. M.; Houben, Edith; Reijnders, Willem N. M.; Spiro, Stephen; Westerhoff, Hans V.; Saunders, Neil

    1999-01-01

    By using the ′lacZ gene, the activities of the nirI, nirS, and norC promoters were assayed in the wild type and in NNR-deficient mutants of Paracoccus denitrificans grown under various growth conditions. In addition, induction profiles of the three promoters in response to the presence of various nitrogenous oxides were determined. Transcription from the three promoters required the absence of oxygen and the presence both of the transcriptional activator NNR and of nitric oxide. The activity of the nnr promoter itself was halved after the cells had been switched from aerobic respiration to denitrification. This response was apparently not a result of autoregulation or of regulation by FnrP, since the nnr promoter was as active in the wild-type strain as it was in NNR- or FnrP-deficient mutants. PMID:10383987

  12. 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

  13. 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

  14. Effect of Nitric Oxide on the Antifungal Activity of Oxidative Stress and Azoles Against Candida albicans.

    PubMed

    Li, De-Dong; Yang, Chang-Chun; Liu, Ping; Wang, Yan; Sun, Yan

    2016-06-01

    Nitric oxide (NO) is a small molecule with a wide range of biological activities in mammalian and bacteria. However, the role of NO in fungi, especially Candida albicans, is not clear. In this study, we confirmed the generation of endogenous NO in C. albicans, and found that the production of endogenous NO in C. albicans was associated with nitric oxide synthase pathway. Our results further indicated that the production of endogenous NO in C. albicans was reduced under oxidative stress such as menadione or H2O2 treatment. Meanwhile, exogenous NO donor, sodium nitroprusside (SNP), synergized with H2O2 against C. albicans. Interestingly, SNP could inhibit the antifungal effect of azoles against C. albicans in vitro, suggesting that NO might be involved in the resistance of C. albicans to antifungals. Collectively, this study demonstrated the production of endogenous NO in C. albicans, and indicated that NO may play an important role in the response of C. albicans to oxidative stress and azoles. PMID:27570314

  15. Oxidant stress, antioxidants and nitric oxide in traffic police of Hyderabad, India.

    PubMed

    Suresh, Y; Sailaja Devi, M M; Manjari, V; Das, U N

    2000-08-01

    Exposure to environmental pollutants is known to be harmful to health, in general, and to lungs in particular. In this respect, traffic police are at particular risk due to the nature of their job, since they are exposed to emissions from the vehicles. Here, we show that in the traffic police of Hyderabad city, India, the plasma levels of lipid peroxides are high, whereas the concentrations of the nitric oxide are low. In addition, the levels of various antioxidants in the RBC lysate such as catalase, superoxide dismutase and glutathione peroxidase were found to be low with no significant alteration in plasma ceruloplasmin levels. These results suggest that exposure to air pollutants, a major portion of which is due to emissions from the vehicles, can increase oxidant stress, decrease the levels of antioxidants and nitric oxide. This imbalance in the oxidant/antioxidant system may lead to lung damage and is likely to cause respiratory problems in individuals exposed to air pollution. PMID:15092903

  16. 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.

  17. Nitric Oxide Synthetic Pathway in Red Blood Cells Is Impaired in Coronary Artery Disease

    PubMed Central

    Eligini, Sonia; Porro, Benedetta; Lualdi, Alessandro; Squellerio, Isabella; Veglia, Fabrizio; Chiorino, Elisa; Crisci, Mauro; Garlaschè, Anna; Giovannardi, Marta; Werba, Josè-Pablo; Tremoli, Elena; Cavalca, Viviana

    2013-01-01

    Background All the enzymatic factors/cofactors involved in nitric oxide (NO) metabolism have been recently found in red blood cells. Increased oxidative stress impairs NO bioavailability and has been described in plasma of coronary artery disease (CAD) patients. The aim of the study was to highlight a potential dysfunction of the metabolic profile of NO in red blood cells and in plasma from CAD patients compared with healthy controls. Methods We determined L-arginine/NO pathway by liquid-chromatography tandem mass spectrometry and high performance liquid chromatography methods. The ratio of oxidized and reduced forms of glutathione, as index of oxidative stress, was measured by liquid-chromatography tandem mass spectrometry method. NO synthase expression and activity were evaluated by immunofluorescence staining and ex-vivo experiments of L-[15N2]arginine conversion to L-[15N]citrulline respectively. Results Increased amounts of asymmetric and symmetric dimethylarginines were found both in red blood cells and in plasma of CAD patients in respect to controls. Interestingly NO synthase expression and activity were reduced in CAD red blood cells. In contrast, oxidized/reduced glutathione ratio was increased in CAD and was associated to arginase activity. Conclusion Our study analyzed for the first time the whole metabolic pathway of L-arginine/NO, both in red blood cells and in plasma, highlighting an impairment of NO pathway in erythrocytes from CAD patients, associated with decreased NO synthase expression/activity and increased oxidative stress. PMID:23940508

  18. 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.

  19. Oxidative stress and nitric oxide pathway in adult patients who are candidates for cardiac surgery: patterns and differences

    PubMed Central

    Cavalca, Viviana; Tremoli, Elena; Porro, Benedetta; Veglia, Fabrizio; Myasoedova, Veronika; Squellerio, Isabella; Manzone, Daniela; Zanobini, Marco; Trezzi, Matteo; Di Minno, Matteo Nicola Dario; Werba, José Pablo; Tedesco, Calogero; Alamanni, Francesco; Parolari, Alessandro

    2013-01-01

    OBJECTIVES We investigated whether oxidative stress and the arginine/nitric oxide pathway differ in control subjects and in adult patients who are candidates for the three most common cardiac surgical operations: coronary bypass surgery, aortic valve replacement for calcific non-rheumatic aortic stenosis or mitral valve repair for degenerative mitral insufficiency. METHODS In this prospective observational study, we studied 165 consecutive patients undergoing surgery from January to June 2011 (coronary bypass surgery, n = 63; aortic valve replacement for calcific non-rheumatic aortic stenosis, n = 51; mitral valve repair for degenerative mitral insufficiency, n = 51). Thirty-three healthy subjects with cardiovascular risk factors similar to surgery patients were also studied (Controls). Oxidative stress (the ratio of reduced and oxidized glutathione and urinary isoprostane), antioxidants (alpha- and gamma tocopherol) and factors involved in nitric oxide synthesis (arginine, symmetric and asymmetric dimethylarginine) were measured before surgery. Analysis of variance general linear models and principal component analysis were used for statistical analysis. RESULTS Surgical patients had increased levels of oxidative stress and decreased levels of antioxidants. Increased levels of nitric oxide inhibitor asymmetric dimethylarginine were detected in surgical candidates, suggesting arginine/nitric oxide pathway impairment. Concerning the differences among surgical procedures, higher oxidative stress and a major imbalance of the ratio between substrate and inhibitors of nitric oxide synthesis were evidenced in patients who were candidates for mitral valve repair with respect to coronary bypass surgery patients and patients with calcific non-rheumatic aortic stenosis. CONCLUSIONS Patients undergoing cardiac surgery have increased oxidative stress and a trend towards an impaired arginine/nitric oxide pathway with respect to Controls. Patients affected by mitral valve

  20. 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...