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1

Nitric oxide  

PubMed Central

Nitric oxide (NO) is a highly inducible molecule and overaccumulated during stress responses, such as drought, cold and pathogen infection. Several key developmental processes within a plant life cycle have been reported to be signaled by this gaseous molecule, and among them seed germination, de-etiolation, gravitropic response or root growth are well-characterized. The importance of NO as a plant growth and stress regulator is emerging considerably, despite the current knowledge about its signaling pathway is still limited. Therefore, the identification and characterization at the molecular level of NO targets is essential to get a deeper insight into this pathway. Here we characterize the effect of NO on root development in Arabidopsis and found that NO application reduces cell lengths in differentiation zone. Additionally, the contribution of the gibberellin (GA) signaling pathway to the NO root-related phenotypes, mainly through DELLA repressors, is also depicted. PMID:22353861

Fernández-Marcos, María; Sanz, Luis; Lorenzo, Óscar

2012-01-01

2

Detection of nitric oxide pollution  

NASA Technical Reports Server (NTRS)

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

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

1973-01-01

3

Oxidative Stress and Compartment of Gene Expression Determine Proatherosclerotic Effects of Inducible Nitric Oxide Synthase  

PubMed Central

Genetic and pharmacological inhibition of inducible nitric oxide synthase (iNOS) decreases atherosclerosis development. Potential proatherogenic effects of iNOS include iNOS mediated oxidative stress and iNOS expression in different cellular compartments. Lesional iNOS can potentially produce nitric oxide radicals (NO), superoxide radicals (O2?), or both; these radicals may then react to form peroxynitrite. Alternatively, O2? radicals from oxidases co-expressed with iNOS could react with NO to produce peroxynitrite. Therefore, the expression profiles of the genes that modulate the redox system in different iNOS-expressing cell compartments may determine the role of iNOS in atherosclerosis. We used apoE (apoE?/?) and apoE/iNOS double knockout (apoE?/?/ iNOS?/?) mice to assess vascular NO, O2?, and peroxynitrite formation by electron spin resonance spectroscopy, high performance liquid chromatography, and 3-nitrotyrosine staining. The relevance of the iNOS expressing cell compartment was tested by bone marrow transplantation. We show that iNOS significantly contributes to vascular NO production and itself produces O2?, leading to peroxynitrite formation in atherosclerotic lesions. Our bone marrow transplantation experiments show that bone marrow derived cells exclusively mediate the proatherosclerotic effects of iNOS in males, while both parenchymal and bone marrow derived iNOS equally contribute to atherosclerosis in females. Moreover, iNOS expression affects vascular remodeling. These findings establish for the first time that the proatherosclerotic effects of iNOS vary with sex in addition to the compartment of its expression. PMID:19465644

Ponnuswamy, Padmapriya; Ostermeier, Eva; Schröttle, Angelika; Chen, Jiqiu; Huang, Paul L.; Ertl, Georg; Nieswandt, Bernhard; Kuhlencordt, Peter J.

2009-01-01

4

Nitric oxide and pulmonary hypertension  

PubMed Central

Pulmonary hypertension is a serious complication of a number of lung and heart diseases that is characterized by peripheral vascular structural remodeling and loss of vascular tone. Nitric oxide can modulate vascular injury and interrupt elevation of pulmonary vascular resistance selectively; however, it can also produce cytotoxic oxygen radicals and exert cytotoxic and antiplatelet effects. The balance between the protective and adverse effects of nitric oxide is determined by the relative amount of nitric oxide and reactive radicals. Nitric oxide has been shown to be clinically effective in the treatment of congenital heart disease, mitrial valvular disease combined with pulmonary hypertension and in orthotropic cardiac transplantation patients. Additionally, new therapeutic modalities for the treatment of pulmonary hypertension, phosphodiesterase inhibitors, natriuretic peptides and aqueous nitric oxide are also effective for treatment of elevated pulmonary vascular resistance. PMID:20498805

2010-01-01

5

Biofiltration of nitric oxide  

SciTech Connect

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

Davidova, Y.B.; Schroeder, E.D.; Chang, D.P.Y. [Univ. of California, Davis, CA (United States). Dept. of Civil and Environmental Engineering

1997-12-31

6

Rate of reaction with nitric oxide determines the hypertensive effect of cell-free hemoglobin.  

PubMed

Administration of extracellular hemoglobin-based oxygen carriers often induces mild increases in blood pressure. In order to test whether nitric oxide (NO) scavenging is responsible for the hypertensive effect, we constructed and tested a set of recombinant hemoglobins that vary in rates of reaction with NO. The results suggest that the rapid reactions of oxy- and deoxyhemoglobin with nitric oxide are the fundamental cause of the hypertension. The magnitude of the blood-pressure effect correlates directly with the in vitro rate of NO oxidation. Hemoglobins with decreased NO-scavenging activity may be more suitable for certain therapeutic applications than those that cause depletion of nitric oxide. PMID:9661203

Doherty, D H; Doyle, M P; Curry, S R; Vali, R J; Fattor, T J; Olson, J S; Lemon, D D

1998-07-01

7

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

PubMed Central

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

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

8

49 CFR 173.337 - Nitric oxide.  

Code of Federal Regulations, 2013 CFR

... 2013-10-01 2013-10-01 false Nitric oxide. 173.337 Section 173.337 Transportation...Preparation and Packaging § 173.337 Nitric oxide. (a) Nitric oxide must be packaged in cylinders conforming to the...

2013-10-01

9

49 CFR 173.337 - Nitric oxide.  

Code of Federal Regulations, 2014 CFR

... 2014-10-01 2014-10-01 false Nitric oxide. 173.337 Section 173.337 Transportation...Preparation and Packaging § 173.337 Nitric oxide. (a) Nitric oxide must be packaged in cylinders conforming to the...

2014-10-01

10

49 CFR 173.337 - Nitric oxide.  

Code of Federal Regulations, 2012 CFR

... 2012-10-01 2012-10-01 false Nitric oxide. 173.337 Section 173.337 Transportation...Preparation and Packaging § 173.337 Nitric oxide. (a) Nitric oxide must be packaged in cylinders conforming to the...

2012-10-01

11

49 CFR 173.337 - Nitric oxide.  

Code of Federal Regulations, 2011 CFR

... 2011-10-01 2011-10-01 false Nitric oxide. 173.337 Section 173.337 Transportation...Preparation and Packaging § 173.337 Nitric oxide. (a) Nitric oxide must be packaged in cylinders conforming to the...

2011-10-01

12

49 CFR 173.337 - Nitric oxide.  

Code of Federal Regulations, 2010 CFR

... 2010-10-01 2010-10-01 false Nitric oxide. 173.337 Section 173.337 Transportation...Preparation and Packaging § 173.337 Nitric oxide. (a) Nitric oxide must be packaged in cylinders conforming to the...

2010-10-01

13

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.

14

Chemiluminescence of nitric oxide  

NASA Technical Reports Server (NTRS)

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.

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

1981-01-01

15

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

PubMed Central

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

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

2014-01-01

16

Plasma levels of nitric oxide metabolites are markedly reduced in normotensive men with electrocardiographically determined left ventricular hypertrophy.  

PubMed

Recent studies have revealed that electrocardiographically determined left ventricular hypertrophy (ECG-LVH) is a risk factor for cardiovascular death not only in hypertensive patients but also in normotensive subjects. However, the underlying mechanisms remain to be elucidated. In this study, we tested our hypothesis that normotensive subjects with ECG-LVH have reduced nitric oxide production. A total of 840 Japanese male workers were enrolled, and 579 eligible subjects were studied. ECG-LVH was assessed according to the Sokolow-Lyon voltage criteria and the Cornell voltage-duration product. The median level of plasma NOx (nitrite plus nitrate), a marker of systemic nitric oxide production, was markedly lower in the normotensive subjects with ECG-LVH (n=73) than in those without (n=506), and the clinical characteristics were significantly different between the 2 groups (each P<0.05). Importantly, a one-to-one propensity score matching analysis showed similar markedly lower median plasma NOx level in the normotensive subjects with ECG-LVH compared with that observed in the matched normotensive subjects without ECG-LVH (P<0.05). Furthermore, the tertiles of the plasma NOx levels were inversely correlated with the prevalence and severity of ECG-LVH (both P<0.05). The lower plasma NOx levels were associated with significantly higher plasma 8-isoprostane levels, a marker of systemic lipid peroxidation (P<0.05). These results provide the first evidence that normotensive subjects with ECG-LVH exhibit defective nitric oxide production, along with increased oxidative stress. Our findings may thus explain, at least in part, a potential mechanism underlying the increased risk of cardiovascular death in normotensive individuals with ECG-LVH. PMID:24914203

Kamezaki, Fumihiko; Tsutsui, Masato; Takahashi, Masao; Sonoda, Shinjo; Kubo, Tatsuhiko; Fujino, Yoshihisa; Adachi, Tetsuo; Abe, Haruhiko; Takeuchi, Masaaki; Mayumi, Toshihiko; Otsuji, Yutaka

2014-09-01

17

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

SciTech Connect

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.

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

18

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

PubMed

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

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

2015-01-01

19

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

PubMed Central

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

Robinson, Jonathan L.; Brynildsen, Mark P.

2013-01-01

20

Nitric oxide and cellular respiration  

Microsoft Academic Search

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

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

1999-01-01

21

Nitric oxide and mitochondrial respiration  

Microsoft Academic Search

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

Guy C Brown

1999-01-01

22

Arginine metabolism: nitric oxide and beyond.  

PubMed Central

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

Wu, G; Morris, S M

1998-01-01

23

Nitric Oxide Production in Plants  

PubMed Central

There is now general agreement that nitric oxide (NO) is an important and almost universal signal in plants. Nevertheless, there are still many controversial observations and opinions on the importance and function of NO in plants. Partly, this may be due to the difficulties in detecting and even more in quantifying NO. Here, we summarize major pathways of NO production in plants, and briefly discuss some methodical problems. PMID:19521475

Planchet, Elisabeth

2006-01-01

24

Nitric Oxide Activates Cyclooxygenase Enzymes  

Microsoft Academic Search

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

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

1993-01-01

25

Nitric Oxide Regulates Wound Healing  

Microsoft Academic Search

Nitric oxide (NO) synthesis occurs during wound healing, but its role has not been defined. To study the effect of NO on wound repair,S-methyl isothiouronium (MITU, a competitive inhibitor of NO synthase) was administered at a dose of 10, 50, and 100 mg\\/kg body weight\\/day, using intraperitoneally implanted miniosmotic pumps. Groups of 10 male Balb\\/C mice underwent a dorsal skin

Michael R. Schäffer; Udaya Tantry; Steven S. Gross; Hannah L. Wasserkrug; Adrian Barbul

1996-01-01

26

Nitric oxide function in atherosclerosis  

PubMed Central

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

Matthys, K. E.

1997-01-01

27

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

E-print Network

Comparison of a thermospheric photochemical model with Student Nitric Oxide Explorer (SNOE) observations of nitric oxide C. A. Barth Laboratory for Atmospheric and Space Physics, University of Colorado] A time-dependent thermospheric model has been used to calculate the nitric oxide density in the lower

Bailey, Scott

28

Role of Nitric Oxide in Anorectal Function of Normal and Neuronal Nitric Oxide Synthase Knockout Mice  

Microsoft Academic Search

PURPOSE: In vitro data suggest that nitric oxide is an important inhibitory neurotransmitter in the internal anal sphincter, and morphologic evidence implies that it mediates the rectoanal inhibitory reflex. This study examined the anatomy, physiology, and pharmacology of the internal sphincter in control and neuronal nitric oxide synthase knockout mice. METHODS: Neuronal nitric oxide synthase, nicotinamide adenosine triphosphate dinucleotide phosphate

Oliver M. Jones; Alison F. Brading; Neil J. Mc C. Mortensen

2003-01-01

29

21 CFR 868.2380 - Nitric oxide analyzer.  

Code of Federal Regulations, 2011 CFR

...2011-04-01 2011-04-01 false Nitric oxide analyzer. 868.2380 Section 868.2380...Monitoring Devices § 868.2380 Nitric oxide analyzer. (a) Identification. The nitric oxide analyzer is a device intended to...

2011-04-01

30

21 CFR 868.5165 - Nitric oxide administration apparatus.  

Code of Federal Regulations, 2014 CFR

...2014-04-01 2014-04-01 false Nitric oxide administration apparatus. 868.5165...Therapeutic Devices § 868.5165 Nitric oxide administration apparatus. (a) Identification. The nitric oxide administration apparatus is a device...

2014-04-01

31

21 CFR 868.5165 - Nitric oxide administration apparatus.  

Code of Federal Regulations, 2012 CFR

...2012-04-01 2012-04-01 false Nitric oxide administration apparatus. 868.5165...Therapeutic Devices § 868.5165 Nitric oxide administration apparatus. (a) Identification. The nitric oxide administration apparatus is a device...

2012-04-01

32

21 CFR 868.2380 - Nitric oxide analyzer.  

Code of Federal Regulations, 2014 CFR

...2014-04-01 2014-04-01 false Nitric oxide analyzer. 868.2380 Section 868.2380...Monitoring Devices § 868.2380 Nitric oxide analyzer. (a) Identification. The nitric oxide analyzer is a device intended to...

2014-04-01

33

21 CFR 868.2380 - Nitric oxide analyzer.  

Code of Federal Regulations, 2012 CFR

...2012-04-01 2012-04-01 false Nitric oxide analyzer. 868.2380 Section 868.2380...Monitoring Devices § 868.2380 Nitric oxide analyzer. (a) Identification. The nitric oxide analyzer is a device intended to...

2012-04-01

34

21 CFR 868.5165 - Nitric oxide administration apparatus.  

Code of Federal Regulations, 2010 CFR

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

2010-04-01

35

21 CFR 868.2380 - Nitric oxide analyzer.  

Code of Federal Regulations, 2010 CFR

...2010-04-01 2010-04-01 false Nitric oxide analyzer. 868.2380 Section 868.2380...Monitoring Devices § 868.2380 Nitric oxide analyzer. (a) Identification. The nitric oxide analyzer is a device intended to...

2010-04-01

36

21 CFR 868.5165 - Nitric oxide administration apparatus.  

Code of Federal Regulations, 2013 CFR

...2013-04-01 2013-04-01 false Nitric oxide administration apparatus. 868.5165...Therapeutic Devices § 868.5165 Nitric oxide administration apparatus. (a) Identification. The nitric oxide administration apparatus is a device...

2013-04-01

37

21 CFR 868.5165 - Nitric oxide administration apparatus.  

Code of Federal Regulations, 2011 CFR

...2011-04-01 2011-04-01 false Nitric oxide administration apparatus. 868.5165...Therapeutic Devices § 868.5165 Nitric oxide administration apparatus. (a) Identification. The nitric oxide administration apparatus is a device...

2011-04-01

38

21 CFR 868.2380 - Nitric oxide analyzer.  

Code of Federal Regulations, 2013 CFR

...2013-04-01 2013-04-01 false Nitric oxide analyzer. 868.2380 Section 868.2380...Monitoring Devices § 868.2380 Nitric oxide analyzer. (a) Identification. The nitric oxide analyzer is a device intended to...

2013-04-01

39

Endogenous Nitric Oxide Promotes Ileal Absorption  

Microsoft Academic Search

Background\\/aims. Nitric oxide (NO) is generated in vascular endothelium and enteric neural plexuses from L-arginine by the action of nitric oxide synthase (NOS). This study tested the hypothesis that NO is a modulator of ileal water and ion transport. Methods. NADPH diaphorase staining was performed on fixed frozen sections of canine ileum. Absorption studies (n = 80) were performed in

Michael M. Maher; Jacqueline D. Gontarek; Ramon E. Jimenez; Paul A. Cahill; Charles J. Yeo

1995-01-01

40

Delivery and monitoring of inhaled nitric oxide  

Microsoft Academic Search

Inhaled nitric oxide is rapidly gaining popularity as a selective pulmonary vasodilator in patients with acute lung injury and pulmonary hypertension. The development of nitric oxide as a drug has bypassed the usual regulatory and commercial processes, and as a result clinicians have devised a wide range of delivery and monitoring systems. This review describes these systems, and discusses their

J. D. Young; O. J. Dyar

1996-01-01

41

Two Dimensional Polymer That Generates Nitric Oxide.  

DOEpatents

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

McDonald, William F. (Utica, OH); Koren, Amy B. (Lansing, MI)

2005-10-04

42

Oleic AcidDependent Modulation of NITRIC OXIDE ASSOCIATED1 Protein Levels Regulates Nitric  

E-print Network

Oleic Acid­Dependent Modulation of NITRIC OXIDE ASSOCIATED1 Protein Levels Regulates Nitric Oxide The conserved cellular metabolites nitric oxide (NO) and oleic acid (18:1) are well-known regulators of disease in the ssi2 mutant was partially restored by a mutation in NITRIC OXIDE ASSOCIATED1 (NOA1) and completely

Kachroo, Pradeep

43

UV Induced Oxidation of Nitric Oxide  

NASA Technical Reports Server (NTRS)

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.

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

2007-01-01

44

Analytical Chemistry of Nitric Oxide  

PubMed Central

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

Hetrick, Evan M.

2013-01-01

45

Nanocarriers for Nitric Oxide Delivery  

PubMed Central

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

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

2011-01-01

46

Calculated Effects of Nitric Oxide Flow Contamination on Scramjet Performance  

NASA Technical Reports Server (NTRS)

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.

Fischer, Karen E.; Rock, Kenneth E.

1995-01-01

47

Nitric Oxide Metabolism in Asthma Pathophysiology  

PubMed Central

Asthma, a chronic inflammatory disease is typically characterized by bronchoconstriction and airway hyper-reactivity. A wealth of studies applying chemistry, molecular and cell biology to animal model systems and human asthma over the last decade have revealed that asthma is associated with increased synthesis of the gaseous molecule nitric oxide (NO). The high NO levels in the oxidative environment of the asthmatic airway lead to greater formation of reactive nitrogen species (RNS) and subsequent oxidation and nitration of proteins, which adversely affect protein functions that are biologically relevant to chronic inflammation. In contrast to the high levels of NO and nitrated products, there are lower levels of beneficial S-nitrosothiols (RSNO), which mediate bronchodilation, due to greater enzymatic catabolism of RSNO in the asthmatic airways. This review discusses the rapidly accruing data linking metabolic products of NO as critical determinants in the chronic inflammation and airway reactivity of asthma. PMID:21718755

Ghosh, Sudakshina; Erzurum, Serpil C.

2011-01-01

48

The First 35Amino Acids and Fatty Acylation Sites Determine the Molecular Targeting of Endothelial Nitric Oxide Synthase into the Golgi Region of Cells: A Green Fluorescent Protein Study  

Microsoft Academic Search

Catalytically active endothelial nitric oxide synthase (eNOS) is located on the Golgi complex and in the caveolae of endothelial cells (EC). Mislocaliza- tion of eNOS caused by mutation of the N-myristoyla- tion or cysteine palmitoylation sites impairs production of stimulated nitric oxide (NO), suggesting that intra- cellular targeting is critical for optimal NO production. To investigate the molecular determinants of

Jianwei Liu; Thomas E. Hughes; William C. Sessa

1997-01-01

49

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

NASA Astrophysics Data System (ADS)

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

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

1997-06-01

50

Hyaluronan fragments activate nitric oxide synthase and the production of nitric oxide by articular chondrocytes  

PubMed Central

Chondrocyte CD44 receptors anchor hyaluronan to the cell surface, enabling the assembly and retention of proteoglycan aggregates in the pericellular matrix. Hyaluronan–CD44 interactions also provide signaling important for maintaining cartilage homeostasis. Disruption of chondrocyte–hyaluronan contact alters CD44 occupancy, initiating alternative signaling cascades. Treatment with hyaluronan oligosaccharides is one approach to uncouple CD44 receptors from its native ligand, hyaluronan. In bovine articular chondrocytes, treatment with hyaluronan oligosaccharides or purified hyaluronan hexasaccharides induced the production of nitric oxide that mirrored nitric oxide production following interleukin-1 treatment. In contrast, 120 and 1260 kDa hyaluronan did not induce production of nitric oxide. Human chondrocytes responded similarly to treatment with hyaluronan or hyaluronan oligosaccharides. Nitric oxide production from chondrocytes was mediated by activation of the inducible nitric oxide synthase, as confirmed by mRNA expression and inhibition of nitric oxide production by diphenyleneiodonium. Co-treatment of chondrocytes with hyaluronan oligosaccharides and interleukin-1 did not demonstrate additive effects. Blocking interleukin-1 receptors with an antagonist did not abolish the production of nitric oxide induced by treatment with hyaluronan oligosaccharides. Moreover, only COS-7 following transfection with a pCD44, not the CD44-null parental cells, responded to treatment with hyaluronan oligosaccharides by releasing nitric oxide. This study demonstrates a novel signaling potential by hyaluronan fragments, in lieu of endogenous hyaluronan–chondrocyte interactions, resulting in the activation of inducible nitric oxide synthase. PMID:16181799

Iacob, Stanca; Knudson, Cheryl B.

2011-01-01

51

Enhancement of nitric oxide production by association of nitric oxide synthase with N-methyl-D-aspartate receptors via  

E-print Network

Enhancement of nitric oxide production by association of nitric oxide synthase with N-time fluorescence imaging using nitric oxide sensitive dye Hirotaka Ishii,*, Keisuke Shibuya,* Yoshihiro Ohta quantitative study demonstrates that the recruit- ment of neuronal nitric oxide synthase (nNOS) beneath N

Kawato, Suguru

52

Nitric oxide synthase activity in mitochondria  

Microsoft Academic Search

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

Pedram Ghafourifar; Christoph Richter

1997-01-01

53

Tetrahydrocannabinol inhibition of macrophage nitric oxide production  

Microsoft Academic Search

?9-Tetrahydrocannabinol (THC) inhibited nitric oxide (NO.) production by mouse peritoneal macrophages activated by bacterial endotoxin lipopolysaccharide (LPS) and interferon-? (IFN)-?). Inhibition of NO. production was noted at THC concentrations as low as 0.5 ?g\\/mL, and was nearly total at 7 ?g\\/mL. Inhibition was greatest if THC was added 1–4 hr before induction of nitric oxide synthase (NOS) by LPS and

Ronald G. Coffey; Yoshimasa Yamamoto; Elizabeth Snella; Susan Pross

1996-01-01

54

Chemospheric processes of nitric oxide in the mesosphere and stratosphere  

Microsoft Academic Search

The behavior of nitrogen oxides in the stratosphere and mesosphere is discussed with the aid of a model which introduces the photodissociation of nitric oxide and the formation of nitric acid. The profiles of the nitric oxide, nitrogen dioxide and nitric acid concentrations are sensitive to the values of the eddy diffusion coefficients which are adopted. The evaluation of the

G. Brasseur; M. Nicolet

1973-01-01

55

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

Microsoft Academic Search

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

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

2006-01-01

56

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

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

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

57

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

PubMed Central

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

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

2005-01-01

58

Nitric Oxide/Cyclic Guanosine Monophosphate Signaling in the Central  

E-print Network

Nitric Oxide/Cyclic Guanosine Monophosphate Signaling in the Central Complex of the Grasshopper oxide/cyclic guanosine monophosphate (cGMP) signaling pathway. The nitric oxide-donor sodium inhibited singing. To identify pu- tative sources of nitric oxide, brains of Ch. biguttulus were subjected

Ganter, Geoffrey

59

Nitric oxide donor superparamagnetic iron oxide nanoparticles.  

PubMed

This work reports a new strategy for delivering nitric oxide (NO), based on magnetic nanoparticles (MNPs), with great potential for biomedical applications. Water-soluble magnetic nanoparticles were prepared through a co-precipitation method by using ferrous and ferric chlorides in acidic solution, followed by a mercaptosuccinic acid (MSA) coating. The thiolated nanoparticles (SH-NPs) were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), transmission electron microscopy (TEM), and vibrating sample magnetometry (VSM). The results showed that the SH-NPs have a mean diameter of 10nm and display superparamagnetic behavior at room temperature. Free thiol groups on the magnetite surface were nitrosated through the addition of an acidified nitrite solution, yielding nitrosated magnetic nanoparticles (SNO-NPs). The amount of NO covalently bound to the nanoparticles surface was evaluated by chemiluminescense. The SNO-NPs spontaneously released NO in aqueous solution at levels required for biomedical applications. This new magnetic NO-delivery vehicle has a great potential to generate desired amounts of NO directed to the target location. PMID:25427482

Molina, Miguel M; Seabra, Amedea B; de Oliveira, Marcelo G; Itri, Rosangela; Haddad, Paula S

2013-03-01

60

Nitric oxide activates cyclooxygenase enzymes.  

PubMed Central

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 microgram/ml, 18 h) caused an increase in the release of nitrite (NO2-) and prostaglandin E2 (PGE2), products of NOS and COX, respectively. Production of both NO2- and PGE2 was blocked by the NOS inhibitors NG-monomethyl-L-arginine or aminoguanidine. The effects of NG-monomethyl-L-arginine or aminoguanidine were reversed by coincubation with L-Arg, the precursor for NO synthesis, but not by D-Arg. RAW264.7 cells stimulated for 18 h with lipopolysaccharide in L-Arg-free medium (to reduce NO generation by the endogenous NOS pathway) failed to release NO2- and accumulated at least 4-fold less PGE2 when compared to cells in the presence of L-Arg. PGE2 production elicited by a 15-min arachidonic acid treatment of lipopolysaccharide-induced RAW264.7 cells in L-Arg-deficient medium was decreased 3-fold when compared to the release obtained with cells induced in medium containing L-Arg. To examine the NO activation of the induced form of COX in the absence of an endogenous L-Arg, human fetal fibroblasts were first stimulated for 18 h with interleukin 1 beta. These cells released PGE2 but not NO2-, consistent with the induction of COX but not NOS in the fibroblast. Exogenous NO either as a gaseous solution or released by a NO donor, sodium nitroprusside or glyceryl trinitrate, increased COX activity in the interleukin 1 beta-stimulated fibroblasts by 5-fold; these effects were abolished by coincubation with hemoglobin (10 microM), which binds and inactivates NO, but not by methylene blue, an inhibitor of the soluble guanylate cyclase. Furthermore, sodium nitroprusside (0.25-1 mM) increased arachidonic acid-stimulated PGE2 production by murine recombinant COX-1 and COX-2. These results demonstrate that NO enhances COX activity through a mechanism independent of cGMP and suggest that, in conditions in which both the NOS and COX systems are present, there is an NO-mediated increase in the production of proinflammatory prostaglandins that may result in an exacerbated inflammatory response. The data suggest that NO directly interacts with COX to cause an increase in the enzymatic activity. Images Fig. 2 Fig. 3 PMID:7688473

Salvemini, D; Misko, T P; Masferrer, J L; Seibert, K; Currie, M G; Needleman, P

1993-01-01

61

Nitric Oxide Formation by Meteoroids in the Upper Atmosphere  

NASA Technical Reports Server (NTRS)

The process of nitric oxide formation during atmospheric entry of meteoroids is analyzed theoretically. An ablating meteoroid is assumed to be a point source in a uniform flow with a continuum regime evolving in its wake. The amount of nitric oxide produced by high-temperature reactions of air in the continuum regime is calculated by numerical integration of chemical-rate equations. This is accomplished by assuming that flow properties are constant across the reacting region, the radius of the region being determined from considerations of shock-wave formation and molecular diffusion. The results, when summed over the observed mass, velocity, and entry-angle distributions of meteoroids, provide annual global production rates of nitric oxide as a function of altitude. The peak production of nitric oxide is found to occur at altitudes between 9 x 10(exp 4) and 10(exp 5) m, the total annual rate being about 4 x 10(exp 7) kg. The present results suggest that the large concentration of nitric oxide observed below 9.5 x 10(exp 4) m could be attributed to meteoroids instead of photodissociation of nitrogen into metastable, 2D-state atoms, as has been previously hypothesized.

Menees, Gene P.; Park, Chul

1976-01-01

62

Regulation of Tracheal Ciliary Beat Frequency by Nitric Oxide Synthase Substrate L-Arginine  

Microsoft Academic Search

Objectives: Our purpose was to investigate the role of nitric oxide (NO) synthase substrate L-arginine (L-arg) in the regulation of airway ciliary beat frequency (CBF). Methods: We studied the effects of L-arg on CBF of rabbit tracheal epithelial cells by using high-speed digital microscopy and determined the expression and distribution of neuronal nitric oxide synthase (nNOS), inducible nitric oxide synthase

Jian Jiao; Demin Han; Na Meng; Shanzhe Jin; Luo Zhang

2010-01-01

63

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

NASA Technical Reports Server (NTRS)

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.

Cabell, Karen F.; Rock, Kenneth E.

2003-01-01

64

Nitric oxide as a secretory product of mammalian cells  

Microsoft Academic Search

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.

CARL NATHAN

1992-01-01

65

Nitric oxide production in arterial vessels of cirrhotic rats  

Microsoft Academic Search

Indirect evidence exists implicating vascular nitric oxide in the pathogenesis of arterial vasodilation in cirrhosis. In the current study, a coincubation assay to estimate the vascular nitric oxide production was developed and the nitric oxide production by arterial segments of cirrhotic and control rats was assessed. In the assay, measurement of reporter monolayer cell-associated cGMP levels allows the influence of

Josefa Ros; Wladimiro Jimenez; Santiago Lamas; Joan Claria; Vicente Arroyo; Francisca Rivera; Joan Rodes

1995-01-01

66

Oxidation of nitroxyl anion to nitric oxide by copper ions  

PubMed Central

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

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

2000-01-01

67

Induction of nitric oxide synthase in demyelinating regions of multiple sclerosis brains.  

PubMed

The amount of messenger RNA encoding human inducible nitric oxide synthase and the presence and distribution of NADPH diaphorase were determined in tissue sections from multiple sclerosis (MS) and control brains. Levels of human nitric oxide synthase messenger RNA were markedly elevated in MS brains when compared to normal control brains. NADPH diaphorase activity, a histochemical stain reflecting nitric oxide synthase catalytic activity, was detected in reactive astrocytes in active demyelinating MS lesions and at the edge of chronic active demyelinating lesions. Control brains did not contain NADPH diaphorase-positive astrocytes. These results implicate the free radical nitric oxide in the pathogenesis of demyelinating MS lesions. PMID:7526776

Bö, L; Dawson, T M; Wesselingh, S; Mörk, S; Choi, S; Kong, P A; Hanley, D; Trapp, B D

1994-11-01

68

Nitric oxide and the immune response  

Microsoft Academic Search

During the past two decades, nitric oxide (NO) has been recognized as one of the most versatile players in the immune system. It is involved in the pathogenesis and control of infectious diseases, tumors, autoimmune processes and chronic degenerative diseases. Because of its variety of reaction partners (DNA, proteins, low–molecular weight thiols, prosthetic groups, reactive oxygen intermediates), its widespread production

Christian Bogdan

2001-01-01

69

Nitric oxide therapy in sickle cell disease  

Microsoft Academic Search

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

Mark T Gladwin; Alan N Schechter

2001-01-01

70

Formation of nitric oxide from nitroxyl anion: role of quinones and ferricytochrome c  

PubMed Central

Our previous finding that copper ions oxidize nitroxyl anion released from Angeli's salt to nitric oxide prompted us to examine if copper-containing enzymes shared this property. The copper-containing enzyme, tyrosinase, which catalyses the hydroxylation of monophenols to diphenols and the subsequent oxidation of these to the respective unstable quinone, failed to generate nitric oxide from Angeli's salt by itself, but did so in the presence of tyrosine. L-DOPA, the initial product of the reaction of tyrosinase with tyrosine, was not the active species, since it failed to generate nitric oxide from Angeli's salt. Nevertheless, L-DOPA and two other substrates, namely, catechol and tyramine did produce nitric oxide from Angeli's salt in the presence of tyrosinase, suggesting involvement of the respective unstable quinones. In support, we found that 1,4-benzoquinone produced a powerful nitric oxide signal from Angeli's salt. Coenzyme Qo, an analogue of ubiquinone, failed to generate nitric oxide from Angeli's salt by itself, but produced a powerful signal in the presence of its mitochondrial complex III cofactor, ferricytochrome c. Experiments conducted on rat aortic rings with the mitochondrial complex III inhibitor, myxothiazol, to determine if this pathway was responsible for the vascular conversion of nitroxyl to nitric oxide were equivocal: relaxation to Angeli's salt was inhibited but so too was that to unrelated relaxants. Thus, certain quinones oxidize nitroxyl to nitric oxide. Further work is required to determine if endogenous quinones contribute to the relaxant actions of nitroxyl donors such as Angeli's salt. PMID:11156574

Buyukafsar, Kansu; Nelli, Silvia; Martin, William

2001-01-01

71

Quantitative determination of nitric oxide production in haemocytes: nitrite reduction activity as a potential pathway of NO formation in haemolymph of Galleria mellonella larvae.  

PubMed

The generation of nitric oxide by Galleria mellonella larvae haemocytes has been investigated. For this purpose, a fluorescent method, specific for detection of NO, has been developed. The method is based on the application of fluorescence probe DAF-FM diacetate and nitronyl nitroxyl radical, NNR, which accelerates the NO-dependent formation of fluorescence product, DAF-FM triazole. The key feature of the method is the registration and analysis of differential kinetics, namely, the difference of kinetics obtained in samples with NNR and without NNR. This approach allows us to exclude any other kinetic processes not related to triazole formation. The differential kinetics were calibrated versus NO generation rate and the resulting low limit of method sensitivity was obtained as about 0.4-0.5 nM/min. The generation of nitric oxide by the haemocytes of insects treated with LPS in vivo has been detected at a rate of 0.5-0.7 nM/min. However, the production of NO in haemocyte suspensions treated with both the substrate, l-arginine, and the inhibitor, l-NAME, of NOS, has not been detected within method sensitivity. These data provide only the upper level of NO generation by haemocytes but cannot be used to draw definite conclusions about NOS as a source of NO. Meanwhile, it is known, that NO can be formed by NOS independent mechanism. Indeed, we have observed a significant increase in NO generation in the samples of haemocytes intracellularly loaded with nitrite. Moreover, adding nitrite to lysed haemocytes results in the higher NO generation rate. After addition of 500 ?M nitrite, the rates of NO generation in the samples are determined to be 2 and 20-30 nM/min, respectively. The nitrite/nitrate content of haemocytes and lymph were found to be 5 and 50 ?M, respectively. The detected nitrite reduction activity of haemocytes allowed us to estimate the generation rate of nitric oxide as 0.05-0.5 nM/min from endogenous nitrite. It is thus assumed that the observed nitrite reduction activity in haemocytes is dominant in the increased NO production during immune response of the G. mellonella larvae. PMID:24406682

Semenova, Alexandra D; Glazachev, Yuriy I; Slepneva, Irina A; Glupov, Viktor V

2014-02-15

72

Neuroprotective properties of nitric oxide and S-nitrosoglutathione  

SciTech Connect

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

Rauhala, Pekka [Institute of Biomedicine, Pharmacology, Biomedicum Helsinki, P.O. Box 63, University of Helsinki 00014, Helsinki (Finland)]. E-mail: pekka.rauhala@helsinki.fi; Andoh, Tsugunobu [Department of Applied Pharmacology, Toyama Medical and Pharmaceutical University, Toyama (Japan); Chiueh, C.C. [Laboratory of Clinical Sciences, NIMH, National Institute of Health, Bethesda, MD 29892-1264 (United States); Taipei Medical University, 250 Wu-Sing Street, Taipei 100, Taiwan (China)

2005-09-01

73

Glucosamine Inhibits Inducible Nitric Oxide Synthesis  

Microsoft Academic Search

Glucosamine is widely used in Europe for treatment of arthritis in humans. Based on recent findings that excess production of nitric oxide (NO) by inducible NO synthase (iNOS) mediates the pathogenesis of arthritis, we hypothesized that glucosamine may inhibit NO synthesis. To test this hypothesis, we used an in vivo rat model of lipopolysaccharide (LPS)-induced inflammation. Intravenous administration of d-glucosamine

Cynthia J. Meininger; Katherine A. Kelly; Hui Li; Tony E. Haynes; Guoyao Wu

2000-01-01

74

Brain nitric oxide synthase is a haemoprotein.  

PubMed

Brain nitric oxide (NO) synthase showed pyridine haemochrome spectra typical of ferroprotoporphyrin IX-containing enzymes. The haem content of purified NO synthase was in the range 0.7-0.9 mol/mol of 160 kDa subunit. In the presence of CO, NO, KCN and miconazole, the L-citrulline-forming activity of NO synthase was markedly diminished, demonstrating that enzyme-bound haem is involved in enzymic NO synthesis. PMID:1280109

Klatt, P; Schmidt, K; Mayer, B

1992-11-15

75

Functional role of nitric oxide in plants  

Microsoft Academic Search

The review considers involvement of nitric oxide (NO) in regulation of basic physiological processes underlying growth, development,\\u000a and senescence in plants. The NO sources in plants, as well as direct and indirect NO signaling mechanisms are also reviewed.\\u000a Particular attention is paid to the role of this secondary messenger in plant responses to various abiotic stresses, such\\u000a as mechanical injury,

Yu. A. Krasylenko; A. I. Yemets; Ya. B. Blume

2010-01-01

76

Modulation of nitric oxide bioavailability by erythrocytes  

NASA Astrophysics Data System (ADS)

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

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

2001-09-01

77

Nitric oxide releasing material adsorbs more fibrinogen.  

PubMed

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

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

2013-11-01

78

Modulation of nitric oxide bioavailability by erythrocytes  

PubMed Central

Nitric oxide (NO) activates soluble guanylyl cyclase in smooth muscle cells to induce vasodilation in the vasculature. However, as hemoglobin (Hb) is an effective scavenger of NO and is present in high concentrations inside the red blood cell (RBC), the bioavailability of NO would be too low to elicit soluble guanylyl cyclase activation in the presence of blood. Therefore, NO bioactivity must be preserved. Here we present evidence suggesting that the RBC participates in the preservation of NO bioactivity by reducing NO influx. The NO uptake by RBCs was increased and decreased by altering the degree of band 3 binding to the cytoskeleton. Methemoglobin and denatured hemoglobin binding to the RBC membrane or cytoskeleton also were shown to contribute to reducing the NO uptake rate of the RBC. These alterations in NO uptake by the RBC, hence the NO bioavailability, were determined to correlate with the vasodilation of isolated blood vessels. Our observations suggest that RBC membrane and cytoskeleton associated NO-inert proteins provide a barrier for NO diffusion and thus account for the reduction in the NO uptake rate of RBCs. PMID:11573011

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

2001-01-01

79

Vascular nitric oxide: formation and function  

PubMed Central

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

Jin, Richard C; Loscalzo, Joseph

2010-01-01

80

Biological nitric oxide signalling: chemistry and terminology.  

PubMed

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

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

2013-08-01

81

Biological nitric oxide signalling: chemistry and terminology  

PubMed Central

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

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

2013-01-01

82

Updated Role of Nitric Oxide in Disorders of Erythrocyte Function  

PubMed Central

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

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

2013-01-01

83

Oxidative desulfurization of askale coal by nitric acid solution  

SciTech Connect

Efficient use of fossil fuels is of utmost importance in a world that depends on these for the greatest part of its energy needs. Although lignite is a widely used fossil fuel, its sulfur content limits its consumption. This study aims to capture combustible sulfur in the ash by oxidizing it with solution of nitric acid solution. Thus, the combustible sulfur in the coal was converted to sulfate form in the ash. Parameters affecting the conversion of sulfur were determined to be nitric acid concentration, reaction time and mean particle size at constant (near room) temperature and shaking rate. The maximum desulfurization efficiency reached was 38.7% of the original combustible sulfur with 0.3 M nitric acid solution, 16 h of reaction time and 0.1 mm mean particle size.

Guru, M. [Gazi University, Ankara (Turkey). Dept. of Chemical Engineering

2007-07-01

84

Nitric Oxide: An Endogenous Modulator of Leukocyte Adhesion  

Microsoft Academic Search

The objective of this study was to determine whether endogenous nitric oxide (NO) inhibits leukocyte adhesion to vascular endothelium. This was accomplished by superfusing a cat mesenteric preparation with inhibitors of NO production, N^G-monomethyl-L-arginine (L-NMMA) or N^G-nitro-L-arginine methyl ester (L-NAME), and observing single (30-mu m diameter) venules by intravital video microscopy. Thirty minutes into the superfusion period the number of

P. Kubes; M. Suzuki; D. N. Granger

1991-01-01

85

Nitric oxide, oxidants, and protein tyrosine nitration  

Microsoft Academic Search

The occurrence of protein tyrosine nitration under disease conditions is now firmly established and represents a shift from the signal transducing physiological actions of NO to oxidative and potentially pathogenic pathways. Tyrosine nitration is mediated by reactive nitrogen species such as peroxynitrite anion (ONOO-) and nitrogen dioxide (NO2), formed as secondary products of NO metabolism in the presence of oxidants

Rafael Radi

2004-01-01

86

Nitric Oxide Myoglobin: Crystal Structure and Analysis of Ligand Geometry  

E-print Network

Nitric Oxide Myoglobin: Crystal Structure and Analysis of Ligand Geometry Eric Allen Brucker,1 John School of Medicine, Cleveland, Ohio ABSTRACT The structure of the ferrous nitric oxide form of native oxide ligand is bent with respect to the heme plane: the Fe-N-O angle is 112°. This angle is smaller

Phillips, George N. Jr.

87

Inhaled nitric oxide in chronic obstructive lung disease  

SciTech Connect

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.

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

1993-01-30

88

Satellite measurements of nitric oxide in the polar region  

NASA Technical Reports Server (NTRS)

Ultraviolet measurements of the (1, 0) gamma band of nitric oxide in fluorescence by a satellite at high latitudes show nitric oxide concentrations which are highly variable in both time and space. The average nitric oxide concentration is 3 to 4 times higher at high latitudes than at midlatitudes. If auroral activity is responsible for the larger nitric oxide densities and if the reaction N(2D) + O2 is the source of NO, then auroral processes must be more efficient in the production of N(2D) atoms than dayglow processes.

Rusch, D. W.; Barth, C. A.

1975-01-01

89

Hsp90? inhibition modulates nitric oxide production and nitric oxide-induced apoptosis in human chondrocytes  

PubMed Central

Background Hsp90? is a member of the Hsp90 family of protein chaperones. This family plays essential roles in the folding, maturation and activity of many proteins that are involved in signal transduction and transcriptional regulation. The role of this protein in chondrocytes is not well understood, although its increase in osteoarthritic cells has been reported. The present study aimed to explore the role of Hsp90? in key aspects of OA pathogenesis. Methods Human OA chondrocytes were isolated from cartilage obtained from patients undergoing joint replacement surgery, and primary cultured. Cells were stimulated with proinflammatory cytokines (IL-1? or TNF-?) and nitric oxide donors (NOC-12 or SNP). For Hsp90? inhibition, two different chemical inhibitors (Geldanamycin and Novobiocin) were employed, or siRNA transfection procedures were carried out. Gene expression was determined by real-time PCR, apoptosis was quantified by flow cytometry and ELISA, and nitric oxide (NO) production was evaluated by the Griess method. Indirect immunofluorescence assays were performed to evaluate the presence of Hsp90? in stimulated cells. Results Hsp90? was found to be increased by proinflammatory cytokines. Inhibition of Hsp90? by the chemicals Geldanamycin (GA) and Novobiocin (NB) caused a dose-dependent decrease of the NO production induced by IL-1? in chondrocytes, up to basal levels. Immunofluorescence analyses demonstrate that the NO donors NOC-12 and SNP also increased Hsp90?. Chemical inhibition or specific gene silencing of this chaperone reduced the DNA condensation and fragmentation, typical of death by apoptosis, that is induced by NO donors in chondrocytes. Conclusions The present results show how Hsp90? modulates NO production and NO-mediated cellular death in human OA chondrocytes. PMID:22004293

2011-01-01

90

Processes regulating nitric oxide emissions from soils  

PubMed Central

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

Pilegaard, Kim

2013-01-01

91

Transport of Nitric Oxide by Perfluorocarbon Emulsion  

PubMed Central

Perfluorocarbon (PFC) emulsions can transport and release various gases based on concentration gradients. The objective of this study was to determine the possibility of carrying and delivering exogenous nitric oxide (NO) into the circulation by simply loading PFC emulsion with NO prior infusion. PFC was equilibrated with room air (PFC) or 300 ppm NO (PFC-NO) at atmospheric pressure. Isotonic saline solution was used as a volume control (Saline). PFC and PFC-NO were infused at a dose of 3.5 mL/kg in the hamster window chamber model. Blood chemistry, and systemic and microvascular hemodynamic response were measured. Infusion of PFC preloaded with NO reduced blood pressure, induced microvascular vasodilation and increased capillary perfusion; although these changes lasted less than 30 min post infusion. On the other hand, infusion of PFC (without NO) produced vasoconstriction; however, the vasoconstriction was followed by vasodilatation at 30 min post infusion. Plasma nitrite and nitrate increased 15 min after infusion of NO preloaded PFC compared to PFC, 60 min after infusion nitrite and nitrate were not different, and 90 min after infusion plasma S-nitrosothiols increased in both groups. Infusion of NO preloaded PFC resulted in acute vascular relaxation, where as infusion of PFC (without NO) produced vasoconstriction, potentially due to NO sequestration by the PFC micelles. The late effects of PFC infusion are due to NO redistribution and plasma S-nitrosothiols. Gas solubility in PFC can provide a tool to modulate plasma vasoactive NO forms availability and improve microcirculatory function and promote increased blood flow. PMID:23966236

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

2014-01-01

92

Clinical application of nasal nitric oxide measurement in pediatric airway diseases.  

PubMed

Nitric oxide plays an important role in several physiological and pathophysiological processes in the respiratory tract. Different ways to measure nasal nitric oxide levels in children are currently available. The possibility of obtaining nasal nitric oxide measurement from relatively young children, combined with the availability of portable devices that can be used even in the office setting, opens new perspectives for nasal nitric oxide analysis in the pediatric daily practice. This review presents a synopsis about the current clinical applications of nasal nitric oxide measurement in the pediatric clinical practice. A total of 3,775 articles on the topic were identified, of which 883 duplicates were removed, and 2,803 were excluded based on review of titles and abstracts. Eighty-nine full text articles were assessed for eligibility and 32 additional articles were obtained from the reference lists of the retrieved studies. Since very low nasal nitric oxide levels are found in the majority of patients with primary ciliary dyskinesia, most publications support a central role for nasal nitric oxide to screen the disease, and indicate that it is a very helpful first-line tool in the real-life work-up in all age groups. Decreased nasal nitric oxide concentration is also typical of cystic fibrosis, even though nasal nitric oxide is not as low as in primary ciliary dyskinesia. In other upper airway disorders such as allergic rhinitis, rhinosinusitis, nasal polyposis, and adenoidal hypertrophy, clinical utility of nasal nitric oxide is still critically questioned and remains to be established. Since nNO determination is flow dependent, a general consensus from the major investigators in this area is highly desirable so that future studies will be performed with the same flow rate. A shared nNO methodology will enable to overcome the challenges that lie ahead in incorporating nNO measurement into the mainstream clinical setting of pediatric airway diseases. Pediatr Pulmonol. 2015; 50:85-99. © 2014 Wiley Periodicals, Inc. PMID:25156952

Manna, Angelo; Montella, Silvia; Maniscalco, Mauro; Maglione, Marco; Santamaria, Francesca

2015-01-01

93

Amino acids, polyamines, and nitric oxide synthesis in the ovine conceptus  

E-print Network

The objective of this study was to determine concentrations of amino acids and polyamines as well as nitric oxide (NO) and polyamine synthesis in the ovine conceptus (embryo/fetal and associated placental membrane). Ewes were hysterectomized...

Kwon, Hyuk Jung

2005-08-29

94

Mycobacteriocidal Action of Exogenous Nitric Oxide  

PubMed Central

We tested the hypothesis that exposure of extracellular Mycobacterium tuberculosis to low concentrations (<100 ppm) of nitric oxide (NO) for short periods (24 h or less) will result in microbial killing. We observed that NO had both dose- and time-dependent cidal effects that were very significant by two-way analysis of variance (F ratios of 13.4 [P < 0.001] and 98.1 [P < 0.0001], respectively). Conceivably, extracellular bacilli in patients with pulmonary tuberculosis might be vulnerable to exogenous NO. PMID:9925545

Long, Richard; Light, Bruce; Talbot, James A.

1999-01-01

95

Nitric oxide reactions of bio-Inspired zinc and cobalt complexes  

E-print Network

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, ...

Kozhukh, Julia, 1985-

2012-01-01

96

Nitric oxide synthase inhibitors and cerebral vasospasm.  

PubMed

L-arginine is a source of nitric oxide (NO) that is cleaved from the terminal guanidino nitrogen atom by nitric oxide synthase (NOS). NO evokes, because of its free radical properties and affinity to heme, ferrous iron and cysteine, a wide spectrum of physiological and pathophysiological effects. For many years, different exogenous NOS inhibitors were used to elucidate the role of NOS and NO in health and disease. Later, endogenous NOS inhibitors, as asymmetric dimethylarginine (ADMA) were discovered. Endogenous inhibitors as ADMA are produced by post-translational methylation of L-arginine which is catalyzed by a family of protein N-methyltransferases (PRMT), using S-adenosylmethionine as a methyl group donor. ADMA is eliminated by dimethylarginine dimethylaminohydrolases (DDAH I or II). ADMA hydrolysis increases NOS activity and NO production. Furthermore, L-citrulline, a by-product of ADMA hydrolysis as well as of NO production by NOS, can in turn inhibit DDAH. Therefore, endogenous inhibition of NOS can be modified via different ways (1) changing the availability of L-arginine and/or of L-citrulline; (2) stimulating or inhibiting DDAH activity; (3) modifying methylation via regulating availability of adenosylmethionine; or (4) modifying PRMT activity. Research elucidating the role of NOS inhibitors in respect of delayed cerebral vasospasm after subarachnoid hemorrhage is summarized. PMID:21116921

Jung, C S

2011-01-01

97

Nitric oxide rescues thalidomide mediated teratogenicity.  

PubMed

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

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

2012-01-01

98

Nitric oxide in the central nervous system: neuroprotection versus neurotoxicity  

Microsoft Academic Search

At the end of the 1980s, it was clearly demonstrated that cells produce nitric oxide and that this gaseous molecule is involved in the regulation of the cardiovascular, immune and nervous systems, rather than simply being a toxic pollutant. In the CNS, nitric oxide has an array of functions, such as the regulation of synaptic plasticity, the sleep–wake cycle and

Cesare Mancuso; Menotti Calvani; Enrico Rizzarelli; D. Allan Butterfield; Anna Maria Giuffrida Stella; Vittorio Calabrese

2007-01-01

99

A cellular model for screening neuronal nitric oxide synthase inhibitors  

Microsoft Academic Search

Nitric oxide synthase (NOS) inhibitors are potential drug candidates because it has been well demonstrated that excessive production of nitric oxide critically contributes to a range of diseases. Most inhibitors have been screened in vitro using recombinant enzymes, leading to the discovery of a variety of potent compounds. To make inhibition studies more physiologically relevant and bridge the gap between

Jianguo Fang; Richard B. Silverman

2009-01-01

100

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...

101

Nitric Oxide--Some Old and New Perspectives.  

ERIC Educational Resources Information Center

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…

Ainscough, Eric W.; Brodie, Andrew M.

1995-01-01

102

Expired nitric oxide as a marker for childhood asthma  

Microsoft Academic Search

Expression of the inflammatory isoform of the enzyme nitric oxide synthase (NOS) is increased in airway-lining cells of patients with asthma. The NOS product nitric oxide (NO·) was measured in the expired gas of children with asthma. Vital capacity expirates from 21 control subjects and 13 subjects with asthma were assayed by chemiluminescence. Measurements were highly reproducible (coefficient of variation,

Brent V. Nelson; Steven Sears; Jon Woods; Con Yee Ling; John Hunt; Laura M. Clapper; Benjamin Gaston

1997-01-01

103

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

E-print Network

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. ...

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

2004-01-01

104

Cytostasis is required for IL-1 induced nitric oxide production in transformed hamster fibroblasts.  

PubMed

Interleukin-1 (IL-1) is known to inhibit proliferation in some tumor cells. This proinflammatory cytokine also induces nitric oxide production in a variety of cell types. In the present studies we determined if nitric oxide is involved in IL-1 induced growth inhibition in spontaneously transformed hamster embryonic fibroblasts (STHE cells). Both IL-1 alpha and IL-1 beta were found to stimulate nitric oxide production and to reduce 3H-thymidine (TdR) incorporation in high density cultures of STHE cells. However, maximal cytostasis was observed at least 24 h before significant amounts of nitric oxide accumulated in the cultures. In addition, doses of IL-1 which were too low to stimulate nitric oxide synthesis were effective in inducing cytostasis. Furthermore, in low density cultures of STHE cells, IL-1 inhibited DNA synthesis without inducing nitric oxide production. The nitric oxide synthase inhibitor NG-monomethyl-1-arginine (L-NMMA) had no effect on proliferation of cells plated at low density. In contrast, L-NMMA treatment resulted in a 40-60% reduction in IL-1 induced cytostasis in high density cultures. Neutralizing antibodies to IL-1 were found to completely block IL-1 induced cytostasis and nitric oxide production in cells plated at both densities. Although anti-IL-1 alpha and anti-IL-1 beta antibodies were highly specific and did not cross react, anti-tumor necrosis factor-alpha (TNF-alpha) antibody was able to partially suppress activation of STHE cells by both IL-1 alpha and IL-1 beta. These data suggest a potential involvement of endogenous TNF-alpha in IL-1 induced cytostasis and nitric oxide production. Exponentially growing STHE cells produced six-times less nitric oxide than non-proliferating cells. A ten-fold excess of 1-arginine was found to stimulate nitric oxide synthesis, an action that was independent of the rate of cellular proliferation. Taken together these data suggest that nitric oxide is not a major mediator of IL-1 induced cytostasis in STHE cells. Moreover, cytostasis appears to be required for nitric oxide synthesis in these cells. PMID:8952702

Lavnikova, N; Lakhotia, A; Patel, N; Prokhorova, S; Laskin, D L

1996-12-01

105

Nitric oxide availability as a marker of oxidative stress.  

PubMed

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

Pierini, Dan; Bryan, Nathan S

2015-01-01

106

Nitric Oxide Modulators: An Emerging Class of Medicinal Agents  

PubMed Central

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

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

2012-01-01

107

Nitric oxide induces cell death in Taxus cells.  

PubMed

Sodium nitroprusside (SNP), a nitric oxide donor, or centrifugation at 150 times unit gravity, caused a nitric oxide burst in oocyte-derived Taxus brevifolia haploid cultures. This burst, visualized by the specific fluorescent probe 4,5-diaminofluorescein diacetate (DAF-2 DA), preceded a significant increase in nuclear DNA fragmentation and cell death. DNA fragmentation was detected in situ by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) of DNA 3'-OH groups. Nitric oxide formation and cell death were significantly decreased by N(G)-monomethyl-L-arginine (L-NMMA), a nitric oxide-synthase (NOS; EC 1.14.13.39) inhibitor. Our results show that nitric oxide leads to irreversible DNA fragmentation and cell death under stressful conditions, and that its effect can be prevented by L-NMMA. PMID:10960730

Pedroso; Magalhaes; Durzan

2000-08-22

108

Nitric oxide protects endothelium from cadmium mediated leakiness.  

PubMed

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

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

2013-05-01

109

Pharmacology of endothelium-derived nitric oxide and nitrovasodilators.  

PubMed Central

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

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

1991-01-01

110

Role of nitric oxide in pathological responses of the lung to exposure to environmental/occupational agents.  

PubMed

Conflicting evidence exists as to whether nitric oxide expresses damaging/inflammatory or antioxidant/anti-inflammatory properties. Data presented in this review indicate that in vitro or in vivo exposure to selected environmental or occupational agents, such as asbestos, silica, ozone or lipopolysaccharide, can result in up-regulation of inducible nitric oxide synthase by alveolar macrophages and pulmonary epithelial cells. In the case of silica exposure, evidence consistently supports a damaging/inflammatory role of nitric oxide and/or peroxynitrite in the pathogenesis of lung disease. Although conflicting data have been reported, the majority of published studies suggest that nitric oxide plays a damaging role in pulmonary injury resulting from exposure to ozone or asbestos. In contrast, most information supports an anti-inflammatory role of nitric oxide following exposure to lipopolysaccharide. Further investigation is required to elucidate fully the mechanisms involved in determining the role of nitric oxide in the initiation and progression of various pulmonary diseases. PMID:15035823

Zeidler, Patti C; Castranova, Vincent

2004-01-01

111

Modulation of Renal Blood Flow and Vascular Tone by Neuronal Nitric Oxide Synthase-Derived Nitric Oxide  

Microsoft Academic Search

Nitric oxide (NO) formed via neuronal nitric oxide synthase (nNOS) in renal vasculature and tissues and in the brain plays an important role in controlling renal hemodynamics, renal function, and systemic blood pressure. Activation of parasympathetic nitrergic nerves innervating renal vasculature contributes to vasodilatation in renal arteries and pre- and postglomerular arterioles, an increase in renal blood flow, and a

Noboru Toda; Tomio Okamura

2011-01-01

112

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...

113

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

PubMed Central

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

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

2013-01-01

114

Biochemical aspects of nitric oxide synthase feedback regulation by nitric oxide  

PubMed Central

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

Kopincová, Jana; Púzserová, Angelika; Bernátová, Iveta

2011-01-01

115

Superhydrophobic nitric oxide-releasing xerogels.  

PubMed

Superhydrophobic nitric oxide (NO)-releasing xerogels were prepared by spray-coating a fluorinated silane/silica composite onto N-diazeniumdiolate NO donor-modified xerogels. The thickness of the superhydrophobic layer was used to extend NO release durations from 59 to 105h. The resulting xerogels were stable, maintaining superhydrophobicity for up to 1month (the longest duration tested) when immersed in solution, with no leaching of silica or undesirable fragmentation detected. The combination of superhydrophobicity and NO release reduced viable Pseudomonas aeruginosa adhesion by >2-logs. The killing effect of NO was demonstrated at longer bacterial contact times, with superhydrophobic NO-releasing xerogels resulting in 3.8-log reductions in adhered viable bacteria vs. controls. With no observed toxicity to L929 murine fibroblasts, NO-releasing superhydrophobic membranes may be valuable antibacterial coatings for implants as they both reduce adhesion and kill bacteria that do adhere. PMID:24797527

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

2014-08-01

116

An intercomparison of nitric oxide measurement techniques  

NASA Technical Reports Server (NTRS)

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.

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

117

MAP kinases bind endothelial nitric oxide synthase.  

PubMed

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 (k on ? .15 × 10(6) 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

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

2012-01-01

118

Nitric Oxide Signaling in the Microcirculation  

PubMed Central

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

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

2013-01-01

119

Nitric Oxide Release Part I. Macromolecular Scaffolds  

PubMed Central

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

Riccio, Daniel A.; Schoenfisch, Mark H.

2012-01-01

120

Nitric oxide-releasing porous silicon nanoparticles  

PubMed Central

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

2014-01-01

121

Nitric Oxide Synthase Inhibitors as Antidepressants  

PubMed Central

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

Wegener, Gregers; Volke, Vallo

2010-01-01

122

Recent developments in nitric oxide donor drugs  

PubMed Central

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

Miller, M R; Megson, I L

2007-01-01

123

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

NASA Astrophysics Data System (ADS)

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.

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

2010-01-01

124

Piper Sarmentosum Increases Nitric Oxide Production in Oxidative Stress: A Study on Human Umbilical Vein Endothelial Cells  

PubMed Central

OBJECTIVE: Nitric oxide produced by endothelial nitric oxide synthase (eNOS) possesses multiple anti-atherosclerotic properties. Hence, enhanced expression of eNOS and increased Nitric oxide levels may protect against the development of atherosclerosis. Piper sarmentosum is a tropical plant with antioxidant and anti-inflammatory activities. This study aimed to investigate the effects of Piper sarmentosum on the eNOS and Nitric oxide pathway in cultured human umbilical vein endothelial cells (HUVECs). METHODS: HUVECs were divided into four groups: control, treatment with 180 ?M hydrogen peroxide (H2O2), treatment with 150 ?g/mL aqueous extract of Piper sarmentosum, and concomitant treatment with aqueous extract of PS and H2O2 for 24 hours. Subsequently, HUVECs were harvested and eNOS mRNA expression was determined using qPCR. The eNOS protein level was measured using ELISA, and the eNOS activity and Nitric oxide level were determined by the Griess reaction. RESULTS: Human umbilical vein endothelial cells treated with aqueous extract of Piper sarmentosum showed a marked induction of Nitric oxide. Treatment with PS also resulted in increased eNOS mRNA expression, eNOS protein level and eNOS activity in HUVECs. CONCLUSION: Aqueous extract of Piper sarmentosum may improve endothelial function by promoting NO production in HUVECs. PMID:20668629

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

2010-01-01

125

Tetrahydrobiopterin alters superoxide and nitric oxide release in prehypertensive rats.  

PubMed Central

Constitutive nitric oxide synthase (cNOS) with insufficient cofactor (6R)-5,6,7,8-tetrahydrobiopterin (H4B) may generate damaging superoxide (O2-). This study was designed to determine whether cNOS-dependent generation of O2- occurs in spontaneously hypertensive rats (SHR) before the onset of hypertension. Aortas from 4-wk-old SHR and Wistar-Kyoto rats were used. cNOS was stimulated by calcium ionophore A23187. In situ measurements of nitric oxide and hydrogen peroxide by electrochemical sensors and O2- production by chemiluminescence method were performed. Isometric tension was continuously recorded. H4B by high performance liquid chromatography and [3H]citrulline assay were determined in homogenized tissue. The A23187-stimulated production of O2- and its superoxide dismutase product hydrogen peroxide were significantly higher, whereas nitric oxide release was reduced in SHR aortas, with opposite results in the presence of exogenous H4B. Furthermore, NG-monomethyl-L-arginine inhibited the generation of cNOS-dependent O2- by approximately 70%. Natural H4B levels were similar in both strains; however, equivalent cNOS activity required additional H4B in SHR. The endothelium-dependent relaxations to A23187 were significantly inhibited by catalase, and enhanced by superoxide dismutase, only in SHR; however, these enzymes had no effect in the presence of H4B. Thus, dysfunctional cNOS may be a source of O2- in prehypertensive SHR and contribute to the development of hypertension and its vascular complications. PMID:9525996

Cosentino, F; Patton, S; d'Uscio, L V; Werner, E R; Werner-Felmayer, G; Moreau, P; Malinski, T; Lüscher, T F

1998-01-01

126

The oral microbiome and nitric oxide homoeostasis.  

PubMed

The tiny radical nitric oxide (NO) participates in a vast number of physiological functions including vasodilation, nerve transmission, host defence and cellular energetics. Classically produced by a family of specific enzymes, NO synthases (NOSs), NO signals via reactions with other radicals or transition metals. An alternative pathway for the generation of NO is the nitrate-nitrite-NO pathway in which the inorganic anions nitrate (NO3-) and nitrite (NO2-) are reduced to NO and other reactive nitrogen intermediates. Nitrate and nitrite are oxidation products from NOS-dependent NO generation but also constituents in our diet, mainly in leafy green vegetables. Irrespective of origin, active uptake of circulating nitrate in the salivary glands, excretion in saliva and subsequent reduction to nitrite by oral commensal bacteria are all necessary steps for further NO generation. This central role of the oral cavity in regulating NO generation from nitrate presents a new and intriguing aspect of the human microbiome in health and disease. In this review, we present recent advances in our understanding of the nitrate-nitrite-NO pathway and specifically highlight the importance of the oral cavity as a hub for its function. PMID:23837897

Hezel, Mp; Weitzberg, E

2015-01-01

127

Nitric oxide delivery system for biological media.  

PubMed

Developing an understanding of how chronically elevated levels of nitric oxide at sites of inflammation or infection can lead to cancer and other diseases requires ways to expose cells and biomolecules to controlled concentrations of NO for hours to days. To achieve this, a small (65ml) stirred reactor was fabricated that included a flat, porous poly(tetrafluoroethylene) membrane and a loop of poly(dimethylsiloxane) tubing for NO and O(2) delivery, respectively. It was equipped with probes for continuous monitoring of NO and O(2) concentrations. Transport through the membrane and tubing was characterized using separate O(2) depletion experiments. In experiments using only a 10% NO mixture and a buffer that was initially air-equilibrated, constant rates of accumulation were observed for NO(2)(-) (53±2?M/h; n=8), the end product of NO oxidation, as expected. Simultaneous delivery of NO and O(2) yielded steady NO concentrations of 0.7-2.3?M, depending on the tubing length and gas compositions. A model was developed that allows the steady NO and O(2) concentrations and the duration of the transients to be predicted to within a few percent. This system should be useful for exposing cells and biomolecules to concentrations of NO that mimic those in vivo. PMID:21073946

Skinn, Brian T; Lim, Chang Hoon; Deen, William M

2011-01-15

128

Endothelial nitric oxide synthase, vascular integrity and human exceptional longevity  

PubMed Central

Aging is the sum of the deleterious changes that occur as time goes by. It is the main risk factor for the development of cardiovascular disease, and aging of the vasculature is the event that most often impacts on the health of elderly people. The “free-radical theory of aging” was proposed to explain aging as a consequence of the accumulation of reactive oxygen species (ROS). However, recent findings contradict this theory, and it now seems that mechanisms mediating longevity act through induction of oxidative stress. In fact, calorie restriction ? a powerful way of delaying aging ? increases ROS accumulation due to stimulation of the basal metabolic rate; moreover, reports show that antioxidant therapy is detrimental to healthy aging. We also now know that genetic manipulation of the insulin-like-growth-factor-1/insulin signal (IIS) has a profound impact on the rate of aging and that the IIS is modulated by calorie restriction and physical exercise. The IIS regulates activation of nitric oxide synthase (eNOS), the activity of which is essential to improving lifespan through calorie restriction, as demonstrated by experiments on eNOS knockout mice. Indeed, eNOS has a key role in maintaining vascular integrity during aging by activating vasorelaxation and allowing migration and angiogenesis. In this review, we will overview current literature on these topics and we will try to convince the reader of the importance of vascular integrity and nitric oxide production in determining healthy aging. PMID:23153280

2012-01-01

129

Lack of Central Nitric Oxide Triggers Erectile Dysfuntion in Diabetes  

NSDL National Science Digital Library

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.

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

2007-03-01

130

21 CFR 862.3080 - Breath nitric oxide test system.  

Code of Federal Regulations, 2012 CFR

...DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test Systems § 862.3080 Breath nitric oxide test system. (a) Identification....

2012-04-01

131

21 CFR 862.3080 - Breath nitric oxide test system.  

Code of Federal Regulations, 2011 CFR

...DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test Systems § 862.3080 Breath nitric oxide test system. (a) Identification....

2011-04-01

132

21 CFR 862.3080 - Breath nitric oxide test system.  

Code of Federal Regulations, 2013 CFR

...DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test Systems § 862.3080 Breath nitric oxide test system. (a) Identification....

2013-04-01

133

21 CFR 862.3080 - Breath nitric oxide test system.  

Code of Federal Regulations, 2014 CFR

...DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test Systems § 862.3080 Breath nitric oxide test system. (a) Identification....

2014-04-01

134

Prediction of nitric oxide concentrations during inflammation and carcinogenesis  

E-print Network

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 ...

Chin, Melanie Pei-Heng

2010-01-01

135

Role of nitric oxide in the progression of pneumoconiosis.  

PubMed

Conflicting evidence has been reported as to whether nitric oxide (NO) possesses anti-inflammatory or inflammatory properties. Data are presented indicating that in vitro or in vivo exposure to selected occupational dusts, i.e., crystalline silica, organic dust contaminated with endotoxin, or asbestos, results in upregulation of inducible nitric oxide synthase (iNOS) and the production of NO by alveolar macrophages and pulmonary epithelial cells. Nitric oxide production is associated temporally and anatomically with pulmonary damage, inflammation, and disease progression in response to occupational dusts. Blockage of inducible nitric oxide synthase by administration of NOS inhibitors or in iNOS knockout mice decreases the magnitude of injury and inflammation following in vivo exposure to silica, endotoxin, or asbestos. Therefore, NO may play an important role in the initiation and progression of pneumoconiosis. PMID:14972015

Castranova, V

2004-01-01

136

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

PubMed Central

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

2013-01-01

137

Obesity, insulin resistance, and skeletal muscle nitric oxide synthase  

PubMed Central

The molecular mechanisms responsible for impaired insulin action have yet to be fully identified. Rodent models demonstrate a strong relationship between insulin resistance and an elevation in skeletal muscle inducible nitric oxide synthase (iNOS) expression; the purpose of this investigation was to explore this potential relationship in humans. Sedentary men and women were recruited to participate (means ± SE: nonobese, body mass index = 25.5 ± 0.3 kg/m2, n = 13; obese, body mass index = 36.6 ± 0.4 kg/m2, n = 14). Insulin sensitivity was measured using an intravenous glucose tolerance test with the subsequent modeling of an insulin sensitivity index (SI). Skeletal muscle was obtained from the vastus lateralis, and iNOS, endothelial nitric oxide synthase (eNOS), and neuronal nitric oxide synthase (nNOS) content were determined by Western blot. SI was significantly lower in the obese compared with the nonobese group (?43%; P < 0.05), yet skeletal muscle iNOS protein expression was not different between nonobese and obese groups. Skeletal muscle eNOS protein was significantly higher in the nonobese than the obese group, and skeletal muscle nNOS protein tended to be higher (P = 0.054) in the obese compared with the nonobese group. Alternative analysis based on SI (high and low tertile) indicated that the most insulin-resistant group did not have significantly more skeletal muscle iNOS protein than the most insulin-sensitive group. In conclusion, human insulin resistance does not appear to be associated with an elevation in skeletal muscle iNOS protein in middle-aged individuals under fasting conditions. PMID:22797309

Kraus, Raymond M.; Houmard, Joseph A.; Kraus, William E.; Tanner, Charles J.; Pierce, Joseph R.; Choi, Myung Dong

2012-01-01

138

Synthesis of nitric oxide probes with fluorescence lifetime sensitivity  

PubMed Central

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

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

2013-01-01

139

Mitochondrial Biogenesis in Mammals: The Role of Endogenous Nitric Oxide  

Microsoft Academic Search

Nitric oxide was found to trigger mitochondrial biogenesis in cells as diverse as brown adipocytes and 3T3-L1, U937, and HeLa cells. This effect of nitric oxide was dependent on guanosine 3',5'-monophosphate (cGMP) and was mediated by the induction of peroxisome proliferator-activated receptor gamma coactivator 1alpha, a master regulator of mitochondrial biogenesis. Moreover, the mitochondrial biogenesis induced by exposure to cold

Enzo Nisoli; Emilio Clementi; Clara Paolucci; Valeria Cozzi; Cristina Tonello; Clara Sciorati; Renata Bracale; Alessandra Valerio; Maura Francolini; Salvador Moncada; Michele O. Carruba

2003-01-01

140

Airborne intercomparison of nitric oxide measurement techniques  

NASA Technical Reports Server (NTRS)

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.

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

1987-01-01

141

Hemoglobin-mediated nitric oxide signaling  

PubMed Central

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

Helms, Christine; Kim-Shapiro, Daniel B.

2013-01-01

142

Tapentadol and nitric oxide synthase systems.  

PubMed

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

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

2014-12-01

143

Catecholamines?? Enhancement of Inducible Nitric Oxide Synthase-Induced Nitric Oxide Biosynthesis Involves CAT1 and CAT2A  

Microsoft Academic Search

Catecholamines enhance inducible nitric oxide syn- thase (iNOS) expression that results in nitric oxide (NO) overproduction in lipopolysaccharide (LPS)- stimulated macrophages. L-arginine transport medi- ated by cationic amino acid transporters (including CAT-1, CAT-2, CAT-2A, and CAT-2B) is crucial in regulating iNOS activity. We sought to assess the ef- fects of catecholamines on L-arginine transport and CATisozymeexpressioninstimulatedmacrophages. Confluent RAW264.7 cells were

Wen-Chou Lin; Pei-Shan Tsai; Chun-Jen Huang

2005-01-01

144

Heme/copper assembly mediated nitrite and nitric oxide interconversion.  

PubMed

The heme(a3)/Cu(B) active site of cytochrome c oxidase is responsible for cellular nitrite reduction to nitric oxide; the same center can return NO to the nitrite pool via oxidative chemistry. Here, we show that a partially reduced heme/Cu assembly reduces NO(2)(-) ion, producing nitric oxide. The heme serves as the reductant, but the Cu(II) ion is also required. In turn, a ?-oxo heme-Fe(III)-O-Cu(II) complex facilitates NO oxidation to nitrite; the final products are the reduced heme and Cu(II)-nitrito complexes. PMID:23130610

Hematian, Shabnam; Siegler, Maxime A; Karlin, Kenneth D

2012-11-21

145

Direct chemiluminescence detection of nitric oxide in aqueous solutions using the natural nitric oxide target soluble guanylyl cyclase.  

PubMed

Nitric oxide (NO) is a free radical involved in many physiological processes including regulation of blood pressure, immune response, and neurotransmission. However, the measurement of extremely low, in some cases subnanomolar, physiological concentrations of nitric oxide presents an analytical challenge. The purpose of this methods article is to introduce a new highly sensitive chemiluminescence approach to direct NO detection in aqueous solutions using a natural nitric oxide target, soluble guanylyl cyclase (sGC), which catalyzes the conversion of guanosine triphosphate to guanosine 3',5'-cyclic monophosphate and inorganic pyrophosphate. The suggested enzymatic assay uses the fact that the rate of the reaction increases by about 200 times when NO binds with sGC and, in so doing, provides a sensor for nitric oxide. Luminescence detection of the above reaction is accomplished by converting inorganic pyrophosphate into ATP with the help of ATP sulfurylase followed by light emission from the ATP-dependent luciferin-luciferase reaction. Detailed protocols for NO quantification in aqueous samples are provided. The examples of applications include measurement of NO generated by a nitric oxide donor (PAPA-NONOate), nitric oxide synthase, and NO gas dissolved in buffer. The method allows for the measurement of NO concentrations in the nanomolar range and NO generation rates as low as 100 pM/min. PMID:19751819

Woldman, Yakov Y; Sun, Jian; Zweier, Jay L; Khramtsov, Valery V

2009-11-15

146

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

NASA Astrophysics Data System (ADS)

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

Barker, Susan Lynn Ritenour

1999-11-01

147

Nitric oxide synthases: structure, function and inhibition.  

PubMed Central

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

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

2001-01-01

148

Imaging of nitric oxide in the retina*  

PubMed Central

Nitric oxide (NO) is the most widespread signaling molecule found in the retina in that it can be made by every retinal cell type. NO is able to influence a wide variety of synaptic mechanisms ranging from increasing or decreasing neurotransmitter release to the modulation of gap junction conductivity. Although biochemical methods can analyze overall levels of NO, such methods cannot indicate the specific cell types involved. In the last few years, fluorescent imaging methods utilizing diaminofluorescein have allowed the real-time visualization of neurochemically or light stimulated NO-induced fluorescence (NO-IF) in specific retinal cells. Recent experiments have shown that this NO-IF can be stabilized using paraformaldehyde fixation. This aldehyde stabilization has allowed the imaging of NO production in the dark and in response to light, as well as the neurochemical modulation of light stimulated NO production. The results of these studies indicate that NO is not always freely diffusible and that NO is largely retained in many cells which make it. The NO production in retina is highly damped in that in the absence of stimulation, the endogenous levels of NO production are extremely low. Finally, different neurochemical or light stimulation protocols activate NO production in specific cells and subcellular compartments. Therefore, although the NO signaling is widespread in retina, it is very selectively activated and has different functions in specific retinal cell types. The use of NO imaging will continue to play a critical role in future studies of the function of NO in retina and other neural systems. PMID:16171845

Eldred, William D.; Blute, Todd A.

2006-01-01

149

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

SciTech Connect

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

Elespuru, R.K.; Mark, T.W. [Food and Drug Administration, Rockville, MD (United States)

1995-11-01

150

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

PubMed Central

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

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

2000-01-01

151

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

PubMed Central

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

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

152

TRPV3 regulates nitric oxide synthase-independent nitric oxide synthesis in the skin.  

PubMed

Nitric oxide (NO) is an unstable signalling molecule synthesized de novo mainly from L-arginine by NO synthase (NOS) enzymes. Nitrite reduction can also produce NO, predominantly within body fluids (for example, saliva, sweat and blood plasma) and under extreme hypoxic and acidic conditions. It remains unknown if intracellular canonical signalling pathways regulate nitrite-dependent NO production. Here we examine NO production in the skin, a hypoxic tissue enriched in nitrites wherein NO has important roles in wound healing and other biological processes. We show that activation of TRPV3, a heat-activated transient receptor potential ion channel expressed in keratinocytes, induces NO production via a nitrite-dependent pathway. TRPV3 and nitrite are involved in keratinocyte migration in vitro and in wound healing and thermosensory behaviours in vivo. Our study demonstrates that activation of an ion channel can induce NOS-independent NO production in keratinocytes. PMID:21712817

Miyamoto, Takashi; Petrus, Matt J; Dubin, Adrienne E; Patapoutian, Ardem

2011-01-01

153

Consumption of biogenic nitric oxide in hydrated soil.  

PubMed

An experimental study was conducted in order to determine the relationship of nitric oxide (NO) consumption to water-filled pore space in soil. A test system that included the capability to blend gases, test soil samples, and analyze off-gases was used to conduct the study. The experimental set consisted of three replicates at five different levels of soil water content and three different levels of soil nitrogen in a sandy loam soil: unamended soil, soil fertilized at 56.2 kg N per ha (50 lb N acre(-1)), and soil fertilized at 112.3 kg N per ha (100 lb N acre(-1)). The average NO consumption rates were 7.1x10(-13) g-NO cm(-3) soil, 3.5x10(-11) g-NO cm(-3) soil, and 1.5x10(-10) g-NO cm(-3) soil, respectively. PMID:11916050

Rammon, Desirée A; Peirce, J Jeffrey

2002-01-01

154

Kinetics of the reaction of nitric oxide with hydrogen  

NASA Technical Reports Server (NTRS)

Mixtures of NO and H2 diluted in argon or krypton were heated by incident shock waves, and the infrared emission from the fundamental vibration-rotation band of NO at 5.3 microns was used to monitor the time-varying NO concentration. The reaction kinetics were studied in the temperature range 2400-4500 K using a shock-tube technique. The decomposition of nitric oxide behind the shock was found to be modeled well by a fifteen-reaction system. A principle result of the study was the determination of the rate constant for the reaction H + NO yields N + OH, which may be the rate-limiting step for NO removal in some combustion systems. Experimental values of k sub 1 were obtained for each test through comparisons of measured and numerically predicted NO profiles.

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

1974-01-01

155

The nitric oxide hypothesis of brain aging.  

PubMed

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

McCann, S M

1997-01-01

156

Nitric Oxide in Astrocyte-Neuron Signaling  

SciTech Connect

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.

Nianzhen Li

2002-06-27

157

Pain Modulation by Nitric Oxide in the Spinal Cord  

PubMed Central

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

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

2009-01-01

158

Parameters controlling nitric oxide emissions from gas turbine combustors  

NASA Technical Reports Server (NTRS)

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.

Heywood, J. B.; Mikus, T.

1973-01-01

159

Nitric acid oxidation of vapor grown carbon nanofibers  

Microsoft Academic Search

Vapor grown carbon nanofibers (Pyrograf III™) with 100–300 nm diameters and ?10–100 ?m lengths were oxidized in 69–71 wt.% nitric acid (115 °C) for various times (10 min to 24 h). These fibers were remarkably oxidation-resistant. XPS (O1s) showed that the surface atomic oxygen percent increased from 6.3 to 18.3–22.5% for 10–90 min oxidations followed by a drop to 14–15%

Priya V. Lakshminarayanan; Hossein Toghiani; Charles U. Pittman Jr.

2004-01-01

160

Structural and biological studies on bacterial nitric oxide synthase inhibitors  

PubMed Central

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

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

2013-01-01

161

Alveolar nitric oxide and its role in pediatric asthma control assessment  

PubMed Central

Background Nitric oxide can be measured at multiple flow rates to determine proximal (maximum airway nitric oxide flux; JawNO) and distal inflammation (alveolar nitric oxide concentration; CANO). The main aim was to study the association among symptoms, lung function, proximal (maximum airway nitric oxide flux) and distal (alveolar nitric oxide concentration) airway inflammation in asthmatic children treated and not treated with inhaled glucocorticoids. Methods A cross-sectional study with prospective data collection was carried out in a consecutive sample of girls and boys aged between 6 and 16 years with a medical diagnosis of asthma. Maximum airway nitric oxide flux and alveolar nitric oxide concentration were calculated according to the two-compartment model. In asthmatic patients, the asthma control questionnaire (CAN) was completed and forced spirometry was performed. In controls, differences between the sexes in alveolar nitric oxide concentration and maximum airway nitric oxide flux and their correlation with height were studied. The correlation among the fraction of exhaled NO at 50 ml/s (FENO50), CANO, JawNO, forced expiratory volume in 1 second (FEV1) and the CAN questionnaire was measured and the degree of agreement regarding asthma control assessment was studied using Cohen’s kappa. Results We studied 162 children; 49 healthy (group 1), 23 asthmatic participants without treatment (group 2) and 80 asthmatic patients treated with inhaled corticosteroids (group 3). CANO (ppb) was 2.2 (0.1-4.5), 3 (0.2-9.2) and 2.45 (0.1-24), respectively. JawNO (pl/s) was 516 (98.3-1470), 2356.67 (120–6110) and 1426 (156–11805), respectively. There was a strong association (r?=?0.97) between FENO50 and JawNO and the degree of agreement was very good in group 2 and was good in group 3. There was no agreement or only slight agreement between the measures used to monitor asthma control (FEV1, CAN questionnaire, CANO and JawNO). Conclusions The results for CANO and JawNO in controls were similar to those found in other reports. There was no agreement or only slight agreement among the three measure instruments analyzed to assess asthma control. In our sample, no additional information was provided by CANO and JawNO. PMID:25090994

2014-01-01

162

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

NASA Technical Reports Server (NTRS)

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.

Fuller-Rowell, T.J.

1997-01-01

163

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

PubMed

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

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

2014-06-27

164

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

E-print Network

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 ...

Lim, Mi Hee

2006-01-01

165

The effects of synthetic organoselenium compounds on nitric oxide in DMBA-induced rat liver.  

PubMed

DMBA (7, 12-dimethylbenz[a]anthracene) is known to generate DNA-reactive species during their metabolism, which may enhance oxidative stress in cells. Since selenium is known as a non-enzymic antioxidant, health problems induced by many environmental pollutants, have stimulated the evaluation of relative antioxidant potential of selenium and synthetic organoselenium compounds. Therefore, we aimed to evaluate chemopreventive potential of synthetic organoselenium compounds by monitoring level of liver nitric oxide. In this study, adult female Wistar rats were treated with DMBA and the novel organoselenium compounds (Se I) and (Se II) in the determined doses. DMBA-induced in rats, the effects of organoselenium compounds on nitric oxide levels in rat liver was studied. In this study it has been observed a statistically significant increase in (Nitric Oxide) levels for the liver of rat exposed to DMBA (p<0.05). However with administration of Se I and Se II there was a statistically significant decrease in NO levels (p<0.05). The ability of the organoselenium compounds to prevent oxidative damage induced by DMBA in rat livers was rationalized. Protection against nitric oxide measured in Se I and Se II treated groups were provided by synthesized organoselenium compounds. Se I and Se II both provided chemoprevention against DMBA-induced oxidative stress in rat liver. PMID:20120501

Talas, Zeliha Selamoglu; Bayraktar, Nihayet; Ozdemir, Ilknur; Gok, Yetkin; Yilmaz, Ismet

2009-07-01

166

Fluorescent polycyclic ligands for nitric oxide synthase (NOS) inhibition.  

PubMed

In recent years polycyclic compounds have been shown to exhibit pharmacological profiles of importance in the symptomatic and proposed curative treatment of neurodegenerative diseases (e.g., Parkinson's and Alzheimer's disease). These structures also show modification and improvement of the pharmacokinetic and pharmacodynamic properties of drugs in current use. Nitric oxide (NO) is a molecular messenger involved in a number of physiological processes in mammals. It is synthesised by nitric oxide synthase (NOS) from L-arginine and its overproduction could lead to a number of neurological disorders. The aim of this study was to synthesise a series of novel indazole, indole and other fluorescent derivatives conjugated to polycyclic structures for evaluation in NOS assays. NOS is a target system where fluorescent techniques and fluorescently labelled NOS inhibitors can be used for detecting the biophysical properties of enzyme-ligand interactions and thus facilitate development of novel inhibitors of neurodegeneration. This could lead to a greater insight into the neuroprotective mechanism and a possible cure/treatment for neurodegenerative diseases. A series of compounds incorporating polycyclic structures such as 3-hydroxy-4-aza-8-oxoheptacyclo[9.4.1.0.(2,10)0.(3,14)0.(4,9)0.(9,13)0(12,15)]tetradecane and amantadine as well as suitable fluorescent moieties were selected for synthesis. In the biological evaluation the oxyhaemoglobin (oxyHb) assay was employed to determine the activity of the novel compounds at an enzymatic level of NOS. IC(50) values of the novel fluorescent compounds were compared to that of aminoguanidine (AG) and 7-nitroindazole (7-NI), two known NOS inhibitors, and showed moderate to high affinity (IC(50) values ranging from 7.73 microM to 0.291 microM) for the NOS enzyme. PMID:18805011

Joubert, Jacques; van Dyk, Sandra; Malan, Sarel F

2008-10-01

167

Interactions between nitric oxide and indoleamine 2,3-dioxygenase.  

PubMed

Indoleamine 2,3-dioxygenase (IDO) is a heme-containing enzyme, which catalyzes the initial and rate-determining step of L-tryptophan (L-Trp) metabolism via the kynurenine pathway in nonhepatic tissues. Similar to inducible nitric oxide synthase (iNOS), IDO is induced by interferon-gamma and lipopolysaccharide in the inflammatory response. In vivo studies indicate that the nitric oxide (NO) produced by iNOS inhibits IDO activity by directly interacting with it and by promoting its degradation through the proteasome pathway. In this work, the molecular mechanisms underlying the interactions between NO and human recombinant IDO (hIDO) were systematically studied with optical absorption and resonance Raman spectroscopies. Resonance Raman data show that the heme prosthetic group in the NO-bound hIDO is situated in a unique protein environment and adopts an out-of-plane deformed geometry that is sensitive to L-Trp binding. Under mildly acidic conditions, the proximal heme iron-His bond is prone to rupture, resulting in a five-coordinate (5C) NO-bound species. The bond breakage reaction induces significant conformational changes in the protein matrix, which may account for the NO-induced inactivation of hIDO and its enhanced proteasome-linked degradation in vivo. Moreover, it was found that the NO-induced bond breakage reaction occurs more rapidly in the ferrous protein than in the ferric protein and is fully inhibited by L-Trp binding. The spectroscopic data presented here not only provide the first glimpse of the possible regulatory mechanism of hIDO by NO in the cell at the molecular level, but they also suggest that the NO-dependent regulation can be modulated by cellular factors, such as the NO abundance, pH, redox environment, and L-Trp availability. PMID:16834326

Samelson-Jones, Ben J; Yeh, Syun-Ru

2006-07-18

168

Decoding the Substrate Supply to Human Neuronal Nitric Oxide Synthase  

PubMed Central

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

Habermeier, Alice; Closs, Ellen I.

2013-01-01

169

Hydrogen sulfide cytoprotective signaling is endothelial nitric oxide synthase-nitric oxide dependent  

PubMed Central

Previous studies have demonstrated that hydrogen sulfide (H2S) protects against multiple cardiovascular disease states in a similar manner as nitric oxide (NO). H2S therapy also has been shown to augment NO bioavailability and signaling. The purpose of this study was to investigate the impact of H2S deficiency on endothelial NO synthase (eNOS) function, NO production, and ischemia/reperfusion (I/R) injury. We found that mice lacking the H2S-producing enzyme cystathionine ?-lyase (CSE) exhibit elevated oxidative stress, dysfunctional eNOS, diminished NO levels, and exacerbated myocardial and hepatic I/R injury. In CSE KO mice, acute H2S therapy restored eNOS function and NO bioavailability and attenuated I/R injury. In addition, we found that H2S therapy fails to protect against I/R in eNOS phosphomutant mice (S1179A). Our results suggest that H2S-mediated cytoprotective signaling in the setting of I/R injury is dependent in large part on eNOS activation and NO generation. PMID:24516168

King, Adrienne L.; Polhemus, David J.; Bhushan, Shashi; Otsuka, Hiroyuki; Kondo, Kazuhisa; Nicholson, Chad K.; Bradley, Jessica M.; Islam, Kazi N.; Calvert, John W.; Tao, Ya-Xiong; Dugas, Tammy R.; Kelley, Eric E.; Elrod, John W.; Huang, Paul L.; Wang, Rui; Lefer, David J.

2014-01-01

170

Muller Cell Protection of Rat Retinal Ganglion Cells from Glutamate and Nitric Oxide Neurotoxicity  

Microsoft Academic Search

PURPOSE. Low concentrations of excitotoxic agents such as glutamate and nitric oxide decrease survival rates of purified retinal ganglion cells (RGCs). In the retina, RGCs are ensheathed by retinal Muller glial (RMG) cell processes. The purpose of this study was to determine whether RMG cells could protect RGCs from these excitotoxic injuries. METHODS. RGCs were purified from 7- or 8-day-old

Atsushi Kawasaki; Yasumasa Otori; Colin J. Barnstable

2000-01-01

171

Time course and cellular localization of inducible nitric oxide synthases expression during cardiac allograft rejection  

Microsoft Academic Search

Background. We have demonstrated that inhibition of inducible nitric oxide synthase (NOS) ameliorated acute cardiac allograft rejection. This study determined the time course and cellular localization of inducible NOS expression during the histologic progression of unmodified acute rat cardiac allograft rejection.Methods. Tissue from syngeneic (ACI to ACI) and allogeneic (Lewis to ACI) transplants were harvested on postoperative days 3 through

Neil K Worrall; Thomas P Misko; Mitchell D Botney; Patrick M Sullivan; Jia-J Hui; Gloria M Suau; Pamela T Manning; T. Bruce Ferguson

1999-01-01

172

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

Microsoft Academic Search

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

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

1999-01-01

173

In vivo nitric oxide sensor using non-conducting polymer-modified carbon fiber  

Microsoft Academic Search

Nitric oxide (NO) is emerging as a very important and ubiquitous gaseous messenger in the body. The response characteristics of NO sensors made of non-conducting polymer modified carbon fiber electrodes are investigated to determine their selectivity, sensitivity, and stability for in vivo use. A composite polymer, comprising Nafion, m-phenylenediamine, and resorcinol, showed the best selectivity and stability to amperometric NO

Je-Kyun Park; Peter H Tran; Johnny K. T Chao; Rutwik Ghodadra; Rajagopalan Rangarajan; Nitish V. Thakor

1998-01-01

174

Cellular/Molecular A Calcium-Induced Calcium Influx Factor, Nitric Oxide,  

E-print Network

Cellular/Molecular A Calcium-Induced Calcium Influx Factor, Nitric Oxide, Modulates the Refilling in astrocytes, we imaged the formation of nitric oxide in cultured murine cortical astrocytes using DAF-FM (4 concentrations of ATP induced a Ca2 -dependent production of nitric oxide. We then investigated the roles

Newman, Eric A.

175

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

Microsoft Academic Search

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

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

1970-01-01

176

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

E-print Network

Neuronal nitric oxide synthase in the gill of the killifish, Fundulus heteroclitus Kelly A. Hyndman nitric oxide (NO). Nitric oxide is involved in regulation of a variety of processes, including: vascular. Killifish NOS has 75% amino acid identity to human nNOS, and phylogenetic analysis groups the killifish

Evans, David H.

177

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

E-print Network

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

George, Steven C.

178

Exogenous nitric oxide improves seed germination in wheat against mitochondrial oxidative damage induced by high salinity  

Microsoft Academic Search

Effects of exogenous nitric oxide (NO) on starch degradation, oxidation in mitochondria and K+\\/Na+ accumulation during seed germination of wheat were investigated under a high salinity level. Seeds of winter wheat (Triticum aestivum L., cv. Huaimai 17) were pre-soaked with 0mM or 0.1mM of sodium nitroprusside (SNP, as nitric oxide donor) for 20h just before germination under 300mM NaCl. At

Chunfang Zheng; Dong Jiang; Fulai Liu; Tingbo Dai; Weicheng Liu; Qi Jing; Weixing Cao

2009-01-01

179

Exhaled Nitric Oxide in Chronic Obstructive Pulmonary Disease  

Microsoft Academic Search

Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow obstruction and a neutrophilic inflammation. Exhaled nitric oxide (NO) may be a marker of disease activity in a variety of lung diseases. We measured exhaled NO in patients with documented COPD and investi- gated whether the concentration of exhaled NO is related to the severity of disease as defined by

WASIM MAZIAK; STELIOS LOUKIDES; SARAH CULPITT; PAUL SULLIVAN; SERGEI A. KHARITONOV; PETER J. BARNES

1998-01-01

180

Solar proton events - Stratospheric sources of nitric oxide  

Microsoft Academic Search

The production of nitric oxide (NO) in the stratosphere during each of the solar proton events of November 1960, September 1966, and August 1972 is calculated to have been comparable to or larger than the total average annual production of NO by the action of galactic cosmic rays. It is therefore very important to consider the effect of solar proton

P. J. Crutzen; I. S. A. Isaksen; G. C. Reid

1975-01-01

181

Theoretical investigation of nitric oxide interaction with aluminum phthalocyanine  

Microsoft Academic Search

Nitric oxide (NO) is an extremely toxic compound formed during combustion, predominantly at high temperatures, and it is among the most important atmospheric pollutants. However, this compound has interesting biological activities, since it can control important biological processes in living organisms. With the aim of developing new materials that can be used as selective chemical sensors or as biomedical NO

Valter H. C. Silva; Marcos P. Martins; Heibbe C. B. de Oliveira; Ademir J. Camargo

2011-01-01

182

Nitric Oxide and Neopterin in Bipolar Affective Disorder  

Microsoft Academic Search

Background: There is an increasing interest in the role of nitric oxide (NO) and pterines in the pathophysiology of neuropsychiatric disorders. The results so far show an inconsistent pattern. Methods: In the present study, neopterin and a measure of NO synthesis in plasma of symptomatic and euthymic bipolar affective patients were compared to those of patients with a major depression

R. Hoekstra; D. Fekkes; L. Pepplinkhuizen; A. J. M. Loonen; S. Tuinier; W. M. A. Verhoeven

2006-01-01

183

Estimates of nitric oxide production for lifting spacecraft reentry  

NASA Technical Reports Server (NTRS)

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.

Park, C.

1971-01-01

184

Nitric oxide function and signalling in plant disease resistance  

Microsoft Academic Search

Nitric oxide (NO) is one of only a handful of gaseous signalling molecules. Its discovery as the endothelium- derived relaxing factor (EDRF) by Ignarro revolutionized how NO and cognate reactive nitrogen intermediates, which were previously considered to be toxic molec- ules, are viewed. NO is now emerging as a key signalling molecule in plants, where it orchestrates a plethora of

Jeum Kyu Hong; Byung-Wook Yun; Jeong-Gu Kang; Muhammad Usman Raja; Eunjung Kwon; Kirsti Sorhagen; Chengcai Chu; Yiqin Wang; Gary J. Loake

2008-01-01

185

Biochemistry of Nitric Oxide and Its Redox-Activated Forms  

Microsoft Academic Search

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

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

1992-01-01

186

Fertilizer-induced nitric oxide emissions from agricultural soils  

Microsoft Academic Search

We summarize and evaluate 23 studies of the effect of fertilizer use on nitric oxide (NO) emission from agricultural soils. To quantify this effect we selected only field-scale studies with duration of at least one complete growing season and excluded studies with a legume as the principle crop. Only 6 studies met the established criteria, resulting in a total of

Edzo Veldkamp; Michael Keller

1997-01-01

187

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

PubMed Central

Contrast media- (CM-) induced nephropathy is a serious complication of radiodiagnostic procedures. Available data suggests that the development of prophylaxis strategies is limited by poor understanding of pathophysiology of CM-induced nephropathy. Present study was designed to determine the role of oxidative stress, myeloperoxidase, and nitric oxide in the pathogenesis of iohexol model of nephropathy and its modification with simvastatin (SSTN). Adult Sprague Dawley rats were divided into seven groups. After 24?h of water deprivation, all the rats except in control and SSTN-only groups were injected (10?ml/kg) with 25% glycerol. After 30?min, SSTN (15, 30, and 60?mg/kg) was administered orally, daily for 4 days. Twenty-four hours after the glycerol injection, iohexol was infused (8?ml/kg) through femoral vein over a period of 2?min. All the animals were sacrificed on day 5 and blood and kidneys were collected for biochemical and histological studies. The results showed that SSTN dose dependently attenuated CM-induced rise of creatinine, urea, and structural abnormalities suggesting its nephroprotective effect. A significant increase in oxidative stress (increased lipid hydroperoxides and reduced glutathione levels) and myeloperoxidase (MPO) and decreased nitric oxide in CM group were reversed by SSTN. These findings support the use of SSTN to combat CM-induced nephrotoxicity. PMID:23097681

Al-Otaibi, Ketab E.; Al Elaiwi, Abdulrahman M.; Tariq, Mohammad; Al-Asmari, Abdulrahman K.

2012-01-01

188

Co-induction of nitric oxide synthase and cyclo-oxygenase: interactions between nitric oxide and prostanoids.  

PubMed Central

1. Lipopolysaccharide (LPS) co-induces nitric oxide synthase (iNOS) and cyclo-oxygenase (COX-2) in J774.2 macrophages. Here we have used LPS-activated J774.2 macrophages to investigate the effects of exogenous or endogenous nitric oxide (NO) on COX-2 in both intact and broken cell preparations. NOS activity was assessed by measuring the accumulation of nitrite using the Griess reaction. COX-2 activity was assessed by measuring the formation of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) by radioimmunoassay. Western blot analysis was used to determine the expression of COX-2 protein. We have also investigated whether endogenous NO regulates the activity and/or expression of COX in vivo by measuring NOS and COX activity in the lung and kidney, as well as release of prostanoids from the perfused lung of normal and LPS-treated rats. 2. Incubation of cultured murine macrophages (J774.2 cells) with LPS (1 microgram ml-1) for 24 h caused a time-dependent accumulation of nitrite and 6-keto-PGF1 alpha in the cell culture medium which was first significant after 6 h. The formation of both 6-keto-PGF1 alpha and nitrite elicited by LPS was inhibited by cycloheximide (1 microM) or dexamethasone (1 microM). Western blot analysis showed that J774.2 macrophages contained COX-2 protein after LPS administration, whereas untreated cells contained no COX-2. 3. The accumulation of 6-keto-PGF1 alpha in the medium of LPS-activated J774.2 macrophages was concentration-dependently inhibited by chronic (24 h) exposure to sodium nitroprusside (SNP; 1-1000 microM).(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 6 PMID:7541688

Swierkosz, T A; Mitchell, J A; Warner, T D; Botting, R M; Vane, J R

1995-01-01

189

Ann. Geophysicae 14, 1103--1110 (1996) EGS --Springer-Verlag 1996 Detection of nitric acid and nitric oxides in the terrestrial atmosphere  

E-print Network

Ann. Geophysicae 14, 1103--1110 (1996) EGS -- Springer-Verlag 1996 Detection of nitric acid observations of the vertical distributions and the column densities of nitric acid and nitric oxide concentra and nitric oxides in the terrestrial atmosphere in the middle-infrared spectral region M. I. Ble11 cka, M. De

Paris-Sud XI, Université de

190

Hydrogen peroxide and nitric oxide as signalling molecules in plants  

Microsoft Academic Search

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

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

2002-01-01

191

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

PubMed Central

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

Grisham, Matthew B.

1995-01-01

192

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

PubMed Central

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

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

2004-01-01

193

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

NASA Astrophysics Data System (ADS)

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.

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

2013-07-01

194

Position in Cell Cycle Controls the Sensitivity of Colon Cancer Cells to Nitric Oxide-Dependent Programmed Cell Death  

Microsoft Academic Search

Mounting evidence suggests that the position in the cell cycle of cells exposed to an oxidative stress could determine their survival or apoptotic cell death. This study aimed at determining whether nitric oxide (NO)- induced cell death in colon cancer cells might depend on their position in the cell cycle, based on a clone of the cancer cell line HT29

Anne Jarry; Laetitia Charrier; Chantal Bou-Hanna; Marie-Claire Devilder; Veronique Crussaire; Marc G. Denis; Genevieve Vallette; Christian L. Laboisse

2004-01-01

195

Intracolonic release of nitric oxide during trinitrobenzene sulfonic acid rat colitis.  

PubMed

Nitric oxide is thought to play an important role in modulating the inflammatory process. Recently an increase in the inducible form of nitric oxide synthase (iNOS) has been found in the rat trinitrobenzene sulfonic acid model of experimental colitis, and inhibition of nitric oxide synthase activity resulted in an amelioration of tissue injury. The aim of our study was to evaluate in vivo intracolonic release of nitric oxide in this model of colitis. Experimental colitis was induced in male Sprague-Dawley rats by a single intracolonic administration of trinitrobenzene sulfonic acid. Nitrite levels were determined in rectal dialysates by HPLC. The tissue myeloperoxidase and iNOS and the luminal leukotriene B4 were also measured. Nitrite levels were significantly increased in rectal dialysates during colitis and correlated significantly with tissue myeloperoxidase and iNOS activity. The correlation between nitrite dialysate levels and wall iNOS activity confirms that nitrite in dialysates is produced by inflammatory cells and not by colonic bacterial flora. Determination of nitrite levels in rectal dialysates seems a valuable method to monitor colonic inflammation in rat trinitrobenzene sulfonic acid colitis. PMID:9440646

Ferretti, M; Gionchetti, P; Rizzello, F; Venturi, A; Stella, P; Corti, F; Mizrahi, J; Miglioli, M; Campieri, M

1997-12-01

196

Effect of Helicobacter pylori infection on gastric mucosal pathologic change and level of nitric oxide and nitric oxide synthase  

PubMed Central

AIM: To investigate the level of nitric oxide (NO) and nitrous oxide synthase (NOS) enzyme and its effect on gastric mucosal pathologic change in patients infected with Helicobacter pylori (H pylori ), and to study the pathogenic mechanism of H pylori. METHODS: The mucosal tissues of gastric antrum were taken by endoscopy, then their pathology, H pylori and anti-CagA-IgG were determined. Fifty H pylori positive cases and 35 H pylori negative cases were randomly chosen. Serum level of NO and NOS was detected. RESULTS: One hundred and seven cases (71.33%) were anti-CagA-IgG positive in 150 H pylori positive cases. The positive rate was higher especially in those with pre-neoplastic diseases, such as atrophy, intestinal metaplasia and dysplasia. The level of NO and NOS in positive group was higher than that in negative group, and apparently lower in active gastritis than in pre-neoplastic diseases such as atrophy, intestinal metaplasia and dysplasia. CONCLUSION: H pylori is closely related with chronic gastric diseases, and type I H pylori may be the real factor for H pylori-related gastric diseases. Infection with H pylori can induce elevation of NOS, which produces NO. PMID:16124060

Wang, Yong-Fu; Guo, Chun-Lin; Zhao, Li-Zhen; Yang, Guo-An; Chen, Peng; Wang, Hong-Kun

2005-01-01

197

Nitric oxide-eluting nanocomposite for cardiovascular implants.  

PubMed

Cardiovascular implants must resist thrombosis and intimal hyperplasia, but they are prone to such patency limiting conditions during graft implantation and prior to endothelialisation. Nitric oxide (NO) released from the endothelium has a complex protective role in the cardiovascular system, and this study has addressed: (1) in situ NO release profiles from S-nitrosothiols ((S-Nitroso-N-acetylpenicillamine (SNAP) and (S-Nitrosoglutathione (GSNO)) incorporated into polyhedral oligomeric silsesquioxanepoly(carbonate-urea)urethane (POSS-PCU) coronary artery bypass grafts (CABG) in a physiological pulsatile flow, and (2) the determination of their interaction with endothelial progenitor cells (EPCs), smooth muscle cells, platelets, whole blood kinetics. It was found that 1, 2, and 3 wt% SNAP/GSNO incorporated into POSS-PCU-CABG successfully eluted NO, but optimal elution was evident with 2 %-SNAP-POSS-PCU. NO release determined under static conditions using the Griess assay, and in situ measurements under pulsatile flow using amperometric probe was found to differ, thus confirming the significance of monitoring NO-elution under haemodynamic conditions. 2 %-SNAP-POSS-PCU demonstrated anti-thrombogenic kinetics through thromboelastography measurements, while metabolic activity using Alamar Blue™ assay and scanning electron microscopy demonstrated greater adhesion of EPCs and reduced adhesion of platelets. PMID:24293239

de Mel, Achala; Naghavi, Noora; Cousins, Brian G; Clatworthy, Innes; Hamilton, George; Darbyshire, Arnold; Seifalian, Alexander M

2014-03-01

198

Nitrous Oxide Decomposition over Fe-ZSM-5 in the Presence of Nitric Oxide: A Comprehensive DFT Study  

E-print Network

processes used to produce nitric and adipic acid. Since N2O is the third most important greenhouse gas temperatures.1-4 One peculiarity of the tail gas streams from nitric acid plants is the presence of both N2ONitrous Oxide Decomposition over Fe-ZSM-5 in the Presence of Nitric Oxide: A Comprehensive DFT

Bell, Alexis T.

199

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

PubMed Central

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

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

200

Leukaemia Inhibitory Factor Stimulates Proliferation of Olfactory Neuronal Progenitors via Inducible Nitric Oxide Synthase  

PubMed Central

Neurogenesis continues in the adult brain and in the adult olfactory epithelium. The cytokine, leukaemia inhibitory factor and nitric oxide are both known to stimulate neuronal progenitor cell proliferation in the olfactory epithelium after injury. Our aim here was to determine whether these observations are independent, specifically, whether leukaemia inhibitory factor triggers neural precursor proliferation via the inducible nitric oxide synthase pathway. We evaluated the effects of leukaemia inhibitory factor on inducible form of nitric oxide synthase (iNOS) expression, and cell proliferation in olfactory epithelial cell cultures and olfactory neurosphere-derived cells. Leukaemia inhibitory factor induced expression of iNOS and increased cell proliferation. An iNOS inhibitor and an anti-leukaemia inhibitory factor receptor blocking antibody inhibited leukaemia inhibitory factor-induced cell proliferation, an effect that was reversed by a NO donor. Altogether, the results strongly suggest that leukaemia inhibitory factor induces iNOS expression, increasing nitric oxide levels, to stimulate proliferation of olfactory neural precursor cells. This finding sheds light on neuronal regeneration occurring after injury of the olfactory epithelium. PMID:23024784

Lopez-Arenas, Estefania; Mackay-Sim, Alan; Bacigalupo, Juan; Sulz, Lorena

2012-01-01

201

The role of nitric oxide in the coronary vasoconstriction caused by growth hormone in anaesthetized pigs.  

PubMed

Intravenous injection of growth hormone in anaesthetized pigs has been shown to cause coronary vasoconstriction by antagonizing the vasodilatory effects of 2-adrenergic receptors. Because nitric oxide is believed to modulate or mediate 2-adrenergic effects, the present study was undertaken in the same experimental model to determine the role of nitric oxide in the above response to growth hormone. In fourteen pigs anaesthetized with sodium pentobarbitone, changes in left circumflex or anterior descending coronary blood flow caused by intravenous injection of 0.05 i.u. kg-1 of growth hormone at constant heart rate and arterial blood pressure were assessed using electromagnetic flowmeters. In a first control group of six pigs, growth hormone caused a decrease in coronary blood flow which averaged 13.1 % of the baseline values. In a second group of eight pigs, intravenous administration of N-nitro-L-arginine methyl ester (L-NAME) was used to block the endothelial release of nitric oxide. In these pigs, the subsequent injection of growth hormone did not cause any significant changes in coronary blood flow, even when performed after reversing the increase in arterial blood pressure and coronary vascular resistance caused by L-NAME with continuous intravenous infusion of papaverine. These results indicated that the coronary vasoconstricting effect of growth hormone, known to involve antagonism of 2-adrenergic vasodilatory effect, was mediated by inhibition of nitric oxide release. PMID:10751517

Molinari, C; Battaglia, A; Bona, G; Grossini, E; Mary, D A; Vacca, G

2000-03-01

202

[The role of nitric oxide and taurine in regulation of dogs gastric secretory function].  

PubMed

The influence of taurine and endogenous nitric oxide on the gastric secretion and secretory process alterations by taurine at the nitric oxide synthesis blockade was investigated in chronic experiments on dogs with gastric fistulas. We determined the intensity of gastric secretion during 1,5 hours and quantitative content of hydrochloric acid, pepsine, total proteins and adenile system components. The NO-synthase inhibition by L-NAME evoked an increase of secreted gastric juice volume stimulated by histamine by 160% (P<0,001), the gastric acid content - by 156,4% (P<0,001), pepsine content - by 184,1% (P<0,001) as compared with control. Taurine increases the volume of gastric juice stimulated by histamine on 129,3% (P<0,001), hydrochloric acid - by 151,4% (P<0,001), pepsine - by 172,2% (P<0,001), total proteins - by 60,5% (P<0,001) as compared with control. Blockade of nitric oxide synthesis did not alter the effect of taurine on histamine gastric secretion. The present results suggest that the endogenous nitric oxide provides an inhibitory influence on gastric secretion and did not participate in realization of regulatory effects of taurine on gastric secretory function. PMID:23530413

Hrinchenko, O A; Ianchuk, P I

2012-01-01

203

Transmission of arterial baroreflex signals depends on neuronal nitric oxide synthase.  

PubMed

Because inhibition of neuronal nitric oxide synthase in the nucleus tractus solitarii blocks cardiovascular responses to activation of local glutamate receptors, and because glutamate is a neurotransmitter of baroreceptor afferent nerves, we sought to test the hypothesis that neuronal nitric oxide synthase inhibition would block baroreflex transmission and cause hypertension. We determined reflex heart rate responses to intravenous phenylephrine and sodium nitroprusside in 5 anesthetized rats before and after bilateral microinjection (100 nL) of the neuronal nitric oxide synthase inhibitor AR-R 17477 (7.5 nmol) into the nucleus tractus solitarii. The inhibitor significantly increased mean arterial pressure without affecting heart rate, and it significantly reduced the gain of the baroreflex. After administration of the inhibitor, reflex responses of heart rate to changes in mean arterial pressure were always less than those responses to the same, or less, change in mean arterial pressure in the same animal without administration of the inhibitor. Microinjection of saline (100 nL) bilaterally into the nucleus tractus solitarii did not lead to hypertension or change baroreflex responses. These data support the hypothesis and suggest that neuronal nitric oxide synthase is critical to transmission of baroreflex signals through the nucleus tractus solitarii. PMID:14981065

Talman, William T; Dragon, Deidre Nitschke

2004-04-01

204

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

PubMed

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

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

205

Bacterial flavodoxins support nitric oxide production by Bacillus subtilis nitric-oxide synthase.  

PubMed

Unlike animal nitric-oxide synthases (NOSs), the bacterial NOS enzymes have no attached flavoprotein domain to reduce their heme and so must rely on unknown bacterial proteins for electrons. We tested the ability of two Bacillus subtilis flavodoxins (YkuN and YkuP) to support catalysis by purified B. subtilis NOS (bsNOS). When an NADPH-utilizing bacterial flavodoxin reductase (FLDR) was added to reduce YkuP or YkuN, both supported NO synthesis from either L-arginine or N-hydroxyarginine and supported a linear nitrite accumulation over a 30-min reaction period. Rates of nitrite production were directly dependent on the ratio of YkuN or YkuP to bsNOS. However, the V/Km value for YkuN (5.2 x 10(5)) was about 20 times greater than that of YkuP (2.6 x 10(4)), indicating YkuN is more efficient in supporting bsNOS catalysis. YkuN that was either photo-reduced or prereduced by FLDR transferred an electron to the bsNOS ferric heme at rates similar to those measured for heme reduction in the animal NOSs. YkuN supported a similar NO synthesis activity by a different bacterial NOS (Deinococcus radiodurans) but not by any of the three mammalian NOS oxygenase domains nor by an insect NOS oxygenase domain. Our results establish YkuN as a kinetically competent redox partner for bsNOS and suggest that FLDR/flavodoxin proteins could function physiologically to support catalysis by bacterial NOSs. PMID:17127770

Wang, Zhi-Qiang; Lawson, Rachel J; Buddha, Madhavan R; Wei, Chin-Chuan; Crane, Brian R; Munro, Andrew W; Stuehr, Dennis J

2007-01-26

206

Antenatal Insults Modify Newborn Olfactory Function By Nitric Oxide Produced From Neuronal Nitric Oxide Synthase  

PubMed Central

Newborn feeding, maternal, bonding, growth and wellbeing depend upon intact odor recognition in the early postnatal period. Antenatal stress may affect postnatal odor recognition. We investigated the exact role of a neurotransmitter, nitric oxide (NO), in newborn olfactory function. We hypothesized that olfactory neuron activity depended on NO generated by neuronal NO synthase (NOS). Utilizing in vivo functional manganese enhanced MRI (MEMRI) in a rabbit model of cerebral palsy we had shown previously that in utero hypoxia ischemia (H-I) at E22 (70% gestation) resulted in impaired postnatal response to odorants and poor feeding. With the same antenatal insult, we manipulated NO levels in the olfactory neuron in postnatal day 1 (P1) kits by administration of intranasal NO donors or a highly selective nNOS inhibitor. Olfactory function was quantitatively measured by the response to amyl acetate stimulation by MEMRI. The relevance of nNOS to normal olfactory development was confirmed by the increase of nNOS gene expression from fetal ages to P1 in olfactory epithelium and bulbs. In control kits, nNOS inhibition decreased NO production in the olfactory system and increased MEMRI slope enhancement. In H-I kits the MEMRI slope did not increase, implicating modification of endogenous NO-mediated olfactory function by the antenatal insult. NO donors as a source of exogenous NO did not significantly change function in either group. In conclusion, olfactory epithelium nNOS in newborn rabbits probably modulates olfactory signal transduction. Antenatal H-I injury remote from delivery may affect early functional development of the olfactory system by decreasing NO-dependent signal transduction. PMID:22836143

Drobyshevsky, Alexander; Yu, Lei; Yang, Yirong; Khalid, Syed; Luo, Kehuan; Jiang, Rugang; Ji, Haitao; Derrick, Matthew; Kay, Leslie; Silverman, Richard B.; Tan, Sidhartha

2012-01-01

207

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

PubMed

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

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

1997-01-15

208

Refractory Oxide Coatings on Titanium for Nitric Acid Applications  

NASA Astrophysics Data System (ADS)

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.

Ravi Shankar, A.; Kamachi Mudali, U.

2014-07-01

209

Uncoupled Cardiac Nitric Oxide Synthase Mediates Diastolic Dysfunction  

PubMed Central

Background Heart failure with preserved ejection fraction is one consequence of hypertension and caused by impaired cardiac diastolic relaxation. Nitric oxide (NO) is a known modulator of cardiac relaxation. Hypertension can lead to a reduction in vascular NO, in part because nitric oxide synthase (NOS) becomes uncoupled when oxidative depletion of its co-factor tetrahydrobiopterin (BH4) occurs.Similar events may occur in the heart leading to uncoupled NOS and diastolic dysfunction. Methods and Results In a hypertensive mouse model, diastolic dysfunction was accompanied by cardiac oxidation, a reduction in cardiac BH4, and uncoupled NOS. Compared to sham-operated animals, male mice with unilateral nephrectomy, with subcutaneous implantation of a controlled release deoxycorticosterone acetate (DOCA) pellet, and given 1% saline to drink were mildly hypertensive and had diastolic dysfunction in the absence of systolic dysfunction or cardiac hypertrophy. The hypertensive mouse hearts showed increased oxidized biopterins, NOS-dependent superoxide production, reduced NO production, and phosphorylated phospholamban. Feeding hypertensive mice BH4 (5 mg/day), but not treating with hydralazine or tetrahydroneopterin, improved cardiac BH4 stores, phosphorylated phospholamban levels, and diastolic dysfunction. Isolated cardiomyocyte experiments revealed impaired relaxation that was normalized with acute BH4 treatment. Targeted cardiac overexpression of angiotensin converting enzyme also resulted in cardiac oxidation, NOS uncoupling, and diastolic dysfunction in the absence of hypertension. Conclusions Cardiac oxidation, independent of vascular changes, can lead to uncoupled cardiac NOS and diastolic dysfunction. BH4 may represent a possible treatment for diastolic dysfunction. PMID:20083682

Silberman, Gad A.; Fan, Tai-Hwang M.; Liu, Hong; Jiao, Zhe; Xiao, Hong D.; Lovelock, Joshua D.; Boulden, Beth M.; Widder, Julian; Fredd, Scott; Bernstein, Kenneth E.; Wolska, Beata M.; Dikalov, Sergey; Harrison, David G.; Dudley, Samuel C.

2010-01-01

210

Nitric oxide: considerations for the treatment of ischemic stroke  

PubMed Central

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

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

2012-01-01

211

Nitric oxide in the upper stratosphere - Measurements and geophysical interpretation  

NASA Technical Reports Server (NTRS)

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.

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

1983-01-01

212

Measurement of arginine metabolites: regulators of nitric oxide metabolism.  

PubMed

Arginine is the substrate for nitric oxide synthases (NOS), and arginine availability regulates the production of nitric oxide. Through the activity of methyltransferases, arginine can be methylated to form monomethylarginine (NMMA), asymmetrical dimethylarginine (ADMA), and symmetrical dimethylarginine (SDMA). NMMA and ADMA directly inhibit NOS, whereas SDMA inhibits the cellular import of arginine through the cationic amino acid transporter. Increased levels of methylarginine compounds have been associated with many diseases including atherosclerosis, renal failure, pulmonary hypertension, and preeclampsia. Previous HPLC methods to measure these molecules rely on derivatization with ortho-phthalaldehyde, which is unstable and requires immediate pre- or post-column reactions. We have identified a new fluorometric agent that is stable for at least 1 week and provides chromatographic properties that facilitate separation of these chemically similar compounds by reverse phase chromatography. PMID:24510541

Augustine, Molly S; Rogers, Lynette K

2013-01-01

213

The regulation and pharmacology of endothelial nitric oxide synthase.  

PubMed

Nitric oxide (NO) is a small, diffusible, lipophilic free radical gas that mediates significant and diverse signaling functions in nearly every organ system in the body. The endothelial isoform of nitric oxide synthase (eNOS) is a key source of NO found in the cardiovascular system. This review summarizes the pharmacology of NO and the cellular regulation of endothelial NOS (eNOS). The molecular intricacies of the chemistry of NO and the enzymology of NOSs are discussed, followed by a review of the biological activities of NO. This information is then used to develop a more global picture of the pharmacological control of NO synthesis by NOSs in both physiologic conditions and pathophysiologic states. PMID:16402905

Dudzinski, David M; Igarashi, Junsuke; Greif, Daniel; Michel, Thomas

2006-01-01

214

Role of nitric oxide in regulating cardiac electrophysiology  

PubMed Central

Despite the explosion of new information on nitric oxide (NO), important questions about its role in regulating cardiac electrophysiology remain unanswered. Recent in vitro and in vivo animal studies have discovered a number of new electrophysiological properties of NO, some of which may contribute to a reduction in fatal arrhythmias induced by acute myocardial ischemia. This review summarizes the influences of NO on heart rate, atrioventricular conduction, ventricular repolarization and the development of ventricular arrhythmias during acute myocardial ischemia. PMID:20428454

Wang, Lexin

2001-01-01

215

Role of nitric oxide in implantation and menstruation  

Microsoft Academic Search

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

Kristof Chwalisz; Robert E. Garfield

2000-01-01

216

Altered immune responses in mice lacking inducible nitric oxide synthase  

Microsoft Academic Search

NITRIC oxide (NO) is important in many biological functions1-5. It is generated from L-arginine by the enzyme NO synthase (NOS). The cytokine-inducible NOS (iNOS) is activated by several immunological stimuli, leading to the production of large quantities of NO which can be cytotoxic6. To define the biological role of iNOS further, we generated iNOS mutant mice. These are viable, fertile

Xiao-Qing Wei; I. G. Charles; Austin Smith; Jan Ure; Gui-Jie Feng; Fang-Ping Huang; Damo Xu; W. Muller; Salvador Moncada

1995-01-01

217

What causes nitric oxide to infiltrate the ozone layer?  

NASA Astrophysics Data System (ADS)

At the Earth's poles, energetic particles that are injected into the atmosphere can chemically react and form nitric oxide (NO) molecules, which then descend through the atmosphere and can destroy ozone there. Previous studies have found that intense geomagnetic events lead to the largest descents of NO, but more recent research—following a large flux of NO in a period of quiet geomagnetic activity—suggests that such fluxes can have different origins.

Wendel, JoAnna

2014-12-01

218

Application of a Nitric Oxide Sensor in Biomedicine  

PubMed Central

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

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

2014-01-01

219

Tutorial Review: Electrochemical Nitric Oxide Sensors for Physiological Measurements  

PubMed Central

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

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

2013-01-01

220

Novel nitric oxide signaling mechanisms regulate the erectile response  

Microsoft Academic Search

Nitric oxide (NO) is a physiologic signal essential to penile erection, and disorders that reduce NO synthesis or release in the erectile tissue are commonly associated with erectile dysfunction. NO synthase (NOS) catalyzes production of NO from L-arginine. While both constitutively expressed neuronal NOS (nNOS) and endothelial NOS (eNOS) isoforms mediate penile erection, nNOS is widely perceived to predominate in

A L Burnett

2004-01-01

221

Decreased Exhaled Nitric Oxide Levels in Patients with Mitochondrial Disorders  

PubMed Central

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

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

2013-01-01

222

Nitric oxide synthases: three pieces to the puzzle?  

PubMed

Subarachnoid hemorrhage remains to be a devastating diagnosis in this day and age, with very few effective interventions. Rising evidence is now pointing towards the marked importance of secondary complications after the hemorrhage, and its active role in morbidity and mortality of this stroke. This review will focus on the role of Nitric Oxide Synthases (NOSes) the role they play in the pathogenesis of SAH. PMID:25366612

Attia, Mohammed Sabri; Lass, Eliott; Macdonald, R Loch

2015-01-01

223

Decoding Nitric Oxide Release Rates of Amine-Based Diazeniumdiolates  

PubMed Central

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

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

2013-01-01

224

Disruption of Fas Receptor Signaling by Nitric Oxide in Eosinophils  

PubMed Central

It has been suggested that Fas ligand–Fas receptor interactions are involved in the regulation of eosinophil apoptosis and that dysfunctions in this system could contribute to the accumulation of these cells in allergic and asthmatic diseases. Here, we demonstrate that nitric oxide (NO) specifically prevents Fas receptor–mediated apoptosis in freshly isolated human eosinophils. In contrast, rapid acceleration of eosinophil apoptosis by activation of the Fas receptor occurs in the presence of eosinophil hematopoietins. Analysis of the intracellular mechanisms revealed that NO disrupts Fas receptor–mediated signaling events at the level of, or proximal to, Jun kinase (JNK), but distal to sphingomyelinase (SMase) activation and ceramide generation. In addition, activation of SMase occurs downstream of an interleukin 1 converting enzyme–like (ICE-like) protease(s) that is not blocked by NO. However, NO prevents activation of a protease that targets lamin B1. These findings suggest a role for an additional NO-sensitive apoptotic signaling pathway that amplifies the proteolytic cascade initialized by activation of the Fas receptor. Therefore, NO concentrations within allergic inflammatory sites may be important in determining whether an eosinophil survives or undergoes apoptosis upon Fas ligand stimulation. PMID:9449721

Hebestreit, Holger; Dibbert, Birgit; Balatti, Ivo; Braun, Doris; Schapowal, Andreas; Blaser, Kurt; Simon, Hans-Uwe

1998-01-01

225

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

PubMed

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

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

2014-12-01

226

L-citrulline immunostaining identifies nitric oxide production sites within neurons  

NASA Technical Reports Server (NTRS)

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.

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

2002-01-01

227

The evolution of nitric oxide signalling in vertebrate blood vessels.  

PubMed

Nitric oxide is one of the most important signalling molecules involved in the regulation of physiological function. It first came to prominence when it was discovered that the vascular endothelium of mammals synthesises and releases nitric oxide (NO) to mediate a potent vasodilation. Subsequently, it was shown that NO is synthesised in the endothelium by a specific isoform of nitric oxide synthase (NOS) called NOS3. Following this discovery, it was assumed that an endothelial NO/NOS3 system would be present in all vertebrate blood vessels. This review will discuss the latest genomic, anatomical and physiological evidence which demonstrates that an endothelial NO/NOS3 signalling is not ubiquitous in non-mammalian vertebrates, and that there have been key evolutionary steps that have led to the endothelial NO signalling system being a regulatory system found only in reptiles, birds and mammals. Furthermore, the emerging role of nitrite as an endocrine source of NO for vascular regulation is discussed. PMID:25502832

Donald, John A; Forgan, Leonard G; Cameron, Melissa S

2015-02-01

228

High-latitude nitric oxide in the lower thermosphere  

NASA Technical Reports Server (NTRS)

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 midlatitude value and shows no correlation with the brightness of the instantaneous aurora. A time-dependent model calculation indicates that the ionization and dissociation of N2 by auroral electrons can increase the NO and N(4-S) densities. This increase is dependent on the intensity and duration of the auroral precipitation and on the branching ratio of N(2-D) production by dissociation of N2. A steady state is not reached for NO until 100,000 sec in an aurora characterized by an energy flux of 10 ergs per sq cm sec. Dissociation by the solar ultraviolet radiation competes with horizontal and vertical transport as a loss process for the nitric oxide produced by the aurora. A high NO(plus)/O2(plus) ratio is to be expected in the period following a strong auroral precipitation.

Gerard, J.-C.; Barth, C. A.

1977-01-01

229

An in vivo nitric oxide clamp to investigate the influence of nitric oxide on continuous umbilical blood flow during acute hypoxaemia in the sheep fetus  

PubMed Central

The aims of this study in the ovine fetus were to (1) characterise continuous changes in umbilical blood flow and vascular conductance during acute hypoxaemia and (2) determine the effects of nitric oxide blockade on umbilical blood flow and vascular conductance during normoxic and hypoxaemic conditions using a novel in vivo‘nitric oxide clamp’. Under 1–2 % halothane anaesthesia, seven ovine fetuses were instrumented between 118 and 125 days of gestation (term is ca 145 days) with vascular and amniotic catheters and a flow probe around an umbilical artery. At least 5 days after surgery, all fetuses were subjected to a 3 h protocol: 1 h of normoxia, 1 h of hypoxaemia and 1 h of recovery during fetal i.v. infusion with saline or, 1-2 days later, during combined fetal treatment with the nitric oxide (NO) inhibitor NG-nitro-l-arginine methyl ester (l-NAME, 100 mg kg?1) and the NO donor sodium nitroprusside (NP, 5.1 ± 2.0 ?g kg?1 min?1, the ‘nitric oxide clamp’). Following the end of the 3 h experimental protocol, the infusion of NP was withdrawn to unmask any persisting effects of fetal treatment with l-NAME alone. During acute hypoxaemia, the reduction in arterial partial pressure of O2 (Pa,O2) was similar in fetuses infused with saline or treated with the nitric oxide clamp. In all fetuses, acute hypoxaemia led to a progressive increase in mean arterial blood pressure and a fall in heart rate. In saline-infused fetuses, acute hypoxaemia led to a rapid, but transient, decrement in umbilical vascular conductance. Thereafter, umbilical vascular conductance was maintained and a significant increase in umbilical blood flow occurred, which remained elevated until the end of the hypoxaemic challenge. In contrast, while the initial decrement in umbilical vascular conductance was prevented in fetuses treated with the nitric oxide clamp, the increase in umbilical blood flow during hypoxaemia was similar to that in fetuses infused with saline. After the 1 h recovery period of the acute hypoxaemia protocol, withdrawal of the sodium nitroprusside infusion from fetuses undergoing the nitric oxide clamp led to a significant, but transient, hypertension and a sustained umbilical vasoconstriction. In conclusion, the data reported in this study of unanaesthetised fetal sheep (1) show that minute-by-minute analyses of haemodynamic changes in the umbilical vascular bed reveal an initial decrease in umbilical vascular conductance at the onset of hypoxaemia followed by a sustained increase in umbilical blood flow for the duration of the hypoxaemic challenge, (2) confirm that the increase in umbilical blood flow after 15 min hypoxaemia is predominantly pressure driven, and (3) demonstrate that nitric oxide plays a major role in the maintenance of umbilical blood flow under basal, but not under acute hypoxaemic, conditions. PMID:11731588

Gardner, David S; Powlson, Andrew S; Giussani, Dino A

2001-01-01

230

Chemically Modified Tetracyclines Inhibit Inducible Nitric Oxide Synthase Expression and Nitric Oxide Production in Cultured Rat Mesangial Cells  

Microsoft Academic Search

Tetracyclines inhibit matrix metalloproteinases (MMP) and attenuate connective tissue degradation in a wide variety of human and animal disorders. Chemically modified tetracyclines (CMT) have been synthesized in which the antibacterial potency has been eliminated but in which the anti-MMP efficacy is retained. Nitric oxide (NO) modulates MMP synthesis and activity in mesangial cellsin vitro.Therefore, we examined whether CMT inhibit iNOS

Howard Trachtman; Stephen Futterweit; Robert Greenwald; Susan Moak; Pravin Singhal; Nicholas Franki; Ashok R. Amin

1996-01-01

231

Technical considerations for inhaled nitric oxide therapy: time response to nitric oxide dosing changes and formation of nitrogen dioxide  

Microsoft Academic Search

The aim of the present study was to analyse the time response to nitric oxide (NO) dosing changes as well as the formation\\u000a of nitrogen dioxide (NO2) with different ventilation systems, respirator settings and application sites during NO inhalation. The inspired NO and\\u000a NO2 concentrations were continuously measured using chemiluminiscence within a dummy ventilatory system equipped with two different\\u000a respirator

J. Breuer; F. Waidelich; C. Irtel von Brenndorff; L. Sieverding; W. Rosendahl; W. Baden; M. Gass; J. Apitz

1997-01-01

232

Nitric oxide synthase immunoreactivity in the nematode Trichinella britovi. Evidence for nitric oxide production by the parasite.  

PubMed

Nitric oxide has been extensively studied as an effector molecule of the host immune response against both protozoa and helminths, but parasites can also produce this molecule, through the action of nitric oxide (NO) synthases or NO synthases-like enzymes. The aim of this study was to verify the possible production of NO by Trichinella britovi L(1) larvae and the enzymes involved in this process. The NO synthase immunoreactivity and putative nitric oxide synthase-activity was analysed using antibodies to mammalian NO synthase III and to nitrotyrosine with immunohistochemistry, gold immunocytochemistry and immunoblot analysis and NADPH-diaphorase histochemistry. Our results show that T. britovi L(1) larvae possess an enzymatic activity capable of producing NO. The localisation of this activity, according to the NADPH-diaphorase histochemistry, is both at the cuticular and the internal level. This localisation is confirmed by nitrotyrosine immunohistochemistry both under optical and electron microscopy. Using the NO synthase III antibody, a similar pattern of labelling was found: in particular, electron microscopy showed a localisation of this immunoreactivity in the cuticle and in the stichocytes, where only the alpha2 granules contained gold particles, mainly concentrated at their periphery. Four polypeptides reacting to the NO synthase III antibody are revealed by Western blotting. Their molecular weight ranged from 38 to 50 kDa. A significant reaction of the anti-nitrotyrosine antibody to polypeptides 95, 60, 48 and 39 kDa from the same sample suggested the presence of different nitrosylated proteins. PMID:15111093

Masetti, Massimo; Locci, Teresa; Cecchettini, Antonella; Lucchesi, Paolo; Magi, Marta; Malvaldi, Gino; Bruschi, Fabrizio

2004-05-01

233

Effects of superoxide dismutase mimetics on the activity of nitric oxide in rat aorta  

PubMed Central

A number of structurally distinct superoxide dismutase (SOD) mimetics were examined to determine if they shared the ability of authentic Cu/Zn SOD to produce endothelium-dependent relaxation of rings of rat aorta by protecting basal nitric oxide from destruction by endogenously produced superoxide anion. MnCl2 (10?nM–100??M), CuSO4 (100?nM–1?mM) and CuDIPS (Cu [II]-[diisopropylsalicylate]2; 100?nM–30??M) each mimicked the ability of Cu/Zn SOD (0.1–300?u?ml?1) to produce relaxation of phenylephrine-precontracted aortic rings in a manner inhibited by endothelial removal or treatment with NG-nitro-L-arginine methyl ester (L-NAME, 100??M). In contrast, MnTMPyP (Mn [III] tetrakis [1-methyl-4-pyridyl] porphyrin; 10?nM–30??M) augmented phenylephrine-induced contraction and this was blocked by endothelial removal or treatment with L-NAME (100??M), consistent with destruction rather than protection of basal nitric oxide activity. Pretreatment with Cu/Zn SOD (250?u?ml?1) blocked this augmentation suggesting that it arose paradoxically through destruction of nitric oxide by superoxide anion. The spin trap agents tiron (100?nM–1?mM), tempol (100?nM–1?mM) and PTIYO (4-phenyl-2,2,5,5-tetramethyl imidazolin-1-yloxy-5-oxide; 100?nM–300??M) all failed to promote endothelium-dependent relaxation. In fact, the last two augmented phenylephrine-induced tone and this was blocked by endothelial removal or treatment with L-NAME (100??M), consistent with destruction of basal nitric oxide activity. This destruction was unaffected by pretreatment with Cu/Zn SOD (250?u?ml?1) and probably reflected the direct ability of tempol and PTIYO to destroy nitric oxide. Thus, the ideal SOD mimetic for protection of nitric oxide activity in conditions of oxidant stress still awaits development. PMID:10455262

MacKenzie, Andrew; Filippini, Silvia; Martin, William

1999-01-01

234

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

NASA Astrophysics Data System (ADS)

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

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

2013-07-01

235

A cytochrome c modified-conducting polymer microelectrode for monitoring in vivo changes in nitric oxide  

Microsoft Academic Search

A nitric oxide (NO) microbiosensor based on cytochrome c (cyt c), a heme protein, immobilized onto a functionalized-conducting polymer (poly-TTCA) layer has been fabricated for the in vivo measurement of NO release stimulated by an abuse drug cocaine. Based on the direct electron transfer of cyt c, determination of NO with the cyt c-bonded poly-TTCA electrode was studied using cyclic

Wei Choon Alvin Koh; Eun Sang Choe; Dong Kun Lee; Yoon-Bo Shim

2008-01-01

236

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

Microsoft Academic Search

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

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

1987-01-01

237

A nitric oxide-releasing nonsteroidal anti-inflammatory drug accelerates gastric ulcer healing in rats  

Microsoft Academic Search

Background & Aims: Nonsteroidal anti-inflammatory drugs (NSAIDs) have well-characterized inhibitory effects on gastric ulcer healing. A new class of gastrointestinal-sparing, nitric oxide-releasing NSAID derivatives has been recently described. This study was performed to determine if one of these compounds (nitrofenac) would influence healing of a preexisting ulcer. Methods: Seven days after induction of gastric ulcer with serosal acetic acid, daily

Susan N. Elliott; Webb McKnight; Giuseppe Cirino; John L. Wallace

1995-01-01

238

Mechanisms regulating macrophage-induced nitric oxide production by spontaneously transformed hamster fibroblasts.  

PubMed

Nitric oxide has been implicated as an important effector molecule involved in tumor cell growth and cytotoxicity. In these studies we examined mechanisms regulating nitric oxide production by hamster tumor cells. Cocultures of hamster alveolar macrophages (HAM) and spontaneously transformed hamster embryonic fibroblasts (STHE cells) produced significant quantities of nitric oxide in response to lipopolysaccharide (LPS). Culture supernatants from HAM treated with LPS also stimulated nitric oxide production by STHE cells, whereas tumor cell culture supernatants had no effect on HAM. These data, together with the findings that paraformaldehyde treatment of STHE cells, but not macrophages, completely abrogated nitric oxide production in the cocultures demonstrate that the tumor cells were the source of this mediator. In contrast to STHE cells, STHE-83/20 cells, a highly malignant variant, did not produce nitric oxide in response to HAM or HAM culture supernatants even in the presence of LPS. Both anti-tumor necrosis factor-alpha (TNF-alpha) and anti-interleukin-1alpha (IL-1alpha) antibodies inhibited HAM-induced nitric oxide production by STHE cells. However, the kinetics of their effects were different. Moreover, although the nitric oxide stimulating activity in HAM culture supernatants was abrogated by anti-TNF-alpha antibody, it was only minimally reduced by anti-IL-1alpha antibody. These data demonstrate that TNF-alpha and IL-1alpha play distinct roles in induction of nitric oxide synthesis in STHE cells. HAM were also found to suppress proliferation of STHE cells, an effect that was inhibited by anti-TNF-alpha antibody, but not NG-monomethyl-L-arginine, which blocks nitric oxide synthase. Abrogation of macrophage-induced cytostasis in STHE cells by anti-TNF-alpha antibody was associated with decreased nitric oxide production. Thus TNF-alpha released by macrophages may indirectly activate STHE cells for nitric oxide synthesis by suppressing tumor cell proliferation. PMID:8864131

Lavnikova, N; Prokhorova, S; Burdelia, L; Lakhotia, A; Laskin, D L

1996-10-01

239

Effect of nitric oxide on poliovirus infection of two human cell lines.  

PubMed

The role of nitric oxide after poliovirus infection of the human HeLa (carcinoma) and U937 (promonocytic) cell lines has been analyzed. Both types of cells produced detectable levels of nitric oxide after poliovirus infection. However, this production was not sufficient to limit viral productivity. On the other hand, pretreatment with the nitric oxide donor glycerine trinitrate lengthened the course of poliovirus infection. PMID:9499120

López-Guerrero, J A; Carrasco, L

1998-03-01

240

Modulation of nitric oxide synthase activity in macrophages  

PubMed Central

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

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

1995-01-01

241

Assessing the physiological concentration and targets of nitric oxide in brain tissue  

PubMed Central

Low nanomolar concentrations of nitric oxide activate guanylyl cyclase to produce cGMP, which has diverse physiological effects. Higher concentrations inhibit mitochondrial respiration at cytochrome c oxidase and this has been proposed to be important physiologically, increasing oxygen permeation into tissue (by reducing the oxygen use of cells near blood vessels), activating AMP kinase, and regulating the relationship between cerebral blood flow and oxygen use. It is unclear, however, whether nitric oxide can accumulate physiologically to concentrations at which inhibition of respiration occurs. In rat cerebellar slices, we activated nitric oxide production from each isoform of nitric oxide synthase. Only activation of inducible nitric oxide synthase, which is expressed pathologically, caused any significant inhibition of respiration. Modelling oxygen and nitric oxide concentrations predicted that, in vivo, physiological nitric oxide levels are too low to affect respiration. Even pathologically, the nitric oxide concentration may only rise to 2.5 nm, producing a 1.5% inhibition of respiration. Thus, under physiological conditions, nitric oxide signals do not inhibit respiration but are well-tuned to the dynamic range of guanylyl cyclase activation. PMID:18535091

Hall, Catherine N; Attwell, David

2008-01-01

242

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

PubMed

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

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

2007-08-01

243

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

NASA Technical Reports Server (NTRS)

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

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

1986-01-01

244

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

PubMed

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

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

2006-05-01

245

Release and Elementary Mechanisms of Nitric Oxide in Hair Cells  

PubMed Central

The enzyme nitric oxide (NO) synthase, that produces the signaling molecule NO, has been identified in several cell types in the inner ear. However, it is unclear whether a measurable quantity of NO is released in the inner ear to confer specific functions. Indeed, the functional significance of NO and the elementary cellular mechanism thereof are most uncertain. Here, we demonstrate that the sensory epithelia of the frog saccule release NO and explore its release mechanisms by using self-referencing NO-selective electrodes. Additionally, we investigated the functional effects of NO on electrical properties of hair cells and determined their underlying cellular mechanism. We show detectable amounts of NO are released by hair cells (>50 nM). Furthermore, a hair-cell efferent modulator acetylcholine produces at least a threefold increase in NO release. NO not only attenuated the baseline membrane oscillations but it also increased the magnitude of current required to generate the characteristic membrane potential oscillations. This resulted in a rightward shift in the frequency–current relationship and altered the excitability of hair cells. Our data suggest that these effects ensue because NO reduces whole cell Ca2+ current and drastically decreases the open probability of single-channel events of the L-type and non L-type Ca2+ channels in hair cells, an effect that is mediated through direct nitrosylation of the channel and activation of protein kinase G. Finally, NO increases the magnitude of Ca2+-activated K+ currents via direct NO nitrosylation. We conclude that NO-mediated inhibition serves as a component of efferent nerve modulation of hair cells. PMID:20220083

Lv, Ping; Rodriguez-Contreras, Adrian; Kim, Hyo Jeong; Zhu, Jun; Wei, Dongguang; Choong-Ryoul, Sihn; Eastwood, Emily; Mu, Karen; Levic, Snezana; Song, Haitao; Yevgeniy, Petrov Y.; Smith, Peter J. S.

2010-01-01

246

Pin1 Prolyl Isomerase Regulates Endothelial Nitric Oxide Synthase  

PubMed Central

Objectives The Pin1 prolyl isomerase acts in concert with proline-directed protein kinases to regulate function of protein substrates through isomerization of peptide bonds that link phosphoserine or phosphothreonine to proline. We sought to determine whether Pin1 interacts with endothelial nitric oxide synthase (eNOS) in endothelial cells in a manner that depends on proline-directed phosphorylation of the eNOS enzyme and whether this interaction influences basal or agonist-stimulated eNOS activity. Methods and Results Inhibitors of the ERK 1/2 MAP kinases inhibit proline-directed phosphorylation of eNOS at serine 116 (S116) in bovine aortic endothelial cells (BAECs). Moreover, eNOS and Pin1 can be co-immunoprecipitated from BAECs only when S116 is phosphorylated. In addition, phospho-mimetic S116D eNOS, but not wild-type eNOS, can be co-immunoprecipitated with Pin1 co-expressed in COS-7 cells. Inhibition of Pin1 in BAECs by juglone or by dominant negative Pin1 increases basal and agonist-stimulated NO release from the cells while overexpression of wild-type Pin1 in BAECs suppresses basal and agonist-stimulated NO production. Overexpression of wild-type Pin1 in intact aortae also reduces agonist-induced relaxation of aortic rings. Conclusions Our results demonstrate a novel form of eNOS regulation in endothelial cells and blood vessels through S116 phosphorylation-dependent interaction of eNOS with Pin1. PMID:21051667

Ruan, Ling; Torres, Christina M.; Qian, Jin; Chen, Feng; Mintz, James D.; Stepp, David W.; Fulton, David; Venema, Richard C.

2010-01-01

247

Dysfunctional nitric oxide signalling increases risk of myocardial infarction.  

PubMed

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

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

248

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

NASA Technical Reports Server (NTRS)

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.

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

1998-01-01

249

Low temperature thermal oxidation of nitric oxide in polluted air  

NASA Astrophysics Data System (ADS)

High concentrations of NO x (1500ppb) and high NO ? NO2 conversion rates (100ppbh -1) have been measured in Göteborg during winter-time inversion periods. The conversion takes place without being significantly affected by light and the ozone concentration is always extremely low on these occasions. The dependence of the thermal oxidation 2 NO+ O2? 2 NO2 on temperature, humidity and catalytic activity of different surfaces has been investigated in an extensive kinetic study. The reaction rate has a strong negative temperature dependence with apparent activation energies of -3.5 kj mole -1 for r.h. = 55 % and -7.3 kj mole -1for dry conditions. The reaction is surface catalysed and the experiments indicate that the thermal oxidation takes place in two steps, one rapid equilibrium reaction, forming intermediates such as N 2O 2 or NO 3, and one rate-determining step in which NO 2 is formed. The presence of an aerosol surface increased the reaction rate very slightly, while street surface material had a more significant influence. When the flow reactor walls were coated with salt-snow or road dirt mixtures to simulate the surface of a winter street, the reaction rate increased typically to 3.5 × 10 4M -2s -1 from 2.1 ×10 4M -2s -1 for a clean reactor at -2°C. These values should be compared with the generally accepted value for the reaction rate, which is 1.5 × 10 4M -2s -1 at 25°C. The experimental results allow conversion rates of ~100 NOppbh -1 at rush hours and ~ 40 NO ppb h -1 for normal or low traffic to be rationalized in terms of the thermal NO ? NO2 reaction only, at an NO concentration of ~ 1000 ppb.

Lindqvist, Oliver; Ljungström, Evert; Svensson, Roger

250

Nitric oxide and zinc homeostasis in pulmonary endothelium.  

PubMed

We have shown that zinc-thiolate moieties of the metal binding protein metallothionein (MT) are critical targets for nitric oxide (NO) with resultant increases in intracellular labile zinc. Such an NO-MT-Zn signaling pathway appears to participate in important cardiovascular functions associated with biosynthesis of NO including hypoxic vasoconstriction in the lung. Although downstream effector signaling molecules and critical contractile targets remain unclear, current investigations reveal a contributory role for zinc dependent protein kinases and cytoskeletal proteins in mediating hypoxic induced constriction of pulmonary endothelial cells. PMID:20716286

Li, Huihua; Cao, Rong; Wasserloos, Karla J; Bernal, Paula; Liu, Zhao-Qian; Pitt, Bruce R; St Croix, Claudette M

2010-08-01

251

Antioxidant and nitric oxide synthase activation properties of Auricularia auricula.  

PubMed

In vitro evaluation of antioxidant activities of Auricularia auricula showed significant inhibition of lipid peroxidation, and potent hydroxyl radical scavenging activity when compared with standard drug catechin. IC5o value of crude, boiled and ethanolic extracts of A. auricula represented 403, 510, and 373 microg/ml respectively in case of hydroxyl radical scavenging activity and 310, 572 and 398 microg/ml respectively in case of lipid peroxidation. Furthermore, crude, boiled and ethanolic extracts also increase significantly nitric oxide production (664, 191 and 850 pmole/mg dry wt/hr respectively) over the control. The present results revealed that A. auricula had potential therapeutic use. PMID:15233483

Acharya, Krishnendu; Samui, Krishnendu; Rai, Manjula; Dutta, Bani Brata; Acharya, Rupa

2004-05-01

252

The Moving Frontier in Nitric Oxide-Dependent Signaling  

NSDL National Science Digital Library

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.

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

2004-11-02

253

[Effect of anticonvulsants on the nitric oxide system].  

PubMed

The effect of phenobarbital, carbamazepine, valproate sodium, depakine, topiramate and lamotrigine on the content of NO and NO-synthase activity in white rat brain tissues has been studied. It was established that the action of carbamazepine, valproate sodium, topiramate and lamotrigine decreases the activity of NO-synthase and the level of NO in the brain tissues. The amount of NO does not change while NO-synthase activity increases with the introduction of phenobarbital. The involvement of nitric oxide in the mechanism of action of the studied anticonvulsant drugs is discussed. PMID:23534293

Gromov, L A; Belenichev, I F; Gonchar-Cherdakli, L G; Zhernovaia, G A

2013-01-01

254

Acute right heart syndrome: Rescue treatment with inhaled nitric oxide  

PubMed Central

Acute right heart syndrome is a common occurrence in intensive care units and is associated with a poor prognosis. There is lack of understanding of the involved pathophysiology, standard diagnostic protocols and treatment guidelines. Management goals include ensuring adequate right ventricle (RV) filling, maximizing RV contraction and reducing RV afterload. We describe a 39-year-old female with acute decompensated right heart failure secondary to multiple causes. She was managed with inhaled nitric oxide. Her condition improved, which was evident by a decrease in her pulmonary artery systolic pressure on serial echocardiography, decreased requirement of vasopressors and successful weaning from the ventilator. PMID:24550613

Garg, Ashish; Vignesh, C.; Singh, Vinod Kumar; Ray, Sumit

2014-01-01

255

Production of nitric oxide in host-virus interaction  

PubMed Central

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

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

2010-01-01

256

Immediate effects of spinal manipulation on nitric oxide, substance P and pain perception.  

PubMed

Previous studies have analyzed the effects of spinal manipulation on pain sensitivity by using several sensory modalities, but to our knowledge, no studies have focused on serum biomarkers involved in the nociceptive pathway after spinal manipulation. Our objectives were to determine the immediate effect of cervical and dorsal manipulation over the production of nitric oxide and substance P, and establishing their relationship with changes in pressure pain thresholds in asymptomatic subjects. In this single-blind randomized controlled trial, 30 asymptomatic subjects (16 men) were randomly distributed into 3 groups (n = 10 per group): control, cervical and dorsal manipulation groups. Blood samples were extracted to obtain serum. ELISA assay for substance P and chemiluminescence analysis for nitric oxide determination were performed. Pressure pain thresholds were measured with a pressure algometer at the C5-C6 joint, the lateral epicondyle and the tibialis anterior muscle. Outcome measures were obtained before intervention, just after intervention and 2 h after intervention. Our results indicated an increase in substance P plasma level in the cervical manipulation group (70.55%) when compared with other groups (p < 0.05). This group also showed an elevation in the pressure pain threshold at C5-C6 (26.75%) and lateral epicondyle level (21.63%) immediately after the intervention (p < 0.05). No changes in nitric oxide production were observed. In conclusion, mechanical stimulus provided by cervical manipulation increases substance P levels and pressure pain threshold but does not change nitric oxide concentrations. Part of the hypoalgesic effect of spinal manipulation may be due to the action of substance P. PMID:24674816

Molina-Ortega, Francisco; Lomas-Vega, Rafael; Hita-Contreras, Fidel; Plaza Manzano, Gustavo; Achalandabaso, Alexander; Ramos-Morcillo, Antonio J; Martínez-Amat, Antonio

2014-10-01

257

Platelet aggregation responses are critically regulated in vivo by endogenous nitric oxide but not by endothelial nitric oxide synthase  

PubMed Central

Background and purpose: Although exogenous nitric oxide (NO) clearly modifies platelet function, the role and the source of endogenous NO in vivo remain undefined. In addition, endothelial NO synthase (NOS-3) critically regulates vessel tone but its role in modulating platelet function is unclear. In this paper we have investigated the roles of endogenous NO and NOS-3 in regulating platelet function in vivo and determined the functional contribution made by platelet-derived NO. Experimental approach: We used a mouse model for directly assessing platelet functional responses in situ in the presence of an intact vascular endothelium with supporting in vitro and molecular studies. Key results: Acute NOS inhibition by N?-nitro-L-arginine methyl ester hydrochloride (L-NAME) enhanced platelet aggregatory responses to thrombin and platelets were shown to be regulated primarily by NO sources external to the platelet. Elevation of endogenous NOS inhibitors to mimic effects reported in patients with cardiovascular diseases did not enhance platelet responses. Platelet responsiveness following agonist stimulation was not modified in male or female NOS-3?/? mice but responses in NOS-3?/? mice were enhanced by L-NAME. Conclusions and implications: Platelets are regulated by endogenous NO in vivo, primarily by NO originating from the environment external to the platelet with a negligible or undetectable role of platelet-derived NO. Raised levels of endogenous NOS inhibitors, as reported in a range of diseases were not, in isolation, sufficient to enhance platelet activity and NOS-3 is not essential for normal platelet function in vivo due to the presence of bioactive NO following deletion of NOS-3. PMID:19912226

Tymvios, C; Moore, C; Jones, S; Solomon, A; Sanz-Rosa, D; Emerson, M

2009-01-01

258

Nitric Oxide Synthase: Non-Canonical Expression Patterns  

PubMed Central

Science can move ahead by questioning established or canonical views and, so it may be with the enzymes, nitric oxide synthases (NOS). Nitric oxide (NO) is generated by NOS isoforms that are often described by their tissue-specific expression patterns. NOS1 (nNOS) is abundant in neural tissue, NOS2 is upregulated in activated macrophages and known as inducible NOS (iNOS), and NOS3 (eNOS) is abundant in endothelium where it regulates vascular tone. These isoforms are described as constitutive or inducible, but in this perspective we question the broad application of these labels. Are there instances where “constitutive” NOS (NOS1 and NOS3) are inducibly expressed; conversely, are there instances where NOS2 is constitutively expressed? NOS1 and NOS3 inducibility may be linked to post-translational regulation, making their actual patterns activity much more difficult to detect. Constitutive NOS2 expression has been observed in several tissues, especially the human pulmonary epithelium where it may regulate airway tone. These data suggest that expression of the three NOS enzymes may include non-established patterns. Such information should be useful in designing strategies to modulate these important enzymes in different disease states. PMID:25346730

Mattila, Joshua T.; Thomas, Anita C.

2014-01-01

259

Diurnal variation of nitric oxide in the upper stratosphere  

NASA Technical Reports Server (NTRS)

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.

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

1990-01-01

260

Nitric Oxide Signaling in Hypergravity-Induced Neuronal Plasticity  

NASA Technical Reports Server (NTRS)

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.

Holstein, Gay R.

2003-01-01

261

Exhaled nitric oxide in diagnosis and management of respiratory diseases  

PubMed Central

The analysis of biomarkers in exhaled breath constituents has recently become of great interest in the diagnosis, treatment and monitoring of many respiratory conditions. Of particular interest is the measurement of fractional exhaled nitric oxide (FENO) in breath. Its measurement is noninvasive, easy and reproducible. The technique has recently been standardized by both American Thoracic Society and European Respiratory Society. The availability of cheap, portable and reliable equipment has made the assay possible in clinics by general physicians and, in the near future, at home by patients. The concentration of exhaled nitric oxide is markedly elevated in bronchial asthma and is positively related to the degree of esinophilic inflammation. Its measurement can be used in the diagnosis of bronchial asthma and titration of dose of steroids as well as to identify steroid responsive patients in chronic obstructive pulmonary disease. In primary ciliary dyskinesia, nasal NO is diagnostically low and of considerable value in diagnosis. Among lung transplant recipients, FENO can be of great value in the early detection of infection, bronchioloitis obliterans syndrome and rejection. This review discusses the biology, factors affecting measurement, and clinical application of FENO in the diagnosis and management of respiratory diseases. PMID:19881162

Abba, Abdullah A.

2009-01-01

262

Uncoupling of endothelial nitric oxide synthase after experimental subarachnoid hemorrhage.  

PubMed

We studied whether endothelial nitric oxide synthase (eNOS) is upregulated and uncoupled in large cerebral arteries after subarachnoid hemorrhage (SAH) and also whether this causes cerebral vasospasm in a mouse model of anterior circulation SAH. Control animals underwent injection of saline instead of blood (n=16 SAH and n=16 controls). There was significant vasospasm of the middle cerebral artery 2 days after SAH (lumen radius/wall thickness ratio 4.3 ± 1.3 for SAH, 23.2 ± 2.1 for saline, P<0.001). Subarachnoid hemorrhage was associated with terminal deoxynucleotidyl transferase dUTP nick-end labeling, cleaved caspase-3, and Fluoro-Jade-positive neurons in the cortex and with CA1 and dentate regions in the hippocampus. There were multiple fibrinogen-positive microthromboemboli in the cortex and hippocampus after SAH. Transgenic mice expressing lacZ under control of the eNOS promoter had increased X-gal staining in large arteries after SAH, and this was confirmed by the increased eNOS protein on western blotting. Evidence that eNOS was uncoupled was found in that nitric oxide availability was decreased, and superoxide and peroxynitrite concentrations were increased in the brains of mice with SAH. This study suggests that artery constriction by SAH upregulates eNOS but that it is uncoupled and produces peroxynitrite that may generate microemboli that travel distally and contribute to brain injury. PMID:20517322

Sabri, Mohammed; Ai, Jinglu; Knight, Britta; Tariq, Asma; Jeon, Hyojin; Shang, Xueyuan; Marsden, Philip Anthony; Loch Macdonald, Robert

2011-01-01

263

Endothelial Caveolar Subcellular Domain Regulation of Endothelial Nitric Oxide Synthase  

PubMed Central

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

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

2015-01-01

264

Endothelial nitric oxide synthase transgenic models of endothelial dysfunction  

PubMed Central

Endothelial production of nitric oxide is critical to the regulation of vascular responses, including vascular tone and regional blood flow, leukocyte–endothelial interactions, platelet adhesion and aggregation, and vascular smooth muscle cell proliferation. A relative deficiency in the amount of bioavailable vascular NO results in endothelial dysfunction, with conditions that are conducive to the development of atherosclerosis: thrombosis, inflammation, neointimal proliferation, and vasoconstriction. This review focuses on mouse models of endothelial dysfunction caused by direct genetic modification of the endothelial nitric oxide synthase (eNOS) gene. We first describe the cardiovascular phenotypes of eNOS knockout mice, which are a model of total eNOS gene deficiency and thus the ultimate model of endothelial dysfunction. We then describe S1177A and S1177D eNOS mutant mice as mouse models with altered eNOS phosphorylation and therefore varying degrees of endothelial dysfunction. These include transgenic mice that carry the eNOS S1177A and S1177D transgenes, as well as knockin mice in which the endogenous eNOS gene has been mutated to carry the S1177A and S1177D mutations. Together, eNOS knockout mice and eNOS S1177 mutant mice are useful tools to study the effects of total genetic deficiency of eNOS as well as varying degrees of endothelial dysfunction caused by eNOS S1177 phosphorylation. PMID:20697735

Atochin, Dmitriy N.; Huang, Paul L.

2010-01-01

265

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

PubMed

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

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

2015-04-15

266

Regulation of Endothelial Nitric Oxide Synthase and Postnatal Angiogenesis by Rac1  

PubMed Central

Diminished bioavailability of nitric oxide is a hallmark of endothelial dysfunction and is associated with a broad spectrum of vascular disorders such as impaired angiogenesis. Because Rac1, a Rho family member, mediates cellular motility and generation of reactive oxygen species, it could be involved in the regulation of endothelial nitric oxide production. However, the pathophysiological consequences of postnatal endothelial Rac1 deletion on endothelial function have not been determined. We generated endothelial-specific Rac1 haploinsufficient mice (EC-Rac1+/-) using Cre-loxP technology. The EC-Rac1+/- mice have decreased expression and activity of endothelial nitric oxide synthase (eNOS), impaired endothelium-dependent vasorelaxation, and mild hypertension compared with control (Rac1+/flox) mice. Hind limb ischemia model and aortic capillary sprouting assay showed that eNOS activity and angiogenesis was impaired in EC-Rac1+/- mice. Indeed, Rac1 promotes eNOS gene transcription through p21-activated kinase but not NADPH oxidase, increases eNOS mRNA stability, and enhances eNOS activity by promoting endothelial uptake of l-arginine. These findings indicate that endothelial Rac1 is essential for endothelium-dependent vasomotor response and ischemia-induced angiogenesis. These effects of Rac1 on endothelial function are largely due to the upregulation of eNOS through multiple mechanisms that are mediated, in part, by p21-activated kinase. Therapeutic strategies to enhance Rac1 function, therefore, may be important for preventing endothelial dysfunction. PMID:18599867

Sawada, Naoki; Salomone, Salvatore; Kim, Hyung-Hwan; Kwiatkowski, David J.; Liao, James K.

2008-01-01

267

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

PubMed Central

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

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

2010-01-01

268

The role of nitric oxide radicals in removal of hyper-radiosensitivity by priming irradiation  

PubMed Central

In this study, a mechanism in which low-dose hyper-radiosensitivity (HRS) is permanently removed, induced by low-dose-rate (LDR) (0.2–0.3 Gy/h for 1 h) but not by high-dose-rate priming (0.3 Gy at 40 Gy/h) was investigated. One HRS-negative cell line (NHIK 3025) and two HRS-positive cell lines (T-47D, T98G) were used. The effects of different pretreatments on HRS were investigated using the colony assay. Cell-based ELISA was used to measure nitric oxide synthase (NOS) levels, and microarray analysis to compare gene expression in primed and unprimed cells. The data show how permanent removal of HRS, previously found to be induced by LDR priming irradiation, can also be induced by addition of nitric oxide (NO)-donor DEANO combined with either high-dose-rate priming or exposure to prolonged cycling hypoxia followed by reoxygenation, a treatment not involving radiation. The removal of HRS appears not to involve DNA damage induced during priming irradiation as it was also induced by LDR irradiation of cell-conditioned medium without cells present. The permanent removal of HRS in LDR-primed cells was reversed by treatment with inducible nitric oxide synthase (iNOS) inhibitor 1400W. Furthermore, 1400W could also induce HRS in an HRS-negative cell line. The data suggest that LDR irradiation for 1 h, but not 15 min, activates iNOS, and also that sustained iNOS activation is necessary for the permanent removal of HRS by LDR priming. The data indicate that nitric oxide production is involved in the regulatory processes determining cellular responses to low-dose-rate irradiation. PMID:23685670

Edin, Nina Jeppesen; Sandvik, Joe Alexander; Vollan, Hilde Synnøve; Reger, Katharina; Görlach, Agnes; Pettersen, Erik Olai

2013-01-01

269

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

Microsoft Academic Search

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

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

2005-01-01

270

Nitric oxide and pro-inflammatory cytokines in acute hepatitis B  

Microsoft Academic Search

Background: Experimental studies demonstrate that hepatitis B virus may induce nitric oxide (NO) production in infected hepatocytes. Its presence in acute hepatitis B patients has not been studied. Methods: Serum levels of nitric oxide and its regulatory pro-inflammatory cytokines were detected in 15 patients with uncomplicated acute hepatitis B, 19 blood donors and 15 chronic hepatitis B patients. Cytokines were

Meri Koulentaki; George Notas; Efthimia Petinaki; Vassilis Valatas; Ioannis A Mouzas; Elias Castanas; Elias A Kouroumalis

2004-01-01

271

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

Microsoft Academic Search

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

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

1995-01-01

272

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

E-print Network

Nitric Oxide in Biological Denitrification: Fe/Cu Metalloenzyme and Metal Complex NOx Redox Nitrite Reductase: 1204 2. Copper Nitrite Reductases 1206 B. Nitric Oxide Reductase 1208 1. Structure 1208. Copper-Mediated NO(g) Chemistry 1221 D. Iron Complex-Mediated NO(g) Reactivity 1224 E. Transition Metal

Schroeder, Imke

273

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

PubMed Central

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

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

2011-01-01

274

Formation of an olfactory recognition memory in mice: Reassessment of the role of nitric oxide  

Microsoft Academic Search

The plexiform and granule cell layers of the female mouse accessory olfactory bulb, whose synaptic activities are modified by pheromonal inputs after mating, contain one of the highest densities of nitric oxide synthase in the brain. We tested the hypothesis that exogenous nitric oxide administration can, in principle, permit the formation of a specific pheromonal memory without mating by acting

C. O. Okere; H. Kaba; T. Higuchi

1996-01-01

275

Evidence of an increased nitric oxide production in primary biliary cirrhosis  

Microsoft Academic Search

OBJECTIVE:Although possible implications of nitric oxide in the pathophysiology of liver cirrhosis have been extensively studied, until now few articles have addressed the assessment of nitric oxide production in primary biliary cirrhosis. This study was directed to evaluate circulating nitrosyl-hemoglobin levels as well as neutrophil elastase and soluble adhesion molecule concentrations in this condition, by assuming these parameters as possible

Stefania Battista; Fabrizio Bar; Giulio Mengozzi; Cristina Pollet; Mauro Torchio; Guido Cavalli; Floriano Rosina; Ezio David; Juan Carlos Cutrin; Barbara Cavalieri; Giuseppe Poli; Gianpaolo Molino

2001-01-01

276

A two-compartment model of pulmonary nitric oxide exchange dynamics  

E-print Network

exogenous NO delivered by inhalation as a therapy in such diseases as pulmonary hypertension, acuteA 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

George, Steven C.

277

The Effect of Nuclear Explosions on Stratospheric Nitric Oxide and Ozone  

Microsoft Academic Search

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

Harold Johnston; Garry Whitten; John Birks

1973-01-01

278

Cavity ringdown spectroscopic detection of nitric oxide with a continuous-wave quantum-cascade laser  

E-print Network

require a compact and intense tunable light source. Quantum-cascade QC distributed-feedback DFB lasersCavity ringdown spectroscopic detection of nitric oxide with a continuous-wave quantum-cascade for nitric oxide NO detection based on a cavity ringdown technique was designed and evaluated. A cw quantum-cascade

279

Nitric oxide mediates elicitor-induced saponin synthesis in cell cultures of Panax ginseng  

Microsoft Academic Search

The elicitor oligogalacturonic acid (OGA) stimulated nitric oxide (NO) accumulation in the growth medium of ginseng suspension cultures and induced increased nitric oxide synthase (NOS) activity in ginseng cells. OGA also stimulated accumulation of saponin, transcription of genes encoding squalene synthase (sqs) and squalene epoxidase (sqe), two early enzymes of saponin synthesis, and the accumulation of ?-amyrin synthase protein (?-AS).

Xiangyang Hu; Steven J. Neill; Weiming Cai; Zhangcheng Tang

2003-01-01

280

Nitric oxide signaling in plants: cross-talk with Ca2+ , protein kinases  

E-print Network

1 Nitric oxide signaling in plants: cross-talk with Ca2+ , protein kinases and reactive oxygen of NO signaling in animals and discuss current knowledge of NO signaling in plants, focusing on its interplay regulators of signal transduction. Keywords: Calcium, cell death, nitric oxide, protein kinases, reactive

Paris-Sud XI, Université de

281

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

PubMed

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

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

282

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...

283

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...

284

Topical administration of a novel nitric oxide donor, linear polyethylenimine-nitric oxide\\/nucleophile adduct (DS1), selectively increases vaginal blood flow in anesthetized rats  

Microsoft Academic Search

The aim of the present study was to test the effects of a topical administration of a novel nitric oxide donor, linear polyethylenimine-nitric oxide\\/nucleophile adduct (DS1), on vaginal blood flow and hemodynamics in rats. Laser Doppler flowmetry was used to measure blood flow changes following topical application of DS1 (0.3 or 1.5 mg in 0.15 ml saline) into the vagina

P Pacher; JG Mabley; L Liaudet; OV Evgenov; GJ Southan; GE Abdelkarim; C Szabó; AL Salzman

2003-01-01

285

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

E-print Network

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 ...

Wogan, Gerald N.

286

A Role for Nitric Oxide in Muscle Repair: Nitric Oxide–mediated Activation of Muscle Satellite Cells  

PubMed Central

Muscle satellite cells are quiescent precursors interposed between myofibers and a sheath of external lamina. Although their activation and recruitment to cycle enable muscle repair and adaptation, the activation signal is not known. Evidence is presented that nitric oxide (NO) mediates satellite cell activation, including morphological hypertrophy and decreased adhesion in the fiber-lamina complex. Activation in vivo occurred within 1 min after injury. Cell isolation and histology showed that pharmacological inhibition of nitric oxide synthase (NOS) activity prevented the immediate injury-induced myogenic cell release and delayed the hypertrophy of satellite cells in that muscle. Transient activation of satellite cells in contralateral muscles 10 min later suggested that a circulating factor may interact with NO-mediated signaling. Interestingly, satellite cell activation in muscles of mdx dystrophic mice and NOS-I knockout mice quantitatively resembled NOS-inhibited release of normal cells, in agreement with reports of displaced and reduced NOS expression in dystrophin-deficient mdx muscle and the complete loss of NOS-I expression in knockout mice. Brief NOS inhibition in normal and mdx mice during injury produced subtle alterations in subsequent repair, including apoptosis in myotube nuclei and myotube formation inside laminar sheaths. Longer NOS inhibition delayed and restricted the extent of repair and resulted in fiber branching. A model proposes the hypothesis that NO release mediates satellite cell activation, possibly via shear-induced rapid increases in NOS activity that produce “NO transients.” PMID:10793157

Anderson, Judy E.

2000-01-01

287

Expression of Inducible Nitric Oxide Synthase in Bovine Corneal Endothelial Cells and Keratocytes In Vitro After Lipopolysaccharide and Cytokines Stimulation  

Microsoft Academic Search

Purpose. To determine whether bovine corneal endothelial (BCE) cells and keratocytes express the inducible form of nitric oxide synthase (NOS) after exposure to cytokines and lipopolysac- charide (LPS), and to study the regulation of NOS by growth factors. Methods. Cultures of bovine corneal endothelial cells and keratocytes were exposed to increas- ing concentrations of LPS, interferon-y (IFN-y), and tumor necrosis

Pablo Dighiero; Francine Behar-Cohen; Yves Courtois; Olivier Goureau

1997-01-01

288

A cohort of supporting metabolic enzymes is coinduced with nitric oxide synthase in human tumor cell lines  

Microsoft Academic Search

Although nitric oxide (NO) has cytotoxic activity against certain tumor cell lines, some human tumor cell lines can themselves produce NO by expressing the inducible isoform of NO synthase (iNOS). As rates of cellular NO synthesis play a major role in determining whether NO has cytotoxic or cytoprotective effects at anatomic sites of NO production, identification of cellular processes which

Andreas K. Nussler; Zhi-Ze Liu; Kazuyuki Hatakeyama; David A. Geller; Timothy R. Billiar; Sidney M. Morris

1996-01-01

289

Nitric Oxide Regulates Receptor Activator of Nuclear Factor B Ligand and Osteoprotegerin Expression in Bone Marrow Stromal Cells  

Microsoft Academic Search

Bone remodeling reflects an equilibrium between bone re- sorption and formation. The local expression of receptor ac- tivator of nuclear factor-B ligand (RANKL) and osteoprote- gerin (OPG) in bone determines the entry of monoblastic precursors into the osteoclast lineage and subsequent bone resorption. Nitric oxide (NO) inhibits osteoclastic bone re- sorption in vitro and regulates bone remodeling in vivo .A

XIAN FAN; EILEEN ROY; LIPING ZHU; TAMARA C. MURPHY; CHERYL ACKERT-BICKNELL; C. MICHAEL HART; CLIFFORD ROSEN; MARK S. NANES; JANET RUBIN

2003-01-01

290

Mechanisms of transient nitric oxide and nitrous oxide production in a complex biofilm  

Microsoft Academic Search

Nitric oxide (NO) and nitrous oxide (N2O) are formed during N-cycling in complex microbial communities in response to fluctuating molecular oxygen (O2) and nitrite (NO2?) concentrations. Until now, the formation of NO and N2O in microbial communities has been measured with low spatial and temporal resolution, which hampered elucidation of the turnover pathways and their regulation. In this study, we

Frank Schreiber; Birte Loeffler; Lubos Polerecky; Marcel MM Kuypers; Dirk de Beer

2009-01-01

291

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

PubMed

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

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

2004-08-01

292

Nitric oxide and the pancreas: Morphological base and role in the control of the exocrine pancreatic secretion  

Microsoft Academic Search

The distribution of nitric oxide synthase in both neuronal and non-neuronal pancreatic tissues and the role of nitric oxide in the control of exocrine pancreatic secretion are reviewed in this article. Earlier reports based on in vivo studies suggested that nitric oxide can affect the secretory activity of the exocrine pancreas through changes in pancreatic blood flow. More recently, the

Maria D. Yago; Zsolt Ember; Jaipaul Singh

2001-01-01

293

Effect of Mild Nitric Acid Oxidation on Dispersability, Size, and Structure of Single-Walled Carbon Nanotubes  

E-print Network

Effect of Mild Nitric Acid Oxidation on Dispersability, Size, and Structure of Single-Walled Carbon) with nitric acid increases their dispersability in water, methanol, and N,N-dimethylformamide. Two oxidation conditions carefully. Nitric acid has been the most frequently utilized agent for oxidation of carbon

Resasco, Daniel

294

Antipsychotic, antidepressant, anxiolytic, and anticonvulsant drugs induce type II nitric oxide synthase mRNA in rat brain  

Microsoft Academic Search

Nitric oxide synthase inhibitors have been regarded as potentially beneficial for psychiatric disorders such as depression and schizophrenia, though little is known about how nitric oxide synthases are affected by psychotropic drugs in the brain. Using reverse transcription-polymerase chain reaction analysis, we investigated the effects of short- and long-term oral treatments with several psychotropics on type II nitric oxide synthase

Eiji Suzuki; Toshio Nakaki; Futoshi Shintani; Shigenobu Kanba; Hitoshi Miyaoka

2002-01-01

295

Inhibition of Nitric Oxide Synthase Impairs a Distinct Form of Long-Term Memory in the Honeybee, Apis mellifera  

Microsoft Academic Search

Nitric oxide has been shown to be implicated in neural plasticity that underlies processes of learning and memory. In the honeybee, studies on the role of nitric oxide in associative olfactory learning reveal its specific function in memory formation. Inhibition of nitric oxide synthase during olfactory conditioning impairs a distinct long-term memory that is formed as a consequence of multiple

Uli Müller

1996-01-01

296

Nitric Oxide Synthase is Necessary for Normal Urogenital Development  

PubMed Central

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

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

2014-01-01

297

Nitric Oxide Increases Lysine 48-Linked Ubiquitination Following Arterial Injury  

PubMed Central

Introduction Proteins are targeted for degradation by the addition of a polyubiquitin chain. Chains of ubiquitin linked via lysine 48 (K48) are associated with protein degradation while chains linked via lysine 63 (K63) are associated with intracellular signaling. We have previously shown that nitric oxide (NO) inhibits neointimal hyperplasia in association with increasing the ubiquitination and degradation of UbcH10. The aim of this study is to characterize the effect of arterial injury and NO on K48- or K63-linked ubiquitination of cellular proteins. Methods The rat carotid artery balloon injury model was performed. Treatment groups included control, injury, injury+proline NONOate (PROLI/NO), and PROLI/NO alone. Arteries were harvested at designated time points and sectioned for immunohistochemical analysis of K48- and K63-linked ubiquitination or homogenized for protein analysis. Vascular smooth muscle cells (VSMC) harvested from rat aortae were exposed to the NO donor diethylenetriamine NONOate (DETA/NO). Protein expression was determined by Western blot analysis, or immunoprecipitation and Western blot analysis. Results Arterial injury increased K48-linked ubiquitination in vivo. The addition of PROLI/NO following injury caused a further increase in K48-linked ubiquitination at 1 and 3 days, however, levels returned to that of injury alone by 2 weeks. Interestingly, treatment with PROLI/NO alone increased K48-linked ubiquitination in vivo to levels similar to injury alone. There were minimal changes in K63-linked ubiquitination in all three treatment groups. DETA/NO increased K48-linked ubiquitination in VSMC in vitro but had minimal effects on K63-linked ubiquitination. Low doses of DETA/NO decreased K48-linked ubiquitination of cyclin A and B, while high doses of DETA/NO increased K48-linked ubiquitination of cyclin A and B. Minimal changes were seen in K63-linked ubiquitination of cyclin A and B in vitro. Conclusions Arterial injury and NO increased K48-linked ubiquitination in vivo and in vitro. Remarkably, minimal changes were seen in K63-linked ubiquitination. These novel findings provide important insights into the vascular biology of arterial injury and suggest that one mechanism by which NO may prevent neointimal hyperplasia is through regulation of protein ubiquitination. PMID:21737094

Oustwani, Chris S.; Tsihlis, Nick D.; Vavra, Ashley K.; Jiang, Qun; Martinez, Janet; Kibbe, Melina R.

2011-01-01

298

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

PubMed

Sporadic inclusion body myositis is a severely disabling myopathy. The design of effective treatment strategies is hampered by insufficient understanding of the complex disease pathology. Particularly, the nature of interrelationships between inflammatory and degenerative pathomechanisms in sporadic inclusion body myositis has remained elusive. In Alzheimer's dementia, accumulation of ?-amyloid has been shown to be associated with upregulation of nitric oxide. Using quantitative polymerase chain reaction, an overexpression of inducible nitric oxide synthase was observed in five out of ten patients with sporadic inclusion body myositis, two of eleven with dermatomyositis, three of eight with polymyositis, two of nine with muscular dystrophy and two of ten non-myopathic controls. Immunohistochemistry confirmed protein expression of inducible nitric oxide synthase and demonstrated intracellular nitration of tyrosine, an indicator for intra-fibre production of nitric oxide, in sporadic inclusion body myositis muscle samples, but much less in dermatomyositis or polymyositis, hardly in dystrophic muscle and not in non-myopathic controls. Using fluorescent double-labelling immunohistochemistry, a significant co-localization was observed in sporadic inclusion body myositis muscle between ?-amyloid, thioflavine-S and nitrotyrosine. In primary cultures of human myotubes and in myoblasts, exposure to interleukin-1? in combination with interferon-? induced a robust upregulation of inducible nitric oxide synthase messenger RNA. Using fluorescent detectors of reactive oxygen species and nitric oxide, dichlorofluorescein and diaminofluorescein, respectively, flow cytometry revealed that interleukin-1? combined with interferon-? induced intracellular production of nitric oxide, which was associated with necrotic cell death in muscle cells. Intracellular nitration of tyrosine was noted, which partly co-localized with amyloid precursor protein, but not with desmin. Pharmacological inhibition of inducible nitric oxide synthase by 1400W reduced intracellular production of nitric oxide and prevented accumulation of ?-amyloid, nitration of tyrosine as well as cell death inflicted by interleukin-1? combined with interferon-?. Collectively, these data suggest that, in skeletal muscle, inducible nitric oxide synthase is a central component of interactions between interleukin-1? and ?-amyloid, two of the most relevant molecules in sporadic inclusion body myositis. The data further our understanding of the pathology of sporadic inclusion body myositis and may point to novel treatment strategies. PMID:22436237

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

2012-04-01

299

Regulation of nitric oxide production by ?-opioid receptors during glaucomatous injury.  

PubMed

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

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

2014-01-01

300

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

PubMed Central

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

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

2014-01-01

301

Structural basis for nitrous oxide generation by bacterial nitric oxide reductases  

PubMed Central

The crystal structure of the bacterial nitric oxide reductase (cNOR) from Pseudomonas aeruginosa is reported. Its overall structure is similar to those of the main subunit of aerobic and micro-aerobic cytochrome oxidases (COXs), in agreement with the hypothesis that all these enzymes are members of the haem-copper oxidase superfamily. However, substantial structural differences between cNOR and COX are observed in the catalytic centre and the delivery pathway of the catalytic protons, which should be reflected in functional differences between these respiratory enzymes. On the basis of the cNOR structure, we propose a possible reaction mechanism of nitric oxide reduction to nitrous oxide as a working hypothesis. PMID:22451105

Shiro, Yoshitsugu; Sugimoto, Hiroshi; Tosha, Takehiko; Nagano, Shingo; Hino, Tomoya

2012-01-01

302

Regulation of Injury-Induced Neurogenesis by Nitric Oxide  

PubMed Central

The finding that neural stem cells (NSCs) are able to divide, migrate, and differentiate into several cellular types in the adult brain raised a new hope for restorative neurology. Nitric oxide (NO), a pleiotropic signaling molecule in the central nervous system (CNS), has been described to be able to modulate neurogenesis, acting as a pro- or antineurogenic agent. Some authors suggest that NO is a physiological inhibitor of neurogenesis, while others described NO to favor neurogenesis, particularly under inflammatory conditions. Thus, targeting the NO system may be a powerful strategy to control the formation of new neurons. However, the exact mechanisms by which NO regulates neural proliferation and differentiation are not yet completely clarified. In this paper we will discuss the potential interest of the modulation of the NO system for the treatment of neurodegenerative diseases or other pathological conditions that may affect the CNS. PMID:22997523

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

2012-01-01

303

High serum nitric oxide levels in patients with severe leptospirosis  

PubMed Central

Leptospirosis is a globally distributed zoonosis of major public health importance and is associated with severe disease manifestations such as acute renal failure and pulmonary haemorrhage syndrome. However, the extent to which the pathogenesis of leptospirosis mimics sepsis caused by Gram-negative bacteria remains unknown. The aim of this study was to evaluate serum levels of nitric oxide (NO) in patients diagnosed with severe leptospirosis. Sera from 35 confirmed cases of severe leptospirosis and 13 healthy subjects were analysed. Patients with severe leptospirosis had significantly higher NO levels compared to healthy individuals (30.82 ± 10.90 ?M versus 3.86 ± 1.34 ?M, P<0.001), indicating that this immune mediator plays a role in the underlying systemic inflammatory response. PMID:17196920

Maciel, Elves A. P.; Athanazio, Daniel A.; Reis, Eliana A.G.; Cunha, Fernando Q.; Queiroz, Adriano; Almeida, Deusdelia; McBride, Alan J. A.; Ko, Albert I.; Reis, Mitermayer G.

2007-01-01

304

Visualisation of nitric oxide released by nerve stimulation.  

PubMed

We have visualised nitric oxide (NO) released from the electrically stimulated myenteric plexus and hypogastric nerve. NO was visualised by a reaction with luminol and hydrogen peroxide to generate photons which were counted using a microscope coupled to a photon counting camera. Electrical stimulation of the tissues induced an increase in photon counts which was frequency-dependent and prevented by inhibition of the NO synthase or by tetrodotoxin. The light emitted during nerve stimulation was not only observed at the nerve terminals but also at the axon and soma. Our results indicate that NO released from the whole nerve cell may affect target cells surrounding all parts of the nitrergic neuron. Thus, NO functions as a unique mechanism of synaptic and non-synaptic communication in the nervous system. PMID:9008153

Wiklund, N P; Cellek, S; Leone, A M; Iversen, H H; Gustafsson, L E; Brundin, L; Furst, V W; Flock, A; Moncada, S

1997-01-15

305

Nitric oxide-cyclic GMP signaling in stem cell differentiation  

PubMed Central

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

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

2011-01-01

306

Nitric Oxide Links Mitochondrial Fission to Alzheimer's Disease  

NSDL National Science Digital Library

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.

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

2009-05-05

307

The role of inhaled nitric oxide beyond ARDS  

PubMed Central

Patients with traumatic brain injury complicated by acute respiratory distress syndrome (ARDS) are not uncommon in intensive care unit (ICU). The ventilatory management of patients combined with both of these catastrophic conditions is not straightforward. Evidence-based permissive hypercapnia strategy for ARDS could be fatal in patients with intracranial hypertension. Adjunctive use of inhaled nitric oxide (INO) is well-defined as a rescue therapy in severe ARDS, but its specific role in intracranial hypertension is somewhat uncertain. We report a case, which following traumatic brain injury developed both intracranial hypertension and ARDS. INO was given for ARDS, but coincidentally it also improved the raised intracranial pressure (ICP) and patient's neurological outcome. The case report will be followed by literature review on the role of INO in raised ICP. PMID:24987239

Khan, Muhammad Faisal; Azfar, Mohammad Feroz; Khurshid, Syed Moazzum

2014-01-01

308

Cocoa flavanols: effects on vascular nitric oxide and blood pressure  

PubMed Central

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

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

2011-01-01

309

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

PubMed

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

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

2011-01-01

310

Antibacterial efficacy of exogenous nitric oxide on periodontal pathogens.  

PubMed

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

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

2014-11-01

311

Elevation in Exhaled Nitric Oxide Predicts for Radiation Pneumonitis  

PubMed Central

Purpose Radiation pneumonitis is a major toxicity following thoracic radiotherapy with no method available to accurately predict the individual risk. This is a prospective study to evaluate exhaled nitric oxide as a predictive biomarker for radiation pneumonitis in esophagus cancer patients. Patients and Methods 34 patients prescribed neoadjuvant chemoradiotherapy for esophagus cancer were enrolled in this trial. Each received respiratory surveys and exhaled nitric oxide (NO) measurements before, at the end of, and 1 to 2 months after completing radiotherapy. Pneumonitis toxicity was scored using the Common Terminology Criteria for Adverse Events version 4.0. The demographics, dosimetric factors, and exhaled NO were evaluated for correlation with symptomatic patients (scores ?2). Results 28 patients were evaluable, all received 50.4 Gy with concurrent chemotherapy. Pneumonitis toxcity scores were: 1 grade 3, 3 grade 2, 7 grade 1, and 17 grade 0. Dosimetric factors were not predictive of symptoms. Exhaled NO measured before, at completion, and at restaging were 17.3(8.5; 5.5 - 36.7), 16.0(14.2; 5.8 - 67.7), 14.7(6.2; 5.5 - 28.0) parts per billion respectively. The ratio of exhaled NO at the end of radiotherapy versus pre-treatment was 3.4(1.7 - 6.7) for the symptomatic and 0.8(0.3 - 1.3) for the asymptomatic (P = 0.0017). Elevation in exhaled NO preceded peak symptoms by 33(21 - 50) days. The time to peak symptoms was found to be inversely related to the exhaled NO elevation. Conclusions Elevation in the exhaled NO at the end of radiotherapy was found to predict for radiation pneumonitis symptoms. PMID:21377296

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

2012-01-01

312

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

PubMed Central

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

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

2012-01-01

313

Effects of Nitric Oxide on Neuromuscular Properties of Developing Zebrafish Embryos  

PubMed Central

Nitric oxide is a bioactive signalling molecule that is known to affect a wide range of neurodevelopmental processes. However, its functional relevance to neuromuscular development is not fully understood. Here we have examined developmental roles of nitric oxide during formation and maturation of neuromuscular contacts in zebrafish. Using histochemical approaches we show that elevating nitric oxide levels reduces the number of neuromuscular synapses within the axial swimming muscles whilst inhibition of nitric oxide biosynthesis has the opposite effect. We further show that nitric oxide signalling does not change synapse density, suggesting that the observed effects are a consequence of previously reported changes in motor axon branch formation. Moreover, we have used in vivo patch clamp electrophysiology to examine the effects of nitric oxide on physiological maturation of zebrafish neuromuscular junctions. We show that developmental exposure to nitric oxide affects the kinetics of spontaneous miniature end plate currents and impacts the neuromuscular drive for locomotion. Taken together, our findings implicate nitrergic signalling in the regulation of zebrafish neuromuscular development and locomotor maturation. PMID:24489806

Jay, Michael; Bradley, Sophie; McDearmid, Jonathan Robert

2014-01-01

314

Nitric Oxide and Peroxynitrite in Health and Disease  

PubMed Central

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

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

2008-01-01

315

Novel roles of nitric oxide in hemorrhagic shock.  

PubMed

The aim of the current article is to overview the recent developments in the field of hemorrhagic shock research, as it relates to the roles of nitric oxide (NO) in the pathogenesis of this condition. The first part of the review focuses on the roles of peroxynitrite, a reactive oxidant produced from the reaction of NO and superoxide. The second part of the review deals with the novel findings related to the recently identified regulatory roles of the inducible isoform of nitric oxide synthase (iNOS) in the expression of pro-inflammatory mediators in hemorrhagic shock. (1) The role of peroxynitrite: Immunohistochemical and biochemical evidence demonstrate the production of peroxynitrite in hemorrhagic shock. Peroxynitrite can initiate a wide range of toxic oxidative reactions. These include initiation of tyrosine nitration, lipid peroxidation, direct inhibition of mitochondrial respiratory chain enzymes, inactivation of glyceraldehyde-3-phosphate dehydrogenase, inhibition of membrane sodium/potassium ATP-ase activity, inactivation of membrane sodium channels, and other oxidative modifications of proteins. All these toxicities are likely to play a role in the pathophysiology of hemorrhagic shock. A combined anti-inflammatory agent, mercaptoethylguanidine, which selectively inhibits iNOS and scavenges peroxynitrite, prevents the delayed vascular decompensation and the cellular energetic failure associated with late hemorrhagic shock. Peroxynitrite is a potent trigger of DNA single strand breakage, with subsequent activation of the nuclear enzyme poly (ADP ribose) synthetase (PARS), leading to eventual severe energy depletion of the cells, and necrotic-type cell death. Pharmacological inhibition of PARS, with 3-aminobenzamide or 5-iodo-6-amino-1,2-benzopyrone, improves hemodynamic status and prolongs survival time in rodent and porcine models of severe hemorrhagic shock. (2) Novel signaling roles of induced NO in hemorrhagic shock. Although the severity and duration of shock may dictate the timing and extent of iNOS expression, it is now evident that the up-regulation of iNOS can take place during sustained shock. Accumulated data indicate that iNOS expressed during shock contributes to vascular decompensation, as classically described by Wiggers. In addition, the presence of even low levels of iNOS at the time of resuscitation enhances the inflammatory response that follows the reperfusion state. Pharmacological inhibition of iNOS with N6-(iminoethyl)-L-lysine or genetic inactivation of iNOS (iNOS knockout mice) attenuates the activation of the transcription factors nuclear factor kappa B (NFkappaB) and Signal Transducer and Activator of Transcription 3 (STAT3), and ameliorates the increases in interleukin-6 and G-CSF messenger RNA levels in the lungs and liver. Inhibition of iNOS results in a marked reduction of lung and liver injury produced by hemorrhagic shock. Thus, induced nitric oxide, in addition to being a "final common mediator" of hemorrhagic shock, is essential for the up-regulation of the inflammatory response in resuscitated hemorrhagic shock. Furthermore, a picture of a pathway is evolving that contributes to tissue damage both directly via the formation of peroxynitrite, with its associated toxicities, and indirectly through the amplification of the inflammatory response. PMID:10468045

Szabó, C; Billiar, T R

1999-07-01

316

Nitric oxide (NO) production inhibitory constituents of Tabebuia avellanedae from Brazil.  

PubMed

From the water extract of Brazilian Tabebuia avellanedae, two new iridoids (1, 2) and a new phenylethanoid glycoside (3) have been isolated together with twelve known compounds (4-15). Their structures were determined based on the spectroscopic data. The isolated compounds inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-activated macrophage-like J774.1 cells. Compounds 1, 3, 10, 11, and 12 showed inhibitory activities more potent (IC50, 13.8-26.1 microg/ml) than a positive control N(G)-monomethyl-L-arginine (L-NMMA; IC50, 27.4 microg/ml). PMID:15930790

Awale, Suresh; Kawakami, Tsukasa; Tezuka, Yasuhiro; Ueda, Jun-Ya; Tanaka, Ken; Kadota, Shigetoshi

2005-06-01

317

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

NASA Technical Reports Server (NTRS)

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.

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

2001-01-01

318

Cytotoxic activity and effect on nitric oxide production of tirucallane-type triterpenes.  

PubMed

Hexane extract from the bark of Amphipterygium adstringens, as well as its principal constituents, masticadienonic acid and 3alpha-hydroxymasticadienolic acid, inhibited the growth of five human cancer cell lines. Derivatives of, namely 24,25 S-dihydromasticadienonic acid and masticadienolic acid, were also evaluated. The results showed that both and had greater activity than on colon cancer cell lines. The effects of on the production of nitric oxide (NO) from both resting and lipopolysaccharide-activated macrophages were determined. It was found that and caused an increase in NO release from resting macrophages; in lipopolysaccharide-activated macrophages, only and caused an increase in NO production. PMID:16105229

Chávez, Ibeth Oviedo; Apan, Teresa Ramírez; Martínez-Vázquez, Mariano

2005-09-01

319

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

NASA Technical Reports Server (NTRS)

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.

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

1982-01-01

320

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

PubMed Central

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

Gow, Andrew J.

2006-01-01

321

Myeloperoxidase-Dependent Oxidative Metabolism of Nitric Oxide in the Cystic Fibrosis Airway  

PubMed Central

Background Decreased expired nitric oxide (eNO) is commonly observed in cystic fibrosis (CF) patients and is usually explained by dysregulation of NO synthase (NOS) isoforms in respiratory tract epithelium. Later stages of this disease are accompanied by intense airway infiltration of phagocytes with high NOS activity, abundant levels of the hemoprotein myeloperoxidase (MPO) and significant production of significant reactive oxygen species. Methods This study characterizes the contribution of the high airway levels of MPO to decreased eNO levels in adult CF patients. NO metabolites (NOx) and MPO levels in fresh sputum of control and adult CF patients were determined and related to measurements of eNO and to in vitro consumption of NO in CF sputum. Results Despite essentially equal levels of NOx in sputum, eNO was 2- to 3-fold lower in CF patients compared to healthy controls. In CF patients, eNO levels were negatively associated with sputum peroxidase activity. In vivo correlations were confirmed by ex vivo studies of NO consumption by MPO in CF sputum. Immunodepletion studies confirmed MPO as the major heme peroxidase in CF sputum contributing to the hydrogen peroxide (H2O2)-dependent consumption of NO. Conclusions In CF airways MPO acts as a phagocyte-derived NO oxidase that diminishes NO bioavailability at airway surfaces, possibly identifying this peroxidase as a potential target for therapeutic intervention. PMID:20080069

Chapman, Anna L.P.; Morrissey, Brian M.; Vasu, Vihas T.; Juarez, Maya M.; Houghton, Jessica S.; Li, Chin-Shang; Cross, Carroll E.; Eiserich, Jason P.

2011-01-01

322

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

SciTech Connect

Electricity generation from coal has increased by an average of 51 billion kWh per year over the past 3 years. For this reason cost-effective strategies to control nitrogen oxides (NOx) from coal-fired power plant combustion gases must be developed. Compost biofilters operated at 55°C at an empty bed contact time (EBCT) of 13 seconds were shown to be feasible for removal of nitric oxide (NO) from synthetic flue gas. Denitrifying microbial populations in these biofilters were shown to reduce influent NO feeds by 90 to 95% at inlet NO concentrations of 500 ppmv. Oxygen was shown to have a significant effect on the NO removal efficiency demonstrated by these biofilters. Two biofilters were set up under identical conditions for the purpose of monitoring NO removal as well as changes in the microbial population in the bed medium under anaerobic and aerobic conditions. Changes in the microbial population were monitored to determine the maximum oxygen tolerance of a denitrifying biofilter as well as methods of optimizing microbial populations capable of denitrification in the presence of low oxygen concentrations. Nitric oxide removal dropped to between 10 and 20% when oxygen was present in the influent stream. The inactive compost used to pack the biofilters may have also caused the decreased NO removal efficiency compared to previous biofiltration experiments. Analysis of the bed medium microbial population using environmental scanning electron microscopy indicated significant increases in biomass populating the surface of the compost when compared to unacclimated compost.

Lee, Brady Douglas; Apel, William Arnold; Smith, William Aaron

2004-04-01

323

The role of nitro-reduction and nitric oxide in the toxicity of chloramphenicol.  

PubMed

Recent work on the toxicology of chloramphenicol suggests that its propensity to cause damage to the blood forming organs may be related to its potential for nitro-reduction and the subsequent production of nitric oxide. In this study both aerobic and anaerobic nitro-reduction of chloramphenicol by human foetal and neonatal liver results in the production of the amine derivative. However intermediates of the reaction nitroso- or glutathionesulphinamido-chloramphenicol could not be detected by hplc. Perfusion of chloramphenicol through isolated lobules of human placentae caused a decrease in blood pressure at a time which coincided with a peak of nitric oxide production. However, although the pressure drop could be reversed by an inhibitor of nitric oxide synthetase, the nitric oxide profile remained the same. These observations suggest that involvement of the para-nitro group of chloramphenicol could cause both hemotoxicity and hypotension in susceptible individuals. PMID:10100024

Holt, D E; Bajoria, R

1999-02-01

324

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

Federal Register 2010, 2011, 2012, 2013, 2014

...them at greater risk for death or problems with long-term lung health, brain development, and brain function. Nitric oxide...long-term lung health and brain development and function...bronchopulmonary dysplasia and/or death or...

2010-07-26

325

NOpiates: Novel Dual Action Neuronal Nitric Oxide Synthase Inhibitors with ?-Opioid Agonist Activity  

PubMed Central

A novel series of benzimidazole designed multiple ligands (DMLs) with activity at the neuronal nitric oxide synthase (nNOS) enzyme and the ?-opioid receptor was developed. Targeting of the structurally dissimilar heme-containing enzyme and the ?-opioid GPCR was predicated on the modulatory role of nitric oxide on ?-opioid receptor function. Structure–activity relationship studies yielded lead compound 24 with excellent nNOS inhibitory activity (IC50 = 0.44 ?M), selectivity over both endothelial nitric oxide synthase (10-fold) and inducible nitric oxide synthase (125-fold), and potent ?-opioid binding affinity, Ki = 5.4 nM. The functional activity as measured in the cyclic adenosine monosphospate secondary messenger assay resulted in full agonist activity (EC50 = 0.34 ?M). This work represents a novel approach in the development of new analgesics for the treatment of pain. PMID:24900459

2012-01-01

326

NOpiates: Novel Dual Action Neuronal Nitric Oxide Synthase Inhibitors with ?-Opioid Agonist Activity.  

PubMed

A novel series of benzimidazole designed multiple ligands (DMLs) with activity at the neuronal nitric oxide synthase (nNOS) enzyme and the ?-opioid receptor was developed. Targeting of the structurally dissimilar heme-containing enzyme and the ?-opioid GPCR was predicated on the modulatory role of nitric oxide on ?-opioid receptor function. Structure-activity relationship studies yielded lead compound 24 with excellent nNOS inhibitory activity (IC50 = 0.44 ?M), selectivity over both endothelial nitric oxide synthase (10-fold) and inducible nitric oxide synthase (125-fold), and potent ?-opioid binding affinity, K i = 5.4 nM. The functional activity as measured in the cyclic adenosine monosphospate secondary messenger assay resulted in full agonist activity (EC50 = 0.34 ?M). This work represents a novel approach in the development of new analgesics for the treatment of pain. PMID:24900459

Renton, Paul; Green, Brenda; Maddaford, Shawn; Rakhit, Suman; Andrews, John S

2012-03-01

327

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...

328

Biochemistry of mobile zinc and nitric oxide revealed by fluorescent sensors  

E-print Network

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 ...

Pluth, Michael D.

329

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

E-print Network

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 ...

Pluth, Michael D.

330

Measurement of Nitric Oxide Production from Lymphatic Entothelial Cells Under Mechanical Stimuli  

E-print Network

LEC Lymphatic endothelial cell MCF Material characterization facility MV2 Endothelial growth medium MV2 NaOH Sodium hydroxide NO Nitric oxide NO2- Nitrite NO3- Nitrate v PBS Phosphate buffer saline PDMS Polydimethylsiloxane...

Jafarnejad, Mohammad 1987-

2012-11-16

331

Nitric oxide directly activates calcium-dependent potassium channels in vascular smooth muscle.  

PubMed

Nitric oxide is the major endothelium-derived relaxing factor (EDRF), and it is thought to relax smooth muscle cells by stimulation of guanylate cyclase, accumulation of its product cyclic GMP, and cGMP-dependent modification of several intracellular processes, including activation of potassium channels through cGMP-dependent protein kinase. Here we present evidence that both exogenous nitric oxide and native EDRF can directly activate single Ca(2+)-dependent K+ channels (K+Ca) in cell-free membrane patches without requiring cGMP. Under conditions when guanylate cyclase was inhibited by methylene blue, considerable relaxation of rabbit aorta to nitric oxide persisted which was blocked by charybdotoxin, a specific inhibitor of K+Ca channels. These studies demonstrate a novel direct action of nitric oxide on K+Ca channels. PMID:7512692

Bolotina, V M; Najibi, S; Palacino, J J; Pagano, P J; Cohen, R A

1994-04-28

332

Cell-Trappable Fluorescent Probes for Nitric Oxide Visualization in Living Cells  

E-print Network

Two new cell-trappable fluorescent probes for nitric oxide (NO) are reported based on either incorporation of hydrolyzable esters or conjugation to aminodextran polymers. Both probes are highly selective for NO over other ...

Pluth, Michael D.

333

Nitric oxide inhibits lipopolysaccharide-induced apoptosis in pulmonary artery endothelial cells  

E-print Network

YOUNG-MYEONG KIM,2,3 TIMOTHY R. BILLIAR,2 SIMON A. WATKINS,6 AND BRUCE R. PITT1,3 3Department. Billiar, Simon A. Watkins, and Bruce R. Pitt. Nitric oxide inhibits lipopolysaccharide- induced apoptosis

Engelhardt, John F.

334

Turn-on fluorescent probes for detecting nitric oxide in biology  

E-print Network

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 ...

McQuade, Lindsey Elizabeth, 1981-

2010-01-01

335

Adrenoreceptors and nitric oxide in the cardiovascular system  

PubMed Central

Nitric Oxide (NO) is a small molecule that continues to attract much attention from the scientific community. Since its discovery, it has been evident that NO has a crucial role in the modulation of vascular tone. Moreover, NO is involved in multiple signal transduction pathways thus contributing to the regulation of many cellular functions. NO effects can be either dependent or independent on cGMP, and rely also upon several mechanisms such as the amount of NO, the compartmentalization of the enzymes responsible for its biosynthesis (NOS), and the local redox conditions. Several evidences highlighted the correlation among adrenoreceptors activity, vascular redox status and NO bioavailability. It was suggested a possible crosstalk between NO and oxidative stress hallmarks in the endothelium function and adaptation, and in sympathetic vasoconstriction control. Adrenergic vasoconstriction is a balance between a direct vasoconstrictive effect on smooth muscle and an indirect vasorelaxant action caused by ?2- and ?-adrenergic endothelial receptor-triggered NO release. An increased oxidative stress and a reduction of NO bioavailability shifts this equilibrium causing the enhanced vascular adrenergic responsiveness observed in hypertension. The activity of NOS contributes to manage the adrenergic pathway, thus supporting the idea that the endothelium might control or facilitate ?-adrenergic effects on the vessels and the polymorphic variants in ?2-receptors and NOS isoforms could influence aging, some pathological conditions and individual responses to drugs. This seems to be dependent, almost in part, on differences in the control of vascular tone exerted by NO. Given its involvement in such important mechanisms, the NO pathway is implicated in aging process and in both cardiovascular and non-cardiovascular conditions. Thus, it is essential to pinpoint NO involvement in the regulation of vascular tone for the effective clinical/therapeutic management of cardiovascular diseases (CVD). PMID:24223559

Conti, Valeria; Russomanno, Giusy; Corbi, Graziamaria; Izzo, Viviana; Vecchione, Carmine; Filippelli, Amelia

2013-01-01

336

Kinetic Explanation for Accumulation of Nitrite, Nitric Oxide, and Nitrous Oxide During Bacterial Denitrification †  

PubMed Central

The kinetics of denitrification and the causes of nitrite and nitrous oxide accumulation were examined in resting cell suspensions of three denitrifiers. An Alcaligenes species and a Pseudomonas fluorescens isolate characteristically accumulated nitrite when reducing nitrate; a Flavobacterium isolate did not. Nitrate did not inhibit nitrite reduction in cultures grown with tungstate to prevent formation of an active nitrate reductase; rather, accumulation of nitrite seemed to depend on the relative rates of nitrate and nitrite reduction. Each isolate rapidly reduced nitrous oxide even when nitrate or nitrite had been included in the incubation mixture. Nitrate also did not inhibit nitrous oxide reduction in Alcaligenes odorans, an organism incapable of nitrate reduction. Thus, added nitrate or nitrite does not always cause nitrous oxide accumulation, as has often been reported for denitrifying soils. All strains produced small amounts of nitric oxide during denitrification in a pattern suggesting that nitric oxide was also under kinetic control similar to that of nitrite and nitrous oxide. Apparent Km values for nitrate and nitrite reduction were 15 ?M or less for each isolate. The Km value for nitrous oxide reduction by Flavobacterium sp. was 0.5 ?M. Numerical solutions to a mathematical model of denitrification based on Michaelis-Menten kinetics showed that differences in reduction rates of the nitrogenous compounds were sufficient to account for the observed patterns of nitrite, nitric oxide, and nitrous oxide accumulation. Addition of oxygen inhibited gas production from 13NO3? by Alcaligenes sp. and P. fluorescens, but it did not reduce gas production by Flavobacterium sp. However, all three isolates produced higher ratios of nitrous oxide to dinitrogen as the oxygen tension increased. Inclusion of oxygen in the model as a nonspecific inhibitor of each step in denitrification resulted in decreased gas production but increased ratios of nitrous oxide to dinitrogen, as observed experimentally. The simplicity of this kinetic model of denitrification and its ability to unify disparate observations should make the model a useful guide in research on the physiology of denitrifier response to environmental effectors. PMID:16345900

Betlach, Michael R.; Tiedje, James M.

1981-01-01

337

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

PubMed

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

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

2014-11-01

338

Mitochondrial Nitric Oxide Localization in H9c2 Cells Revealed by Confocal Microscopy  

Microsoft Academic Search

This study shows the presence of all three nitric oxide synthases (NOSs) and NOS activity in H9c2 cells cultured under non-stimulated conditions. By using the 4,5 diaminofluoresceindiacetate (DAF-2DA) fluorimetric nitric oxide (NO•) detection system we observed NO• production in H9c2 cells. As revealed by confocal microscopy, NO• fluorescence colocalizes in mitochondria labeled with Mito-Tracker Red CM-H2Xros. Upon stimulation with acetylcholine

B. Zanella; N. Calonghi; E. Pagnotta; L. Masotti; C. Guarnieri

2002-01-01

339

Modulation of Nitric Oxide Production by Tetracyclines and Chemically Modified Tetracyclines  

Microsoft Academic Search

Chemically modified tetracyclines (CMTs) dose-dependently decreased inducible nitric oxide synthase (iNOS) and, consequently, nitric oxide (NO) formation by the lipopolysaccharide (LPS)-stimulated J774 line. The inhibitory effect was due to a specific reduction in the iNOS protein content in the cells, as attested by Western blot analysis and by the inhibition of iNOS mRNA accumulation. Furthermore, CMTs cause a dose-dependent increase

E. Cillari; S. Milano; P. DAgostino; G. Di Bella; M. La Rosa; C. Barbera; V. Ferlazzo; G. Cammarata; S. Grimaudo; M. Tolomeo; S. Feo

1998-01-01

340

Mitochondrial nitric oxide synthase, mitochondrial brain dysfunction in aging, and mitochondria-targeted antioxidants  

Microsoft Academic Search

This paper reviews the current ideas on nitric oxide (NO) physiology in brain and other mammalian organs and on the subcellular distribution of nitric oxide synthases (NOS) emphasizing on the evidence of a mitochondrial NOS isoform (mtNOS) that exhibits a mean activity of 0.86±0.09 nmol NO\\/min×mg protein in 13 mouse and rat organs. Mammalian brain aging is associated with mitochondrial dysfunction,

Ana Navarro; Alberto Boveris

2008-01-01

341

Role of nitric oxide in renal hemodynamic abnormalities of cyclosporin nephrotoxicity  

Microsoft Academic Search

Role of nitric oxide in renal hemodynamic abnormalities of cyclosporin nephrotoxicity. To evaluate the participation of nitric oxide (NO) in chronic cyclosporin A (CsA) nephrotoxicity, the glomerular hemodynamic response to NO inhibition with N-nitro-L-arginine-methyl-ester (NAME) and stimulation of NO production with L-arginine was studied in unine-phrectomized rats. Chronic CsA administration produced renal vasoconstriction, characterized by increased afferent (AR) and efferent

Norma A Bobadilla; Edilia Tapia; Martha Franco; Pedro López; Sandra Mendoza; Romeo García-Torres; Juan A Alvarado; Jaime Herrera-Acosta

1994-01-01

342

Evidence for the role of nitric oxide in caffeine-induced locomotor activity in mice  

Microsoft Academic Search

Rationale Nitric oxide (NO) is implicated in the acute locomotor activating effects of some addictive drugs such as amphetamine and cocaine, but has not been investigated in the case of caffeine. Objectives We investigated the effects of a nitric oxide synthase (NOS) inhibitor N?-Nitro-l-arginine methyl ester (l-NAME) and a combination of l-arginine, a NO precursor, and l-NAME on caffeine induced

Hakan Kayir; I. Tayfun Uzbay

2004-01-01

343

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

Microsoft Academic Search

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

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

2002-01-01

344

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

NSDL National Science Digital Library

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.

Cristiana Perrotta (Università di Milano)

2010-04-01

345

Nitric oxide and its implications in skin homeostasis and disease – a review  

Microsoft Academic Search

\\u000a Abstract The recent identification of the nitric oxide synthase (NOS) pathway in various cell types in the skin has provided important\\u000a insight into the molecular mechanisms underlying regulatory and homeostatic functions of the skin. Many studies also point\\u000a to perturbations or defects in the signaling cascade of nitric oxide (NO) and reactive nitrogen intermediates as key players\\u000a in skin disease

Daniela Bruch-Gerharz; Thomas Ruzicka; Victoria Kolb-Bachofen

1998-01-01

346

Significance of nitric oxide concentration in plasma and uterine secretes with puerperal endometritis in dairy cows  

Microsoft Academic Search

Endometritis is an inflammation of the endometrial lining of the uterus without systemic signs, which is associated with chronic\\u000a postpartum infection of the uterus with pathogenic bacteria. Nitric oxide (NO) is an inflammatory mediator that among other\\u000a effects causes smooth muscle relaxation and mediated cytoimmunity and inflammation toxicity. To see if the nitric oxide concentration\\u000a in plasma and uterine secrets

DeJun Li; YunFeng Liu; YanFei Li; Ying Lv; XiaoYing Pei; DingZong Guo

2010-01-01

347

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

PubMed Central

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

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

2013-01-01

348

Neuronal Nitric Oxide Synthase Gene Transfer Promotes Cardiac Vagal Gain of Function  

Microsoft Academic Search

Nitric oxide (NO) generated from neuronal nitric oxide synthase (NOS-1) in intrinsic cardiac ganglia has been implicated in parasympathetic-induced bradycardia. We provide direct evidence that NOS-1 acts in a site-specific manner to promote cardiac vagal neurotransmission and bradycardia. NOS-1 gene transfer to the guinea pig right atrium increased protein expression and NOS-1 immu- nolocalization in cholinergic ganglia. It also increased

R. M. Mohan; D. A. Heaton; E. J. F. Danson; S. P. R. Krishnan; S. Cai; K. M. Channon; D. J. Paterson

2002-01-01

349

Changes in the dose of inhaled steroid affect exhaled nitric oxide levels in asthmatic patients  

Microsoft Academic Search

Changes in the dose of inhaled steroid affect exhaled nitric oxide levels in asthmatic patients. S.A. Kharitonov, D.H. Yates, K.F. Chung, P.J. Barnes. ?ERS Journals Ltd 1996. ABSTRACT: An increased concentration of nitric oxide (NO) in the exhaled air of asthmatic patients may reflect inflammation of the airways, and exhaled NO may, therefore, be useful in monitoring asthma control and

S. A. Kharitonov; D. H. Yates; K. F. Chung; P. J. Barnes

1996-01-01

350

Endostatin inhibits nitric oxide and diminishes VEGF and collagen XVIII in squamous carcinoma cells.  

PubMed

Low pO(2) values are a common finding among oral squamous cell carcinomas (SCC). Our objective was to determine the role that oxygen tension plays on the direct tumor effect of endostatin (ES). Squamous carcinoma cell lines were grown under normoxic or hypoxic conditions and treated with endostatin (ES), nitric oxide (NO) donors, NO scavengers, NO synthase inhibitors, or transduced with AdenoVec-hEndo or AdenoVec Null vectors. The expression of vascular endothelial growth factor (VEGF) and collagen XVIII were determined by RT-PCR and protein levels assessed by Western blot analyses. Our studies demonstrated that collagen XVIII and VEGF are expressed and responsive to ES in a limited number of SCC cell lines during normoxia but were most responsive when grown under hypoxic conditions. VEGF and collagen XVIII were downregulated by both ES and transduction of cells with AdenoVec-hEndo. The effects of ES on SCC cells were enhanced by aminoguanidine (Ag), L-NAME, and diphenyleneiodonium chloride (DPI). Endostatin and transduced with ES vectors diminished the levels of NO whereas NO donors enhanced VEGF expression and collagen XVIII expression. In conclusion, the direct effect of endostatins on tumor cells is most effective under conditions of low oxygen tension and can be potentiated by the use of nitric oxide synthase inhibitors or NO scavengers. PMID:15540202

Hebert, Carla; Siavash, Hessam; Norris, Kathleen; Nikitakis, Nikolaos G; Sauk, John J

2005-03-20

351

Interactive effects of mechanical ventilation, inhaled nitric oxide and oxidative stress in acute lung injury.  

PubMed

To compare conventional mechanical ventilation (CMV) and high-frequency oscillatory ventilation (HFOV), with/without inhaled nitric oxide (iNO), for oxygenation, inflammation, antioxidant/oxidative stress status, and DNA damage in a model of acute lung injury (ALI). Lung injury was induced by tracheal infusion of warm saline. Rabbits were ventilated at [Formula: see text] 1.0 and randomly assigned to one of five groups. Overall antioxidant defense/oxidative stress was assessed by total antioxidant performance assay, and DNA damage by comet assay. Ventilatory and hemodynamic parameters were recorded every 30min for 4h. ALI groups showed worse oxygenation than controls after lung injury. After 4h of mechanical ventilation, HFOV groups presented significant improvements in oxygenation. HFOV with and without iNO, and CMV with iNO showed significantly increased antioxidant defense and reduced DNA damage than CMV without iNO. Inhaled nitric oxide did not beneficially affect HFOV in relation to antioxidant defense/oxidative stress and pulmonary DNA damage. Overall, lung injury was reduced using HFOV or CMV with iNO. PMID:24148688

Ronchi, Carlos Fernando; Ferreira, Ana Lucia Anjos; Campos, Fabio Joly; Kurokawa, Cilmery Suemi; Carpi, Mario Ferreira; Moraes, Marcos Aurélio; Bonatto, Rossano Cesar; Yeum, Kyung-Jin; Fioretto, Jose Roberto

2014-01-01

352

Endothelial nitric-oxide synthase activation generates an inducible nitric-oxide synthase-like output of nitric oxide in inflamed endothelium.  

PubMed

High levels of NO generated in the vasculature under inflammatory conditions are usually attributed to inducible nitric-oxide synthase (iNOS), but the role of the constitutively expressed endothelial NOS (eNOS) is unclear. In normal human lung microvascular endothelial cells (HLMVEC), bradykinin (BK) activates kinin B2 receptor (B2R) signaling that results in Ca(2+)-dependent activation of eNOS and transient NO. In inflamed HLMVEC (pretreated with interleukin-1? and interferon-?), we found enhanced binding of eNOS to calcium-calmodulin at basal Ca(2+) levels, thereby increasing its basal activity that was dependent on extracellular l-Arg. Furthermore, B2R stimulation generated prolonged high output eNOS-derived NO that is independent of increased intracellular Ca(2+) and is mediated by a novel G?(i)-, MEK1/2-, and JNK1/2-dependent pathway. This high output NO stimulated with BK was blocked with a B2R antagonist, eNOS siRNA, or eNOS inhibitor but not iNOS inhibitor. Moreover, B2R-mediated NO production and JNK phosphorylation were inhibited with MEK1/2 and JNK inhibitors or MEK1/2 and JNK1/2 siRNA but not with ERK1/2 inhibitor. BK induced Ca(2+)-dependent eNOS phosphorylation at Ser(1177), Thr(495), and Ser(114) in cytokine-treated HLMVEC, but these modifications were not dependent on JNK1/2 activation and were not responsible for prolonged NO output. Cytokine treatment did not alter the expression of B2R, G?(q/11), G?(i1,2), JNK, or eNOS. B2R activation in control endothelial cells enhanced migration, but in cytokine-treated HLMVEC it reduced migration. Both responses were NO-dependent. Understanding how JNK regulates prolonged eNOS-derived NO may provide new therapeutic targets for the treatment of disorders involving vascular inflammation. PMID:23255592

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

2013-02-01

353

Phlebotomus papatasi Saliva Inhibits Protein Phosphatase Activity and Nitric Oxide Production by Murine Macrophages  

PubMed Central

Leishmania parasites, transmitted by phlebotomine sand flies, are obligate intracellular parasites of macrophages. The sand fly Phlebotomus papatasi is the vector of Leishmania major, a causative agent of cutaneous leishmaniasis in the Old World, and its saliva exacerbates parasite proliferation and lesion growth in experimental cutaneous leishmaniasis. Here we show that P. papatasi saliva contains a potent inhibitor of protein phosphatase 1 and protein phosphatase 2A of murine macrophages. We further demonstrate that P. papatasi saliva down regulates expression of the inducible nitric oxide synthase gene and reduces nitric oxide production in murine macrophages. Partial biochemical characterization of the protein phosphatase and nitric oxide inhibitor indicated that it is a small, ethanol-soluble molecule resistant to boiling, proteolysis, and DNase and RNase treatments. We suggest that the P. papatasi salivary protein phosphatase inhibitor interferes with the ability of activated macrophages to transmit signals to the nucleus, thereby preventing up regulation of the induced nitric oxide synthase gene and inhibiting the production of nitric oxide. Since nitric oxide is toxic to intracellular parasites, the salivary protein phosphatase inhibitor may be the mechanism by which P. papatasi saliva exacerbates cutaneous leishmaniasis. PMID:9529078

Waitumbi, John; Warburg, Alon

1998-01-01

354

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

PubMed Central

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

2010-01-01

355

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

PubMed Central

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

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

2012-01-01

356

Overall Rate Constant Measurements of the Reaction of Chloroalkylperoxy Radicals with Nitric Oxide  

E-print Network

Overall Rate Constant Measurements of the Reaction of Chloroalkylperoxy Radicals with Nitric Oxide of the NO reaction with chloroalkylperoxy radicals derived from the Cl-initiated oxidation of several atmospherically the OH-initiated oxidation of alkenes) with NO yielded identical rate constants for all of the alkenes

Elrod, Matthew J.

357

Biochemical Reaction Products of Nitric Oxide as Quantitative Markers of Primary Pulmonary Hypertension  

Microsoft Academic Search

Primary pulmonary hypertension (PPH) is a rare and fatal disease of unknown etiology. Inflammatory oxidant mechanisms and deficiency in nitric oxide (NO) have been implicated in the pathogenesis of pulmonary hypertension. In order to investigate abnormalities in oxidants and antioxidants in PPH, we studied intrapulmonary NO levels, biochemical reaction products of NO, and antioxidants (glu- tathione (GSH), glutathione peroxidase (GPx),

F. TAKAO KANEKO; ALEJANDRO C. ARROLIGA; RAED A. DWEIK; SUZY A. COMHAIR; DANIEL LASKOWSKI; RITA OPPEDISANO; MARY JANE THOMASSEN; SERPIL C. ERZURUM

1998-01-01

358

Neurovascular protection by ischaemic tolerance: role of nitric oxide  

PubMed Central

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

Iadecola, Costantino; Kahles, Timo; Gallo, Eduardo F; Anrather, Josef

2011-01-01

359

Effects of transition metals on nitric oxide synthase catalysis  

PubMed Central

The biosynthesis of nitric oxide (NO) by the enzyme NO synthase (NOS) proceeds by the hydroxylation of l-arginine to form NG-hydroxy-l-arginine followed by the conversion of NG-hydroxy-l-arginine to l-citrulline and NO. The previously identified requirements of this relatively complicated reaction include several protein-bound cofactors: cytochrome P450-type heme, flavin mononucleotide (FMN), flavin adenine dinucleotide (FAD), and tetrahydrobiopterin (H4B). In addition to l-arginine, NOS also requires the substrates NADPH and molecular oxygen. The role of H4B in NOS catalysis has long been a subject of debate and uncertainty fueled, in part, by the failure to detect any dependence of the NOS reaction on nonheme iron, a cofactor integral to catalysis in every other H4B-dependent enzyme. Here we report the ability of NOS to bind transition metals stoichiometrically, and demonstrate that the rate of catalysis is enhanced by nonheme iron. We also show that other divalent transition metals, including Cu, Zn, Co, and Ni, inhibit NOS catalysis. Also, the addition of Cu2+ to NOS inhibits heme reduction, whereas the addition of Fe2+ does not. Overall, the results appear to connect NOS to the known H4B/nonheme iron-dependent hydroxylases, and suggest a similar, if not identical, step in the NOS reaction mechanism. PMID:9736696

Perry, Jason M.; Marletta, Michael A.

1998-01-01

360

Inaccuracies of nitric oxide measurement methods in biological media  

PubMed Central

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

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

2013-01-01

361

Regulation of nitric oxide consumption by hypoxic red blood cells.  

PubMed

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

Han, Tae H; Qamirani, Erion; Nelson, Allyson G; Hyduke, Daniel R; Chaudhuri, Gautam; Kuo, Lih; Liao, James C

2003-10-14

362

Nitric Oxide-Releasing S-Nitrosothiol-Modified Xerogels  

PubMed Central

The synthesis, material characterization, and in vitro biocompatibility of S-nitrosothiol (RSNO)-modified xerogels is described. Thiol-functionalized xerogel films were formed by hydrolysis and co-condensation of 3-mercaptopropyltrimethoxysilane (MPTMS) and methyltrimethoxysilane (MTMOS) sol-gel precursors at varying concentrations. Subsequent thiol nitrosation via acidified nitrite produced RSNO-modified xerogels capable of generating nitric oxide (NO) for up to 2 weeks under physiological conditions. Xerogels also exhibited NO generation upon irradiation with broad-spectrum light or exposure to copper, with NO fluxes proportional to wattage and concentration, respectively. Xerogels were capable of storing up to ?1.31 µmol NO mg?1, and displayed negligible fragmentation over a 2 week period. Platelet and bacterial adhesion to nitrosated films was reduced compared to non-nitrosated controls, confirming the antithrombotic and antibacterial properties of the NO-releasing materials. Fibroblast cell viability was maintained on the xerogel surfaces illustrating the promise of RSNO-modified xerogels as biomedical device coatings. PMID:19501904

Riccio, Daniel A.; Dobmeier, Kevin P.; Hetrick, Evan M.; Privett, Benjamin J.; Paul, Heather S.; Schoenfisch, Mark H.

2009-01-01

363

GAPDH regulates cellular heme insertion into inducible nitric oxide synthase  

PubMed Central

Heme proteins play essential roles in biology, but little is known about heme transport inside mammalian cells or how heme is inserted into soluble proteins. We recently found that nitric oxide (NO) blocks cells from inserting heme into several proteins, including cytochrome P450s, hemoglobin, NO synthases, and catalase. This finding led us to explore the basis for NO inhibition and to identify cytosolic proteins that may be involved, using inducible NO synthase (iNOS) as a model target. Surprisingly, we found that GAPDH plays a key role. GAPDH was associated with iNOS in cells. Pure GAPDH bound tightly to heme or to iNOS in an NO-sensitive manner. GAPDH knockdown inhibited heme insertion into iNOS and a GAPDH mutant with defective heme binding acted as a dominant negative inhibitor of iNOS heme insertion. Exposing cells to NO either from a chemical donor or by iNOS induction caused GAPDH to become S-nitrosylated at Cys152. Expressing a GAPDH C152S mutant in cells or providing a drug to selectively block GAPDH S-nitrosylation both made heme insertion into iNOS resistant to the NO inhibition. We propose that GAPDH delivers heme to iNOS through a process that is regulated by its S-nitrosylation. Our findings may uncover a fundamental step in intracellular heme trafficking, and reveal a mechanism whereby NO can govern the process. PMID:20921417

Chakravarti, Ritu; Aulak, Kulwant S.; Fox, Paul L.; Stuehr, Dennis J.

2010-01-01

364

Inaccuracies of nitric oxide measurement methods in biological media.  

PubMed

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

Hunter, Rebecca A; Storm, Wesley L; Coneski, Peter N; Schoenfisch, Mark H

2013-02-01

365

Nitric oxide release from polydimethylsiloxane-based polyurethanes.  

PubMed

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

Nguyen, Evelyne B; Zilla, Peter; Bezuidenhout, Deon

2014-01-01

366

Nitric oxide removal by wastewater bacteria in a biotrickling filter.  

PubMed

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

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

2014-03-01

367

Nasal nitric oxide levels in healthy pre-school children.  

PubMed

The evaluation of nasal nitric oxide (nNO) has been proposed as a screening tool in children with clinically suspectable primary ciliary dyskinesia. Nevertheless, normal values have been reported for school-aged children. This study was designed to identify normal nNO levels in pre-school children. nNO was assessed in 300 healthy children aged between 1.5 and 7.2. Two hundred and fifty of them were unable to fulfill the guideline requirements for nNO measurement and were assessed by sampling the nasal air continuously with a constant trans-nasal aspiration flow for 30 s during tidal breathing. For those children who were able to cooperate, the average nNO concentration was calculated according to guidelines. A statistically significant relationship between nNO level and age was demonstrated in this study group of pre-school children (p < 0.001). An increase in nNO of about 100 ppb was observed in children older than 6 yr vs. those aged < 3. This study presents a description of normal nNO values in pre-school children. The effect of the age and the eventual presence of rhinitis and snoring need to be considered whenever nNO is evaluated in the clinical practice, in particular in non-cooperative children. PMID:21073540

Piacentini, G L; Bodini, A; Peroni, D G; Sandri, M; Brunelli, M; Pigozzi, R; Boner, A L

2010-12-01

368

Heparin modulation on hepatic nitric oxide synthase in experimental steatohepatitis  

PubMed Central

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

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

2014-01-01

369

Concomitant production of nitric oxide and superoxide in human macrophages.  

PubMed

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

Juliet, Packiasamy A R; Hayashi, Toshio; Iguchi, Akihisa; Ignarro, Louis J

2003-10-17

370

Mathematical modeling of nitric oxide destruction by reburning  

SciTech Connect

A nitric oxide model incorporated into a comprehensive coal combustion model is presented for predicting NO reduction in a 93 kW laboratory-scale single-burner furnace with gaseous fuel reburning. This NO model, including the reburning NO submodel based on 'partial equilibrium' approach, requires the solution of only two transport equations to model the behavior of NO reduction in the reburning process. A number of experiments have been performed in the same furnace, and the experimental data obtained from the optimized reburn configuration was used to validate the model. Effects of the critical kinetic parameters on predicted NO concentrations were investigated in this study, and the reburning NO submodel was further evaluated by including more reactions of NO reduction and by comparing with the global reburning model. Profile comparisons show that the predicted temperature and oxygen concentration are overall in good agreement with the measurements, and the general trend of predicted NO concentration is very similar to that measured. The results of this study show that the present reburning NO submodel is capable to predict quantitatively the NO reduction levels and depicts quite well the observed behavior of NO annihilation in the reburning process. It is expected that this computationally economic model represents a useful technique to simulate the gaseous fuel reburning process in practical combustors. The model presented in this study also provides a basis for further studies. 35 refs., 11 figs., 4 tabs.

Sheng Su; Jun Xiang; Xuexin Sun; Zhongxiao Zhang; Chuguang Zheng; Minghou Xu [Huazhong University of Science and Technology, Wuhan (China). State Key Laboratory of Coal Combustion

2006-08-15

371

New nitric oxide or hydrogen sulfide releasing aspirins.  

PubMed

A new series of (((R-oxy)carbonyl)oxy)methyl esters of aspirin (ASA), bearing nitric oxide (NO) or hydrogen sulfide (H(2)S) releasing groups, was synthesized, and the compounds were evaluated as new ASA co-drugs. All the products were quite stable in buffered solution at pH 1 and 7.4. Conversely, they were all rapidly metabolized, producing ASA and the NO/H(2)S releasing moiety used for their preparation. Consequent on ASA release, the compounds were capable of inhibiting collagen-induced platelet aggregation of human platelet-rich plasma (PRP). The simple NO/H(2)S donor substructures were able to relax contracted rat aorta strips, with a NO- and H(2)S-dependent mechanism, respectively, but they either did not trigger antiaggregatory activity or displayed antiplatelet potency markedly below that of the related co-drug. The new products might provide a safer and improved alternative to the use of ASA principally in its anti-inflammatory and antithrombotic applications. PMID:21688846

Lazzarato, Loretta; Chegaev, Konstantin; Marini, Elisabetta; Rolando, Barbara; Borretto, Emily; Guglielmo, Stefano; Joseph, Sony; Di Stilo, Antonella; Fruttero, Roberta; Gasco, Alberto

2011-08-11

372

Direct actions of nitric oxide on rat neurohypophysial K+ channels  

PubMed Central

Nitric oxide (NO) has been shown to modulate neuropeptide secretion from the posterior pituitary. Here we show that NO activates large-conductance Ca2+-activated K+ (BK) channels in posterior pituitary nerve terminals. NO, generated either by the photolysis of caged-NO or with chemical donors, irreversibly enhanced the component of whole-terminal K+ current due to BK channels and increased the activity of BK channels in excised patches. NO also inhibited the transient A-current. The time courses of these effects on K+ current were very different; activation of BK channels developed slowly over several minutes whereas inhibition of A-current immediately followed NO uncaging. Activation of BK channels by NO occurred in the presence of guanylyl cyclase inhibitors and after removal of ATP or GTP from the pipette solution, suggesting a cGMP-independent signalling pathway. The sulfhydryl alkylating agent N-ethyl maleimide (NEM) increased BK channel activity. Pretreatment with NEM occluded NO activation. NO activation of BK channels occurred independently of voltage and cytoplasmic Ca2+ concentration. In addition, NO removed the strict Ca2+ requirement for channel activation, rendering channels highly active even at nanomolar Ca2+ levels. These results suggest that NO, or a reactive nitrogen byproduct, chemically modifies nerve terminal BK channels or a closely associated protein and thereby produces an increase in channel activity. Such activation is likely to inhibit impulse activity in posterior pituitary nerve terminals and this may explain the inhibitory action of NO on secretion. PMID:10517809

Ahern, Gerard P; Hsu, Shyue-Fang; Jackson, Meyer B

1999-01-01

373

Regulation of Inducible Nitric Oxide Synthase Gene in Glial Cells  

PubMed Central

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

Saha, Ramendra N.; Pahan, Kalipada

2007-01-01

374

Molecular dynamics simulation of nitric oxide in myoglobin  

USGS Publications Warehouse

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.

Lee, Myung Won; Meuwly, Markus

2012-01-01

375

Nitric Oxide-Dependent Posttranslational Modification in Plants: An Update  

PubMed Central

Nitric oxide (NO) has been demonstrated as an essential regulator of several physiological processes in plants. The understanding of the molecular mechanism underlying its critical role constitutes a major field of research. NO can exert its biological function through different ways, such as the modulation of gene expression, the mobilization of second messengers, or interplays with protein kinases. Besides this signaling events, NO can be responsible of the posttranslational modifications (PTM) of target proteins. Several modifications have been identified so far, whereas metal nitrosylation, the tyrosine nitration and the S-nitrosylation can be considered as the main ones. Recent data demonstrate that these PTM are involved in the control of a wide range of physiological processes in plants, such as the plant immune system. However, a great deal of effort is still necessary to pinpoint the role of each PTM in plant physiology. Taken together, these new advances in proteomic research provide a better comprehension of the role of NO in plant signaling. PMID:23203119

Astier, Jeremy; Lindermayr, Christian

2012-01-01

376

Electrospun nitric oxide releasing bandage with enhanced wound healing.  

PubMed

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 14day NO release study, the dressings released 79?molNOg(-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

Lowe, A; Bills, J; Verma, R; Lavery, L; Davis, K; Balkus, K J

2015-02-01

377

Concepts of neural nitric oxide-mediated transmission  

PubMed Central

As a chemical transmitter in the mammalian central nervous system, nitric oxide (NO) is still thought a bit of an oddity, yet this role extends back to the beginnings of the evolution of the nervous system, predating many of the more familiar neurotransmitters. During the 20 years since it became known, evidence has accumulated for NO subserving an increasing number of functions in the mammalian central nervous system, as anticipated from the wide distribution of its synthetic and signal transduction machinery within it. This review attempts to probe beneath those functions and consider the cellular and molecular mechanisms through which NO evokes short- and long-term modifications in neural performance. With any transmitter, understanding its receptors is vital for decoding the language of communication. The receptor proteins specialised to detect NO are coupled to cGMP formation and provide an astonishing degree of amplification of even brief, low amplitude NO signals. Emphasis is given to the diverse ways in which NO receptor activation initiates changes in neuronal excitability and synaptic strength by acting at pre- and/or postsynaptic locations. Signalling to non-neuronal cells and an unexpected line of communication between endothelial cells and brain cells are also covered. Viewed from a mechanistic perspective, NO conforms to many of the rules governing more conventional neurotransmission, particularly of the metabotropic type, but stands out as being more economical and versatile, attributes that presumably account for its spectacular evolutionary success. PMID:18588525

Garthwaite, John

2008-01-01

378

Differential Modulation of Nitric Oxide Synthases in Aging: Therapeutic Opportunities  

PubMed Central

Vascular aging is the term that describes the structural and functional disturbances of the vasculature with advancing aging. The molecular mechanisms of aging-associated endothelial dysfunction are complex, but reduced nitric oxide (NO) bioavailability and altered vascular expression and activity of NO synthase (NOS) enzymes have been implicated as major players. Impaired vascular relaxation in aging has been attributed to reduced endothelial NOS (eNOS)-derived NO, while increased inducible NOS (iNOS) expression seems to account for nitrosative stress and disrupted vascular homeostasis. Although eNOS is considered the main source of NO in the vascular endothelium, neuronal NOS (nNOS) also contributes to endothelial cells-derived NO, a mechanism that is reduced in aging. Pharmacological modulation of NO generation and expression/activity of NOS isoforms may represent a therapeutic alternative to prevent the progression of cardiovascular diseases. Accordingly, this review will focus on drugs that modulate NO bioavailability, such as nitrite anions and NO-releasing non-steroidal anti-inflammatory drugs, hormones (dehydroepiandrosterone and estrogen), statins, resveratrol, and folic acid, since they may be useful to treat/to prevent aging-associated vascular dysfunction. The impact of these therapies on life quality in elderly and longevity will be discussed. PMID:22737132

Cau, Stefany B. A.; Carneiro, Fernando S.; Tostes, Rita C.

2012-01-01

379

Nitric oxide produced by ultraviolet-irradiated keratinocytes stimulates melanogenesis.  

PubMed Central

Ultraviolet (UV) radiation is the main physiological stimulus for human skin pigmentation. Within the epidermal-melanin unit, melanocytes synthesize and transfer melanin to the surrounding keratinocytes. Keratinocytes produce paracrine factors that affect melanocyte proliferation, dendricity, and melanin synthesis. In this report, we show that normal human keratinocytes secrete nitric oxide (NO) in response to UVA and UVB radiation, and we demonstrate that the constitutive isoform of keratinocyte NO synthase is involved in this process. Next, we investigate the melanogenic effect of NO produced by keratinocytes in response to UV radiation using melanocyte and keratinocyte cocultures. Conditioned media from UV-exposed keratinocytes stimulate tyrosinase activity of melanocytes. This effect is reversed by NO scavengers, suggesting an important role for NO in UV-induced melanogenesis. Moreover, melanocytes respond to NO-donors by decreased growth, enhanced dendricity, and melanogenesis. The rise in melanogenesis induced by NO-generating compounds is associated with an increased amount of both tyrosinase and tyrosinase-related protein 1. These observations suggest that NO plays an important role in the paracrine mediation of UV-induced melanogenesis. PMID:9045865

Roméro-Graillet, C; Aberdam, E; Clément, M; Ortonne, J P; Ballotti, R

1997-01-01

380

Spectrophotometric determination of uranium and plutonium present together in nitric acid solutions  

Microsoft Academic Search

A method is described for the spectrophotometric determination of uranium(VI) and plutonium(IV) in nitric acid solutions. Uranium is determined as a light-absorbing complex with arsenazo III in 0.05 M nitric acid at lambda = 654 nm, plutonium as a light-absorbing complex with xylenol orange in 0.1 M nitric acid at lambda = 540 nm. For the determination of uranium, DTPA

B. I. Levakov; V. B. Mishenev; N. Yu. Nezgovorov; G. K. Ryazanova; G. A. Timofeev

1987-01-01

381

Hydrogen peroxide differentially modulates cardiac myocyte nitric oxide synthesis  

PubMed Central

Nitric oxide (NO) and hydrogen peroxide (H2O2) are synthesized within cardiac myocytes and play key roles in modulating cardiovascular signaling. Cardiac myocytes contain both the endothelial (eNOS) and neuronal (nNOS) NO synthases, but the differential roles of these NOS isoforms and the interplay of reactive oxygen species and reactive nitrogen species in cardiac signaling pathways are poorly understood. Using a recently developed NO chemical sensor [Cu2(FL2E)] to study adult cardiac myocytes from wild-type, eNOSnull, and nNOSnull mice, we discovered that physiological concentrations of H2O2 activate eNOS but not nNOS. H2O2-stimulated eNOS activation depends on phosphorylation of both the AMP-activated protein kinase and kinase Akt, and leads to the robust phosphorylation of eNOS. Cardiac myocytes isolated from mice infected with lentivirus expressing the recently developed H2O2 biosensor HyPer2 show marked H2O2 synthesis when stimulated by angiotensin II, but not following ?-adrenergic receptor activation. We discovered that the angiotensin-II-promoted increase in cardiac myocyte contractility is dependent on H2O2, whereas ?-adrenergic contractile responses occur independently of H2O2 signaling. These studies establish differential roles for H2O2 in control of cardiac contractility and receptor-dependent NOS activation in the heart, and they identify new points for modulation of NO signaling responses by oxidant stress. PMID:21896719

Sartoretto, Juliano L.; Kalwa, Hermann; Pluth, Michael D.; Lippard, Stephen J.; Michel, Thomas

2011-01-01

382

Studies on the oxidation of hexamethylbenzene 1: Oxidation of hexamethylbenzene with nitric acid  

NASA Technical Reports Server (NTRS)

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.

Chiba, K.; Tomura, S.; Mizuno, T.

1986-01-01

383

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

PubMed Central

OBJECTIVES We investigated whether oxidative stress and the arginine/nitric oxide pathway differ in control subjects and in adult patients who are candidates for the three most common cardiac surgical operations: coronary bypass surgery, aortic valve replacement for calcific non-rheumatic aortic stenosis or mitral valve repair for degenerative mitral insufficiency. METHODS In this prospective observational study, we studied 165 consecutive patients undergoing surgery from January to June 2011 (coronary bypass surgery, n = 63; aortic valve replacement for calcific non-rheumatic aortic stenosis, n = 51; mitral valve repair for degenerative mitral insufficiency, n = 51). Thirty-three healthy subjects with cardiovascular risk factors similar to surgery patients were also studied (Controls). Oxidative stress (the ratio of reduced and oxidized glutathione and urinary isoprostane), antioxidants (alpha- and gamma tocopherol) and factors involved in nitric oxide synthesis (arginine, symmetric and asymmetric dimethylarginine) were measured before surgery. Analysis of variance general linear models and principal component analysis were used for statistical analysis. RESULTS Surgical patients had increased levels of oxidative stress and decreased levels of antioxidants. Increased levels of nitric oxide inhibitor asymmetric dimethylarginine were detected in surgical candidates, suggesting arginine/nitric oxide pathway impairment. Concerning the differences among surgical procedures, higher oxidative stress and a major imbalance of the ratio between substrate and inhibitors of nitric oxide synthesis were evidenced in patients who were candidates for mitral valve repair with respect to coronary bypass surgery patients and patients with calcific non-rheumatic aortic stenosis. CONCLUSIONS Patients undergoing cardiac surgery have increased oxidative stress and a trend towards an impaired arginine/nitric oxide pathway with respect to Controls. Patients affected by mitral valve regurgitation show more pronounced perturbations in these pathways. The clinical implications of these findings need to be investigated. PMID:24014619

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

2013-01-01

384

[Physical activity and endothelial dysfunction in type 2 diabetic patients: the role of nitric oxide and oxidative stress].  

PubMed

Type 2 diabetic patients have an increased level of systemic free radicals, which severely restrict the bioavailability of endothelium-derived nitric oxide (NO) and thus contribute to the development of an endothelial dysfunction. This review analyses the influence of physical training on molecular development mechanisms of the endothelial dysfunction and determines the significance of regular physical exercise for the endothelial function in type 2 diabetic patients. Systematic training reinforces the endogenic antioxidative capacity and results in a reduction in oxidative stress. Training - also combined with a change in diet - furthermore reduces hyperglycaemic blood sugar levels, thus curbing a major source of free radicals in diabetes. Moreover, physical exercise enhances vascular NO synthesis through an increased availability/activity of endothelial NO synthases (eNOS). Endurance, as well as resistance training with submaximal intensity or a combination of both forms of training is suitable to effectively improve the endothelial function in type 2 diabetic patients in the long term. PMID:21360292

Brinkmann, Christian; Schwinger, Robert H G; Brixius, Klara

2011-06-01

385

Reduced nitric oxide bioavailability contributes to skeletal muscle microvessel rarefaction in the metabolic syndrome.  

PubMed

This study tested the hypothesis that chronically elevated oxidant stress contributes to impaired active hyperemia in skeletal muscle of obese Zucker rats (OZR) vs. lean Zucker rats (LZR) through progressive deteriorations in microvascular structure. Twelve-week-old LZR and OZR were given 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (tempol) in the drinking water for approximately 4 wk. Subsequently, perfusion of in situ gastrocnemius muscle was determined during incremental elevations in metabolic demand, while a contralateral skeletal muscle arteriole and the gastrocnemius muscle was removed to determine dilator reactivity, vessel wall mechanics, and microvessel density. Under control conditions, active hyperemia was impaired at all levels of metabolic demand in OZR, and this was correlated with a reduced microvessel density, increased arteriolar stiffness, and impaired dilator reactivity. Chronic tempol ingestion improved perfusion during moderate to high metabolic demand only and was associated with improved arteriolar reactivity and microvessel density; passive vessel mechanics were unaltered. Combined antioxidant therapy and nitric oxide synthase inhibition in OZR prevented much of the restored perfusion and microvessel density. In LZR, treatment with N(omega)-nitro-L-arginine methyl ester (L-NAME) hydrochloride and hydralazine (to prevent hypertension) impaired active hyperemia, dilator reactivity, and microvessel density, although arteriolar distensibility was not altered. These results suggest that with the development of the metabolic syndrome, chronic reductions in nitric oxide bioavailability, in part via the scavenging actions of oxidative free radicals, contribute to a loss of skeletal muscle microvessels, leading to impaired muscle perfusion with elevated metabolic demand. PMID:15802560

Frisbee, Jefferson C

2005-08-01

386

Nitric oxide synthase 2 (NOS2) expression in histologically normal margins of oral squamous cell carcinoma  

PubMed Central

The activity of Nitric Oxide Synthase 2 (NOS2) was found in oral squamous cell carcinomas (OSCC) but not in normal mucosa. Molecular changes associated to early carcinogenesis have been found in mucosa near carcinomas, which is considered a model to study field cancerization. The aim of the present study is to analyze NOS2 expression at the histologically normal margins of OSCC. Study Design: Eleven biopsy specimens of OSCC containing histologically normal margins (HNM) were analyzed. Ten biopsies of normal oral mucosa were used as controls. The activity of NOS2 was determined by immunohistochemistry. Salivary nitrate and nitrite as well as tobacco and alcohol consumption were also analyzed. The Chi-squared test was applied. Results: Six out of the eleven HNM from carcinoma samples showed positive NOS2 activity whereas all the control group samples yielded negative (p=0.005). No statistically significant association between enzyme expression and tobacco and/or alcohol consumption and salivary nitrate and nitrite was found. Conclusions: NOS2 expression would be an additional evidence of alterations that may occur in a state of field cancerization before the appearance of potentially malignant morphological changes. Key words:Field cancerization, oral squamous cell carcinoma, Nitric Oxide Synthase 2 (NOS2), malignity markers. PMID:24316703

Itoiz, María E.; Guiñazú, Natalia; Piccini, Daniel; Gea, Susana; López-de Blanc, Silvia

2014-01-01

387

Terahertz spectroscopy of N$^{18}$O and isotopic invariant fit of several nitric oxide isotopologs  

E-print Network

A tunable far-infrared laser sideband spectrometer was used to investigate a nitric oxide sample enriched in 18O between 0.99 and 4.75 THz. Regular, electric dipole transitions were recorded between 0.99 and 2.52 THz, while magnetic dipole transitions between the 2Pi(1/2) and 2Pi(3/2) spin-ladders were recorded between 3.71 and 4.75 THz. These data were combined with lower frequency data of N(18)$O (unlabeled atoms refer to (14)N and (16)O, respectively), with rotational data of NO, (15)NO, N(17)O, and (15)N(18)O, and with heterodyne infrared data of NO to be subjected to one isotopic invariant fit. Rotational, fine and hyperfine structure parameters were determined along with vibrational, rotational, and Born-Oppenheimer breakdown corrections. The resulting spectroscopic parameters permit prediction of rotational spectra suitable for the identification of various nitric oxide isotopologs especially in the interstellar medium by means of rotational spectroscopy.

Müller, Holger S P; Takahashi, Kazumasa; Tomaru, Kazuko; Matsushima, Fusakazu

2014-01-01

388

Nitric oxide boosts TLR-4 mediated lipocalin 2 expression in chondrocytes.  

PubMed

Lipocalin 2 (LCN2) has recently emerged as a novel adipokine involved in different processes including arthritis and chondrocyte inflammatory response. However, little is known about its activity on chondrocyte homeostasis and its regulation by nitric oxide (NO) Hence, we performed a set of experiments aimed to achieve a better understanding of this relationship. Cell vitality was tested in the ATDC5 cell line by the MTT colorimetric assay. Protein expression and gene expression was evaluated by Western blot and real time RT-PCR, respectively. NO production (determined as nitrite accumulation) was assayed by the Griess reaction. First, we demonstrated that LCN2 decreased murine chondrocytes vitality. Next, LCN2 co-stimulation with LPS enhanced NOS2 protein expression by murine chondrocytes. In addition, inhibition of LPS-induced nitric oxide production by aminoguanidine, a selective NOS2 inhibitor, significantly reduced LPS-mediated LCN2 expression. In contrast, treatment of murine chondrocytes with sodium nitroprussiate (SNP), a classic NO donor, scarcely induced LCN2 expression. Intriguingly, SNP addition to LPS-challenged chondrocytes, treated with aminoguanidine, provoked a strong induction of LCN2 expression. Finally, murine ATDC5 cells, co-cultured with LPS pre-challenged macrophages, had higher LCN2 expression in comparison with murine chondrocytes co-cultured with non pre-challenged macrophages. In this work we have described for the first time that NO is able to exert a control on LCN2 expression, suggesting the existence of a feedback loop regulating its expression. PMID:23483583

Gómez, Rodolfo; Scotece, Morena; Conde, Javier; Lopez, Veronica; Pino, Jesus; Lago, Francisca; Gómez-Reino, Juan J; Gualillo, Oreste

2013-07-01

389

Mechanism of Liver Injury during Obstructive Jaundice: Role of Nitric Oxide, Splenic Cytokines, and Intestinal Flora  

PubMed Central

To elucidate the roles of enteric bacteria and immunological interactions among liver, spleen and intestine in the pathogenesis of liver injury during obstructive jaundice, we studied the effects of antibiotics and splenectomy on bile-duct-ligated C57BL mice. When animals were subjected to bile-duct-ligation (BDL), plasma levels of bilirubin, alanine aminotransferase and aspartate aminotransferase increased markedly. However, the increases in plasma transaminases were significantly lower in splenectomized or antibiotics-treated groups than in the control BDL group. Histological examination revealed that liver injury was also low in the two groups. BDL markedly increased plasma level of interferon-? (IFN-?) and the expression of inducible nitric oxide synthase (iNOS) in liver and spleen. These changes were suppressed either by splenectomy or administration of antibiotics. Kinetic analysis revealed that BDL-induced liver injury and the increase of interleukin-10 (IL-10) and INF-? were lower in iNOS?/? than in wild type animals. BDL markedly increased the expression of IgA in colonic mucosa. These observations suggest that enteric bacteria, nitric oxide and cytokines including IFN-? and IL-10 derived from spleen and intestines form a critical network that determines the extent of liver injury during obstructive jaundice. PMID:18398495

Hong, Ji-Young; F. Sato, Eisuke; Hiramoto, Keiichi; Nishikawa, Manabu; Inoue, Masayasu

2007-01-01

390

Ventilation and oxygenation induce endothelial nitric oxide synthase gene expression in the lungs of fetal lambs.  

PubMed Central

At birth, ventilation and oxygenation immediately decrease pulmonary vascular resistance (PVR) and increase pulmonary blood flow (PBF); more gradual changes occur over the next several hours. Nitric oxide, produced by endothelial nitric oxide synthase (eNOS), mediates these gradual changes. To determine how ventilation and oxygenation affect eNOS gene expression, 12 fetal lambs were ventilated for 8 h without changing fetal descending aortic blood gases or pH (rhythmic distension) or with 100% oxygen (O2 ventilation). Vascular pressures and PBF were measured. Total RNA, protein, and tissue sections were prepared from lung tissue for RNase protection assays, Western blotting, and in situ hybridization. O2 ventilation increased PBF and decreased PVR more than rhythmic distension (P < 0.05). Rhythmic distension increased eNOS mRNA expression; O2 ventilation increased eNOS mRNA expression more and increased eNOS protein expression (P < 0.05). To define the mechanisms responsible for these changes, ovine fetal pulmonary arterial endothelial cells were exposed to 1, 21, or 95% O2 or to shear stress. 95% O2 increased eNOS mRNA and protein expression (P < 0.05). Shear stress increased eNOS mRNA and protein expression (P < 0.05). Increased oxygenation but more importantly increased PBF with increased shear stress induce eNOS gene expression and contribute to pulmonary vasodilation after birth. PMID:9294110

Black, S M; Johengen, M J; Ma, Z D; Bristow, J; Soifer, S J

1997-01-01

391

Measurements of atmospheric nitric oxide from Nimbus 7 SBUV ultraviolet spectral scan data  

NASA Technical Reports Server (NTRS)

Results are given of SBUV (solar backscattered ultraviolet instrument) measurements from Nimbus 7, when - one day per month - it is operated in a spectral scan mode, scanning from 160 nm to 400 nm in 0.2-nm steps. By measuring the intensity of a series of nitric oxide (NO) gamma band fluorescence features in this wavelength range, it has been possible to estimate the amount of NO in the upper stratosphere and mesosphere. The background of atmospherically scattered sunlight normally masks the much weaker NO gamma band emission, but these emission features are discriminated by subtracting a synthetic spectrum calculated for a model atmosphere that includes only Rayleigh scattering and absorption by ozone and oxygen. The resulting difference plot clearly reveals features resulting from processes not included in the simple model, such as NO gamma band emission. Nitric oxide is inferred by measuring the absolute intensity of various bands relative to the adjacent background and relating this intensity to total NO above an altitude determined by the backscattering contribution function for that band. NO observations near the solstice and at various latitudes are reported.

Mcpeters, R. D.

1985-01-01

392

Symmetric dimethylarginine alters endothelial nitric oxide activity in glomerular endothelial cells.  

PubMed

Circulating symmetric dimethylarginine (SDMA) is increased in patients with chronic kidney disease. SDMA is considered an inert metabolite, but because it can transported into cells, we studied the effect of SDMA on glomerular endothelial cells. SDMA suppressed VEGF-induced endothelial nitric oxide synthase (eNOS) phosphorylation and nitric oxide production, but not VEGFR2 activation and signaling leading to eNOS activation. SDMA caused eNOS uncoupling and increased superoxide anion production in response to VEGF. All these effects were blocked by preventing cellular uptake of SDMA with a molar excess of arginine. These data show that SDMA interferes with nitric oxide production by uncoupling eNOS and leads to oxidative stress in glomerular endothelial cells. In conclusion, our data show that SDMA is not an inert metabolite and that it could contribute to oxidative stress in the renal endothelium. PMID:25283600

Feliers, Denis; Lee, Duck-Yoon; Gorin, Yves; Kasinath, Balakuntalam S

2015-01-01

393

Insulin-stimulated phosphorylation of endothelial nitric oxide synthase at serine-615 contributes to nitric oxide synthesis.  

PubMed

Insulin stimulates endothelial NO (nitric oxide) synthesis via PKB (protein kinase B)/Akt-mediated phosphorylation and activation of eNOS (endothelial NO synthase) at Ser-1177. In previous studies, we have demonstrated that stimulation of eNOS phosphorylation at Ser-1177 may be required, yet is not sufficient for insulin-stimulated NO synthesis. We therefore investigated the role of phosphorylation of eNOS at alternative sites to Ser-1177 as candidate parallel mechanisms contributing to insulin-stimulated NO synthesis. Stimulation of human aortic endothelial cells with insulin rapidly stimulated phosphorylation of both Ser-615 and Ser-1177 on eNOS, whereas phosphorylation of Ser-114, Thr-495 and Ser-633 was unaffected. Insulin-stimulated Ser-615 phosphorylation was abrogated by incubation with the PI3K (phosphoinositide 3-kinase) inhibitor wortmannin, infection with adenoviruses expressing a dominant-negative mutant PKB/Akt or pre-incubation with TNFalpha (tumour necrosis factor alpha), but was unaffected by high culture glucose concentrations. Mutation of Ser-615 to alanine reduced insulin-stimulated NO synthesis, whereas mutation of Ser-615 to aspartic acid increased NO production by NOS in which Ser-1177 had been mutated to an aspartic acid residue. We propose that the rapid PKB-mediated stimulation of phosphorylation of Ser-615 contributes to insulin-stimulated NO synthesis. PMID:19925457

Ritchie, Stuart A; Kohlhaas, Christine F; Boyd, Alasdair R; Yalla, Krishna C; Walsh, Kenneth; Connell, John M C; Salt, Ian P

2010-02-15

394

Amplification of nitric oxide synthase expression by nitric oxide in interleukin 1 beta-stimulated rat mesangial cells.  

PubMed Central

Nitric oxide (NO) plays an important role in immunological reactions as a host defense mechanism against tumor cells and invasive microorganisms, but it may also damage healthy tissue. The excessive formation of NO in IL-1 beta-stimulated renal mesangial cells not only alters glomerular filtration, but it may also cause tissue injury and thus contribute to the pathogenesis of certain forms of glomerulonephritis. We report here that, although NO alone has no evident effect on NO synthase expression, it potently augments IL-1 beta-stimulated NO synthase expression in mesangial cells. NO donors such as sodium nitroprusside and S-nitroso-N-acetyl-D,L-penicillamine markedly increase IL-1 beta-induced NO synthase mRNA and protein levels as well as enzyme activity. Nuclear run-on experiments suggest that NO acts to increase IL-1 beta-induced NO synthase gene expression at the transcriptional level. Furthermore, inhibition of NO synthesis by different pharmacological approaches reduces IL-1 beta-induced NO synthase expression, thus suggesting that NO functions in a positive feedback loop that speeds up and strengthens its own biosynthesis. We suggest that this potent amplification mechanism forms the basis for the excessive formation of NO in acute and chronic inflammatory diseases. Images PMID:7535802

Mühl, H; Pfeilschifter, J

1995-01-01

395

l-arginine infusion decreases plasma total homocysteine concentrations through increased nitric oxide production and decreased oxidative status in Type II diabetic patients  

Microsoft Academic Search

Aims\\/hypothesis. Hyperhomocysteinaemia increases cardiovascular risk in Type II (non-insulin-dependent) diabetes mellitus by augmenting oxidative stress and reducing nitric oxide availability. In vitro, nitric oxide decreases homocysteine by its conversion to the vasodilative and antioxidant compound S-nitrosohomocysteine. We investigated whether or not changes in nitric oxide availability decrease homocysteine concentrations in vivo. Methods. The study group consisted of 20 normotensive, normolipidaemic,

M. Cassone Faldetta; O. Laurenti; G. Desideri; M. C. Bravi; O. De Luca; M. C. Marinucci; G. De Mattia; C. Ferri

2002-01-01

396

Insulin Stimulates Glucose Transport Via Nitric Oxide\\/Cyclic GMP Pathway in Human Vascular Smooth Muscle Cells  

Microsoft Academic Search

Objective—In cultured human vascular smooth muscle cells, insulin increases cyclic GMP production by inducing nitric oxide (NO) synthesis. The aim of the present study was to determine whether in these cells the insulin-stimulated NO\\/cyclic GMP pathway plays a role in the regulation of glucose uptake. Methods and Results—Glucose transport in human vascular smooth muscle cells was measured as uptake of

L. Bergandi; F. Silvagno; I. Russo; C. Riganti; G. Anfossi; E. Aldieri; D. Ghigo; M. Trovati; A. Bosia

2009-01-01

397

Inducible nitric oxide synthase (iNOS)-like immunoreactivity in argyrophilic, tau-positive astrocytes in progressive supranuclear palsy  

Microsoft Academic Search

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

Takashi Komori; Noriyuki Shibata; Makio Kobayashi; Shoichi Sasaki; Makoto Iwata

1998-01-01

398

Increased expression and cellular localization of inducible nitric oxide synthase and cyclooxygenase 2 in Helicobacter pylori gastritis  

Microsoft Academic Search

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

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

399

Keratinocyte-Derived Chemotactic Cytokines: Expressional Modulation by Nitric Oxide in Vitro and during Cutaneous Wound Repair in Vivo  

Microsoft Academic Search

Inhibition of inducible nitric oxide-synthase (iNOS) enzymatic activity during cutaneous wound repair leads to severely impaired tissue regeneration. To assess whether disturbed leukocyte infiltration might participate in impaired repair, we determined expressional kinetics of neutrophil-attracting macrophage inflammatory protein-2 (MIP-2), and monocyte-attracting macrophage chemoattractant protein-1 (MCP-1) using an excisional wound healing model in mice. MCP-1 was induced in epithelial keratinocytes upon

Christian Wetzler; Heiko Kämpfer; Josef Pfeilschifter; Stefan Frank

2000-01-01

400

para-Substituted N-Nitroso-N-oxybenzenamine Ammonium Salts: A New Class of Redox-sensitive Nitric Oxide Releasing  

E-print Network

Oxide Releasing Compounds Andrea D. McGill, Wei Zhang, Joanne Wittbrodt, Jianqiang Wang, H. Bernhard constitute a new class of-redox sensitive nitric oxide (NO) releasing compounds. These compounds yield nitric oxide and the corresponding nitrosobenzene derivatives by a spontaneous dissociation mechanism after

Schlegel, H. Bernhard

401

Therapeutic hypothermia cardioprotection via Akt- and nitric oxide-mediated attenuation of mitochondrial oxidants  

PubMed Central

Therapeutic hypothermia (TH) is a promising cardioprotective treatment for cardiac arrest and acute myocardial infarction, but its cytoprotective mechanisms remain unknown. In this study, we developed a murine cardiomyocyte model of ischemia-reperfusion injury to better determine the mechanisms of TH cardioprotection. We hypothesized that TH manipulates Akt, a survival kinase that mediates mitochondrial protection by modulating reactive oxygen species (ROS) and nitric oxide (NO) generation. Cardiomyocytes, isolated from 1- to 2-day-old C57BL6/J mice, were exposed to 90 min simulated ischemia and 3 h reperfusion. For TH, cells were cooled to 32°C during the last 20 min of ischemia and the first hour of reperfusion. Cell viability was evaluated by propidium iodide and lactate dehydrogenase release. ROS production was measured by 6-carboxy-2?,7?-dichlorodihydrofluorescein diacetate and mitochondrial membrane potential (??m) by 5,5?,6,6?-tetrachloro-1,1?,3,3?-tetraethylbenzimidazoly-carbocyanine iodide (JC-1). Phospho (p)-Akt (Thr308), p-Akt (Ser473), and phosphorylated heat shock protein 27 (p-HSP27) (Ser82) were analyzed by Western blot analysis. TH attenuated reperfusion ROS generation, increased NO, maintained ??m, and decreased cell death [19.3 ± 3.3% (n = 11) vs. 44.7 ± 2.7% (n = 10), P < 0.001]. TH also increased p-Akt during ischemia before reperfusion. TH protection and attenuation of ROS were blocked by the inhibition of Akt and NO synthase but not by a cGMP inhibitor. HSP27, a regulator of Akt, also exhibited increased phosphorylation (Ser82) during ischemia with TH. We conclude that TH cardioprotection is mediated by enhanced Akt/HSP27 phosphorylation and enhanced NO generation, resulting in the attenuation of ROS generation and the maintenance of ??m following ischemia-reperfusion. PMID:20382860

Shao, Zuo-Hui; Sharp, Willard W.; Wojcik, Kimberly R.; Li, Chang-Qing; Han, Mei; Chang, Wei-Tien; Ramachandran, Srinivasan; Li, Jing; Hamann, Kimm J.

2010-01-01

402

Reduction of nitric oxide catalyzed by hydroxylamine oxidoreductase from an anammox bacterium.  

PubMed

The hydroxylamine oxidoreductase (HAO) from the anammox bacterium, Candidatus Kuenenia stuttgartiensis has been reported to catalyze the oxidation of hydroxylamine (NH2OH) to nitric oxide (NO) by using bovine cytochrome c as an oxidant. In contrast, we investigated whether the HAO from anammox bacterium strain KSU-1 could catalyze the reduction of NO with reduced benzyl viologen (BVred) and the NO-releasing reagent, NOC 7. The reduction proceeded, resulting in the formation of NH2OH as a product. The oxidation rate of BVred was proportional to the concentration of BVred itself for a short period in each experiment, a situation that was termed quasi-steady state. The analyses of the states at various concentrations of HAO allowed us to determine the rate constant for the catalytic reaction, (2.85 ± 0.19) × 10(5) M(-1) s(-1), governing NO reduction by BVred and HAO, which was comparable to that reported for the HAO from the ammonium oxidizer, Nitrosomonas with reduced methyl viologen. These results suggest that the anammox HAO functions to adjust anammox by inter-conversion of NO and NH2OH depending on the redox potential of the physiological electron transfer protein in anammox bacteria. PMID:24996970

Irisa, Tatsuya; Hira, Daisuke; Furukawa, Kenji; Fujii, Takao

2014-12-01

403

Evidence for nonvesicular nitric oxide release evoked by nerve activation.  

PubMed

The gaseous nature of nitric oxide (NO) has led to the general assumption that its release from neurons during nerve stimulation is independent of vesicular storage. However, recent findings have shown that NO can exist intracellularly as part of more stable bioactive molecules, suggesting that the role of vesicular exocytosis for NO release cannot be excluded simply based on the chemical nature of NO itself. We have used botulinum toxin B (BTX B) to directly address the role of vesicular exocytosis for NO release. BTX B cleaves the synaptic vesicle protein synaptobrevin/VAMP, and by this inhibits Ca++-mediated exocytic release of neurotransmitters. As a target organ we used the guinea-pig enteric nervous system, which innervates the gastrointestinal tract, and in which both classical neurotransmitters as well as NO are released and influence smooth muscle activity. As expected, BTX B (0.1 microM) blocked the nerve stimulation-induced cholinergic and tachykininergic smooth muscle contractions, and markedly inhibited the nerve stimulation-evoked release of [3H]-choline. In contrast, BTX B (0.1 microM) had no effect on nerve stimulation-evoked relaxations, which were equally inhibited by an NO-synthase inhibitor as well as by a selective inhibitor of soluble guanylyl cyclase. In addition, nerve stimulation-evoked NO synthase-dependent outflow of NO/NO2- was unaffected by BTX B (0.1 microM). These findings suggest that the neuronal release of endogenous NO is independent of intact synaptobrevin/VAMP, and therefore provide further evidence that nerve-mediated release of further NO is nonvesicular. PMID:10762359

Olgart, C; Gustafsson, L E; Wiklund, N P

2000-04-01

404

Energy Landscapes and Catalysis in Nitric-oxide Synthase*  

PubMed Central

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

Sobolewska-Stawiarz, Anna; Leferink, Nicole G. H.; Fisher, Karl; Heyes, Derren J.; Hay, Sam; Rigby, Stephen E. J.; Scrutton, Nigel S.

2014-01-01

405

Nitric oxide, antioxidants and prooxidants in plant defence responses  

PubMed Central

In plant cells the free radical nitric oxide (NO) interacts both with anti- as well as prooxidants. This review provides a short survey of the central roles of ascorbate and glutathione—the latter alone or in conjunction with S-nitrosoglutathione reductase—in controlling NO bioavailability. Other major topics include the regulation of antioxidant enzymes by NO and the interplay between NO and reactive oxygen species (ROS). Under stress conditions NO regulates antioxidant enzymes at the level of activity and gene expression, which can cause either enhancement or reduction of the cellular redox status. For instance chronic NO production during salt stress induced the antioxidant system thereby increasing salt tolerance in various plants. In contrast, rapid NO accumulation in response to strong stress stimuli was occasionally linked to inhibition of antioxidant enzymes and a subsequent rise in hydrogen peroxide levels. Moreover, during incompatible Arabidopsis thaliana-Pseudomonas syringae interactions ROS burst and cell death progression were shown to be terminated by S-nitrosylation-triggered inhibition of NADPH oxidases, further highlighting the multiple roles of NO during redox-signaling. In chemical reactions between NO and ROS reactive nitrogen species (RNS) arise with characteristics different from their precursors. Recently, peroxynitrite formed by the reaction of NO with superoxide has attracted much attention. We will describe putative functions of this molecule and other NO derivatives in plant cells. Non-symbiotic hemoglobins (nsHb) were proposed to act in NO degradation. Additionally, like other oxidases nsHb is also capable of catalyzing protein nitration through a nitrite- and hydrogen peroxide-dependent process. The physiological significance of the described findings under abiotic and biotic stress conditions will be discussed with a special emphasis on pathogen-induced programmed cell death (PCD). PMID:24198820

Groß, Felicitas; Durner, Jörg; Gaupels, Frank

2013-01-01

406

Nitric oxide targets oligodendrocytes and promotes their morphological differentiation.  

PubMed

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. GLIA 2015;63:383-399. PMID:25327839

Garthwaite, Giti; Hampden-Smith, Kathryn; Wilson, Gary W; Goodwin, David A; Garthwaite, John

2015-03-01

407

Nitric oxide targets oligodendrocytes and promotes their morphological differentiation  

PubMed Central

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

Garthwaite, Giti; Hampden-Smith, Kathryn; Wilson, Gary W; Goodwin, David A; Garthwaite, John

2015-01-01

408

Modulation by nitric oxide of prostaglandin biosynthesis in the rat.  

PubMed Central

1. Modulation of prostaglandin biosynthesis in vivo by either exogenous or endogenous nitric oxide (NO) has been studied in the rat using arachidonic acid (AA)-induced paw oedema and measuring both the foot volume and the amount of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), the stable metabolite of prostacyclin (PGI2), in the oedematous fluid recovered from inflamed paws. 2. Paw injections of 150 or 300 nmol of AA were virtually inactive whereas 600 nmol produced a moderate oedema which was greatly reduced by the NO synthase inhibitor L-NG-nitro arginine methyl ester (L-NAME, 100 nmol/paw) and the NO scavenger haemoglobin (Hb, 30 mumol/paw), but unaffected by the inhibitor of the soluble guanylate cyclase, methylene blue (Mb, 3 mumol/paw) and L-arginine (15 mumol/paw). 3. The NO-donors (10 mumol/paw) 3-morpholino-sydnonimine-hydrochloride (SIN-1), S-nitroso-N-acetyl-D, L-penicillamine (SNAP) and sodium nitroprusside (SNP) significantly potentiated the paw oedema induced by AA (300 nmol/paw). 4. SIN-1 (2.5, 5 and 10 mumol/paw) produced a significant dose-dependent increase of the oedema induced by AA which was correlated with increased amounts of 6-keto-PGF1 alpha in the fluid recovered from inflamed paws. 5. Both oedema and prostaglandin biosynthesis induced by the combination AA+SIN-1 were greatly suppressed by either Hb (30 mumol/paw) or indomethacin (3 mumol/paw or 5 mg kg-1 s.c.) but unaffected by Mb (3 mumol/paw).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7533614

Sautebin, L; Ialenti, A; Ianaro, A; Di Rosa, M

1995-01-01

409

Inactivation of nitric oxide by rat cerebellar slices.  

PubMed

Nitric oxide (NO) functions as an intercellular messenger throughout the brain. For this role to be performed efficiently, there must be a mechanism for neutralizing NO, but whether an active biological process exists, or whether NO is lost mainly through diffusion is unclear. To investigate this issue, rat cerebellar slices were exposed to constant levels of NO and the cGMP generated within the slice used as an indicator of NO concentrations therein. NO was about 1000-fold less potent in slices (EC50, 1 microM) than in separated cells from the same tissue (EC50, 1.6 nM), consistent with access of NO to the slice interior being greatly hindered by inactivation. Supporting this interpretation, immunohistochemical analysis indicated a marked concentration gradient of cGMP across the thickness of slices exposed to subsaturating NO concentrations, signifying a marked NO gradient. Several known NO-degrading processes, including reaction with lipid peroxyl radicals, erythrocytes and superoxide ions, were eliminated as contributing factors, indicating a novel mechanism. A diffusion-inactivation model was used to estimate the kinetics of NO consumption by the slices. The best fits to experimental data indicated a Michaelis-Menten-type reaction having a Vmax of 1-2 microM s-1 and a Km of around 10 nM. The rates predict that inactivation would impose a very short half-life (<10 ms) on NO in physiological concentrations (up to 10 nM) and that it would play an important role in shaping the NO concentration profiles when it is synthesized by multiple nearby sites. PMID:16973697

Hall, C N; Garthwaite, J

2006-12-01

410

Fluorinated Xerogel-Derived Microelectrodes for Amperometric Nitric Oxide Sensing  

PubMed Central

An amperometric fluorinated xerogel-derived nitric oxide (NO) microelectrode is described. A range of fluorine-modified xerogel polymers were synthesized via the co-hydrolysis and condensation of alkylalkoxy- and fluoroalkoxysilanes. Such polymers were evaluated as NO sensor membranes to identify the optimum composition for maximizing NO permeability while providing sufficient selectivity for NO in the presence of common interfering species. By taking advantage of both the versatility of sol–gel chemistry and the “poly(tetrafluoroethylene) (PTFE)-like” high NO permselective properties of the xerogels, the performance of the fluorinated xerogel-derived sensors was excellent, surpassing all miniaturized NO sensors reported to date. In contrast to previous electrochemical NO sensor designs, xerogel-based NO microsensors were fabricated using a simple, reliable dip-coating procedure. An optimal permselective membrane was achieved by synthesizing xerogels of methyltrimethoxysilane (MTMOS) and 20% (heptadecafluoro-1,1,2,2-tetrahydrodecyl)trimethoxysilane (17FTMS, balance MTMOS) under acid-catalyzed conditions. The resulting NO microelectrode had a conical tip of ~20 ?m in diameter and ~55 mm in length, and exhibited sensitivities of 7.91 pA·nM?1 from 0.2 to 3.0 nM (R2 = 0.9947) and 7.60 nA·mM?1 from 0.5 to 4.0 ?M (R2 = 0.9999), detection limit of 83 pM (S/N = 3), response time (t95%) of <3 sec, and selectivity (logKNO,jamp) of ?5.74,

Shin, Jae Ho; Privett, Benjamin J.; Kita, Justin M.; Wightman, R. Mark; Schoenfisch, Mark H.

2009-01-01

411

Bronchodilator action of inhaled nitric oxide in guinea pigs.  

PubMed Central

The effects of inhaling nitric oxide (NO) on airway mechanics were studied in anesthetized and mechanically ventilated guinea pigs. In animals without induced bronchoconstriction, breathing 300 ppm NO decreased baseline pulmonary resistance (RL) from 0.138 +/- 0.004 (mean +/- SE) to 0.125 +/- 0.002 cmH2O/ml.s (P less than 0.05). When an intravenous infusion of methacholine (3.5-12 micrograms/kg.min) was used to increase RL from 0.143 +/- 0.008 to 0.474 +/- 0.041 cmH2O/ml.s (P less than 0.05), inhalation of 5-300 ppm NO-containing gas mixtures produced a dose-related, rapid, consistent, and reversible reduction of RL and an increase of dynamic lung compliance. The onset of bronchodilation was rapid, beginning within 30 s after commencing inhalation. An inhaled NO concentration of 15.0 +/- 2.1 ppm was required to reduce RL by 50% of the induced bronchoconstriction. Inhalation of 100 ppm NO for 1 h did not produce tolerance to its bronchodilator effect nor did it induce substantial methemoglobinemia (less than 2%). The bronchodilating effects of NO were additive with the effects of inhaled terbutaline, irrespective of the sequence of NO and terbutaline administration. Inhaling aerosol generated from S-nitroso-N-acetylpenicillamine also induced a rapid and profound decrease of RL from 0.453 +/- 0.022 to 0.287 +/- 0.022 cmH2O/ml.s, which lasted for over 15 min in guinea pigs broncho-constricted with methacholine. Our results indicate that low levels of inhaled gaseous NO, or an aerosolized NO-releasing compound are potent bronchodilators in guinea pigs. PMID:1644915

Dupuy, P M; Shore, S A; Drazen, J M; Frostell, C; Hill, W A; Zapol, W M

1992-01-01

412

Nitric oxide, antioxidants and prooxidants in plant defence responses.  

PubMed

In plant cells the free radical nitric oxide (NO) interacts both with anti- as well as prooxidants. This review provides a short survey of the central roles of ascorbate and glutathione-the latter alone or in conjunction with S-nitrosoglutathione reductase-in controlling NO bioavailability. Other major topics include the regulation of antioxidant enzymes by NO and the interplay between NO and reactive oxygen species (ROS). Under stress conditions NO regulates antioxidant enzymes at the level of activity and gene expression, which can cause either enhancement or reduction of the cellular redox status. For instance chronic NO production during salt stress induced the antioxidant system thereby increasing salt tolerance in various plants. In contrast, rapid NO accumulation in response to strong stress stimuli was occasionally linked to inhibition of antioxidant enzymes and a subsequent rise in hydrogen peroxide levels. Moreover, during incompatible Arabidopsis thaliana-Pseudomonas syringae interactions ROS burst and cell death progression were shown to be terminated by S-nitrosylation-triggered inhibition of NADPH oxidases, further highlighting the multiple roles of NO during redox-signaling. In chemical reactions between NO and ROS reactive nitrogen species (RNS) arise with characteristics different from their precursors. Recently, peroxynitrite formed by the reaction of NO with superoxide has attracted much attention. We will describe putative functions of this molecule and other NO derivatives in plant cells. Non-symbiotic hemoglobins (nsHb) were proposed to act in NO degradation. Additionally, like other oxidases nsHb is also capable of catalyzing protein nitration through a nitrite- and hydrogen peroxide-dependent process. The physiological significance of the described findings under abiotic and biotic stress conditions will be discussed with a special emphasis on pathogen-induced programmed cell death (PCD). PMID:24198820

Groß, Felicitas; Durner, Jörg; Gaupels, Frank

2013-01-01

413

Endothelial Nitric Oxide Synthase Regulation in Female Genital Tract Structures  

PubMed Central

Introduction Female sexual arousal disorder (FSAD) is a major component of female sexual dysfunctions, affecting 25–70% of women. The mechanisms of FSAD are poorly understood. Estrogen contributes to the control of genital blood flow during the sexual response. Vascular effects of estrogen are mostly attributed to its regulation of endothelial nitric oxide (NO) production. However, the role of endothelial NO synthase (eNOS) and the mechanisms that regulate eNOS in female genital tract structures are largely unknown. Aim To review available evidence of the mechanisms of eNOS regulation in female genital tract structures. Methods This article reviews the literature that relates to the role of NO and eNOS in female sexual arousal and its modulation by estrogen. Main Outcome Measures Association between female sexual arousal, NO, and eNOS. Results The NO/cyclic guanosine monophosphate pathway is believed to have a primary role in the regulation of clitoral and vaginal blood flow, and smooth muscle relaxation during sexual arousal. Estrogen is critical for maintaining vaginal and clitoral blood flow and vaginal transudate production. Estrogen regulates eNOS by genomic mechanisms, involving augmented mRNA transcription and protein synthesis, and by non-genomic mechanisms, which occur without alterations in gene expression. However, limited studies have evaluated the physiological role of endothelial NO and the molecular mechanisms of eNOS regulation in the female genital tract. Conclusions The effects of estrogen on increasing genital blood flow and smooth muscle relaxation have been attributed mostly to regulation of eNOS. However, the exact mechanisms of eNOS regulation in female genital tract structures and the molecular basis for the eNOS defect with aging and vascular diseases warrant further investigation. PMID:19138376

Musicki, Biljana; Liu, Tongyun; Lagoda, Gwen A.; Bivalacqua, Trinity J.; Strong, Travis D.; Burnett, Arthur L.

2009-01-01

414

Inhibition of vesicular stomatitis virus infection by nitric oxide.  

PubMed Central

Inhibitory effects of nitric oxide (NO) on vesicular stomatitis virus (VSV) infection were investigated by using a VSV-susceptible mouse neuroblastoma cell line, NB41A3. Productive VSV infection of NB41A3 cells was significantly inhibited by an organic NO donor, S-nitro-N-acetylpenicillamine (SNAP), while the control compound N-acetylpenicillamine (NAP) had no effect. Survival rate of VSV-infected cells was greatly increased by the treatment with SNAP, while the NAP treatment did not have any effect. Adding SNAP 30 min prior to infection resulted in complete inhibition of viral production when a low multiplicity of infection (MOI) was used. Substantial inhibition of viral production was also obtained with treating cells 6 h earlier before infection with a higher MOI. Activating the neuronal NO synthase by treating cells with N-methyl-D-aspartate (NMDA) led to significant inhibition of viral production by cells infected at the three doses of virus tested (MOIs of 0.1, 1, and 5). The inhibitory effect of NMDA on viral infection was totally blocked by the NO synthase inhibitor N-methyl-L-arginine. However, adding hemoglobin, a strong NO-binding protein and thus an inactivator of NO activity, did not reverse the NMDA-induced inhibition of viral production, suggesting that NO might exert its antiviral effects inside the NO-producing cells. Collectively, these data support the anti-VSV effects of NO, which might be one of the important factors of natural immunity in controlling the initial stages of VSV infection in the central nervous system. PMID:7533852

Bi, Z; Reiss, C S

1995-01-01

415

Antioxidants Modulate the Antiproliferative Effects of Nitric Oxide on Vascular Smooth Muscle Cells and Adventitial Fibroblasts by Regulating Oxidative Stress  

PubMed Central

Background S-nitrosothiols (SNO) release nitric oxide (NO) through interaction with ascorbic acid (AA). However, little is known about their combined effect in the vasculature. The aim of this study is to investigate the effect of AA on SNO-mediated NO release, proliferation, cell cycle progression, cell death and oxidative stress in vascular cells. Methods VSMC and adventitial fibroblasts (AF) harvested from the aortae of Sprague Dawley rats were treated with AA, ± S-nitrosoglutathione (GSNO), or ± diethylenetriamine NONOate (DETA/NO). NO release, proliferation, cell cycle progression, cell death, and oxidative stress were determined by the Greiss reaction, [3H]-thymidine incorporation, flow cytometry, trypan blue exclusion, and DCF staining, respectively. Results AA increased NO release from GSNO 3-fold (p<0.001). GSNO and DETA/NO significantly decreased proliferation, but AA abrogated this effect (p<0.05). Mirroring the proliferation data, changes in cell cycle progression induced by GSNO and DETA/NO were reversed by addition of AA. GSNO- and DETA/NO-mediated increases in oxidative stress were significantly decreased by addition of AA (p<0.001). Conclusion Despite causing increased NO release from GSNO, AA reduced the antiproliferative and cell cycle effects of GSNO and DETA/NO through modulation of oxidative stress. PMID:21944289

Gregory, Elaine K.; Vavra, Ashley K.; Moreira, Edward S.; Havelka, George E.; Jiang, Qun; Lee, Vanessa R.; Van Lith, Robert; Ameer, Guillermo A.; Kibbe, Melina R.

2011-01-01

416

Biological Tyrosine Nitration: A Pathophysiological Function of Nitric Oxide and Reactive Oxygen Species  

Microsoft Academic Search

Analytical and immunological methodologies and occasionally both methodologies have been applied to detect and quantify 3-nitrotyrosine in almost every major organ system. In certain diseases increased levels of 3-nitrotyrosine have been correlated with elevated levels of other indices of oxidative stress. Numerous reports have established that nitration is a biological process derived from the biochemical interaction of nitric oxide or

Harry Ischiropoulos

1998-01-01

417

Analysis of Human Peripheral Blood Samples from Fatal and Nonfatal Cases of Ebola (Sudan) Hemorrhagic Fever: Cellular Responses, Virus Load, and Nitric Oxide Levels  

Microsoft Academic Search

Peripheral blood samples obtained from patients during an outbreak of Ebola virus (Sudan species) disease in Uganda in 2000 were used to phenotype peripheral blood mononuclear cells (PBMC), quantitate gene expression, measure antigenemia, and determine nitric oxide levels. It was determined that as the severity of disease increased in infected patients, there was a corresponding increase in antigenemia and leukopenia.

Anthony Sanchez; Matthew Lukwiya; Daniel Bausch; Siddhartha Mahanty; Angela J. Sanchez; Kent D. Wagoner; Pierre E. Rollin

2004-01-01

418

Nitric oxide and nitrogen dioxide content of whole-air samples obtained at altitudes from 12 to 30 km  

SciTech Connect

Whole air samples were obtained in the stratosphere using a liquid helium-cooled cryosampler mounted on a balloon platform. Approximately 1 g mol of sample was obtained at each of three altitudes per balloon flight and was maintained at 4 K until desorption just prior to analysis. Samples were obtained at six altitudes ranging from 12 to 30 km and at five latitudes from 9 to 64/sup 0/. Nitric oxide and the sum of nitric oxide and nitrogen dioxide content of the samples were determined using two chemiluminescence analyzers. Results from flights conducted between 1977 and 1981 are correlated with atmospheric motions and other significant variables and evaluated in terms of both one- and two-dimensional models of the stratosphere.

Gallagher, C.C.; Forsberg, C.A.; Pieri, R.V.; Faucher, G.A.; Calo, J.M.

1985-08-20

419

Nitric oxide inhibits calpain-mediated proteolysis of talin in skeletal muscle cells  

NASA Technical Reports Server (NTRS)

We tested the hypothesis that nitric oxide can inhibit cytoskeletal breakdown in skeletal muscle cells by inhibiting calpain cleavage of talin. The nitric oxide donor sodium nitroprusside prevented many of the effects of calcium ionophore on C(2)C(12) muscle cells, including preventing talin proteolysis and release into the cytosol and reducing loss of vinculin, cell detachment, and loss of cellular protein. These results indicate that nitric oxide inhibition of calpain protected the cells from ionophore-induced proteolysis. Calpain inhibitor I and a cell-permeable calpastatin peptide also protected the cells from proteolysis, confirming that ionophore-induced proteolysis was primarily calpain mediated. The activity of m-calpain in a casein zymogram was inhibited by sodium nitroprusside, and this inhibition was reversed by dithiothreitol. Previous incubation with the active site-targeted calpain inhibitor I prevented most of the sodium nitroprusside-induced inhibition of m-calpain activity. These data suggest that nitric oxide inhibited m-calpain activity via S-nitrosylation of the active site cysteine. The results of this study indicate that nitric oxide produced endogenously by skeletal muscle and other cell types has the potential to inhibit m-calpain activity and cytoskeletal proteolysis.

Koh, T. J.; Tidball, J. G.

2000-01-01

420

Caffeinated Nitric Oxide-releasing Lozenge Improves Cycling Time Trial Performance.  

PubMed

Boosting nitric oxide production during exercise by various means has been found to improve exercise performance. We investigated the effects of a nitric oxide releasing lozenge with added caffeine (70?mg) on oxygen consumption during steady-state exercise and cycling time trial performance using a double-blinded randomized, crossover experimental design. 15 moderately trained cyclists (7 females and 8 males) were randomly assigned to ingest the caffeinated nitric oxide lozenge or placebo 5?min before exercise. Oxygen consumption and blood lactate were assessed at rest and at 50%, 65% and 75% maximal oxygen consumption. Exercise performance was assessed by time to complete a simulated 20.15?km cycling time-trial course. No significant treatment effects for oxygen consumption or blood lactate at rest or during steady-state exercise were observed. However, time-trial performance was improved by 2.1% (p<0.01) when participants consumed the nitric oxide lozenge (2?424±69?s) compared to placebo (2?476±78?s) and without a significant difference in rating of perceived exertion. These results suggest that acute supplementation with a caffeinated nitric oxide releasing lozenge may be a practical and effective means of improving aerobic exercise performance. PMID:25285468

Lee, J; Kim, H T; Solares, G J; Kim, K; Ding, Z; Ivy, J L

2015-02-01

421

The role of nitric oxide in digoxin-induced arrhythmias in guinea-pigs.  

PubMed

We have investigated the effects of nitric oxide synthase inhibitor (L-NAME), nitric oxide precursor (L-arginine) and nitric oxide donor (sodium nitroprusside) on digoxin-induced arrhythmias both in guinea-pig isolated hearts and in anaesthetised animals. Sodium nitroprusside (0.1 mumol kg-1 min.-1 for 70 min.) caused a marked inhibition in mortality and arrhythmia score but L-NAME (10 mg kg-1) and L-arginine (30 mg kg-1 intravenous bolus followed by 10 mg kg-1 min.-1 for 60 min.) treatments were ineffective in anaesthetised guinea-pigs. None of the drugs markedly affected the time of onset of first arrhythmias or ventricular fibrillation incidence. In isolated heart experiments, nitric oxide generated by either L-arginine (1 mM) or sodium nitroprusside (1 mM) significantly reduced the arrhythmia score whereas L-NAME (1 mM) had no effect. Ventricular fibrillation incidence was totally abolished by sodium nitroprusside and none of the hearts treated with L-arginine had an irreversible ventricular fibrillation. L-NAME decreased ventricular tachycardia duration but increased ventricular fibrillation duration. There were no marked changes in the time of onset of first arrhythmias with these drugs in in vitro experiments. These results suggest that nitric oxide may play a modulatory role in the digoxin-induced arrhythmias in guinea-pigs. PMID:9974183

Altu?, S; Uzun, O; Demiryürek, A T; Cakici, I; Abacio?lu, N; Kanzik, I

1999-01-01

422

Monoclonal L-citrulline immunostaining reveals nitric oxide-producing vestibular neurons  

NASA Technical Reports Server (NTRS)

Nitric oxide is an unstable free radical that serves as a novel messenger molecule in the central nervous system (CNS). In order to understand the interplay between classic and novel chemical communication systems in vestibular pathways, the staining obtained using a monoclonal antibody directed against L-citrulline was compared with the labeling observed using more traditional markers for the presence of nitric oxide. Brainstem tissue from adult rats was processed for immunocytochemistry employing a monoclonal antibody directed against L-citrulline, a polyclonal antiserum against neuronal nitric oxide synthase, and/or NADPH-diaphorase histochemistry. Our findings demonstrate that L-citrulline can be fixed in situ by vascular perfusion, and can be visualized in fixed CNS tissue sections by immunocytochemistry. Further, the same vestibular regions and cell types are labeled by NADPH-diaphorase histochemistry, by the neuronal nitric oxide synthase antiserum, and by our anti-L-citrulline antibody. Clusters of L-citrulline-immunoreactive neurons are present in subregions of the vestibular nuclei, including the caudal portion of the inferior vestibular nucleus, the magnocellular portion of the medial vestibular nucleus, and the large cells in the ventral tier of the lateral vestibular nucleus. NADPH-diaphorase histochemical staining of these neurons clearly demonstrated their multipolar, fusiform and globular somata and long varicose dendritic processes. These results provide support for the suggestion that nitric oxide serves key roles in both vestibulo-autonomic and vestibulo-spinal pathways.

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

2001-01-01

423

Trigeminocardiac Reflex by Mandibular Extension on Rat Pial Microcirculation: Role of Nitric Oxide  

PubMed Central

In the present study we have extended our previous findings about the effects of 10 minutes of passive mandibular extension in anesthetized Wistar rats. By prolonging the observation time to 3 hours, we showed that 10 minutes mandibular extension caused a significant reduction of the mean arterial blood pressure and heart rate respect to baseline values, which persisted up to 160 minutes after mandibular extension. These effects were accompanied by a characteristic biphasic response of pial arterioles: during mandibular extension, pial arterioles constricted and after mandibular extension dilated for the whole observation period. Interestingly, the administration of the opioid receptor antagonist naloxone abolished the vasoconstriction observed during mandibular extension, while the administration of N?-Nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor, abolished the vasodilation observed after mandibular extension. Either drug did not affect the reduction of mean arterial blood pressure and heart rate induced by mandibular extension. By qRT-PCR, we also showed that neuronal nitric oxide synthase gene expression was significantly increased compared with baseline conditions during and after mandibular extension and endothelial nitric oxide synthase gene expression markedly increased at 2 hours after mandibular extension. Finally, western blotting detected a significant increase in neuronal and endothelial nitric oxide synthase protein expression. In conclusion mandibular extension caused complex effects on pial microcirculation involving opioid receptor activation and nitric oxide release by both neurons and endothelial vascular cells at different times. PMID:25551566

Lapi, Dominga; Federighi, Giuseppe; Fantozzi, M. Paola; del Seppia, Cristina; Ghione, Sergio; Colantuoni, Antonio; Scuri, Rossana

2014-01-01

424

Localized cell stimulation by nitric oxide using a photoactive porous coordination polymer platform  

PubMed Central

Functional cellular substrates for localized cell stimulation by small molecules provide an opportunity to control and monitor cell signalling networks chemically in time and space. However, despite improvements in the controlled delivery of bioactive compounds, the precise localization of gaseous biomolecules at the single-cell level remains challenging. Here we target nitric oxide, a crucial signalling molecule with site-specific and concentration-dependent activities, and we report a synthetic strategy for developing spatiotemporally controllable nitric oxide-releasing platforms based on photoactive porous coordination polymers. By organizing molecules with poor reactivity into polymer structures, we observe increased photoreactivity and adjustable release using light irradiation. We embed photoactive polymer crystals in a biocompatible matrix and achieve precisely controlled nitric oxide delivery at the cellular level via localized two-photon las