Sample records for determine nitric oxide

  1. Nitric oxide

    Microsoft Academic Search

    Richard A. Robbins; Matthew B. Grisham

    1997-01-01

    Nitric oxide (NO) is a gas with diverse biological activities produced from arginine by NO synthases. It is capable of interacting with a number of molecules, most notably superoxide, forming peroxynitrite, which, in turn, can mediate bactericidal or cytotoxic reactions. Nitric oxide also mediates smooth muscle relaxation, neurotransmission, and modulation of inflammation in a number of organ systems and pathophysiologic

  2. Colorimetric Methods for the Determination of Nitric Oxide Concentration in Neutral Aqueous Solutions

    Microsoft Academic Search

    Raymond W. Nims; John F. Darbyshire; Joseph E. Saavedra; Danae Christodoulou; Ingeborg Hanbauer; George W. Cox; Matthew B. Grisham; Franciose Laval; John A. Cook; Murali C. Krishna; David A. Wink

    1995-01-01

    Two convenient colorimetric methods are described for the determination of nitric oxide (NO) concentration in neutral aqueous solutions. Both techniques take advantage of the fact that nitrosating and oxidizing intermediates are generated in the course of the NO\\/O2 reaction. In the first method, 2,2?-azinobis(3-ethylbenzthiazoline-6-sulfonic acid) is oxidized to the corresponding cation radical, imparting to the solution an intense green color

  3. Enhanced colonic nitric oxide generation and nitric oxide synthase activity in ulcerative colitis and Crohn's disease

    Microsoft Academic Search

    D Rachmilewitz; J S Stamler; D Bachwich; F Karmeli; Z Ackerman; D K Podolsky

    1995-01-01

    Recent studies have suggested that nitric oxide (NO.), the product of nitric oxide synthase in inflammatory cells, may play a part in tissue injury and inflammation through its oxidative metabolism. In this study the colonic generation of oxides of nitrogen (NOx) and nitric oxide synthase activity was determined in ulcerative colitis and Crohn's disease. Colonic biopsy specimens were obtained from

  4. 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

  5. Hippocampus and nitric oxide.

    PubMed

    Hu, Yao; Zhu, Dong-Ya

    2014-01-01

    Since it was first identified to play an important role in relaxation of blood vessels, nitric oxide has been demonstrated to regulate many biological processes, especially in the central nervous system. Of the three types of enzymes that produce nitric oxide in humans and rodents, neuronal type is found almost exclusively in the nervous system. This gaseous molecule is a nonclassical neurotransmitter, which maintains the activities of neural cells and regulates the normal functions of brain. It appears to play a role in promoting the transfer of nerve signals from one neuron to another, maintaining the synaptic strength. Meanwhile, nitric oxide is a unique regulator on neurogenesis and synaptogenesis, producing the positive or negative effects upon different signal pathways or cellular origins and locations. Based on its significant roles in neural plasticity, nitric oxide is involved in a number of central nervous diseases, such as ischemia, depression, anxiety, and Alzheimer's disease. Clarifying the profiles of nitric oxide in the brain tissues and its participation in pathophysiological processes opens a new avenue for development of new therapeutic strategies. Thus, this chapter specifies the effects of nitric oxide in the hippocampus, a key structure implicated in the modulation of mood and memories, exhibiting the trend of future research on nitric oxide. PMID:25189386

  6. Nitric oxide as an antioxidant

    SciTech Connect

    Kanner, J.; Harel, S.; Granit, R. (Department of Food Science, Volcani Center, Bet Dagan (Israel))

    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.

  7. C-reactive protein levels determine systemic nitric oxide bioavailability in patients with coronary artery disease

    Microsoft Academic Search

    Stephan Fichtlscherer; Susanne Breuer; Volker Schachinger; Stefanie Dimmeler; Andreas M. Zeiher

    Aim Elevated C-reactive protein (CRP) levels are associated with impaired endothelial vasoreactivity in patients with coronary artery disease (CAD). Because inflammatory cytokines experimentally reduce basal and stimulated endothelial nitric oxide (NO) release, we hypothesised that patients with elevated CRP-levels are characterised by a systemic impairment in NO bioavailability. Methods and results Forearm blood flow (FBF) responses were measured by venous

  8. Reference Values and Determinants of Fractional Concentration of Exhaled Nitric Oxide in Healthy Children

    PubMed Central

    Cho, Hyun-Ju; Jung, Young-Ho; Yang, Song-I; Lee, Eun; Kim, Hyung Young; Seo, Ju-Hee; Kwon, Ji-Won; Kim, Byoung-Ju; Kim, Hyo-Bin; Lee, So-Yeon; Song, Dae Jin; Kim, Woo Kyung; Jang, Gwang Cheon; Shim, Jung Yeon

    2014-01-01

    Purpose Measurement of the fractional concentration of exhaled nitric oxide (FeNO) is a quantitative, noninvasive, simple, safe method of assessing airway inflammation. While FeNO measurement has been standardized, reference values for elementary school children are scarce. The aim of this study was to establish reference values for FeNO in children. Methods FeNO was measured in elementary school children at 6-12 years of age in Seoul, Korea, following American Thoracic Society guidelines and using a chemiluminescence analyzer (NIOX Exhaled Nitric Oxide Monitoring System, Aerocrine, Sweden). A total of 1,252 children completed a modified International Study of Asthma and Allergy in Children (ISAAC) questionnaire; FeNO was measured in 1,063 children according to the protocol and in 808 children defined as healthy controls. Results Mean FeNO were 10.32 ppb, 16.58 ppb, and 12.36 ppb in non-atopic, atopic, and all 808 healthy controls, respectively. FeNO was not associated with age and gender. The FeNO reference equations were determined by multiple linear regression analysis, taking into account the variables of age, height, weight, total IgE, eosinophil percent, and bronchial hyper-responsiveness (methacholine PC20). FeNO=0.776+0.003×total IgE+0.340×eosinophil percent; coefficient of determination (R2)=0.084 in the 501 healthy non-atopic controls. FeNO=-18.365+1.536×eosinophil percent, R2=0.183 in the 307 healthy atopic controls; and FeNO=-7.888+0.130×Height+0.004×total IgE+1.233×eosinophil percent, R2=0.209 in the 808 all healthy controls. Eosinophil percent was correlated with FeNO in all healthy controls. FeNO was not associated with BMI. Conclusion This study provides reference values for FeNO that can be used to evaluate airway inflammation in elementary school children. Determinants that could most accurately predict FeNO in healthy school-age children were assessed. PMID:24587955

  9. Student Nitric Oxide Explorer

    NASA Astrophysics Data System (ADS)

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

    1996-10-01

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

  10. Reference Ranges and Determinant Factors for Exhaled Nitric Oxide in a Healthy Korean Elderly Population

    PubMed Central

    Jo, Eun-Jung; Song, Woo-Jung; Kim, Tae-Wan; Park, Heung-Woo; Kim, Tae-Bum; Kim, Sang-Heon; Hur, Gyu-Young; Lee, Jae-Hyung; Yoon, Ho-Joo; Cho, Nam-Ho; Moon, Hee-Bom; Min, Kyung-Up

    2014-01-01

    Purpose Exhaled nitric oxide (NO) is a useful non-invasive biomarker for asthma diagnosis; however, the literature suggests that exhaled NO levels may be affected by demographic factors. The present analysis investigated determinant factors that present exhaled NO reference levels for Korean elderly adults. Methods For reference levels, we analyzed the baseline data of healthy adult participants in the Ansung cohort. The fraction of exhaled NO (FeNO) was measured by NIOX MINO®. The characterization of the subjects was performed through structured questionnaires, spirometry, and methacholine challenge tests. To validate the diagnostic utility of the determined reference levels, asthma patients were recruited from medical institutions for FeNO measurement. Results A total of 570 healthy subjects were analyzed (mean age, 59.9±12.3; male, 37.0%) for reference levels. FeNO levels significantly correlated with weight, height, body mass index, atopy, or forced expiratory volume in 1 second % predicted by simple linear regression analysis. Multiple linear regression analysis identified gender as an independent determinant for FeNO levels; subsequently, the reference values for FeNO were 18.2±10.6 ppb (5th to 95th percentile, 6.0 to 37.4 ppb) for males and 12.1±6.9 ppb (5th to 95th percentile, 2.5 to 27.0 ppb) for females. The diagnostic utility of FeNO reference levels was validated by receiver operating curve analysis (area under curve, 0.900 for males and 0.885 for females) for diagnosing asthma. The optimal cutoff values for the prediction of asthma were 30.5 ppb for males and 20.5 ppb for females. Conclusions The current analysis presented reference ranges and the diagnostic utility of FeNO levels for asthma in Korean elderly adults. PMID:25374749

  11. Inhaled nitric oxide fails to confer the pulmonary protection provided by distal stimulation of the nitric oxide pathway at the level of cyclic guanosine monophosphate

    Microsoft Academic Search

    Yoshifumi Naka; Dilip K. Roy; Arthur J. Smerling; Robert E. Michler; Craig R. Smith; David M. Stern; Mehmet C. Oz; David J. Pinsky

    1995-01-01

    It has been suggested that inhaled nitric oxide gas may be beneficial after lung transplantation, because endogenous levels of pulmonary nitric oxide decline rapidly after reperfusion. However theoretical concerns remain about the formation of highly toxic oxidants during the quenching of nitric oxide by superoxide. To determine whether distal stimulation of the nitric oxide–cyclic guanosine monophosphate pathway at the level

  12. An effective method of scavenging nitric oxide.

    PubMed

    Squire, S; Kightley, R; Petros, A J

    1996-09-01

    We report an effective method of scavenging nitric oxide and nitrogen dioxide. We have compared three agents, a commercially available filter, soda lime and activated charcoal, for their effectiveness and duration of action. Complete absorption of nitric oxide and nitrogen dioxide for a period of 170 h was obtained using the commercial filter. However, soda lime and charcoal were unable to successfully scavenge either gas. The resistance characteristics of this filter when dry or humidified were determined. PMID:8949828

  13. Delivering nitric oxide with nanoparticles.

    PubMed

    Quinn, John F; Whittaker, Michael R; Davis, Thomas P

    2015-05-10

    While best known for its important signalling functions in human physiology, nitric oxide is also of considerable therapeutic interest. As such, nanoparticle-based systems which enable the sustained exogenous delivery of nitric oxide have been the subject of considerable investigation in recent years. Herein we review the various nanoparticle systems that have been used to date for nitric oxide delivery, and explore the array of potential therapeutic applications that have been reported. Specifically, we discuss the modification of sol-gel based silica particles, functionalised metal/metal oxide nanoparticles, polymer-coated metal nanoparticles, dendrimers, micelles and star polymers to impart nitric oxide release capability. We also consider the various areas in which therapeutic applications are envisaged: wound healing, antimicrobial applications, cardiovascular treatments, sexual medicine and cancer treatment. Finally, we discuss possible future directions for this versatile and potentially important technology. PMID:25665865

  14. 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.

  15. Nitric Oxide-Releasing Compounds

    NSDL National Science Digital Library

    The five WebWare Molecules for December derive from the article Nitrogen-Based Diazeniumdiolates: Versatile Nitric Oxide-Releasing Compounds for Biomedical Research and Potential Clinical Applications by Joseph E. Saavedra and Larry K. Keefer.

  16. 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.

  17. 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 [Department of Radiotherapy, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels (Belgium)] [Department of Radiotherapy, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels (Belgium); De Ridder, Mark, E-mail: mark.deridder@uzbrussel.be [Department of Radiotherapy, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels (Belgium)

    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.

  18. Iridium oxide and palladium modified nitric oxide microsensor

    Microsoft Academic Search

    Yuezhong Xian; Wenliang Sun; Jian Xue; Min Luo; Litong Jin

    1999-01-01

    An electrochemical microsensor, constructed by chemical modification of Nafion, poly(vinyl pyridine) (PVP), palladium and iridium oxide onto a platinum microelectrode, has been developed for the determination of nitric oxide (NO). This microsensor exhibits excellent catalytic activity toward NO oxidation, which is confirmed by differential pulse voltammetry. Cyclic voltammetry and differential pulse amperometry are also performed to measure NO. The catalytic

  19. Nitric Oxide Synthase and Xanthine Oxidase Activities in the Spermatic Vein of Patients with Varicocele: A Potential Role for Nitric Oxide and Peroxynitrite in Sperm Dysfunction

    Microsoft Academic Search

    Dionisios Mitropoulos; George Deliconstantinos; Anastasios Zervas; Vassiliki Villiotou; Constantinos Dimopoulos; John Stavrides

    1996-01-01

    PurposeThe oxidative and reductive stresses within the varicocele veins were estimated. Nitric oxide synthase and xanthine oxidase activities, as well as nitric oxide, S-nitrosothiols and superoxide release within the spermatic vein in patients with varicocele, and the role of the noxious oxidant peroxynitrite formed from nitric oxide and superoxide in sperm dysfunction were determined.

  20. Satellite measurements of the backscattered ultraviolet to determine ozone trends, volcanic SO2, and nitric oxide

    NASA Technical Reports Server (NTRS)

    Mcpeters, Richard

    1993-01-01

    Measurements of the atmospheric backscattered UV albedo have been used from satellites for more than 20 years to measure ozone. The longest continuous record has been from the Solar Backscattered Ultraviolet instrument (SBUV) and TOMS on the Nimbus 7 satellite, which have been in operation since November of 1978. Because of degradation in space of the diffuser plate used to measure extraterrestrial solar flux, it has been necessary to develop new techniques to maintain the calibration of these instruments. Calibration is maintained by requiring that ozone measured by different wavelength pairs be consistent, and by requiring that ozone measured at different solar zenith angles be consistent. This technique of using a geophysical quantity, ozone, as a transfer standard for wavelength calibration is very powerful. The recalibrated data have been used to measure total ozone trends to an accuracy of +/- 1.3 percent 2(sigma) error over ten years. No significant trends are found near the equator, but significant trends larger than predicted by homogeneous chemistry are found at middle to high latitudes in both hemispheres. In addition, UV albedo data have been used to measure SO2 using band structure in the 300-310 nm range, and to measure nitric oxide in the upper stratosphere and mesosphere using the (10) and (02) NO gamma band fluorescence features.

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

    PubMed Central

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

    2014-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1995-01-01

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

  3. Flavonoids as Scavengers of Nitric Oxide Radical

    Microsoft Academic Search

    S. A. B. E. Vanacker; M. N. J. L. Tromp; G. R. M. M. Haenen; W. J. F. Vandervijgh; A. Bast

    1995-01-01

    Flavonoids are a group of naturally occurring compounds used, e.g., in the treatment of vascular endothelial damage. They are known to be excellent scavengers of oxygen free radicals. Since the nitric oxide radical (.NO) probably plays a role in this pathology, the .NO scavenging capacity of the flavonoids was determined. It was found that the flavonoids are very potent .NO

  4. 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 ...

  5. Is nitric oxide luteolytic or antiluteolytic?

    Microsoft Academic Search

    Y. S. Weems; E. Lennon; T. Uchima; A. Raney; K. Goto; A. Ong; H. Zaleski; C. W. Weems

    2005-01-01

    Nitric oxide (NO) has been reported to be luteolytic based on treatment of cows in vivo with an inhibitor of nitric oxide synthase (NOS-produces NO), which delayed the decline in progesterone by two to three days [Jaroszewki J, Hansel, W. Intraluteal administration of a nitric oxide synthase blocker stimulates progesterone, oxytocin secretion and prolongs the life span of the bovine

  6. Nitric oxide and cellular respiration

    Microsoft Academic Search

    M. Brunori; A. Giuffrè; P. Sarti; G. Stubauer; M. T. Wilson

    1999-01-01

    The role of nitric oxide (NO) as a signalling molecule involved in many pathophysiological processes (e.g., smooth muscle relaxation, inflammation, neurotransmission, apoptosis) has been elaborated during the last decade. Since NO has also been found to inhibit cellular respiration, we review here the available information on the interactions of NO with cytochrome c oxidase (COX), the terminal enzyme of the

  7. Nitric oxide and mitochondrial respiration

    Microsoft Academic Search

    Guy C Brown

    1999-01-01

    Nitric oxide (NO) and its derivative peroxynitrite (ONOO?) inhibit mitochondrial respiration by distinct mechanisms. Low (nanomolar) concentrations of NO specifically inhibit cytochrome oxidase in competition with oxygen, and this inhibition is fully reversible when NO is removed. Higher concentrations of NO can inhibit the other respiratory chain complexes, probably by nitrosylating or oxidising protein thiols and removing iron from the

  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 and brain hyperexcitability.

    PubMed

    Ferraro, Giuseppe; Sardo, Pierangelo

    2004-01-01

    Nitric oxide (NO) is a gaseous messenger involved in atypical forms of intercellular communications, able to exert a strong functional modulation of several neurotransmitter systems. In particular, NO heavily influences the excitatory neurotransmitter glutamate, mainly through NMDA receptors, and the inhibitory neurotransmitter GABA, mainly through GABA A receptors. Due to the involvement of glutamate and GABA in a delicate balance conditioning the functional status of the neural cells, this interaction suggests a role for NO in regulating neuronal excitability and its transition towards hyperexcitability phenomena. This article reviews the main knowledge about the relationships existing between the activity of the NO system and the experimental aspects of epilepsy, focusing on the somewhat antithetic findings about the proconvulsant or the anticonvulsant roles exerted by nitric oxide. PMID:15341192

  10. Nitric Oxide Activates Cyclooxygenase Enzymes

    Microsoft Academic Search

    Daniela Salvemini; Thomas P. Misko; Jaime L. Masferrer; Karen Seibert; Mark G. Currie; Philip Needleman

    1993-01-01

    We have evaluated the role of nitric oxide (NO) on the activity of the constitutive and induced forms of cyclooxygenase (COX; COX-1 and COX-2, respectively). Induction of NO synthase (NOS) and COX (COX-2) in the mouse macrophage cell line RAW264.7 by Escherichia coli lipopolysaccharide (1 mu g\\/ml, 18 h) caused an increase in the release of nitrite (NO^-_2) and prostaglandin

  11. Nitric Oxide Synthase and Postischemic Liver Injury

    Microsoft Academic Search

    Shigeyuki Kawachi; Ian N. Hines; F. Stephen Laroux; Jason Hoffman; Sulamain Bharwani; Laura Gray; David Leffer; Matthew B. Grisham

    2000-01-01

    The objective of this study was to determine what roles the endothelial cell and inducible isoforms of nitric oxide synthase (eNOS, iNOS) play in ischemia and reperfusion (I\\/R)-induced liver injury in vivo in mice genetically deficient in each isoform of NOS. We found that 45 min of partial (70%) liver ischemia and 5 h of reperfusion induced substantial liver injury

  12. Resveratrol and endothelial nitric oxide.

    PubMed

    Xia, Ning; Förstermann, Ulrich; Li, Huige

    2014-01-01

    Nitric oxide (NO) derived from the endothelial NO synthase (eNOS) has antihypertensive, antithrombotic, anti-atherosclerotic and antiobesogenic properties. Resveratrol is a polyphenol phytoalexin with multiple cardiovascular and metabolic effects. Part of the beneficial effects of resveratrol are mediated by eNOS. Resveratrol stimulates NO production from eNOS by a number of mechanisms, including upregulation of eNOS expression, stimulation of eNOS enzymatic activity and reversal of eNOS uncoupling. In addition, by reducing oxidative stress, resveratrol prevents oxidative NO inactivation by superoxide thereby enhancing NO bioavailability. Molecular pathways underlying these effects of resveratrol involve SIRT1, AMPK, Nrf2 and estrogen receptors. PMID:25302702

  13. 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

  14. 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.

  15. 21 CFR 868.5165 - Nitric oxide administration apparatus.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...2010-04-01 2010-04-01 false Nitric oxide administration apparatus. 868...Therapeutic Devices § 868.5165 Nitric oxide administration apparatus. (a) Identification. The nitric oxide administration apparatus is a...

  16. Role of exhaled nitric oxide in asthma

    Microsoft Academic Search

    Deborah H Yates

    2001-01-01

    Nitric oxide (NO), an evanescent atmospheric gas, has recently been discovered to be an important biological mediator in animals and humans. Nitric oxide plays a key role within the lung in the modulation of a wide variety of functions including pulmonary vascular tone, nonadrenergic non-cholinergic (NANC) transmission and modification of the inflammatory response. Asthma is characterized by chronic airway inflammation

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. Exhaled nitric oxide in sarcoidosis

    PubMed Central

    Wilsher, M; Fergusson, W; Milne, D; Wells, A

    2005-01-01

    Background: Increased production of nitric oxide (NO) by the lower respiratory tract is viewed as a marker of airway inflammation in asthma and bronchiectasis. NO is a potentially important immune modulator, inhibiting the release of several key pro-inflammatory cytokines. As sarcoidosis is characterised by granulomatous airway inflammation, we hypothesised that exhaled NO levels might be raised in sarcoidosis and correlate with the morphological extent and functional severity of disease. Methods: Fifty two patients with sarcoidosis (29 men) of mean age 42 years underwent thin section computed tomography (CT), pulmonary function tests, and measurement of exhaled NO. Results: Exhaled NO levels (median 6.8 ppb, range 2.4–21.8) did not differ significantly from values in 44 control subjects, and were not related to the extent of individual CT abnormalities or the level of pulmonary function impairment. Conclusion: Exhaled NO levels are not increased in pulmonary sarcoidosis. PMID:16244094

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

    NASA Technical Reports Server (NTRS)

    Fischer, Karen E.; Rock, Kenneth E.

    1995-01-01

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

  3. Cogeneration of electric energy and nitric oxide.

    PubMed

    Vayenas, C G; Farr, R D

    1980-05-01

    A solid electrolyte fuel cell operating on ammonia fuel has been constructed and tested. The yield of nitric oxide can exceed 60 percent with simultaneous electric energy production. Two dimensionless numbers have been identified which govern the product selectivity and power output of this fuel cell. The cell appears to be a promising candidate for nitric acid and electric energy cogeneration. PMID:17732844

  4. Nitric oxide bioavailability in malaria.

    PubMed

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

    2005-09-01

    Rational development of adjunct or anti-disease therapy for severe Plasmodium falciparum malaria requires cellular and molecular definition of malarial pathogenesis. Nitric oxide (NO) is a potential target for such therapy but its role during malaria is controversial. It has been proposed that NO is produced at high levels to kill Plasmodium parasites, although the unfortunate consequence of elevated NO levels might be impaired neuronal signaling, oxidant damage and red blood cell damage that leads to anemia. In this case, inhibitors of NO production or NO scavengers might be an effective adjunct therapy. However, increasing amounts of evidence support the alternate hypothesis that NO production is limited during malaria. Furthermore, the well-documented NO scavenging by cell-free plasma hemoglobin and superoxide, the levels of which are elevated during malaria, has not been considered. Low NO bioavailability in the vasculature during malaria might contribute to pathologic activation of the immune system, the endothelium and the coagulation system: factors required for malarial pathogenesis. Therefore, restoring NO bioavailability might represent an effective anti-disease therapy. PMID:16039159

  5. Lipopolysaccharide and cytokines induce nitric oxide synthase and produce nitric oxide in cultured normal human melanocytes

    Microsoft Academic Search

    Irene Machado Rocha; Lidia Andreu Guillo

    2001-01-01

    \\u000a Abstract The role of nitric oxide in normal and pathological conditions of human skin is still poorly understood. In this study we\\u000a have demonstrated by immunobloting the expression of an inducible nitric oxide synthase isoform (iNOS) in cultured normal\\u000a human melanocytes treated with bacterial lipopolysaccharide, tumor necrosis factor-· and interferon-Á. Nitric oxide was also\\u000a detected in the culture medium and

  6. Nitric Oxide Synthases and Atrial Fibrillation

    PubMed Central

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

    2012-01-01

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

  7. Nitric oxide production by Tunguska meteor

    NASA Technical Reports Server (NTRS)

    Park, C.

    1978-01-01

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

  8. Anticonvulsant drugs, oxidative stress and nitric oxide.

    PubMed

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

    2011-01-01

    Nitric Oxide (NO) is thought to play a fundamental role in the genesis and the spreading of epileptiform hyperactivity, although its function is unclear and controversial. As a free radical, NO may cause oxidative stress, which is emerging as an important mechanism in the etiology of seizure-induced neuronal death. Here we investigated the role of NO in seizure mechanisms through oxidative stress generation by studying the effect of anticonvulsant drugs such as amino oxyacetic acid (AAOA), valproate (VALP), diazepam (DIAZ) and gabapentin (GBPTNA) on oxidative stress in the brain, estimated as free carbonyls by the method of Dalle and Rossi, and by measuring NO by the indirect method based on the Griess reaction. Results show that, except for AAOA and VALP, anticonvulsants did not significantly affect or decreased free carbonyls, but reversed the oxidative stress produced by pentylenetetrazole (PTZ) induced convulsions. Anticonvulsants except AAOA diminished NO levels and with the exception of VALP, counteracted the increase in NO generated by PTZ. Anticonvulsants decreased oxidative stress and NO especially in hippocampus (HI) and cortex (CX), and reversed PTZ effects on both parameters. PTZ diminished NO in HI, which could be explained since PTZ caused an increase on endothelial NO synthase but a decrease in neuronal NOS expression in this brain area. Since the drugs studied are modulating GABA levels, our results suggest that seizures generated by alterations in GABAergic transmission produce oxidative stress caused by NO, which can be reversed by anticonvulsants. The effects described differ among the brain regions studied and the NO synthase isoform affected. PMID:22423579

  9. Nitric oxide synthase activity in mitochondria

    Microsoft Academic Search

    Pedram Ghafourifar; Christoph Richter

    1997-01-01

    In the present study we show the existence of a functional nitric oxide synthase (NOS) in rat liver mitochondria. The enzyme uses l-arginine (l-arg) to produce nitric oxide (NO) and l-citrulline, and is Ca2+-dependent. l-Arg analogues, N?-monomethyl-l-arg and N?-nitro-l-arg, inhibit the enzyme, and d-arginine is not a substrate for it. We found mitochondrial NOS (mtNOS) activity associated with the inner

  10. Nucleus accumbens nitric oxide immunoreactive interneurons receive nitric oxide and ventral subicular afferents in rats.

    PubMed

    French, S J; Ritson, G P; Hidaka, S; Totterdell, S

    2005-01-01

    The nitric oxide generating neurons of the nucleus accumbens exert a powerful influence over striatal function, in addition, these nitrergic inputs are in a position to regulate the dopaminergic and glutamatergic inputs on striatal projection neurons. It was the aim of this study to establish the source of the glutamatergic drive to nitric oxide synthase interneurons of the nucleus accumbens. The nucleus accumbens nitric oxide-generating neurons receive asymmetrical, excitatory, presumably glutamatergic inputs. Possible sources of these inputs could be the limbic and cortical regions known to project to this area. To identify sources of the excitatory inputs to the nitric oxide synthase-containing interneurons of the nucleus accumbens in the rat we first examined the ultrastructural morphology of asymmetrical synaptic specializations contacting nitric oxide synthase-immunohistochemically labeled interneurons in the nucleus accumbens. Neurons were selected from different regions of the nucleus accumbens, drawn using camera lucida, processed for electron microscopic analysis, and the boutons contacting nitric oxide synthase-labeled dendrites were photographed and correlated to the drawings. Using vesicle size as the criterion the source was predicted to be either the prefrontal cortex or the ventral subiculum of the hippocampus. To examine this prediction, a further study used anterograde tracing from both the prefrontal cortex and the ventral subiculum, and nitric oxide synthase immunohistochemistry with correlated light and electron microscopy. Based on appositions by anterogradely labeled fibers, selected nitric oxide synthase-labeled neurons within the nucleus accumbens, were examined with electron microscopic analysis. With this technique we confirmed the prediction that subicular afferent boutons make synaptic contact with nitric oxide synthase interneurons, and demonstrated anatomically that nitric oxide synthase boutons make synaptic contact with the dendritic arbors of nitric oxide synthase interneurons. We suggest that the subicular input may excite the nitric oxide synthase neurons synaptically, while the nitric oxide synthase-nitric oxide synthase interactions underlie a nitric oxide signaling network which propagates hippocampal information, and expands the hippocampus's influence on 'gating' information flow across the nucleus accumbens. PMID:16084659

  11. Nitric Oxide and Salmonella Pathogenesis

    PubMed Central

    Henard, Calvin A.; Vázquez-Torres, Andrés

    2011-01-01

    Nitric oxide (NO) and its congeners contribute to the innate immune response to Salmonella. This enteric pathogen is exposed to reactive nitrogen species (RNS) in the environment and at different anatomical locations during its infectious cycle in vertebrate hosts. Chemical generation of RNS enhances the gastric barrier to enteropathogenic bacteria, while products of the Salmonella pathogenicity island 1 type III secretion system and Salmonella-associated molecular patterns stimulate transcription of inducible NO synthase (iNOS) by cells of the mononuclear phagocytic cell lineage. The resulting NO, or products that arise from its interactions with oxygen (O2) or iron and low-molecular weight thiols, are preferentially bacteriostatic against Salmonella, while reaction of NO and superoxide (O2?) generates the bactericidal compound peroxynitrite (ONOO?). The anti-Salmonella activity of RNS emanates from the modification of redox active thiols and metal prosthetic groups of key molecular targets of the electron transport chain, central metabolic enzymes, transcription factors, and DNA and DNA-associated proteins. In turn, Salmonella display a plethora of defenses that modulate the delivery of iNOS-containing vesicles to phagosomes, scavenge and detoxify RNS, and repair biomolecules damaged by these toxic species. Traditionally, RNS have been recognized as important mediators of host defense against Salmonella. However, exciting new findings indicate that Salmonella can exploit the RNS produced during the infection to foster virulence. More knowledge of the primary RNS produced in response to Salmonella infection, the bacterial processes affected by these toxic species, and the adaptive bacterial responses that protect Salmonella from nitrosative and oxidative stress associated with NO will increase our understanding of Salmonella pathogenesis. This information may assist in the development of novel therapeutics against this common enteropathogen. PMID:21833325

  12. [Nitric oxide and lipid peroxidation].

    PubMed

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

    1995-01-01

    Nitric oxide (NO) is a free radical produced enzymatically in biological systems from the guanidino group of L-arginine. Its large spectrum of biological effects is achieved through chemical interactions with different targets including oxygen (O2), superoxide (O2o-) and other oxygen reactive species (ROS), transition metals and thiols. Superoxide anions and other ROS have been reported to react with NO to produce peroxynitrite anions that can decompose to form nitrogen dioxide (NO2) and hydroxyl radial (OHo). Thus, NO has been reported to have a dual effect on lipid peroxidation (prooxidant via the peroxynitrite or antioxydant via the chelation of ROS). In the present study we have investigated in different models the in vitro and in vivo action of NO on lipid peroxidation. Copper-induced LDL oxidation were used as an in vitro model. Human LDL (100 micrograms ApoB/ml) were incubated in oxygene-saturated PBS buffer in presence or absence of Cu2+ (2.5 microM) with increasing concentrations of NO donnors (sodium nitroprussiate or nitroso-glutathione). LDL oxidation was monitored continuously for conjugated diene formation (234 nm) and 4-hydroxynonenal (HNE) accumulation. Exogenous NO prevents in a dose dependent manner the progress of copper-induced oxidation. Ischaemia-reperfusion injury (I/R), characterized by an overproduction of ROS, is used as an in vivo model. Anaesthetized rats were submitted to 1 hour renal ischaemia following by 2 hours of reperfusion. Sham-operated rats (SOP) were used as control. Lipid peroxidation was evaluated by measuring the HNE accumulated in rats kidneys in presence or absence of L-arginine or D-arginine infusion. L-arginine, but not D-arginine, enhances HNE accumulation in I/R but not in SOP (< 0.050 pmol/g tissue in SOP versus 0.6 nmol/g tissue in I/R), showing that, in this experimental conditions, NO produced from L-arginine, enhances the toxicity of ROS. This study shows that the pro- or antioxydant effects of NO are different in vivo and in vitro and could be driven by environmental conditions such as pH, relative concentrations of NO and ROS, ferryl species. PMID:8673627

  13. Exhaled Nitric Oxide Production by Nitric Oxide Synthase-deficient Mice

    Microsoft Academic Search

    WOLFGANG STEUDEL; MAX KIRMSE; JÖRG WEIMANN; ROMAN ULLRICH; JONATHAN HROMI; WARREN M. ZAPOL

    2000-01-01

    Nitric oxide (NO) is produced in the nasal cavities, airways, and lungs and is exhaled by normal animals and humans. Although in- creased exhaled NO concentrations in airway inflammation have been associated with increased airway expression of nitric oxide synthase 2 (NOS 2), it is uncertain which NOS isoform is responsi- ble for baseline levels of exhaled NO. We therefore

  14. 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.

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

    Microsoft Academic Search

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

    2010-01-01

    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

  16. Estimation of the nitric oxide formed from hydroxylamine by Nitrosomonas

    PubMed Central

    Anderson, J. H.

    1965-01-01

    1. Nitric oxide that was produced by reducing nitrite with an excess of acidified potassium iodide under nitrogen in Warburg respirometer flasks was rapidly absorbed by a solution of permanganate in sodium hydroxide held in the side arm. A small amount of nitrous oxide (or nitrogen) that was also produced was not absorbed. 2. By using a quantitative method for the recovery of nitrite from samples of the alkaline permanganate, it was found that the sum of the nitrite N formed and the residual nitrous oxide N was equivalent to the nitrite N used to generate the gases. These results showed that alkaline permanganate completely oxidized nitric oxide to nitrite. The method was suitable for determining 0·4–20 ?moles of nitric oxide. 3. The technique was used to determine the nitric oxide content of the nitrogenous gas that was produced anaerobically from hydroxylamine by an extract of the autotrophic nitrifying micro-organism Nitrosomonas in the presence of methylene blue as electron acceptor. PMID:14342235

  17. 21 CFR 862.3080 - Breath nitric oxide test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...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 asthma. A breath nitric oxide test system combines...

  18. Nitric Oxide/Cyclic Guanosine Monophosphate Signaling in the Central

    E-print Network

    Ganter, Geoffrey

    -(5 hydroxymethyl-2 -furyl)-1-benzyl indazole (YC-1) induced cGMP-associated immunoreactivity in both the upper pathways Nitric oxide synthase (NOS) leading to the Ca2 / calmodulin-stimulated formation of nitric oxide

  19. 21 CFR 862.3080 - Breath nitric oxide test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...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 asthma. A breath nitric oxide test system combines...

  20. 21 CFR 862.3080 - Breath nitric oxide test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...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 asthma. A breath nitric oxide test system combines...

  1. 21 CFR 862.3080 - Breath nitric oxide test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...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 asthma. A breath nitric oxide test system combines...

  2. 21 CFR 862.3080 - Breath nitric oxide test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...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 asthma. A breath nitric oxide test system combines...

  3. DMSO: EFFECT ON BLADDER AFFERENT NEURONS AND NITRIC OXIDE RELEASE

    Microsoft Academic Search

    Lori A. Birder; Anthony J. Kanai; William C. de Groat

    1997-01-01

    PurposeInterstitial cystitis (IC), a chronic disorder of the urinary bladder, is characterized by increased voiding frequency, urgency and pain. Patients with IC also exhibit reduced urinary nitric oxide synthase activity. Intravesical administration of dimethyl sulfoxide (DMSO) has been used to provide symptomatic relief in patients with IC. The present experiments were undertaken to determine if intravesical DMSO affects neural pathways

  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 as a secretory product of mammalian cells

    Microsoft Academic Search

    CARL NATHAN

    1992-01-01

    Evolution has resorted to nitric oxide (NO), a tiny, reactive radical gas, to mediate both ser- voregulatory and cytotoxic functions. This article reviews how different forms of nitric oxide synthase help confer specificity and diversity on the effects of this remarkable signaling molecule.- Nathan, C. Nitric oxide as a secre- tory product of mammalian cells. FASEBJ. 6: 3051-3064; 1992.

  6. How the Location of Superoxide Generation Influences the ?-Cell Response to Nitric Oxide.

    PubMed

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

    2015-03-20

    Cytokines impair the function and decrease the viability of insulin-producing ?-cells by a pathway that requires the expression of inducible nitric oxide synthase (iNOS) and generation of high levels of nitric oxide. In addition to nitric oxide, excessive formation of reactive oxygen species, such as superoxide and hydrogen peroxide, has been shown to cause ?-cell damage. Although the reaction of nitric oxide with superoxide results in the formation of peroxynitrite, we have shown that ?-cells do not have the capacity to produce this powerful oxidant in response to cytokines. When ?-cells are forced to generate peroxynitrite using nitric oxide donors and superoxide-generating redox cycling agents, superoxide scavenges nitric oxide and prevents the inhibitory and destructive actions of nitric oxide on mitochondrial oxidative metabolism and ?-cell viability. In this study, we show that the ?-cell response to nitric oxide is regulated by the location of superoxide generation. Nitric oxide freely diffuses through cell membranes, and it reacts with superoxide produced within cells and in the extracellular space, generating peroxynitrite. However, only when it is produced within cells does superoxide attenuate nitric oxide-induced mitochondrial dysfunction, gene expression, and toxicity. These findings suggest that the location of radical generation and the site of radical reactions are key determinants in the functional response of ?-cells to reactive oxygen species and reactive nitrogen species. Although nitric oxide is freely diffusible, its biological function can be controlled by the local generation of superoxide, such that when this reaction occurs within ?-cells, superoxide protects ?-cells by scavenging nitric oxide. PMID:25648890

  7. Oxidation of nitroxyl anion to nitric oxide by copper ions

    PubMed Central

    Nelli, Silvia; Hillen, Mark; Buyukafsar, Kansu; Martin, William

    2000-01-01

    This study made use of a nitric oxide-sensitive electrode to examine possible means of generating nitric oxide from nitroxyl anion (NO?) released upon the decomposition of Angeli's salt. Our results show that copper ions (from CuSO4) catalyze the rapid and efficient oxidation of nitroxyl to nitric oxide. Indeed, the concentrations of copper required to do so (0.1–100??M) are roughly 100-times lower than those required to generate equivalent amounts of nitric oxide from S-nitroso-N-acetyl-D,L-penicillamine (SNAP). Experiments with ascorbate (1?mM), which reduces Cu2+ ions to Cu+, and with the Cu2+ chelators, EDTA and cuprizone, and the Cu+ chelator, neocuproine, each at 1?mM, suggest that the oxidation is catalyzed by copper ions in both valency states. Some compounds containing other transition metals, i.e. methaemoglobin, ferricytochrome c and Mn(III)TMPyP, were much less efficient than CuSO4 in catalyzing the formation of nitric oxide from nitroxyl, while FeSO4, FeCl3, MnCl2, and ZnSO4 were inactive. Of the copper containing enzymes examined, Cu-Zn superoxide dismutase and ceruloplasmin were weak generators of nitric oxide from nitroxyl, even at concentrations (2500 and 30?u?ml?1, respectively) vastly greater than are present endogenously. Two others, ascorbate oxidase (10?u?ml?1) and tyrosinase (250?u?ml?1) were inactive. Our findings suggest that a copper-containing enzyme may be responsible for the rapid oxidation of nitroxyl to nitric oxide by cells, but the identity of such an enzyme remains elusive. PMID:10991931

  8. Nitric oxide inhibits wound collagen synthesis

    Microsoft Academic Search

    Arti Shukla; Anamika M. Rasik; Ravi Shankar

    1999-01-01

    Nitric oxide (NO) is a messenger molecule which regulates many physiological functions like immunity, vascular tone and serves as a neurotransmitter. Although it is known to participate in healing process, its role in collagen synthesis is not clear. Therefore, the present investigation was done to study the role of NO in wound collagen synthesis. Rats received full thickness, circular (8

  9. 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

  10. Nitric Oxide Is Required for Root Organogenesis

    Microsoft Academic Search

    Gabriela Carolina Pagnussat; Marcela Simontacchi; Susana Puntarulo; Lorenzo Lamattina

    2002-01-01

    In this report, we demonstrate that nitric oxide (NO) mediates the auxin response leading the adven- titious root formation. A transient increase in NO concentration was shown to be required and to be part of the molecular events involved in adventitious root development induced by indole acetic acid (IAA). The discovery of signal molecules involved in the intricate network that

  11. Nitric oxide synthases: structure, function and inhibition

    Microsoft Academic Search

    Wendy K. ALDERTON; Chris E. COOPER; Richard G. KNOWLES

    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 in- formation on the enzyme structure at all levels from primary (amino acid sequence) to quaternary (dimerization, association with other proteins) structure.

  12. Nitric oxide production in critically ill patients

    Microsoft Academic Search

    H R Wong; J A Carcillo; G Burckart; S S Kaplan

    1996-01-01

    OBJECTIVE: To measure serum nitrite and nitrate levels in critically ill children as indicators of endogenous nitric oxide (NO) production. HYPOTHESIS: Endogenous NO production is increased in children with conditions characterised by immune stimulation. DESIGN: Prospective descriptive study in a multidisciplinary paediatric intensive care unit. PATIENTS: 137 consecutive critically ill children with a variety of clinical conditions. INTERVENTIONS: Using a

  13. Nitric Oxide Synthase Inhibition and Cerebrovascular Regulation

    Microsoft Academic Search

    Costantino Iadecola; Dale A. Pelligrino; Michael A. Moskowitz; Niels A. Lassen

    1994-01-01

    Summary: There is increasing evidence that nitric oxide (NO) is an important molecular messenger involved in a wide variety of biological processes. Recent data suggest that NO is also involved in the regulation of the cerebral circulation. Thus, NO participants in the maintenance of resting cerebrovascular tone and may play an important role in selected vasodilator responses of the cerebral

  14. 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...

  15. 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...

  16. Nitric oxide therapy in sickle cell disease

    Microsoft Academic Search

    Mark T Gladwin; Alan N Schechter

    2001-01-01

    Recent clinical and experimental data suggest that nitric oxide (NO) may play a role in the pathogenesis and therapy of sickle cell disease. NO, a soluble gas continuously synthesized in endothelial cells by the NO synthase (NOS) enzyme systems, regulates basal vascular tone and endothelial function, and maintains blood oxygenation via hypoxic pulmonary vasoconstriction and reduced shunt physiology. These vital

  17. Nitric oxide function in the skin

    Microsoft Academic Search

    M.-M Cals-Grierson; A. D Ormerod

    2004-01-01

    Endogenously produced nitric oxide (NO) has a remarkably diverse range of biological functions, including a role in neurotransmission, smooth muscle relaxation, and the response to immunogens. Over the last 10 years, it has become clear that this extraordinary molecular messenger also plays a vital role in the skin, orchestrating normal regulatory processes and underlying some of the pathophysiological ones. We

  18. Evaluation of nitric oxide production by lactobacilli

    Microsoft Academic Search

    J. Xu; W. Verstraete

    2001-01-01

    Six strains of Lactobacillus fermentum and Lactobacillus plantarum were investigated for nitric oxide (NO) production. First, the potential presence of NO synthase was examined. None of the strains of L. fermentum and L. plantarum examined produced NO from L-arginine under aerobic conditions. Interestingly, all L. fermentum strains expressed strong L-arginine deiminase activity. All L. fermentum strains produced NO in MRS

  19. Modulatory role of nitric oxide in cardiac performance.

    PubMed

    Smilji?, Sonja; Nestorovi?, Vojkan; Savi?, Sla?ana

    2014-01-01

    Nitric oxide is produced by almost all cardiac cells, endothelial cells, cardiomyocytes and nerve fibers. It is synthesized by an enzyme, a nitric oxide synthase, which occurs in endothelial, neural and inducible form. The distribution of nitric oxide synthase in the heart is characterized by a pronounced non-uniformity. Nitric oxide exerts its effects in physiological and pathophysiological conditions. The physiological effects of low concentrations of nitric oxide, which is released in the normal conditions under the influence of constituent enzymes, occur via cyclic guanosine monophosphate. The synthesized nitric oxide exhibits its effect in the cells where it is produced, in an autocrine manner, or by diffusing into the neighboring cells, in a paracrine manner. Nitric oxide acts by regulating the coronary vessel tonus, affecting the contractility of cardiomyocytes, generating an inotropic effect in a dose-dependent manner and controlling the cellular respiration. Other effects of nitric oxide in the cardiovascular system include the hyperpolarization of the smooth muscle cells in blood vessels, the inhibition of the monocyte adhesion, the inhibition of platelet migration, adhesion and aggregation and the proliferation of smooth muscle cells and fibroblasts. The anti-atherosclerotic effects of nitric oxide are based on these effects. Nitric oxide is a weak free radical in gaseous state, and the cytotoxic and/or the cytoprotective effects of the higher concentrations of nitric oxide are related to the chemical structure of nitric oxide as a free radical. The excessive production of nitric oxide by the activation of inducible nitric oxide synthase can lead to major irregularities in the function of cardiomyocytes and cardiac insufficiency. Understanding the nitric oxide molecular mechanisms of signaling pathways in the heart can provide a new strategic approach to prevention and treatment of cardiovascular diseases. PMID:25546983

  20. Pomegranate juice protects nitric oxide against oxidative destruction and enhances the biological actions of nitric oxide.

    PubMed

    Ignarro, Louis J; Byrns, Russell E; Sumi, Daigo; de Nigris, Filomena; Napoli, Claudio

    2006-09-01

    Pomegranate juice (PJ), which is a rich source of potent flavonoid antioxidants, was tested for its capacity to protect nitric oxide (NO) against oxidative destruction and enhance the biological actions of NO. Employing chemiluminescence headspace analysis, PJ was found to be a potent inhibitor of superoxide anion-mediated disappearance of NO. PJ was much more potent than Concord grape juice, blueberry juice, red wine, ascorbic acid, and DL-alpha-tocopherol. As little as 3 microl of a 6-fold dilution of PJ, in a reaction volume of 5000 microl, produced a marked antioxidant effect, whereas 300 microl of undiluted blueberry juice or nearly 1000 microl of undiluted Concord grape juice were required to produce similar effects. PJ and other antioxidant-containing products were found to augment the anti-proliferative action of NO (DETA/NO) on vascular smooth muscle cell (rat aorta) proliferation. PJ was much more effective than the other products tested and elicited no effects when tested alone in the absence of added NO. Similarly, neither PJ nor the other products enhanced the anti-proliferative action of alpha-difluoromethylornithine, a stable substance that inhibits cell growth by NO-independent mechanisms. In order to determine whether PJ is capable of increasing the production of NO by vascular endothelial cells, PJ was tested for its capacity to upregulate and/or activate endothelial NO synthase (eNOS) in bovine pulmonary artery endothelial cells. PJ elicited no effects on eNOS protein expression or catalytic activity. Moreover, PJ did not enhance promoter activity in the eNOS gene (COS-7 cells transfected with eNOS). These observations indicate that PJ possesses potent antioxidant activity that results in marked protection of NO against oxidative destruction, thereby resulting in augmentation of the biological actions of NO. PMID:16626982

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

    PubMed

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

    2014-09-01

    Nitric oxide (NO) and NO synthase-1 (NOS1) are involved in the stress response and in depression. We compared NOS-NO alterations in rats exposed to chronic unpredictable stress (CUS) with alterations in major depressive disorder (MDD) in humans. In the hypothalamus of male CUS rats we determined NOS activity, and in the paraventricular nucleus (PVN) we determined NOS1-immunoreactive (ir) cell densities and co-localization of NOS1 with stress-related neuropeptides corticotropin-releasing hormone (CRH), vasopressin (AVP) or oxytocin (OXT). We measured plasma NO levels and cortisol in male medicine-naïve MDD patients and plasma NO and corticosterone (CORT) in CUS rats. In the CUS rat total NOS activity in the hypothalamus (P=0.018) and NOS1-ir cell density in the PVN were both significantly decreased (P=0.018), while NOS1 staining was mainly expressed in OXT-ir neurons in this nucleus. Interestingly, plasma NO levels were significantly increased both in male CUS rats (P=0.001) and in male MDD patients (P<0.001). Plasma CORT levels were increased in male CUS rats (P=0.001), while male MDD patients did not show a significant change in cortisol levels. In conclusion, the changes in plasma and hypothalamic NOS-NO of CUS rats and MDD were similar. The male CUS rat model may thus help us with our investigation of the mechanism underlying NOS-NO alterations in depression. PMID:25001963

  2. Increase in brain nitric oxide synthase activity in daunorubicin-treated rats.

    PubMed

    Joshi, P; Vig, P J; Veerisetty, V; Cameron, J A; Sekhon, B S; Desaiah, D

    1996-02-01

    Anthracyclines such as daunorubicin are very effective anticancer agents. These drugs are known to cause side effects including cardiotoxicity. Anthracyclines are neurotoxic to laboratory animals. Nitric oxide is a novel and very important chemical messenger in the brain. However, at higher levels, nitric oxide causes well defined neurotoxicity. Therefore, we determined nitric oxide synthase activity in rat brain after daunorubicin treatment in an effort to explain the neurotoxicity produced by anthracyclines. Male Sprague-Dawley rats were treated with different subcutaneous doses of daunorubicin (0.1-4.0 mg/kg/week for five weeks) while control animals were injected with phosphate buffered saline. There was a significant increase (80%) of nitric oxide synthase activity in daunorubicin-treated animals as compared to controls. This activity was inhibited by N-monomethyl-L-arginine (NMMA), nitroarginine, N-6-aminohexyl-5-chloro-1-napthalene sulfonamide (W-7), a calmodulin antagonist, suggesting that the nitric oxide synthase activity is calmodulin dependent. Further, our in vitro studies demonstrated that daunorubicin interacted with calmodulin as measured by N-phenyl-1-napthylamine (NPN) fluorescence. These results indicate that daunorubicin increases nitric oxide synthase activity in rat brain which may increase the levels of nitric oxide. The increased levels of nitric oxide may cause neurotoxicity. Our results further indicate that daunorubicin interacts with calmodulin and enhances nitric oxide synthase activity which is dependent on calmodulin. PMID:8822043

  3. 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 [Vrije Universiteit Brussel, Cancer Research Unit, Brussels (Belgium); De Ridder, Mark, E-mail: mark.deridder@uzbrussel.b [Vrije Universiteit Brussel, Cancer Research Unit, Brussels (Belgium); UZ Brussel, Oncologisch Centrum, Radiotherapie, Universite catholique de Louvain, Brussels (Belgium); Verovski, Valeri N. [UZ Brussel, Oncologisch Centrum, Radiotherapie, Universite catholique de Louvain, Brussels (Belgium); Sonveaux, Pierre [Unit of Pharmacology and Therapeutics, Universite catholique de Louvain, Brussels (Belgium); Jordan, Benedicte F. [Unit of Biomedical Magnetic Resonance, Universite catholique de Louvain, Brussels (Belgium); Law, Kalun; Monsaert, Christinne [Vrije Universiteit Brussel, Cancer Research Unit, Brussels (Belgium); Van den Berge, Dirk L.; Verellen, Dirk [UZ Brussel, Oncologisch Centrum, Radiotherapie, Universite catholique de Louvain, Brussels (Belgium); Feron, Olivier [Unit of Pharmacology and Therapeutics, Universite catholique de Louvain, Brussels (Belgium); Gallez, Bernard [Unit of Biomedical Magnetic Resonance, Universite catholique de Louvain, Brussels (Belgium); Storme, Guy A. [Vrije Universiteit Brussel, Cancer Research Unit, Brussels (Belgium); UZ Brussel, Oncologisch Centrum, Radiotherapie, Universite catholique de Louvain, Brussels (Belgium)

    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.

  4. Elevated vitreous nitric oxide levels in patients with proliferative diabetic retinopathy

    Microsoft Academic Search

    Gürsel Yilmaz; Peter Esser; Norbert Kociek; Pinar Aydin; Klaus Heimann

    2000-01-01

    PURPOSE: The aim of this study was to determine nitric oxide levels in the vitreous of patients with proliferative diabetic retinopathy.METHODS: Using the spectrophotometric method based on Griess reaction, we measured levels of nitrite, the stable product of nitric oxide, in the vitreous of 21 eyes of 21 patients who underwent vitrectomy for the treatment of proliferative diabetic retinopathy with

  5. Oxidation of DOPAC by nitric oxide: effect of superoxide dismutase

    Microsoft Academic Search

    Joao Laranjinha; Enrique Cadenas

    2002-01-01

    This study aimed to characterize the redox interaction between 3,4-dihydroxyphenylacetic acid (DOPAC) and nitric oxide (ÆNO), and to assess the reductive and oxidative decay pathways of the DOPAC semiquinone originating from this interaction. The reaction between DOPAC and ÆNO led to the formation of the DOPAC semiquinone radical, detected by electron paramagnetic resonance (EPR) and stabilized by Mg2+, and the

  6. Paraxanthine: Connecting Caffeine to Nitric Oxide Neurotransmission

    PubMed Central

    Orrú, Marco; Guitart, Xavier

    2013-01-01

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

  7. Nitric oxide production by Tunguska meteor

    Microsoft Academic Search

    1978-01-01

    The nonequilibrium chemical processes of nitric oxide formation are computed for the wake of the Tunguska meteor of 1908. The wake characteristics are derived by carrying out an optically-thick radiation field analysis for ablation of the meteoroid. The wake flow field is approximated by a one-dimensional, well-stirred reactor model. Known characteristics of the Tunguska event are imposed as constraints, and

  8. Aminoguanidine selectively inhibits inducible nitric oxide synthase.

    PubMed Central

    Griffiths, M. J.; Messent, M.; MacAllister, R. J.; Evans, T. W.

    1993-01-01

    1. Endotoxin induces nitric oxide synthase in vascular tissue, including rat main pulmonary artery. Currently available agents that cause inhibition of nitric oxide synthase are relatively non-selective between the constitutive and inducible forms of the enzyme. 2. Aminoguanidine caused a dose-dependent increase in phenylephrine-induced tension in intact and endothelium-denuded pulmonary artery rings from endotoxin-treated rats, but had no effect on sham-treated controls. 3. Contraction caused by aminoguanidine in endothelium-denuded vessels from endotoxin-treated rats was unaffected by indomethacin (10 microM), and by cimetidine and mepyramine (both 10 microM), excluding an effect of aminoguanidine mediated by arachidonic acid metabolites or histamine. 4. Contraction caused by aminoguanidine in endothelium-denuded vessels from endotoxin-treated rats was abolished by L-arginine (2 mM) and L-NG-monomethyl arginine (300 microM), but unaffected by D-arginine and D-NG-monomethyl arginine, suggesting that its action is mediated by the L-arginine/nitric oxide pathway.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7507781

  9. Updated Role of Nitric Oxide in Disorders of Erythrocyte Function

    PubMed Central

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

    2013-01-01

    Nitric oxide is a potent vasodilator that plays a critical role in disorders of erythrocyte function. Sickle cell disease, paroxysmal nocturnal hemoglobinuria and banked blood preservation are three conditions where nitric oxide is intimately related to dysfunctional erythrocytes. These conditions are accompanied by hemolysis, thrombosis and vasoocclusion. Our understanding of the interaction between nitric oxide, hemoglobin, and the vasculature is constantly evolving, and by defining this role we can better direct trials aimed at improving the treatments of disorders of erythrocyte function. Here we briefly discuss nitric oxide’s interaction with hemoglobin through the hypothesis regarding S-nitrosohemoglobin, deoxyhemoglobin, and myoglobin as nitrite reductases. We then review the current understanding of the role of nitric oxide in sickle cell disease, paroxysmal nocturnal hemoglobinuria, and banked blood, and discuss therapeutics in development to target nitric oxide in the treatment of some of these disorders. PMID:23534951

  10. A functional nitric oxide reductase model

    PubMed Central

    Collman, James P.; Yang, Ying; Dey, Abhishek; Decréau, Richard A.; Ghosh, Somdatta; Ohta, Takehiro; Solomon, Edward I.

    2008-01-01

    A functional heme/nonheme nitric oxide reductase (NOR) model is presented. The fully reduced diiron compound reacts with two equivalents of NO leading to the formation of one equivalent of N2O and the bis-ferric product. NO binds to both heme Fe and nonheme Fe complexes forming individual ferrous nitrosyl species. The mixed-valence species with an oxidized heme and a reduced nonheme FeB does not show NO reduction activity. These results are consistent with a so-called “trans” mechanism for the reduction of NO by bacterial NOR. PMID:18838684

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

    PubMed

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

    2013-03-01

    Nitric oxide is a potent vasodilator that plays a critical role in disorders of erythrocyte function. Sickle cell disease, paroxysmal nocturnal hemoglobinuria and banked blood preservation are three conditions where nitric oxide is intimately related to dysfunctional erythrocytes. These conditions are accompanied by hemolysis, thrombosis and vasoocclusion. Our understanding of the interaction between nitric oxide, hemoglobin, and the vasculature is constantly evolving, and by defining this role we can better direct trials aimed at improving the treatments of disorders of erythrocyte function. Here we briefly discuss nitric oxide's interaction with hemoglobin through the hypothesis regarding Snitrosohemoglobin, deoxyhemoglobin, and myoglobin as nitrite reductases. We then review the current understanding of the role of nitric oxide in sickle cell disease, paroxysmal nocturnal hemoglobinuria, and banked blood, and discuss therapeutics in development to target nitric oxide in the treatment of some of these disorders. PMID:23534951

  12. Nitric oxide modulation of norepinephrine production in acupuncture points

    Microsoft Academic Search

    Jia-Xu Chen; Basil O. Ibe; Sheng-Xing Ma

    2006-01-01

    The purpose of this study was to examine the levels of norepinephrine (NE) turnover in skin tissues and to determine the effect of nitric oxide (NO) on NE production in acupuncture points (acupoints) and meridians. The rats were pretreated with ?-methyl-tyrosine methyl ester and intravenously infused with l-(2,3,5,6-3H)-tyrosine. Blood was withdrawn and skin tissues were excised from the low skin

  13. Docosahexaenoic acid affects endothelial nitric oxide synthase in caveolae

    Microsoft Academic Search

    Qiurong Li; Qiang Zhang; Meng Wang; Fuzhong Liu; Sumin Zhao; Jian Ma; Nan Luo; Ning Li; Yousheng Li; Guowang Xu; Jieshou Li

    2007-01-01

    n?3 Polyunsaturated fatty acids are assumed to play an important role in the prevention and treatment of atherosclerosis. Endothelial nitric-oxide synthase (eNOS) is responsible for cardiovascular homeostasis involving in regulation of vascular function, and the subcellular localization is critical for its activation. Here we determined the effect of docosahexaenoic acid (DHA, 22:6 n?3) on distribution of eNOS and its activity.

  14. Nitric oxide synthesis in patients with infective gastroenteritis

    Microsoft Academic Search

    P Forte; R S Dykhuizen; E Milne; A McKenzie; C C Smith; N Benjamin

    1999-01-01

    BACKGROUNDThere is evidence that endogenous nitrate synthesis is notably increased in patients with infective gastroenteritis.AIMSTo determine whether this is due to nitric oxide (NO) production via the l-arginine\\/NO pathway.METHODSSeven male patients with community acquired bacterial gastroenteritis and 15 healthy male volunteers participated in this study. All patients had stool culture positive infective gastroenteritis. A bolus of 200 mgl-[15N]2-arginine was administered

  15. Oxidative Stress, Nitric Oxide, and Diabetes

    PubMed Central

    Pitocco, Dario; Zaccardi, Francesco; Di Stasio, Enrico; Romitelli, Federica; Santini, Stefano A.; Zuppi, Cecilia; Ghirlanda, Giovanni

    2010-01-01

    In the recent decades, oxidative stress has become focus of interest in most biomedical disciplines and many types of clinical research. Increasing evidence from research on several diseases show that oxidative stress is associated with the pathogenesis of diabetes, obesity, cancer, ageing, inflammation, neurodegenerative disorders, hypertension, apoptosis, cardiovascular diseases, and heart failure. Based on this research, the emerging concept is that oxidative stress is the “final common pathway”, through which risk factors of several diseases exert their deleterious effects. Oxidative stress causes a complex dysregulation of cell metabolism and cell-cell homeostasis. In this review, we discuss the role of oxidative stress in the pathogenesis of insulin resistance and beta-cell dysfunction. These are the two most relevant mechanisms in the pathophysiology of type 2 diabetes, and in the pathogenesis of diabetic vascular complications, the leading cause of death in diabetic patients. PMID:20703435

  16. Effect of Nitric Oxide on Anterior Segment Physiology in Monkeys

    PubMed Central

    Heyne, Galen W.; Kiland, Julie A.; Kaufman, Paul L.; Gabelt, B'Ann T.

    2013-01-01

    Purpose. To determine the effect of the nitric oxide donor, sodium nitroprusside (SNP), and the nitric oxide synthase (NOS) inhibitor, L-nitro-arginine-methylester (L-NAME), on IOP, mean arterial pressure (MAP), pupil diameter (PD), refraction (Rfx), aqueous humor formation (AHF), and outflow facility (OF) in monkeys. Methods. Monkeys were treated with single or multiple topical treatments of 500 ?g SNP or L-NAME to one eye. IOP was determined by Goldmann applanation tonometry, PD with vernier calipers in room light, Rfx by Hartinger coincidence refractometry, AHF by fluorophotometry, and MAP with a blood pressure monitor. OF was determined by two-level constant pressure perfusion following anterior chamber exchange. Results. Following four topical treatments with 500 ?g SNP, 30 minutes apart, IOP was significantly decreased from 2 to 6 hours compared with the contralateral control with the maximum IOP reduction of 20% at 3 hours (P < 0.001). PD, Rfx, and AHF were unchanged. Effects on MAP were variable. OF after SNP exchange was significantly increased by 77% (P < 0.05) at 10?3 M. Topical L-NAME had no effect on IOP, PD, Rfx, or MAP. Conclusions. Enhancement of nitric oxide concentration at targeted tissues in the anterior segment may be a useful approach for IOP reduction for glaucoma therapy. Additional studies are warranted before conclusions can be made regarding the effect of NOS inhibition on ocular physiology in nonhuman primates. PMID:23800771

  17. Inhaled nitric oxide in chronic obstructive lung disease

    SciTech Connect

    Tiihonen, J.; Hakola, P.; Paanila, J.; Turtiainen (Univ. of Kuopio (Finland). 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.

  18. Processes regulating nitric oxide emissions from soils

    PubMed Central

    Pilegaard, Kim

    2013-01-01

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

  19. 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

  20. Nitric Oxide Scavenging by Red Cell Microparticles

    PubMed Central

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

    2013-01-01

    Red cell microparticles form during the storage of red blood cells and in diseases associated with red cell breakdown and asplenia, including hemolytic anemias such as sickle cell disease. These small phospholipid vesicles that are derived from red blood cells have been implicated in the pathogenesis of transfusion of aged stored blood and hemolytic diseases, via activation of the hemostatic system and effects on nitric oxide (NO) bioavailability. Red cell microparticles react with the important signaling molecule NO almost as fast as cell-free hemoglobin, about one-thousand times faster than red cell encapsulated hemoglobin. The degree to which this fast reaction with NO by red cell microparticles impacts NO bioavailability depends on several factors that are explored here. In the context of stored blood preserved in ADSOL, we find that both cell-free hemoglobin and red cell microparticles increase as a function of duration of storage and the proportion of extra erythrocytic hemoglobin in the red cell microparticles fraction is about 20% throughout storage. Normalized by hemoglobin concentration, the NO scavenging ability of cell-free hemoglobin is slightly higher than red cell microparticles as determined by a chemiluminescent NO scavenging assay. Computational simulations show that the degree to which red cell microparticles scavenge NO will depend substantially on whether they enter the cell-free zone next to the endothelial cells. Single microvessel myography experiments performed under laminar flow conditions demonstrate that microparticles significantly enter the cell-free zone and inhibit acetylcholine, endothelial-dependent and NO-dependent vasodilation. Taken together, these data suggest that as little as five micromolar hemoglobin in red cell microparticles, an amount formed after the infusion of one unit of aged stored packed red blood cells, has the potential to reduce NO bioavailability and impair endothelial-dependent vasodilation. PMID:24051181

  1. Nitric oxide reactions of bio-Inspired zinc and cobalt complexes

    E-print Network

    Kozhukh, Julia, 1985-

    2012-01-01

    Chapter 1. Bioinorganic Chemistry of Nitric Oxide and of Some of Its Targets The redox-active nature of nitric oxide (NO) regulates the chemistry and roles of NO in biology. The interactions of NO with nitric oxide synthases, ...

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

    PubMed

    Liu, Yong-Biao

    2013-12-01

    There is a great demand for safe and effective alternative fumigants to replace methyl bromide and other toxic fumigants for postharvest 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. Four insect species including western flower thrips, Frankliniella occidentalis (Pergande) (Thysanoptera Thripidae); aphid, Nasonovia ribisnigri (Mosley) (Homoptera: Aphididae); confused flour beetle, Tribolium confusum Jacquelin du Val (Coleoptera: Tenebrionidae); and rice weevil, Sitophilus oryzae (L.) (Coleoptera: Curculionidae), at various life stages were fumigated with 0.1-2.0% nitric oxide under ultralow oxygen levels of < or = 50 ppm in 1.9-liter glass jars at 2-25 degrees C depending on insect species. Fumigations were effective against all four insect species. Efficacy of nitric oxide fumigation increased with nitric oxide concentration, treatment time, and temperature. There were also considerable variations among insect species as well as life stages in susceptibility to nitric oxide fumigation. Complete control of thrips was achieved in 2 and 8 h with 2.0 and 0.2% nitric oxide, respectively, at 2 degrees C. At the same temperature, complete control of the aphid was achieved in 3, 9, and 12 h with 1.0, 0.5, and 0.2% nitric oxide, respectively. Larvae, pupae, and adults of confused flour beetle were effectively controlled in 24 h with 0.5% nitric oxide at 20 degrees C. Complete mortality of confused flour beetle eggs was achieved in 24 h with 2.0% nitric oxide at 10 degrees C. Rice weevil adults and eggs were effectively controlled with 1.0% nitric oxide in 24 and 48 h, respectively, at 25 degrees C. These results indicate that nitric oxide has potential as a fumigant for postharvest pest control. PMID:24498723

  3. Distribution of nitric oxide synthase immunoreactivity in the mouse brain

    Microsoft Academic Search

    Stefano Gotti; Monica Sica; Carla Viglietti-Panzica; Giancarlo Panzica

    2005-01-01

    Nitric oxide (NO) is a gaseous intercellular messenger with a wide range of neural functions. NO is synthesized by activation of different isoforms of nitric oxide synthases (NOS). At present NOS immunoreactivity has been described in mouse brain in restricted and definite areas and no detailed mapping studies have yet been reported for NOS immunoreactivity. We have studied the distribution

  4. DIFFERENTIAL NITRIC OXIDE PRODUCTION BY CHICKEN IMMUNE CELLS

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  5. 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…

  6. High-latitude nitric oxide in the lower thermosphere

    Microsoft Academic Search

    J.-C. Gérard; C. A. Barth

    1977-01-01

    High-latitude observations of fluorescent nitric oxide gamma bands were made before and during a strong magnetic storm with the Ogo 4 ultraviolet spectrometer. Brightness measurements of the (1--0) gamma band of nitric oxide indicate a slow buildup of NO during the disturbed period. The NO column density reaches a value as high as a factor of 8 greater than the

  7. Immunohistochemical characterization of placental nitric oxide synthase expression in preeclampsia

    Microsoft Academic Search

    Mohamed S. Ghabour; Annie L. W. Eis; Diane E. Brockman; Jennifer S. Pollock; Leslie Myatt

    1995-01-01

    OBJECTIVE: Our purpose was to compare the expression of endothelial nitric oxide synthase in the placenta and umbilical cord of preeclamptic placenta with that of the normotensive placenta.STUDY DESIGN: We compared placental endothelial nitric oxide synthase expression in preeclamptic (n = 3) with that in normal (n = 3) pregnancies. Frozen sections of umbilical cords, chorionic plate vessels, and terminal

  8. Impaired Nitric Oxide Synthase Signaling Dissociates Social Investigation and Aggression

    Microsoft Academic Search

    Brian C. Trainor; Joanna L. Workman; Ruth Jessen; Randy J. Nelson

    2007-01-01

    A combination of social withdrawal and increased aggression is characteristic of several mental disorders. Most previous studies have investigated the neurochemical bases of social behavior and aggression independently, as opposed to how these behaviors are regulated in concert. Neuronal nitric oxide synthase (nNOS) produces gaseous nitric oxide, which functions as a neurotransmitter and is known to affect several types of

  9. Role of Nitric Oxide in Cocaine-Induced Acute Hypertension

    Microsoft Academic Search

    Wa Mo; Ashok K. Singh; Jose A. L. Arruda; George Dunea

    1998-01-01

    Cocaine causes acute hypertension by blocking catecholamine reuptake. There is evidence that it also impairs the peripheral endothelial nitric oxide system, which is normally vasodilatory. We further explored the role of nitric oxide in cocaine-induced vasoconstriction in anesthetized rats, and in vitro by using isolated carotid artery segments. Cocaine administered intravenously in rats increased mean arterial pressure by 30 to

  10. Expression pattern of neuronal nitric oxide synthase in embryonic zebrafish

    Microsoft Academic Search

    Kar Lai Poon; Michael Richardson; Chen Sok Lam; Hoon Eng Khoo; Vladimir Korzh

    2003-01-01

    Nitric oxide synthase catalyzes the production of nitric oxide, a multifunctional signaling molecule that affects diverse aspects of animal physiology such as cell proliferation, differentiation, neurotransmission and apoptosis. Here, we report the cloning and expression pattern of the zebrafish nnos. This gene was mapped to zebrafish linkage group 5. The spatial and temporal expression pattern of nnos in embryonic zebrafish

  11. 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.

  12. Nitric oxide and inflammatory periodontal disease.

    PubMed

    Parwani, Simran R; Parwani, Rajkumar N

    2015-01-01

    Free radicals are species capable of independent existence that contain 1 or more unpaired electrons. These species are beneficial to the host if secreted in appropriate amounts, and may act as powerful antibacterial agents or help in the regulation of vascular tone in the endothelium. In healthy individuals, there is an appropriate balance between free radicals and their scavengers. This balance can be shifted to an unhealthy pro-oxidant state when the production of free radicals is increased, resulting in serious cell damage leading to progressive inflammatory diseases of the periodontium and periapical tissues, and/or precancerous and cancerous lesions of the oral cavity. Free radicals can be important biomarkers for these diseases when clinical symptoms are not present. Nitric oxide (NO) is a free radical gas and an inflammatory biomarker. The aim of this paper is to present the role of NO in periodontal health and inflammation. PMID:25734284

  13. Nitric oxide rescues thalidomide mediated teratogenicity

    PubMed Central

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

    2012-01-01

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

  14. Fluorescence-based detection methodologies for nitric oxide using transition metal scaffolds

    E-print Network

    Hilderbrand, Scott A. (Scott Alan), 1976-

    2004-01-01

    Chapter 1. Fluorescence-Based Detection Methodologies for Nitric Oxide: A Review. Chapter 2. Cobalt Chemistry with Mixed Aminotroponimine Salicylaldimine Ligands: Synthesis, Characterization, and Nitric Oxide Reactivity. ...

  15. Cellular antioxidant and pro-oxidant actions of nitric oxide

    Microsoft Academic Search

    Mahesh S Joshi; Julie L Ponthier; Jack R Lancaster

    1999-01-01

    We describe a biphasic action of nitric oxide (NO) in its effects on oxidative killing of isolated cells: low concentrations protect against oxidative killing, while higher doses enhance killing, and these two effects occur by distinct mechanisms. While low doses of NO (from (Z)-1-[N-(3-ammonio propyl)-N-(n-propyl)-amino]-diazen-1-ium-1,22 diolate [PAPA\\/NO] or S-nitroso-N-acetyl-L-penicillamine [SNAP] prevent killing of rat hepatocytes byt-butylhydroperoxide (tBH), further increasing doses

  16. Nitric oxide availability as a marker of oxidative stress.

    PubMed

    Pierini, Dan; Bryan, Nathan S

    2015-01-01

    Nitric oxide (NO) is widely considered one of the most important molecules produced in the human body, acting as a necessary regulator in a vast array of vital physiological functions, namely, blood pressure, immune response, and neural communication. Healthy endothelium is defined by the ability to produce adequate levels of NO. Reactive oxygen species (ROS) play a major role in NO-based cell signaling. ROS can affect NO availability both from production to post-production scavenging and lead to a myriad of vascular disorders due to compromised NO functionality. In 2004, it was identified in animal models that oxidative stress plays a significant role in the development of hypertension, in part by inactivation of NO (Ghosh et al., Br J Pharmacol 141(4):562-573, 2004). It was thus concluded that NO bioavailability was reduced in the presence of ROS. We speculated that the accurate detection of NO and quantification in biological matrices is critical as a marker of oxidative stress (Bryan et al., Proc Natl Acad Sci USA 101(12):4308-4313, 2004). The elucidation of new mechanisms and signaling pathways involving NO hinges on our ability to specifically, selectively, and sensitively detect and quantify NO and all relevant NO products and metabolites in complex biological matrices. Here, we present a method for the rapid and sensitive analysis of nitrite and nitrate by HPLC as well as detection of free NO in biological samples using in vitro ozone-based chemiluminescence with chemical derivatization to determine molecular source of NO as well as ex vivo with organ bath myography. This approach ties fundamental biochemistry to functional response. PMID:25323499

  17. 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...

  18. Oxidative stress and nitric oxide related parameters in type II diabetes mellitus: effects of glycemic control

    Microsoft Academic Search

    Ahmet Ayd?n; Hilmi Orhan; Ahmet Sayal; Metin Özata; Gönül ?ahin; A?k?n I??mer

    2001-01-01

    Objectives: The aim of this study is to investigate the status of oxidative stress and nitric oxide related parameters in type II diabetes mellitus (DM) patients in which heart disease, atherosclerosis, retinopathy, and nephropathy commonly occur, and also to determine the effect of glycemic control on these parameters.Design and methods: Erythrocyte copper zinc-superoxide dismutase (CuZn-SOD), erythrocyte and plasma selenium dependent

  19. Nitric oxide and oxidative stress in vascular disease

    Microsoft Academic Search

    Ulrich Förstermann; Eur J Physiol

    2010-01-01

    Endothelium-derived nitric oxide (NO) is a paracrine factor that controls vascular tone, inhibits platelet function, prevents\\u000a adhesion of leukocytes, and reduces proliferation of the intima. An enhanced inactivation and\\/or reduced synthesis of NO is\\u000a seen in conjunction with risk factors for cardiovascular disease. This condition, referred to as endothelial dysfunction,\\u000a can promote vasospasm, thrombosis, vascular inflammation, and proliferation of vascular

  20. Nitric oxide\\/cGMP pathway components in the Leydig cells of the human testis

    Microsoft Academic Search

    M. S. Davidoff; R. Middendorff; B. Mayer; J. deVente; D. Koesling; A. F. Holstein

    1996-01-01

    .   In this study we sought to determine whether the main components of the nitric oxide (NO) pathway are localized within the\\u000a Leydig cells of the human testis and whether the soluble guanylyl cyclase (sGC), the enzyme that accounts for NO effects,\\u000a is functionally active in these cells. Using an amplified immunocytochemical technique, immunoreactivity for nitric oxide\\u000a synthase (NOS-I), sGC

  1. The Role of Nitric Oxide and NMDA Receptors in the Development of Motor Neuron Dendrites

    Microsoft Academic Search

    Fiona M. Inglis; Fran Furia; Katharine E. Zuckerman; Stephen M. Strittmatter; Robert G. Kalb

    1998-01-01

    Nitric oxide (NO) has been implicated in the establishment of precise synaptic connectivity throughout the neuroaxis in sev- eral species. To determine the contribution of NO to NMDA receptor-dependent dendritic growth in motor neurons, we ad- ministered the NMDA antagonist MK-801 to wild-type mice and neuronal nitric oxide synthase (nNOS) knock-out mice between postnatal days 7 and 14. Compared to

  2. Impaired nitric oxide-mediated vasodilation in patients with non-insulin-dependent diabetes mellitus

    Microsoft Academic Search

    Stephen B. Williams; Jorge A. Cusco; Mary-Anne Roddy; Michael T. Johnstone; Mark A. Creager

    1996-01-01

    Objectives. This study sought to determine whether nitric oxide-mediated vasodilation is abnormal in patients with non-insulin-dependent diabetes mellitus.Background. Multiple investigations, both in experimental models and in patients with insulin-dependent diabetes mellitus, demonstrate impaired endothelium-dependent vasodilation. Decreased availability of endothelium-derived nitric oxide may contribute to the high prevalence of vascular disease in diabetes.Methods. Vascular reactivity was measured in the forearm resistance

  3. Reduced nitric oxide synthase activity in rats with chronic renal disease due to glomerulonephritis

    Microsoft Academic Search

    Laszlo Wagner; Amy Riggleman; Aaron Erdely; William Couser; Chris Baylis

    2002-01-01

    Reduced nitric oxide synthase activity in rats with chronic renal disease due to glomerulonephritis.BackgroundAnimal studies with systemic nitric oxide synthase (NOS) inhibition and renal ablation, suggest that NO deficiency is both a cause and a consequence of chronic renal disease (CRD).MethodsThis study examined a glomerulonephritis (GN) model of CRD to determine if NO is deficient. In addition to measuring indices

  4. Nitric oxide metabolites in nasal lavage fluid of patients with house dust mite allergy

    Microsoft Academic Search

    I M Garrelds; J G van Amsterdam; C de Graaf-in't Veld; R Gerth van Wijk; F J Zijlstra

    1995-01-01

    BACKGROUND--The role of nitric oxide in the early and late phase of the allergic process was investigated in patients with allergic rhinitis against house dust mite and the effect of fluticasone propionate aqueous nasal spray was determined. METHODS--Production of nitric oxide (measured as nitrite+nitrate) in vivo in nasal mucosa was examined in 24 patients with rhinitis allergic to the house

  5. Biochemical aspects of nitric oxide synthase feedback regulation by nitric oxide

    PubMed Central

    Kopincová, Jana; Púzserová, Angelika; Bernátová, Iveta

    2011-01-01

    Nitric oxide (NO) is a small gas molecule derived from at least three isoforms of the enzyme termed nitric oxide synthase (NOS). More than 15 years ago, the question of feedback regulation of NOS activity and expression by its own product was raised. Since then, a number of trials have verified the existence of negative feedback loop both in vitro and in vivo. NO, whether released from exogenous donors or applied in authentic NO solution, is able to inhibit NOS activity and also intervenes in NOS expression processes by its effect on transcriptional nuclear factor NF-?B. The existence of negative feedback regulation of NOS may provide a powerful tool for experimental and clinical use, especially in inflammation, when massive NOS expression may be detrimental. PMID:21753901

  6. Nitric oxide, nitrotyrosine, and nitric oxide modulators in asthma and chronic obstructive pulmonary disease

    Microsoft Academic Search

    Sergei A. Kharitonov; Peter J. Barnes

    2003-01-01

    Nitric oxide (NO), a simple free-radical gas, elicits a diverse range of physiologic and pathophysiologic effects, and plays\\u000a an important role in pulmonary diseases. Nitrosative stress and nitration of proteins in airway epithelium may be responsible\\u000a for steroid resistance in asthma and their ineffectiveness in chronic obstructive pulmonary disease (COPD), supporting the\\u000a potential role of future therapeutic strategies aimed at

  7. 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

  8. Nitric Oxide Release Part I. Macromolecular Scaffolds

    PubMed Central

    Riccio, Daniel A.; Schoenfisch, Mark H.

    2012-01-01

    Summary The roles of nitric oxide (NO) in physiology and pathophysiology merit the use of NO as a therapeutic for certain biomedical applications. Unfortunately, limited NO payloads, too rapid NO release, and the lack of targeted NO delivery have hindered the clinical utility of NO gas and low molecular weight NO donor compounds. A wide-variety of NO-releasing macromolecular scaffolds has thus been developed to improve NO’s pharmacological potential. In this tutorial review, we provide an overview of the most promising NO release scaffolds including protein, organic, inorganic, and hybrid organic-inorganic systems. The NO release vehicles selected for discussion were chosen based on their enhanced NO storage, tunable NO release characteristics, and potential as therapeutics. PMID:22362355

  9. Antiobesogenic role of endothelial nitric oxide synthase.

    PubMed

    Sansbury, Brian E; Hill, Bradford G

    2014-01-01

    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 antiobesity 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 antiobesogenic effects. PMID:25189393

  10. 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

  11. Recent developments in nitric oxide donor drugs

    PubMed Central

    Miller, M R; Megson, I L

    2007-01-01

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

  12. 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

  13. Nitric oxide and mitochondria in metabolic syndrome.

    PubMed

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

    2015-01-01

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

  14. MAP kinases bind endothelial nitric oxide synthase

    PubMed Central

    Chrestensen, Carol A.; McMurry, Jonathan L.; Salerno, John C.

    2012-01-01

    Endothelial nitric oxide synthase (eNOS) contains a motif similar to recognition sequences in known MAPK binding partners. In optical biosensing experiments, eNOS bound p38 and ERK with ?100 nM affinity and complex kinetics. Binding is diffusion-limited (kon ? .15 × 106 M?1 s?1). Neuronal NOS also bound p38 but exhibited much slower and weaker binding. p38-eNOS binding was inhibited by calmodulin. Evidence for a ternary complex was found when eNOS bound p38 was exposed to CaM, increasing the apparent dissociation rate. These observations strongly suggest a direct role for MAPK in regulation of NOS with implications for signaling pathways including angiogenesis and control of vascular tone. PMID:23650581

  15. 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.

  16. Efficient nitrosation of glutathione by nitric oxide?

    PubMed Central

    Kolesnik, Bernd; Palten, Knut; Schrammel, Astrid; Stessel, Heike; Schmidt, Kurt; Mayer, Bernd; Gorren, Antonius C.F.

    2013-01-01

    Nitrosothiols are increasingly regarded as important participants in a range of physiological processes, yet little is known about their biological generation. Nitrosothiols can be formed from the corresponding thiols by nitric oxide in a reaction that requires the presence of oxygen and is mediated by reactive intermediates (NO2 or N2O3) formed in the course of NO autoxidation. Because the autoxidation of NO is second order in NO, it is extremely slow at submicromolar NO concentrations, casting doubt on its physiological relevance. In this paper we present evidence that at submicromolar NO concentrations the aerobic nitrosation of glutathione does not involve NO autoxidation but a reaction that is first order in NO. We show that this reaction produces nitrosoglutathione efficiently in a reaction that is strongly stimulated by physiological concentrations of Mg2+. These observations suggest that direct aerobic nitrosation may represent a physiologically relevant pathway of nitrosothiol formation. PMID:23660531

  17. 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

  18. 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

  19. 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.

  20. [Inducible nitric oxide synthase expression and nitric oxide production by monocytes in systemic sclerosis].

    PubMed

    Menkès, C J; Allanore, Y; Borderie, D; Hilliquin, P; Hernvann, A; Ekindjian, O; Kahan, A

    2001-01-01

    We investigated nitric oxide (NO) production and inducible NO synthase (iNOS) expression by cultured peripheral blood mononuclear cells (PBMC) in systemic sclerosis (SSc). Eighteen patients with SSc were compared to two control groups: 16 rheumatoid arthritis patients (RA) and 23 mechanical sciatica patients. The sum of nitrites and nitrates was determined by fluorimetry in sera and spectrophotometry in supernatants. Inducible iNOS was detected in cultured PBMC by immunofluorescence, immunoblot and flow cytometry with or without IL-1 beta + TNF alpha, IL-4 or IFN gamma from day 1 to day 5. NO metabolite concentrations in the plasma were lower in SSc (34.3 mumol/l +/- 2.63 SEM) than in RA (48.3 mumol/l +/- 2.2; p < 0.02) and sciatica (43.3 mumol/l +/- 5.24; p < 0.03) patients. iNOS was detected in cultured monocytes in the 3 groups but induction occurred on day 1 in RA, day 2 in sciatica and only on day 3 in SSc, whatever the stimulus. The concentrations of NO metabolites are decreased in SSc patients and the induction of iNOS in PBMC is delayed. Low levels of NO, a vasodilator, may be involved in vasospasm, which is critical in SSc. This may suggest therapeutic implications. PMID:11501260

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

    PubMed Central

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

    2014-01-01

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

  2. Comparison between the Acute Pulmonary Vascular Effects of Oxygen with Nitric Oxide and Sildenafil

    PubMed Central

    Day, Ronald W.

    2015-01-01

    Objective: Right heart catheterization is performed in patients with pulmonary arterial hypertension to determine the severity of disease and their pulmonary vascular reactivity. The acute pulmonary vascular effect of inhaled nitric oxide is frequently used to identify patients who will respond favorably to long-term vasodilator therapy. This study sought to determine whether the acute pulmonary vascular effects of oxygen with nitric oxide and intravenous sildenafil are similar. Methods: A retrospective, descriptive study of 13 individuals with pulmonary hypertension who underwent heart catheterization and acute vasodilator testing was performed. The hemodynamic measurements during five phases (21–53% oxygen, 100% oxygen, 100% oxygen with 20?ppm nitric oxide, 21–51% oxygen, and 21–51% oxygen with 0.05–0.29?mg/kg intravenous sildenafil) of the procedures were compared using analysis of variance. A linear regression analysis and a Bland Altman plot were used to compare the percent change in mean pulmonary arterial pressure and the percent change in pulmonary vascular resistance from baseline with oxygen and nitric oxide, and from baseline with sildenafil. Results: Mean pulmonary arterial pressure and pulmonary vascular resistance acutely decreased with 100% oxygen with nitric oxide and 21–51% oxygen with sildenafil. Pulmonary blood flow during sildenafil was greater than pulmonary blood flow during 100% oxygen and 100% oxygen with nitric oxide. The pH, right atrial pressure, and left atrial pressure did not change during the five phase of heart catheterization. Mean pulmonary arterial pressure (millimeter of mercury, mean?±?standard error of the mean) was 38?±?4 during 21–53% oxygen, 32?±?3 during 100% oxygen, 29?±?2 during 100% oxygen with nitric oxide, 37?±?3 during 21–51% oxygen, and 32?±?2 during 21–51% oxygen with sildenafil. There was not a significant correlation between the percent change in pulmonary vascular resistance from baseline with oxygen and nitric oxide, and from baseline with sildenafil (r2?=?0.011, p?=?0.738). The Bland Altman analysis demonstrated statistical agreement between the effects of oxygen with nitric oxide and sildenafil. However, differences were large enough to limit the interchangeable use of these vasodilators in a clinical setting. Conclusion: Oxygen with nitric oxide and sildenafil decreased pulmonary vascular resistance. However, the pulmonary vascular effects of oxygen and nitric oxide do not reliably predict the acute response to sildenafil. Additional studies are needed to determine whether the acute response to sildenafil can be used to predict the long-term response to treatment with an oral phosphodiesterase V inhibitor. PMID:25785258

  3. Nitric oxide, an endothelial cell relaxation factor, inhibits neutrophil superoxide anion production via a direct action on the NADPH oxidase.

    PubMed Central

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

    1992-01-01

    Nitric oxide provokes vasodilation and inhibits platelet aggregation. We examined the effect of nitric oxide on superoxide anion production by three sources: activated intact neutrophils, xanthine oxidase/hypoxanthine, and the NADPH oxidase. Nitric oxide significantly inhibited the generation of superoxide anion by neutrophils exposed to either FMLP (10(-7)M) or PMA (150 ng/ml) (IC50 = 30 microM). To determine whether the effect of nitric oxide on the respiratory burst was due to simple scavenging of O2+, kinetic studies that compared effects on neutrophils and the cell-free xanthine oxidase system were performed. Nitric oxide inhibited O2+ produced by xanthine oxidase only when added simultaneously with substrate, consistent with the short half-life of NO in oxygenated solution. In contrast, the addition of nitric oxide to neutrophils 20 min before FMLP resulted in the inhibition of O2+ production, which suggests formation of a stable intermediate. The effect of nitric oxide on the cell-free NADPH oxidase superoxide-generating system was also examined: The addition of NO before arachidonate activation (t = -6 min) significantly inhibited superoxide anion production. Nitric oxide did not inhibit O2+ when added at NADPH initiation (t = 0). Treatment of the membrane but not cytosolic component of the oxidase was sufficient to inhibit O2+ generation. The data suggest that nitric oxide inhibits neutrophil O2+ production via direct effects on membrane components of the NADPH oxidase. This action must occur before the assembly of the activated complex. PMID:1325992

  4. 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...

  5. Decreased gene expression of neuronal nitric oxide synthase in hypothalamus and brainstem of rats in heart failure

    Microsoft Academic Search

    Kaushik. P. Pate; Kun Zhang; Irving H. Zucker; Teresa L. Krukoff

    1996-01-01

    Nitric oxide may act at autonomic sites in the brain to regulate sympathetic outflow. Our goal was to determine whether gene expression of the neuronal isoform of nitric oxide synthase (nNOS) is altered in discrete autonomic brain regions of rats in the chronic phase of heart failure compared to sham-operated control rats. Experiments were performed in rats 4 to 5

  6. 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.

  7. 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

  8. Biomimetic and microbial reduction of nitric oxide

    SciTech Connect

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

    1995-12-31

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

  9. The Oxyhemoglobin Reaction of Nitric Oxide

    NASA Astrophysics Data System (ADS)

    Gow, Andrew J.; Luchsinger, Benjamin P.; Pawloski, John R.; Singel, David J.; Stamler, Jonathan S.

    1999-08-01

    The oxidation of nitric oxide (NO) to nitrate by oxyhemoglobin is a fundamental reaction that shapes our understanding of NO biology. This reaction is considered to be the major pathway for NO elimination from the body; it is the basis for a prevalent NO assay; it is a critical feature in the modeling of NO diffusion in the circulatory system; and it informs a variety of therapeutic applications, including NO-inhalation therapy and blood substitute design. Here we show that, under physiological conditions, this reaction is of little significance. Instead, NO preferentially binds to the minor population of the hemoglobin's vacant hemes in a cooperative manner, nitrosylates hemoglobin thiols, or reacts with liberated superoxide in solution. In the red blood cell, superoxide dismutase eliminates superoxide, increasing the yield of S-nitrosohemoglobin and nitrosylated hemes. Hemoglobin thus serves to regulate the chemistry of NO and maintain it in a bioactive state. These results represent a reversal of the conventional view of hemoglobin in NO biology and motivate a reconsideration of fundamental issues in NO biochemistry and therapy.

  10. Detecting and Understanding the Roles of Nitric Oxide in biology

    E-print Network

    Tonzetich, Zachary J.

    We are pursuing a dual strategy for investigating the chemistry of nitric oxide as a biological signaling agent. In one approach, metal-based fluorescent sensors for the detection of NO in living cells are evaluated, and ...

  11. Lack of Central Nitric Oxide Triggers Erectile Dysfuntion in Diabetes

    NSDL National Science Digital Library

    PhD Kaushik P. Patel (University of Nebraska Cellular and Integrative Physiology)

    2007-03-01

    Journal article "Lack of central nitric oxide triggers erectile dysfuntion in diabetes", by Kaushik P. Patel, Keshore R. Bidasee, William G. Mayhan, and Zeng Hong, found in the APS journal of Regulatory, Integrative, and Comparative Physiology.

  12. Hydrogen peroxide differentially modulates cardiac myocyte nitric oxide synthesis

    E-print Network

    Sartoretto, Juliano

    Nitric oxide (NO) and hydrogen peroxide (H(subscript 2)O(subscript 2)) are synthesized within cardiac myocytes and play key roles in modulating cardiovascular signaling. Cardiac myocytes contain both the endothelial (eNOS) ...

  13. Generation, Translocation, and Action of Nitric Oxide in Living Systems

    E-print Network

    Tennyson, Andrew G.

    Nitric oxide (NO) is a gaseous diatomic radical that is involved in a wide range of physiological and pathological functions in biology. Conceptually, the biochemistry of NO can be separated into three stages: generation ...

  14. Prediction of nitric oxide concentrations during inflammation and carcinogenesis

    E-print Network

    Chin, Melanie Pei-Heng

    2010-01-01

    Nitric oxide is a biological messenger which is synthesized enzymatically throughout the body and which has numerous physiological functions, including roles in blood pressure control, regulation of clotting, and ...

  15. Nitric Oxide and the Control of Firefly Flashing

    E-print Network

    Lewis, Sara

    lantern (6). Light production involves an adenosine triphosphate­ and O2-dependent luciferin-lu- ciferase by nitric oxide (NO) gas in the presence of oxygen and that NO scavengers block biolumi- nescence induced

  16. The effect of multiple allergen immunotherapy on exhaled nitric oxide in adults with allergic rhinitis

    PubMed Central

    2013-01-01

    Background There is a lack of objective measures of the clinical efficacy of allergen immunotherapy which relies on patients’ perception about the effect of this treatment. We studied whether the fraction of exhaled nitric oxide is affected by multiple allergen immunotherapy in polysensitized adult subjects with allergic rhinitis. We also looked for associations between exhaled nitric oxide and subjects’ demographics, symptom scores, and pulmonary function tests. Methods Twenty adult, polysensitized subjects with seasonal and perennial allergic rhinitis who chose to undergo allergen immunotherapy were enrolled. They were evaluated at baseline, and 4, 8, 12, 24, and 52 weeks later. Exhaled nitric oxide was reported as the mean of triplicate determinations. Findings Our results indicate that multiple allergen immunotherapy did not affect exhaled nitric oxide levels and such levels did not correlate with subjects’ demographics and pulmonary function tests. However, exhaled nitric oxide was associated with rhinoconjuctivitis and asthma symptom scores at the end of the study. Conclusions In polysensitized adult subjects with allergic rhinitis, exhaled nitric oxide levels are unaffected by multiple allergen immunotherapy. PMID:23958488

  17. Ganoderma lucidum inhibits inducible nitric oxide synthase expression in macrophages

    Microsoft Academic Search

    Connie W. H. Woo; Ricky Y. K. Man; Yaw L. Siow; Patrick C. Choy; Eric W. Y. Wan; Chak S. Lau; Karmin O

    2005-01-01

    Nitric oxide (NO) is a principal mediator in many physiological and pathological processes. Overproduction of NO via the inducible nitric oxide synthase (iNOS) has cytotoxic effect through the formation of peroxynitrite with superoxide anion. The iNOS is mainly expressed in macrophages and is able to produce large amount of NO. The expression of iNOS is mainly regulated at the transcriptional

  18. [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

  19. The high-output nitric oxide pathway: role and regulation

    Microsoft Academic Search

    Qiao-wen Xie; Carl Nathan

    1994-01-01

    Nitric oxide synthase (NOS) catalyzes the production of nitric oxide (NO), a short-lived radical gas with physiological or pathophysiological roles in nearly every organ system. The inducible NO synthase (iNOS) is a high-output isoform compared to the two constitutive NOSs. The iNOS from murine macrophages tightly binds calmodulin as a subunit, and its activity is not dependent on exogenous calmodulin

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

    Microsoft Academic Search

    Christoph A. Schmitt; Verena M. Dirsch

    2009-01-01

    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

  1. Nitric oxide synthase in human parathyroid glands and parathyroid adenomas

    Microsoft Academic Search

    Lena Luts; Anders Bergenfelz; Jan Alumets; Frank Sundler

    1996-01-01

    Nitric oxide (NO) is a novel gaseous intercellular transmitter thought to play important physiological roles in the regulation\\u000a of blood flow and hormone secretion in, for example, the pituitary, the thyroid, and the endocrine pancreas. Whether nitric\\u000a oxide synthase (NOS) is present in the human parathyroid glands has not yet been demonstrated. In the present study, histologically\\u000a normal, but functionally

  2. Detection and determination of the {Fe(NO)(2)} core vibrational features in dinitrosyl-iron complexes from experiment, normal coordinate analysis, and density functional theory: an avenue for probing the nitric oxide oxidation state.

    PubMed

    Dai, Ruei Jang; Ke, Shyue Chu

    2007-03-01

    As it is now well-established that nitric oxide plays an important role in many physiological processes, there is a renewed interest in dinitrosyl-iron complexes (DNICs). The question concerning the electronic structure of DNICs circles around the formal oxidation states of the iron and nitric oxide of the Fe(NO)2 core. Previous infrared measurements of nu(NO) alone point out inconsistencies in assigning electron configurations and charges on metals, inherent from the measurement of one parameter external to the metal. This work represents the first experimental and theoretical attempt to assign vibrational modes for the {Fe(NO)2}9 core of DNICs. The following complexes are investigated, [PPN][S5Fe(NO)2] (1), [PPN][Se5Fe(NO)2] (2), [PPN][(SPh)2Fe(NO)2] (3), and [PPN][(SePh)2Fe(NO)2] (4). The analysis of isotopically edited Raman data together with normal coordinate calculation permitted assignment of nu(NO) and nu(Fe-NO) stretching and delta(Fe-N-O) bending modes in these complexes. The assignments proposed are the first ever reported for the DNICs; a comparison of nu(NO) and nu(Fe-NO) stretching frequencies in DNICs is now feasible. The Fe(NO)2 core electronic configuration in these complexes is described as {Fe1+(*NO)2}. Results from 1 and 3 have been complemented by density functional theory (DFT) frequency calculations. In addition to providing a reasonably correct account of the observed frequencies, DFT calculations also give a good account of the frequency shifts upon 15NO substitution providing the first link between DFT and Raman spectroscopies for DNICs. Through the use of a combination of NO intraligand and metal-ligand vibrational data for the Fe(NO)2 core, normal coordinate analysis gives a NO stretching force constant, which compared to molecular NO gas, is significantly reduced for all four complexes. The hybrid U-B3LYP/6-311++G(3d,2p) density functional method has been employed to analyze the molecular orbital compositions of predominantly NO orbitals based on the crystal structure of complex 1. The molecular orbital not only revealed the bonding nature of the {Fe(NO)2}9 core but also provided a qualitative correct account of the observed low NO vibrational frequencies. The calculation shows that the NO is involved in a strong donor bonding interaction with the Fe1+. This donor bonding interaction involves the 5sigma molecular orbital of the NO, which is sigma-bonding with respect to the intramolecular NO bond, and removal of electron density from this orbital destabilizes the NO bond. Though it is too ambiguous to extrapolate a nu(Fe-NO)/nu(NO) correlation line for {Fe(NO)2}9 DNICs based only on the data reported here, the feasibility of using a vibrational systematics diagram to extract the electron configurations and charges on metals is demonstrated based on the vibrational data available in the literature for iron-nitrosyl complexes. The data provided here can be used as a model for the determination of effective charges on iron and the bonding of nitric oxides to metals in DNICs. PMID:17295535

  3. 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.

  4. Nitric oxide in legume-rhizobium symbiosis.

    PubMed

    Meilhoc, Eliane; Boscari, Alexandre; Bruand, Claude; Puppo, Alain; Brouquisse, Renaud

    2011-11-01

    Nitric oxide (NO) is a gaseous signaling molecule with a broad spectrum of regulatory functions in plant growth and development. NO has been found to be involved in various pathogenic or symbiotic plant-microbe interactions. During the last decade, increasing evidence of the occurrence of NO during legume-rhizobium symbioses has been reported, from early steps of plant-bacteria interaction, to the nitrogen-fixing step in mature nodules. This review focuses on recent advances on NO production and function in nitrogen-fixing symbiosis. First, the potential plant and bacterial sources of NO, including NO synthase-like, nitrate reductase or electron transfer chains of both partners, are presented. Then responses of plant and bacterial cells to the presence of NO are presented in the context of the N(2)-fixing symbiosis. Finally, the roles of NO as either a regulatory signal of development, or a toxic compound with inhibitory effects on nitrogen fixation, or an intermediate involved in energy metabolism, during symbiosis establishment and nodule functioning are discussed. PMID:21893254

  5. Tapentadol and nitric oxide synthase systems.

    PubMed

    Bujalska-Zadro?ny, Magdalena; Woli?ska, Renata; G?si?ska, Emilia; Nagraba, ?ukasz

    2015-04-01

    Tapentadol, a new analgesic drug with a dual mechanism of action (?-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

  6. Nitric oxide modulates sensitivity to ABA.

    PubMed

    Lozano-Juste, Jorge; León, José

    2010-03-01

    Nitric oxide (NO) is a gas with crucial signaling functions in plant defense and development. As demonstrated by generating a triple nia1nia2noa1-2 mutant with extremely low levels of NO (February 2010 issue of Plant Physiology), NO is synthesized in plants through mainly two different pathways involving nitrate reductase (NR/NIA) and NO Associated 1 (AtNOA1) proteins. Depletion of basal NO levels leads to a priming of ABA-triggered responses that causes hypersensitivity to this hormone and results in enhanced seed dormancy and decreased seed germination and seedling establishment in the triple mutant. NO produced under non-stressed conditions represses inhibition of seed developmental transitions by ABA. Moreover, NO plays a positive role in post-germinative vegetative development and also exerts a critical control of ABA-related functions on stomata closure. The triple nia1nia2noa1-2 mutant is hypersensitive to ABA in stomatal closure thus resulting in a extreme phenotype of resistance to drought. In the light of the recent discovery of PYR/PYL/RCAR as a family of potential ABA receptors, regulation of ABA sensitivity by NO may be exerted either directly on ABA receptors or on downstream signaling components; both two aspects that deserve our present and future attention. PMID:20168082

  7. 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

  8. 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.

  9. 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

  10. 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...

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

    Microsoft Academic Search

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

    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

  12. 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

    Microsoft Academic Search

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

    2007-01-01

    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,

  13. Inducible Nitric Oxide Synthase Expression in Human Colorectal Cancer

    PubMed Central

    Cianchi, Fabio; Cortesini, Camillo; Fantappiè, Ornella; Messerini, Luca; Schiavone, Nicola; Vannacci, Alfredo; Nistri, Silvia; Sardi, Iacopo; Baroni, Gianna; Marzocca, Cosimo; Perna, Federico; Mazzanti, Roberto; Bechi, Paolo; Masini, Emanuela

    2003-01-01

    To investigate the potential involvement of the nitric oxide (NO) pathway in colorectal carcinogenesis, we correlated the expression and the activity of inducible nitric oxide synthase (iNOS) with the degree of tumor angiogenesis in human colorectal cancer. Tumor samples and adjacent normal mucosa were obtained from 46 surgical specimens. Immunohistochemical expression of iNOS, vascular endothelial growth factor (VEGF), and CD31 was analyzed on paraffin-embedded tissue sections. iNOS activity and cyclic GMP levels were assessed by specific biochemical assays. iNOS protein expression was determined by Western blot analysis. iNOS and VEGF mRNA levels were evaluated using Northern blot analysis. Both iNOS and VEGF expressions correlated significantly with intratumor microvessel density (rs = 0.31, P = 0.02 and rs = 0.67, P < 0.0001, respectively). A significant correlation was also found between iNOS and VEGF expression (P = 0.001). iNOS activity and cyclic GMP production were significantly higher in the cancer specimens than in the normal mucosa (P < 0.0001 and P < 0.0001, respectively), as well as in metastatic tumors than in nonmetastatic ones (P = 0.002 and P = 0.04, respectively). Western and Northern blot analyses confirmed the up-regulation of the iNOS protein and gene in the tumor specimens as compared with normal mucosa. NO seems to play a role in colorectal cancer growth by promoting tumor angiogenesis. PMID:12598314

  14. On the protective mechanisms of nitric oxide in acute pancreatitis

    PubMed Central

    Werner, J; Castillo, C; Rivera, J; Kollias, N; Lewandrowski, K; Rattner, D; Warshaw, A

    1998-01-01

    Background—Ectopic protease activation, microcirculatory changes, and leucocyte activation are the main events in the pathogenesis of acute pancreatitis. Nitric oxide (NO) is known to be a key mediator in the normal and inflamed pancreas. ?Aims—To investigate the targets on which NO exerts its effect in caerulein induced pancreatitis. ?Methods—Acute pancreatitis was induced in rats which additionally received either the NO synthase substrate, L-arginine; the NO donor, sodium nitroprusside; or the NO synthase inhibitor, N-nitro-L-arginine methyl ester (L-NAME). At six hours, pancreatic injury (oedema, leucocyte content, ectopic trypsinogen activation) was analysed and pancreatic oxygenation and perfusion were determined. A direct influence of NO on amylase secretion and trypsinogen activation was evaluated separately in vitro. ?Results—Both NO donors reduced the grade of inflammation. L-NAME increased the severity of inflammation, while decreasing pancreatic tissue oxygenation. Although neither amylase secretion nor intracellular trypsinogen activation in caerulein stimulated pancreatic acini was influenced by either NO donors or inhibitors, both NO donors decreased intrapancreatic trypsinogen activation peptide (TAP) and pancreatic oedema in vivo, and L-NAME increased TAP. ?Conclusions—NO protects against injury caused by pancreatitis in the intact animal but has no discernible effect on isolated acini. It is likely that in pancreatitis NO acts indirectly via microcirculatory changes, including inhibition of leucocyte activation and preservation of capillary perfusion. ?? Keywords: acute pancreatitis; nitric oxide; microcirculation; leucocytes; pancreatic secretion PMID:9863487

  15. Nitric oxide formation from nitrite in zebrafish.

    PubMed

    Jensen, Frank B

    2007-10-01

    Nitrite is a potential nitric oxide (NO) donor and may have important biological functions at low concentrations. The present study tests the hypothesis that nitrite accumulation across the gills in fish will cause a massive NO production from nitrite. Zebrafish were exposed to three different nitrite levels for variable time periods, and changes in blood nitrosylhemoglobin (HbNO), methemoglobin (metHb), oxygenated hemoglobin (oxyHb) and deoxygenated hemoglobin (deoxyHb) were evaluated by spectral deconvolution. Blood HbNO (a biomarker of internal NO production) was low in controls, increased to a stable level around 3.7% of total Hb in fish exposed to 0.6 mmol l(-1) nitrite, and to 12.1% (at day 2) in fish exposed to 2 mmol l(-1) nitrite. The very high HbNO levels testify to an extensive conversion of nitrite to NO. With deoxyHb-mediated reduction of nitrite being a major NO-producing mechanism, the data reveal the significance of this mechanism, when hemoglobin cycles between full and intermediate oxygen saturations in the arterial-venous circulation. Fish exposed to 0.6 mmol l(-1) nitrite for up to 5 days could be divided into responding (with elevated metHb) and non-responding individuals. Exposure to 2 mmol l(-1) nitrite caused a time-dependent increase in metHb to 59% of total Hb within 2 days. Taking HbNO into account, the functional (potential O2 carrying) Hb was reduced to 29% at this stage. Total blood [Hb] was also significantly decreased. In spite of the reduced blood O2 capacitance, and the possibility that excess NO may inhibit mitochondrial respiration, whole animal routine oxygen consumption was not depressed. PMID:17872992

  16. 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

  17. Peroxynitrite: mediator of the toxic action of nitric oxide.

    PubMed

    Bartosz, G

    1996-01-01

    Peroxynitrite (oxoperoxonitrate(-1)), anion of peroxynitrous acid, is thought to mediate the toxic action of nitric oxide and superoxide anion. Peroxynitrite is formed in a fast reaction between these species, reacts with all classes of biomolecules, is cytotoxic, and is thought to be involved in many pathological phenomena. Its main reactions involve one- and two-electron oxidation and nitration. Protein nitration is often used as a footprint of peroxynitrite reactions in vivo. Nitration of tyrosine and of tyrosyl residues in proteins may be an important mechanism of derangement of biochemical signal transduction by this compound. However, apparently beneficial effects of peroxynitrite have also been described, among them formation of nitric oxide and nitric oxide donors in reactions of peroxynitrite with thiols and alcohols. PMID:9104501

  18. 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

  19. Nitric Oxide in Tanzanian Children with Malaria: Inverse Relationship between Malaria Severity and Nitric Oxide Production\\/Nitri c Oxide Synthase Type 2 Expression

    Microsoft Academic Search

    Nicholas M. Anstey; J. Brice Weinberg; Mushtaq Y. Hassanali; Esther D. Mwaikambo; Denis Manyenga; Mary A. Misukonis; Derrick R. Arnellefi; Donna Hollis; Malcolm I. McDonald; Donald L. Granger

    1996-01-01

    Summary Nitric oxide (NO)-related activity has been shown to be protective against Plasmodium faki- parum in vitro. It has been hypothesized, however, that excess NO production contributes to the pathogenesis of cerebral malaria. The purpose of this study was to compare markers of NO production (urinary and plasma nitrate + nitrite (NO~)), leukocyte-inducible nitric oxide syn- thase type 2 (NOS2),

  20. Induction of nitric oxide production by bovine mammary epithelial cells and blood leukocytes.

    PubMed

    Boulanger, V; Bouchard, L; Zhao, X; Lacasse, P

    2001-06-01

    A recent study from our laboratory has shown that significant amounts of nitric oxide are released by somatic cells recovered during endotoxin-induced mastitis. The present study was undertaken to investigate which cell type(s) among milk somatic cell population can produce nitric oxide under inflammatory conditions. Nitric oxide release from mammary epithelial cell lines and from bovine neutrophils and monocytes extracted from blood was measured in response to cytokines and Escherichia coli lipopolysaccharides. An epithelial cell line isolated from bovine mammary gland, FbE cells, was found to release nitric oxide after exposure to interleukin-1beta. This nitric oxide production was completely abolished by addition of L-N6-(1-iminoethyl) lysine, a potent inducible nitric oxide synthase inhibitor. Bovine monocytes produced nitric oxide in response to recombinant bovine interferon-gamma alone or in combination with E. coli lipopolysaccharides. In these cells, nitric oxide release was reduced by the addition of inducible nitric oxide synthase inhibitors L-N6-(1-iminoethyl) lysine and aminoguanidine. Lipopolysaccharides and recombinant bovine interferon-gamma increased nitric oxide synthase mRNA in neutrophils, but nitric oxide release could not be detected under any of the experimental conditions used. These results show that bovine epithelial cells and mononuclear phagocytes produce nitric oxide under inflammatory conditions and suggest that these cell populations are responsible for nitric oxide release observed during mastitis. PMID:11417702

  1. Environmental exposures, nitric oxide synthase genes, and exhaled nitric oxide in asthmatic children.

    PubMed

    Spanier, Adam J; Kahn, Robert S; Hornung, Richard W; Wang, Ning; Sun, Guangyun; Lierl, Michelle B; Lanphear, Bruce P

    2009-08-01

    Exhaled nitric oxide (FeNO), a measure of airway inflammation, is being explored as a tool to guide asthma management in children. Investigators have identified associations of genetic polymorphisms in nitric oxide synthase genes (NOS1 and NOS3) with FeNO levels; however, none have explored whether these polymorphisms modify the relationship of environmental exposures with FeNO. The objective of this project was to evaluate the association of NOS polymorphisms and environmental exposures with FeNO levels among children with asthma. We conducted a 12-month prospective cohort study of 225 tobacco-smoke exposed children (6-12 years) with doctor-diagnosed asthma. We assessed environmental exposures (tobacco, indoor allergens, & airborne particulates), polymorphisms in NOS1 (an intronic AAT tandem repeat) and NOS3 (G894T), and FeNO levels. There was no association of NOS1 or NOS3 polymorphisms with FeNO levels. There were no significant interactions of environmental exposures and the NOS1 polymorphism with FeNO levels. In contrast, there was an interaction of the NOS3 polymorphism and airborne nicotine concentration with FeNO levels (P = 0.01). Among GG genotype individuals, nicotine exposure did not affect FeNO levels; however, among individuals with at least one T allele, higher nicotine exposure was associated with lower FeNO levels (approximately 5 ppb decrease from the lowest to the highest quartile). We conclude that genetic differences may explain some of the conflicting results in studies of the effects of tobacco smoke exposure on FeNO levels and may make FeNO interpretation difficult for a subset of children with asthma. PMID:19603529

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

  3. Evaluation of nitric oxide production by lactobacilli.

    PubMed

    Xu, J; Verstraete, W

    2001-08-01

    Six strains of Lactobacillus fermentum and Lactobacillus plantarum were investigated for nitric oxide (NO) production. First, the potential presence of NO synthase was examined. None of the strains of L. fermentum and L. plantarum examined produced NO from L-arginine under aerobic conditions. Interestingly, all L. fermentum strains expressed strong L-arginine deiminase activity. All L. fermentum strains produced NO in MRS broth, but the NO was found to be chemically derived from nitrite, which was produced by L. fermentum from nitrate present in the medium. Indeed all L. fermentum strains express nitrate reductase under anaerobic conditions. Moreover, one strain, L. fermentum LF1, had nitrate reductase activity under aerobic conditions. It was also found that L. fermentum strains JCM1173 and LF1 possessed ammonifying nitrite reductase. The latter strain also had denitrifying nitrite reductase activity at neutral pH under both anaerobic and aerobic conditions. The LF1 strain is thus capable of biochemically converting nitrate to NO. NO and nitrite produced from nitrate by lactobacilli may constitute a potential antimicrobial mechanism. studied in a rat acute liver injury model (Adawi et al. 1997). The results indicate that Lactobacillus plantarum DSM 9842 may possess NOS (Adawi et al. 1997). However, NO production from L-arginine has not been investigated in pure cultures of L. plantarum. According to the results of a 15N enrichment experiment, traces of (NO2-+NO3-)-N (total oxidised nitrogen: TON), which seemed to be formed by the resting cells of Lactobacillus fermentum IFO3956, appeared to be derived from L-arginine (Morita et al. 1997). Therefore, it was suggested that L. fermentum may possess a NOS. However, NO produced from L-arginine was not directly measured and a NOS inhibitor test was not performed by Morita et al. (1997). It is known that L-arginine deiminase (ADI) in bacteria may convert L-arginine to NH4+ (Cunin et al. 1986), which may be further oxidised to TON via nitrification by bacteria. Therefore, 15N enrichment experiments could not definitely conclude that L. fermentum possess NOS to convert L-arginine directly to NO. In this study, six Lactobacillus strains belonging to L. plantarum and L. fermentum were measured for NO production in MRS broth. The metabolism of nitrate and L-arginine by the Lactobacillus cell suspensions was also studied. The possibility that NO and nitrite production by lactobacilli may be a potential probiotic trait is also discussed. PMID:11549028

  4. Nitric oxide measurement study: Volume I. Optical calibration

    SciTech Connect

    Dodge, L.G.; Colket, M.B. III; Zabielski, M.F.; Dusek, J.; Seery, D.J.

    1980-05-01

    Calibration devices suitable for providing known amounts of nitric oxide (NO) at temperatures ranging from 300 K to 2000 K and pressures of 0.5 atm (50.7kPa) to 2.0 atm (203kPa) are described with their design considerations. Methods for confirming nitric oxide concentrations are given. The spectroscopic theory for the absorption of ultraviolet radiation in the gamma (0,0) band of nitric oxide is reviewed. Experimental values for oscillator strengths and broadening parameters for NO with various collision partners are provided. Experimental results confirming the adequacy of a computer spectral model and, hence, the calibration are presented along with the details of the model. Finally, the results of an empirical calibration of an infrared gas correlation spectrometer are given.

  5. 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.

  6. 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 burst gas composition is close to stoichiometric and gas temperatures are highest. It has been 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 NO sub x emissions. Data from a number of different combustor concepts are analyzed and shown to be in reasonable agreement with predictions. The NO sub x 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 NO sub x emissions burner type.

  7. Pain Modulation by Nitric Oxide in the Spinal Cord

    PubMed Central

    Freire, Marco Aurélio M.; Guimarães, Joanilson S.; Leal, Walace Gomes; Pereira, Antonio

    2009-01-01

    Nitric oxide (NO) is a versatile messenger molecule first associated with endothelial relaxing effects. In the central nervous system (CNS), NO synthesis is primarily triggered by activation of N-methyl-D-aspartate (NMDA) receptors and has a Janus face, with both beneficial and harmful properties. There are three isoforms of the NO synthesizing enzyme nitric oxide synthase (NOS): neuronal (nNOS), endothelial (eNOS), and inducible nitric oxide synthase (iNOS), each one involved with specific events in the brain. In the CNS, nNOS is involved with modulation of synaptic transmission through long-term potentiation in several regions, including nociceptive circuits in the spinal cord. Here, we review the role played by NO on central pain sensitization. PMID:20011139

  8. DOES BRACHIAL ARTERY FMD PROVIDE A BIOASSAY FOR NITRIC OXIDE?

    PubMed Central

    Wray, D. Walter; Witman, Melissa A. H.; Ives, Stephen J.; McDaniel, John; Trinity, Joel D.; Conklin, Jamie D.; Supiano, Mark A.; Richardson, Russell S.

    2013-01-01

    This study sought to better define the role of nitric oxide (NO) in brachial artery flow-mediated vasodilation (FMD) in young, healthy humans. Brachial artery blood velocity and diameter were determined (ultrasound Doppler) in eight volunteers (26 ± 1 yrs) before and after 5-min forearm circulatory occlusion with and without intra-arterial infusion of the endothelial nitric oxide synthase (eNOS) inhibitor L-NMMA (0.48 mg/dl/min). Control (CON) and L-NMMA trials were performed with the occlusion cuff placed in the traditional distal position, as well as proximal to the measurement site. FMD was significantly reduced, but not abolished, by L-NMMA in the distal cuff trial (8.9 ± 1.3 to 6.0 ± 0.7%, CON vs. L-NMMA, P = 0.02), with no effect of L-NMMA on FMD with proximal cuff placement (10.6 ± 1.2 to 12.4 ± 1.7%, CON vs. L-NMMA, P = 0.39). When the reduction in shear stimulus following L-NMMA was taken into account, no drug difference was observed for either distal (0.26 ± 0.02 to 0.23 ± 0.03, CON vs. L-NMMA, P = 0.40) or proximal (0.23 ± 0.08 to 0.23 ± 0.03, CON vs. L-NMMA, P = 0.89) FMD trials. These findings challenge the assertion that NO is obligatory for brachial artery FMD, and call into question the sensitivity of this procedure for non-invasive determination of NO bioavailability in young, healthy humans. PMID:23774225

  9. Structural and biological studies on bacterial nitric oxide synthase inhibitors

    PubMed Central

    Holden, Jeffrey K.; Li, Huiying; Jing, Qing; Kang, Soosung; Richo, Jerry; Silverman, Richard B.; Poulos, Thomas L.

    2013-01-01

    Nitric oxide (NO) produced by bacterial NOS functions as a cytoprotective agent against oxidative stress in Staphylococcus aureus, Bacillus anthracis, and Bacillus subtilis. The screening of several NOS-selective inhibitors uncovered two inhibitors with potential antimicrobial properties. These two compounds impede the growth of B. subtilis under oxidative stress, and crystal structures show that each compound exhibits a unique binding mode. Both compounds serve as excellent leads for the future development of antimicrobials against bacterial NOS-containing bacteria. PMID:24145412

  10. 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.

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

    PubMed

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

    2014-06-27

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

  12. Metal-based turn-on fluorescent probes for nitric oxide sensing

    E-print Network

    Lim, Mi Hee

    2006-01-01

    Chapter 1. Metal-Based Turn-On Fluorescent Probes for Sensing Nitric Oxide. Nitric oxide, a reactive free radical, regulates a variety of biological processes. The absence of tools to detect NO directly, rapidly, specifically ...

  13. Multifaceted role of nitric oxide in an in vitro mouse neuronal injury model: transcriptomic profiling defines the temporal recruitment of death signalling cascades

    PubMed Central

    Peng, Zhao Feng; Chen, Minghui Jessica; Manikandan, Jayapal; Melendez, Alirio J; Shui, Guanghou; Russo-Marie, Françoise; Whiteman, Matthew; Beart, Philip M; Moore, Philip K; Cheung, Nam Sang

    2012-01-01

    Abstract Nitric oxide is implicated in the pathogenesis of various neuropathologies characterized by oxidative stress. Although nitric oxide has been reported to be involved in the exacerbation of oxidative stress observed in several neuropathologies, existent data fail to provide a holistic description of how nitrergic pathobiology elicits neuronal injury. Here we provide a comprehensive description of mechanisms contributing to nitric oxide induced neuronal injury by global transcriptomic profiling. Microarray analyses were undertaken on RNA from murine primary cortical neurons treated with the nitric oxide generator DETA-NONOate (NOC-18, 0.5 mM) for 8–24 hrs. Biological pathway analysis focused upon 3672 gene probes which demonstrated at least a ±1.5-fold expression in a minimum of one out of three time-points and passed statistical analysis (one-way anova, P < 0.05). Numerous enriched processes potentially determining nitric oxide mediated neuronal injury were identified from the transcriptomic profile: cell death, developmental growth and survival, cell cycle, calcium ion homeostasis, endoplasmic reticulum stress, oxidative stress, mitochondrial homeostasis, ubiquitin-mediated proteolysis, and GSH and nitric oxide metabolism. Our detailed time-course study of nitric oxide induced neuronal injury allowed us to provide the first time a holistic description of the temporal sequence of cellular events contributing to nitrergic injury. These data form a foundation for the development of screening platforms and define targets for intervention in nitric oxide neuropathologies where nitric oxide mediated injury is causative. PMID:21352476

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

    PubMed

    Guthrie, Micah J; Kang-Mieler, Jennifer J

    2014-03-01

    Nitric oxide (NO) plays an important physiological role in normal and pathological retinas. Intraretinal NO concentrations have not been directly measured due to lack of NO electrodes capable of determining their location in the retina. The microelectrodes described here allow recording of the intraretinal electroretinogram (ERG) and NO concentration from the same location, with ERGs used to determine retinal depth. Double-barreled electrodes were constructed with one barrel serving as a reference/voltage recording barrel and the other containing a Nafion-coated carbon fiber used to detect NO amperometrically. Nafion coating imparted a high selectivity for NO versus ascorbic acid (2000:1). In vivo rodent experiments demonstrated that the electrodes could record intraretinal ERGs and NO current with minimal retinal thickness deformation (9%), allowing for retinal NO depth profile measurements. Comparison of NO depth profiles under control conditions and under nitric oxide synthase (NOS) inhibition by 5 mM L-NG-Nitroarginine methyl ester (L-NAME) verified that the recorded current was attributable to NO. NO concentrations from control profiles ( n = 4) were 2.37 ± 0.34 ?M at the choroid and 1.12 ± 0.14 ?M at the retinal surface. NO concentrations from L-NAME profiles ( n = 4) were significantly lower at 0.83 ± 0.15 ?M at the choroid ( p = 0.006) and 0.27 ± 0.04 ?M at the retinal surface ( p = 0.001). Localized regions of increased NO (100-400 nM) were seen in the inner retina under control conditions but not after L-NAME. The dual ERG-NO electrode may be a valuable tool in evaluating the role of NO in normal and diseased retinas. PMID:24043366

  15. Pulmonary Nanoparticle Exposure Disrupts Systemic Microvascular Nitric Oxide Signaling

    PubMed Central

    Nurkiewicz, Timothy R.; Porter, Dale W.; Hubbs, Ann F.; Stone, Samuel; Chen, Bean T.; Frazer, David G.; Boegehold, Matthew A.; Castranova, Vincent

    2009-01-01

    We have shown that pulmonary nanoparticle exposure impairs endothelium dependent dilation in systemic arterioles. However, the mechanism(s) through which this effect occurs is/are unclear. The purpose of this study was to identify alterations in the production of reactive species and endogenous nitric oxide (NO) after nanoparticle exposure, and determine the relative contribution of hemoproteins and oxidative enzymes in this process. Sprague-Dawley rats were exposed to fine TiO2 (primary particle diameter ?1 ?m) and TiO2 nanoparticles (primary particle diameter ?21 nm) via aerosol inhalation at depositions of 4–90 ?g per rat. As in previous intravital experiments in the spinotrapezius muscle, dose-dependent arteriolar dilations were produced by intraluminal infusions of the calcium ionophore A23187. Nanoparticle exposure robustly attenuated these endothelium-dependent responses. However, this attenuation was not due to altered microvascular smooth muscle NO sensitivity because nanoparticle exposure did not alter arteriolar dilations in response to local sodium nitroprusside iontophoresis. Nanoparticle exposure significantly increased microvascular oxidative stress by ?60%, and also elevated nitrosative stress fourfold. These reactive stresses coincided with a decreased NO production in a particle deposition dose-dependent manner. Radical scavenging, or inhibition of either myeloperoxidase or nicotinamide adenine dinucleotide phosphate oxidase (reduced) oxidase partially restored NO production as well as normal microvascular function. These results indicate that in conjunction with microvascular dysfunction, nanoparticle exposure also decreases NO bioavailability through at least two functionally distinct mechanisms that may mutually increase local reactive species. PMID:19270016

  16. 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

  17. Activation of inducible nitric oxide synthase by Taraxacum officinale in mouse peritoneal macrophages

    Microsoft Academic Search

    Hyung-Min Kim; Chang-Hwan Oh; Cha-Kwon Chung

    1999-01-01

    The objective of the current study was to determine the effect of Taraxacum officinale (TO) on the production of nitric oxide (NO). Stimulation of mouse peritoneal macrophages with TO after the treatment of recombinant interferon-? (rIFN-?) resulted in increased NO synthesis. TO had no effect on NO synthesis by itself. When TO was used in combination with rIFN-?, there was

  18. Exhaled Nitric Oxide and Bronchoalveolar Lavage Nitrite\\/Nitrate in Active Pulmonary Sarcoidosis

    Microsoft Academic Search

    DEARBHAILE M. O'DONNELL; JOHN MOYNIHAN; GERALDINE A. FINLAY; VERA M. KEATINGS; CLARE M. O'CONNOR; PAUL M C LOUGHLIN; MUIRIS X. FITZGERALD

    1997-01-01

    Increased exhaled nitric oxide (NO) may reflect respiratory tract inflammation in untreated asthmat- ics. We compared exhaled NO and bronchoalveolar lavage (BAL) nitrate\\/nitrite (NO 3 2 \\/NO 2 2 ) in 10 patients who had untreated, active pulmonary sarcoidosis with those of normal control subjects. Ex- haled NO concentrations, determined by chemiluminescence, were similar in patients and control subjects (peak

  19. Cystic Fibrosis Transmembrane Conductance Regulator-Dependent Regulation of Epithelial Inducible Nitric Oxide Synthase Expression

    Microsoft Academic Search

    Wendy K. Steagall; Heather L. Elmer; Kristine G. Brady; Thomas J. Kelley

    2000-01-01

    Recent evidence has shown that the inducible form of nitric oxide (NO) synthase (NOS2) has reduced ex- pression in airway epithelia of patients with cystic fibrosis (CF) despite the presence of chronic inflamma- tion. The goal of this paper is to determine whether NOS2 expression is regulated by the presence of func- tional CF transmembrane conductance regulator (CFTR). Using a

  20. Role of inducible nitric oxide synthase expression and peroxynitrite formation in guinea pig ileitis

    Microsoft Academic Search

    Mark J. S. Miller; Jane H. Thompson; Xiao-Jing Zhang; Halina Sadowska-Krowicka; Jane L. Kakkis; Upender K. Munshi; Manuel Sandoval; Janet L. Rossi; Sandra Eloby-Childress; Joseph S. Beckman; Yao Zu Ye; Charles P. Rodi; Pamela T. Manning; Mark G. Currie; David A. Clark

    1995-01-01

    Background & Aims Inflammatory bowel disease is characterized by increased synthesis of nitric oxide. The aim of this study was to determine if inducible NO synthase (iNOS) was responsible for tissue injury, potentially via peroxynitrite formation, in the guinea pig model of gut inflammation. Methods Inflammation was induced in guinea pig ileum by intraluminal administration of the hapten trinitrobenzene sulfonic

  1. Kinetics of nitric oxide synthase induction by Propionibacterium adidum and lipopolysaccharide

    Microsoft Academic Search

    Mounir Dhouib; Jean-Louis Gendrault; Alain-André Lugnier

    1995-01-01

    Conditions for the induction of rat liver Ca2+-independent nitric oxide synthase were determined with killed Propionibacterium avidum, and compared with lipopolysaccharide endotoxin. Similar maximal induction was obtained intraperitoneally with the two types of inducers but killed Propionibacterium avidum gave a long-lasting induction while lipopolysaccharide displayed a rapid and short response. Moreover, the induction resulting from an intravenous administration of killed

  2. Inhibition of nitric oxide synthase and soluble guanylate cyclase induces cardiodepressive effects in normal rat hearts

    Microsoft Academic Search

    Georg Kojda; Karin Kottenberg; Eike Noack

    1997-01-01

    Exogenous nitric oxide (NO) has been shown to modulate the contractile force of rat cardiac myocytes. We sought to determine whether endogenous NO-production in the isolated normal rat heart has an effect on myocardial contractility. Hearts of male Wistar rats were investigated using a constant flow perfused non-paced Langendorff preparation. Changes of contractile parameters such as left ventricular peak pressure,

  3. Pulmonary Vascular Effects of Inhaled Nitric Oxide and Oxygen Tension in Bronchopulmonary Dysplasia

    Microsoft Academic Search

    Peter M. Mourani; D. Dunbar Ivy; Dexiang Gao; Steven H. Abman

    2004-01-01

    Pulmonary hypertension contributes significantly to morbidity and mortality in bronchopulmonary dysplasia (BPD), but little is known about the relative contribution of arterial tone, structural remodel- ing, and vessel density to pulmonary hypertension, especially in older patients. To determine the role of high pulmonary vascular tone in pulmonary hypertension, we studied the acute effects of oxygen tension, inhaled nitric oxide (iNO),

  4. Exhaled Nitric Oxide Levels and Airway Responsiveness to Adenosine 5?Monophosphate in Subjects with Nasal Polyposis

    Microsoft Academic Search

    L. Prieto; T. Seijas; V. Gutiérrez; S. Uixera; L. Bruno; R. López

    2004-01-01

    Background:It is widely appreciated that asthma is an inflammatory disease of the airways associated with airway hyperresponsiveness, and that nasal polyposis and asthma are related diseases. The objective of this study was to determine differences in exhaled nitric oxide (ENO) levels and airway responsiveness to adenosine 5?-monophosphate (AMP) between nonasthmatic patients with nasal polyposis and healthy controls. Methods: Twenty patients

  5. NITRIC OXIDE DESTRUCTION IN THE FUEL-BED BURNING REGIME OF SPREADER STOKERS

    EPA Science Inventory

    The article gives results of an experimental study of nitric oxide (NO) destruction in the fuel-bed of a coal-fired spreader stoker. NO was injected into the coal bed and freeboard flame zone under varying local stoichiometries to determine the fate of NO in the primary combustio...

  6. 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...

  7. Airway nitric oxide release is reduced after PBS inhalation in asthma Hye-Won Shin,1

    E-print Network

    George, Steven C.

    Airway nitric oxide release is reduced after PBS inhalation in asthma Hye-Won Shin,1 David A, Fitzpatrick A, Gaston B, George SC. Airway nitric oxide release is reduced after PBS inhalation in asthma. J.2006.--Exhaled nitric oxide (NO) is elevated in asthma, but the underlying mechanisms remain poorly understood

  8. 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

  9. Inhibition of inducible nitric oxide synthase ameliorates rat lung allograft rejection

    Microsoft Academic Search

    Takeshi Shiraishi; Steven R. DeMeester; Neil K. Worrall; Jon H. Ritter; Thomas P. Misko; T. Bruce Ferguson; Joel D. Cooper; G. Alexander Patterson

    1995-01-01

    Recently, the inducible isoform of nitric oxide synthase has been shown to be an important immunomodulation molecule in allograft rejection. We have observed the production of nitric oxide during rejection and the effect of nitric oxide synthase inhibition on allograft rejection in a rat lung transplant model. Rat left lung allotransplants were performed in two strain combinations: brown Norway–to–F344 (major

  10. Experimental and Theoretical Study of Nitric Oxide Formation in Internal Combustion Engines

    Microsoft Academic Search

    GEORGE A. LAVOIE; JOHN B. HEYWOOD; JAMES C. KECK

    1970-01-01

    The nonequilibrium formation of nitric oxide within the internal combustion engine cylinder is examined. A thermodynamic model which predicts the properties of the burnt and unburnt gases during the combustion process is developed. A set of reactions which govern the formation of nitric oxide is proposed, and rate equations for nitric oxide concentrations as a function of time in the

  11. Nitric oxide production by chicken macrophages activated by acemannan, a complex carbohydrate extracted from Aloe Vera

    Microsoft Academic Search

    K. Karaca; J. M. Sharma; R. Nordgren

    1995-01-01

    Cultures of normal chicken spleen cells and HD11 line cells produce nitric oxide (NO) in response to Acemannan, a complex carbohydrate derived from the Aloe vera plant. Neither cell type produced detectable amounts of NO in response to similar concentrations of yeast mannan, another complex carbohydrate. Nitric oxide production was dose dependent and inhibitable by the nitric oxide synthase inhibitor

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

    SciTech Connect

    Liu Jing [Department of Physiological Sciences, Center for Veterinary Health Sciences, 264 McElroy Hall, Oklahoma State University, Stillwater, OK 74078 (United States)]. E-mail: jing.pope@okstate.edu; Gupta, Ramesh C. [Breathitt Veterinary Center, Murray State University, Hopkinsville, KY 42241 (United States); Goad, John T. [Breathitt Veterinary Center, Murray State University, Hopkinsville, KY 42241 (United States); Karanth, Subramanya [Department of Physiological Sciences, Center for Veterinary Health Sciences, 264 McElroy Hall, Oklahoma State University, Stillwater, OK 74078 (United States); Pope, Carey [Department of Physiological Sciences, Center for Veterinary Health Sciences, 264 McElroy Hall, Oklahoma State University, Stillwater, OK 74078 (United States)

    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.

  13. Nitric oxide emissions from a central California dairy

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  14. Nitric oxide: NO apoptosis or turning it ON?

    Microsoft Academic Search

    Bernhard Brüne

    2003-01-01

    Nitric oxide (NO) is known for its diverse activities throughout biology. Among signaling qualities, NO affects cellular decisions of life and death either by turning on apoptotic pathways or by shutting them off. Although copious reports support both notions, the dichotomy of NO actions remains unsolved. Proapoptotic pathways of NO are compatible with established signaling circuits appreciated for mitochondria-dependent roads

  15. Nitric Oxide Is Protective in Listeric Meningoencephalitis of Rats

    Microsoft Academic Search

    K. A. Remer; T. W. Jungi; R. Fatzer; M. G. Tauber; S. L. Leib

    2001-01-01

    dent effects of intracisternal inoculation with L. monocytogenes on survival and activity were noted; 104 L. mono- cytogenes organisms induced a self-limiting brain infection. Bacteria invaded the basal meninges, chorioid plexus and ependyme, spread to subependymal tissue and hippocampus, and disappeared by day 7. This was paralleled by recruitment and subsequent disappearance of macrophages expressing inducible nitric oxide synthase (iNOS)

  16. Nitric oxide metabolites in cystic fibrosis lung disease

    Microsoft Academic Search

    H Grasemann; I Ioannidis; R P Tomkiewicz; H de Groot; B K Rubin; F Ratjen

    1998-01-01

    Although the activity of nitric oxide (NO) synthases are increased in lung tissue of patients with cystic fibrosis, the concentrations of nasal and exhaled NO have recently been found to be decreased in cystic fibrosis. This could either be due to reduced NO formation or metabolism of NO within airway fluids. In this study, the stable NO metabolites, nitrate and

  17. 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...

  18. Higher level of plasma nitric oxide in spontaneously hypertensive rats

    Microsoft Academic Search

    Chin-Chen Wu; Mao-Hsiung Yen

    1999-01-01

    We had detected a slightly, but significantly, higher level of plasma nitrite\\/nitrate in the sponstanously hypertensive rat (SHR) by using the nitric oxide (NO) analyzer (Sievers 280 NOA), which converts nitrate (including nitrate converted from nitrite) to NO. Here, we examined whether the release of NO from protein-bound dinitrosyl nonheme iron complexes (DNIC) contributes to the elevated plasma nitrate level

  19. 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.

  20. A global inventory of nitric oxide emissions from soils

    Microsoft Academic Search

    Eric A. Davidson; Wendy Kingerlee

    1997-01-01

    Over 60 published papers reporting field measurements of emissions of nitric oxide (NO) from soil are reviewed, and over 100 annual estimates of NO emissions were made for various types of ecosystems, including agricultural fields. These data were stratified by biome and the mean of each stratum was multiplied by an estimate of the biome area. A few strata were

  1. A polarographic method for measuring dissolved nitric oxide

    Microsoft Academic Search

    B. O Jensen; J Skeidsvoll; H Holmsen

    1997-01-01

    A polarographic method for measuring the concentration of authentic nitric oxide (NO) in aqueous solutions is described. When solutions of NO were injected into aqueous solutions containing dissolved oxygen, NO reacted with oxygen to give nitrite. The amount of nitrite formed in this reaction (analyzed by capillary electrophoresis) was compared with the amount of oxygen consumed (measured by polarography). We

  2. 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...

  3. Role of nitric oxide in genotoxicity: Implication for carcinogenesis

    Microsoft Academic Search

    Emanuela Felley-Bosco

    1998-01-01

    Reactive oxygen species can initiate carcinogenesis by virtue of their capacity to react with DNA and cause mutations. Recently, it has been suggested that nitric oxide (NO) and its derivatives produced in inflamed tissues could contribute to the carcinogenesis process. Genotoxicity of NO follows its reaction with oxygen and superoxide. It can be due either to direct DNA damage or

  4. Biochemistry of Nitric Oxide and Its Redox-Activated Forms

    Microsoft Academic Search

    Jonathan S. Stamler; David J. Singel; Joseph Loscalzo

    1992-01-01

    Nitric oxide (NO^bullet), a potentially toxic molecule, has been implicated in a wide range of biological functions. Details of its biochemistry, however, remain poorly understood. The broader chemistry of nitrogen monoxide (NO) involves a redox array of species with distinctive properties and reactivities: NO^+ (nitrosonium), NO^., and NO^- (nitroxyl anion). The integration of this chemistry with current perspectives of NO

  5. Neuronal Nitric Oxide Synthase Is Associated with Airway Obstruction in BALB\\/c Mice Exposed to Ozone

    Microsoft Academic Search

    An-Soo Jang; Inseon-S. Choi; Jong-Un Lee

    2003-01-01

    Background: The functional role of nitric oxide (NO) and the various nitric oxide synthase (NOS) isoforms in asthma is controversial. Objective: To investigate the role of NO in mice exposed to ozone, three known isoforms of NOS [inducible NOS (iNOS), neuronal NOS (nNOS), and endothelial NOS (eNOS)] were studied. Methods: The expression of iNOS, nNOS, and eNOS was determined in

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

    PubMed

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

    2010-12-01

    Fruits and vegetables are key foods whose high ingestion is associated with the improvement of numerous pathological conditions, including hypertension. Such health promoting actions have been increasingly ascribed to the antioxidant characteristics of different polyphenols in fruits and vegetables. Consequently, based on this assumption, many beverages and foods rich in polyphenols, grape, tea, cocoa, and soy products and many of their chemical constituents purified, are being studied both, as antioxidants and antihypertensive agents. This paper reviews the current evidence linking high polyphenol consumption with reductions in blood pressure. Basic chemical aspects of flavanols, flavonols, isoflavones and stilbenes, as possible responsible for the observed effects of those foods on blood pressure are included. Human interventions studies by using grapes and wine, cocoa and chocolate, black and green tea, soy products, and purified compounds ((+)-catequin, quercetin, (-)-epigallocatechin gallate) are summarized. The discussed hypothesis, strongly supported by experimental data in animals, is that by regulating nitric oxide bioavailability, polyphenols present in fruits and vegetables affect endothelial function and as a consequence, blood pressure. Even when data are not definitive and many questions remain open, the whole evidence is encouraging to start considering diets that can provide a benefit to hypertensive subjects, and those benefits will be more significant in people that do not have controlled his/her elevated blood pressure. PMID:20874688

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

    Microsoft Academic Search

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

    2002-01-01

    It is now clear that hydrogen peroxide (H2O2) and nitric oxide (NO) function as signalling molecules in plants. A wide range of abiotic and biotic stresses results in H2O2 generation, from a variety of sources. H2O2 is removed from cells via a number of anti- oxidant mechanisms, both enzymatic and non- enzymatic. Both biotic and abiotic stresses can induce NO

  8. Synthesis and Characterization of a Linear Dinitrosyl-Triiron Complex; Comparison to a Flavodiiron Nitric Oxide Reductase Intermediate

    E-print Network

    Victor, Eric

    Nitric oxide is released during the immune response by the host during bacterial infection. To counteract this response, bacteria have evolved nitric oxide reductases to convert NO to N[subscript 2]O. Some of these nitric ...

  9. Nitric oxide as a mediator of inflammation?—You had better believe it

    PubMed Central

    Grisham, Matthew B.

    1995-01-01

    Nitric oxide has enigmatic qualities in inflammation. In order to appreciate the precise contributions of nitric oxide to a pathophysiological process, one must account for enzyme source, coproduction of oxidants and antioxidant defences, time, rate of nitric oxide production, cellular source, peroxynitrite formation and effects on DNA (mutagenesis/apoptosis). We contend that there is ample evidence to consider nitric oxide as a molecular aggressor in inflammation, particularly chronic inflammation. Therapeutic benefit can be achieved by inhibition of inducible nitric oxide synthase and not the donation of additional nitric oxide. Furthermore, there is growing appreciation that nitric oxide and products derived thereof, are critical components linking the increased incidence of cancer in states of chronic inflammation. PMID:18475670

  10. 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.

  11. Practical nitric oxide measurement employing a nitric oxide-selective electrode

    NASA Astrophysics Data System (ADS)

    Ichimori, K.; Ishida, H.; Fukahori, M.; Nakazawa, H.; Murakami, E.

    1994-08-01

    An NO-selective electrode was developed as an easily applicable tool for a real-time nitric oxide (NO) measurement. The working electrode (0.2 mm diam) was made from Pt/Ir alloy coated with a three-layered membrane. The counterelectrode was made from a carbon fiber. When a stable NO donor, S-nitroso-N-acetyl-dl-penicillamine, was applied, the electrode current increased in a dose-dependent fashion. The current and calculated NO concentration showed a linear relationship in the range from 0.2 nM (S/N=1) to 1 ?M of NO. The response of the electrode was 1.14±0.09 s. The effects of temperature, pH, and chemicals other than NO on the electrode current were also evaluated. Electrodes which were placed in the luminal side of rat aortic rings exhibited 30 pA of current due to NO generation induced by the addition of 10-6 M of acetylcholine. The current was eliminated in the presence of 50 ?M NG-monomethyl-L-arginine, an inhibitor of NO synthase. Thus, this NO-selective electrode is applicable to real-time NO assay in biological systems.

  12. Hypocholesterolemic properties of nitric oxide. In vivo and in vitro studies using nitric oxide donors.

    PubMed

    Kurowska, E M; Carroll, K K

    1998-05-20

    Previous results suggested that changes in the activity of nitric oxide (NO) can influence metabolism of apo B-containing lipoproteins. Therefore, we studied effects of exogenous NO donors and physiological NO precursors on metabolism of these lipoproteins. In rabbits, addition of 0.03% sodium nitroprusside (NaNP) to a semipurified, cholesterol-free, casein diet counteracted the elevation of LDL cholesterol induced by this diet but did not alter liver lipids after 4 weeks of feeding. In HepG2 cells, addition of nontoxic concentrations of another NO donor, S-nitroso-N-acetylpenicillamine (SNAP) to culture medium caused a dose-dependent reduction of medium apo B after 24 h. At the concentration 0.5 mM, SNAP significantly decreased medium apo B by 50% without altering total synthesis and secretion of proteins and without altering rates of cellular sterol synthesis. In cells incubated with L-arginine, reduction of medium apo B was not associated with increased NO production whereas in those exposed to N-OH-Arg medium apo B levels were not altered. We concluded that synthetic NO donors can reduce hypercholesterolemia by affecting apo B metabolism directly in the liver, via the sterol-independent mechanism. PMID:9593815

  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^?-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. Static high pressure study of nitric oxide chemistry: proposed mechanism for nitric oxide detonation. [Shock initiated detonation

    SciTech Connect

    Swanson, B.I.; Agnew, S.F.; Greiner, N.R.

    1985-01-01

    The chemistry of nitric oxide under static high pressure conditions has been studied using diamond anvil cells and spectroscopic methods. Pressurized samples warmed rapidly to room temperature undergo facile disproportionation to form N/sub 2/O, N/sub 2/O/sub 3/, N/sub 2/O/sub 4/, and NO/sup +/NO/sub 3//sup -/. Nitric oxide maintained at 80 K is observed to react at ca. 2.5 GPa to form, dominantly, N/sub 2/, O/sub 2/, and NO/sup +/NO/sub 3//sup -/. The complex chemistry of nitric oxide is best explained in terms of two competing primary reaction mechanisms involving the direct formation of N/sub 2/ and O/sub 2/, and disproportionation to form N/sub 2/O and NO/sup +/NO/sub 3//sup -/. The disproportionation reaction, which is favored under higher temperature conditions, releases two-thirds of the total energy content, and is believed to be important in the early chemistry accompanying shock-initiation of nitric oxide. Laboratory scale detonation studies, where the gaseous products are analyzed spectroscopically, show evidence for, dominantly, disproportionation and a small amount of N/sub 2//O/sub 2/ production. This study points to the importance of condensed phase concerted reactions as well as ions and ionic reaction mechanisms in the shock initiated detonation of HE's. 14 refs., 3 figs., 1 tab.

  15. 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

  16. Human blood platelets lack nitric oxide synthase activity.

    PubMed

    Böhmer, Anke; Gambaryan, Stepan; Tsikas, Dimitrios

    2014-10-31

    Abstract Reports on expression and functionality of nitric oxide synthase (NOS) activity in human blood platelets and erythrocytes are contradictory. We used a specific gas chromatography-mass spectrometry (GC-MS) method to detect NOS activity in human platelets. The method measures simultaneously [(15)N]nitrite and [(15)N]nitrate formed from oxidized (15)N-labeled nitric oxide ((15)NO) upon its NOS-catalyzed formation from the substrate l-[guanidino-(15)N2]-arginine. Using this GC-MS assay, we did not detect functional NOS in non-stimulated platelets and in intact platelets activated by various agonists (adenosine diphosphate, collagen, thrombin, or von Willebrand factor) or lysed platelets. l-[guanidino-nitro]-Arginine-inhibitable NOS activity was measured after addition of recombinant human endothelial NOS to lysed platelets. Previous and recent studies from our group challenge expression and functionality of NOS in human platelets and erythrocytes. PMID:25360996

  17. 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...

  18. Investigating Antithyroid Effects of Propylthiouracil on the Ischemia and Reperfusion Injury in Rat’ Kidney and Determining the Role of Nitric Oxide in Mediating this Effect

    PubMed Central

    Tofangchiha, Shahnaz; Moazen Jamshidi, Seyed Mir Mansoor; Emami, Hamed; Dormanesh, Banafshe

    2014-01-01

    Background: Renal ischemia/reperfusion injury (IRI) is a major problem in renal transplantation, which occurs during the process of organ retrieval and storage, and is closely associated with acute rejection episodes and late allograft failure. Recent studies have revealed a new phenomenon called “chemical preconditioning” that can induce tolerance against the ischemic stress via a variety of proposed pathways especially nitric oxide (NO) system. Propylthiouracil (PTU) is suggested to modulate the intracellular NO signaling. Objectives: In this study, we investigated the preconditioning properties of chronic pretreatment with PTU in preventing renal IRI. In addition, we evaluated the involvement of NO pathway. Materials and Methods: Sixty adult male Wistar rats were allocated into six groups. All groups underwent right nephrectomy 15 days before intervention. In groups 1 (Chronic PTU + L-NG-nitro arginine methyl ester [L-NAME]) and 2 (Chronic PTU) oral PTU (500 mg/L in water) treatment was started 15 days before right nephrectomy to achieve the therapeutic plasma level of PTU. Fourteen days after nephrectomy, animals received either L-NAME (10 mg/kg) or its vehicle and renal IRI was induced 45 minutes later. Groups 3 and 4 (Control) received respectively L-NAME (10 mg/kg) and its vehicle 45 minutes before IRI. The last two groups were normal sham operated rats and PTU + sham. Rats were killed 24 hours after IRI. The blood samples were collected and assessed for serum blood urea nitrogen (BUN) and creatinine (Cr) level, and tissue samples were fixed in formalin for histopathologic scoring of tubular damage (H-score). Results: The mean BUN, Cr, and H-score of control group were 176.66 ± 12.24 mmol/L, 4.45 ± 0.44 ?mol/L, and 83.5% ± 3.5%, respectively. Chronic pretreatment with PTU significantly improved BUN (40.4 ± 6.1 mmol/L), Cr (0.96 ± 0.068 ?mol/L), and H-score (7.83% ± 4.02%) in IRI animals in comparison to those that were not treated with chronic PTU (P < 0.001) and L-NAME; however, it did not completely reversed the chronic PTU-induced protection (BUN, 93.33 ± 12.22 mmol/L; Cr, 2.7 ± 1.15 ?mol/L, and H-score, 24.83% ± 3.5%). There was no significant difference between rats that were treated with L-NAME alone (group 5) and the control group. Conclusions: Our study demonstrates that preconditioning of kidney with chronic PTU administration protects renal tissue against IRI and this phenomenon was mediated through NO system. The results suggest a potential indication for using PTU to protect the kidney before transplantations and to reduce the risk of tissue rejection afterwards. PMID:25763197

  19. 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.

  20. Role of polymorphisms of inducible nitric oxide synthase and endothelial nitric oxide synthase in idiopathic environmental intolerances.

    PubMed

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

    2015-01-01

    Oxidative stress and inflammation play a pathogenetic role in idiopathic environmental intolerances (IEI), namely, multiple chemical sensitivity (MCS), fibromyalgia (FM), and chronic fatigue syndrome (CFS). Given the reported association of nitric oxide synthase (NOS) gene polymorphisms with inflammatory disorders, we aimed to investigate the distribution of NOS2A -2.5?kb (CCTTT) n as well as Ser608Leu and NOS3 -786T>C variants and their correlation with nitrite/nitrate levels, in a study cohort including 170 MCS, 108 suspected MCS (SMCS), 89 FM/CFS, and 196 healthy subjects. Patients and controls had similar distributions of NOS2A Ser608Leu and NOS3 -786T>C polymorphisms. Interestingly, the NOS3 -786TT genotype was associated with increased nitrite/nitrate levels only in IEI patients. We also found that the NOS2A -2.5?kb (CCTTT)11 allele represents a genetic determinant for FM/CFS, and the (CCTTT)16 allele discriminates MCS from SMCS patients. Instead, the (CCTTT)8 allele reduces by three-, six-, and tenfold, respectively, the risk for MCS, SMCS, and FM/CFS. Moreover, a short number of (CCTTT) repeats is associated with higher concentrations of nitrites/nitrates. Here, we first demonstrate that NOS3 -786T>C variant affects nitrite/nitrate levels in IEI patients and that screening for NOS2A -2.5?kb (CCTTT) n polymorphism may be useful for differential diagnosis of various IEI. PMID:25878398

  1. 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 of the mission. Perhaps the key component to SNOE's success was the unique very strong camaraderie that existed among the SNOE team. Over 120 students contributed in a substantive way to SNOE. They have all gone on to exciting careers in the aerospace industry and brought dramatic success to STEDI's goal. In this talk we will describe the student involvement in SNOE as well as the SNOE observations and the insights into Sun - Earth connections we have obtained from them.

  2. Evidence for mutagenesis by nitric oxide during nitrate metabolism in Escherichia coli.

    PubMed

    Weiss, Bernard

    2006-02-01

    In Escherichia coli, nitrosative mutagenesis may occur during nitrate or nitrite respiration. The endogenous nitrosating agent N2O3 (dinitrogen trioxide, nitrous anhydride) may be formed either by the condensation of nitrous acid or by the autooxidation of nitric oxide, both of which are metabolic by-products. The purpose of this study was to determine which of these two agents is more responsible for endogenous nitrosative mutagenesis. An nfi (endonuclease V) mutant was grown anaerobically with nitrate or nitrite, conditions under which it has a high frequency of A:T-to-G:C transition mutations because of a defect in the repair of hypoxanthine (nitrosatively deaminated adenine) in DNA. These mutations could be greatly reduced by two means: (i) introduction of an nirB mutation, which affects the inducible cytoplasmic nitrite reductase, the major source of nitric oxide during nitrate or nitrite metabolism, or (ii) flushing the anaerobic culture with argon (which should purge it of nitric oxide) before it was exposed to air. The results suggest that nitrosative mutagenesis occurs during a shift from nitrate/nitrite-dependent respiration under hypoxic conditions to aerobic respiration, when accumulated nitric oxide reacts with oxygen to form endogenous nitrosating agents such as N2O3. In contrast, mutagenesis of nongrowing cells by nitrous acid was unaffected by an nirB mutation, suggesting that this mutagenesis is mediated by N2O3 that is formed directly by the condensation of nitrous acid. PMID:16428385

  3. Ruthenium complexes as nitric oxide scavengers: a potential therapeutic approach to nitric oxide-mediated diseases

    PubMed Central

    Fricker, S P; Slade, Elizabeth; Powell, N A; Vaughan, O J; Henderson, G R; Murrer, B A; Megson, I L; Bisland, S K; Flitney, F W

    1997-01-01

    Ruthenium(III) reacts with nitric oxide (NO) to form stable ruthenium(II) mononitrosyls. Several Ru(III) complexes were synthesized and a study made of their ability to bind NO, in vitro and also in several biological systems following expression of the inducible isoform of nitric oxide synthase (iNOS). Here we report on the properties of two, related polyaminocarboxylate-ruthenium complexes: potassium chloro[hydrogen(ethylenedinitrilo)tetraacetato]ruthenate (=JM1226; CAS no.14741-19-6) and aqua[hydrogen(ethylenedinitrilo)tetraacetato]ruthenium (=JM6245; CAS no.15282-93-6).Binding of authentic NO by aqueous solutions of JM1226 yielded a product with an infrared (IR) spectrum characteristic of an Ru(II)-NO adduct. A compound with a similar IR spectrum was obtained after reacting JM1226 with S-nitroso-N-acetylpenicillamine (SNAP).The effect of JM1226 or JM6245 on nitrite (NO2?) accumulation in cultures of macrophages (RAW 264 line) 18?h after stimulating cells with lipolysaccharide (LPS) and interferon-? (IFN?) was studied. Activation of RAW264 cells increased NO2? levels in the growth medium from (mean±1 s.e.mean) 4.9±0.5???M to 20.9±0.4??M. This was blocked by actinomycin D (10??M) or cycloheximide (5??M). The addition of JM1226 or JM6245 (both 100??M) to activated RAW264 cells reduced NO2? levels to 7.6±0.2??M and 8.8±0.6??M, respectively. NG-methyl-L-arginine (L-NMMA; 250??M) similarly reduced NO2? levels, to 6.1±0.2??M.The effect of JM1226 or JM6245 on NO-mediated tumour cell killing by LPS+IFN?-activated macrophages (RAW 264) was studied in a co-culture system, using a non-adherent murine mastocytoma (P815) line as the ‘target' cell. Addition of JM1226 or JM6245 (both 100??M) to the culture medium afforded some protection from macrophage-mediated cell killing: target cell viability increased from 54.5±3.3% to 93.2±7.1% and 80.0±4.6%, respectively (n=6).Vasodilator responses of isolated, perfused, pre-contracted rat tail arteries elicited by bolus injections (10??l) of SNAP were attenuated by the addition of JM1226 or JM6245 (10?4?M) to the perfusate: the ED50 increased from 6.0??M (Krebs only) to 1.8?mM (Krebs+JM6245) and from 7??M (Krebs only) to 132??M (Krebs+JM1226). Oxyhaemoglobin (5??M) increased the ED50 value for SNAP from 8??M to 200??M.Male Wistar rats were injected with bacterial LPS (4?mg?kg?1; i.p.) to induce endotoxaemia. JM1226 and JM6245 (both 100??M) fully reversed the hyporesponsiveness to phenylephrine of tail arteries isolated from animals previously (24?h earlier) injected with LPS. Blood pressure recordings were made in conscious LPS-treated rats using a tail cuff apparatus. A single injection of JM1226 (100?mg?kg?1, i.p.) administered 20?h after LPS (4?mg?kg?1, i.p.) reversed the hypotension associated with endotoxaemia.The results show that JM1226 and JM6245 are able to scavenge NO in biological systems and suggest a role for these compounds in novel therapeutic strategies aimed at alleviating NO-mediated disease states. PMID:9421293

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

    PubMed

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

    2013-11-30

    Impaired platelet responsiveness to nitric oxide (NO resistance) is a common characteristic of many cardiovascular disease states and represents an independent risk factor for cardiac events and mortality. NO resistance reflects both scavenging of NO by superoxide (O2(-)), and impairment of the NO receptor, soluble guanylate cyclase (sGC). There is thus an urgent need for circumvention of NO resistance in order to improve clinical outcomes. Nitroxyl (HNO), like NO, produces vasodilator and anti-aggregatory effects, largely via sGC activation, but is not inactivated by O2(-). We tested the hypothesis that HNO circumvents NO resistance in human platelets. In 57 subjects with or without ischemic heart disease, platelet responses to the HNO donor isopropylamine NONOate (IPA/NO) and the NO donor sodium nitroprusside (SNP) were compared. While SNP (10?M) induced 29±3% (p<0.001) inhibition of platelet aggregation, IPA/NO (10?M) caused 75±4% inhibition (p<0.001). In NO-resistant subjects (n=28), the IPA/NO:SNP response ratio was markedly increased (p<0.01), consistent with partial circumvention of NO resistance. Similarly, cGMP accumulation in platelets was greater (p<0.001) with IPA/NO than with SNP stimulation. The NO scavenger carboxy-PTIO (CPTIO, 200?M) inhibited SNP and IPA/NO responses by 92±7% and 17±4% respectively (p<0.001 for differential inhibition), suggesting that effects of IPA/NO are only partially NO-mediated. ODQ (10?M) inhibited IPA/NO responses by 36±8% (p<0.001), consistent with a contribution of sGC/haem to IPA/NO inhibition of aggregation. There was no significant relationship between whole blood ROS content and IPA/NO responses. Thus the HNO donor IPA/NO substantially circumvents platelet NO resistance while acting, at least partially, as a haem-mediated sGC activator. PMID:24012721

  5. 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.

  6. The copper catalysed reduction of nitric oxide by ammonia in aqueous solution studied by membrane inlet mass spectrometry

    Microsoft Academic Search

    Péter Pénzeli; László Dózsa; Hans Degn

    1998-01-01

    The copper(II)–ammonia–nitric oxide reaction system in aqueous solution was studied by the measurement of dissolved nitric oxide with membrane inlet mass spectrometry. When the reaction was initiated by the addition of ammonia and copper(II) chloride to a saturated solution of nitric oxide, nitric oxide was found to be consumed in a two-stage reaction. Approximately 2 moles nitric oxide per mole

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

    PubMed

    Sharma, Kavita; Chakrapani, Harinath

    2014-12-01

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

  8. 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.

  9. In vivo detection of nitric oxide distribution in mice.

    PubMed

    Komarov, Andrei M

    2002-01-01

    This paper discusses in vivo detection of nitric oxide (NO) distribution in endotoxin-treated mice using L-band (1.1 GHz) electron paramagnetic resonance spectroscopy (EPR) in combination with the hydrophilic NO trapping complex: N-methyl-D-glucamine dithiocarbamate and iron (MGD-Fe). MGD-Fe-NO complex is found in the upper abdomen (liver region), lower abdomen (kidney and urinary bladder) and head region of ICR mice. Experiments with nitric oxide synthase (NOS) inhibition and 15N-labeled L-arginine as NOS substrate verify the origin of trapped NO from L-arginine. However, contribution from a 'nonenzymatic' NO generation pathway can not be ruled out. This paper further examines potential artifacts, which may arise in experiments using dithiocarbamate-iron complexes as NO trapping agents. PMID:12162457

  10. Nitric oxide release: part III. Measurement and reporting.

    PubMed

    Coneski, Peter N; Schoenfisch, Mark H

    2012-05-21

    Nitric oxide's expansive physiological and regulatory roles have driven the development of therapies for human disease that would benefit from exogenous NO administration. Already a number of therapies utilizing gaseous NO or NO donors capable of storing and delivering NO have been proposed and designed to exploit NO's influence on the cardiovascular system, cancer biology, the immune response, and wound healing. As described in Nitric oxide release: Part I. Macromolecular scaffolds and Part II. Therapeutic applications, the preparation of new NO-release strategies/formulations and the study of their therapeutic utility are increasing rapidly. However, comparison of such studies remains difficult due to the diversity of scaffolds, NO measurement strategies, and reporting methods employed across disciplines. This tutorial review highlights useful analytical techniques for the detection and measurement of NO. We also stress the importance of reporting NO delivery characteristics to allow appropriate comparison of NO between studies as a function of material and intended application. PMID:22362308

  11. Nitric oxide synthase from cerebellum catalyzes the formation of equimolar quantities of nitric oxide and citrulline from L-arginine.

    PubMed

    Bush, P A; Gonzalez, N E; Griscavage, J M; Ignarro, L J

    1992-06-30

    This study examined whether constitutive nitric oxide (NO) synthase from rat cerebellum catalyzes the formation of equimolar amounts of NO plus citrulline from L-arginine under various conditions. Citrulline was determined by monitoring the formation of 3H-citrulline from 3H-L-arginine. NO was determined by monitoring the formation of total NOx (NO+nitrite [NO2-] + nitrate [NO3-]) by chemiluminescence after reduction of NOx to NO by acidic vanadium (III). Equal quantities of NO plus citrulline were generated from L-arginine and the formation of both products was linear for about 20 min at 37 degrees C provided L-arginine was present in excess to maintain a zero order reaction rate. Deletion of NADPH, addition of the calmodulin antagonist calmidazolium, or addition of NO synthase inhibitors (NG-methyl-L-arginine, NG-amino-L-arginine) abolished or markedly inhibited the formation of both NO and citrulline. The Km for L-arginine (14 microM; 18 microM) and the Vmax of the reaction (0.74 nmol/min/mg protein; 0.67 nmol/min/mg protein) were the same whether NO or citrulline formation, respectively, was monitored. These observations indicate clearly that NO and citrulline are formed in equimolar quantities from L-arginine by the constitutive isoform of NO synthase from rat cerebellum. PMID:1378272

  12. Regulation of Nitric Oxide Synthase 2 in Rabbit Corneal Cells

    Microsoft Academic Search

    William J. O'Brien; Tom Heimann; Li-Shih Tsao; Bruce T. Seet; Grant McFadden; Jerry L. Taylor

    2001-01-01

    PURPOSE. The purpose of these studies was to investigate the role of interferon-g (IFN-g), tumor necrosis factor-a (TNF-a), interleukin 1b (IL-1b), and transforming growth factor-b (TGF-b) in the regulation of inducible nitric oxide synthase (NOS2) activity in rabbit corneal cells. METHODS. Rabbit corneal epithelial, stromal, and endothelial cells were grown in culture and treated with cytokines and growth factors, alone

  13. Reactive oxygen species and nitric oxide in viral diseases

    Microsoft Academic Search

    Ernst Peterhans

    1997-01-01

    Metabolites derived from superoxide (o2\\u000a •?) and nitric oxide (NO•) play an important role in antimicrobial and antitumoral defense, but may also harm the host. Low\\u000a levels of such metabolites can also facilitate viral replication because of their mitogenic effects on cells. Most viruses\\u000a grow better in proliferating cells, and indeed, many viruses induced in their host cell changes similar

  14. Nitric Oxide: A Physiologic Mediator of Penile Erection

    NASA Astrophysics Data System (ADS)

    Burnett, Arthur L.; Lowenstein, Charles J.; Bredt, David S.; Chang, Thomas S. K.; Snyder, Solomon H.

    1992-07-01

    Nitric oxide (NO) is a cytotoxic agent of macrophages, a messenger molecule of neurons, and a vasodilator produced by endothelial cells. NO synthase, the synthetic enzyme for NO, was localized to rat penile neurons innervating the corpora cavernosa and to neuronal plexuses in the adventitial layer of penile arteries. Small doses of NO synthase inhibitors abolished electrophysiologically induced penile erections. These results establish NO as a physiologic mediator of erectile function.

  15. Relevance of nitric oxide in pain mechanisms and pain management

    Microsoft Academic Search

    Piotr K. Janicki; Magdalena Jeske-Janicka

    1998-01-01

    Nitric oxide (NO) may be involved in the mechanisms of pain generation and transmission throughout the central and peripheral\\u000a nervous systems (including brain and spinal cord and perivascular tissue and peripheral nerve terminals) and locally released\\u000a pain mediators (including formation of inflammation and vascular edema). NO mechanisms are also involved in the analgesic\\u000a activity of nonsteroidal anti-inflammatory drugs, opioids, and

  16. Role of nitric oxide in implantation and menstruation

    Microsoft Academic Search

    Kristof Chwalisz; Robert E. Garfield

    2000-01-01

    Nitric oxide (NO) is a major paracrine mediator of various biological processes, including vascu- lar functions and inflammation. In blood vessels, NO is produced by the low-input constitutive endothelial NO synthase (eNOS) and is a potent vasodilator and platelet aggregation inhibitor. The inducible NOS isoform (iNOS) is capable of producing NO at high concentrations which have pro-inflammatory properties. Immuno- histochemical

  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. Relation Between Plasma Nitric Oxide Levels and Diabetic Retinopathy

    Microsoft Academic Search

    Naohiro Izumi; Taiji Nagaoka; Fumihiko Mori; Eiichi Sato; Atsushi Takahashi; Akitoshi Yoshida

    2006-01-01

    Purpose  Nitric oxide (NO) plays an important role in homeostatic vasodilation and the regulation of blood flow. On the other hand,\\u000a excess release of NO causes various vascular complications. There are only a few reports on the relationship between plasma\\u000a NO levels and microvascular complications, especially diabetic retinopathy (DR) in patients with type 2 diabetes. The purpose\\u000a of this study was

  19. Diethylcarbamazine (DEC) Does Not Induce Nitric Oxide (NO) Synthesis

    Microsoft Academic Search

    T. V. Rajan; Leonard D. Shultz; Subash Babu; John Doukas; Dale Greiner; Pat Porte

    1998-01-01

    Rajan, T. V., Shultz, L. D., Babu, S., Doukas, J., Greiner, D., and Porte, P. 1998. Diethylcarbamazine (DEC) does not induce nitric oxide (NO) synthesis.Experimental Parasitology88, 217–222. Diethylcarbomazine (DEC) was discovered in 1947 as a potent therapeutic agent in lymphatic filariasis and has been a mainstay of antifilarial therapy over the past five decades (R. I. Hewitt,et al., 1947,Journal of

  20. Glycosylated PROLI/NO Derivatives as Nitric Oxide Prodrugs

    PubMed Central

    Nandurdikar, Rahul S.; Maciag, Anna E.; Hong, Sam Y.; Chakrapani, Harinath; Citro, Michael L.; Keefer, Larry K.; Saavedra, Joseph E.

    2009-01-01

    GlcNAc-PROLI/NO prodrugs that are activated by N-acetylglucosaminidase to release nitric oxide (NO) are described. A classical acid-amine coupling is used to bi-functionalize these PROLI/NO prodrugs, which on activation generate up to 4 moles of NO, a peptide residue and an N-acetylglucosamine residue. Many of the prodrugs synthesized are efficient sources of intracellular NO. PMID:19954198

  1. Nitric oxide and NAD-dependent protein modification

    Microsoft Academic Search

    Lee J. McDonald; Joel Moss

    1994-01-01

    Nitric oxide (NO) has been suggested to act as a regulator of endogenous intracellular ADP-ribosylation, based on radiolabelling of proteins in tissue homogenates incubated with [32P]NAD and No. After the NO-stimulated modification was replicated in a defined system containing only the purified acceptor protein, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), the hypothesis of NO-stimulation of an endogenous ADP-ribosyltransferase became moot. The NO-stimulated, NAD-dependent

  2. Influence of endothelial nitric oxide synthase polymorphisms in psoriasis risk

    Microsoft Academic Search

    Pablo Coto-Segura; Eliecer Coto; Albert Mas-Vidal; Blanca Morales; Victoria Alvarez; Marta Díaz; Belén Alonso; Jorge Santos-Juanes

    Nitric oxide (NO) is a potent regulator of keratinocyte growth and differentiation that has been implicated in the pathogenesis\\u000a of psoriasis (Ps). The NOS3 ?786 T\\/C (SNP id rs2070744; http:\\/\\/www.ensembl.org), intron 4 variable number tandem repeat (VNTR), and Glu298Asp (SNP id rs1799983) polymorphisms, have been associated with\\u000a differences in NO plasma concentrations and with the risk of hypertension (HT) and

  3. Application of a Nitric Oxide Sensor in Biomedicine

    PubMed Central

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

    2014-01-01

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

  4. Pleiotropic contributions of nitric oxide to aggressive behavior

    Microsoft Academic Search

    Randy J. Nelson; Brian C. Trainor; Silvana Chiavegatto; Gregory E. Demas

    2006-01-01

    Male mice with targeted deletion of the genes encoding the neuronal (NOS-1?\\/? or nNOS?\\/?) isoform of nitric oxide synthase display altered aggressive behaviors. Male nNOS-1?\\/? mice are more aggressive than wild-type (WT) mice in all testing paradigms. Testosterone is necessary, but not sufficient, for evoking the persistent aggression, and that serotonin (5-HT) metabolism is altered in male nNOS-1?\\/? mice. The

  5. Regulation of the nitric oxide system in human adipose tissue

    Microsoft Academic Search

    Stefan Engeli; Jürgen Janke; Kerstin Gorzelniak; Jana Böhnke; Nila Ghose; Carsten Lindschau; Friedrich C. Luft; Arya M. Sharma

    2004-01-01

    Nitric oxide (NO) is involved in adipose tissue biology by influencing adipogenesis, insulin-stimulated glu- cose uptake, and lipolysis. The enzymes responsible for NO formation in adipose cells are endothelial NO synthase (eNOS) and inducible NO synthase (iNOS), whereas neu- ronal NO synthase (bNOS) is not expressed in adipocytes. We characterized the expression pattern and the influence of adipogenesis, obesity, and

  6. Decoding nitric oxide release rates of amine-based diazeniumdiolates.

    PubMed

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

    2013-08-01

    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 (R(2) = 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

  7. INHIBITION OF NITRIC OXIDE SYNTHASE BY COBALAMINS AND COBINAMIDES*

    PubMed Central

    Weinberg, J. Brice; Chen, Youwei; Jiang, Ning; Beasley, Bethany E.; Salerno, John C.; Ghosh, Dipak K.

    2009-01-01

    Cobalamins (Cbl) are important co-factors for methionine synthase and methylmalonyl-coA mutase. Certain corrins also bind nitric oxide (NO), quenching its bioactivity. To determine if corrins would inhibit NO synthase (NOS), we measured their effects on 14-C-L-arginine-to-14-C-L-citrulline conversion by NOS1, NOS2, and NOS3. Hydroxocobalamin (OH-Cbl), cobinamide (Cbi), and dicyanocobinamide (CN2-Cbi) potently inhibited all isoforms, whfile cyanocobalamin, methylcobalamin, and adenosylcobalamin had much less effect. OH-Cbl and CN2-Cbi prevented binding of the oxygen analog carbon monoxide (CO) to the reduced NOS1 and NOS2 heme active site. CN2-Cbi did not react directly with NO or CO. Spectral perturbation analysis showed that CN2-Cbi interacted directly with the purified NOS1 oxygenase domain. NOS inhibition by corrins was rapid and not reversed by dialysis with L-arginine, tetrahydrobiopterin. Molecular modeling indicated that corrins could access the unusually large heme and substrate-binding pocket of NOS. Best fits were obtained in the “base-off” conformation of the lower axial dimethylbenzimidazole ligand. CN2-Cbi inhibited interferon-?-activated Raw264.7 mouse macrophage NO production. We show for the first time that certain corrins directly inhibit NOS, suggesting that these agents (or their derivatives) may have pharmacological utility. Endogenous cobalamins and cobinamides might play important roles regulating NOS activity in normal and pathological conditions. PMID:19328848

  8. Abnormal pressure-natriuresis in hypertension: role of nitric oxide.

    PubMed

    Granger, J P; Alexander, B T

    2000-01-01

    The kidneys have a critical role in long-term control of arterial pressure by regulating extracellular fluid and plasma volume. According to the renal body fluid feedback mechanism for long-term control, persistent hypertension can only occur as a result of a reduction in renal sodium excretory function or a hypertensive shift in the pressure-natriuresis relationship. Although an abnormal relationship between renal perfusion pressure and renal sodium excretion has been identified in every type of hypertension where it has been sought, factors responsible for this effect are still unclear. Nitric oxide (NO) is produced within the kidney and plays an important role in the control of many intrarenal processes which regulate the renal response to changes in perfusion pressure and thus, help determine plasma volume and blood pressure. Numerous studies have shown that long-term inhibition of NO synthesis results in a chronic rightward shift and marked attenuation in renal pressure-natriuresis. Recent studies have shown that certain animal models of genetic hypertension and forms of human hypertension areas are associated with a decrease in NO synthesis. Reductions in NO synthesis reduces renal sodium excretory function not only through direct actions on the renal vasculature, but through modulation of other vasoconstrictor processes and through direct and indirect alterations in tubular sodium transport. The causes and consequences of the dysregulation of NO in hypertension and other renal disease processes remain an important area of investigation. PMID:10691795

  9. Human leucocytes in asthenozoospermic patients: endothelial nitric oxide synthase expression.

    PubMed

    Buldreghini, E; Hamada, A; Macrì, M L; Amoroso, S; Boscaro, M; Lenzi, A; Agarwal, A; Balercia, G

    2014-12-01

    In a basic study at the Andrology Unit, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, Ancona, Italy, we evaluated the pattern of mRNA endothelial nitric oxide synthase (eNOS) expression in human blood leucocytes isolated from normozoospermic fertile and asthenozoospermic infertile men to elucidate any pathogenic involvement in sperm cell motility. Forty infertile men with idiopathic asthenozoospermia and 45 normozoospermic fertile donors, age-matched, were included. Semen parameters were evaluated, and expression analysis of mRNA was performed in human leucocytes using reverse transcription polymerase chain reaction. Sperm volume, count, motility and morphology were determined, and eNOS expression and Western blotting analyses were performed. A positive correlation was observed between the concentrations of NO and the percentage of immotile spermatozoa. The mRNA of eNOS was more expressed in peripheral blood leucocytes isolated from asthenozoospermic infertile men versus those of fertile normozoospermic men (7.46 ± 0.38 versus 7.06 ± 0.56, P = 0.0355). A significant up-regulation of eNOS gene in peripheral blood leucocytes was 1.52-fold higher than that of fertile donors. It is concluded that eNOS expression and activity are enhanced in blood leucocytes in men with idiopathic asthenozoospermia. PMID:24386917

  10. Photochemical production and consumption mechanisms of nitric oxide in seawater.

    PubMed

    Olasehinde, Emmanuel F; Takeda, Kazuhiko; Sakugawa, Hiroshi

    2010-11-15

    Nitric oxide (NO•) is an active odd-nitrogen species that plays a critical role in determining the levels of ozone (O?) and other nitrogen species in the troposphere. Here, we provide experimental evidence for photochemical formation of NO• in seawater. Photoproduction rates and overall scavenging rate constants were measured by irradiation of surface seawater samples collected from the Seto Inland Sea, Japan. Photoproduction rates of NO• ranged from 8.7 × 10?¹² M s?¹ to 38.8 × 10?¹² M s?¹ and scavenging rate constants were 0.05-0.33 s?¹. The steady state concentrations of NO• in seawater, which were calculated from the photoproduction rates and scavenging rate constants were in the range 2.4-32 × 10?¹¹ M. Estimation from the scavenging rate constant showed that the NO• lifetime in seawater was a few seconds. Our results indicate that nitrite photolysis plays a crucial role in the formation of NO•, even though we cannot exclude minor contributions from other sources. Analysis of filtered and unfiltered seawater samples showed no significant difference in NO• photoformation rates, which suggests a negligible contribution of NO• produced by photobiological processes. Using an estimated value of the Henry's law constant (kH ? 0.0019 M atm?¹), a supersaturation of surface seawater of 2 to 3 orders of magnitude was estimated. On the basis of the average values of the surface seawater concentration and the atmospheric NO• concentration, a sea-to-air NO• flux was estimated. PMID:20954706

  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. Nitric oxide-induced suspended animation promotes survival during hypoxia

    PubMed Central

    Teodoro, Rita O.; O’Farrell, Patrick H.

    2003-01-01

    Oxygen plays a key role in energy metabolism. However, there are organisms that survive severe shortfalls in oxygen. Drosophila embryos rapidly arrest development upon severe hypoxia and recover upon restoration of oxygen, even days later. Stabilization of the normally unstable engrailed RNA and protein preserved the localized striped pattern of this embryonic patterning gene during 3 days in hypoxia. Severe hypoxia blocked expression of a heat-shock-inducible lacZ transgene. Cyanide, a metabolic poison, did not immediately block gene expression or turnover, arguing against a passive response to energy limitation. In contrast, nitric oxide, a putative hypoxia signal, induced a reversible arrest of development, gene expression and turnover. Reciprocally, a nitric oxide scavenger allowed continued gene expression and turnover during hypoxia, but it reduced hypoxia tolerance. We suggest that hypoxia-induced stasis preserves the status quo of embryonic processes and promotes survival. Our data implicate nitric oxide as a mediator of this response and provide a system in which to investigate its action. PMID:12554658

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  14. Impaired nitric oxide synthase-dependent dilatation of cerebral arterioles in type II diabetic rats.

    PubMed

    Schwaninger, RoseAnn M; Sun, Hong; Mayhan, William G

    2003-11-14

    The goals of this study were to determine the effects of type II diabetes mellitus on nitric oxide synthase-dependent responses of cerebral arterioles and on endothelial nitric oxide synthase (eNOS) protein in cerebral arterioles. We examined dilatation of cerebral (pial) arterioles in 13-15 week old male lean and diabetic obese Zucker rats in response to nitric oxide synthase-dependent agonists (acetylcholine and adenosine diphosphate (ADP)) and a nitric oxide synthase-independent agonist (nitroglycerin). We found that acetylcholine (10 microM) increased cerebral arteriolar diameter by 10 +/- 3% (mean +/- SE) in lean Zucker rats, but by only 2 +/- 2% in diabetic obese Zucker rats (p<0.05). In addition, ADP (100 microM) increased cerebral arteriolar diameter by 20 +/- 2% in lean Zucker rats, but by only 8 +/- 2% in diabetic obese Zucker rats (p<0.05). In contrast, nitroglycerin produced similar vasodilatation in lean and diabetic obese Zucker rats. Thus, impaired dilatation of cerebral arterioles in diabetic obese Zucker rats is not related to non-specific impairment of vasodilatation. Following these functional studies, we harvested cerebral microvessels for Western blot analysis of eNOS protein. We found that eNOS protein was significantly higher in diabetic obese Zucker rats than in lean Zucker rats (p<0.05). Thus, type II diabetes mellitus impairs nitric oxide synthase-dependent responses of cerebral arterioles. In addition, eNOS protein from cerebral blood vessels is increased in diabetic obese Zucker rats. PMID:14572882

  15. Plant mitochondria: source and target for nitric oxide.

    PubMed

    Igamberdiev, Abir U; Ratcliffe, R George; Gupta, Kapuganti J

    2014-11-01

    Plant mitochondria generate nitric oxide (NO) under anoxia through the action of cytochrome c oxidase and other electron transport chain components on nitrite. This reductive mechanism operates under aerobic conditions at high electron transport rates. Indirect evidence also indicates that the oxidative pathway of NO production may be associated with mitochondria. We review the consequences of mitochondrial NO production, including the inhibition of oxygen uptake by cytochrome c oxidase, the inhibition of aconitase and succinate dehydrogenase, the induction of alternative oxidase, and the nitrosylation of several proteins, including glycine decarboxylase. The importance of these events in adaptation to abiotic and biotic stresses is discussed. PMID:24561220

  16. Nitric oxide enhances MPP +-induced hydroxyl radical generation via depolarization activated nitric oxide synthase in rat striatum

    Microsoft Academic Search

    Toshio Obata; Yasumitsu Yamanaka

    2001-01-01

    We examined the effect of NG-nitro-l-arginine methyl ester (l-NAME), a nitric oxide synthase (NOS) inhibitor, on extracellular potassium ion concentration ([K+]o)-enhanced hydroxyl radical (·OH) generation due to 1-methyl-4-phenylpyridinium ion (MPP+) was examined in the rat striatum. Rats were anesthetized, and sodium salicylate in Ringer’s solution (0.5 nmol\\/?l per min) was infused through a microdialysis probe to detect the generation of

  17. Fractional exhaled nitric oxide in clinical trials: an overview.

    PubMed

    Häussermann, Sabine; Kappeler, Dominik; Schmidt, Anje; Siekmeier, Rüdiger

    2013-01-01

    Designing clinical trials in asthma it is crucial to find the perfect primary endpoint for showing bioequivalence, especially when the investigational medicinal product is not a bronchodilator, but a substance, which suppresses the inflammatory process, e.g. inhalative corticosteroids (ICS). In the past, lung function parameters were used as the primary endpoint, which entails a long study duration and hundreds of patients. The measurement of fractional exhaled nitric oxide (FeNO) is established as a non-invasive marker for eosinophilic inflammation, and several guidelines focus on that diagnosis. FeNO is a surrogate measure of eosinophilic inflammation and at the same time, eosinophilic airway inflammation is usually steroid responsive. Thus, FeNO should be a part of the clinical management of asthma in ambulatory settings in conjunction with other conventional methods of asthma assessment. Furthermore, FeNO should be used to determine the presence or absence of eosinophilic airway inflammation, to determine the likelihood of steroid responsiveness, to measure response to steroid therapy, and level of inflammation control. In addition, FeNO is a useful tool to monitor patient ICS treatment adherence and allergen exposure. FeNO may be used to predict steroid responsiveness and as a measure to determine the optimal treatment of airway inflammation. FeNO has all characteristics of a good marker for bioequivalence measurements in the market approval process of generic ICS products. With a reliable study design in terms of patient population, concomitant medication, equipment and other factors, which can influence the measurement, efficient clinical trials can be performed, with a relatively short treatment time of 2-4 weeks and 50-100 patients. PMID:23835984

  18. Rate of nitric oxide release in the lung and factors influencing the concentration of exhaled nitric oxide.

    PubMed

    Sato, K; Sakamaki, T; Sumino, H; Sakamoto, H; Hoshino, J; Masuda, H; Sawada, Y; Mochida, M; Ohyama, Y; Kurashina, T; Nakamura, T; Ono, Z

    1996-06-01

    The level of nitric oxide (NO) in exhaled air fluctuates in normal individuals depending on the physiological conditions. We evaluated the effects of duration of exhalation and breath-holding on the exhaled concentrations of NO in 16 normal human volunteers. Exhaled gas corresponding to vital capacity was collected in 6-liter Tedlar bags and analyzed by chemiluminescence. The NO concentration in exhaled gas increased significantly in proportion to the duration of exhalation [P = 0.009 +/- 0.011 (SD)] and was increased after breath-holding. There was no significant difference in the exhaled NO concentration among 10-s phases of a 30-s exhalation, as determined from multiple breath collections. The NO released from the airways is presumably unaffected by fluctuation of exhalation speed. The NO release rate, calculated from a single regression analysis between the NO concentration and the duration of exhalation, was 39 +/- 29 pmol/s, a value which was about fourfold greater in nine patients with bronchial asthma. PMID:8764215

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

    PubMed Central

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

    2013-01-01

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

  20. Nitric oxide regulates multiple functions and fate of adult progenitor and stem cells.

    PubMed

    Bonafè, Francesca; Guarnieri, Carlo; Muscari, Claudio

    2015-03-01

    Nitric oxide is an endogenous gas which exerts autocrine/paracrine actions by different signaling pathways and/or direct interactions with intracellular compounds and structures. Several processes are regulated by nitric oxide in stem cells including self-renewal, viability, migration, proliferation, and differentiation. The modulation of cell functions depends on its concentrations because opposite effects can be observed when low and high levels of nitric oxide are compared. Here, the responses to nitric oxide of adult stem/progenitor cells which are often used in regenerative medicine, including mesenchymal stem cells, hematopoietic stem cells, neural stem cells, endothelial progenitor cells, satellite cells, and fibro-adipogenic precursor cells, are reviewed. Therapeutic strategies which employ drugs releasing nitric oxide or modulating nitric oxide intracellular pathways are suggested to perform new ex vivo preconditioning or in vivo treatments suitable for stem/progenitor cell therapy and tissue engineering applications. PMID:25526859

  1. Enhanced nitric oxide production is closely associated with serum lipid concentrations in adolescents

    Microsoft Academic Search

    Jong Weon Choi

    2004-01-01

    Background: To investigate whether nitric oxide (NO) production is associated with serum lipid concentrations and body mass index (BMI), we measured serum nitrate and nitrites (NOx) concentrations, serum lipid profiles, and anthropometric parameters in 319 adolescents. Methods: Serum NOx concentrations were determined using the Griess reaction. Serum concentrations of triglyceride, total cholesterol, and low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein

  2. ?-tocopherol increased nitric oxide synthase activity in blood vessels of spontaneously hypertensive rats

    Microsoft Academic Search

    Mohammad Ali Newaz; N. N. A. Nawal; C. H. Rohaizan; N. Muslim; A. Gapor

    1999-01-01

    Antioxidant protection provided by different doses of ?-tocopherol was compared by determining nitric oxide synthase (NOS) activity in blood vessels of spontaneously hypertensive rats (SHR) treated with ?-tocopherol.SHR were divided into four groups namely hypertensive control (C), treatment with 17 mg of ?-tocopherol\\/kg diet (?1), 34 mg of ?-tocopherol\\/kg diet (?2), and 170 mg of ?-tocopherol\\/kg diet (?3). Wister Kyoto

  3. Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide

    Microsoft Academic Search

    L. J. Ignarro; G. M. Buga; K. S. Wood; R. E. Byrns; G. Chaudhuri

    1987-01-01

    The objective of this study was to determine whether nitric oxide (NO) is responsible for the vascular smooth muscle relaxation elicited by endothelium-derived relaxing factor (EDRF). EDRF is an unstable humoral substance released from artery and vein that mediates the action of endothelium-dependent vasodilators. NO is and unstable endothelium-independent vasodilator that is released from vasodilator drugs such as nitroprusside and

  4. Nitric oxide nerves in the uterus are parasympathetic, sensory, and contain neuropeptides

    Microsoft Academic Search

    Raymond E. Papka; Daniel L. McNeill; Donna Thompson; Harald H. H. W. Schmidt

    1995-01-01

    Nitric oxide (NO) is synthesized in neurons and is a potent relaxor of vascular and nonvascular smooth muscle. The uterus contains abundant NO-synthesizing nerves which could be autonomic and\\/or sensory. This study was undertaken to determine: 1) the source(s) of NO-synthesizing nerves in the rat uterus and 2) what other neuropeptides or transmitter markers might coexist with NO in these

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

    Microsoft Academic Search

    Ismail Aytekin; Serap Unubol Aypak

    2011-01-01

    The serum levels of calcium, phosphorus, magnesium, copper, zinc and iron and of nitric oxide, retinol, and ?-carotene were\\u000a determined in Sakiz ewes that had experienced an abortion and in healthy controls. Ten healthy and 25 aborted Sakiz sheep\\u000a were selected from Afyon zone in western Turkey. Their ages ranged between 2 and 4 years weighing between 40 and 60 kg at

  6. Impairment of nitric oxide-mediated relaxations in anaesthetized autoperfused streptozotocin-induced diabetic rats

    Microsoft Academic Search

    Javier Angulo; Leocadio Rodríguez-Mañas; Concepción Peiró; Marta Neira; Jesús Marín; Carlos F. Sánchez-Ferrer

    1998-01-01

    This work was designed to determine in vivo the influence of the metabolic control of streptozotocin-induced diabetic rats,\\u000a measured by the levels of haemoglobin glycosylation in blood (HbA1c), on developing vascular endothelial dysfunction. For this, the vasoactive responses to basal and stimulated endothelial\\u000a nitric oxide (NO) were studied using the technique of the anaesthetized autoperfused rat, analyzing the responses to

  7. Exercise training reverses age-induced inducible nitric oxide synthase upregulation

    E-print Network

    Song, Wook

    2005-02-17

    homeostasis and prevent free radical-related damage. However, at high levels, chronic production of ?NO represents a formidable vehicle for pathology. Reid (135) suggested a biphasic response for nitric oxide on Ca2+ release dependent on nitric oxide... concentration and time of exposure. Recent studies indicated that overproduction of nitric oxide may be involved in muscle wasting, or cachexia, consistently observed with chronic heart failure, cancer, AIDS, and sepsis (2, 3, 29, 65). Elevated iNOS levels...

  8. Impaired Vasorelaxation in Inbred Mice Is Associated with Alterations in Both Nitric Oxide and Super Oxide Pathways

    Microsoft Academic Search

    Chun Chen; Vyacheslav A. Korshunov; Michael P. Massett; Chen Yan; Bradford C. Berk

    2007-01-01

    Recently, we showed that genetic factors determine flow-dependent vascular remodeling. Among five inbred mouse strains, the SJL strain developed the largest intima in response to low flow. Because SJL mice have a spontaneous mutation in superoxide dismutase 2 (SOD-2) we tested the hypothesis that strain-specific variations in vascular function are due to alterations in redox and nitric oxide (NO) pathways.

  9. 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-? (IFN?). 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

  10. 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.

  11. J Neurochem . Author manuscript Impact of endogenous nitric oxide on microglial cell energy metabolism

    E-print Network

    Paris-Sud XI, Université de

    ; antagonists & inhibitors ; metabolism ; Adenosine Triphosphate ; Animals ; Cell Line ; Cell Respiration ; drug cytokines, nitric oxide (NO) and reactive oxygen species (ROS), which may exacerbate neuronal damage

  12. REDUCTION OF NITRIC OXIDE WITH METAL SULFIDES

    EPA Science Inventory

    The report gives results of research to determine the technical feasibility of using metal sulfide for the chemical reduction of NOx to N2. Nineteen different metal sulfides were investigated, using a test gas of pure NO. Although most sulfides resulted in some NO reduction, BaS,...

  13. Kinetics of nitric oxide synthase induction by Propionibacterium avidum and lipopolysaccharide.

    PubMed

    Dhouib, M; Gendrault, J L; Lugnier, A A

    1995-12-01

    Conditions for the induction of rat liver Ca2(+)-independent nitric oxide synthase were determined with killed Propionibacterium avidum, and compared with lipopolysaccharide endotoxin. Similar maximal induction was obtained intraperitoneally with the two types of inducers but killed Propionibacterium avidum gave a long-lasting induction while lipopolysaccharide displayed a rapid and short response. Moreover, the induction resulting from an intravenous administration of killed Propionibacterium avidum reached 60 times that of the control whereas lipopolysaccharide treatment induced a 24-fold stimulation only. It is noteworthy that with the first inducer the nitric oxide activity was stable with time whereas with the second one it dropped after 8 h. Whatever the route of administration of killed Propionibacterium avidum, some huge vacuolated Kupffer cells were found in the liver whose parenchyma was almost normal. Numerous monocytes, and unaltered Kupffer cells, were observed. Kupffer cells were identified to be responsible for the uptake of killed Propionibacterium avidum. PMID:8748697

  14. Nitric oxide does not contribute to the hypotension of heatstroke.

    PubMed

    Ryan, K L; Tehrany, M R; Jauchem, J R

    2001-03-01

    The purpose of this study was to determine whether nitric oxide (NO) contributes to the hypotensive state induced by prolonged environmental heat (EH) stress. Ketamine-anesthetized rats were instrumented for the measurement of arterial blood pressure, electrocardiogram, and temperature at four sites. Rats were exposed to EH (ambient temperature, 40 +/- 1 degrees C) until mean arterial blood pressure (MAP) decreased to 75 mmHg, which was arbitrarily defined as the induction of heatstroke. In addition to cardiovascular and temperature measurements, the time required to reach this MAP end point and the subsequent survival time were measured. In three separate experimental series, the competitive NO synthesis inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) was administered (0, 10, or 100 mg/kg) either before, during (30 min after initiation of EH), or immediately after EH. L-NAME administered at any of these times transiently increased MAP. L-NAME infusion either before or during EH did not alter the EH time required to decrease MAP to 75 mmHg, but L-NAME pretreatment did decrease the colonic temperature at which this MAP end point was reached. L-NAME infusion before or after EH did not affect subsequent survival time, but L-NAME administered during EH significantly decreased survival time. The administration of L-NAME at any time point, therefore, did not prove beneficial in either preventing or reversing heatstroke. Taken together, these data suggest that NO does not mediate the hypotension associated with heatstroke. PMID:11181607

  15. Sustained Release Nitric Oxide from Long Lived Circulating Nanoparticles

    PubMed Central

    Cabrales, Pedro; Han, George; Roche, Camille; Nacharaju, Parimala; Friedman, Adam J.; Friedman, Joel M.

    2010-01-01

    The current limitations of nitric oxide (NO) delivery systems has stimulated an extraordinary interest in the development of compounds that generate NO in a controlled and sustained manner with a heavy emphasis on the treatment of cardiovascular disease states. This work describes the positive physiological response to the infusion of NO releasing nanoparticles prepared using a new platform based on hydrogel/glass hybrid nanoparticles. When exposed to moisture, these nanoparticles slowly release therapeutic levels of NO, previously generated through thermal reduction of nitrite to NO trapped within the dry particles. The controlled and sustained release of NO observed from these nanoparticles (NO-np) is regulated by its hydration over extended periods of time. In a dose-dependent manner, circulating NO-np both decreased mean arterial blood pressure and increased exhaled concentrations of NO over a period of several hours. Circulating NO-np induced vasodilatation and increased microvascular perfusion during their several hour circulation lifetime. Control nanoparticles (Control-np; without nitrite) did not induce changes in arterial pressure, although a decrease in the number of capillaries perfused and increase in leukocyte rolling and immobilization in the microcirculation was observed. The NO released by the NO-np prevents the inflammatory response observed after infusion of Control-np. These data suggest that NO release from NO-np is advantageous relative to other NO releasing compounds, because it does not depend on chemical decomposition or enzymatic catalysis; it is only determined by the rate of hydration. Based on the observed physiological properties, NO-np has clear potential as a therapeutic agent and as a research tool to increase our understanding of NO signaling mechanisms within the vasculature. PMID:20460149

  16. Cough and Exhaled Nitric Oxide Levels: What Happens with Exercise?

    PubMed Central

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

    2013-01-01

    Cough associated with exertion is often used as a surrogate marker of asthma. However, to date there are no studies that have objectively measured cough in association with exercise in children. Our primary aim was to examine whether children with a pre-existing cough have an increase in cough frequency during and post-exercise. We hypothesized that children with any coughing illness will have an increase in cough frequency post-exercise regardless of the presence of exercise-induced broncho-constriction (EIB) or atopy. In addition, we hypothesized that Fractional exhaled nitric oxide (FeNO) levels decreases post-exercise regardless of the presence of EIB or atopy. Children with chronic cough and a control group without cough undertook an exercise challenge, FeNO measurements and a skin prick test, and wore a 24-h voice recorder to objectively measure cough frequency. The association between recorded cough frequency, exercise, atopy, and presence of EIB was tested. We also determined if the change in FeNO post exercise related to atopy or EIB. Of the 50 children recruited (35 with cough, 15 control), 7 had EIB. Children with cough had a significant increase in cough counts (median 7.0, inter-quartile ranges, 0.5, 24.5) compared to controls (2.0, IQR 0, 5.0, p?=?0.028) post-exercise. Presence of atopy or EIB did not influence cough frequency. FeNO level was significantly lower post-exercise in both groups but the change was not influenced by atopy or EIB. Cough post-exertion is likely a generic response in children with a current cough. FeNO level decreases post-exercise irrespective of the presence of atopy or EIB. A larger study is necessary confirm or refute our findings. PMID:24400276

  17. Nitric oxide synthesis in patients with infective gastroenteritis

    PubMed Central

    Forte, P; Dykhuizen, R; Milne, E; McKenzie, A; Smith, C; Benjamin, N

    1999-01-01

    BACKGROUND—There is evidence that endogenous nitrate synthesis is notably increased in patients with infective gastroenteritis.?AIMS—To determine whether this is due to nitric oxide (NO) production via the L-arginine/NO pathway.?METHODS—Seven male patients with community acquired bacterial gastroenteritis and 15 healthy male volunteers participated in this study. All patients had stool culture positive infective gastroenteritis. A bolus of 200 mg L-[15N]2-arginine was administered intravenously after an overnight fast. Urine was collected for the next 36 hours. Urinary [15N:14N]nitrate ratio was assessed by dry combustion in an isotope ratio mass spectrometer.?RESULTS—Mean 36 hour total urinary nitrate excretion in the gastroenteritis group was 5157 (577) µmol compared with 2594 (234) µmol in the control group (p<0.001). Thirty six hour urinary [15N]nitrate excretion was considerably higher in the gastroenteritis group compared with the control group (13782 (1665) versus 1698 (98) ?mol; p<0.001). These values represent 1.129 (0.139)% and 0.138 (0.007)% of [15N]nitrogen administered (p<0.001), respectively. Corrected 36 hour urinary [15N]nitrate excretion for urinary creatinine was also significantly higher in the patient compared with the control group (1934 (221) versus 303 (35) ?mol/mmol; p<0.001).?CONCLUSION—Results show notably enhanced nitrate synthesis due to increased activity of the L-arginine/NO pathway in patients with infective gastroenteritis.???Keywords: endothelium derived relaxing factor; L-[15N]2-arginine; nitrates; infection; diarrhoea PMID:10446102

  18. Dysfunctional nitric oxide signalling increases risk of myocardial infarction.

    PubMed

    Erdmann, Jeanette; Stark, Klaus; Esslinger, Ulrike B; Rumpf, Philipp Moritz; Koesling, Doris; de Wit, Cor; Kaiser, Frank J; Braunholz, Diana; Medack, Anja; Fischer, Marcus; Zimmermann, Martina E; Tennstedt, Stephanie; Graf, Elisabeth; Eck, Sebastian; Aherrahrou, Zouhair; Nahrstaedt, Janja; Willenborg, Christina; Bruse, Petra; Brænne, Ingrid; Nöthen, Markus M; Hofmann, Per; Braund, Peter S; Mergia, Evanthia; Reinhard, Wibke; Burgdorf, Christof; Schreiber, Stefan; Balmforth, Anthony J; Hall, Alistair S; Bertram, Lars; Steinhagen-Thiessen, Elisabeth; Li, Shu-Chen; März, Winfried; Reilly, Muredach; Kathiresan, Sekar; McPherson, Ruth; Walter, Ulrich; Ott, Jurg; Samani, Nilesh J; Strom, Tim M; Meitinger, Thomas; Hengstenberg, Christian; Schunkert, Heribert

    2013-12-19

    Myocardial infarction, a leading cause of death in the Western world, usually occurs when the fibrous cap overlying an atherosclerotic plaque in a coronary artery ruptures. The resulting exposure of blood to the atherosclerotic material then triggers thrombus formation, which occludes the artery. The importance of genetic predisposition to coronary artery disease and myocardial infarction is best documented by the predictive value of a positive family history. Next-generation sequencing in families with several affected individuals has revolutionized mutation identification. Here we report the segregation of two private, heterozygous mutations in two functionally related genes, GUCY1A3 (p.Leu163Phefs*24) and CCT7 (p.Ser525Leu), in an extended myocardial infarction family. GUCY1A3 encodes the ?1 subunit of soluble guanylyl cyclase (?1-sGC), and CCT7 encodes CCT?, a member of the tailless complex polypeptide 1 ring complex, which, among other functions, stabilizes soluble guanylyl cyclase. After stimulation with nitric oxide, soluble guanylyl cyclase generates cGMP, which induces vasodilation and inhibits platelet activation. We demonstrate in vitro that mutations in both GUCY1A3 and CCT7 severely reduce ?1-sGC as well as ?1-sGC protein content, and impair soluble guanylyl cyclase activity. Moreover, platelets from digenic mutation carriers contained less soluble guanylyl cyclase protein and consequently displayed reduced nitric-oxide-induced cGMP formation. Mice deficient in ?1-sGC protein displayed accelerated thrombus formation in the microcirculation after local trauma. Starting with a severely affected family, we have identified a link between impaired soluble-guanylyl-cyclase-dependent nitric oxide signalling and myocardial infarction risk, possibly through accelerated thrombus formation. Reversing this defect may provide a new therapeutic target for reducing the risk of myocardial infarction. PMID:24213632

  19. Sulfur dioxide upregulates the aortic nitric oxide pathway in rats.

    PubMed

    Li, Junling; Li, Ruijin; Meng, Ziqiang

    2010-10-25

    Sulfur dioxide (SO(2)) is a common gaseous pollutant. It is also, however, endogenously generated from sulfur-containing amino acids. Recent studies have demonstrated that rat blood pressure can be lowered by SO(2)-exposure in vivo and that vasodilation caused by SO(2) at low concentrations (<450 microM) is endothelium-dependent in rat aorta. However, effects of SO(2) on nitric oxide synthase (NOS) and nitric oxide (NO) production have not been previously studied in rat aorta. The objective of the present study is to assess the effects of acute (10 min) and prolonged (2h) stimulation with different concentrations of SO(2) on NO/cGMP pathway in isolated rat aorta. The results show that: (1) the acute and prolonged pretreatments with SO(2) produced an inhibition of vasoconstrictions induced by norepinephrine. (2) SO(2) potentiated activity of endothelial nitric oxide synthase (eNOS), but not of induced NOS (iNOS). (3) SO(2) could increase expression of eNOS gene on the transcription and translation levels in rat aorta. (4) SO(2) enhanced NO formation in aortic tissue. (5) The level of cGMP in rat aorta was increased by SO(2) and no change of cAMP. These findings led to the conclusion: there were acute and prolonged effects of SO(2) on the NO/cGMP signalling pathway; and SO(2) could upregulate the eNOS-NO-cGMP pathway and at least partly by which the SO(2) might cause vasodilation and inhibition to vasoconstriction. PMID:20674563

  20. 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?

  1. 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.

  2. The Moving Frontier in Nitric Oxide-Dependent Signaling

    NSDL National Science Digital Library

    Carl Nathan (Weill Cornell Medical College; Department of Microbiology and Immunology REV)

    2004-11-02

    New discoveries are expanding our view of the role of nitric oxide (NO) in mammalian physiology by revealing new types, amounts, and fates of molecules modified in vivo by NO and its derivatives, as well as the profound augmentation of some of NO’s actions at physiologic levels of O2. Investigators have identified a new form of endogenous reversible N-nitrosation reactions in vivo, that of proteins; a new class of endogenously nitrated bioactive molecules in vivo, nitro-fatty acids; and the ability of NO-dependent posttranslational modifications to control the half-life and destination of key regulatory proteins.

  3. Nitric oxide-sensitive pulmonary hypertension in congenital rubella syndrome.

    PubMed

    Raimondi, Francesco; Migliaro, Fiorella; Di Pietro, Elisa; Borgia, Francesco; Rapacciuolo, Antonio; Capasso, Letizia

    2015-01-01

    Persistent pulmonary hypertension is a very rare presentation of congenital virus infection. We discuss the case of complete congenital rubella syndrome presenting at echocardiography with pulmonary hypertension that worsened after ductus ligation. Cardiac catheterization showed a normal pulmonary valve and vascular tree but a PAP = 40?mmHg. The infant promptly responded to inhaled nitric oxide while on mechanical ventilation and was later shifted to oral sildenafil. It is not clear whether our observation may be due to direct viral damage to the endothelium or to the rubella virus increasing the vascular tone via a metabolic derangement. PMID:25785205

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

    PubMed Central

    Raimondi, Francesco; Migliaro, Fiorella; Di Pietro, Elisa; Borgia, Francesco; Rapacciuolo, Antonio; Capasso, Letizia

    2015-01-01

    Persistent pulmonary hypertension is a very rare presentation of congenital virus infection. We discuss the case of complete congenital rubella syndrome presenting at echocardiography with pulmonary hypertension that worsened after ductus ligation. Cardiac catheterization showed a normal pulmonary valve and vascular tree but a PAP = 40?mmHg. The infant promptly responded to inhaled nitric oxide while on mechanical ventilation and was later shifted to oral sildenafil. It is not clear whether our observation may be due to direct viral damage to the endothelium or to the rubella virus increasing the vascular tone via a metabolic derangement. PMID:25785205

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

    NASA Technical Reports Server (NTRS)

    Reid, Ian A.

    1994-01-01

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

  6. DNA Methylation in the Arginase–Nitric Oxide Synthase Pathway Is Associated with Exhaled Nitric Oxide in Children with Asthma

    PubMed Central

    Byun, Hyang-Min; Wang, Xinhui; Salam, Muhammad T.; Siegmund, Kim; Gilliland, Frank D.

    2011-01-01

    Rationale: Genetic variation in arginase (ARG) and nitric oxide synthase (NOS) has been associated with exhaled nitric oxide (FeNO) levels in children. Little is known about whether epigenetic variation in these genes modulates FeNO. Objectives: To evaluate whether DNA methylation in ARG and NOS genes is associated with FeNO. Methods: A subset of 940 participants in the Children's Health Study were selected for this study. Children were eligible if they had FeNO measurements and buccal cells collected on the same day. CpG loci located in the promoter regions of NOS1, NOS2A, NOS3, ARG1, and ARG2 genes were analyzed. Multiple loci in each gene were evaluated individually and averaged together. DNA methylation was measured using a bisulfite–polymerase chain reaction pyrosequencing assay. Linear regression models were used to investigate the association between DNA methylation and FeNO and whether associations differed by asthma status. Measurements and Main Results: DNA methylation in ARG2 was significantly associated with FeNO. A 1% increase in average DNA methylation of ARG2 was associated with a 2.3% decrease in FeNO (95% confidence interval, ?4 to ?0.6). This association was significantly larger in children with asthma (%diff = ?8.7%) than in children with no asthma (%diff = ?1.6%; pint = 0.01). Differences in FeNO by asthma status were also observed for ARG1 (%diffasthma = ?4.4%; %diffnon-asthma = 0.3%; pint = 0.02). DNA methylation in NOS genes was not associated with FeNO. Conclusions: DNA methylation in ARG1 and ARG2 is associated with FeNO in children with asthma and suggests a possible role for epigenetic regulation of nitric oxide production. PMID:21512169

  7. 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 ?M. And, their inhibitory activity was more than L-N(6)-(1-iminoethyl)-lysine, a selective inhibitor of inducible nitric oxide synthase (IC50=27.1 ?M). 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

  8. 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

  9. Nitric Oxide and Cancer Therapy: The Emperor has NO Clothes

    PubMed Central

    Hickok, Jason R.; Thomas, Douglas D.

    2013-01-01

    The role of nitric oxide (NO·) as a mediator of cancer phenotype has led researchers to investigate strategies for manipulating in vivo production and exogenous delivery of this molecule for therapeutic gain. Unfortunately, NO· serves multiple functions in cancer physiology. In some instances, NO· or nitric oxide synthase (NOS) levels correlate with tumor suppression and in other cases they are related to tumor progression and metastasis. Understanding this dichotomy has been a great challenge for researchers working in the field of NO· and cancer therapy. Due to the unique chemical and biochemical properties of NO·, it’s interactions with cellular targets and the subsequent downstream signaling events can be vastly different based upon tumor heterogeneity and microenvironment. Simple explanations for the vast range of NO-correlated behaviors will continue to produce conflicting information about the relevance of NO· and cancer. Paying considerable attention to the chemical properties of NO· and the methodologies being used will remove many of the discrepancies in the field and allow for in depth understanding of when NO-based chemotherapeutics will have beneficial outcomes. PMID:20236067

  10. 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 ?mol/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 ?mol/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

  11. Endothelial Caveolar Subcellular Domain Regulation of Endothelial Nitric Oxide Synthase

    PubMed Central

    Ramadoss, Jayanth; Pastore, Mayra B.; Magness, Ronald R.

    2015-01-01

    SUMMARY Complex regulatory processes alter the activity of endothelial nitric oxide synthase (eNOS) leading to nitric oxide (NO) production by endothelial cells under various physiological states. These complex processes require specific sub-cellular eNOS partitioning between plasma membrane caveolar domains and non-caveolar compartments.eNOS translocation from the plasma membrane to intracellular compartments is important for eNOS activation and subsequent NO biosynthesis. We present data reviewing and interpreting information: 1) the coupling of endothelial plasma membrane receptor systems in the caveolar structure relative to eNOS trafficking; 2) how eNOS trafficking relates to specific protein-protein interaction for inactivation and activation of eNOS; and 3) how these complex mechanisms confer specific subcellular location relative to eNOS multi-site phosphorylation and signaling.Dysfunction in regulation of eNOS activation may contribute to several disease states; in particular gestational endothelial abnormalities (preeclampsia, gestational diabetes, etc) that have life-long deleterious health consequences that predispose the offspring to develop hypertensive disease, type II diabetes and adiposity.1 PMID:23745825

  12. Impaired Nitric Oxide Synthase Signaling Dissociates Social Investigation and Aggression

    PubMed Central

    Trainor, Brian C.; Workman, Joanna L.; Jessen, Ruth; Nelson, Randy J.

    2007-01-01

    A combination of social withdrawal and increased aggression is characteristic of several mental disorders. Most previous studies have investigated the neurochemical bases of social behavior and aggression independently, as opposed to how these behaviors are regulated in concert. Neuronal nitric oxide synthase (nNOS) produces gaseous nitric oxide, which functions as a neurotransmitter and is known to affect several types of behavior including mating and aggression. Compared with wild-type mice, we observed that nNOS knockout mice showed reduced behavioral responses to an intruder behind a wire barrier. Similar results were observed in mice treated with the selective nNOS inhibitor 3-bromo-7-nitroindazole (3BrN). In habituation–dishabituation tests, treatment with 3BrN did not block recognition of male urine but did attenuate investigation time compared with oil-treated animals. Finally, nNOS knockout mice and 3BrN treated mice were significantly more aggressive than wild-type and oil-treated males, respectively. In general, these behavioral effects are less pronounced in pair-housed males compared with singly-housed males. Thus, nNOS inhibition results in a phenotype that displays reduced social investigation and increased aggression. These data suggest that further study of nNOS signaling is warranted in mental disorders characterized by social withdrawal and increased aggression. PMID:17469926

  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. 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.

  15. Nitric oxide signaling contributes to ectopic orofacial neuropathic pain.

    PubMed

    Sugiyama, T; Shinoda, M; Watase, T; Honda, K; Ito, R; Kaji, K; Urata, K; Lee, J; Ohara, K; Takahashi, O; Echizenya, S; Iwata, K

    2013-12-01

    Inferior alveolar nerve (IAN) injury induces persistent ectopic pain which spreads to a wide area in the orofacial region. Its exact mechanism remains unclear. We investigated the involvement of nitric oxide (NO) in relation to ectopic orofacial pain caused by IAN transection (IANX). We assessed the changes in mechanical sensitivity of the whisker pad skin following IANX, neuronal nitric oxide synthase (nNOS) expression in the trigeminal ganglion (TG), and the functional significance of NO in relation to the mechanical allodynia following intra-TG administration of a chemical precursor to NO and selective nNOS inhibitors. IANX induced mechanical allodynia, which was diminished by intra-TG administration of selective nNOS inhibitors. NO metabolites and nNOS immunoreactive neurons innervating the lower lip were also increased in the TG. Intra-TG administration of nNOS substrate induced the mechanical allodynia. The present findings suggest that NO released from TG neurons regulates the excitability of TG neurons innervating the whisker pad skin, and the enhancement of TG neuronal excitability may underlie ectopic mechanical allodynia. PMID:24130220

  16. How to protect liver graft with nitric oxide

    PubMed Central

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

    2011-01-01

    Organ preservation and ischemia reperfusion injury associated with liver transplantation play an important role in the induction of graft injury. One of the earliest events associated with the reperfusion injury is endothelial cell dysfunction. It is generally accepted that endothelial nitric oxide synthase (e-NOS) is cell-protective by mediating vasodilatation, whereas inducible nitric oxide synthase mediates liver graft injury after transplantation. We conducted a critical review of the literature evaluating the potential applications of regulating and promoting e-NOS activity in liver preservation and transplantation, showing the most current evidence to support the concept that enhanced bioavailability of NO derived from e-NOS is detrimental to ameliorate graft liver preservation, as well as preventing subsequent graft reperfusion injury. This review deals mainly with the beneficial effects of promoting “endogenous” pathways for NO generation, via e-NOS inducer drugs in cold preservation solution, surgical strategies such as ischemic preconditioning, and alternative “exogenous” pathways that focus on the enrichment of cold storage liquid with NO donors. Finally, we also provide a basic bench-to-bed side summary of the liver physiology and cell signalling mechanisms that account for explaining the e-NOS protective effects in liver preservation and transplantation. PMID:21734799

  17. The role of nitric oxide in experimental cerulein induced pancreatitis.

    PubMed Central

    Um, Soon Ho; Kwon, Yong Dae; Kim, Chang Duck; Lee, Hong Sik; Jeen, Yoon Tae; Chun, Hoon Jai; Lee, Sang Woo; Choi, Jae Hyun; Ryu, Ho Sang; Hyun, Jin Hai

    2003-01-01

    An enhanced formation of nitric oxide (NO), due to the induction of inducible nitric oxide synthase (iNOS), has been implicated in the pathogenesis of shock and inflammation, but its role in acute pancreatitis still remains controversial. To clarify the role of NO in acute pancreatitis, the present experiment investigated the expression of iNOS and the effect of NOS inhibition on cerulein-induced pancreatitis in rats. Group I received intraperitoneal (ip) injection of normal saline. Group II received two ip injections of cerulein (20 microgram/kg). Group III received injections of N(G)-nitro-L-arginine methyl ester (L-NAME) (30 mg/kg) with cerulein. Group IV received L-arginine (250 mg/kg) with cerulein and L-NAME. The expression of iNOS in the pancreas was examined by western blot analysis. The plasma concentration of NO metabolites was measured. The severity of pancreatitis was assessed by measuring serum amylase, pancreas water content and histopathological examination. Compared with controls, the cerulein group displayed significantly increased expression of iNOS and raised plasma NO metabolites. Treatment with L-NAME significantly decreased hyperamylasemia, plasma NO level, and the extent of pancreatic injury. Treatment with L-arginine reversed the effects of L-NAME. These findings suggest that an enhanced formation of NO by iNOS plays an important role in the development of acute pancreatitis, and inhibition of NO production has the beneficial effects in reducing pancreas injury. PMID:12923328

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

    PubMed Central

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

    2012-01-01

    Fractional exhaled nitric oxide (FeNO) is a non-invasive marker of airway inflammation in asthma and respiratory allergy. Environmental factors, especially indoor and outdoor air quality, may play an important role in triggering acute exacerbations of respiratory symptoms. The authors have reviewed the literature reporting effects of outdoor and indoor pollutants on FeNO in children. Although the findings are not consistent, urban and industrial pollution—mainly particles (PM2.5 and PM10), nitrogen dioxide (NO2), and sulfur dioxide (SO2)—as well as formaldehyde and electric baseboard heating have been shown to increase FeNO, whilst ozone (O3) tends to decrease it. Among children exposed to Environmental Tobacco Smoke (ETS) with a genetic polymorphisms in nitric oxide synthase genes (NOS), a higher nicotine exposure was associated with lower FeNO levels. Finally, although more studies are needed in order to better investigate the effect of gene and environment interactions which may affect the interpretation of FeNO values in the management of children with asthma, clinicians are recommended to consider environmental exposures when taking medical histories for asthma and respiratory allergy. Further research is also needed to assess the effects of remedial interventions aimed at reducing/abating environmental exposures in asthmatic/allergic patients. PMID:22162708

  19. Constitutive nitric oxide synthase is present in normal human keratinocytes.

    PubMed

    Baudouin, J E; Tachon, P

    1996-03-01

    Normal human keratinocytes in culture exhibit a nitric oxide synthase (NOS) activity ranging from 50 to 150 pmol/min/mg of protein. The enzyme is cytosolic and requires the presence of calcium, nicotinamide adenine dinucleotide phosphate, reduced form (NADPH), and flavin adenine dinucleotide. Calmodulin antagonists (trifluoperazine and calmidazolium) inhibit the enzyme activity. We show that NG-nitro-L-arginine inhibits NOS more potently than NG-monomethyl-L-arginine and that L-canavanine is a weak inhibitor. NOS was partially purified using a 2',5'-ADP Sepharose affinity column eluted with NADPH. A partially purified fraction was analyzed by sodium dodecyl sulfate-polyacrylamide gel electro-phoresis and Western blotting. A protein with an apparent molecular weight of 152 kDa cross-reacted with monoclonal antibodies raised against the neuronal constitutive isoform of NOS. The enzyme had a Vmax of 7.3 nmol/min/mg of protein and a Km for L-arginine of 22.3 microM. These results indicate that normal human keratinocytes contain a constitutive nitric oxide synthase related to NOS I. PMID:8648171

  20. 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

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

    PubMed Central

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

    2010-01-01

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

  2. Nitric Oxide Not Apoptosis Mediates Differential Killing of Mycobacterium bovis in Bovine Macrophages

    PubMed Central

    Esquivel-Solís, Hugo; Vallecillo, Antonio J.; Benítez-Guzmán, Alejandro; Adams, L. Garry; López-Vidal, Yolanda; Gutiérrez-Pabello, José A.

    2013-01-01

    To identify the resistance phenotype against Mycobacterium bovis in cattle, we used a bactericidal assay that has been considered a marker of this trait. Three of 24 cows (12.5%) were phenotyped as resistant and 21 as susceptible. Resistance of bovine macrophages (M?) to BCG challenge was evaluated for its association with SLC11A1 GT microsatellite polymorphisms within 3?UTR region. Twenty-three cows (95.8%) had a GT13 genotype, reported as resistant, consequently the SLC11A1polymorphism was not in agreement with our bactericidal assay results. M? of cows with resistant or susceptible phenotype were challenged in vitro with virulent M. bovis field strain or BCG, and nitric oxide production, bacterial killing and apoptosis induction were measured in resting and LPS-primed states. M. bovis field strain induced more apoptosis than BCG, although the difference was not significant. Resistant M? controlled better the replication of M. bovis (P<0.01), produced more nitric oxide (P<0.05) and were slightly more prone to undergo apoptosis than susceptible cells. LPS pretreatment of M? enhanced all the functional parameters analyzed. Inhibition of nitric oxide production with nG-monomethyl-L-arginine monoacetate enhanced replication of M. bovis but did not modify apoptosis rates in both resistant and susceptible M?. We conclude that nitric oxide production not apoptosis is a major determinant of macrophage resistance to M. bovis infection in cattle and that the influence of SLC11A1 gene 3?UTR polymorphism is not associated with this event. PMID:23691050

  3. Nitric Oxide (NO) and Lactic Acid Bacteria-Contributions to Health, Food Quality, and Safety

    Microsoft Academic Search

    Aynur Gül Karahan; M. Lütfü Çakmakçi; Buket Cicioglu-Aridogan; Arzu Kart-Gündogdu

    2005-01-01

    In this article, the effects of nitric oxide (NO) and nitric oxide producer bacteria on food quality, safety, and human health care high lighted. NO, which was previously recognized as a toxic gas, has attracted attention in the last two decades due to its vital role in many physiological processes of animals and plants. Particularly, it is important to note

  4. The effect of inhaled nitric oxide on the carrageenan-induced paw edema.

    PubMed

    Coelho, Carly Faria; Vieira, Rodolfo P; Lopes-Martins, Patrícia Sardinha Leonardo; Teixeira, Simone Aparecida; Borbely, Alexandre Urban; Gouvea, Irene Maria; Frigo, Lucio; Lopes-Martins, Rodrigo Álvaro Brandão

    2015-01-01

    Inhaled nitric oxide therapy reaches not only pulmonary vessels, but also other vasculatures, presenting anti-inflammatory effects. Therefore, this study investigated the effects of inhaled nitric oxide on a mice model of carrageenan-induced paw edema. Paw edema was induced in male Swiss mice (20-30 g) by subplantar injection of carrageenan (0.05 ml of a 1% suspension in 0.9% saline). The evaluation of time-course edema (mililiter) was measured by plethysmometry until 12 h following carrageenan administration. Thirty minutes after carrageenan injection, some groups received inhaled nitric oxide (300 ppm at variable doses and times) or Indometacin (INDO 5 mg/Kg, v.o), while others received sildenafil (1 mg/Kg, i.p) or rolipram (3 mg/Kg, i.p.) with or without inhaled nitric oxide. Paws were assessed for edema levels by plethysmometry, mieloperoxidase activity and histological analysis. Inhaled nitric oxide significantly reduced carrageenan-induced paw edema, mieloperoxidase activity and inflammatory infiltrate, although similar results were also observed in sildenafil and rolipram treated groups. In addition, significant effects between inhaled nitric oxide with pharmacological therapy was observed. Inhaled nitric oxide presents anti-inflammatory effects on carrageenan-induce paw edema, as observed through reduced edema, mieloperoxidase activity and neutrophil infiltration, indicating that inhaled nitric oxide therapy goes beyond lung vascular effects. PMID:25070733

  5. A two-compartment model of pulmonary nitric oxide exchange dynamics

    E-print Network

    George, Steven C.

    A two-compartment model of pulmonary nitric oxide exchange dynamics NIKOLAOS M. TSOUKIAS AND STEVEN- compartment model of pulmonary nitric oxide exchange dynamics. J. Appl. Physiol. 85(2):653­666, 1998.--The in theoretical studies to assist in the interpretation of the experimental results. We have developed a two-compartment

  6. Nitric Oxide in Biological Denitrification: Fe/Cu Metalloenzyme and Metal Complex NOx Redox Chemistry

    E-print Network

    Schroeder, Imke

    Nitric Oxide in Biological Denitrification: Fe/Cu Metalloenzyme and Metal Complex NOx Redox Nitric Oxide Sensors, Scavengers, and Delivery Agents 1227 IV. Concluding Remarks 1229 V. Acknowledgments the funda- mental coordination chemistry of the metal ions and their interactions with NOx species

  7. Pathophysiological Assessment of Nitric Oxide (Given as Sodium Nitroprusside) in Acute Ischaemic Stroke

    Microsoft Academic Search

    R. J. Butterworth; A. Cluckie; S. H. D. Jackson; M. Buxton-Thomas; P. M. W. Bath

    1998-01-01

    Acute ischaemic stroke is characterised by reductions in local cerebral blood flow (CBF) and activation of circulating platelets and leucocytes. Nitric oxide is a vasodilator and can inhibit these circulating cells. The aim of this study was to assess the effect of nitric oxide on platelet function and regional CBF in patients with acute ischaemic stroke. Sodium nitroprusside (SNP), a

  8. 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...

  9. Inhibition of neuronal nitric oxide reduces anxiety-like responses to pair housing

    Microsoft Academic Search

    Joanna L. Workman; Brian C. Trainor; M. Sima Finy; Randy J. Nelson

    2008-01-01

    Many psychological disorders are characterized by anxiety and alterations in social interactions. Recent studies demonstrate that the chemical messenger nitric oxide (NO) can regulate both anxiety and social behaviours. We tested whether an enzyme that produces NO in the brain, neuronal nitric oxide synthase (nNOS), serves as an interface between social interactions and anxiety-like behaviour. Several investigators have observed that

  10. Nitric oxide-overproducing transformants of Pseudomonas fluorescens with enhanced biocontrol of tomato bacterial wilt

    Microsoft Academic Search

    Yanqing Wang; Qian Yang; Yukio Tosa; Hitoshi Nakayashiki; Shigeyuki Mayama

    2005-01-01

    The relation between nitric oxide (NO) production and the protective ability of Pseudomonas fluorescens T5 against bacterial wilt disease in tomato was examined. The endogenous nitric oxide reductase gene of T5 was disrupted by homologous recombination using a suicide plasmid. Three disruptants were obtained, and all had higher levels of NO production. Infection with Ralstonia solanacearum was reduced in tomato

  11. 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...

  12. Nitric oxide produced by activated astrocytes rapidly and reversibly inhibits cellular respiration

    Microsoft Academic Search

    Guy C. Brown; Juan P. Bolaños; Simon J. R. Heales; John B. Clark

    1995-01-01

    Cultured astrocytes, activated to express the inducible form of nitric oxide synthase, produced up to 1 ?M nitric oxide (NO) measured by a NO-selective electrode, while non-activated cells produced no detectable NO. The production of NO was associated with an inhibition of cellular respiration, measured simultaneously by an oxygen electrode. The inhibition of respiration was rapidly reversed by inhibiting the

  13. Nitric oxide-mediated inhibition of androgen receptor activity: possible implications for prostate cancer progression

    Microsoft Academic Search

    M V Cronauer; Y Ince; R Engers; L Rinnab; W Weidemann; C V Suschek; M Burchardt; H Kleinert; J Wiedenmann; H Sies; R Ackermann; K-D Kröncke

    2007-01-01

    Chronic inflammation increases the risk of cancer and many cancers, including prostate cancer, arise at sites of chronic inflammation. Inducible nitric oxide synthase (iNOS) is an enzyme dominantly expressed during inflammatory reactions. Although synthesis of high amounts of nitric oxide (NO) by iNOS has been demonstrated in pathophysiological processes, such as acute or chronic inflammation, autoimmune diseases or tumorigenesis, the

  14. 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

  15. 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...

  16. The Effect of Nuclear Explosions on Stratospheric Nitric Oxide and Ozone

    Microsoft Academic Search

    Harold Johnston; Garry Whitten; John Birks

    1973-01-01

    This article reviews the derivation by Foley and Ruderman of the injection of nitric oxide into the stratosphere by nuclear bomb tests and compares it with similar studies. Upper and lower limits of this pollutant are estimated by us and compared with the amount and distribution of nitric oxide in the stratosphere possible from supersonic transports. The effect on ozone

  17. Increased gene expression of neuronal nitric oxide synthase in brain of adult spontaneously hypertensive rats

    Microsoft Academic Search

    Dorota Plochocka-Zulinska; Teresa L Krukoff

    1997-01-01

    Neuronal nitric oxide is hypothesized to participate in regulation of autonomic function by decreasing sympathetic output to the periphery. This hypothesis predicts that gene expression of neuronal nitric oxide synthase is increased during states of heightened sympathetic activity. To test the hypothesis, we measured gene expression in the spontaneously hypertensive rat (SHR), a genetic model of hypertension in which sympathetic

  18. Hypoxia tolerance, nitric oxide, and nitrite: lessons from extreme animals.

    PubMed

    Fago, Angela; Jensen, Frank B

    2015-03-01

    Among vertebrates able to tolerate periods of oxygen deprivation, the painted and red-eared slider turtles (Chrysemys picta and Trachemys scripta) and the crucian carp (Carassius carassius) are the most extreme and can survive even months of total lack of oxygen during winter. The key to hypoxia survival resides in concerted physiological responses, including strong metabolic depression, protection against oxidative damage and-in air-breathing animals-redistribution of blood flow. Each of these responses is known to be tightly regulated by nitric oxide (NO) and during hypoxia by its metabolite nitrite. The aim of this review is to highlight recent work illustrating the widespread roles of NO and nitrite in the tolerance to extreme oxygen deprivation, in particular in the red-eared slider turtle and crucian carp, but also in diving marine mammals. The emerging picture underscores the importance of NO and nitrite signaling in the adaptive response to hypoxia in vertebrate animals. PMID:25729057

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

    PubMed Central

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

    2012-01-01

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

  20. 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...

  1. Nitric oxide activation of Keap1/Nrf2 signaling in human colon carcinoma cells

    E-print Network

    Wogan, Gerald N.

    The transcription factor NF-E2-related nuclear factor 2 (Nrf2) regulates expression of genes that protect cells from oxidative damage. Here, we characterized nitric oxide (•NO)-induced Nrf2–Kelch-like ECH-associated protein ...

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

    PubMed Central

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

    1997-01-01

    The role of nitric oxide in obliterative bronchiolitis development, i.e., chronic rejection, was investigated in the heterotopic rat tracheal allograft model. An increase in the intragraft inducible nitric oxide synthase (iNOS) mRNA and mononuclear inflammatory cell iNOS immunoreactivity was demonstrated during progressive loss of respiratory epithelium and airway occlusion in nontreated allografts compared to syngeneic grafts. In nontreated allografts, however, intragraft nitric oxide production was decreased, most likely because of loss of iNOS epithelial expression. Treatment with aminoguanidine, a preferential inhibitor of inducible nitric oxide synthase, was associated with enhanced proliferation of alpha-smooth muscle actin immunoreactive cells and the intensity of obliterative bronchiolitis early after transplantation. Aminoguanidine treatment did not affect iNOS mRNA synthesis or intragraft nitric oxide production, but decreased iNOS immunoreactivity in smooth muscle cells. Treatment with L-arginine, a precursor of nitric oxide, significantly reduced obliterative changes. L-arginine supplementation enhanced intragraft iNOS mRNA synthesis and iNOS immunoreactivity in capillary endothelial and smooth muscle cells as well as intragraft nitric oxide production. Immunohistochemical analysis of allografts showed that neither iNOS inhibition nor supplementation of the nitric oxide pathway affected the number of graft-infiltrating CD4+ and CD8+ T cells, ED1+ and ED3+ macrophages, immune activation with expression of IL-2R or MHC class II, or production of macrophage or Th1 cytokines. In contrast, L-arginine treatment was associated with increased staining for Th2 cytokines IL-4 and IL-10. In conclusion, this study demonstrates that nitric oxide has a protective role in obliterative bronchiolitis development in this model, and suggests that nitric oxide either directly or indirectly inhibits smooth muscle cell proliferation and modulates immune response towards Th2 cytokines. PMID:9399944

  3. Role of Ammonia and Nitric Oxide in the Decrease in Plasma Prolactin Levels in Prehepatic Portal Hypertensive Male Rats

    Microsoft Academic Search

    Camila Scorticati; Juan C. Perazzo; Valeria Rettori; Samuel M. McCann; Andrea De Laurentiis

    2006-01-01

    Objectives: Since very little is known about neuroendocrine changes that occur in portal-systemic hepatic encephalopathy, we studied plasma prolactin (PRL) levels and the involvement of hyperammonemia, nitric oxide (NO) and dopaminergic and adrenergic systems in the control of this hormone secretion in a male rat model of prehepatic portal hypertension (PH). Methods: We conducted in vivo studies to determine plasma

  4. Role of nitric oxide in modulating permeability of hamster cheek pouch in response to adenosine 5?-diphosphate and bradykinin

    Microsoft Academic Search

    William G. Mayhan

    1992-01-01

    The goal of this study was to determine the role of the synthesis and release of nitric oxide in modulating alterations in microvascular permeability of the hamster cheek pouch in response to adenosine 5'-diphosphate and bradykinin. We used intravital fluorescent microscopy to examine the permeability of the hamster cheek pouch to agonists before and following application of enzymatic inhibitors of

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

    PubMed

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

    2015-03-13

    As the core structure of flavonoids, flavone has been proved to possess anticancer effects. Flavone's growth inhibitory functions are related to NO. NO is synthesized by nitric oxide synthase (NOS), and generally increased in a variety of cancer cells. NO regulates multiple cellular responses by S-nitrosylation. In this study, we explored flavone-induced regulations on nitric oxide (NO)-related cellular processes in breast cancer cells. Our results showed that, flavone suppresses breast cancer cell proliferation and induces apoptosis. Flavone restrains NO synthesis by does-dependent inhibiting NOS enzymatic activity. The decrease of NO generation was detected by fluorescence microscopy and flow cytometry. Flavone-induced inhibitory effect on NOS activity is dependent on intact cell structure. For the NO-induced protein modification, flavone treatment significantly down-regulated protein S-nitrosylation, which was detected by "Biotin-switch" method. The present study provides a novel, NO-related mechanism for the anticancer function of flavone. PMID:25680459

  6. 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

  7. Nitrous oxide and nitric oxide emissions from an irrigated cotton field in Northern China

    Microsoft Academic Search

    Chunyan Liu; Xunhua Zheng; Zaixing Zhou; Shenghui Han; Yinghong Wang; Kai Wang; Wangguo Liang; Ming Li; Deli Chen; Zhiping Yang

    2010-01-01

    Cotton is one of the major crops worldwide and delivers fibers to textile industries across the globe. Its cultivation requires\\u000a high nitrogen (N) input and additionally irrigation, and the combination of both has the potential to trigger high emissions\\u000a of nitrous oxide (N2O) and nitric oxide (NO), thereby contributing to rising levels of greenhouse gases in the atmosphere. Using an

  8. Increased concentrations of nitrite in synovial fluid and serum samples suggest increased nitric oxide synthesis in rheumatic diseases

    Microsoft Academic Search

    A J Farrell; D R Blake; R M Palmer; S Moncada

    1992-01-01

    Cytokines induce nitric oxide synthesis by endothelial cells, macrophages and polymorphonuclear leucocytes, indicating a role for nitric oxide in inflammatory processes. Nitric oxide production was therefore measured indirectly as nitrite in serum and synovial fluid samples from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) together with serum samples from healthy volunteers matched for age and sex. Serum nitrite concentrations

  9. Modified peptide nucleic acids are internalized in mouse macrophages RAW 264.7 and inhibit inducible nitric oxide synthase

    Microsoft Academic Search

    Sonia Scarfi; Marco Giovine; Anna Gasparini; Gianluca Damonte; Enrico Millo; Marina Pozzolini; Umberto Benatti

    1999-01-01

    Overexpression of inducible nitric oxide synthase causes the production of high levels of nitric oxide, which, under pathological conditions, leads to immunosuppression and tissue damage. The results recently obtained using peptide nucleic acids, rather than traditional oligonucleotides as antigen and antisense molecules, prompted us to test their efficacy in the regulation of nitric oxide production, thereby overcoming the obstacle of

  10. Detailed methods for the quantification of nitric oxide in aqueous solutions using either an oxygen monitor or EPR.

    PubMed

    Venkataraman, S; Martin, S M; Schafer, F Q; Buettner, G R

    2000-09-15

    The interest in nitric oxide has grown with the discovery that it has many biological functions. This has heightened the need for methods to quantify nitric oxide. Here we report two separate methods for the quantification of aqueous stock solutions of nitric oxide. The first is a new method based on the reaction of nitric oxide with oxygen in liquid phase (*NO + O2 + 2H2O --> 4HNO2); an oxygen monitor is used to measure the consumption of oxygen by nitric oxide. This method offers the advantages of being both simple and direct. The presence of nitrite or nitrate, frequent contaminants in nitric oxide stock solutions, does not interfere with the quantification of nitric oxide. Measuring the disappearance of dissolved oxygen, a reactant, in the presence of known amounts of nitric oxide has provided verification of the 4:1 stoichiometry of the reaction. The second method uses electron paramagnetic resonance spectroscopy (EPR) and the nitric oxide trap [Fe2+-(MGD)2], (MGD = N-methyl-D-glucamine dithiocarbamate). The nitrosyl complex is stable and easily quantitated as a room temperature aqueous solution. These two methods are validated with Sievers 280 Nitric Oxide Analyzer and cross-checked with standards using UV-Vis spectroscopy. The practical lower limits for measuring the concentration of nitric oxide using the oxygen monitor approach and EPR are approximately 3 microM and 500 nM, respectively. Both methods provide straightforward approaches for the standardization of nitric oxide in solution. PMID:11025201

  11. Nitric oxide reduction in the postflame region of pulverized coal flames

    SciTech Connect

    Miller, G.P.; Lester, T.W.; Cheng, M.T. (Dept. of Mechanical Engineering, Louisiana State Univ., Baton Rouge, LA (US))

    1991-06-01

    This paper reports on a computer model developed to perform three simulations of nitric oxide reduction in the postflame region of a downflow combustor burning Utah bituminous coal at stoichiometric ratios (SR) of 0.8 and 0.4, where SR = 1/{phi}, and {phi} is fuel equivalence ratio. Comparisons to experiment are made for all three cases. The contributions of both homogeneous and heterogeneous mechanisms to nitric oxide reduction in coal combustion are inferred from the simulations. The first simulation, in which soot was assumed to be the only route for NO reduction, determined the percentage soot yield needed in order for heterogeneous NO reduction on soot to account for the experimental results. The results indicate that required soot yields are consistent with those measured experimentally in pulverized coal flames. The second simulation, in which soot oxidation was added to the first model and where the gas-phase species profiles were calculated using a 119-reaction, 27-species carbon/hydrogen/ oxygen reaction set, showed that all the soot was rapidly oxidized for SR = 0.8, but that no appreciable soot was oxidized at SR = 0.4, due to the much lower OH radical concentrations.

  12. Nitric Oxide Synthase is Necessary for Normal Urogenital Development

    PubMed Central

    Bond, Christopher; Cakir, Omer Onur; McVary, Kevin T.; Podlasek, Carol A.

    2014-01-01

    Introduction Neuronal nitric oxide synthase (NOS-I) is significantly decreased with Cavernous Nerve (CN) injury in Erectile Dysfunction (ED) models. Increased apoptosis and collagen deposition accompany decreased NOS/CN injury, however these changes are typically attributed to the altered signaling of other factors, and a contribution of NOS in maintenance of urogenital structures has not previously been examined. Morphological changes in the corpora cavernosa occur at the same time as decreased NOS, suggesting a potential connection between decreased/inhibited NOS and morphological changes associated with ED. In this study we propose that NOS impacts urogenital morphology during development and will examine this hypothesis by NOS inhibition with L-NAME. Methods Primary outcomes were H&E, western and TUNEL to determine if penis, prostate and bladder morphology were altered with L-NAME treatment of Postnatal day 4 (P4) Sprague Dawley rats for 8 days. Tissue weight and immunohistochemical analysis for NOS were performed. Secondary evaluation of NOS-I regulation by Sonic Hedgehog (SHH) was examined by SHH inhibition in the pelvic ganglia (PG) and NOS-I protein was quantified by western in the PG/CN and penis. Nos abundance was quantified by RT-PCR during urogenital development and after CN injury. Results Apoptosis increased and penis, prostate and bladder morphology were altered with L-NAME. NOS inhibition decreased bladder weight 25%. SHH inhibition decreased NOS-I 35% in the PG/CN and 47% in the penis. Nos-III expression spiked within the first two weeks after birth in the penis but remained abundant in the adult. In the prostate, Nos-III was abundant immediately after birth and declined steadily with age. Nos-I expression in the PG/CN decreased sharply with CN injury and returned to baseline by 7 days. Conclusions NOS is required for normal urogenital development. Since NOS is decreased with ED, it may contribute to the abnormal morphology observed in ED patients and animal models. PMID:24900949

  13. Nitric oxide emissions from conventional vegetable fields in southeastern China

    NASA Astrophysics Data System (ADS)

    Mei, Baoling; Zheng, Xunhua; Xie, Baohua; Dong, Haibo; Zhou, Zaixing; Wang, Rui; Deng, Jia; Cui, Feng; Tong, Huajun; Zhu, Jianguo

    We conducted multi-year observations of nitric oxide (NO) fluxes from typical vegetable fields in the Yangtze River delta, which is located in southeastern China. Flux measurements were performed manually twice per week at intervals of 2-3 days, in both fertilized and unfertilized fields, over an investigation period of 1448 days (September 2004-August 2008). In total, twelve vegetable-growing periods and a short fallow period were investigated. On average, the NO fluxes from the fertilized plots were 21 times higher than fluxes from the unfertilized plots ( p < 0.001). Peak NO emissions usually occurred soon after the addition of nitrogenous fertilizer. Peak emissions took place during about 15% of the whole investigation time, but contributed to approximately 89% of the total NO release. The annual background NO emissions (from fields without nitrogen amendment) were observed at 0.290 ± 0.019 (standard deviation of 3 observations) kg N ha -1. The total amounts of NO emitted during the individual vegetable-growing periods correlated positively and exponentially with the products of seasonal mean soil temperatures and nitrogen addition rates ( R2 = 0.87, p < 0.001). The mean direct NO emission factor (EF d, the loss rate of fertilizer nitrogen via NO emissions) for the four-year period was determined to be 0.51% ± 0.11% (standard error of 3 observations). The EF ds of individual vegetable-growing seasons ranged from 0.05% to 1.24%, varying linearly and positively with the products of seasonal mean soil temperatures and nitrogen addition rates ( R2 = 0.58, p < 0.01). The observed interaction of soil temperature and nitrogen addition on NO emission in seasonal totals and EF ds occurred in soils with moisture contents ranging from 55% to 100% water-filled pore space (mean: 79%; standard deviation: 9%). The results of this study indicate that when other conditions remain relatively stable, the direct emission factor, a key parameter for compiling an inventory of NO emissions from vegetable fields, may vary with not only soil temperature but also nitrogen addition.

  14. 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%.

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

    PubMed Central

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

    1997-01-01

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

  16. Downregulation of nitric oxide by electroacupuncture against hypoxic-ischemic brain damage in rats via nuclear factor-?B/neuronal nitric oxide synthase

    PubMed Central

    LIU, YICHEN; LI, WEIGUANG; HU, LINYAN; LIU, YING; LI, BAOQUAN; SUN, CHANGQING; ZHANG, CHENGGANG; ZOU, LIPING

    2015-01-01

    The present study aimed to investigate the role of nitric oxide (NO) against perinatal hypoxic-ischemic brain damage (HIBD) in rats by electroacupuncture (EA) and to examine its potential neuroprotective mechanism. NO content, the number of positive cells, neuronal nitric oxide synthase (nNOS) and nuclear factor-?B (NF-?B) in rat cortex cells were determined. The results demonstrated that treatment with EA significantly downregulated the NO content in the cortex cells (*P<0.05, **P<0.01, compared with the control groups) and alleviated cell damage in the cortex of rats with HIBD. The activator, S-adenosyl-L-methionine and the inhibitor, hydroxylamine of cystathionine-?-synthase (CBS), aggravated and remitted the hypoxic damage in the cortex cells, respectively. In addition, treatment with EA significantly downregulated the expression of nNOS and NF-?B in the rat cortex cells (*P<0.05, **P<0.01, compared with the control groups). The results also indicated that treatment with EA downregulated the NO content of cortical cells against HIBD via the NF-?B/nNOS pathway and further implied that the hydrogen sulfide/CBS system may be involved in the process. The present study provided a significant reference for the prevention and treatment of HIBD using the EA technique and also described a novel protective mechanism. PMID:25374015

  17. Regulation of Nitric Oxide Production by ?-Opioid Receptors during Glaucomatous Injury

    PubMed Central

    Husain, Shahid; Abdul, Yasir; Singh, Sudha; Ahmad, Anis; Husain, Mahvash

    2014-01-01

    To determine the roles of nitric oxide in glaucomatous injury and its regulation by ?-opioid-receptor activation, animals were treated with: 1) a selective inducible nitric oxide synthase (iNOS) inhibitor (aminoguanidine; AG; 25 mg/kg, i.p.); 2) ?-opioid-receptor agonist (SNC-121; 1 mg/kg, i.p.); or 3) with both drugs simultaneously for 7 days, once daily. The loss in retinal ganglion cell (RGC) numbers and their function in glaucomatous eyes were significantly improved in the presence of AG or SNC-121; however, we did not see any significant additive or synergistic effects when animals were treated with both drugs simultaneously. The levels of nitrate-nitrite were significantly increased in the glaucomatous retina when compared with normal retina (normal retina 86±9 vs. glaucomatous retina 174±10 mM/mg protein), which was reduced significantly when animals were treated either with SNC-121 (121±7 mM/mg protein; P<0.05) or AG (128±10 mM/mg protein; P<0.05). Additionally, SNC-121-mediated reduction in nitrate-nitrite levels was not only blocked by naltrindole (a ?-opioid-receptor antagonist), but naltrindole treatment potentiated the nitrate-nitrite production in glaucomatous retina (235±4 mM/mg protein; P<0.001). As expected, naltrindole treatment also fully-blocked SNC-121-mediated retina neuroprotection. The nitrotyrosine level in the glaucomatous retina was also increased, which was significantly reduced in the SNC-121-treated animals. Additionally, the expression level of iNOS was clearly increased over the control levels in the glaucomatous retina and optic nerves, which was also reduced by SNC-121 treatment. In conclusion, our data support the notion that nitric oxide plays a detrimental role during glaucomatous injury and inhibition of nitric oxide production provided RGC neuroprotection. Furthermore, ?-opioid receptor activation regulates the production of nitric oxide via inhibiting the activity of iNOS in the retina and optic nerve. PMID:25329670

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

    PubMed

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

    2011-06-15

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

  19. Synthesis, ocular effects, and nitric oxide donation of imidazole amidoximes.

    PubMed

    Oresmaa, L; Kotikoski, H; Haukka, M; Oksala, O; Pohjala, E; Vapaatalo, H; Moilanen, E; Vainiotalo, P; Aulaskari, P

    2006-09-01

    Novel 1-R-imidazole-5-amidoximes and 1-R-5-cyano-imidazole-4-amidoximes (R: H, Me, Bn) were prepared from their corresponding nitriles and were tested for their efficacy to lower intraocular pressure (IOP) in rabbits. The ability of these compounds to donate nitric oxide (NO) was studied by observing the stimulation of formation of cyclic guanosine-3',5'-monophosphate (cGMP) in the incubation of porcine iris-ciliary body. In the incubation experiments, 1-methylimidazole-5-amidoxime and 1(H)-imidazole-4(5)-amidoxime stimulated formation of cGMP indicating NO donating ability of these compounds. 1-Methylimidazole-5-amidoxime lowered IOP significantly after intravitreal injection. PMID:16762462

  20. Nitric Oxide Links Mitochondrial Fission to Alzheimer's Disease

    NSDL National Science Digital Library

    Benedikt Westermann (Universitat Bayreuth; Institut fur Zellbiologie and Bayreuther Zentrum fur Molekulare Biowissenschaften REV)

    2009-05-05

    Mitochondrial dysfunction is a hallmark of ?-amyloid (A?)–induced neuronal injury in the pathogenesis of Alzheimer’s disease. Neurotoxic A? peptide, thought to be a key mediator of Alzheimer’s disease, may be imported into human brain mitochondria, where it inhibits key enzymes of respiratory metabolism. Nitric oxide (NO) produced in response to A? induces S-nitrosylation of the mitochondrial division protein, dynamin-related protein 1 (Drp-1), which leads to excessive mitochondrial fission, synaptic loss, and neuronal damage. Furthermore, brains of patients with Alzheimer’s disease contain high amounts of S-nitrosylated Drp-1. A?-dependent mitochondrial fragmentation likely enhances the decline in bioenergetic capacity of damaged mitochondria and therefore contributes to neuronal injury and pathogenesis of Alzheimer’s disease.

  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. The role of nitric oxide in the object recognition memory.

    PubMed

    Pitsikas, Nikolaos

    2015-05-15

    The novel object recognition task (NORT) assesses recognition memory in animals. It is a non-rewarded paradigm that it is based on spontaneous exploratory behavior in rodents. This procedure is widely used for testing the effects of compounds on recognition memory. Recognition memory is a type of memory severely compromised in schizophrenic and Alzheimer's disease patients. Nitric oxide (NO) is sought to be an intra- and inter-cellular messenger in the central nervous system and its implication in learning and memory is well documented. Here I intended to critically review the role of NO-related compounds on different aspects of recognition memory. Current analysis shows that both NO donors and NO synthase (NOS) inhibitors are involved in object recognition memory and suggests that NO might be a promising target for cognition impairments. However, the potential neurotoxicity of NO would add a note of caution in this context. PMID:24933185

  3. 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.

  4. 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.

  5. Nitroxyl (HNO): the Cinderella of the nitric oxide story.

    PubMed

    Irvine, Jennifer C; Ritchie, Rebecca H; Favaloro, Joanne L; Andrews, Karen L; Widdop, Robert E; Kemp-Harper, Barbara K

    2008-12-01

    Until recently, most of the biological effects of nitric oxide (NO) have been attributed to its uncharged state (NO*), yet NO can also exist in the reduced state as nitroxyl (HNO or NO(-)). Putatively generated from both NO synthase (NOS)-dependent and -independent sources, HNO is rapidly emerging as a novel entity with distinct pharmacology and therapeutic advantages over its redox sibling, NO*. Thus, unlike NO*, HNO can target cardiac sarcoplasmic ryanodine receptors to increase myocardial contractility, can interact directly with thiols and is resistant to both scavenging by superoxide (*O2-) and tolerance development. HNO donors are protective in the setting of heart failure in which NO donors have minimal impact. Here, we discuss the unique pharmacology of HNO versus NO* and highlight the therapeutic potential of HNO donors in the treatment of cardiovascular disease. PMID:18835046

  6. 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

  7. 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.

  8. Nitric oxide in the middle to upper thermosphere

    NASA Technical Reports Server (NTRS)

    Siskind, David E.; Rusch, David W.

    1992-01-01

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

  9. 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

  10. Nitric oxide counters ethylene effects on ripening fruits

    PubMed Central

    Manjunatha, Girigowda; Gupta, Kapuganti J.; Lokesh, Veeresh; Mur, Luis AJ; Neelwarne, Bhagyalakshmi

    2012-01-01

    Ethylene plays a key role in promoting fruit ripening, so altering its biosynthesis/signaling could be an important means to delay this process. Nitric oxide (NO)-generated signals are now being shown to regulate ethylene pathways. NO signals have been shown to transcriptionally repress the expression of genes involved in ethylene biosynthesis enzymes and post-translationally modify methionine adenosyl transferase (MAT) activity through S-nitrosylation to reduce the availably of methyl groups required to produce ethylene. Additionally, NO cross-talks with plant hormones and other signal molecules and act to orchestrate the suppression of ethylene effects by modulating enzymes/proteins that are generally triggered by ethylene signaling at post-climacteric stage. Thus, medication of endogenous NO production is suggested as a strategy to postpone the climacteric stage of many tropical fruits. PMID:22499176

  11. 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 ?m. 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 (? = 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

  12. Photoinduced release of nitroxyl and nitric oxide from diazeniumdiolates.

    PubMed

    Lymar, Sergei V; Shafirovich, Vladimir

    2007-06-21

    Aqueous photochemistry of diazen-1-ium-1,2,2-triolate (Angeli's anion) and (Z)-1[N-(3-aminopropyl)-N-(3-aminopropyl)amino]diazen-1-ium-1,2-diolate (DPTA NONOate) has been investigated by laser kinetic spectroscopy. In neutral aqueous solutions, 266 nm photolysis of these diazeniumdiolates generates a unique spectrum of primary products including the ground-state triplet (3NO-) and singlet (1HNO) nitroxyl species and nitric oxide (NO*). Formation of these spectrophotometrically invisible products is revealed and quantitatively assayed by analyzing a complex set of their cross-reactions leading to the formation of colored intermediates, the N2O2*- radical and N3O3- anion. The experimental design employed takes advantage of the extremely slow spin-forbidden protic equilibration between 3NO- and 1HNO and the vast difference in their reactivity toward NO*. To account for the kinetic data, a novel combination reaction, 3NO-+1HNO, is introduced, and its rate constant of 6.6x10(9) M-1 s-1 is measured by competition with the reduction of methyl viologen by 3NO-. The latter reaction occurring with 2.1x10(9) M-1 s-1 rate constant and leading to the stable, colored methyl viologen radical cation is useful for detection of 3NO-. The distributions of the primary photolysis products (Angeli's anion: 22% 3NO-, 58% 1HNO, and 20% NO*; DPTA NONOate: 3% 3NO-, 12% 1HNO, and 85% NO*) show that neither diazeniumdiolate is a highly selective photochemical generator of nitroxyl species or nitric oxide, although the selectivity of DPTA NONOate for NO* generation is clearly greater. PMID:17488001

  13. Nitric oxide, oxygen, and prostacyclin in children with pulmonary hypertension

    PubMed Central

    Turanlahti, M; Laitinen, P; Sarna, S; Pesonen, E

    1998-01-01

    Objective—To test the vasodilatory response of the pulmonary vascular bed in children with pulmonary hypertension.?Design—Prospective dose response study in which the effects of inhaled nitric oxide (NO) are compared with those of oxygen and intravenous prostacyclin.?Patients and interventions—The vasodilator test was performed in 20 patients in whom mean pulmonary artery pressure (PAPm) was ? 40 mm Hg and/or pulmonary vascular resistance index was ? 4 Um2. Haemodynamic effects of inhaled NO (20, 40, and 80 ppm) at a fractional inspired oxygen (FiO2) value of 0.3, pure oxygen, oxygen at FiO2 0.9-1.0 combined with NO as above or with intravenous prostacyclin at 10 and 20 ng/kg/min were measured.?Result—NO decreased PAPm with a dose response from 20 to 40 ppm (mean change at 40 ppm ?5.50, 95% confidence interval (CI) ?7.98 to ?3.02 mm Hg). Maximal decrease in the ratio of pulmonary to systemic vascular resistance was achieved with a combination of NO 80 ppm and oxygen (?0.18, 95% CI ?0.26 to ?0.10). Increase in the pulmonary flow index was greatest with pure oxygen in those with an intracardiac shunt (8.52, 95% CI ?0.15 to 17.20 l/min/m2). Neither NO nor oxygen altered systemic arterial pressure but intravenous prostacyclin lowered systemic arterial pressure and resistance.?Conclusions—NO selectively reduces pulmonary vascular resistance and pressure maximally at 40 ppm. Oxygen reduces pulmonary vascular resistance and NO potentiates this reduction without affecting the systemic circulation. Prostacyclin vasodilates the pulmonary and the systemic circulations.?? Keywords: pulmonary hypertension;  nitric oxide;  prostacyclin;  congenital heart disease;  children PMID:9538311

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

    Arora, Dhruv P; Boon, Elizabeth M

    2012-05-11

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

  16. Elevation in Exhaled Nitric Oxide Predicts for Radiation Pneumonitis

    SciTech Connect

    Guerrero, Thomas, E-mail: tguerrero@mdanderson.org [Division of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX (United States); Martinez, Josue [Department of Statistics, Texas A and M University, College Station, TX (United States); McCurdy, Matthew R. [Department of Radiation Oncology, Baylor College of Medicine, Houston, TX (United States); Wolski, Michael [Department of Radiation Oncology, University of Texas Medical Branch, Galveston, TX (United States); McAleer, Mary Francis [Division of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States)

    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.

  17. Potent activation of nitric oxide synthase by garlic: a basis for its therapeutic applications.

    PubMed

    Das, I; Khan, N S; Sooranna, S R

    1995-01-01

    Garlic (Allium sativum L.) is thought to have a variety of therapeutic applications including inhibition of platelet aggregation. Many of the therapeutic actions of garlic parallel the physiological effects of nitric oxide and may be explained by its ability to increase nitric oxide synthase activity intracellularly. Our studies showed that both water and alcoholic extracts of garlic are very potent inhibitors of platelet aggregation induced by epinephrine and ADP. Similar dilutions of garlic extract also activated nitric oxide synthase activity in isolated platelets in vitro. The same extract was also very effective in activating nitric oxide synthase activity in placental villous tissue. The addition of garlic extracts increased nitric oxide synthase activity in a dose-dependent manner. Nitrite levels in the supernatants of incubated placental villous tissue were similarly increased. Activation of calcium-dependent nitric oxide synthase and the subsequent production of nitric oxide is probably the most novel mechanism yet claimed by which garlic can exert its therapeutic properties. PMID:7555034

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

    PubMed Central

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

    2012-01-01

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

  19. Selective reduction of nitric oxides with ammonia using a cellular block catalyst

    SciTech Connect

    M.V. D'yakov; A.I. Kozlov; E.S. Lukin [and others] [D.I. Mendeleev Russian Chemical Engineering University, Moscow (Russian Federation)

    2004-03-15

    An aluminum-vanadium cellular block catalyst for selective reduction of nitric oxides with ammonia has been developed. With an average degree of conversion of oxides over 90%, the efficiency of the proposed catalyst is significantly higher than that of industrial catalysts currently used. Such catalyst can be recommended for use in selective plants for purification of waste gases from nitric oxides, which makes it possible to significantly decrease the cost of making a catalyst block.

  20. 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.

  1. Exhaled nitric oxide predicts asthma relapse in children with clinical asthma remission

    Microsoft Academic Search

    W. Hofhuis; Jongste de J. C; M. W. H. Pijnenburg

    2005-01-01

    BACKGROUND: Nitric oxide in exhaled air (FE(NO)) is a marker of\\u000a eosinophilic airway inflammation. A study was undertaken to determine\\u000a whether FE(NO) predicts asthma relapse in asymptomatic asthmatic children\\u000a in whom inhaled corticosteroids are discontinued. METHODS: Forty children\\u000a (21 boys) of mean age 12.2 years on a median dose of 400 mug budesonide or\\u000a equivalent (range 100-400) were included. FE(NO)

  2. New aspects of the interactions between the cardiovascular nitric oxide system and natriuretic peptides.

    PubMed

    Costa, María A; Arranz, Cristina T

    2011-03-11

    Arterial blood pressure is regulated by a variety of endocrine, autocrine and neuronal systems. Natriuretic peptides and nitric oxide are important factors that exert synergistic vascular and cardiac actions and their activities are closely linked. The existence of a novel signal transduction mechanism involved in activation of nitric oxide synthase via natriuretic peptides is currently being explored. Since several cardiovascular disorders are associated with dysfunction of natriuretic peptides activity, selective modulation of the natriuretic peptides pathway represents an important therapeutic target. This review article highlights the current findings on cross-talk between natriuretic peptides and the nitric oxide system. PMID:21329665

  3. 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.

  4. 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.

  5. Endothelium-derived relaxing factor (nitric oxide) has protective actions in the stomach

    Microsoft Academic Search

    W. K. MacNaughton; J. L. Wallace; G. Cirino

    1989-01-01

    The role that nitric oxide, an endothelium-derived relaxing factor, may play in the regulation of gastric mucosal defense was investigated by assessing the potential protective actions of this factor against the damage caused by ethanol in an ex vivo chamber preparation of the rat stomach. Topical application of glyceryl trinitrate and sodium nitroprusside, which have been shown to release nitric

  6. 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

  7. Oxidative stress during post-hypoxic-ischemic reperfusion in the newborn lamb: the effect of nitric oxide synthesis inhibition.

    PubMed

    Dorrepaal, C A; van Bel, F; Moison, R M; Shadid, M; van de Bor, M; Steendijk, P; Berger, H M

    1997-03-01

    Post-hypoxic-ischemic (HI) reperfusion induces endothelium and neurons to produce excessive amounts of nitric oxide and superoxide, leading to peroxynitrite formation, release of protein-bound metal ions (i.e. iron), and cytotoxic oxidants. We produced severe HI in 18 newborn lambs and serially determined plasma prooxidants (non-protein-bound iron), lipid peroxidation (malondialdehyde), and antioxidative capacity [ratio of ascorbic acid/dehydroascorbic acid (AA/DHA), alpha-tocopherol, sulfhydryl groups, allantoin/uric acid ratio, and vitamin A] in blood effluent from the brain before and at 15, 60, 120, and 180 min after HI. The lambs were divided in three groups: six received a placebo (CONT), six received low dose (10 mg/kg/i.v.) N omega-nitro-L-arginine (NLA-10) to block nitric oxide production, and six received high dose NLA (40 mg/kg/i.v.; NLA-40), immediately after completion of HI. Non-protein-bound iron increased in all groups after HI but was significantly lower in both NLA groups at 180 min post-HI (p < 0.05), the AA/DHA ratio showed a consistent decrease in CONT (at 60 min post-HI, p < 0.05), but remained stable in NLA lambs. alpha-Tocopherol decreased steadily in the CONT, but not in the NLA lambs [180 post-H: 1.9 +/- 0.9 versus 4.2 +/- 0.7 microM (NLA-40), p < 0.05). Malondialdehyde was significantly higher in CONT lambs 120 min post-H compared with NLA groups [0.61 +/- 017 versus 0.44 +/- 0.05 microM (NLA-40), p < 0.05]. Vitamin A and sulfhydryl groups did not differ among groups. We conclude that post-H inhibition of nitric oxide synthesis diminishes non-protein-bound iron increment and preserves antioxidant capacity. PMID:9078529

  8. Effects of inhaled nitric oxide on regional blood flow are consistent with intravascular nitric oxidedelivery

    PubMed Central

    Cannon, Richard O.; Schechter, Alan N.; Panza, Julio A.; Ognibene, Frederick P.; Pease-Fye, Margaret E.; Waclawiw, Myron A.; Shelhamer, James H.; Gladwin, Mark T.

    2001-01-01

    Nitric oxide (NO) may be stabilized by binding to hemoglobin, by nitrosating thiol-containing plasma molecules, or by conversion to nitrite, all reactions potentially preserving its bioactivity in blood. Here we examined the contribution of blood-transported NO to regional vascular tone in humans before and during NO inhalation. While breathing room air and then room air with NO at 80 parts per million, forearm blood flow was measured in 16 subjects at rest and after blockade of forearm NO synthesis with NG-monomethyl-L-arginine (L-NMMA) followed by forearm exercise stress. L-NMMA reduced blood flow by 25% and increased resistance by 50%, an effect that was blocked by NO inhalation. With NO inhalation, resistance was significantly lower during L-NMMA infusion, both at rest and during repetitive hand-grip exercise. S-nitrosohemoglobin and plasma S-nitrosothiols did not change with NO inhalation. Arterial nitrite levels increased by 11% and arterial nitrosyl(heme)hemoglobin levels increased tenfold to the micromolar range, and both measures were consistently higher in the arterial than in venous blood. S-nitrosohemoglobin levels were in the nanomolar range, with no significant artery-to-vein gradients. These results indicate that inhaled NO during blockade of regional NO synthesis can supply intravascular NO to maintain normal vascular function. This effect may have application for the treatment of diseases characterized by endothelial dysfunction. PMID:11457881

  9. Effects of nitric oxide on cholesterol metabolism in macrophages.

    PubMed

    Shimizu, H; Taniguchi, T; Ishikawa, Y; Yokoyama, M

    1997-03-21

    Nitric oxide (NO) is associated with atherogenic process by inhibiting the proliferation of vascular smooth muscle cells, adhesion of monocyte/macrophages, aggregation and adhesion of platelets and oxidation of LDL, but it is not clear whether NO affects cellular cholesterol metabolism or not. We investigated cholesterol metabolism in murine macrophages (J774A.1) by regulating NO production. Incubation with S-nitroso-N-acetylpenicillamine (SNAP), an NO donor, had no influence on cellular cholesterol accumulation induced by LDL or acetylated LDL (acetyl-LDL). Lipopolysaccharide (LPS) stimulated NO production in a dose-dependent manner in the presence of LDL or acetyl-LDL but did not change LDL-induced cellular cholesterol accumulation. In the presence of acetyl-LDL, LPS stimulated NO production but significantly inhibited cholesteryl ester accumulation in a dose-dependent manner (37.7% decrease by 100 micrograms/ml of LPS), but LPS simulation did not change free cholesterol content. NG-monomethyl-L-arginine (L-NMMA), inhibitor of NO synthase, suppressed NO production and addition of L-arginine restored NO production, but these regulations did not alter LPS-induced esterified cholesterol reduction. These results suggest that NO generation in atherosclerotic lesions does not influence cholesterol metabolism in macrophages. PMID:9105561

  10. Development of a novel fluorometric assay for nitric oxide utilizing sesamol and its application to analysis of nitric oxide-releasing drugs.

    PubMed

    Abe, Seiji; Nakabayashi, Shigeo; Murayama, Jun-Ichiro; Sano, Yoshihiro; Ohno, Ken-Ichi; Maeda, Masako; Arakawa, Hidetoshi

    2010-01-01

    Nitric oxide (NO) is related to various physiological effects as well as to numerous diseases caused by accentuation of NO production. Measurement of NO in cells and tissues is difficult as NO readily reacts with other molecules; furthermore, its half-life as a radical is fleeting. Currently, many NO pharmaceuticals are marketed as therapeutic agents for ischemic disease. Consequently, the identification of NO radicals and determination of generation rate from pharmaceuticals is very important when the effect of the medicinal supply is estimated. In this study, we developed a fluorometric assay for NO employing sesamol (3,4-methylenedioxyphenol) as a fluorometric substrate. Sesamol is converted to a fluorescent derivative (ex. 365?nm, em. 447?nm), which is dimmer in the presence of NO. The detection limit of NO with this method is 400?fmol; moreover, NO generated from drugs can be measured. PMID:19924673

  11. 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-? 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.

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

    PubMed Central

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

    2015-01-01

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

  13. The detection of nitric oxide and its reactivity with transition metal thiolate complexes

    E-print Network

    Tennyson, Andrew Gregory

    2008-01-01

    Nitric oxide (NO) is a molecule that is essential for life and regulates both beneficial and harmful processes. Because this gaseous radical influences many aspects of health and disease, we wish to explore the relationship ...

  14. Seminaphthofluorescein-Based Fluorescent Probes for Imaging Nitric Oxide in Live Cells

    E-print Network

    Pluth, Michael D.

    Fluorescent turn-on probes for nitric oxide based on seminaphthofluorescein scaffolds were prepared and spectroscopically characterized. The Cu(II) complexes of these fluorescent probes react with NO under anaerobic ...

  15. Neuronal nitric oxide synthase in the gill of the killifish, Fundulus heteroclitus

    E-print Network

    Evans, David H.

    nNOS to nerve fibers and epithelial cells adjacent to mitochondrion-rich cells (ion transporting heteroclitus; Gill; Killifish; Neuronal nitric oxide; Ion transport; Nerve; Vascular tone; Mitochondrion

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

    SciTech Connect

    Bredt, D.S.; Snyder, S.H. (Johns Hopkins Univ. School of Medicine, Baltimore (USA))

    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.

  17. Inducible Nitric Oxide Synthase Mediates Retinal Apoptosis in Ischemic Proliferative Retinopathy

    E-print Network

    Boyer, Edmond

    , 1994) and structural changes in a model of retinopathy of prematurity (Lachapelle et al., 1999 after the resolution of neovascular complications in retinopathy of prematurity (Fulton and Hansen, 1996Inducible Nitric Oxide Synthase Mediates Retinal Apoptosis in Ischemic Proliferative Retinopathy

  18. Biochemical Adaptations in Pseudomonas fluorescens Exposed to Nitric Oxide, an Endogenous Antibacterial Agent

    E-print Network

    Appanna, Vasu

    Biochemical Adaptations in Pseudomonas fluorescens Exposed to Nitric Oxide, an Endogenous supérieures Title of Thesis Titre de la thèse BIOCHEMICAL ADAPTATIONS IN PSEUDOMONAS FLUORESCENS EXPOSED. fluorescens engineers an elaborate metabolic network to generate ATP whilst withstanding the injurious effects

  19. Biochemistry of mobile zinc and nitric oxide revealed by fluorescent sensors

    E-print Network

    Pluth, Michael D.

    Biological mobile zinc and nitric oxide (NO) are two prominent examples of inorganic compounds involved in numerous signaling pathways in living systems. In the past decade, a synergy of regulation, signaling, and translocation ...

  20. Turn-on fluorescent probes for detecting nitric oxide in biology

    E-print Network

    McQuade, Lindsey Elizabeth, 1981-

    2010-01-01

    Chapter 1. Investigating the Biological Roles of Nitric Oxide and Other Reactive Nitrogen Species Using Fluorescent Probes: This chapter presents an overview of recent progress in the field of reactive nitrogen species ...

  1. Nitric oxide (NO) production correlates with renal insufficiency and multiple organ dysfunction syndrome in severe sepsis

    Microsoft Academic Search

    P. H. P. Groeneveld; K. M. C. Kwappenberg; J. A. M. Langermans; P. H. Nibbering; L. Curtis

    1996-01-01

    Objective: To investigate whether the production of nitric oxide (NO) relates to the develop- ment of renal insufficiency and multiple organ dysfunction syn- drome (MODS) in patients with severe sepsis. Design: Prospective study in 23 patients with severe sepsis. Setting.\\

  2. 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.

  3. Pathophysiology of endotoxin: microvascular dysfunction, and the roles of VEGF and nitric oxide (NO)

    E-print Network

    Naftanel, Mark Andrew

    2013-02-22

    Vascular endothelial growth factor (VEGF) elicits nitric oxide (NO)-dependent vasodilation and plays major roles in angiogenesis and wound healing. Although bacterial endotoxin (LPS) has been shown to alter endothelial NO synthase (ec...

  4. 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...

  5. Ground-based remote sensing of nitric oxide and ozone in the Antarctic middle atmosphere

    NASA Astrophysics Data System (ADS)

    Espy, Patrick; Hartogh, Paul; Clilverd, Mark; Holmén, Kim

    Nitric oxide, which reacts catalytically to destroy ozone, can be produced in great abundance in the middle atmosphere during energetic particle precipitation triggered by solar storms. During the Antarctic winter, the strong polar vortex can rapidly transport the nitric oxide downward, and this process links ozone recovery in the upper stratosphere to solar activity. A new microwave radiometer has been developed at the British Antarctic Survey to simultaneously measure profiles of ozone and nitric oxide between 30 and 80 km, deep within the Antarctic polar vortex at Troll Station (72S, 2.5E). A third channel will be used to infer the average vertical transport velocities near the mesopause using carbon monoxide. Details of the programme and first results from the instrument will be presented, with upper limits on the autumnal production and transport of nitric oxide provided.

  6. Methicillin-resistant Staphylococcus aureus Bacterial Nitric-oxide Synthase Affects Antibiotic Sensitivity

    E-print Network

    Nizet, Victor

    Methicillin-resistant Staphylococcus aureus Bacterial Nitric-oxide Synthase Affects Antibiotic of Medicine, New York, New York 10016 Background: Methicillin-resistant Staphylococcus aureus (MRSA) generates activities to reduce MRSA pathology and increase antibiotic effectiveness. Staphylococcus aureus infections

  7. 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

  8. 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(?)-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

  9. Iron deficiency suppresses ileal nitric oxide synthase activity.

    PubMed

    Goldblatt, M I; Choi, S H; Swartz-Basile, D A; Nakeeb, A; Sarna, S K; Pitt, H A

    2001-01-01

    Intestinal motility disorders are more common in women of childbearing age who are prone to iron deficiency anemia. The neurotransmitters nitric oxide (NO) and acetylcholine (ACh) play a key role in ileal smooth muscle relaxation and contraction, respectively. Iron-containing heme is known to be a cofactor for nitric oxide synthase (NOS), the enzyme responsible for NO production. Therefore we tested the hypothesis that iron deficiency would downregulate ileal NOS activity without affecting the ileum's response to ACh. Twelve adult female prairie dogs were fed either an iron-supplemented (Fe+) (200 ppm) (n = 6) or an iron-deficient (Fe-) (8 ppm) (n = 6) diet for 8 weeks. Ileal circular muscle strips were harvested to measure responses to ACh and electrical field stimulation. Under nonadrenergic noncholinergic (NANC) conditions, Nomega-nitro-L-arginine (L-NNA), an NOS inhibitor, and VIP(10-28), a vasoactive intestinal peptide (VIP) inhibitor, were added prior to electrical field stimulation. NANC inhibitory responses are expressed as a percentage of optimal relaxation from EDTA. The excitatory response to ACh was similar in both groups (1.1 +/- 0.3 N/cm(2) vs. 1.5 +/- 0.3 N/cm(2), P = 0.45). The inhibitory response to electrical field stimulation under NANC conditions was greater in the Fe+ group (34.7 +/- 2.9%) compared to the Fe- group (23.9 +/- 3.2%; P<0.01). L-NNA eliminated the inhibitory response in the Fe+ group (0.02 +/- 0.02%) but not in the Fe- group (8.38 +/- 2.15%; P <0.01). VIP(10-28) led to greater relaxation in the Fe+ animals (45.8 +/- 6.6%) than in the Fe- animals (23.4 +/- 5.8%; P <0.05). Both L-NNA and VIP(10-28) had no inhibitory response (0.02 +/- 0.02%) in the Fe+ animals, whereas the Fe- animals had some residual inhibition (2.54 +/- 1.04%; P <0.05). These data suggest that ileal NANC relaxation is due to NOS and that iron deficiency results in (1) decreased NANC relaxation, (2) a compensatory relaxation due to a non-NOS, non-VIP mechanism, and (3) a normal excitatory response. We conclude that iron deficiency suppresses ileal NOS activity. PMID:11985981

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

    NASA Astrophysics Data System (ADS)

    Roelle, Paul A.; Aneja, Viney P.

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

  11. 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

  12. Calreticulin promotes angiogenesis via activating nitric oxide signalling pathway in rheumatoid arthritis.

    PubMed

    Ding, H; Hong, C; Wang, Y; Liu, J; Zhang, N; Shen, C; Wei, W; Zheng, F

    2014-11-01

    Calreticulin (CRT) is a multi-functional endoplasmic reticulum protein implicated in the pathogenesis of rheumatoid arthritis (RA). The present study was undertaken to determine whether CRT was involved in angiogenesis via the activating nitric oxide (NO) signalling pathway. We explored the profile of CRT expression in RA (including serum, synovial fluid and synovial tissue). In order to investigate the role of CRT on angiogenesis, human umbilical vein endothelial cells (HUVECs) were isolated and cultured in this study for in-vitro experiments. Our results showed a significantly higher concentration of CRT in serum (5·4?±?2·2?ng/ml) of RA patients compared to that of osteoarthritis (OA, 3·6?±?0·9?ng/ml, P?nitric oxide (NO) production and phosphorylation level of endothelial nitric oxide synthase (eNOS) were measured in HUVECs following CRT stimulation, while the total eNOS expression was not significantly changed. Furthermore, CRT promoted the proliferation, migration and tube formation of HUVECs, which were significantly inhibited by a specific eNOS inhibitor. These findings suggested that CRT may be involved in angiogenesis events in RA through NO signalling pathways, which may provide a potential therapeutic target in the treatment of RA. PMID:24988887

  13. Evidence of nitric-oxide-induced surface band bending of indium tin oxide

    NASA Astrophysics Data System (ADS)

    Hu, Jianqiao; Pan, Jisheng; Zhu, Furong; Gong, Hao

    2004-06-01

    The interaction of indium tin oxide (ITO) film with nitric oxide (NO) has been investigated in situ by a four-point probe and x-ray photoelectron spectroscopy (XPS). The XPS N 1s peak emerged at a high binding energy of 404 eV indicating that NO was molecularly adsorbed on ITO surface. The adsorption of NO on ITO surface also induced a 0.2 eV shift in its valence band maximum to the low binding energy side leading to an upward surface band bending. We have shown that the increase in the ITO sheet resistance was attributed to its surface band bending.

  14. 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.

  15. Inducible nitric oxide synthase of macrophages. Present knowledge and evidence for species-specific regulation

    Microsoft Academic Search

    T. W. Jungi; H. Adler; B. Adler; M. Thöny; M. Krampe; E. Peterhans

    1996-01-01

    An important mechanism by which macrophages (M?) halt the growth of and eliminate a broad array of intracellular pathogens is the production of nitric oxide (NO). NO generation is catalyzed by inducible nitric oxide synthase (iNOS) converting arginine into citrulline and NO. In murine M?, iNOS activity is regulated largely at the transcriptional level. LPS and IFN-? induce iNOS, IL-4

  16. Nitric Oxide Signaling in Pain and Nociceptor Sensitization in the Rat

    Microsoft Academic Search

    K. O. Aley; Gordon McCarter; Jon D. Levine

    1998-01-01

    We investigated the role of nitric oxide (NO) in inflammatory hyperalgesia. Coinjection of prostaglandin E2 (PGE2) with the nitric oxide synthase (NOS) inhibitor N G-methyl-L-arginine (L- NMA) inhibited PGE2-induced hyperalgesia. L-NMA was also able to reverse that hyperalgesia. This suggests that NO con- tributes to the maintenance of, as well as to the induction of, PGE2-induced hyperalgesia. Consistent with the

  17. Nitric oxide down-regulates connective tissue growth factor in rat mesangial cells

    Microsoft Academic Search

    Annette Keil; Ingrid E Blom; Roel Goldschmeding; Harald D Rupprecht

    2002-01-01

    Nitric oxide down-regulates connective tissue growth factor in rat mesangial cells.BackgroundNitric oxide (NO) exerts complex regulatory actions on mesangial cell (MC) biology, such as inhibition of proliferation, adhesion or contractility and induction of apoptosis. In our previous studies the NO-donor S-nitroso-glutathione (GSNO) was found to be a potent inhibitor of MC growth. This effect was mediated at least in part

  18. Bench-to-bedside review: Inhaled nitric oxide therapy in adults

    Microsoft Academic Search

    Benedict C Creagh-Brown; Mark JD Griffiths; Timothy W Evans

    2009-01-01

    ABSTRACT: Nitric oxide (NO) is an endogenous mediator of vascular tone and host defence. Inhaled nitric oxide (iNO) results in preferential pulmonary vasodilatation and lowers pulmonary vascular resistance. The route of administration delivers NO selectively to ventilated lung units so that its effect augments that of hypoxic pulmonary vasoconstriction and improves oxygenation. This 'Bench-to-bedside' review focuses on the mechanisms of

  19. Garlic prevents hypertension induced by chronic inhibition of nitric oxide synthesis

    Microsoft Academic Search

    José Pedraza-Chaverrí; Edilia Tapia; Omar N. Medina-Campos; Martha Franco

    1998-01-01

    It has been reported that garlic activates nitric oxide synthase in vitro and that chronic inhibition of nitric oxide (NO) synthesis by N?-nitro-L-arginine-methyl-ester (L-NAME) induces arterial hypertension in rats. In this work, we studied the effect of oral administration of L-NAME for 4 weeks on control and garlic-fed rats. Basal systolic blood pressure was recorded 4 weeks after garlic supplementation,

  20. Nitric oxide and P-glycoprotein modulate the phagocytosis of colon cancer cells

    PubMed Central

    Kopecka, Joanna; Campia, Ivana; Brusa, Davide; Doublier, Sophie; Matera, Lina; Ghigo, Dario; Bosia, Amalia; Riganti, Chiara

    2011-01-01

    Abstract The anticancer drug doxorubicin induces the synthesis of nitric oxide, a small molecule that enhances the drug cytotoxicity and reduces the drug efflux through the membrane pump P-glycoprotein (Pgp). Doxorubicin also induces the translocation on the plasma membrane of the protein calreticulin (CRT), which allows tumour cells to be phagocytized by dendritic cells. We have shown that doxorubicin elicits nitric oxide synthesis and CRT exposure only in drug-sensitive cells, not in drug-resistant ones, which are indeed chemo-immunoresistant. In this work, we investigate the mechanisms by which nitric oxide induces the translocation of CRT and the molecular basis of this chemo-immunoresistance. In the drug-sensitive colon cancer HT29 cells doxorubicin increased nitric oxide synthesis, CRT exposure and cells phagocytosis. Nitric oxide promoted the translocation of CRT in a guanosine monophosphate (cGMP) and actin cytoskeleton-dependent way. CRT translocation did not occur in drug-resistant HT29-dx cells, where the doxorubicin-induced nitric oxide synthesis was absent. By increasing nitric oxide with stimuli other than doxorubicin, the CRT exposure was obtained also in HT29-dx cells. Although in sensitive cells the CRT translocation was followed by the phagocytosis, in drug-resistant cells the phagocytosis did not occur despite the CRT exposure. In HT29-dx cells CRT was bound to Pgp and only by silencing the latter the CRT-operated phagocytosis was restored, suggesting that Pgp impairs the functional activity of CRT and the tumour cells phagocytosis. Our work suggests that the levels of nitric oxide and Pgp critically modulate the recognition of the tumour cells by dendritic cells, and proposes a new potential therapeutic approach against chemo-immunoresistant tumours. PMID:20716130

  1. Expression of type 2 nitric oxide synthase and p21 in oral squamous cell carcinoma

    Microsoft Academic Search

    P. A. Brennan; M. Palacios-Callender; T. Umar; S. Tant; J. D. Langdon

    2002-01-01

    Abstract.Nitric oxide (NO) has a complex role in tumour biology. Most cancer research has focused on the enzyme nitric oxide synthase-2 (NOS2), an inducible isoform responsible for prolonged NO production. In normal cells exposed to high NO concentrations, the tumour-suppressor gene, p53, promotes apoptosis via the p21 pathway, in an attempt to safeguard against potential NO-mediated DNA damage. In cancer

  2. Sexual dimorphism in the aging kidney: Effects on injury and nitric oxide system

    Microsoft Academic Search

    Aaron Erdely; Ziv Greenfeld; Laszlo Wagner; Chris Baylis

    2003-01-01

    Sexual dimorphism in the aging kidney: Effects on injury and nitric oxide system.BackgroundMale gender confers enhanced susceptibility to development of age-dependent kidney damage. In other models of progressive renal disease, development of injury is linked to declines in renal nitric oxide synthase (NOS) capacity.MethodsWe investigated the in vitro characteristics of the renal NOS system in young (3 to 5 months),

  3. A Simplified Reactive Flow Model of Gas Turbine Combustors for Predicting Nitric Oxide Emission

    Microsoft Academic Search

    MASASHI KATSUKI; YUKIO MIZUTANI

    1977-01-01

    An axi-symmetrical two-dimensional mechanistic model of gas turbine combustors has been developed which enables us to make point-by-point arguments on the formation and destruction of nitric oxide taking both chemical reactions of finite rate and turbulent transport processes into account simultaneously. Two-dimensional distribution maps of velocities, temperature, nitric oxide concentration and equivalence ratio, as well as the variation of combustion

  4. Biological Roles of Acid and Neutral Sphingomyelinases and Their Regulation by Nitric Oxide

    NSDL National Science Digital Library

    Cristiana Perrotta (Università di Milano)

    2010-04-01

    Generation of the pleiotropic sphingolipid mediator ceramide by acid and neutral sphingomyelinases is a key event in many cellular pathophysiological processes including survival, death, proliferation, and differentiation, in which also the short-lived gaseous messenger nitric oxide plays a crucial role. This review describes how the outcome of these key cellular processes is finely tuned by surprising and complex interplays among nitric oxide, ceramide, and their effectors.

  5. Effects Of Inhaled Nitric Oxide And Oxygen In High Altitude Pulmonary Edema

    Microsoft Academic Search

    Inder S. Anand; B. A. K. Prasad; Sumeet S. Chugh; K. R. M. Rao; David N. Cornfield; Carlos E. Milla; Navneet Singh; Surjit Singh; William Selvamurthy

    The use of inhaled nitric oxide in acutely ill patients with high altitude pulmonary edema was first reported in 1998. We\\u000a demonstrated that both nitric oxide and oxygen cause an acute decrease in pulmonary artery pressure, intrapulmonary shunting\\u000a and improvement in oxygenation. There appears to be an additive effect on pulmonary hemodynamics and an even greater effect\\u000a on gas exchange

  6. Effect of nitric oxide modulation on TGF-?1 and matrix proteins in chronic cyclosporine nephrotoxicity

    Microsoft Academic Search

    Fuad S Shihab; Hong Yi; William M Bennett; Takeshi F Andoh

    2000-01-01

    Effect of nitric oxide modulation on TGF-?1 and matrix proteins in chronic cyclosporine nephrotoxicity.BackgroundChronic cyclosporine (CsA) nephrotoxicity is characterized by interstitial fibrosis and afferent arteriolar hyalinosis. L-arginine (L-Arg), the substrate for nitric oxide (NO) synthase and N-nitro-L-arginine-methyl ester (L-NAME), the NO synthase inhibitor, were shown to modulate acute CsA nephrotoxicity. However, the mechanism of fibrosis in chronic CsA nephrotoxicity remains

  7. Nitric oxide-forming reactions of the water-soluble nitric oxide spin-trapping agent, MGD.

    PubMed

    Tsuchiya, K; Jiang, J J; Yoshizumi, M; Tamaki, T; Houchi, H; Minakuchi, K; Fukuzawa, K; Mason, R P

    1999-08-01

    The objective of this study was to elucidate the nitric oxide-forming reactions of the iron-N-methyl-D-glucamine dithiocarbamate (Fe-MGD) complex from the nitrogen-containing compound hydroxyurea. The Fe2+(MGD)2 complex is commonly used in electron paramagnetic resonance (EPR) spectroscopic detection of NO both in vivo and in vitro. The reaction of Fe2+(MGD)2 with NO yields the resultant NO-Fe2+(DETC)2 complex, which has a characteristic triplet EPR signal. It is widely believed that only NO reacts with Fe2+(MGD)2 to form the NO-Fe2+(MGD)2 complex. In this report, the mechanism leading to the formation of NO-Fe2+(MGD)2 was investigated using oxygen-uptake studies in conjunction with the EPR spin-trapping technique. We found that the air oxidation of Fe2+(MGD)2 complex results in the formation of the Fe3+(MGD)3 complex, presumably concomitantly with superoxide (O3*-). Dismutation of superoxide forms hydrogen peroxide, which can subsequently reduce Fe3+(MGD)3 back to Fe2+(MGD)2. The addition of NO to the Fe3+(MGD)3 complex resulted in the formation of the NO-Fe2+(MGD)2 complex. Hydroxyurea is not considered to be a spontaneous NO donor, but has to be oxidized in order to form NO. We present data showing that in the presence of oxygen, Fe2+(MGD)2 can oxidize hydroxyurea to yield the stable NO-Fe2+(MGD)2 complex. These results imply that hydroxyurea can be oxidized by reactive oxygen species that are formed from the air oxidation of the Fe2+(MGD)2 complex. Formation of the NO-Fe2+(MGD)2 complex in this case could erroneously be interpreted as spontaneous formation of NO from hydroxyurea. The chemistry of the Fe2+(MGD)2 complexes in aerobic conditions must be taken into account in order to avoid erroneous conclusions. In addition, the use of these complexes may contribute to the overall oxidative stress of the system under investigation. PMID:10468208

  8. 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.

  9. Inhibition of nitric oxide production in RAW264.7 macrophages by cannabinoids and palmitoylethanolamide

    Microsoft Academic Search

    Ruth A. Ross; Heather C. Brockie; Roger G. Pertwee

    2000-01-01

    We have investigated the inhibition of lipopolysaccharide stimulated nitric oxide production in RAW264.7 macrophages by the cannabinoids and the putative cannabinoid CB2-like receptor ligand, palmitoylethanolamide. (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo-[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone mesylate ((+)-WIN55212) and, to a lesser extent (?)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxy-propyl)cyclohexan-1-ol (CP55940), significantly inhibited lipopolysaccharide stimulated nitric oxide production. The level of inhibition was found to be dependent on the concentration of lipopolysaccharide used to induce nitric

  10. Regulation of nitric oxide generation by up-regulated arginase I in rat spinal cord injury

    PubMed Central

    Imagama, Takashi; Ogino, Keiki; Takemoto, Kei; Kato, Yoshihiko; Kataoka, Hideo; Suzuki, Hidenori; Ran, Zhang; Setiawan, Heri; Fujikura, Yoshihisa; Taguchi, Toshihiko

    2012-01-01

    Recently, arginase is suggested to regulate nitric oxide production by competing with nitric oxide synthase for the same substrate, L-arginine, in experimental asthma. We investigated the role of arginase and its relationship to nitric oxide production after spinal cord injury. Rats were subjected to laminectomy and complete transection of their spinal cords (injury group) or laminectomy only (sham group). In the injury group, arginase I was increased in the macrophages at the transection edge, and the peak was observed 48 h after spinal cord injury. However, nitric oxide production decreased significantly in the injury group despite increased nitric oxide synthase2 mRNA expression compared with the sham group. We also demonstrated the reduction in L-arginine concentrations, which was inversely associated with changes in arginase activity. Therefore, arginase appeared to regulate nitric oxide production by consuming L-arginine. The regulation of arginase activity and L-arginine levels may improve nitroxidative stress and reduce tissue damage in spinal cord injury. PMID:22798716

  11. 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

  12. Involvement of nitric oxide in long-term potentiation of spinal nociceptive responses in rats.

    PubMed

    Zhang, Xi-Chun; Zhang, Yu-Qiu; Zhao, Zhi-Qi

    2005-08-01

    Nitric oxide plays an important role in spinal nociception. The present study explored the effects of nitric oxide on the spinal long-term potentiation associated with nociception. (1) Nitric oxide synthase inhibitor L-NAME (1 mM, 20 microl) and the nitric oxide scavenger hemoglobin (2 mg/ml, 20 mul) strikingly blocked the induction of tetanic sciatic stimulation-induced spinal long-term potentiation of C-fiber-evoked field potentials. L-arginine, a substrate of nitric oxide synthase, completely reversed L-NAME-induced inhibition. However, D-NAME (1 mM, 20 microl), an inactive form of L-NAME, had little effect on the spinal LTP. (2) The same tetanic sciatic stimulation induced long-term thermal hyperalgesia, which was blocked by pre-application of L-NAME. These results suggest the involvement of nitric oxide in the spinal long-term potentiation of C-fiber-evoked field potentials and related behavior changes. PMID:16012348

  13. Laser absorption of nitric oxide for thermometry in high-enthalpy air

    NASA Astrophysics Data System (ADS)

    Spearrin, R. M.; Schultz, I. A.; Jeffries, J. B.; Hanson, R. K.

    2014-12-01

    The design and demonstration of a laser absorption sensor for thermometry in high-enthalpy air is presented. The sensor exploits the highly temperature-sensitive and largely pressure-independent concentration of nitric oxide in air at chemical equilibrium. Temperature is thus inferred from an in situ measurement of nascent nitric oxide. The strategy is developed by utilizing a quantum cascade laser source for access to the strong fundamental absorption band in the mid-infrared spectrum of nitric oxide. Room temperature measurements in a high-pressure static cell validate the suitability of the Voigt lineshape model to the nitric oxide spectra at high gas densities. Shock-tube experiments enable calibration of a collision-broadening model for temperatures between 1200–3000?K. Finally, sensor performance is demonstrated in a high-pressure shock tube by measuring temperature behind reflected shock waves for both fixed-chemistry experiments where nitric oxide is seeded, and for experiments involving nitric oxide formation in shock-heated mixtures of N2 and O2. Results show excellent performance of the sensor across a wide range of operating conditions from 1100–2950?K and at pressures up to 140?atm.

  14. Epithelial autotoxicity of nitric oxide: role in the respiratory cytopathology of pertussis.

    PubMed

    Heiss, L N; Lancaster, J R; Corbett, J A; Goldman, W E

    1994-01-01

    Bordetella pertussis releases a specific peptidoglycan fragment known as tracheal cytotoxin (TCT) that reproduces the respiratory epithelial cytopathology of whooping cough (pertussis). In vitro, TCT inhibits DNA synthesis in hamster trachea epithelial cells and causes specific destruction of ciliated cells in explants of human and hamster respiratory epithelium. We have recently demonstrated that TCT triggers production of intracellular interleukin 1 by respiratory epithelial cells, and this cytokine may act as an intermediate signal in the generation of TCT toxicity. Here we report the identification of a subsequent critical step in this pathway: induction of nitric oxide synthesis in the respiratory epithelium. The toxic effects of nitric oxide are consistent with spectroscopic evidence of the formation of iron-dinitrosyl-dithiolate complexes in TCT-treated cells. Aconitase, with its iron-sulfur center, is one expected target of nitric oxide, and TCT inhibited 80% of the activity of this enzyme in respiratory epithelial cells. The deleterious effects of TCT and interleukin 1 were dramatically attenuated by the nitric oxide synthase inhibitors NG-monomethyl-L-arginine and aminoguanidine. These results indicate that nitric oxide mediates the toxicity of TCT for the respiratory epithelium, thus implicating a central role for nitric oxide in the pathogenesis of pertussis. PMID:7506415

  15. Effect on renin release of inhibiting renal nitric oxide synthesis in anaesthetized dogs.

    PubMed

    Naess, P A; Christensen, G; Kirkebøen, K A; Kiil, F

    1993-06-01

    Nitric oxide plays an important role in the regulation of basal renal blood flow. This study was performed to examine whether selective inhibition of renal nitric oxide synthesis affects renin release in vivo. Accordingly, in six barbiturate-anaesthetized dogs renin release was examined before and after intrarenal infusion of the selective inhibitor of nitric oxide synthesis, NG-nitro-L-arginine (NOARG). NOARG was infused into the renal artery to yield a renal arterial blood concentration of 0.4 mumol ml-1. NOARG did not change systemic arterial blood pressure and glomerular filtration rate, but reduced basal renal blood flow by 26 +/- 2%. Urine flow, sodium and potassium excretion were reduced after inhibition of renal nitric oxide synthesis. Basal renin release (3 +/- 2 micrograms AI min-1) was not altered by NOARG infusion (1 +/- 1 micrograms AI min-1). To stimulate renin release the renal artery was constricted to a renal perfusion pressure of 50 mmHg. At this perfusion pressure infusion of NOARG reduced renin release significantly from 48 +/- 11 micrograms AI min-1 to 14 +/- 4 micrograms AI min-1. In conclusion, inhibition of renal nitric oxide synthesis reduces basal renal blood flow and reduces renin release stimulated by renal arterial constriction. These findings indicate that renal nitric oxide modulates both renal blood flow and renin release in vivo. PMID:8352025

  16. Do synthetic Fe-zeolites mimic biological Fe-porphyrins in reactions with nitric oxide?

    Microsoft Academic Search

    Mickaël Rivallan; Bryan Bromley; Lioubov Kiwi-Minsker

    2010-01-01

    Iron containing ZSM-5 zeolites is extremely active in nitrous oxide decomposition. This reaction involves atomic oxygen species known as “alpha oxygen” on iron sites. Despite the multiple techniques devoted to its characterization, the active sites’ structure remains nevertheless unknown. Herein, these centers are quantified via surface titration by nitrous oxide followed by temperature programmed desorption and characterized via nitric oxide

  17. Effects of estrous synchronization on response to nitric oxide donors, nitric oxide synthase inhibitors, and endothelin-1 in vitro.

    PubMed

    Weems, Y S; Randel, R D; Tatman, S; Lewis, A W; Neuendorff, D A; Weems, C W

    2004-10-01

    Two experiments were conducted to determine the effects of nitric oxide (NO) donors, endothelin-(ET-1), and NO synthase (NOS) inhibitors on bovine luteal function in vitro. In experiment 1, estrus in Brahman cows was synchronized with Synchro-Mate-B (SMB) and day-13-14 corpora luteal slices were weighed, diced and incubated in vitro. Treatments (100 ng/ml) were: vehicle, N[see symbol in text]-nitro-L-arginine-L-methyl ester (L-NAME), N(G)-monomethyl-L-arginine acetate (L-NMMA), diethylenetriamine (DETA), DETA-NONOate, sodium nitroprusside (SNP), or ET-1. In experiment 2, estrus was synchronized with Lutalyse, a Controlled Intravaginal Progesterone Releasing Device (CIDR), or cows were not synchronized. Corpora lutea were collected, weighed, and luteal slices were weighed, diced and incubated in vitro with treatments. Treatments (100ng/ml) were: vehicle, L- NAME, L-NMMA, DETA, DETA-NONOate, sodium nitroprusside, S-nitroso-N-acetylpenicillamine (SNAP) or endothelin-1. Tissues were incubated in M- 199 for 1 h without treatments and for 4 and 8 h in both experiments with treatments in both experiments. Media were analyzed for progesterone, prostaglandins E2 and F2alpha (PGE2, PGF2alpha) by radioimmunoassay (RIA). Hormone data in experiments 1 and 2 were analyzed by 2 x 7 and 3 x 2 x 8 factorial design for analysis of variance (ANOVA), respectively. Luteal weights in experiment 2 were analyzed by a one-way ANOVA. Concentrations of progesterone in media were similar (P > or = 0.05) among treatments within experiments. Concentrations of PGE2 in media in experiment 1 were undetectable in 90 and 57% of the samples at 4 and 8 h, respectively. PGF2alpha increased (P < or = 0.05) with time, but did not differ (P > or = 0.05) among treatments. Secretion of PGF2alpha was not affected by treatments (P > or = 0.05). In experiment 2, luteal weights of the induced estrous cycle were decreased (P < or = 0.05) by Lutalyse. Concentrations of PGE2 and PGF2alpha increased (P < or = 0.05) with time in control of all three synchronization regimens. DETA-NONOate, SNAP, sodium nitroprusside (NO donors) and ET-1 increased (P < or = 0.05) PGE2 except in the CIDR synchronized group (P > or = 0.05). No treatment increased (P > or = 0.05) PGF2alpha in any synchronization regimen. It is concluded that either SMB containing norgestomet or a CIDR containing progesterone alters luteal secretion of PGE2, Lutalyse lowers luteal weights in the induced estrous cycle, and NO or ET-1 given alone are not luteolytic agents. It is suggested that NO and ET-1 could have indirect antiluteolytic/luteotropic effects via increasing PGE2 secretion by luteal tissue rather than being luteolytic. PMID:15560115

  18. Nitric oxide-nitric oxide synthase regulates key maturational events during chondrocyte terminal differentiation.

    PubMed

    Teixeira, Cristina C; Ischiropoulos, Harry; Leboy, Phoebe S; Adams, Sherrill L; Shapiro, Irving M

    2005-07-01

    The goal of this investigation was to explore the mechanism by which NOS and NO serve to regulate events linked to chondrocyte terminal differentiation. NOS isoform expression and NO adducts in chick growth cartilage were detected by immunohistochemistry and Western blot analysis. All NOS isoforms were expressed in chick growth plate chondrocytes with the highest levels present in the hypertrophic region. The enzymes were active since nitrosocysteine and nitrotyrosine residues were detected in regions of the epiphysis with the highest levels of NOS expression. Maturing chick sternal chondrocytes evidenced an increase in NO release and a rise in NOS protein levels. When treated with NOS inhibitors, there was a decrease in the alkaline phosphatase activity of the hypertrophic cells. On the other hand, NO donors caused a small but significant elevation in alkaline phosphatase activity. Transient transfections of chondrocytes with an endothelial NOS isoform caused an increase in collagen type X promoter activity. Induction of both collagen type X expression and alkaline phosphatase activity was blocked by inhibitors of the cGMP pathway. These findings indicate that NO is generated by three NOS isoforms in terminally differentiated chondrocytes. The expression of NOS and the generation of NO enhanced maturation by upregulating alkaline phosphatase and collagen type X expression. Since expression of these two determinants was blocked by inhibitors of the cGMP pathway, it is concluded that NO metabolism is required for development of the mature chondrocyte phenotype. PMID:15869914

  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. S-nitrosothiol-modified dendrimers as nitric oxide delivery vehicles.

    PubMed

    Stasko, Nathan A; Fischer, Thomas H; Schoenfisch, Mark H

    2008-03-01

    The synthesis and characterization of two generation-4 polyamidoamine (PAMAM) dendrimers with S-nitrosothiol exteriors are reported. The hyperbranched macromolecules were modified with either N-acetyl-D, L-penicillamine (NAP) or N-acetyl-L-cysteine (NACys) and analyzed via 1H and 13C NMR, UV absorption spectroscopy, MALDI-TOF mass spectrometry, and size exclusion chromatography. Treatment of the dendritic thiols with nitrite solutions yielded the corresponding S-nitrosothiol nitric oxide (NO) donors (G4-SNAP, G4-NACysNO). Chemiluminescent NO detection demonstrated that the dendrimers were capable of storing approximately 2 micromol NO x mg (-1) when exposed to triggers of S-nitrosothiol decomposition (e.g., light and copper). The kinetics of NO release were found to be highly dependent on the structure of the nitrosothiol (i.e., tertiary vs primary) and exhibited similar NO release characteristics to classical small molecule nitrosothiols reported in the literature. As a demonstration of utility, the ability of G4-SNAP to inhibit thrombin-mediated platelet aggregation was assayed. At equivalent nitrosothiol concentrations (25 microM), the G4-SNAP dendrimer resulted in a 62% inhibition of platelet aggregation, compared to only 17% for the small molecule NO donor. The multivalent NO storage, the dendritic effects exerted on nitrosothiol stability and reactivity, and the utility of dendrimers as drug delivery vehicles highlight the potential of these constructs as clinically useful S-nitrosothiol-based therapeutics. PMID:18247567

  1. Complex Inhibitory Effects of Nitric Oxide on Autophagy

    PubMed Central

    Sarkar, Sovan; Korolchuk, Viktor I.; Renna, Maurizio; Imarisio, Sara; Fleming, Angeleen; Williams, Andrea; Garcia-Arencibia, Moises; Rose, Claudia; Luo, Shouqing; Underwood, Benjamin R.; Kroemer, Guido; O'Kane, Cahir J.; Rubinsztein, David C.

    2011-01-01

    Summary Autophagy, a major degradation process for long-lived and aggregate-prone proteins, affects various human processes, such as development, immunity, cancer, and neurodegeneration. Several autophagy regulators have been identified in recent years. Here we show that nitric oxide (NO), a potent cellular messenger, inhibits autophagosome synthesis via a number of mechanisms. NO impairs autophagy by inhibiting the activity of S-nitrosylation substrates, JNK1 and IKK?. Inhibition of JNK1 by NO reduces Bcl-2 phosphorylation and increases the Bcl-2–Beclin 1 interaction, thereby disrupting hVps34/Beclin 1 complex formation. Additionally, NO inhibits IKK? and reduces AMPK phosphorylation, leading to mTORC1 activation via TSC2. Overexpression of nNOS, iNOS, or eNOS impairs autophagosome formation primarily via the JNK1–Bcl-2 pathway. Conversely, NOS inhibition enhances the clearance of autophagic substrates and reduces neurodegeneration in models of Huntington's disease. Our data suggest that nitrosative stress-mediated protein aggregation in neurodegenerative diseases may be, in part, due to autophagy inhibition. PMID:21726807

  2. Nitric oxide enhances Th9 cell differentiation and airway inflammation

    PubMed Central

    Niedbala, Wanda; Besnard, Anne-Gaelle; Nascimento, Daniele Carvalho; Donate, Paula Barbim; Sonego, Fabiane; Yip, Edwin; Guabiraba, Rodrigo; Chang, Hyun-Dong; Fukada, Sandra Y.; Salmond, Robert J.; Schmitt, Edgar; Bopp, Tobias; Ryffel, Bernhard; Liew, Foo Y.

    2014-01-01

    Th9 cells protect hosts against helminthic infection but also mediate allergic disease. Here we show that nitric oxide (NO) promotes Th9 cell polarization of murine and human CD4+ T cells. NO de-represses the tumor suppressor gene p53 via nitrosylation of Mdm2. NO also increases p53-mediated IL-2 production, STAT5 phosphorylation and IRF4 expression, all essential for Th9 polarization. NO also increases the expression of TGF?R and IL-4R, pivotal to Th9 polarization. OVA-sensitized mice treated with an NO donor developed more severe airway inflammation. Transferred Th9 cells induced airway inflammation, which was exacerbated by NO and blocked by anti-IL-9 antibody. Nos2?/? mice had less Th9 cells and developed attenuated eosinophilia during OVA-induced airway inflammation compared to wild-type mice. Our data demonstrate that NO is an important endogenous inducer of Th9 cells and provide a hitherto unrecognized mechanism for NO-mediated airway inflammation via the expansion of Th9 cells. PMID:25099390

  3. 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

  4. S-Nitrosothiol-Modified Dendrimers as Nitric Oxide Delivery Vehicles

    PubMed Central

    Stasko, Nathan A.; Fischer, Thomas H.

    2013-01-01

    The synthesis and characterization of two generation-4 polyamidoamine (PAMAM) dendrimers with S-nitrosothiol exteriors are reported. The hyperbranched macromolecules were modified with either N-acetyl-D,L-penicillamine (NAP) or N-acetyl-L-cysteine (NACys) and analyzed via 1H and 13C-NMR, UV absorption spectroscopy, MALDI-TOF mass spectrometry, and size exclusion chromatography. Treatment of the dendritic thiols with nitrite solutions yielded the corresponding S-nitrosothiol nitric oxide (NO) donors (G4-SNAP, G4-NACysNO). Chemiluminescent NO detection demonstrated that the dendrimers were capable of storing ~2 ?mol NO·mg?1 when exposed to triggers of S-nitrosothiol decomposition (e.g., light and copper). The kinetics of NO-release were found to be highly dependent on the structure of the nitrosothiol (i.e., tertiary vs. primary) and exhibited similar NO-release characteristics to classical small molecule nitrosothiols reported in the literature. As demonstration of utility, the ability of G4-SNAP to inhibit thrombin-mediated platelet aggregation was assayed. At equivalent nitrosothiol concentrations (25 ?M), the G4-SNAP dendrimer resulted in a 62% inhibition of platelet aggregation, compared to only 17% for the small molecule NO donor. The multivalent NO storage, the dendritic effects exerted on nitrosothiol stability and reactivity, and the utility of dendrimers as drug delivery vehicles highlight the potential of these constructs as clinically useful S-nitrosothiol-based therapeutics. PMID:18247567

  5. Nasal nitric oxide is reduced in patients with HIV.

    PubMed

    Palm, J; Lidman, C; Graf, P; Alving, K; Lundberg, J

    2000-03-01

    The gas nitric oxide (NO) is present in high concentrations in human nasal airways. Since NO is known to inhibit the growth of bacteria and viruses, it has been suggested that airborne NO represents the first line of defence against pathogens in the upper airways. Low nasal NO levels have been reported previously in patients susceptible to upper airway infection. Since HIV-positive patients are at risk for respiratory tract infections, including sinusitis, we studied the levels of NO in the upper and lower airways of these patients. A cross-sectional study with age-matched HIV patients and controls was carried out. Nasal and orally exhaled NO were measured in 31 HIV patients and 26 controls using a well-established chemiluminescence method developed for measurements of gaseous NO in the airways. Nasal NO was 21%, lower (p < 0.05, Student's t-test) in HIV patients than in controls, whereas orally exhaled NO did not differ between the two groups. We conclude that nasal NO is reduced in patients with HIV infection. The reduction in nasal NO may contribute to the decreased resistance to airway infections in these patients. PMID:10894420

  6. Hydrogen sulfide and nitric oxide interactions in inflammation.

    PubMed

    Lo Faro, Maria Letizia; Fox, Bridget; Whatmore, Jacqueline L; Winyard, Paul G; Whiteman, Matthew

    2014-09-15

    Together with carbon monoxide (CO), nitric oxide (NO) and hydrogen sulfide (H2S) form a group of physiologically important gaseous transmitters, sometimes referred to as the "gaseous triumvirate". The three molecules share a wide range of physical and physiological properties: they are small gaseous molecules, able to freely penetrate cellular membranes; they are all produced endogenously in the body and they seem to exert similar biological functions. In the cardiovascular system, for example, they are all vasodilators, promote angiogenesis and protect tissues against damage (e.g. ischemia-reperfusion injury). In addition, they have complex roles in inflammation, with both pro- and anti-inflammatory effects reported. Researchers have focused their efforts in understanding and describing the roles of each of these molecules in different physiological systems, and in the past years attention has also been given to the gases interaction or "cross-talk". This review will focus on the role of NO and H2S in inflammation and will give an overview of the evidence collected so far suggesting the importance of their cross-talk in inflammatory processes. PMID:24929214

  7. Concomitant production of nitric oxide and superoxide in human macrophages.

    PubMed

    Juliet, Packiasamy A R; Hayashi, Toshio; Iguchi, Akihisa; Ignarro, Louis J

    2003-10-17

    Many harmful effects of nitric oxide are caused by the reaction of NO with superoxide anion. The present study was carried out to find out the concomitant production of superoxide and to investigate a suitable inhibitor of NO, which is produced by iNOS. THP-1 cells were differentiated into macrophages by PMA and cytokine. Addition of L-NAME showed decrement in superoxide production. Addition of apocynin, aminoguanidine or ONO 1714 brought about a significant reduction in superoxide production. The expressions of p67 and p47(phox) were reduced by the addition of apocynin, aminoguanidine or ONO 1714 whereas xanthine oxidase and cyclooxygenase did not have a major role in superoxide production. The results of the present study show that iNOS and NADPH oxidase play an important role in superoxide release. It suggests that addition of iNOS inhibitor together with apocynin may be more effective in case of therapeutic application in disease conditions like atherosclerosis. PMID:14521919

  8. Variation of nitric oxide concentration before the Kobe earthquake, Japan

    NASA Astrophysics Data System (ADS)

    Matsuda, Tokiyoshi; Ikeya, Motoji

    The variation and spatial distribution of the atmospheric concentration of nitric oxide (NO) near the epicenter of the Kobe earthquake at local time 5:46, 17 January 1995 have been studied using data at monitoring stations of the local environmental protection agencies. The concentration of NO 8 days before the earthquake was 199 ppb, about ten times larger than the average peak level of 19 ppb, accompanying the retrospectively reported precursory earthquake lightning, increase of radon concentration in well water and of the counts of electromagnetic (EM) signals. The reported thunderstorm over the Japan Sea about 150 km away was too far for the thunder-generated NO to reach the epicenter area. The concentration of NO was also found to have increased before other major earthquakes (Magnitude>5.0) in Japan. Atmospheric discharges by electric charges or EM waves before earthquakes may have generated NO. However, the generation of NO by human activities of fuel combustion soon after holidays is enormously high every year, which makes it difficult to clearly link the increase with the earthquakes. The increase soon after the earthquake due to traffic jams is clear. The concentration of NO should be monitored at a several sites away from human activities as background data of natural variation and to study its generation at a seismic area before a large earthquake.

  9. Regulation of nitric oxide consumption by hypoxic red blood cells.

    PubMed

    Han, Tae H; Qamirani, Erion; Nelson, Allyson G; Hyduke, Daniel R; Chaudhuri, Gautam; Kuo, Lih; Liao, James C

    2003-10-14

    The homeostasis of nitric oxide (NO) is attained through a balance between its production and consumption. Shifts in NO bioavailability have been linked to a variety of diseases. Although the regulation of NO production has been well documented, its consumption is largely thought to be unregulated. Here, we have demonstrated that under hypoxic conditions, NO accelerates its own consumption by increasing its entry into RBCs. When RBCs were exposed to NO (1:400 NO/heme ratio) under hypoxic conditions to form HbFe(II)NO, the consumption rate of NO increased significantly. This increase in NO consumption converted the bioactivity of serotonin from a vasodilator to a vasoconstrictor in isolated coronary arterioles. We identified HbFe(II)NO as a potential mediator of accelerated NO consumption. Accelerated NO consumption by HbFe(II)NO-bearing RBCs may contribute to hypoxic pulmonary vasoconstriction and the rebound effect seen on termination of NO inhalation therapy. Furthermore, accelerated NO consumption may exacerbate ischemia-mediated vasospasm and nitrate tolerance. Finally, this phenomenon may be an evolved mechanism to stabilize the vasculature in sepsis. PMID:14523233

  10. 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 ?mol 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

  11. Gastrointestinal bacteria generate nitric oxide from nitrate and nitrite.

    PubMed

    Sobko, T; Reinders, C I; Jansson, E; Norin, E; Midtvedt, T; Lundberg, J O

    2005-12-01

    Denitrifying bacteria in soil generate nitric oxide (NO) from nitrite as a part of the nitrogen cycle, but little is known about NO production by commensal bacteria. We used a chemiluminescence assay to explore if human faeces and different representative gut bacteria are able to generate NO. Bacteria were incubated anaerobically in gas-tight bags, with or without nitrate or nitrite in the growth medium. In addition, luminal NO levels were measured in vivo in the intestines in germ-free and conventional rats, and in rats mono-associated with lactobacilli. We show that human faeces can generate NO after nitrate or nitrite supplementation. Lactobacilli and bifidobacteria generated much NO from nitrite, but only a few of the tested strains produced NO from nitrate and at much lower levels. In contrast, Escherichia coli, Bacteroides thetaiotaomicron, and Clostridium difficile did not produce significant amounts of NO either with nitrate or nitrite. NO generation in the gut lumen was also observed in vivo in conventional rats but not in germ-free rats or in rats mono-associated with lactobacilli. We conclude that NO can be generated by the anaerobic gut flora in the presence of nitrate or nitrite. Future studies will reveal its biological significance in regulation of gastrointestinal integrity. PMID:16183308

  12. Neurovascular protection by ischaemic tolerance: role of nitric oxide

    PubMed Central

    Iadecola, Costantino; Kahles, Timo; Gallo, Eduardo F; Anrather, Josef

    2011-01-01

    Abstract Nitric oxide (NO) has emerged as a key mediator in the mechanisms of ischaemic tolerance induced by a wide variety of preconditioning stimuli. NO is involved in the brain protection that develops either early (minutes–hours) or late (days–weeks) after the preconditioning stimulus. However, the sources of NO and the mechanisms underlying the protective effects differ substantially. While in early preconditioning NO is produced by the endothelial and neuronal isoform of NO synthase, in delayed preconditioning NO is synthesized by the inducible or ‘immunological’ isoform of NO synthase. Furthermore, in early preconditioning, NO acts through the canonical cGMP pathway, possibly through protein kinase G and opening of mitochondrial KATP channels. In late preconditioning, the protection is mediated by peroxynitrite formed by the reaction of NO with superoxide derived from the enzyme NADPH oxidase. The mechanisms by which peroxynitrite exerts its protective effect may include improvement of post-ischaemic cerebrovascular function, leading to enhancement of blood flow to the ischaemic territory, and expression of prosurvival genes resulting in cytoprotection. The evidence suggests that NO can engage highly effective and multifunctional prosurvival pathways, which could be exploited for the prevention and treatment of cerebrovascular pathologies. PMID:21746790

  13. Nitric oxide synthase in hypoxic or ischemic brain injury.

    PubMed

    Liu, Haiting; Li, Jiao; Zhao, Fengyan; Wang, Huiqing; Qu, Yi; Mu, Dezhi

    2015-01-01

    Abstract Hypoxic or ischemic stress causes many serious brain injuries, including stroke and neonatal hypoxia ischemia encephalopathy. During brain hypoxia ischemia processes, nitric oxide (NO) may play either a neurotoxic or a neuroprotective role, depending upon factors such as the NO synthase (NOS) isoform, the cell type by which NO is produced, and the temporal stage after the onset of the hypoxic ischemic brain injury. Excessive NO production can be neurotoxic, leading to cascade reactions of excitotoxicity, inflammation, apoptosis, and deteriorating primary brain injury. In contrast, NO produced by endothelial NOS plays a neuroprotective role by maintaining cerebral blood flow and preventing neuronal injury, as well as inhibiting platelet and leukocyte adhesion. Sometimes, NO-derived inducible NOS and neuronal NOS in special areas may also play neuroprotective roles. Therefore, this review summarizes the different roles and the regulation of the three NOS isoforms in hypoxic or ischemic brain injury as revealed in research in recent years, focusing on the neurotoxic role of the three NOS isoforms involved in mechanisms of hypoxic or ischemic brain injury. PMID:25720056

  14. 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 ?GB?C = 1.7–2.0 kcal/mol. The reverse barrier is ?GB?C = 0.7 kcal/mol, which agrees well with the experimental value of 0.7 kcal/mol, estimated from kinetic data.

  15. 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

  16. Regulation of Inducible Nitric Oxide Synthase Gene in Glial Cells

    PubMed Central

    Saha, Ramendra N.; Pahan, Kalipada

    2007-01-01

    Elevated levels of NO produced within the central nervous system (CNS) are associated with the pathogenesis of neuroinflammatory and neurodegenerative human diseases such as multiple sclerosis, HIV dementia, brain ischemia, trauma, Parkinson's disease, and Alzheimer's disease. Resident glial cells in the CNS (astroglia and microglia) express inducible nitric oxide synthase (iNOS) and produce high levels of NO in response to a wide variety of proinflammatory and degenerative stimuli. Although pathways resulting in the expression of iNOS may vary in two different glial cells of different species, the intracellular signaling events required for the expression of iNOS in these cells are slowly becoming clear. Various signaling cascades converge to activate several transcription factors that control the transcription of iNOS in glial cells. The present review summarizes different results and discusses current understandings about signaling mechanisms for the induction of iNOS expression in activated glial cells. A complete understanding of the regulation of iNOS expression in glial cells is expected to identify novel targets for therapeutic intervention in NO-mediated neurological disorders. PMID:16771683

  17. Role of nitric oxide on purinergic signalling in the cochlea

    PubMed Central

    2010-01-01

    In the inner ear, there is considerable evidence that extracellular adenosine 5?-triphosphate (ATP) plays an important role in auditory neurotransmission as a neurotransmitter or a neuromodulator, although the potential role of adenosine signalling in the modulation of auditory neurotransmission has also been reported. The activation of ligand-gated ionotropic P2X receptors and G protein-coupled metabotropic P2Y receptors has been reported to induce an increase of intracellular Ca2+ concentration ([Ca2+]i) in inner hair cells (IHCs), outer hair cells (OHCs), spiral ganglion neurons (SGNs), and supporting cells in the cochlea. ATP may participate in auditory neurotransmission by modulating [Ca2+]i in the cochlear cells. Recent studies showed that extracellular ATP induced nitric oxide (NO) production in IHCs, OHCs, and SGNs, which affects the ATP-induced Ca2+ response via the NO-cGMP-PKG pathway in those cells by a feedback mechanism. A cross-talk between NO and ATP may therefore exist in the auditory signal transduction. In the present article, I review the role of NO on the ATP-induced Ca2+ signalling in IHCs and OHCs. I also consider the possible role of NO in the ATP-induced Ca2+ signalling in SGNs and supporting cells. PMID:20806013

  18. Reduction in Basal Nitric Oxide Activity Causes Albuminuria

    PubMed Central

    Ott, Christian; Schneider, Markus P.; Delles, Christian; Schlaich, Markus P.; Schmieder, Roland E.

    2011-01-01

    OBJECTIVE The barrier function of the glomerular filter has been studied for decades. Albuminuria reflects a malfunction of this barrier, and in animals dysfunctional endothelial nitric-oxide (NO) synthase results in albuminuria. We aimed to analyze the importance of NO for the glomerular barrier function in humans. RESEARCH DESIGN AND METHODS To assess the effect of endothelial dysfunction on albuminuria, we measured the urine albumin-to-creatinine ratio (UACR) both before and after the blockade of NO synthases (NOSs) with systemic infusion of NG-monomethyl-l-arginine (l-NMMA) in two distinct study populations. In population A, 62 hypertensive patients with type 2 diabetes and, in population B, 22 patients with hypercholesterolemia but without hypertension or type 2 diabetes were examined. All subjects had normal renal function. RESULTS There was a significant increase in the UACR in response to NOS inhibition with l-NMMA in hypertensive patients with type 2 diabetes (study population A) and in patients with hypercholesterolemia (study population B). Linear regression analyses revealed that the change in mean arterial presssure in response to l-NMMA was not related to the increase in the UACR in response to l-NMMA in either population, even after adjusting for filtration fraction. CONCLUSIONS NOS inhibition provokes albuminuria that is unrelated to changes in blood pressure. It is noteworthy that this finding was evident in patient groups prone to endothelial dysfunction and albuminuria. Thus, acute deterioration of endothelial function by reducing NO activity causes an increase in albuminuria. PMID:21270268

  19. Nitric oxide release from polydimethylsiloxane-based polyurethanes.

    PubMed

    Nguyen, Evelyne B; Zilla, Peter; Bezuidenhout, Deon

    2014-01-01

    Localized nitric oxide (NO) release from polymeric materials holds much promise for the prevention of coagulation often associated with implantable and extracorporeal blood-contacting devices. Films of polyurethane (PU) containing incorporated polyethyleneimine were thus exposed to NO gas to form diazeniumdiolates (NONOates) in situ. Donor incorporation and NO gas exposure did not affect the mechanical properties of the films. The NO release capacity increased with increasing polydimethylsiloxane (PDMS) content in the soft segment of the PU: total capacity could be more than doubled (P<0.05) from 0.093 ± 0.028 to 0.225 ± 0.004 mmol/g when the PDMS content was increased from 0 to 100%. Release kinetics were best approximated using a modified Korsemeyer-Peppas power law (R2=0.95-0.99). Despite the resultant rapid initial decrease in NO release rates, values above that observed for quiescent endothelial cells (0.83 pmol·cm(-2)·s(-1)) were maintained for extended periods of 5-10 days, while rates above that of a stimulated endothelium (2.7-6.8 pmol·cm(-2)·s(-1)) were achieved for the first 24 hours. This method of NONOate formation may be advantageous, as potential premature NO release by exposure of diazeniumdiolated donors during incorporation, processing and storage, can be avoided by in situ diazoniumdiolation closer to the time of implantation. PMID:24744231

  20. On the radiative coupling between mesospheric and thermospheric nitric oxide

    NASA Astrophysics Data System (ADS)

    Siskind, David E.

    1994-11-01

    A photochemical model of nitric oxide from 40 to 250 km has been used to study the distribution of NO in the mesosphere and lower thermosphere. The model includes a parameterization of NO photolysis that can account for the opacity of a varying thermospheric NO layer. This model is used to test the suggestion that increases in thermospheric NO which increase this opacity 'shield' NO at lower altitudes by decreasing the photolytic destruction rate. The model was 'tuned' to reproduce two recent observations of thermospheric NO, the high latitude rocket experiment of Eparvier and Barth (1992) and the midlatitude ground-based microwave experiment of Clancy et al. (1992). In the first case, the model indicated that the large thermospheric NO layer could have caused significant shielding and up to a factor of 2 effect on the mesospheric NO is seen. On the other hand, for the midlatitude observation the NO optical pathlength was too small to be significant. A time dependent version of the model was used to study the response of mesospheric NO to auroral energy input during winter. Under conditions which combine rapid transport and NO self-shielding, the model suggests that NO density increases could propagate into the upper stratosphere.

  1. 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.

  2. Nitric oxide inhibition of soot oxidation by oxygen atoms at 298/sup 0/Ktiation

    SciTech Connect

    Wicke, B.G.; Grady, K.A.

    1987-01-01

    Nitric oxide is observed to inhibit the rate of soot oxidation by oxygen atoms at 298 K. Small amounts of added NO reduce the rates of production of CO/sub 2/ and CO by up to 35%. The authors show experimentally that NO is not reducing the gas phase O atom concentration. Thermal description mass spectrometry is used to measure the small adsorption of NO on the soot; this NO adsorption corresponds to 1.5% of the carbon atoms on the surface of the individual soot spheres. This inhibition is interpreted in terms of a relatively small number of reactive sites on the soot at which soot gasification occurs and which are effectively blocked by NO. When considered together with our previously reported work on oxidation of soot by oxygen atoms at 298 K, these results allow a partial mechanism to be formulated for this soot oxidation process.

  3. Differential distribution of nicotinamide adenine dinucleotide phosphate-diaphorase and neural nitric oxide synthase in the rat choroid plexus. A histochemical and immunocytochemical study

    Microsoft Academic Search

    G. Sancesario; A. Reiner; G. Figueredo-Cardenas; M. Morello; G. Bernardi

    1996-01-01

    This study used NADPH diaphorase (NADPHd) histochemistry and neuronal nitric oxide synthase immunocytochemistry to examine the localization of nitric oxide synthase in the choroid plexus of the lateral ventricles and the fourth ventricle of rat brain. That the NADPHd reaction product in choroid plexus was specific to nitric oxide synthase was evaluated: (i) by comparison to immunocytochemical labelling for nitric

  4. 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

  5. Nitric oxide is a signal for NNR-mediated transcription activation in Paracoccus denitrificans.

    PubMed

    Van Spanning, R J; Houben, E; Reijnders, W N; Spiro, S; Westerhoff, H V; Saunders, N

    1999-07-01

    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

  6. Involvement of nitric oxide in biofilm dispersal of Pseudomonas aeruginosa.

    PubMed

    Barraud, Nicolas; Hassett, Daniel J; Hwang, Sung-Hei; Rice, Scott A; Kjelleberg, Staffan; Webb, Jeremy S

    2006-11-01

    Bacterial biofilms at times undergo regulated and coordinated dispersal events where sessile biofilm cells convert to free-swimming, planktonic bacteria. In the opportunistic pathogen Pseudomonas aeruginosa, we previously observed that dispersal occurs concurrently with three interrelated processes within mature biofilms: (i) production of oxidative or nitrosative stress-inducing molecules inside biofilm structures, (ii) bacteriophage induction, and (iii) cell lysis. Here we examine whether specific reactive oxygen or nitrogen intermediates play a role in cell dispersal from P. aeruginosa biofilms. We demonstrate the involvement of anaerobic respiration processes in P. aeruginosa biofilm dispersal and show that nitric oxide (NO), used widely as a signaling molecule in biological systems, causes dispersal of P. aeruginosa biofilm bacteria. Dispersal was induced with low, sublethal concentrations (25 to 500 nM) of the NO donor sodium nitroprusside (SNP). Moreover, a P. aeruginosa mutant lacking the only enzyme capable of generating metabolic NO through anaerobic respiration (nitrite reductase, DeltanirS) did not disperse, whereas a NO reductase mutant (DeltanorCB) exhibited greatly enhanced dispersal. Strategies to induce biofilm dispersal are of interest due to their potential to prevent biofilms and biofilm-related infections. We observed that exposure to SNP (500 nM) greatly enhanced the efficacy of antimicrobial compounds (tobramycin, hydrogen peroxide, and sodium dodecyl sulfate) in the removal of established P. aeruginosa biofilms from a glass surface. Combined exposure to both NO and antimicrobial agents may therefore offer a novel strategy to control preestablished, persistent P. aeruginosa biofilms and biofilm-related infections. PMID:17050922

  7. 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.

  8. 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.

  9. Nitric oxide metabolites induced in Anopheles stephensi control malaria parasite infection

    PubMed Central

    Peterson, Tina M.L.; Gow, Andrew J.; Luckhart, Shirley

    2007-01-01

    Malaria parasite infection in anopheline mosquitoes is limited by inflammatory levels of nitric oxide metabolites. To assess the mechanisms of parasite stasis or toxicity, we investigated the biochemistry of these metabolites within the blood-filled mosquito midgut. Our data indicate that nitrates, but not nitrites, are elevated in the Plasmodium-infected midgut. Although levels of S-nitrosothiols do not change with infection, blood proteins are S-nitrosylated after ingestion by the mosquito. In addition, photolyzable nitric oxide, which can be attributed to metal nitrosyls, is elevated following infection and, based on the abundance of hemoglobin, likely includes heme iron nitrosyl. The persistance of oxyhemoglobin throughout blood digestion and changes in hemoglobin conformation in response to infection suggest that hemoglobin catalyzes the synthesis of nitric oxide metabolites in a reducing environment. Provision of urate, a potent reductant and scavenger of oxidants and nitrating agents, as a dietary supplement to mosquitoes increased parasite infection levels relative to allantoin-fed controls, suggesting that nitrosative and/or oxidative stresses negatively impact developing parasites. Collectively, our results reveal a unique role for nitric oxide in an oxyhemoglobin-rich environment. In contrast to facilitating oxygen delivery by hemoglobin in the mammalian vasculature, nitric oxide synthesis in the blood-filled mosquito midgut drives the formation of toxic metabolites that limit parasite development. PMID:17157200

  10. Open randomised controlled trial of inhaled nitric oxide and early dexamethasone in high risk preterm infants

    PubMed Central

    Subhedar, N; Ryan, S; Shaw, N

    1997-01-01

    AIM—To determine whether treatment with inhaled nitric oxide (NO) and/or dexamethasone reduces the incidence of chronic lung disease (CLD) and/or death in high risk preterm infants.?METHODS—Infants below 32 weeks of gestation were recruited at 96 hours of age if they were deemed to be at high risk of developing CLD. Infants were randomly assigned to one of four treatment groups using a factorial design: (1) 5-20 parts per million inhaled NO for 72 hours; (2) 0.5-1 mg/kg/day intravenous dexamethasone for 6 days; (3) both drugs together; (4) continued conventional management.?RESULTS—Forty two infants were randomised: 10 infants received inhaled NO alone; 11 dexamethasone alone; 10 both treatments; and 11 neither treatment. There was no difference in the combined incidence of CLD and/or death before discharge from hospital between either infants treated with inhaled NO and controls (RR 1.05, 95% CI 0.84-1.25), or those treated with dexamethasone and controls (RR 0.95, 95% CI 0.79-1.18).?CONCLUSIONS—At 96 hours of age, neither treatment with inhaled NO nor dexamethasone prevented CLD or death.?? Keywords: randomised controlled trial; nitric oxide; dexamethasone; chronic lung disease PMID:9462187

  11. Synaptic inputs onto spiking local interneurons in crayfish are depressed by nitric oxide.

    PubMed

    Aonuma, Hitoshi; Newland, Philip L

    2002-08-01

    We have analyzed the action of nitric oxide on the synaptic inputs of spiking local interneurons that form part of the local circuits in the terminal abdominal ganglion of the crayfish, Pacifastacus leniusculus. Increasing the availability of NO in the ganglion by bath applying the NO donor SNAP, or the substrate for its synthesis, L-arginine, caused a depression of synaptic inputs onto the interneurons evoked by electrically stimulating mechanosensory neurons in nerve 2 of the terminal ganglion. Conversely, reducing the availability of NO by bath application of an NO scavenger, PTIO, and an inhibitor of nitric oxide synthase, L-NAME, increased the amplitude of the evoked potentials. These results suggest that elevated NO concentration causes a depression of the synaptic inputs to spiking local interneurons. To determine whether these effects could be mediated through an NO/cGMP signaling pathway we bath applied a membrane permeable analogue of cGMP, 8-br-cGMP, which decreased the amplitude of the inputs to the interneurons. Bath application of an inhibitor of soluble guanlylyl cyclase, ODQ, produced an increase in the amplitude of the synaptic inputs. Our results suggest that NO causes a depression of synaptic inputs to spiking local interneurons probably by acting through an NO/cGMP signaling pathway. Moreover, application of NO scavengers modulates the inputs to these interneurons, suggesting that NO is continuously providing a powerful and dynamic means of modulating the outputs of local circuits. PMID:12124752

  12. Efficacy of surface-generated nitric oxide against Candida albicans adhesion and biofilm formation.

    PubMed

    Privett, Benjamin J; Nutz, Steven T; Schoenfisch, Mark H

    2010-11-01

    This report details the efficacy of nitric oxide (NO)-releasing xerogel surfaces composed of N-(6-aminohexyl)aminopropyl trimethoxysilane (AHAP3) and isobutyltrimethoxysilane (BTMOS) against Candida albicans adhesion, viability, and biofilm formation. A parallel plate flow cell assay was used to examine the effect of NO on planktonic fungal cells. Nitric oxide fluxes as low as 14 pmol cm(-2) s(-1) were sufficient to reduce fungal adhesion by ?49% over the controls after 90 min. By utilizing a fluorescence live/dead assay and replicate plating, NO flux was determined to reduce fungal viability in a dose-dependent manner. The formation of C. albicans biofilms on NO-releasing xerogel-coated silicon rubber (SiR) coupons was impeded when compared to control (non-NO-releasing) and bare SiR surfaces. The synergistic efficacy of NO and silver sulfadiazine against adhered fungal cells and biofilms is reported with increased killing and biofilm inhibition over NO alone. PMID:21082455

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

    PubMed Central

    Gamba, Juliana; Gamba, Luana T.; Rodrigues, Gabriela S.; Kiyomoto, Beatriz H.; Moraes, Carlos T.; Tengan, Celia H.

    2013-01-01

    Nitric oxide (NO) is a free radical and a signaling molecule in several pathways, produced by nitric oxide synthase (NOS) from the conversion of l-arginine to citrulline. Supplementation of l-arginine has been used to treat MELAS (mitochondrial encephalopathy with lactic acidosis and stroke like syndrome), a mitochondrial disease caused by the m.3243A>G mutation. Low levels of serum arginine and endothelium dysfunction have been reported in MELAS and this treatment may increase NO in endothelial cells and promote vasodilation, decreasing cerebral ischemia and strokes. Although clinical benefits have been reported, little is known about NO synthesis in MELAS. In this study we found that osteosarcoma derived cybrid cells with high levels of m.3243A>G had increased nitrite, an NO metabolite, and increased intracellular NO, demonstrated by an NO fluorescent probe (DAF-FM). Muscle vessels from patients with the same mutation had increased staining in NADPH diaphorase, suggestive of increased NOS. These results indicate increased production of NO in cells harboring the m.3243A>G, however no nitrated protein was detected by Western blotting. Further studies are necessary to clarify the exact mechanisms of l-arginine effect to determine the appropriate clinical use of this drug therapy. PMID:23263669

  14. Site of pulmonary vasodilation by inhaled nitric oxide in the perfused lung

    SciTech Connect

    Rimar, S.; Gillis, C.N. [Yale Univ. School of Medicine, New Haven, CT (United States)

    1995-05-01

    Site of pulmonary vasodilation by inhaled nitric oxide in the perfused lung. To determine the site of inhaled nitric oxide (NO)-induced pulmonary vasodilation, a double vascular occlusion technique was used with rabbit lungs ventilated and perfused at 20 ml/min with Krebs solution containing 3% dextran and 30 {mu}M indomethacin. Inhaled NO (120 ppm for 3% min) reduced pulmonary vasoconstriction produced by U-46619 infusion (0.5 -1.2 nmol/min), significantly decreasing total resistance (RT) [1,080 {plus_minus} 51 (SE) vs. 1,545 {plus_minus} 109 mmHg-min/l; P < 0.01]. Acetylcholine infusion (ACh; 2-5 nmol/min) and nitroglycerin (NTG; 0.35 {mu}mol) likewise decreased RT. Arterial resistance (Ra) was also significantly less with inhaled NO, ACh, and NTG compared with U-46619 alone. Venous resistance (Rv), however, was unchanged. When the direction of perfusion was reversed in the lung, inhaled NO, ACh, and NTG significantly decreased RT compared with U-46619 alone, and Rv was also reduced by all three agents. After electrolysis-induced acute lung injury, inhaled NO significantly reduced both RT and Ra compared with U-46619 alone, whereas Rv was unaffected. Our results demonstrate that inhaled NO gas affects primarily the arterial (precapillary) component of the pulmonary circulation but, under conditions of extreme venous constriction, may dilate the postcapillary component as well. 25 refs., 4 figs.

  15. Evidence for nitric oxide acting as a luteolytic factor in the human corpus luteum.

    PubMed

    Fridén, B E; Runesson, E; Hahlin, M; Brännström, M

    2000-05-01

    The aims of the present study were to characterize the expression and cellular localization of isoforms of nitric oxide synthase (NOS) in the human corpus luteum (CL) and to determine the effects of nitric oxide (NO) on CL steroidogenesis. Immunoblotting analyses revealed that endothelial NOS (eNOS) is the most abundant isoform in human CL with highest values during the late luteal phase. Immunoreactive eNOS was localized predominantely in the theca lutein layer, being particularly abundant in endothelial cells, but with positive staining also in some steroidogenic cells. Immunoreactive inducible NOS (iNOS) was also detected, but to lesser degree, and did not display apparent phase-specific changes. The effect of NO on CL steroid synthesis was examined using human chorionic gonadotrophin (HCG)-stimulated dispersed CL cells cultured in vitro. Progesterone production was significantly decreased (P < 0.05) by the NO donor spermine NONOate (10(-5) mol/l) in cells of the late, but not mid-, luteal phase. To investigate a potential link between NO and the local prostaglandins (PG), concentrations of PGF(2alpha) and PGE(2) were measured in culture medium. NO significantly increased (P < 0.05) concentrations of both PGF(2alpha) and PGE(2) during the late luteal phase. It is concluded that NO may be luteolytic in the human CL of menstruation. PMID:10775642

  16. Borna disease virus P protein inhibits nitric oxide synthase gene expression in astrocytes

    SciTech Connect

    Peng Guiqing [State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072 (China); Zhang Fengmin [College of Basic Medical Science, Harbin Medical University, Harbin 150081 (China); Zhang Qi; Wu Kailang; Zhu Fan [State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072 (China); Wu Jianguo [State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072 (China)], E-mail: jwu@edu.edu.cn

    2007-09-30

    Borna disease virus (BDV) is one of the potential infectious agents involved in the development of central nervous system (CNS) diseases. Neurons and astrocytes are the main targets of BDV infection, but little is known about the roles of BDV infection in the biological effects of astrocytes. Here we reported that BDV inhibits the activation of inducible nitric oxide synthase (iNOS) in murine astrocytes induced by bacterial LPS and PMA. To determine which protein of BDV is responsible for the regulation of iNOS expression, we co-transfected murine astrocytes with reporter plasmid iNOS-luciferase and plasmid expressing individual BDV proteins. Results from analyses of reporter activities revealed that only the phosphoprotein (P) of BDV had an inhibitory effect on the activation of iNOS. In addition, P protein inhibits nitric oxide production through regulating iNOS expression. We also reported that the nuclear factor kappa B (NF-{kappa}B) binding element, AP-1 recognition site, and interferon-stimulated response element (ISRE) on the iNOS promoter were involved in the repression of iNOS gene expression regulated by the P protein. Functional analysis indicated that sequences from amino acids 134 to 174 of the P protein are necessary for the regulation of iNOS. These data suggested that BDV may suppress signal transduction pathways, which resulted in the inhibition of iNOS activation in astrocytes.

  17. Endothelial-constitutive nitric oxide synthase exists in airways and diesel exhaust particles inhibit the effect of nitric oxide

    SciTech Connect

    Muto, Emiko; Hayashi, Toshio; Yamada, Kazuyoshi [Nagoya Univ. School of Medicine (Japan)] [and others] [Nagoya Univ. School of Medicine (Japan); and others

    1996-12-31

    Diesel exhaust particles (DEP) are an important cause of air pollution and are thought to be responsible for some respiratory ailments, but the exact mechanism is not known. We evaluated whether DEP inhibit nitric oxide (NO) synthesis in bronchi as No is present in the exhaled air and has a physiological role in the respiratory tract. Aortic rings were also examined for comparison. We observed that acetylcholine (ACh) induced contraction of the bronchi was partially attenuated by the simultaneous release of NO. When bronchial rings were incubated either with N{sup G}-methyl-L-arginine (L-NMA): an inhibitor of NO synthase (NOS) or with DEP, the contraction to ACh was abolished. The source of the NOS was the bronchial epithelium and this endothelial-constitutive NOS was demonstrated by immunohistochemistry. DEP like L-NMA inhibited the ACh induced endothelium dependent relaxation in the aortic rings. The inhibition of NO release by DEP and L-NMA from bronchial and aortic rings was also confirmed by a selective NO electrode. We conclude that inhibition of NO availability by DEP may in part be responsible for the adverse respiratory effects seen by inhalation of these particles in polluted air. 27 refs., 6 figs.

  18. Nitric oxide-independent vasodilator rescues heme-oxidized soluble guanylate cyclase from proteasomal degradation.

    PubMed

    Meurer, Sabine; Pioch, Sylke; Pabst, Tatjana; Opitz, Nils; Schmidt, Peter M; Beckhaus, Tobias; Wagner, Kristina; Matt, Simone; Gegenbauer, Kristina; Geschka, Sandra; Karas, Michael; Stasch, Johannes-Peter; Schmidt, Harald H H W; Müller-Esterl, Werner

    2009-07-01

    Nitric oxide (NO) is an essential vasodilator. In vascular diseases, oxidative stress attenuates NO signaling by both chemical scavenging of free NO and oxidation and downregulation of its major intracellular receptor, the alphabeta heterodimeric heme-containing soluble guanylate cyclase (sGC). Oxidation can also induce loss of the heme of sGC, as well as the responsiveness of sGC to NO. sGC activators such as BAY 58-2667 bind to oxidized/heme-free sGC and reactivate the enzyme to exert disease-specific vasodilation. Here, we show that oxidation-induced downregulation of sGC protein extends to isolated blood vessels. Mechanistically, degradation was triggered through sGC ubiquitination and proteasomal degradation. The heme-binding site ligand BAY 58-2667 prevented sGC ubiquitination and stabilized both alpha and beta subunits. Collectively, our data establish oxidation-ubiquitination of sGC as a modulator of NO/cGMP signaling and point to a new mechanism of action for sGC activating vasodilators by stabilizing their receptor, oxidized/heme-free sGC. PMID:19478201

  19. Nitric oxide synthase inhibitors and nitric oxide donors modulate the biosynthesis of thaxtomin A, a nitrated phytotoxin produced by Streptomyces spp

    Microsoft Academic Search

    Michael J. Wach; Johan A. Kers; Stuart B. Krasnoff; Rosemary Loria; Donna M. Gibson

    2005-01-01

    Evidence for the involvement of a bacterial nitric oxide synthase (NOS) in the biosynthesis of a phytotoxin is presented. Several species of Streptomyces bacteria produce secondary metabolites with unusual nitrogen groups, such as thaxtomin A (ThxA), which contains a nitroindole moiety. ThxA is a phytotoxin made by three pathogenic Streptomyces species that cause common scab of potato. All three species

  20. The endothelial nitric oxide synthase ?786 T>C polymorphism and the exercise-induced blood pressure and nitric oxide responses among men with elevated blood pressure

    Microsoft Academic Search

    Amanda L. Augeri; Gregory J. Tsongalis; Jaci L. Van Heest; Carl M. Maresh; Paul D. Thompson; Linda S. Pescatello

    2009-01-01

    ObjectiveA polymorphism (?786 T>C) in the promoter region of the endothelial nitric oxide synthase gene (eNOS) has important functional characteristics. We examined the influence of eNOS ?786 T>C (rs2070744) on the BP and NO response to acute dynamic exercise.

  1. 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...

  2. Insulin-Induced Arteriolar Dilation after Tyrosine Kinase and Nitric Oxide Synthase Inhibition in Hamster Cheek Pouch Microcirculation

    Microsoft Academic Search

    S. Bertuglia; A. Colantuoni

    1998-01-01

    We investigated the effects of tyrosine kinase (TK) and nitric oxide synthase (NOS) inhibition on insulin-induced dilation of arterioles. We determined the arteriolar diameter, red blood cell velocity (VRBC) and blood flow changes in hamster cheek pouch microcirculation as affected by insulin in presence of TK and NOS inhibitors, genistein, piceatannol and NG-monomethyl-L-arginine (L-NMMA). Microvessels were visualized by a fluorescent

  3. Inducible nitric oxide synthase (iNOS)-like immunoreactivity in argyrophilic, tau-positive astrocytes in progressive supranuclear palsy

    Microsoft Academic Search

    Takashi Komori; Noriyuki Shibata; Makio Kobayashi; Shoichi Sasaki; Makoto Iwata

    1998-01-01

    The immunoreactivity to the free radical-related enzymes, nitric oxide synthase (NOS) and superoxide dismutase (SOD), was\\u000a examined in brain tissue in progressive supranuclear palsy (PSP). To determine the relationship between the immunoexpression\\u000a of these enzymes and tau-positive, argyrophilic cytoplasmic inclusions, which are constantly present in PSP brains, double-label\\u000a immunohistochemistry was applied. We demonstrated for the first time that strong inducible

  4. Increased expression and cellular localization of inducible nitric oxide synthase and cyclooxygenase 2 in Helicobacter pylori gastritis

    Microsoft Academic Search

    Sidong Fu; Kalathur S. Ramanujam; Annie Wong; George T. Fantry; Cinthia B. Drachenberg; Stephen P. James; Stephen J. Meltzer; Keith T. Wilson

    1999-01-01

    Background & Aims: Inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 are important regulators of mucosal inflammation and epithelial cell growth. To determine the role of iNOS and COX-2 in Helicobacter pylori–induced tissue injury, we compared their gene expression in H. pylori–induced gastritis with that in normal gastric mucosa and in non–H. pylori gastritis. Methods: In 43 patients, we assessed

  5. Overexpression of endothelium-derived nitric oxide synthase isoform 3 in the vasculature of human pancreatic tumor biopsies

    Microsoft Academic Search

    A. K. Nussler; S. Gansauge; F. Gansauge; U. Fischer; U. Butzer; P. G. Kremsner; H. G. Beger

    1998-01-01

    Cellular nitric oxide (NO) synthesis determines whether NO has cytoprotective or cytotoxic effects at anatomic sites; thus\\u000a it is important to identify potential NO synthase isoforms in tumor tissue and tumor cell lines which might be involved in\\u000a tumor development or destruction. Incubation of human pancreatic adenocarcinoma cell lines (AsPc-1, BxPc-3, CaPan-2) with\\u000a cytokines resulted in increased NO formation, indicating

  6. Inhaled nitric oxide therapy during the transport of neonates with persistent pulmonary hypertension or severe hypoxic respiratory failure

    Microsoft Academic Search

    Calvin G. Lowe; Johnn G. Trautwein

    2007-01-01

    Our aim was to determine whether starting inhaled nitric oxide (iNO) on critically ill neonates with severe hypoxemic respiratory\\u000a failure and\\/or persistent pulmonary hypertension (PPH), at a referring hospital at the start of transport, decreases the need\\u000a for extracorporeal membrane oxygenation (ECMO), lessens the number of hospital days and improves survival in comparison with\\u000a those patients who were started on

  7. Inhibition of nitric oxide and soluble guanylyl cyclase signaling affects olfactory neuron activity in the moth, Manduca sexta

    Microsoft Academic Search

    Caroline H. Wilson; Thomas A. Christensen; Alan J. Nighorn

    2007-01-01

    Nitric oxide is emerging as an important modulator of many physiological processes including olfaction, yet the function of\\u000a this gas in the processing of olfactory information remains poorly understood. In the antennal lobe of the moth, Manduca sexta, nitric oxide is produced in response to odor stimulation, and many interneurons express soluble guanylyl cyclase, a well-characterized\\u000a nitric oxide target. We

  8. Elevated Exhaled Nitric Oxide in Allergen-Provoked Asthma Is Associated with Airway Epithelial iNOS

    PubMed Central

    Roos, Abraham B.; Mori, Michiko; Grönneberg, Reidar; Österlund, Christina; Claesson, Hans-Erik; Wahlström, Jan; Grunewald, Johan; Eklund, Anders; Erjefält, Jonas S.; Lundberg, Jon O.; Nord, Magnus

    2014-01-01

    Background Fractional exhaled nitric oxide is elevated in allergen-provoked asthma. The cellular and molecular source of the elevated fractional exhaled nitric oxide is, however, uncertain. Objective To investigate whether fractional exhaled nitric oxide is associated with increased airway epithelial inducible nitric oxide synthase (iNOS) in allergen-provoked asthma. Methods Fractional exhaled nitric oxide was measured in healthy controls (n?=?14) and allergic asthmatics (n?=?12), before and after bronchial provocation to birch pollen out of season. Bronchoscopy was performed before and 24 hours after allergen provocation. Bronchial biopsies and brush biopsies were processed for nitric oxide synthase activity staining with nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d), iNOS immunostaining, or gene expression analysis of iNOS by real-time PCR. NADPH-d and iNOS staining were quantified using automated morphometric analysis. Results Fractional exhaled nitric oxide and expression of iNOS mRNA were significantly higher in un-provoked asthmatics, compared to healthy controls. Allergic asthmatics exhibited a significant elevation of fractional exhaled nitric oxide after allergen provocation, as well as an accumulation of airway eosinophils. Moreover, nitric oxide synthase activity and expression of iNOS was significantly increased in the bronchial epithelium of asthmatics following allergen provocation. Fractional exhaled nitric oxide correlated with eosinophils and iNOS expression. Conclusion Higher fractional exhaled nitric oxide concentration among asthmatics is associated with elevated iNOS mRNA in the bronchial epithelium. Furthermore, our data demonstrates for the first time increased expression and activity of iNOS in the bronchial epithelium after allergen provocation, and thus provide a mechanistic explanation for elevated fractional exhaled nitric oxide in allergen-provoked asthma. PMID:24587191

  9. Heterologous NNR-Mediated Nitric Oxide Signaling in Escherichia coli

    PubMed Central

    Hutchings, Matthew I.; Shearer, Neil; Wastell, Sarah; van Spanning, Rob J. M.; Spiro, Stephen

    2000-01-01

    The transcription factor NNR from Paracoccus denitrificans was expressed in a strain of Escherichia coli carrying a plasmid-borne fusion of the melR promoter to lacZ, with a consensus FNR-binding site 41.5 bp upstream of the transcription start site. This promoter was activated by NNR under anaerobic growth conditions in media containing nitrate, nitrite, or the NO+ donor sodium nitroprusside. Activation by nitrate was abolished by a mutation in the molybdenum cofactor biosynthesis pathway, indicating a requirement for nitrate reductase activity. Activation by nitrate was modulated by the inclusion of reduced hemoglobin in culture media, because of the ability of hemoglobin to sequester nitric oxide and nitrite. The ability of nitrate and nitrite to activate NNR is likely due to the formation of NO (or related species) during nitrate and nitrite respiration. Amino acids potentially involved in NNR activity were replaced by site-directed mutagenesis, and the activities of NNR derivatives were tested in the E. coli reporter system. Substitutions at Cys-103 and Tyr-35 significantly reduced NNR activity but did not abolish the response to reactive nitrogen species. Substitutions at Phe-82 and Tyr-93 severely impaired NNR activity, but the altered proteins retained the ability to repress an FNR-repressible promoter, so these mutations have a “positive control” phenotype. It is suggested that Phe-82 and Tyr-93 identify an activating region of NNR that is involved in an interaction with RNA polymerase. Replacement of Ser-96 with alanine abolished NNR activity, and the protein was undetectable in cell extracts. In contrast, NNR in which Ser-96 was replaced with threonine retained full activity. PMID:11053388

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

    PubMed

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

    2015-04-01

    Connexins (Cxs) and endothelial nitric oxide synthase (eNOS) contribute to the adaptation of endothelial and smooth muscle cells to hemodynamic changes. To decipher the in vivo interplay between these proteins, we studied Cx40-null mice, a model of renin-dependent hypertension which displays an altered endothelium-dependent relaxation of the aorta because of reduced eNOS levels. These mice, which were either untreated or subjected to the 1-kidney, 1-clip (1K1C) procedure, a model of volume-dependent hypertension, were compared with control mice submitted to either the 1K1C or the 2-kidney, 1-clip (2K1C) procedure, a model of renin-dependent hypertension. All operated mice became hypertensive and featured hypertrophy and altered Cx expression of the aorta. The combination of volume- and renin-dependent hypertension in Cx40-/- 1K1C mice raised blood pressure and cardiac weight index. Under these conditions, all aortas showed increased levels of Cx40 in endothelial cells and of both Cx37 and Cx45 in smooth muscle cells. In the wild-type 1K1C mice, the interactions between Cx40 and Cx37 with eNOS were enhanced, resulting in increased NO release. The Cx40-eNOS interaction could not be observed in mice lacking Cx40, which also featured decreased levels of eNOS. In these animals, the volume overload caused by the 1K1C procedure resulted in increased phosphorylation of eNOS and in a higher NO release. The findings provide evidence that Cx40 and Cx37 play an in vivo role in the regulation of eNOS. PMID:25712722

  11. ASCORBATE IN AQUEOUS HUMOR AUGMENTS NITRIC OXIDE PRODUCTION BY MACROPHAGES*

    PubMed Central

    McKenna, Kyle C.; Beatty, Kelly M.; Scherder, Rebecca C.; Li, Fuwang; Liu, Huanbo; Chen, Alex F.; Ghosh, Arnab; Stuehr, Dennis

    2012-01-01

    Immunosuppressive molecules within the aqueous humor (AqH) are thought to preserve ocular immune privilege by inhibiting pro-inflammatory nitric oxide (NO) production by macrophages (M?s). Consistent with previous observations, we observed that although M?s stimulated in the presence of AqH expressed NO-synthase-2 (NOS2) protein, nitrite concentrations in culture supernatants, an indirect measure NO production, did not increase. Interestingly, NOS2 enzymatic activity, as measured by the conversion of L-arginine (L-Arg) into L-citrulline, was augmented in lysates of M?s stimulated in the presence of AqH. These data suggested that intracellular L-arg may have been limited by AqH. However, we observed increased mRNA expression of the L-arg transporter, CAT2B, and increased L-arg uptake in M?s stimulated in the presence of AqH. Arginases were expressed by stimulated M?s but competition for L-arg with NOS2 was excluded. Expression of GTP cyclohydrolase which produces tetrahydrobiopterin (H4B), an essential cofactor for NOS2 homodimerization, increased after M? stimulation in the presence or absence of AqH and NOS2 homodimers formed. Taken together these data provided no evidence for inhibited NOS2 enzymatic activity by AqH suggesting that a factor within AqH may have interfered with the measurement of nitrite. Indeed, we observed that nitrite standards were not measurable in the presence of AqH and this effect was due to ascorbate in AqH. Controlling for interference by ascorbate revealed that AqH augmented NO production in M?s via ascorbate which limited degradation of H4B. Therefore, AqH may augment NO production in macrophages by stabilizing H4B and increasing intracellular L-Arg. PMID:23241881

  12. Nitric oxide targets oligodendrocytes and promotes their morphological differentiation.

    PubMed

    Garthwaite, Giti; Hampden-Smith, Kathryn; Wilson, Gary W; Goodwin, David A; Garthwaite, John

    2015-03-01

    In the central nervous system, nitric oxide (NO) transmits signals from one neurone to another, or from neurones to astrocytes or blood vessels, but the possibility of oligodendrocytes being physiological NO targets has been largely ignored. By exploiting immunocytochemistry for cGMP, the second messenger generated on activation of NO receptors, oligodendrocytes were found to respond to both exogenous and endogenous NO in cerebellar slices from rats aged 8 days to adulthood. Atrial natriuretic peptide, which acts on membrane-associated guanylyl cyclase-coupled receptors, also raised oligodendrocyte cGMP in cerebellar slices. The main endogenous source of NO accessing oligodendrocytes appeared to be the neuronal NO synthase isoform, which was active even under basal conditions and in a manner that was independent of glutamate receptors. Oligodendrocytes in brainstem slices were also shown to be potential NO targets. In contrast, in the optic nerve, oligodendrocyte cGMP was raised by natriuretic peptides but not NO. When cultures of cerebral cortex were continuously exposed to low NO concentrations (estimated as 40-90 pM), oligodendrocytes responded with a striking increase in arborization. This stimulation of oligodendrocyte growth could be replicated by low concentrations of 8-bromo-cGMP (maximum effect at 1 µM). It is concluded that oligodendrocytes are probably widespread targets for physiological NO (or natriuretic peptide) signals, with the resulting rise in cGMP serving to enhance their growth and maturation. NO might help coordinate the myelination of axons to the ongoing level of neuronal activity during development and could potentially contribute to adaptive changes in myelination in the adult. PMID:25327839

  13. Nitric oxide synthase modulates angiogenesis in response to tissue ischemia.

    PubMed Central

    Murohara, T; Asahara, T; Silver, M; Bauters, C; Masuda, H; Kalka, C; Kearney, M; Chen, D; Symes, J F; Fishman, M C; Huang, P L; Isner, J M

    1998-01-01

    We tested the hypothesis that endothelial nitric oxide synthase (eNOS) modulates angiogenesis in two animal models in which therapeutic angiogenesis has been characterized as a compensatory response to tissue ischemia. We first administered L-arginine, previously shown to augment endogenous production of NO, to normal rabbits with operatively induced hindlimb ischemia. Angiogenesis in the ischemic hindlimb was significantly improved by dietary supplementation with L-arginine, compared to placebo-treated controls; angiographically evident vascularity in the ischemic limb, hemodynamic indices of limb perfusion, capillary density, and vasomotor reactivity in the collateral vessel-dependent ischemic limb were all improved by oral L-arginine supplementation. A murine model of operatively induced hindlimb ischemia was used to investigate the impact of targeted disruption of the gene encoding for ENOS on angiogenesis. Angiogenesis in the ischemic hindlimb was significantly impaired in eNOS-/- mice versus wild-type controls evaluated by either laser Doppler flow analysis or capillary density measurement. Impaired angiogenesis in eNOS-/- mice was not improved by administration of vascular endothelial growth factor (VEGF), suggesting that eNOS acts downstream from VEGF. Thus, (a) eNOS is a downstream mediator for in vivo angiogenesis, and (b) promoting eNOS activity by L-arginine supplementation accelerates in vivo angiogenesis. These findings suggest that defective endothelial NO synthesis may limit angiogenesis in patients with endothelial dysfunction related to atherosclerosis, and that oral L-arginine supplementation constitutes a potential therapeutic strategy for accelerating angiogenesis in patients with advanced vascular obstruction. PMID:9616228

  14. Nitric oxide targets oligodendrocytes and promotes their morphological differentiation

    PubMed Central

    Garthwaite, Giti; Hampden-Smith, Kathryn; Wilson, Gary W; Goodwin, David A; Garthwaite, John

    2015-01-01

    In the central nervous system, nitric oxide (NO) transmits signals from one neurone to another, or from neurones to astrocytes or blood vessels, but the possibility of oligodendrocytes being physiological NO targets has been largely ignored. By exploiting immunocytochemistry for cGMP, the second messenger generated on activation of NO receptors, oligodendrocytes were found to respond to both exogenous and endogenous NO in cerebellar slices from rats aged 8 days to adulthood. Atrial natriuretic peptide, which acts on membrane-associated guanylyl cyclase-coupled receptors, also raised oligodendrocyte cGMP in cerebellar slices. The main endogenous source of NO accessing oligodendrocytes appeared to be the neuronal NO synthase isoform, which was active even under basal conditions and in a manner that was independent of glutamate receptors. Oligodendrocytes in brainstem slices were also shown to be potential NO targets. In contrast, in the optic nerve, oligodendrocyte cGMP was raised by natriuretic peptides but not NO. When cultures of cerebral cortex were continuously exposed to low NO concentrations (estimated as 40–90 pM), oligodendrocytes responded with a striking increase in arborization. This stimulation of oligodendrocyte growth could be replicated by low concentrations of 8-bromo-cGMP (maximum effect at 1 µM). It is concluded that oligodendrocytes are probably widespread targets for physiological NO (or natriuretic peptide) signals, with the resulting rise in cGMP serving to enhance their growth and maturation. NO might help coordinate the myelination of axons to the ongoing level of neuronal activity during development and could potentially contribute to adaptive changes in myelination in the adult. PMID:25327839

  15. Prostacyclin prevents nitric oxide-induced megakaryocyte apoptosis

    PubMed Central

    Gabriel Pozner, Roberto; Negrotto, Soledad; D'Atri, Lina Paola; Lidia Kotler, Mónica; Angela Lazzari, María; Martin Gomez, Ricardo; Schattner, Mirta

    2005-01-01

    We have previously demonstrated that nitric oxide (NO) triggers CD34+-derived megakaryocyte apoptosis. We here show that prostacyclin (PGI2) inhibits PAPA/NO-induced megakaryocyte death detected by fluorescent microscopy and flow cytometry. The cAMP-specific phosphodiesterase inhibitor, Ro 20-1724, and the permeable analog dibutyryl-cAMP also delayed apoptosis. PGI2 effect was fully prevented when adenylyl cyclase activity was suppressed by SQ 22536, and partially reversed by the permeable protein kinase A inhibitor PKI 14-22 amide. ELISA showed that while both PGI2 and NO alone or synergistically raised cAMP, only NO was able to increase intracellular cGMP levels. Treatment of megakaryocytes with PGI2 abolished both basal and NO-raised cGMP levels. Addition of 8-pCPT-cGMP or activation of soluble guanylyl cyclase by BAY 41-2272 induced cell death in a concentration-dependent manner, and ODQ, an inhibitor of guanylyl cyclase, prevented both PAPA/NO- or BAY 41-2272-induced apoptosis. Specific cGMP phosphodiesterase inhibition by Zaprinast or suppression of adenylyl cyclase by SQ 22536 enhanced the PAPA/NO proapoptotic effect. PGI2 completely inhibited NO-mediated generation and the increased activity of the cleaved form of caspase-3. In conclusion, our results demonstrate that contrary to their well-known direct and synergistic inhibitory effects on platelets, PGI2 and NO regulate opposite megakaryocyte survival responses through a delicate balance between intracellular cyclic nucleotide levels and caspase-3 activity control. PMID:15778737

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

    PubMed Central

    Freschi, Luciano

    2013-01-01

    Nitric oxide (NO) is currently considered a ubiquitous signal in plant systems, playing significant roles in a wide range of responses to environmental and endogenous cues. During the signaling events leading to these plant responses, NO frequently interacts with plant hormones and other endogenous molecules, at times originating remarkably complex signaling cascades. Accumulating evidence indicates that virtually all major classes of plant hormones may influence, at least to some degree, the endogenous levels of NO. In addition, studies conducted during the induction of diverse plant responses have demonstrated that NO may also affect biosynthesis, catabolism/conjugation, transport, perception, and/or transduction of different phytohormones, such as auxins, gibberellins, cytokinins, abscisic acid, ethylene, salicylic acid, jasmonates, and brassinosteroids. Although still not completely elucidated, the mechanisms underlying the interaction between NO and plant hormones have recently been investigated in a number of species and plant responses. This review specifically focuses on the current knowledge of the mechanisms implicated in NO–phytohormone interactions during the regulation of developmental and metabolic plant events. The modifications triggered by NO on the transcription of genes encoding biosynthetic/degradative enzymes as well as proteins involved in the transport and signal transduction of distinct plant hormones will be contextualized during the control of developmental, metabolic, and defense responses in plants. Moreover, the direct post-translational modification of phytohormone biosynthetic enzymes and receptors through S-nitrosylation will also be discussed as a key mechanism for regulating plant physiological responses. Finally, some future perspectives toward a more complete understanding of NO–phytohormone interactions will also be presented and discussed. PMID:24130567

  17. Carnosine facilitates nitric oxide production in endothelial f-2 cells.

    PubMed

    Takahashi, Satoru; Nakashima, Yukiko; Toda, Ken-Ichi

    2009-11-01

    We examined the effect of carnosine (beta-alanyl-histidine) on nitric oxide (NO) production and endothelial NO synthase (eNOS) activation in endothelial F-2 cells. Carnosine enhanced NO production in a dose-dependent manner, and the stimulatory effect of carnosine was observed at concentrations exceeding 5 mM. The carnosine-stimulated NO production was inhibited by N(G)-nitro-L-arginine methyl ester, but not by N(G)-nitro-D-arginine methyl ester. In contrast, beta-alanine, histidine (carnosine components) and anserine (N-methyl carnosine) failed to increase NO production. Carnosine had no effect on NO production for the initial 5 min, but thereafter resulted in a gradual increase in NO production up to 15 min. Carnosine did not induce phosphorylation of eNOS at Ser1177. The carnosine-induced increase in NO production was observed even when extracellular Ca2+ was depleted by ethylene glycol bis(2-aminoethyl ether)-N,N,N'-N'-tetraacetic acid however, the effect was abolished upon depletion of intracellular Ca2+ by BAPTA. After F-2 cells were incubated with carnosine for 4 min, intracellular Ca2+ concentration gradually increased. The carnosine-induced increase in intracellular Ca2+ concentration occurred even in the absence of extracellular Ca2+. These results indicate that carnosine facilitates NO production in endothelial F-2 cells. It is also suggested that eNOS is activated by Ca2+, which might be released from intracellular Ca2+ stores in response to carnosine. PMID:19881293

  18. Initiation and detonation measurements on liquid nitric oxide

    SciTech Connect

    Schott, G.L.; Davis, W.C.; Chiles, W.C.

    1989-01-01

    Measurements are reported on detonations of homogeneous liquid nitric oxide initially at T = 119 K, /rho//sub o/ = 1.28 g/cm/sup 3/. Plane-shock initiation in mirror-covered wedges demonstrated detonation in preshocked material (superdetonation) that overtook the smooth input shock. Its transverse irregularities continued in the unsupported detonation. The input shock ran ca. 3 mm at U/sub I/ = 3.8 /plus minus/ 0.2 km/s. Behind it the fluid had u/sub p/ = 0.89 /plus minus/ 0.02 km/s, p = 4.3 /plus minus/ 0.03 GPa, /rho/ = 1.67 /plus minus/ 0.03 g/cm/sup 3/, and the superdetonation had D*/sub lab/ /approx/6.9 km/s. In 356-mm long graphite tubes with 25.4-mm inner diameter, measured detonation velocity is D = 5552 /plus minus/ 3 m/s. Failure diameter in graphite is below 8 mm. Free-surface velocities of 1- and 2-mm aluminum plates terminating the detonation axis were near 1.5 km/s approximately as predicted for CJ flow at D/sub /infinity// = 5564 m/s, u/sub p/ = 1.34 km/s impinging on aluminum. Electronic streak photography at d = 20.6 mm in brass registered a smoothly convex detonation front with apparent brightness temperature of 1735 /plus minus/ 40 K as it reached an end window asynchronously. 20 refs., 5 figs., 3 tabs.

  19. The effect of high altitude on nasal nitric oxide levels.

    PubMed

    Altundag, Aytug; Salihoglu, Murat; Cayonu, Melih; Cingi, Cemal; Tekeli, Hakan; Hummel, Thomas

    2014-09-01

    The aim of the present study was to investigate whether nasal nitric oxide (nNO) levels change in relation to high altitude in a natural setting where the weather conditions were favorable. The present study included 41 healthy volunteers without a history of acute rhinosinusitis within 3 weeks and nasal polyposis. The study group consisted of 31 males (76 %) and 10 females (24 %) and the mean age of the study population was 38 ± 10 years. The volunteers encamped for 2 days in a mountain village at an altitude of 1,500 m above sea level (masl) and proceeded to highlands at an altitude of 2,200 masl throughout the day. The measurements of nNO were done randomly, either first at the mountain village or at sea level. Each participant had nNO values both at sea level and at high altitude at the end of the study. The nNO values of sea level and high altitude were compared to investigate the effect of high altitude on nNO levels. The mean of average nNO measurements at the high altitude was 74.2 ± 41 parts-per-billion (ppb) and the mean of the measurements at sea level was 93.4 ± 45 ppb. The change in nNO depending on the altitude level was statistically significant (p < 0.001). The current investigation showed that nNO levels were decreased at high altitude even if the weather conditions were favorable, such as temperature, humidity, and wind. PMID:24972544

  20. Energy Landscapes and Catalysis in Nitric-oxide Synthase*

    PubMed Central

    Sobolewska-Stawiarz, Anna; Leferink, Nicole G. H.; Fisher, Karl; Heyes, Derren J.; Hay, Sam; Rigby, Stephen E. J.; Scrutton, Nigel S.

    2014-01-01

    Nitric oxide (NO) plays diverse roles in mammalian physiology. It is involved in blood pressure regulation, neurotransmission, and immune response, and is generated through complex electron transfer reactions catalyzed by NO synthases (NOS). In neuronal NOS (nNOS), protein domain dynamics and calmodulin binding are implicated in regulating electron flow from NADPH, through the FAD and FMN cofactors, to the heme oxygenase domain, the site of NO generation. Simple models based on crystal structures of nNOS reductase have invoked a role for large scale motions of the FMN-binding domain in shuttling electrons from the FAD-binding domain to the heme oxygenase domain. However, molecular level insight of the dynamic structural transitions in NOS enzymes during enzyme catalysis is lacking. We use pulsed electron-electron double resonance spectroscopy to derive inter-domain distance relationships in multiple conformational states of nNOS. These distance relationships are correlated with enzymatic activity through variable pressure kinetic studies of electron transfer and turnover. The binding of NADPH and calmodulin are shown to influence interdomain distance relationships as well as reaction chemistry. An important effect of calmodulin binding is to suppress adventitious electron transfer from nNOS to molecular oxygen and thereby preventing accumulation of reactive oxygen species. A complex landscape of conformations is required for nNOS catalysis beyond the simple models derived from static crystal structures of nNOS reductase. Detailed understanding of this landscape advances our understanding of nNOS catalysis/electron transfer, and could provide new opportunities for the discovery of small molecule inhibitors that bind at dynamic protein interfaces of this multidimensional energy landscape. PMID:24610812