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1

Subcellular and cellular locations of nitric oxide synthase isoforms as determinants of health and disease  

Microsoft Academic Search

The effects of nitric oxide in biological systems depend on its steady-state concentration and where it is being produced. The organ where nitric oxide is produced is relevant, and within the organ, which types of cells are actually contributing to this production seem to play a major determinant of its effect. Subcellular compartmentalization of specific nitric oxide synthase enzymes has

Cleva Villanueva; Cecilia Giulivi

2010-01-01

2

Paracrine purinergic signaling determines lung endothelial nitric oxide production  

PubMed Central

Although the vascular bed is a major source of nitric oxide (NO) production, factors regulating the production remain unclear. We considered the role played by paracrine signaling. Determinations by fluorescence microscopy in isolated, blood-perfused rat and mouse lungs revealed that a brief lung expansion enhanced cytosolic Ca2+ (Ca2+cyt) oscillations in alveolar epithelial (AEC) and endothelial (EC) cells, and NO production in EC. Furthermore, as assessed by a novel microlavage assay, alveolar ATP production increased. Intra-alveolar microinfusion of the purinergic receptor antagonist, PPADS, and the nucleotide hydrolyzing enzyme, apyrase, each completely blocked the Ca2+cyt and NO responses in EC. Lung expansion induced Ca2+cyt oscillations in mice lacking the P2Y1, but not the P2Y2, purinergic receptors, which were located in the perivascular interstitium basolateral to AEC. Prolonged lung expansion instituted by mechanical ventilation at high tidal volume increased EC expression of nitrotyrosine, indicating development of nitrosative stress in lung microvessels. These findings reveal a novel mechanism in which mechanically induced purinergic signaling couples cross-compartmental Ca2+cyt oscillations to microvascular NO production.

Kiefmann, Rainer; Islam, Mohammad N.; Lindert, Jens; Parthasarathi, Kaushik; Bhattacharya, Jahar

2009-01-01

3

A simplified method for the determination of nitric oxide in biological solutions.  

PubMed

A new simplified procedure for determination of nitric oxide (NO) in biological solutions is described utilizing a new reducing system of nitric oxide prior to chemiluminescence. Advantages of the new method makes heating of the reducing solution unnecessary and avoids cooling and condensation of generated vapors. Only traces of acid with a high boiling point are used. The method permits analysis of small sample volumes (200 microL). The basal production of nitric oxide by freshly harvested endothelial cells ranged from 100 to 880 picomoles. PMID:1435070

Termin, A; Hoffmann, M; Bing, R J

1992-01-01

4

A new tool for superoxide and nitric oxide radicals determination using suitable enzymatic sensors  

Microsoft Academic Search

A new tool for radical determination is investigated. Superoxide and nitric oxide radicals have been determined using their modulating action on three different enzymatic sensors based on tyrosinase, superoxide dismutase (SOD), and galactose oxidase (GAO), respectively. Basic research was carried out to study the inhibition or activation effect of the two radicals considered on the enzyme sensor's response and experimentally

L Campanella; L Persi; M Tomassetti

2000-01-01

5

The Kinetics and Redox State of Nitric Oxide Determine the Biological Consequences in Lung Adenocarcinoma  

Microsoft Academic Search

Few studies have explored the mechanistic basis for the apparent paradoxical effects of nitric oxide and its interrelated redox species (NOX) in cancer biology. Our aim was to determine the differential effects of the redox state and kinetics of nitrosative species on the key cancer processes of apoptosis. Therefore, a murine lung adenocarcinoma cell line was exposed to various NOX

Brandon G. Bentz; Neal D. Hammer; Brett Milash; Slobodanka Klein; David M. Burnett; James A. Radosevich; G. Kenneth Haines III

2007-01-01

6

Amperometric determination of nitric oxide at a carbon nanotube modified electrode with redox polymer coating  

Microsoft Academic Search

A novel chemically modified electrode based on an osmium complex-containing redox polymer film coated on single-walled carbon\\u000a nanotube (SWNT) modified glassy carbon electrode (GCE) has been described for the determination of nitric oxide. The results\\u000a showed that the oxidation current increased significantly at the SWNT\\/redox polymer coated GCE, as compared to that observed\\u000a on a bare GCE- and SWNT-modified GCE.

Junjie Fei; Shengshui Hu; Kwok-Keung Shiu

2011-01-01

7

Nitric oxide and cardiovascular disease.  

PubMed Central

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

McIntyre, M.; Dominiczak, A. F.

1997-01-01

8

A novel fiber optic biosensor for nitric oxide determination based on vicinal diaminobenzozcridine fluorescent probe  

NASA Astrophysics Data System (ADS)

A novel fiber optic biosensor for the determination of nitric oxide based on vicinal diaminobenzozcridine (VDABA) fluorescent probe was designed and fabricated. The reaction conditions between VDABA and NO, which include concentration of VDABA, temperature and pH, were studied in-depth. The sensitivity of VDABA for NO detection under the optimum conditions and its optical properties were also investigated. The fluorescence responses were concentration-dependent and a good linear relationship (R2=0.9863) was observed over the range 1.8×10-6 to 9×10-6 mol/L NO, the regression equation was F = 3.8889[NO] (mol/L)+217.2. Besides, a complex sensitive film embedding VDABA in cellulose acetate (CA) was prepared, and a fiber optic NO biosensor was fabricated using this film. Then the change of fluorescence phase shift of this biosensor was studied preliminarily by means of the lock-in technology.

Ding, Liyun; Huang, Lanfen; Huang, Jun; Zhong, Yunming; Fan, Dian

2010-04-01

9

Determination of nitric oxide generation in mammalian neurons using dichlorofluorescin diacetate and flow cytometry  

Microsoft Academic Search

A method for the rapid detection of intracellular nitric oxide (NO) generation in dissociated cerebellar granule cells using dichlorofluorescin (DCFH) and flow cytometry was developed. DCFH can be oxidized specifically by NO and this was assessed by 1) the use of SIN-1 (10 nM-100 ?M), and NO donor, that induced a concentration-dependent increase in dichlorofluorescein (DCF) fluorescence and 2) the

Cecilia Gabriel; Antonio Camins; Francesc X. Sureda; Leticia Aquirre; Elena Escubedo; Mercè Pallàs; Jorge Camarasa

1997-01-01

10

Nitric oxide in invertebrates  

Microsoft Academic Search

Nitric oxide (NO) is considered an important signaling molecule implied in different physiological processes, including nervous\\u000a transmission, vascular regulation, immune defense, and in the pathogenesis of several diseases. The presence of NO is well\\u000a demonstrated in all vertebrates. The recent data on the presence and roles of NO in the main invertebrate groups are reviewed\\u000a here, showing the widespread diffusion

Marco Colasanti; Giorgio Venturini

1998-01-01

11

Determination of nitric oxide using horseradish peroxidase by UV second-order derivative spectrometry.  

PubMed

Based on the reaction of horseradish peroxidase (HRP) with nitric oxide (NO), a novel detection method of NO has been developed. The method uses second-order derivative spectrometry in an anaerobic phosphate buffer solution. The effects of pH and HRP concentration on the determination of NO in HRP system were investigated, and the conditions for the measurements were optimized. Some possible coexisting substances, such as nitrite, nitrate and hydrogen peroxide, were tested. The linear regression equation of standard curve was found to be h = 8.89 x 10(-2)c(NO)-1.56 x 10(-3) with the relevant coefficient of 0.9966 (n = 5) in the NO concentration range of 0.085-1.3 microM. The relative standard deviations were less than 3%. Based on the standard deviation of 5 blank measurements and a signal-to-noise ratio of 3, the detection limit for NO was 0.032 microM. The proposed method was successfully applied to the determination of NO levels in serum samples. PMID:20009336

Qiang, Li; Zhou, Jie

2009-12-01

12

Analytical method for determination of nitric oxide in zebrafish larvae: toxicological and pharmacological applications.  

PubMed

Zebrafish are currently used at various stages of the drug discovery process and can be a useful and cost-effective alternative to some mammalian models. Nitric oxide (NO) plays an important role in physiology of zebrafish. The availability of appropriate analytical techniques to quantify the NO is crucial for studying its role in physiological and pathological conditions. This work aimed at establishing a high-performance liquid chromatography method for determination of NO levels in zebrafish larvae. Attempts were also made to assess the normal levels of NO at the first days postfertilization and the possible changes under pathological conditions. The method validation was quantitatively evaluated in terms of sensitivity, specificity, precision, accuracy, linearity, and recovery. NO levels from zebrafish larvae at the first days postfertilization and larvae challenged to N(G)-nitro-L-arginine methyl ester, sodium nitroprusside, Escherichia coli lipopolysaccharide, and copper sulfate were analyzed. The samples were derivatized with 2,3-diaminonaphthalene, and fluorescence detection was used for the indirect determination of NO. The method showed a good performance for all validation parameters evaluated and was efficient to monitor changes in NO concentration under physiological and pathophysiological conditions. This method might represent a powerful tool to be applied in NO studies with zebrafish larvae. PMID:22200653

Leite, Carlos Eduardo; Teixeira, Ariane da Cruz; Cruz, Fernanda Fernandes; Concatto, Simone Cervieri; Amaral, Jefferson Henrich; Bonan, Carla Denise; Campos, Maria Martha; Morrone, Fernanda Bueno; Battastini, Ana Maria Oliveira

2011-12-06

13

Fully automatic flow method for the determination of scavenging capacity against nitric oxide radicals.  

PubMed

In the present work, a fluorimetric automatic method based on multisyringe flow injection analysis (MSFIA) was developed for in vitro evaluation of scavenging capacity against nitric oxide (NO) using 4,5-diaminofluorescein (DAF-2) as an NO-selective fluorogenic probe. The MSFIA manifold was assembled to perform the in-line generation of NO and the competitive reaction of putative scavenger molecules and DAF-2 with NO at conditions close to those found in vivo regarding temperature (37 degrees C), pH (7.4), and concentration of NO (less than 1 microM). This approach allowed the evaluation of scavenging capacity against NO by endogenous antioxidant molecules, pharmaceutical compounds, and human plasma. IC(50) values were calculated for rutin (1.30 +/- 0.02 microM, positive control), cysteine (321 +/- 8 microM), reduced glutathione (1106 +/- 93 microM), uric acid (134 +/- 12 microM), dipyrone (1.36 +/- 0.06 microM), and captopril (363 +/- 28 microM). A high degree of automation was attained as the successive dilution of antioxidant standard solutions required for IC(50) assessment was performed automatically, in a dilution chamber placed in the flow system. A determination throughput of 16 h(-1) and a good precision were attained (relative standard deviation between 1.6 and 9.0%), fostering the application of the proposed method to routine/screening analysis of scavenging capacity against NO. PMID:20563794

Ribeiro, Joana P N; Magalhães, Luís M; Segundo, Marcela A; Reis, Salette; Lima, José L F C

2010-06-20

14

A multiwall carbon nanotubes film-modified carbon fiber ultramicroelectrode for the determination of nitric oxide radical in liver mitochondria  

Microsoft Academic Search

A novel chemically modified electrode based on the multiwall carbon nanotubes (MWNTs) film-coated carbon fiber ultramicroelectrode (CFUE) has been described for the determination of nitric oxide radical (·NO). The electrochemical behaviors of MWNTs-modified CFUE have been characterized in 0.2 mmol L?1 K4Fe(CN)6 and 0.1 mol L?1 KCl solution. The Nafion film was used to avoid some electroactive interferences. The amount

Yazhen Wang; Qing Li; Shengshui Hu

2005-01-01

15

Demystified ... Nitric oxide  

PubMed Central

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

Stuart-Smith, K

2002-01-01

16

Nitric oxide in the lung  

Microsoft Academic Search

Nitric oxide is produced by many cell types in the lung and plays an important physiologic role in the regulation of pulmonary vasomotor tone by several known mechanisms. Nitric oxide stimulates soluble guanylyl cyclase, resulting in increased levels of cyclic GMP in lung smooth muscle cells. The gating of K+ and Ca2+ channels by cyclic GMP binding is thought to

Barry Weinberger; Diane E. Heck; Debra L. Laskin; Jeffrey D. Laskin

1999-01-01

17

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

Microsoft Academic Search

BACKGROUND: The diverse physiological and pathological role of nitric oxide in innate immune defenses against many intra and extracellular pathogens, have led to the development of various methods for determining nitric oxide (NO) synthesis. NO metabolites, nitrite (NO2-) and nitrate (NO3-) are produced by the action of an inducible Anopheles culicifacies NO synthase (AcNOS) in mosquito mid-guts and may be

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

2008-01-01

18

Nitric oxide and cancer  

PubMed Central

Nitric oxide (NO) is a lipophilic, highly diffusible and short-lived physiological messenger which regulates a variety of important physiological responses including vasodilation, respiration, cell migration, immune response and apoptosis. NO is synthesized by three differentially gene-encoded NO synthase (NOS) in mammals: neuronal NOS (nNOS or NOS-1), inducible NOS (iNOS or NOS-2) and endothelial NOS (eNOS or NOS-3). All isoforms of NOS catalyze the reaction of L-arginine, NADPH and oxygen to NO, L-citrulline and NADP. NO may exert its cellular action by cGMP-dependent as well as by cGMP-independent pathways including postranslational modifications in cysteine (S-nitrosylation or S-nitrosation) and tyrosine (nitration) residues, mixed disulfide formation (S-nitrosoglutathione or GSNO) or promoting further oxidation protein stages which have been related to altered protein function and gene transcription, genotoxic lesions, alteration of cell-cycle check points, apoptosis and DNA repair. NO sensitizes tumor cells to chemotherapeutic compounds. The expression of NOS-2 and NOS-3 has been found to be increased in a variety of human cancers. The multiple actions of NO in the tumor environment is related to heterogeneous cell responses with particular attention in the regulation of the stress response mediated by the hypoxia inducible factor-1 and p53 generally leading to growth arrest, apoptosis or adaptation.

Muntane, Jordi; la Mata, Manuel De

2010-01-01

19

Nitric oxide synthase in invertebrates.  

PubMed

The gas nitric oxide is now recognized as an important signalling molecule that is synthesized from L-arginine by the enzyme nitric oxide synthase. This enzyme can be localized by different methods, including immunocytochemistry and the histochemical reaction for NADPH diaphorase. It has been demonstrated in various vertebrate cells and tissues, and recently several studies dealing with the production of nitric oxide in invertebrates have been published. Diploblastic animals, flatworms and nematodes seem to lack NADPH diaphorase activity but it has been found in the rest of the phyla studied. The most frequently reported sites for the production of nitric oxide are the central and peripheral nervous systems and, in primitive molluscs, the muscle cells. In insects, it has also been described in the Malpighian tubules. The roles of nitric oxide in invertebrates are closely related to the physiological actions described in vertebrates, namely, neurotransmission, defence, and salt and water balance. The recent cloning of the first nitric oxide synthase from an invertebrate source could open interesting avenues for further studies. PMID:8575940

Martínez, A

1995-10-01

20

Nitric oxide nanoparticles  

PubMed Central

Nitric oxide (NO) is a critical component of host defense against invading pathogens; however, its therapeutic utility is limited due to a lack of practical delivery systems. Recently, a NO-releasing nanoparticulate platform (NO-np) was shown to have in vitro broad-spectrum antimicrobial activity and in vivo pre-clinical efficacy in a dermal abscess model. To extend these findings, both topical (TP) and intralesional (IL) NO-np administration was evaluated in a MRSA intramuscular murine abscess model and compared with vancomycin. All treatment arms accelerated abscess clearance clinically, histologically, and by microbiological assays on both days 4 and 7 following infection. However, abscesses treated with NO-np via either route demonstrated a more substantial, statistically significant decrease in bacterial survival based on colony forming unit assays and histologically revealed less inflammatory cell infiltration and preserved muscular architecture. These data suggest that the NO-np may be an effective addition to our armament for deep soft tissue infections.

Schairer, David O.; Martinez, Luis R.; Blecher, Karin; Chouake, Jason S.; Nacharaju, Parimala; Gialanella, Philip; Friedman, Joel M.; Nosanchuk, Joshua D.; Friedman, Adam J.

2012-01-01

21

Iridium oxide and palladium modified nitric oxide microsensor  

Microsoft Academic Search

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

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

1999-01-01

22

A kinetic platform to determine the fate of nitric oxide in Escherichia coli.  

PubMed

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

2013-05-02

23

Direct single cell determination of nitric oxide synthase related metabolites in identified nitrergic neurons.  

PubMed

The biochemical characterization of individual nitrergic (NO releasing) neurons is a non-trivial task both in vertebrate and invertebrate preparations. In spite of numerous efforts, there are limited data related to intracellular concentrations of essential metabolites involved in NO synthesis and degradation. This situation creates controversies in both identification of nitrergic neurons and the selection of reliable reporters of NOS activity in heterogeneous cell populations. We take advantage of identified neurons from the pulmonate mollusc Lymnaea stagnalis to perform direct single cell microanalysis of intracellular concentrations of the major nitric oxide synthase (NOS) related metabolites such as arginine, citrulline, argininosuccinate, NO(2)(-),and NO(3)(-). Capillary electrophoresis protocols have been developed to quantitate levels of these metabolites in single identified neurons from the buccal, cerebral, and pedal ganglia using laser-induced fluorescence and conductivity detection. The limits of detection (LODs) for arginine (Arg) and citrulline (Cit) are 84 amol (11nM) and 110 amol (15 nM), respectively, and LODs for NO(2)(-)and NO(3)(-) are <200 amol (<10nM) each. We report that intracellular concentrations of NOS related metabolites are in the millimolar range and less than 1% of a single cell is required for microchemical analysis. From four cell types tested, only the esophageal motoneuron B2 contains active NOS, and they also contain surprisingly high nitrite levels (up to 5mM) compared to other neurons tested (peptidergic B4, dopaminergic RPeD1, and serotonergic CGC). These B2 neurons also exhibit an Arg/Cit ratio susceptible to the selective NOS inhibitor l-iminoethyl-N-ornithine whereas others neurons do not even though they all may contain NOS transcripts. On the contrary, we found that absolute concentrations of other NOS related metabolites including nitrates are not reliable markers of NOS activity and demonstrate the need for multiple assays for NOS activity. PMID:15811510

Moroz, Leonid L; Dahlgren, Robin L; Boudko, Dmitry; Sweedler, Jonathan V; Lovell, Peter

2005-04-01

24

49 CFR 173.337 - Nitric oxide.  

Code of Federal Regulations, 2010 CFR

... 2 2010-10-01 2010-10-01 false Nitric oxide. 173.337 Section 173.337 Transportation...Gases; Preparation and Packaging § 173.337 Nitric oxide. (a) Nitric oxide must be packaged in cylinders conforming to...

2010-10-01

25

49 CFR 173.337 - Nitric oxide.  

Code of Federal Regulations, 2010 CFR

... 2 2009-10-01 2009-10-01 false Nitric oxide. 173.337 Section 173.337 Transportation...Gases; Preparation and Packaging § 173.337 Nitric oxide. (a) Nitric oxide must be packaged in cylinders conforming to...

2009-10-01

26

Salivary contribution to exhaled nitric oxide  

Microsoft Academic Search

Dietary and metabolic nitrate is distributed from the blood to the saliva by active uptake in the salivary glands, and is reduced to nitrite in the oral cavity by the action of certain bacteria. Since it has been reported that nitric oxide may be formed nonenzymatically from nitrite this study aimed to determine whether salivary nitrite could influence measurements of

W. Zetterquist; C. Pedroletti; J. O. n. Lundberg; K. Alving

1999-01-01

27

Flavonoids as Scavengers of Nitric Oxide Radical  

Microsoft Academic Search

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

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

1995-01-01

28

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

29

Nitric oxide, a biological effector  

Microsoft Academic Search

Nitric oxide has been used for more than 20 years as an electron paramagnetic resonance probe of oxygen binding sites in oxygen-carriers and oxygen-metabolizing metalloenzymes. The high reactivity of NO with oxygen and the superoxide anion and its high affinity for metalloproteins led biochemists to consider NO as a highly toxic compound for a living cell. This assertion has recently

Y. Henry; C. Ducrocq; J.-C. Drapier; D. Servent; C. Pellat; A. Guissani

1991-01-01

30

Nitric oxide synthases and osteoarthritis  

Microsoft Academic Search

The production of nitric oxide (NO) by chondrocytes is increased in human osteoarthritis. The excessive production of NO inhibits\\u000a matrix synthesis and promotes its degradation. Furthermore, by reacting with oxidants such as superoxide anion, NO promotes\\u000a cellular injury and renders the chondrocyte susceptible to cytokine-induced apoptosis. Thus, NO produced by activated chondrocytes\\u000a in diseased cartilage may modulate disease progression in

Jose U. Scher; Michael H. Pillinger; Steven B. Abramson

2007-01-01

31

Nitric oxide and oxygen radicals: a question of balance  

Microsoft Academic Search

The production of superoxide and nitric oxide individually has been associated with the development of several diseases but only recently has it been realised that interactions between them may also be important in disease pathology. The central hypothesis which is emerging is that the balance between nitric oxide and superoxide generation is a critical determinant in the aetiology of many

Victor Darley-Usmar; Helen Wiseman; Barry Halliwell

1995-01-01

32

Manganese potentiates nitric oxide production by microglia.  

PubMed

Manganese toxicity has been associated with clinical symptoms of neurotoxicity which are similar to the symptoms observed in Parkinson's disease. Earlier reports indicated that reactive microglia was present in the substantia nigra of patients with Parkinson's disease. Using N9 microglial cells, the current study was designed to determine whether high levels of manganese were associated with microglial activation. Results indicated that manganese significantly increased the bacterial lipopolysaccharide-induced nitric oxide production. This potent activity of manganese was not shared by other transition metals tested, including iron, cobalt, nickel, copper and zinc. Immunohistochemical staining and Western blot analysis indicated that manganese increased the cellular production of inducible nitric oxide synthase. Northern blot analysis indicated that manganese likely increased iNOS gene transcription since this agent increased the mRNA level of the inducible nitric oxide synthase. In contrast to other transition metals tested, manganese did not appear to be cytotoxic to microglial cells. These results suggested that manganese could induce sustained production of neurotoxic nitric oxide by activated microglial cells, which might cause detrimental consequences to surrounding neurons. PMID:10320780

Chang, J Y; Liu, L Z

1999-05-01

33

Nitric oxide and gastric relaxation.  

PubMed

Pentagastrin enhanced the volume increase caused by isobaric gastric distension in conscious dogs. This effect could be abolished by inhibitors of acid secretion and mimicked by histamine. The increased compliance after pentagastrin was not affected by L-nitroarginine (L-NNA), a blocker of nitric oxide (NO) synthase. L-NNA itself reduced the volume increases caused by isobaric gastric distension. Intralipid administration into the duodenum led to a gastric relaxation sensitive to inhibition by L-NNA. The inhibitory effect of L-NNA was partially reversed by L-arginine. Pentagastrin induces a gastric relaxation via a mechanism that involves gastric secretion but not nitric oxide, whereas intraduodenal intralipid induces a gastric relaxation via a NO-dependent mechanism. PMID:7995223

Schuurkes, J A; Meulemans, A L

1994-12-01

34

How Cytotoxic is Nitric Oxide?  

Microsoft Academic Search

Nitric oxide (NO) shows an unusual divergence of action, being utilised both as a physiological signalling molecule, and as a toxic mediator. NO-mediated cellular injury may arise by a variety of mechanisms, including disruption of mitochondrial respiration, enzyme inhibition, lipid peroxidation and genetic mutation. Toxicity is largely mediated via intermediates such as N2O3 and peroxynitrite, arising from the reaction of

M. P. Gordge

1998-01-01

35

Nitric Oxide and Bronchial Hyperresponsiveness  

Microsoft Academic Search

\\u000a Increasing evidence points to an important role for nitric oxide (NO) in the regulation of pulmonary functions and in pulmonary\\u000a disease [1–4]. NO is present in exhaled air of animals and humans [1, 5]. The respiratory tract, nerves endothelial cells, vascular and airway smooth muscle cells, inflammatory cells (macrophages,\\u000a neutrophils, mast cells) and the airway epithelium are sources for NO

Frans P. Nijkamp; Gert Folkerts

36

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.

Matthys, K. E.

1997-01-01

37

The Production of Nitric Oxide In Ammonia Oxidation Flames  

Microsoft Academic Search

Product compositions for ammonia\\/oxygen and ammonia\\/oxygen\\/nitrogen premixed, atmospheric pressure flames were experimentally determined. Nitric oxide concentrations in excess of equilibrium levels were observed over the entire experimental equivalence ratio range of 0.40 to 1.85.

R. F. SAWYER; W. J. McLEAN; C. M. MAES JR

1972-01-01

38

Whole Body Nitric Oxide Synthesis in Healthy Men Determined from [15N]arginine-to- [15N]citrulline Labeling  

Microsoft Academic Search

The rates of whole body nitric oxide (NO) synthesis, plasma arginine flux, and de novo arginine synthesis and their relationships to urea production, were examined in a total of seven healthy adults receiving an L-amino acid diet for 6 days. NO synthesis was estimated by the rate of conversion of the [15N]guanidino nitrogen of arginine to plasma [15N]ureido citrulline and

Leticia Castillo; Louis Beaumier; Alfred M. Ajami; Vernon R. Young

1996-01-01

39

Mechanisms for nitric oxide synthesis in plants  

Microsoft Academic Search

The discovery that nitric oxide (NO) acts as a signal fundamentally shifted our understanding of free rad- icals from toxic by-products of oxidative metabolism to key regulators of cellular functions. This discovery has led to intense investigation into the synthesis of NO in both animals and plants. Nitric oxide synthases (NOS) are the primary sources of NO in animals and

Nigel M. Crawford

2006-01-01

40

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

41

Quasi-simultaneous determination of antioxidative activities against superoxide anion and nitric oxide by a combination of sequential injection analysis and flow injection analysis with chemiluminescence detection  

Microsoft Academic Search

A method that combines sequential injection analysis (SIA), flow injection analysis and chemiluminescence (CL) detection was\\u000a developed for the quasi-simultaneous determination of antioxidative activities against superoxide anion $$\\u000a{\\\\left( {{\\\\text{O}}^{ - }_{2} } \\\\right)}\\u000a$$ and nitric oxide (NO). The antioxidative activity was expressed as the decrease in luminol CL intensity caused by the quenching\\u000a of $${\\\\text{O}}^{ - }_{2} $$

Aoi Miyamoto; Kuniko Nakamura; Naoya Kishikawa; Yoshihito Ohba; Kenichiro Nakashima; Naotaka Kuroda

2007-01-01

42

21 CFR 868.5165 - Nitric oxide administration apparatus.  

Code of Federal Regulations, 2010 CFR

...2009-04-01 2009-04-01 false Nitric oxide administration apparatus. 868...Therapeutic Devices § 868.5165 Nitric oxide administration apparatus. (a) Identification. The nitric oxide administration apparatus is a...

2009-04-01

43

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...Therapeutic Devices § 868.5165 Nitric oxide administration apparatus. (a) Identification. The nitric oxide administration apparatus is a...

2010-04-01

44

Role of oxidative stress and nitric oxide in atherothrombosis  

PubMed Central

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

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

2008-01-01

45

Asthma, viruses, and nitric oxide.  

PubMed

Over the last two decades there has been a worldwide increase in the morbidity and mortality associated with asthma, a chronic inflammatory disease of the airways. There is a growing body of evidence that suggests there is an association between upper respiratory viral infections, particularly rhinovirus infections, and asthma exacerbations. Virally induced airways hyperreactivity has been associated with elevated numbers of inflammatory cells in the bronchial mucosa. Upon virus infection, respiratory epithelial cells produce proinflammatory cytokines, including IL-6, IL-8, RANTES, and GM-CSF, which could contribute to the increased inflammatory cell recruitment noted in the airways. Whether or not a viral infection triggers an asthma attack may depend upon many factors, including the types of inflammatory cells recruited to the airways, the viral load, and variations in the host antiviral response. There is evidence to support the idea that eosinophils from asthmatic and symptomatic atopic subjects may be primed to respond to chemotactic cytokines produced by infected epithelial cells. Rhinovirus infections may therefore enhance airway eosinophilia in asthmatics, leading to airway hyperresponsiveness and impaired pulmonary function. Nitric oxide is a potent inhibitor of both rhinovirus-induced cytokine production and viral replication and may play an important role in the host response to viral infections. Based upon these observations, we speculate that nitric oxide donors may represent a novel therapeutic approach for the treatment of rhinovirus infections and viral exacerbations of asthma. PMID:10193439

Sanders, S P

1999-03-01

46

Nitric oxide production by arsenite.  

PubMed

Arsenic can either enhance or reduce nitric oxide (NO) production, depending on the type of cell, the species and dose of arsenical tested. The mechanisms of how arsenic increases or decreases NO production remain unclear. Because NO is associated with many pathological conditions, it is conceivable that in those arsenic-target tissues, the NO production may be upregulated by continuous arsenic exposure, and a prolonged over-production of NO may cause inflammation hence a pathological condition. A prolonged interference with the normal physiological level of NO may also play a role in the initiation, promotion, and progression of arsenic-related human cancers. Suppression of NO production has been shown to reduce arsenite-induced oxidative DNA damage, inhibition of pyrimidine dimer excision, and micronuclei. However, a completely reliable story on how NO is involved in arsenic-related human disease is still lacking. PMID:14643419

Gurr, Jia-Ran; Yih, Ling-Huei; Samikkannu, Thangavel; Bau, Da-Tian; Lin, Shu-Yu; Jan, Kun-Yan

2003-12-10

47

Role of exhaled nitric oxide in asthma  

Microsoft Academic Search

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

Deborah H Yates

2001-01-01

48

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

49

FORUM The Toxicology of Inhaled Nitric Oxide  

Microsoft Academic Search

Inhaled nitric oxide is a targeted pulmonary vasodilator that improves clinical outcomes for newborn patients with persistent pulmonary hypertension of the newborn, and may be effective in treating some premature patients with acute respiratory distress syndrome or lung disease of prematurity. Nitric oxide is now recognized as playing an important role in the regulation of di- verse physiological processes. However,

Barry Weinberger; Debra L. Laskin; Diane E. Heck; Jeffrey D. Laskin

50

Nitric oxide evolution and perception.  

PubMed

Various experimental data indicate signalling roles for nitric oxide (NO) in processes such as xylogenesis, programmed cell death, pathogen defence, flowering, stomatal closure, and gravitropism. However, it still remains unclear how NO is synthesized. Nitric oxide synthase-like activity has been measured in various plant extracts, NO can be generated from nitrite via nitrate reductase and other mechanisms of NO generation are also likely to exist. NO removal mechanisms, for example, by reaction with haemoglobins, have also been identified. NO is a gas emitted by plants, with the rate of evolution increasing under conditions such as pathogen challenge or hypoxia. However, exactly how NO evolution relates to its bioactivity in planta remains to be established. NO has both aqueous and lipid solubility, but is relatively reactive and easily oxidized to other nitrogen oxides. It reacts with superoxide to form peroxynitrite, with other cellular components such as transition metals and haem-containing proteins and with thiol groups to form S-nitrosothiols. Thus, diffusion of NO within the plant may be relatively restricted and there might exist 'NO hot-spots' depending on the sites of NO generation and the local biochemical micro-environment. Alternatively, it is possible that NO is transported as chemical precursors such as nitrite or as nitrosothiols that might function as NO reservoirs. Cellular perception of NO may occur through its reaction with biologically active molecules that could function as 'NO-sensors'. These might include either haem-containing proteins such as guanylyl cyclase which generates the second messenger cGMP or other proteins containing exposed reactive thiol groups. Protein S-nitrosylation alters protein conformation, is reversible and thus, is likely to be of biological significance. PMID:17975211

Neill, Steven; Bright, Jo; Desikan, Radhika; Hancock, John; Harrison, Judith; Wilson, Ian

2007-11-01

51

Intestinal Preconditioning Is Mediated by a Transient Increase in Nitric Oxide  

Microsoft Academic Search

The effect of ischemic preconditioning on the intestine, as well the implication of nitric oxide and prostacyclin in this process has been evaluated. Thus, intestinal ischemia-reperfusion was induced in rats, and the protection conferred by previous preconditioning was evaluated. In addition, the effect of nitric oxide inhibition and the administration of nitric oxide were determined. Results show that the increases

G. Hotter; D. Closa; M. Prados; L. Fernández-Cruz; N. Prats; E. Gelp??; J. Roselló-Catafau

1996-01-01

52

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.

Hetrick, Evan M.

2013-01-01

53

Airway nitric oxide in microgravity  

NASA Astrophysics Data System (ADS)

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

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

2005-10-01

54

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.

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

2011-01-01

55

Nitric oxide in primary ciliary dyskinesia.  

PubMed

Nitric oxide is continually synthesised in the respiratory epithelium and is upregulated in response to infection or inflammation. Primary ciliary dyskinesia (PCD) is characterised by recurrent sinopulmonary infections due to impaired mucociliary clearance. Despite chronic infections, nasal nitric oxide in such patients is markedly reduced and is used as a screening test for this condition. These low levels were first described >15 yrs ago but the underlying mechanisms have yet to be fully elucidated. We review epithelial nitric oxide synthesis, release and measurement in the upper airways with particular reference to PCD. The key hypotheses that have been proposed to explain the low nitric oxide levels in this condition are explored and the potential benefits of augmenting airway nitric oxide levels are considered. Further work in these patients clarifying both whether the respiratory epithelium is able to biosynthesise normal levels of nitric oxide and the role played by abnormalities in the anatomy of the paranasal sinuses is essential. While nitric oxide augmentation is unlikely to be beneficial in common PCD phenotypes, it has potential in the treatment of secondary dyskinesias and may also improve treatment of bacterial infections, particularly where biofilms are implicated. PMID:22408195

Walker, Woolf T; Jackson, Claire L; Lackie, Peter M; Hogg, Claire; Lucas, Jane S

2012-03-09

56

Nitric oxide synthase in human placenta.  

PubMed

Nitric oxide synthase is demonstrated immunohistochemically in the cytosol, on granules, and on syncytiotrophoblasts membranes. The enzyme is also detected on placental villous stroma cells, and on endothelial cells. The histochemical staining method NADPH-diaphorase stains the syncytiotrophoblasts intensely, and stroma cells more weakly. Membranes of syncytiotrophoblasts immobilized on nitrocellulose paper are also stained by NADPH-diaphorase, and by antisera to nitric oxide synthase. Oxidases of sex steroid synthesis do, however, influence placental trophoblasts and there are discrepancies in the staining pattern of endothelial cells. Caution should therefore be exercised when using NADPH-diaphorase as a staining method for nitric oxide synthase in placenta. PMID:7522475

Kristoffersen, E K; Ulvestad, E

1994-07-01

57

C-nitroso donors of nitric oxide.  

PubMed

A complete understanding of the biological activity of nitric oxide (NO) is complicated by the different reactivity profiles of its various species and by the often complex decomposition behavior of the NO progenitors in common use. Here, we report that appropriately substituted C-nitroso compounds act solely as donors of neutral nitric oxide through a first-order homolytic C-N bond scission to release up to 88% nitric oxide in DMSO at 25 degrees C. The reaction produces a carbon radical, and the yield of nitric oxide is dependent on the availability of radical traps. C-Nitroso compounds are sources of biologically active neutral NO and display potent NO bioactivity in a rabbit aortic ring assay. PMID:19146387

Chakrapani, Harinath; Bartberger, Michael D; Toone, Eric J

2009-02-20

58

Nitric Oxide Gene Therapy for Prostate Cancer.  

National Technical Information Service (NTIS)

Traditional therapies for advanced prostate cancer are unable to cure a majority of patients. One approach to therapy is over-production of inducible nitric oxide synthase (iNOS) within the tumor by injecting replication defective adenovirus containing th...

E. Armour

1999-01-01

59

Nitric Oxide Gene Therapy for Prostate Cancer.  

National Technical Information Service (NTIS)

Traditional therapies for advanced prostate cancer are unable to cure a majority of patients. An approach to therapy we have tested involves production of nitric oxide (NO) by introduction of replication defective adenovirus containing the DNA sequences f...

E. P. Armour

2001-01-01

60

Electron beam fluorescence measurements of nitric oxide  

Microsoft Academic Search

Measurement of nitric oxide in hypersonic flows is of interest for the operation of combustion- and shock-driven wind tunnels and in the high-temperature air chemistry produced by high-Mach-number shock waves during hypersonic flight. The electron beam fluorescence spectrum from nitric oxide in argon background gas was experimentally studied as a function of electron beam energy. Spectrally resolved fluorescence from the

Robert J. Cattolica

1989-01-01

61

Nitric oxide and excitation–contraction coupling  

Microsoft Academic Search

Excitation–contraction (EC) coupling is driven by an ion-channel-mediated calcium cycle that produces myofilament contraction and relaxation. Even though nitric oxide synthases (NOS) were definitively described within the heart a decade ago, the role that nitric oxide (NO) plays in cardiac regulation remains highly controversial. There is a growing consensus, however, that NO modulates the activity of several key calcium channels

Joshua M Hare

2003-01-01

62

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

63

Antifibrotic Role of Inducible Nitric Oxide Synthase  

Microsoft Academic Search

Long-term treatment in rats with l-NAME, an isoform-non-specific inhibitor of nitric oxide synthase (NOS), leads to fibrosis of the heart and kidney, suggesting that nitric oxide (NO) may play a role in preventing tissue fibrosis. In this process, a likely target of NO is the quenching of reactive oxygen species (ROS) through peroxynitrite formation, and one possible source for this

M. G. Ferrini; D. Vernet; T. R. Magee; A. Shahed; A. Qian; J. Rajfer; N. F. Gonzalez-Cadavid

2002-01-01

64

Effect of Nitric Oxide on Anammox Bacteria?  

PubMed Central

The effects of nitrogen oxides on anammox bacteria are not well known. Therefore, anammox bacteria were exposed to 3,500 ppm nitric oxide (NO) in the gas phase. The anammox bacteria were not inhibited by the high NO concentration but rather used it to oxidize additional ammonium to dinitrogen gas under conditions relevant to wastewater treatment.

Kartal, Boran; Tan, Nico C. G.; Van de Biezen, Erwin; Kampschreur, Marlies J.; Van Loosdrecht, Mark C. M.; Jetten, Mike S. M.

2010-01-01

65

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

66

Nitric oxide and salmonella pathogenesis.  

PubMed

Nitric oxide (NO) and its congeners contribute to the innate immune response to Salmonella. This enteric pathogen is exposed to reactive nitrogen species (RNS) in the environment and at different anatomical locations during its infectious cycle in vertebrate hosts. Chemical generation of RNS enhances the gastric barrier to enteropathogenic bacteria, while products of the Salmonella pathogenicity island 1 type III secretion system and Salmonella-associated molecular patterns stimulate transcription of inducible NO synthase (iNOS) by cells of the mononuclear phagocytic cell lineage. The resulting NO, or products that arise from its interactions with oxygen (O(2)) or iron and low-molecular weight thiols, are preferentially bacteriostatic against Salmonella, while reaction of NO and superoxide ([Formula: see text]) generates the bactericidal compound peroxynitrite (ONOO-). The anti-Salmonella activity of RNS emanates from the modification of redox active thiols and metal prosthetic groups of key molecular targets of the electron transport chain, central metabolic enzymes, transcription factors, and DNA and DNA-associated proteins. In turn, Salmonella display a plethora of defenses that modulate the delivery of iNOS-containing vesicles to phagosomes, scavenge and detoxify RNS, and repair biomolecules damaged by these toxic species. Traditionally, RNS have been recognized as important mediators of host defense against Salmonella. However, exciting new findings indicate that Salmonella can exploit the RNS produced during the infection to foster virulence. More knowledge of the primary RNS produced in response to Salmonella infection, the bacterial processes affected by these toxic species, and the adaptive bacterial responses that protect Salmonella from nitrosative and oxidative stress associated with NO will increase our understanding of Salmonella pathogenesis. This information may assist in the development of novel therapeutics against this common enteropathogen. PMID:21833325

Henard, Calvin A; Vázquez-Torres, Andrés

2011-04-20

67

Nitric Oxide and Salmonella Pathogenesis  

PubMed Central

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

Henard, Calvin A.; Vazquez-Torres, Andres

2011-01-01

68

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

69

Exhaled Nitric Oxide Production by Nitric Oxide Synthase-deficient Mice  

Microsoft Academic Search

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

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

2000-01-01

70

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

NASA Astrophysics Data System (ADS)

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

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

2006-11-01

71

Rate of Nitric Oxide Scavenging by hemoglobin bound to haptoglobin  

PubMed Central

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

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

2008-01-01

72

Inhaled Nitric Oxide Delivery by Anesthesia Machines  

Microsoft Academic Search

Inhaled nitric oxide (NO) is a selective pulmonary vaso- dilator used to treat intraoperative pulmonary hyper- tension and hypoxemia. In contrast to NO delivered by critical care ventilators, NO delivered by anesthesia machines can be complicated by rebreathing. We eval- uated two methods of administering NO intraopera- tively: via the nitrous oxide (N2O) flowmeter and via the INOvent (Datex-Ohmeda, Madison,

Patrizia Ceccarelli; Luca M. Bigatello; Dean Hess; Jean Kwo; Luis Melendez

2000-01-01

73

Using nitric oxide to treat tendinopathy.  

PubMed

Nitric oxide (NO) is a small free radical generated by a family of enzymes, the nitric oxide synthases (NOSs). Following injury to a tendon, NO is induced by all three isoforms of NOS and NOS activity is also upregulated in tendinopathy. In animal models when NOS activity is inhibited by competitive inhibitors of NOS, tendon healing is reduced. When additional NO is added, tendon healing is enhanced. In humans, in three randomised clinical trials, we have shown that NO delivered via a transdermal patch enhances the subjective and objective recovery of patients with tennis elbow, Achilles tendinosis and supraspinatus tendinosis. PMID:17289859

Murrell, George A C

2007-02-08

74

Airway nitric oxide in Duchenne muscular dystrophy.  

PubMed

The expression of muscle membrane-associated neuronal nitric oxide synthase (NOS1) is significantly impaired in Duchenne muscular dystrophy. Mean (+/- SEM) exhaled NO in 13 male patients with Duchenne muscular dystrophy was significantly lower than in 11 healthy age-matched male control subjects (7.5 +/- 1.4 vs 16.6 +/- 3.2 parts per billion, P <.02) or 17 adult male control subjects (18.5 +/- 1.8 parts per billion, P <.001). These findings provide indirect evidence that NOS1 contributes significantly to fractional exhaled nitric oxide in healthy children. PMID:12091865

Straub, Volker; Ratjen, Felix; Amthor, Helge; Voit, Thomas; Grasemann, Hartmut

2002-07-01

75

Laser studies of nitric oxide clusters  

SciTech Connect

Molecular clusters of nitric oxide have been formed in supersonic jets and studied using laser techniques. Positive cluster ions are produced by two-photon ionization and characterized by time-of-flight mass spectroscopy. Negative cluster ions are formed by Rydberg electron transfer from laser-excited rubidium atoms and likewise detected by time-of-flight techniques. Many cluster ion distributions exhibit intensity anomalies ( magic numbers'') which reflect special stability due to structural, electronic, or dynamic factors. Here we discuss the formation and characterization of both positive and negative ions of nitric oxide clusters, (NO)[sup [plus minus

Carman, H.S. Jr.; Desai, S.R.; Feigerle, C.S.; Miller, J.C. (Chemical Physics Section, Oak Ridge National Laboratory, P.O. Box 2008, Oak Ridge, Tennessee 37831-6125 (United States))

1993-10-20

76

21 CFR 862.3080 - Breath nitric oxide test system.  

Code of Federal Regulations, 2013 CFR

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

2013-04-01

77

Nitric Oxide Formation in Combustion Processes with Strong Recirculation.  

National Technical Information Service (NTIS)

The principal objective of the combustion experiments was to obtain information on the nitric oxide formation process in a continuous flow combustion system in which the flame is stabilized by recirculation. Specifically, the factors affecting nitric oxid...

C. T. Bowman L. S. Cohen M. N. Director

1973-01-01

78

MULTIPLE SCLEROSIS: PSYCHOSOMATIC ORIGINS AND THE ROLE OF NITRIC OXIDE  

Microsoft Academic Search

Two signs that endothelial nitric oxide may be chronically depleted in multiple sclerosis are that patients tend to be very heat-sensitive, and their platelets are sticky. Sensitivity to stress may reveal depletion of the parasympathetic transmitter neuronal nitric oxide. Other reasons to suspect endothelial nitric oxide depletion in multiple sclerosis are apparent deficiencies of sex hormones, magnesium, and zinc. Estrogen,

Peter Good

79

Localization of Nitric Oxide Synthase in the Adult Rat Brain  

Microsoft Academic Search

The distribution of the immunoreactivity to nitric oxide synthase has been examined from rostral to caudal areas of the rat central nervous system using light microscopy. Endogenous nitric oxide synthase was located using a specific polyclonal antiserum, produced against affinity purified nitric oxide synthase from whole rat brain, following the avidin-biotin peroxidase procedure. Immunoreactive cell bodies and processes showed a

J. Rodrigo; D. R. Springall; O. Uttenthal; M. L. Bentura; F. Abadia-Molina; V. Riveros-Moreno; R. Martinez-Murillo; J. M. Polak; S. Moncada

1994-01-01

80

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

81

Abnormalities in Nitric Oxide and Its Derivatives in Lung Cancer  

Microsoft Academic Search

Rationale: A cellular prooxidant state promotes cells to neoplastic growth, in part because of modification of proteins and their func- tions. Reactive nitrogen species formed from nitric oxide (NO) or its metabolites, can lead to protein tyrosine nitration, which is ele- vated in lung cancer. Objective: To determine the alteration in these NO derivatives and the role they may play

Fares A. Masri; Suzy A. A. Comhair; Thomas Koeck; Weiling Xu; Allison Janocha; Sudakshina Ghosh; Raed A. Dweik; Joseph Golish; Michael Kinter; Dennis J. Stuehr; Serpil C. Erzurum; Kulwant S. Aulak

2005-01-01

82

Low Nitric Oxide Production in Patients with Chronic Renal Failure  

Microsoft Academic Search

Background: Rats with chronic renal failure have a low nitric oxide (NO) production and a diminished NO excretion. The supplementation of L-arginine has an inhibitory effect on the progression of renal insufficiency. Methods: The present study was designed to determine whether chronic renal failure patients have a low NO production. Plasma and urine nitrate (NO3) and nitrite (NO2), stable metabolites

M. Blum; T. Yachnin; Y. Wollman; T. Chernihovsky; G. Peer; I. Grosskopf; E. Kaplan; D. Silverberg; S. Cabili; A. Iaina

1998-01-01

83

Blood-pressure variability is buffered by nitric oxide  

Microsoft Academic Search

The baroreflex constitutes the only hitherto known buffer of rapid blood pressure oscillations. In order to investigate the influence of nitric oxide (NO) and the sinoaortic and cardiopulmonary baroreflex pathways on the dynamic properties of blood pressure control, we determined the power spectra of 24-h blood pressure time series of conscious dogs. This was done in the intact state (n

Benno Nafz; Armin Just; Harald M. Stau?; Claus D. Wagner; Heimo Ehmke; Hartmut R. Kirchheim; Pontus B. Persson

1996-01-01

84

Electrochemical detection of nitric oxide using polymer modified electrodes  

Microsoft Academic Search

Electrochemical sensors based on chemical surface modification are very attractive because they combine high sensitivity of amperometry with new dimensions of selectivity and stability provided by the surface modifier. This review shows a few strategies employed to facilitate the detection, determination and monitoring of nitric oxide using polymer modified electrodes. Conducting and nonconducting polymer films and composite films are considered.

Aleksander Ciszewski; Grzegorz Milczarek

2003-01-01

85

DMSO: EFFECT ON BLADDER AFFERENT NEURONS AND NITRIC OXIDE RELEASE  

Microsoft Academic Search

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

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

1997-01-01

86

Failure of L-NAME to cause inhibition of nitric oxide synthesis: Role of inducible nitric oxide synthase  

Microsoft Academic Search

We addressed the hypothesis that administration of nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) does not result in a sustained suppression of nitric oxide (NO) synthesis, because of a compensatory expression of inducible nitric oxide synthase (iNOS). L-NAME was administered in the drinking water (0.1–1.0 mg\\/ml) for 7 days to guinea pigs and rats. Nitric oxide synthesis was assessed

M. J. S. Miller; J. H. Thompson; X. Liu; S. Eloby-Childress; H. Sadowska-Krowicka; X-Jing Zhang; D. A. Clark

1996-01-01

87

Urinary Nitric Oxide in Newborns with Infections  

Microsoft Academic Search

Background: Neonatal sepsis is a major problem in newborn nurseries because of the difficulty in early diagnosis and because of the high morbidity and mortality. The objective of the present study was to investigate whether urinary nitric oxide (NO) levels could be useful for the diagnosis of infected newborns. Methods: Newborns with suspected infection according to previously defined criteria between

Ebru Ergenekon; Esin Koç; Güler Özturk

2000-01-01

88

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

89

Reduced Nasal Nitric Oxide in Diffuse Panbronchiolitis  

Microsoft Academic Search

Diffuse panbronchiolitis (DPB) is a pulmonary disease of unknown origin with inflammation in the respiratory bronchioles, bron- chiectasis, and recurrent sinusitis. Patients with DPB suffer from chronic airway infections resulting from mucociliary dysfunction. Whereas a high concentration of nasal nitric oxide (NO) has been documented in healthy subjects, only two diseases are known to reduce nasal NO: primary ciliary dyskinesia

HITOSHI NAKANO; HIROSHI IDE; MASANOBU IMADA; SHINOBU OSANAI; TORU TAKAHASHI; KENJIROU KIKUCHI; JUN IWAMOTO

2000-01-01

90

Nitric Oxide Levels in Disruptive Behavioral Disorder  

Microsoft Academic Search

There are various evidences of the role of nitric oxide (NO) in several neuropsychiatric disorders. However, there is no clinical study which investigated the role of NO in disruptive behavioral disorders (DBD). The aim of this study is to investigate the relation between NO levels and DBD. NO levels were measured in serum from 45 patients diagnosed as having DBD

Fatma Varol Tas; Taner Guvenir; Gultekin Tas; Burcu Cakaloz; Murat Ormen

2006-01-01

91

Summary: Systemic Effects of Inhaled Nitric Oxide  

Microsoft Academic Search

Many effects of inhaled nitric oxide (NO) are not explained by the convention that NO activates pulmonary guanylate cyclase or is inactivated by ferrous deoxy- or oxyheme. Inhaled NO can affect blood flow to a variety of systemic vascular beds, particularly under conditions of ischemia\\/reperfusion. It affects leukocyte adhesion and rolling in the systemic periphery. Inhaled NO therapy can over-

Benjamin Gaston

2006-01-01

92

Nitric oxide and endothelin in pathophysiological settings  

Microsoft Academic Search

The role of the endothelium, is now known to encompass the generation of many potent cytokines which impact endothelial cells, adjacent tissue such as smooth muscle cells, and distant sites in an autocrine, paracrine, and endocrine manner, respectively. This review addresses two of these cytokines, nitric oxide and endothelin, and describes how each effects the functions of endothelial cells, including

Tracy E. Hunley; Shigeki Iwasaki; Toshio Homma; Valentina Kon

1995-01-01

93

Nitric oxide signalling via cytoskeleton in plants  

Microsoft Academic Search

Nitric oxide (NO) in plant cell mediates processes of growth and development starting from seed germination to pollination, as well as biotic and abiotic stress tolerance. However, proper understanding of the molecular mechanisms of NO signalling in plants has just begun to emerge. Accumulated evidence suggests that in eukaryotic cells NO regulates functions of proteins by their post-translational modifications, namely

Alla I. Yemets; Yuliya A. Krasylenko; Dmytro I. Lytvyn; Yarina A. Sheremet; Yaroslav B. Blume

2011-01-01

94

Nitric Oxide Releasing Compositions and Associated Methods.  

National Technical Information Service (NTIS)

Dendritic nitric oxide donors having the formula: (P)-((A)(sub y))(sub x)-((NO)(sub z))(sub q) wherein P is a core that comprises a biocompatible polymer; A is a branching unit monomer that comprises at least one end group capable of reversibly attaching ...

J. L. West L. J. Taite

2005-01-01

95

Nitric oxide in the human respiratory cycle  

Microsoft Academic Search

Interactions of nitric oxide (NO) with hemoglobin (Hb) could regulate the uptake and delivery of oxygen (O2) by subserving the classical physiological responses of hypoxic vasodilation and hyperoxic vasconstriction in the human respiratory cycle. Here we show that in in vitro and ex vivo systems as well as healthy adults alternately exposed to hypoxia or hyperoxia (to dilate or constrict

Timothy J. McMahon; Richard E. Moon; Ben P. Luschinger; Martha S. Carraway; Anne E. Stone; Bryant W. Stolp; Andrew J. Gow; John R. Pawloski; Paula Watke; David J. Singel; Claude A. Piantadosi; Jonathan S. Stamler

2002-01-01

96

The nitric oxide hypothesis of aging  

Microsoft Academic Search

Nitric oxide (NO), generated by endothelial (e) NO synthase (NOS) and neuronal (n) NOS, plays a ubiquitous role in the body in controlling the function of almost every, if not every, organ system. Bacterial and viral products, such as bacterial lipopolysaccharide (LPS), induce inducible (i) NOS synthesis that produces massive amounts of NO toxic to the invading viruses and bacteria,

S. M McCann; J Licinio; M.-L Wong; W. H Yu; S Karanth; V Rettorri

1998-01-01

97

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

98

Nitric oxide flow tagging in unseeded air  

Microsoft Academic Search

A scheme for molecular tagging velocimetry is presented that can be used in air f lows without any kind of seeding. The method is based on the local and instantaneous creation of nitric oxide (NO) molecules from N2 and O2 in the waist region of a focused ArF excimer laser beam. This NO distribution is advected by the f low

Nico Dam; R. J. H. Klein-Douwel; Nanna M. Sijtsema; J. J. ter Meulen

2001-01-01

99

Modulation of nitric oxide synthase by nitric oxide donor compounds in migraine  

Microsoft Academic Search

A controlled study was performed to assess the involvement of the nitric oxide pathway in migraine pathophysiology. Thirteen\\u000a patients with migraine without aura and seven clinically healthy subjects (C) were selected. All of the migraine patients\\u000a were studied both before, during an asymptomatic phase (t\\u000a 0), and 1 h after the administration of 5 mg isosorbide dinitrate, a nitric oxide

P. Martelletti; M. Giacovazzo; S. D’Alò; M. G. Cifone; G. Stirparo; C. Rinaldi

1998-01-01

100

Nitric Oxide in Skeletal Muscle: Inhibition of Nitric Oxide Synthase Inhibits Walking Speed in Rats  

Microsoft Academic Search

Nitric oxide (NO·) is a multifunctional messenger molecule generated by a family of enzymes called the nitric oxide synthases (NOSs). Although NOSs have been identified in skeletal muscle, specifically brain NOS (bNOS) and endothelial NOS (eNOS), their role has not been well clarified. The goals of this investigation were to (1) characterize the immunoreactivity, Ca2+ dependence, and activity of NOS

Min-Xia Wang; Dédée F. Murrell; Csaba Szabo; Russell F. Warren; Maria Sarris; George A. C. Murrell

2001-01-01

101

Role of lipid rafts in ceramide and nitric oxide signaling in the ischemic and preconditioned hearts  

Microsoft Academic Search

Nitric oxide plays a crucial role in myocardial ischemia reperfusion injury as well as in myocardial adaptation to ischemic stress. To understand the dichotomy of nitric oxide behavior in the ischemic myocardium, isolated rat hearts were subjected to ischemia\\/reperfusion protocol. The tissue contents of sphingomyelin (SM), ceramide and sphingosine were determined by high performance thin layer chromatography (HPTLC). The myocardial

Peter Der; Jianhua Cui; Dipak K. Das

2006-01-01

102

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

103

Is nitric oxide the retrograde messenger  

SciTech Connect

Nitric oxide is one of the more bizarre messenger molecules used by cells. Dissolved in the aqueous cellular fluids, it slips right through membranes that would contain other molecules and is so reactive that it disappears within moments of its production. Yet it seems to play an important role in many parts of the body, including the brain. Four years ago it was shown to trigger blood vessel relaxation, and its discovery in the brain the following year left neuroscientists speculating about a number of roles it may play there. Now, in a collection of data comes evidence for a particularly exciting role: nitric oxide may be a key chemical player in the storage of memories in the brain.

Not Available

1991-11-29

104

Nitroreductase-activated nitric oxide (NO) prodrugs.  

PubMed

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

Sharma, Kavita; Sengupta, Kundan; Chakrapani, Harinath

2013-08-22

105

Nitric Oxide Signaling in Health and Disease  

Microsoft Academic Search

\\u000a \\u000a \\u000a \\u000a \\u000a \\u000a • \\u000a \\u000a \\u000a \\u000a Nitric oxide is a key signaling molecule in the cardiovascular, immune, and nervous system.\\u000a \\u000a \\u000a \\u000a \\u000a • \\u000a \\u000a \\u000a \\u000a There are three enzymes that produce NO from l-arginine, two are constitutive and produce low amounts of NO for short periods of time, the other inducible and can produce\\u000a high levels of NO for prolonged periods.\\u000a \\u000a \\u000a \\u000a \\u000a \\u000a • \\u000a \\u000a \\u000a \\u000a Nitric oxide reacts primarily with transition metals

Nathan S. Bryan; Jack R. Lancaster Jr

106

Nitric oxide and inflammatory mediators in the perpetuation of osteoarthritis  

Microsoft Academic Search

Articular chondrocyte production of nitric oxide (NO) and other inflammatory mediators, such as eicosanoids and cytokines,\\u000a are increased in human osteoarthritis. The excessive production of nitric oxide inhibits matrix synthesis and promotes its\\u000a degradation. Furthermore, by reacting with oxidants such as superoxide anion, nitric oxide promotes cellular injury and renders\\u000a the chondrocyte susceptible to cytokine-induced apoptosis. PGE2 exerts anabolic and

Steven B. Abramson; Mukundan Attur; Ashok R. Amin; Robert Clancy

2001-01-01

107

New Areas for Investigation: Nitric Oxide  

Microsoft Academic Search

\\u000a Nitric oxide (NO) has been implicated in the regulation of several physiological and pathological events. In the respiratory\\u000a mucosa, NO synthases can be found mainly in ciliated epithelium. In addition to controlling ciliary beat frequency and providing\\u000a antimicrobial activity, NO is implicated in the pathophysiology of nasal polyposis, including recruitment of inflammatory\\u000a cells, inhibiting apotosis of eosinophils, disturbance of the

Edwin Tamashiro; Caroline A. Banks; Noam A. Cohen

108

Histochemical methods for detecting nitric oxide synthase  

Microsoft Academic Search

Summary  The three isoforms of nitric oxide synthase (NOS), neuronal (nNOS), endothelial (eNOS), and inducible (iNOS), can be visualized in cells and tissues by NADPH-diaphorase (NADPH-d) histochemistry, immunocytochemistry and in situ hybridization. Histochemical demonstration of NADPH-d shows the formazan final reaction product as a solid blue deposit. The ultrastructural localization of NADPH-d in the rat hippocampus showed an electron-dense deposit on

Julian E. Beesley; Kent BR

1995-01-01

109

Phosphodiesterase regulation of nitric oxide signaling  

Microsoft Academic Search

Nitric oxide regulation of the cardiovascular system involves both cGMP-dependent and independent mechanisms. The former directly interacts with the family of catabolic phosphodiesterases (PDEs) that control cGMP levels and thus distal effects such as protein kinase G stimulation. Growing evidence supports an important role of several PDEs, including PDE1, PDE2, and PDE5, in the regulation of cGMP in both vascular

David A. Kass; Eiki Takimoto; Takahiro Nagayama; Hunter C. Champion

2007-01-01

110

Nitric oxide synthase in cerebral ischemia  

Microsoft Academic Search

The results of our continuing studies on the role of nitric oxide (NO) in cellular mechanisms of ischemic brain damage as\\u000a well as related reports from other laboratories are summarized in this paper. Repetitive ip administration ofN\\u000a G-nitro-L-arginine (L-NNA), a NO synthase (NOS) inhibitor, protected against neuronal necrosis in the gerbil hippocampal CA1\\u000a field after transient forebrain ischemia with a

Toshiaki Nagafuji; Masakazu Sugiyama; Toru Matsui; Atsushi Muto; Shigetaka Naito

1995-01-01

111

Role of nitric oxide in inflammatory diseases  

Microsoft Academic Search

.  Nitric oxide (NO) is a signaling molecule that plays a key role in the pathogenesis of inflammation. It gives an anti-inflammatory\\u000a effect under normal physiological conditions. On the other hand, NO is considered as a pro-inflammatory mediator that induces\\u000a inflammation due to over production in abnormal situations. NO is synthesized and released into the endothelial cells by the\\u000a help of

J. N. Sharma; A. Al-Omran; S. S. Parvathy

2007-01-01

112

Modulation of autoimmune diseases by nitric oxide  

Microsoft Academic Search

Nitric oxide (NO) is an intercellular messenger that performs a number of functions, including neurotransmission, vasodilatation,\\u000a inhibition of platelet aggregation, and modulation of leukocyte adhesion. NO has recently been shown to act as a potent cytotoxic\\u000a effector molecule as well as to play an important role in the pathogenesis of organ-specific autoimmunity. NO may also modulate\\u000a the immune response by

Vijay K. Singh; Shikhar Mehrotra; Prem Narayan; Chandra M. Pandey; Shyam S. Agarwal

2000-01-01

113

Nitric Oxide and Choroidal Blood Flow Regulation  

Microsoft Academic Search

Purpose. Nitric oxide (NO) has been found to be an endothelial-derived relaxing factor mediating the vasodilatation that results from the stimulation of muscarinic endothelial recep- tors. It also has been identified as a putative neurotransmitter of parasympathetic origin in choroidal perivascular autonomic fibers. The authors investigated a potential role of NO in choroidal blood flow (ChBF) regulation. Methods. Local ChBF

R. M. Mann; C. E. Riva; R. A. Stone; G. E. Barnes; S. D. Cranstoun

114

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

SciTech Connect

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

Rounbehler, D.P.

1988-10-04

115

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

SciTech Connect

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

Stadler, J.; Curran, R.D.; Ochoa, J.B.; Harbrecht, B.G.; Hoffman, R.A.; Simmons, R.L.; Billiar, T.R. (Univ. of Pittsburgh, PA (USA))

1991-02-01

116

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.

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

2013-01-01

117

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

118

Nitric oxide measurements in a flame by laser fluorescence  

Microsoft Academic Search

Laser fluorescence measurements have been performed to detect nitric oxide in a CH4-O2-N2 flame at atmospheric pressure. For these measurements a frequency-doubled tunable dye laser was used to excite the UV gamma-bands of nitric oxide. Sensitivities were adequate to detect naturally occurring levels of nitric oxide that were in the 20-30-ppm range. Higher sensitivities can be achieved using other currently

D. R. Grieser; R. H. Barnes

1980-01-01

119

Nitric oxide measurements in a flame by laser fluorescence  

Microsoft Academic Search

Laser fluorescence measurements have been performed to detect nitric oxide in a CHâ--Oâ--Nâ flame at atmospheric pressure. For these measurements a frequency-doubled tunable dye laser was used to excite the UV ..gamma..-bands of nitric oxide. Sensitivities were adequate to detect naturally occurring levels of nitric oxide that were in the 20--30-ppm range. Higher sensitivities can be achieved using other currently

Daniel R. Grieser; Russell H. Barnes

1980-01-01

120

The role of nitric oxide in multiple sclerosis  

Microsoft Academic Search

During the past decade nitric oxide has emerged as an important mediator of physiological and pathophysiological processes.\\u000a Elevated nitric oxide biosynthesis has been associated with nonspecific immune-mediated cellular cytotoxicity and the pathogenesis\\u000a of chronic, inflammatory autoimmune diseases including rheumatoid arthritis, insulin-dependent diabetes, inflammatory bowel\\u000a disease, and mutiple sclerosis. Recent evidence suggests, however, that nitric oxide is also immunoregulatory and suppresses

John F. Parkinson; Branislava Mitrovic; Jean E. Merrill

1997-01-01

121

Nitric Oxide Administration Using an Oxygen Hood: A Pilot Trial  

Microsoft Academic Search

BackgroundWe have shown earlier that inhaled nitric oxide (iNO) administered by oxygen hood reduces pulmonary hypertension in an animal model (J Perinatol 2002; 22:50-6). Our objective in this study was to determine feasibility of iNO by oxygen hood in neonates with elevated alveolar-arterial oxygen gradients (A-aDO2).Methods\\/Principal FindingsMasked randomized controlled pilot trial. Inclusion criteria were: gestation?34 weeks, age100 torr, while oxygenation

Namasivayam Ambalavanan; George T. El-Ferzli; Claire Roane; Robert Johnson; Waldemar A. Carlo; Linda Wright

2009-01-01

122

Obesity reduces the bioavailability of nitric oxide in juveniles  

Microsoft Academic Search

Objective:There is growing evidence that nitric oxide (NO) is critically involved in obesity and its clinical consequences like cardiovascular disease, hypertension and diabetes. We hypothesize that NO is already involved in the pathophysiology of juvenile obesity. We here determined the role of NO, its metabolites arginine and citrulline in obese and normal weight children.Design:We investigated 57 obese and 57 normal

H-J Gruber; C Mayer; H Mangge; G Fauler; N Grandits; M Wilders-Truschnig

2008-01-01

123

a Global Reaction Rate for Nitric Oxide Reburning  

Microsoft Academic Search

An investigation of a global reburning-NO reaction, which is the reduction pathway of nitric oxide (NO) by reaction with hydrocarbons, was conducted. The global reburning-NO rate expression and its rate constants were determined. This global reburning-NO rate constant can be expressed as 2.72 times 10 ^6exp(-18,800\\/RT) (gmole\\/cm^3 s). This expression is applicable to atmospheric pressure, an equivalence ratio range of

Wei Chen

1994-01-01

124

Endothelial nitric oxide synthase in hypoxic newborn porcine pulmonary vessels  

Microsoft Academic Search

AIMSTo determine if the failure of neonatal pulmonary arteries to dilate is due to a lack of nitric oxide synthase (NOS).METHODSA monoclonal antibody to endothelial NOS was used to demonstrate the distribution and density of NOS in the developing porcine lung after a period in hypobaric hypoxia. Newborn piglets were made hypertensive by exposure to hypobaric hypoxia (50.8 kPa) from

A A Hislop; D R Springall; H Oliveira; J S Pollock; J M Polak; S G Haworth

1997-01-01

125

Tetrahydrobiopterin Alters Superoxide and Nitric Oxide Release in Prehypertensive Rats  

Microsoft Academic Search

Constitutive nitric oxide synthase (cNOS) with insufficient cofactor (6R)-5,6,7,8-tetrahydrobiopterin (H 4 B) may gener- ate damaging superoxide (O 2 2 ). This study was designed to determine whether cNOS-dependent generation of O 2 2 oc- curs 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 cal-

Francesco Cosentino; Stephen Patton; Livius V. d'Uscio; Ernst R. Werner; Gabriele Werner-Felmayer; Pierre Moreau; Tadeusz Malinski; Thomas F. Lüscher

126

The metabolic fate of long-term inhaled nitric oxide  

Microsoft Academic Search

Purpose: The fate of inhaled nitric oxide (NO) has not been precisely defined in critically ill patients. This study aimed at defining the effects of long-term NO inhalation on circulating NO byproduct levels.Material and Methods: During NO therapy, plasma and urine from 13 critically ill patients were sampled daily for determination of the stable byproducts of NO (nitrite [NO2?] and

Jean-Charles Preiser; Daniel De Backer; Frédéric Debelle; Bernard Vray; Jean-Louis Vincent

1998-01-01

127

Neuronal Nitric Oxide Synthase and Dystrophin-Deficient Muscular Dystrophy  

Microsoft Academic Search

Neuronal nitric oxide synthase (nNOS) in fast-twitch skeletal muscle fibers is primarily particulate in contrast to its greater solubility in brain. Immunohistochemistry shows nNOS localized to the sarcolemma, with enrichment at force transmitting sites, the myotendinous junctions, and costameres. Because this distribution is similar to dystrophin, we determined if nNOS expression was affected by the loss of dystrophin. Significant nNOS

Wen-Jinn Chang; Susan T. Iannaccone; Kim S. Lau; Bettie Sue S. Masters; Timothy J. McCabe; Kirk McMillan; Roanna C. Padre; Melissa J. Spencer; James G. Tidball; James T. Stull

1996-01-01

128

Processes regulating nitric oxide emissions from soils.  

PubMed

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

2013-05-27

129

Nitric oxide as a cellular antioxidant: A little goes a long way  

Microsoft Academic Search

Nitric oxide (NO) is an effective chain-breaking antioxidant in free radical-mediated lipid oxidation (LPO). It reacts rapidly with peroxyl radicals as a sacrificial chain-terminating antioxidant. The goal of this work was to determine the minimum threshold concentration of NO required to inhibit Fe2+-induced cellular lipid peroxidation. Using oxygen consumption as a measure of LPO, we simultaneously measured nitric oxide and

Stephen G. Hummel; Anthony J. Fischer; Sean M. Martin; Freya Q. Schafer; Garry R. Buettner

2006-01-01

130

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. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 101A: 3201-3210, 2013. PMID:23554300

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

2013-04-02

131

Serum, urinary, and salivary nitric oxide in rheumatoid arthritis: complexities of interpreting nitric oxide measures  

Microsoft Academic Search

Nitric oxide (NO) may play important roles in rheumatoid arthritis (RA). RA is an inflammatory disease involving joints and other systems including salivary glands. To assess NO production in RA patients, we compared levels of serum, urine, and salivary nitrite and nitrate (NOx) in patients with RA and normal subjects, and we examined the relationships of these measures to disease

J Brice Weinberg; Thomas Lang; William E Wilkinson; David S Pisetsky; E William St Clair

2006-01-01

132

Contrasting effects of diethylenetriamine–nitric oxide, a spontaneously releasing nitric oxide donor, on pregnant rat uterine contractility in vitro versus in vivo  

Microsoft Academic Search

Objective: The aim of the study was to investigate the in vitro (on tension) and in vivo (on intrauterine pressure) effects of a spontaneously releasing nitric oxide adduct, diethylenetriamine–nitric oxide, on rat uterine contractility. Study design: Contractile responses to the nitric oxide donor diethylenetriamine–nitric oxide on isometric tension of rat uterine strips (in vitro) and on intrauterine pressure (in vivo)

Catalin Buhimschi; Irina Buhimschi; Chandrasekhar Yallampalli; Kristof Chwalisz; Robert E. Garfield

1997-01-01

133

Estrogen regulation of nitric oxide and inducible nitric oxide synthase (iNOS) in immune cells: Implications for immunity, autoimmune diseases, and apoptosis  

Microsoft Academic Search

Nitric oxide plays a central role in the physiology and pathology of diverse tissues including the immune system. It is clear that the levels of nitric oxide must be carefully regulated to maintain homeostasis. Appropriate levels of nitric oxide derived from iNOS assist in mounting an effective defense against invading microbes. Conversely, inability to generate nitric oxide results in serious,

Ebru Karpuzoglu; S. Ansar Ahmed

2006-01-01

134

Nitric Oxide is a Potential Diagnostic Marker for Hepatocellular Carcinoma  

PubMed Central

Hepatocellular carcinoma (HCC) is the fifth most common cancer in men and the seventh most common in women. This cancer varies widely in incidence throughout the world, with rising incidence in Egypt. HCC is considered the second most frequent cause of cancer incidence and mortality among men in Egypt. This study aimed to estimate the serum levels of nitric oxide (NO) and glutathione reductase in order to evaluate their role as oxidative status markers in HCC development and progression. For this purpose, serum levels of these parameters were assessed in 50 HCC patients, and 30 cirrhotic patients in addition to 15 healthy subjects as a control group. In the present study, glutathione reductase activity showed a significant increase in HCC as compared to the control group (P= 0.019). On the other hand, no significant difference was observed between the cirrhotic and HCC patients (P= 0.492). Serum NO was significantly higher in patients with HCC than in cirrhotic patients (P= 0.001) or the control group (P= 0.001), with a sensitivity of (74%) and specificity of (88.89%) at a cut-off level of 614.1 ?mol/l. While AFP, alpha-fetoprotein, at a cutoff level of 200 ng/ml had a sensitivity of (52%), the specificity was (100%). Indeed, nitric oxide was high in 62.5% of AFP-negative HCC patients. In conclusion, glutathione reductase has no role in HCC diagnosis. However, nitric oxide is a potential diagnostic marker for HCC. The simultaneous determination of serum nitric oxide and AFP gave significant improvement in the detection of HCC patients compared to that of AFP alone.

Eissa, Laila A.; Eisa, Nada H.; Ebrahim, Mohamed A.; Ragab, Maha; El-Gayar, Amal M.

2013-01-01

135

Nitric Oxide is a Potential Diagnostic Marker for Hepatocellular Carcinoma.  

PubMed

Hepatocellular carcinoma (HCC) is the fifth most common cancer in men and the seventh most common in women. This cancer varies widely in incidence throughout the world, with rising incidence in Egypt. HCC is considered the second most frequent cause of cancer incidence and mortality among men in Egypt. This study aimed to estimate the serum levels of nitric oxide (NO) and glutathione reductase in order to evaluate their role as oxidative status markers in HCC development and progression. For this purpose, serum levels of these parameters were assessed in 50 HCC patients, and 30 cirrhotic patients in addition to 15 healthy subjects as a control group. In the present study, glutathione reductase activity showed a significant increase in HCC as compared to the control group (P= 0.019). On the other hand, no significant difference was observed between the cirrhotic and HCC patients (P= 0.492). Serum NO was significantly higher in patients with HCC than in cirrhotic patients (P= 0.001) or the control group (P= 0.001), with a sensitivity of (74%) and specificity of (88.89%) at a cut-off level of 614.1 ?mol/l. While AFP, alpha-fetoprotein, at a cutoff level of 200 ng/ml had a sensitivity of (52%), the specificity was (100%). Indeed, nitric oxide was high in 62.5% of AFP-negative HCC patients. In conclusion, glutathione reductase has no role in HCC diagnosis. However, nitric oxide is a potential diagnostic marker for HCC. The simultaneous determination of serum nitric oxide and AFP gave significant improvement in the detection of HCC patients compared to that of AFP alone. PMID:24106672

Eissa, Laila A; Eisa, Nada H; Ebrahim, Mohamed A; Ragab, Maha; El-Gayar, Amal M

2013-08-08

136

Catalepsy induced by nitric oxide synthase inhibitors  

Microsoft Academic Search

1.1. Previous study showed that NG-nitro-l-arginine (l-NOARG), an inhibitor of nitric oxide synthase, induces catalepsy in a dose-dependent manner in male albino-Swiss mice.2.2. The objective of the present work was to further investigate this effect, extending it to other NOS inhibitors.3.3. Results showed that l-NOARG (40–80 mg\\/kg IP), NG-nitro-l-arginine methylester (l-NAME, 40–160 mg\\/kg IP) or NG-monomethyl-l-arginine (l-NMMA, 80 mg\\/kg IP)

E. A. Del Bel; C. A. da Silva; F. S. Guimarães

1998-01-01

137

Laser Induced Fluorescence Measurements and Modeling of Nitric Oxide in High-Pressure Premixed Flames.  

National Technical Information Service (NTIS)

Laser-induced fluorescence (LIF) has been applied to the quantitative measurement of nitric oxide (NO) in premixed, laminar, high-pressure flames. Their chemistry was also studied using three current kinetics schemes to determine the predictive capabiliti...

J. R. Reisel N. M. Laurendeau

1994-01-01

138

Occupational exposure during nitric oxided inhalational therapy in a pediatric intensive care setting  

Microsoft Academic Search

Objective: To determine the amount of occupational expo- sure to nitric oxide (NO) and nitro- gen dioxide (NO2) during NO in- halational therapy. Design: In a standard pediatric in- tensive care room, 800 ppm NO was

D. G. Markhorst; T. Leenhoven; J. W. Uiterwijk; J. Meulenbelt; A. J. van Vught

1996-01-01

139

Formation of Nitric (Nitrogen) Oxides in Firebox Processes during Gas Combustion.  

National Technical Information Service (NTIS)

The conditions of nitric oxide formation in the combustion of fuel in boiler fireboxes were examined and equations were obtained for the evaluational determination of the NO output in the combustion zone. It was demonstrated, that under the conditions cha...

A. V. Markovskii I. Y. Sigal N. A. Gurevich S. S. Nizhnik

1974-01-01

140

Novel substrates for nitric oxide synthases.  

PubMed

Enzymatic generation of nitric oxide (NO) by nitric oxide synthase (NOS) consists of two oxidation steps. The first step converts L-arginine to N(G)-hydroxy-L-arginine (NOHA), a key intermediate, and the second step converts NOHA to NO and L-citrulline. To fully probe the substrate specificity of the second enzymatic step, an extensive structural screening was carried out using a series of N-alkyl (and N-aryl) substituted-N'-hydroxyguanidines (1-14). Among the eleven N-alkyl-N'-hydroxyguanidines evaluated, N-n-propyl (2), N-iso-propyl (3), N-n-butyl (4), N-s-butyl (5), N-iso-butyl (6), N-pentyl (8) and N-iso-pentyl (9) derivatives were efficiently oxidized by the three isoenzymes of NOS (nNOS, iNOS and eNOS) to generate NO. N-Butyl-N'-hydroxyguanidine (4) was the best substrate for iNOS (K(m)=33 microM) and N-iso-propyl-N'-hydroxyguanidine (3) was the best substrate for nNOS (K(m)=56 microM). When the alkyl substituents were too small (such as ethyl 1) or too large (such as hexyl 10 and cyclohexyl 11), the activity decreased significantly. This suggests that the van der Waals interaction between the alkyl group and the hydrophobic cavity in the NOS active site contributes significantly to the relative reactivity of compounds 3-11. Moreover, five N-aryl-N'-hydroxyguanidines were found to be good substrates for iNOS, but not substrates for eNOS and nNOS. N-phenyl-N'-hydroxyguanidine was the best substrate among them (K(m)=243 microM). This work demonstrates that N-alkyl substituted hydroxyguanidine compounds are novel NOS substrates which 'short-circuit' the first oxidation step of NOS, and N-aryl substituted hydroxyguanidine compounds are isoform selective NOS substrate. PMID:12110328

Xian, Ming; Fujiwara, Noriko; Wen, Zhong; Cai, Tingwei; Kazuma, Satoshi; Janczuk, Adam J; Tang, Xiaoping; Telyatnikov, Vladislav V; Zhang, Yingxin; Chen, Xinchao; Miyamoto, Yasuhide; Taniguchi, Naoyuki; Wang, Peng George

2002-09-01

141

Nitric oxide rescues thalidomide mediated teratogenicity  

PubMed Central

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.

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

2012-01-01

142

Melatonin and its precursors scavenge nitric oxide  

SciTech Connect

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

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

1998-12-01

143

Melatonin and its precursors scavenge nitric oxide.  

PubMed

Nitric oxide (NO) scavenging activity of melatonin, N-acetyl-5-hydroxytryptamine, serotonin, 5-hydroxytryptophan and L-tryptophan was examined by the Griess reaction using flow injection analysis. 1-Hydroxy-2-oxo-3-(N-methyl-3-aminopropyl)-3-methyl-1-triazene (NOC-7) was used as NO generator. The Griess reagent stoichiometrically reacts with NO2-, which was converted by a cadmium-copper reduction column from the stable end products of NO oxidation. Except for tryptophan, all the compounds examined scavenged NO in a dose-dependent manner. Melatonin, which has a methoxy group in the 5-position and an acetyl side chain, exhibited the most potent scavenging activity among the compounds tested. Serotonin, N-acetyl-5-hydroxytryptamine, and 5-hydroxytryptophan, respectively, showed moderate scavenging activity compared to melatonin. Tryptophan, which has neither a methoxy nor a hydroxyl group in the 5-position, exhibited the least NO scavenging activity. PMID:10535765

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

1999-10-01

144

Nitric oxide induces acrosome reaction in cryopreserved bovine spermatozoa.  

PubMed

The aim of this work was to study the effect of nitric oxide on acrosome reaction (AR) and the participation of protein kinases and reactive oxygen species in the AR of cryopreserved bovine spermatozoa. Spermatozoa were capacitated in Tyrode's albumin lactate pyruvate medium with heparin (10 IU ml(-1)) and then incubated with different concentrations of sodium nitroprusside (SNP) (1-200 micromol l(-1)). Methylene blue and haemoglobin were used to confirm the role of nitric oxide as an inducer of the AR. The participation of protein kinase A (PKA) , protein kinase C (PKC) and protein tyrosine kinase was evaluated using specific inhibitors of these enzymes (H-89, 50 micromol l(-1); bisindolylmaleimide I, 0.1 micromol l(-1) and genistein, 3 micromol l(-1)). The role of hydrogen peroxide or superoxide anion was evaluated by incubation with catalase or superoxide dismutase respectively. AR percentages were determined by the fluorescence technique with chlortetracycline. The highest levels of AR were obtained in capacitated spermatozoa treated with 5-200 micromol l(-1) SNP (24.8 +/- 1.8%). The presence of PKA, PKC and protein tyrosine kinase inhibitors likewise decreased AR percentages. The addition of superoxide dismutase had no effect on the AR level but catalase completely blocked it. These results indicate that nitric oxide induces AR in capacitated spermatozoa involving hydrogen peroxide and the participation of PKA, PKC and protein tyrosine kinase as part of the signal transduction mechanism which lead to the AR in cryopreserved bovine spermatozoa. PMID:16266394

Rodriguez, P C; O'Flaherty, C M; Beconi, M T; Beorlegui, N B

2005-10-01

145

Kinetic Modeling of Nitric-Oxide-Associated Reaction Network  

Microsoft Academic Search

Purpose  Nitric oxide and superoxide are the two important free radicals in the biological system. The coexistence of both free radicals in the physiological milieu gives rise to intricate oxidative and nitrosative reactions, which have been implicated in many physiological and\\/or pathophysiological conditions, such as vasodilatation and inflammation. It is difficult, if not impossible, to study the complexity of the nitric

Teh-Min Hu; William L. Hayton; Susan R. Mallery

2006-01-01

146

Nitric Oxide Activates Metalloprotease Enzymes in Articular Cartilage  

Microsoft Academic Search

Nitric oxide (NO.) is a multifunctional messenger molecule generated by a family of enzymes, collectively termed the nitric oxide synthases. We investigated the role of NO. in the modulation of two metal-dependent proteolytic enzymes (collagenase and stromelysin) which are activated during inflammatory and infective arthritis. The inflammatory mediators interleukin-1? (IL-1?), tumor necrosis factor-? (TNF-?) and the bacterial cell wall fragment

G. A. C. Murrell; D. Jang; R. J. Williams

1995-01-01

147

Nitric Oxide Emissions From a Cooled Porous Disk Burner  

Microsoft Academic Search

Nitric oxide emissions from a premixed propane-air flame were controlled by extracting energy from a steady state reaction zone using a cooled flat flame porous metal disk burner. Energy flux variations and, hence, nitric oxide formation rate changes were obtained for specific mixtures by changing the fuel-air inlet velocity. It was possible to stabilize flames for inlet flow velocities of

BRUCE D. PETERS; GARY L. BORMAN

1973-01-01

148

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

149

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...

150

CAFFEIC ACID-DRIVEN FORMATION OF NITRIC OXIDE FROM NITRITE  

Microsoft Academic Search

Nitric oxide (NO) is synthesized in vivo by a group of nitric oxide synthases, exhibiting a wide array of biological actions. Much less attention has been devoted to the non enzymatic production of NO. However, it has been shown that in acid\\/reducing environments nitrite may be reduced to NO. Examples include ischemia-reperfusion situations and the oral and stomach cavities. Due

Bruno Gago; João Laranjinha

151

Nitric oxide in myogenesis and therapeutic muscle repair.  

PubMed

Nitric oxide is a short-lived intracellular and intercellular messenger. The first realisation that nitric oxide is important in physiology occurred in 1987 when its identity with the endothelium-derived relaxing factor was discovered. Subsequent studies have shown that nitric oxide possesses a number of physiological functions that are essential not only to vascular homeostasis but also to neurotransmission, such as in the processes of learning and memory and endocrine gland regulation, as well as inflammation and immune responses. The discovery in 1995 that a splice variant of the neuronal nitric oxide synthase is localised at the sarcolemma via the dystrophin-glycoprotein complex and of its displacement in Duchenne muscular dystrophy has stimulated a host of studies exploring the role of nitric oxide in skeletal muscle physiology. Recently, nitric oxide has emerged as a relevant messenger also of myogenesis that it regulates at several key steps, especially when the process is stimulated for muscle repair following acute and chronic muscle injuries. Here, we will review briefly the mechanisms and functions of nitric oxide in skeletal muscle and discuss its role in myogenesis, with specific attention to the promising nitric oxide-based approaches now being explored at the pre-clinical and clinical level for the therapy of muscular dystrophy. PMID:22821188

De Palma, Clara; Clementi, Emilio

2012-07-22

152

Rapid Reversibility of Nitric Oxide Induced Platelet Inhibition  

Microsoft Academic Search

Nitric oxide is known to attenuate human platelet activation. Mechanistically this is achieved by stimulation of soluble guanylyl cyclase, followed by cGMP production, and concomitant protein phosphorylation. Although inhibitory actions of nitric oxide on various platelet parameters are well documented, considerably less information is available on the reversibility of this effect. In order to study the onset of proaggregatory signaling

Bernhard Brüne; Kerstin Hanstein

1998-01-01

153

Nitric oxide air pollution: detection by optoacoustic spectroscopy.  

PubMed

Nitric oxide is detected by a new technique in which tunable infrared radiation from a spin-flip Raman laser is used to measure the absorption spectrumn of a gas sample by optoacoustic spectroscopy. This technique is sensitive enough to detect a concentration of 0.01 part per million of nitric oxide pollution in air samples. PMID:5087479

Kreuzer, L B; Patel, C K

1971-07-01

154

Stratospheric Nitric Oxide: Measurements during Daytime and Sunset  

Microsoft Academic Search

Measurements of the temporal variation in the stratospheric nitric oxide concentration covering a time period from 11:00 to 20:30 local time show the effect of solar ultraviolet sunset. The experimental results strongly support the theorized role of nitric oxide as a catalyst in the destruction of ozone and its importance in the stratospheric ozone balance.

E. G. Burkhardt; C. A. Lambert; C. K. N. Patel

1975-01-01

155

Highly sensitive determination of nitric oxide in biologic samples by a near-infrared BODIPY-based fluorescent probe coupled with high-performance liquid chromatography.  

PubMed

Nitric oxide (NO) acts as an important regulator and mediator in numerous processes of biological systems. In this work, the analytical potential of a novel near-infrared (NIR, >600nm) BODIPY-based fluorescent probe for NO, 8-(3,4-diaminophenyl)-4,4-difluoro-4-bora-3a,4a-diaza-di(1,2-dihydro) naphtho[b, g]s-indacene (DANPBO-H) has been evaluated in high performance liquid chromatography (HPLC). In 25mM pH 6.50 borate buffer, DANPBO-H reacted with NO to give the corresponding triazole, DANPBO-H-T, at 35°C for 20min. DANPBO-H-T was eluted using a mobile phase of methanol/tetrahydrofuran/50mM pH 7.00 H3Cit-NaOH buffer (81:7:12, v/v/v) in 4min on a C8 column and detected with fluorescence detection at excitation and emission wavelengths of 621 and 631nm, respectively. The limit of detection (LOD) (signal-to-noise=3) reached to 5.50×10(-10)M. Excellent selectivity was observed against other reactive oxygen/nitrogen species. Various representative biological matrixes including the whole blood and organs of mice, the pangen and radical of rice, human vascular endothelial (ECV-304) cells and mouse macrophage (RAW 264.7) cells were used to verify the feasibility and resistance to interfering effects from complex biological sample matrixes of the developed DANPBO-H-based HPLC method. Compared to the existing derivatization-based HPLC methods for NO, the proposed method eliminates interfering effects from complex biological sample matrixes efficiently owing to the fluorescence detection in the NIR region, and is more advantageous and robust for the sensitive and selective determination of NO in complex biological samples. PMID:24148412

Zhang, Hui-Xian; Chen, Jian-Bo; Guo, Xiao-Feng; Wang, Hong; Zhang, Hua-Shan

2013-05-24

156

The Iron-Catalyzed Oxidation of Hydrazine by Nitric Acid  

SciTech Connect

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

Karraker, D.G.

2001-07-17

157

Methylene tetrahydrofolate reductase (MTHFR) and nitric oxide synthase (ecNOS) genes and risks of peripheral arterial disease and coronary heart disease: Edinburgh artery study  

Microsoft Academic Search

Hyperhomocysteinaemia and reduced nitric oxide synthesis may each result in endothelial dysfunction predisposing to atherogenesis. Genetic variants of methylene tetrahydrofolate reductase (MTHFR) and endothelial nitric oxide synthase (ecNOS) influence homocysteine metabolism and nitric oxide synthesis, respectively and might thus be determinants of the risk of atherosclerotic disease. The aim of our study was to identify, in a general population sample,

F. G. R Fowkes; A. J Lee; C. M Hau; A Cooke; J. M Connor; G. D. O Lowe

2000-01-01

158

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

2013-03-07

159

Preparation of Standards and Measurement of Nitric Oxide, Nitroxyl, and Related Oxidation Products  

Microsoft Academic Search

Nitric oxide (NO) is a vasodilator, neurotransmitter, and inflammatory mediator which is unstable at physiologic O2 tensions. NO?s susceptibility to oxidation accounts for its short biological half-life in vivo and greatly complicates its measurement. Measuring NO requires an understanding of the redox reactions and partitioning that determine its survival and distribution. In aqueous solutions NO rapidly partitions to the gas

Stephen L. Archer; Pamela J. Shultz; John B. Warren; Vaclav Hampl; Eugene G. DeMaster

1995-01-01

160

Inactivation of Nitric Oxide by Uric Acid  

PubMed Central

The 1980 identification of nitric oxide (NO) as an endothelial cell-derived relaxing factor resulted in an unprecedented biomedical research of NO and established NO as one of the most important cardiovascular, nervous and immune system regulatory molecule. A reduction in endothelial cell NO levels leading to “endothelial dysfunction” has been identified as a key pathogenic event preceding the development of hypertension, metabolic syndrome, and cardiovascular disease. The reduction in endothelial NO in cardiovascular disease has been attributed to the action of oxidants that either directly react with NO or uncouple its substrate enzyme. In this report, we demonstrate that uric acid (UA), the most abundant antioxidant in plasma, reacts directly with NO in a rapid irreversible reaction resulting in the formation of 6-aminouracil and depletion of NO. We further show that this reaction occurs preferentially with NO even in the presence of oxidants peroxynitrite and hydrogen peroxide and that the reaction is at least partially blocked by glutathione. This study shows a potential mechanism by which UA may deplete NO and cause endothelial dysfunction, particularly under conditions of oxidative stress in which UA is elevated and intracellular glutathione is depleted.

Gersch, Christine; Palii, Sergiu P.; Kim, Kyung Mee; Angerhofer, Alexander; Johnson, Richard J.; Henderson, George N.

2009-01-01

161

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

PubMed Central

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

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

2010-01-01

162

The nitric oxide hypothesis of aging.  

PubMed

Nitric oxide (NO), generated by endothelial (e) NO synthase (NOS) and neuronal (n) NOS, plays a ubiquitous role in the body in controlling the function of almost every, if not every, organ system. Bacterial and viral products, such as bacterial lipopolysaccharide (LPS), induce inducible (i) NOS synthesis that produces massive amounts of NO toxic to the invading viruses and bacteria, but also host cells by inactivation of enzymes leading to cell death. The actions of all forms of NOS are mediated not only by the free radical oxidant properties of this soluble gas, but also by its activation of guanylate cyclase (GC), leading to the production of cyclic guanosine monophosphate (cGMP) that mediates many of its physiological actions. In addition, NO activates cyclooxygenase and lipoxygenase, leading to the production of physiologically relevant quantities of prostaglandin E2 (PGE2) and leukotrienes. In the case of iNOS, the massive release of NO, PGE2, and leukotrienes produces toxic effects. Systemic injection of LPS causes induction of interleukin (IL)-1 beta mRNA followed by IL-beta synthesis that induces iNOS mRNA with a latency of two and four hours, respectively, in the anterior pituitary and pineal glands, meninges, and choroid plexus, regions outside the blood-brain barrier, and shortly thereafter, in hypothalamic regions, such as the temperature-regulating centers, paraventricular nucleus containing releasing and inhibiting hormone neurons, and the arcuate nucleus, a region containing these neurons and axons bound for the median eminence. We are currently determining if LPS similarly activates cytokine and iNOS production in the cardiovascular system and the gonads. Our hypothesis is that recurrent infections over the life span play a significant role in producing aging changes in all systems outside the blood-brain barrier via release of toxic quantities of NO. NO may be a major factor in the development of coronary heart disease (CHD). Considerable evidence has accrued indicating a role for infections in the induction of CHD and, indeed, patients treated with a tetracycline derivative had 10 times less complications of CHD than their controls. Stress, inflammation, and infection have all been shown to cause induction of iNOS in rats, and it is likely that this triad of events is very important in progression of coronary arteriosclerosis leading to coronary occlusion. Aging of the anterior pituitary and pineal with resultant decreased secretion of pituitary hormones and the pineal hormone, melatonin, respectively, may be caused by NO. The induction of iNOS in the temperature-regulating centers by infections may cause the decreased febrile response in the aged by loss of thermosensitive neurons. iNOS induction in the paraventricular nucleus may cause the decreased nocturnal secretion of growth hormone (GH) and prolactin that occurs with age, and its induction in the arcuate nucleus may destroy luteinizing hormone-releasing hormone (LHRH) neurons, thereby leading to decreased release of gonadotropins. Recurrent infections may play a role in aging of other parts of the brain, because there are increased numbers of astrocytes expressing IL-1 beta throughout the brain in aged patients. IL-1 and products of NO activity accumulate around the plaques of Alzheimer's, and may play a role in the progression of the disease. Early onset Parkinsonism following flu encephalitis during World War I was possibly due to induction of iNOS in cells adjacent to substantia nigra dopaminergic neurons leading to death of these cells, which, coupled with ordinary aging fall out, led to Parkinsonism. The central nervous system (CNS) pathology in AIDS patients bears striking resemblance to aging changes, and may also be largely caused by the action of iNOS. Antioxidants, such as melatonin, vitamin C, and vitamin E, probably play an important acute and chronic role in reducing or eliminating the oxidant damage produced by NO. PMID:9951625

McCann, S M; Licinio, J; Wong, M L; Yu, W H; Karanth, S; Rettorri, V

163

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

Microsoft Academic Search

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

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

1996-01-01

164

Minimal effects of nitric oxide on spatial blood flow heterogeneity of the dog heart  

Microsoft Academic Search

Eleven Beagle dogs were studied to elucidate the possible role of L-arginine-derived nitric oxide on local blood flow distribution in left and right ventricular myocardium. Local blood flow\\u000a was determined in 256 samples from the left and 64 samples from the right ventricle per heart using the tracer microsphere\\u000a technique (mean sample mass 319 ± 131 mg). Nitric oxide production

Andreas Deussen; Michael Sonntag; Christian W. Flesche; Raimund M. Vogel

1997-01-01

165

Heat shock enhances transcriptional activation of the murine inducible nitric oxide synthase gene  

Microsoft Academic Search

There is considerable interest in determining the conditions leading to enhanced inducible nitric oxide synthase (iNOS) gene expression and nitric oxide (NO) biosynthesis. Using in vivo footprinting, we demonstrate that heat shock of murine macrophages concurrent with lipopolysaccharide (LPS) treatment stimulated changes in guanine methylation sensitivity at -898\\/9, at a putative partial heat shock element (HSE) and at -893\\/4, a

Christopher E. P. Goldring; Sylvie Reveneau; Aurélie Chantome; Alena Pance; Christophe Fleury; David A. Hume; David Sester; Bernard Mignotte; Jean-François Jeannin

2000-01-01

166

Original Contribution Nitric oxide as a cellular antioxidant: A little goes a long way  

Microsoft Academic Search

Nitric oxide (NO S) is an effective chain-breaking antioxidant in free radical-mediated lipid oxidation (LPO). It reacts rapidly with peroxyl radicals as a sacrificial chain-terminating antioxidant. The goal of this work was to determine the minimum threshold concentration of NO S required to inhibit Fe2+-induced cellular lipid peroxidation. Using oxygen consumption as a measure of LPO, we simultaneously measured nitric

Stephen G. Hummel; Anthony J. Fischer; Sean M. Martin; Freya Q. Schafer; Garry R. Buettner

167

Original Contribution Evidence of cardiovascular protection by moderate alcohol: Role of nitric oxide  

Microsoft Academic Search

Epidemiological evidence indicates that moderate alcohol consumption reduces the incidence of heart disease. Endothelial nitric oxide synthase (eNOS) is a key regulator of vascular homeostasis and myocardial functions through the controlled production of nitric oxide ( SNO). These studies were conducted to determine if the apparent alcohol-associated cardioprotection is mediated, in part, through modulation of the eNOS protein and activity

Laila H. Abou-agag; Nicholas K. Khoo; Ralf Binsack; C. Roger White; Victor Darley-Usmare; Hernan E. Grenett; Francois M. Booyse; Fen Zhou; Dale A. Parks

168

Nitric oxide and carbon monoxide permeation through glassy polymeric membranes for carbon dioxide separation  

Microsoft Academic Search

Minor components present in polymeric membrane gas separation can have a significant influence on the separation performance. Carbon monoxide and nitric oxide exist in post-combustion gas streams and can therefore influence CO2 transport through membranes designed for that application. Here, the permeability of nitric oxide (NO) through three glassy polymeric membranes (polysulfone, Matrimid 5218 and 6FDA-TMPDA) was determined and found

Colin A. Scholes; George Q. Chen; Geoff W. Stevens; Sandra E. Kentish

2011-01-01

169

Nitric-oxide myoglobin as an inhibitor of lipid oxidation  

Microsoft Academic Search

The effect of nitric-oxide myoglobin (MbNO) on lipid oxidation was studied in linoleate and ?-carotene-linoleate aqueous model\\u000a systems and compared with that of metmyoglobin (MMb) and oxymyoglobin (MbO2) in short- and long-term reactions. While MMb and MbO2 had a clear prooxidative effect, MbNO, under the same conditions, acted as an antioxidant. The specific antioxidative activity\\u000a of MbNO was maintained even

Joseph Kanner; Itamar Ben-Gera; Shura Berman

1980-01-01

170

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

Microsoft Academic Search

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

Sergei A. Kharitonov; Peter J. Barnes

2003-01-01

171

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

Microsoft Academic Search

Nitric oxide is an important messenger molecule in many physiological processes. The addition of NO via NO-flurbiprofen enhances\\u000a the material properties of healing tendon, however, flurbiprofen has a detrimental effect on healing. We asked if NO delivered\\u000a by a cyclooxygenase 3 inhibitor (paracetamol\\/acetaminophen) would enhance healing in a rat Achilles tendon healing model.\\u000a Rats were injected subcutaneously daily with NO-paracetamol,

George A. C. Murrell; Gongyao Tang; Richard C. Appleyard; Piero del Soldato; Min-Xia Wang

2008-01-01

172

Nitric Oxide and Respiratory Helminthic Diseases  

PubMed Central

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

Muro, Antonio; Perez-Arellano, Jose-Luis

2010-01-01

173

Nitric oxide release: part II. Therapeutic applications.  

PubMed

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

Carpenter, Alexis W; Schoenfisch, Mark H

2012-02-24

174

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.

Riccio, Daniel A.; Schoenfisch, Mark H.

2012-01-01

175

Nitric Oxide Release Part II. Therapeutic Applications  

PubMed Central

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

Carpenter, Alexis W.; Schoenfisch, Mark H.

2012-01-01

176

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.

Miller, M R; Megson, I L

2007-01-01

177

Efficient nitrosation of glutathione by nitric oxide?  

PubMed Central

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

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

2013-01-01

178

Nitric oxide-induced calcium release: activation of type 1 ryanodine receptor by endogenous nitric oxide.  

PubMed

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

Kakizawa, Sho; Yamazawa, Toshiko; Iino, Masamitsu

2012-12-17

179

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

PubMed

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

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

2001-01-01

180

Role of nitric oxide in diabetic complications.  

PubMed

Diabetic vascular disease is accompanied by decreased formation of the vasodilators, nitric oxide (NO), and prostacyclin and increased formation of vasoconstrictor eicosanoids, which exacerbate the progression of vascular disease. Similarities between the dysfunction introduced by short-term effects of elevated glucose and long-term effects of diabetes suggest that the alteration in endothelial factors in diabetes primarily results from exposure of endothelial cells to elevated glucose, although undoubtedly hyperlipidemia contributes as well. A key alteration in endothelial cell phenotype is increased formation of reactive oxygen species. This is in part due to uncoupling of endothelial NO synthase such that it generates superoxide anion in addition to NO. This is responsible for NO synthase to produce peroxynitrite, a damaging molecule. Peroxynitrite inactivates prostacyclin synthase leading to the accumulation of inflammatory and prothrombotic eicosanoids. This not only helps to explain the impairment of endothelial vasodilator mechanisms, but also increased progression of vascular disease. Many of these cellular abnormalities can be prevented by adequate scavenging of oxygen-derived free radicals or by blocking the actions of the eicosanoids at thromboxane (TP) receptors. Exposure to elevated glucose also gives rise to oxidants in smooth muscle, and recent studies indicate that oxidation of cysteine thiols under these conditions may prevent physiological NO signaling. As a result, the responsiveness to NO is impaired and accounts in part for abnormal endothelium-dependent vasodilation. PMID:16280643

Cohen, Richard A

181

Electrochemical detection of nitric oxide using polymer modified electrodes.  

PubMed

Electrochemical sensors based on chemical surface modification are very attractive because they combine high sensitivity of amperometry with new dimensions of selectivity and stability provided by the surface modifier. This review shows a few strategies employed to facilitate the detection, determination and monitoring of nitric oxide using polymer modified electrodes. Conducting and nonconducting polymer films and composite films are considered. The most significant achievements reached in this field, during the last decade, are critically reviewed. The collected data are also presented in three tables. PMID:18969158

Ciszewski, Aleksander; Milczarek, Grzegorz

2003-09-30

182

Ice particle growth in the presence of nitric oxide  

NASA Astrophysics Data System (ADS)

An experimental study was undertaken to examine the effects of nitric oxide (NO) on ice crystal growth. This study focused on growth rates and ice crystal habit. A chamber was used to grow ice at controlled temperature and supersaturation, and images of ice crystals were obtained using a video camera. Ice crystals grow more quickly when NO concentrations are elevated above background to 370 and 710 ppb and lengthen (c-axis growth) more quickly than they thicken (a-axis growth). The results have implications for ice crystal growth in thunderstorms and may aid in determining whether an air parcel in a thunderstorm originated from an electrically active region.

Peterson, Harold; Hallett, John

2012-03-01

183

Nitric oxide-induced oxidation of alpha-tocopherol.  

PubMed

Exposure of alpha-tocopherol (alpha-T) to nitric oxide under aerobic conditions resulted in a complex oxidation process whose final outcome was dictated by the nature of the reaction medium. In a cyclohexane solution, a prevailing route led to a mixture of relatively unstable polar products positive to Griess reagent. On standing at room temperature these were partially converted to the novel 2,3-dimethyl-4-acetyl-4-hydroxy-5-nitroso-2-cyclopentenone derivative. Reaction of alpha-T via a secondary oxidation path led to the formation of alpha-tocopherylquinone (alpha-TQ) as well as of little amounts of the corresponding nitrite ester. A quite different product pattern was observed when the reaction was carried out on a suspension of alpha-T in 0.1 M phosphate buffer, pH 7.4. Besides a significant formation of alpha-TQ and its nitrite ester, product analysis revealed a characteristic pattern of apolar compounds consisting of a yellow dimer and a series of related oligomers. These results provide an improved chemical background to inquire into the role of alpha-T in nitric oxide-induced tissue injury. PMID:8931945

d'Ischia, M; Novellino, L

1996-10-01

184

Novel agents for cancer prevention based on nitric oxide.  

PubMed

NO (nitric oxide) biology has provided the impetus for the development of anticancer agents based on their ability to release NO. NO-NSAIDs (NO-donating non-steroidal anti-inflammatory drugs), consisting of a conventional NSAID to which an NO-releasing moiety is covalently attached, are promising chemopreventive agents against cancer. Compared with their parent compounds, NO-NSAIDs are up to several hundred times more potent in inhibiting the growth of cancer cell lines and prevent colon and pancreatic cancer in animal models. Their chemopreventive effect is due to inhibition of proliferation, induction of cell death and inhibition of cell-cycle-phase transitions. NO-ASA (NO-aspirin), the best-studied NO-NSAID, induces oxidative stress in target cells. Major downstream signalling effects involve the Wnt, NOS2 (nitric oxide synthase 2), MAPK (mitogen-activated protein kinase), NF-kappaB (nuclear factor kappaB) and Nrf2 (nuclear factor-erythroid 2 p45 subunit-related factor 2) pathways. NO-NSAIDs, particularly NO-ASA, appear to be safe compounds, as suggested by many animal and early human studies. An ongoing clinical trial is designed to determine whether NO-ASA can inhibit early stages of colon carcinogenesis in subjects at risk for colon cancer. It is clinical trials that will ultimately determine the role of NO-NSAIDs in cancer prevention and perhaps treatment. PMID:17956352

Rigas, B

2007-11-01

185

Nitric Oxide Synthase in Toxic Epidermal Necrolysis and Stevens–Johnson Syndrome  

Microsoft Academic Search

Toxic epidermal necrolysis and Stevens–Johnson syndrome are severe cutaneous drug reactions of unknown mechanism. Nitric oxide can cause apoptosis and necrosis. The inducible form of nitric oxide synthase generates large amounts of nitric oxide and has been described in human skin. We propose that a large burst of nitric oxide in toxic epidermal necrolysis and Stevens–Johnson syndrome may cause the

Lisa H. Lerner; Abrar A. Qureshi; Bhaskar V. Reddy; Ethan A. Lerner

2000-01-01

186

Effect of paraquat exposure on nitric oxide-responsive genes in rat mesencephalic cells  

Microsoft Academic Search

When neural cells are exposed to paraquat, nitric oxide generation increases primarily due to an increase in the expression of the inducible isoform of nitric oxide synthase. The nitric oxide generated has controversial actions in paraquat exposure, as both protective and harmful effects have been described previously. While the actions mediated by nitric oxide in neural cells have been well

José M. Morán; Miguel A. Ortiz-Ortiz; Luz M. Ruiz-Mesa; Mireia Niso-Santano; Jose M. Bravosanpedro; Rubén Gómez Sánchez; Rosa A. González-Polo; José M. Fuentes

2010-01-01

187

Nitric Oxide Stimulating Dietary Supplements: Introducing Glycine Propionyl-L-Carnitine (GPLC)  

Microsoft Academic Search

Nitric oxide (NO?), initially known as endothelium derived relaxing factor (EDRF), is biosynthesized within the body from L-arginine and oxygen by a variety of nitric oxide synthase enzymes (Collier and Vallance, 1991). Nitric oxide is a gaseous chemical compound that acts as an important signaling molecule within the human body. Nitric oxide has been shown to decrease platelet and leukocyte

Richard J. Bloomer

188

Nitric oxide and energy metabolism in mammals.  

PubMed

Nitric oxide (NO) is a signaling molecule synthesized from L-arginine by NO synthase in animals. Increasing evidence shows that NO regulates the mammalian metabolism of energy substrates and that these effects of NO critically depend on its concentrations at the reaction site and the period of exposure. High concentrations of NO (in the micromolar range) irreversibly inhibit complexes I, II, III, IV, and V in the mitochondrial respiratory chain, whereas physiological levels of NO (in the nanomolar range) reversibly reduce cytochomrome oxidase. Thus, NO reduces oxygen consumption by isolated mitochondria to various extents. In intact cells, through cGMP and AMP-activated protein kinase signaling, physiological levels of NO acutely stimulate uptake and oxidation of glucose and fatty acids by skeletal muscle, heart, liver, and adipose tissue, while inhibiting the synthesis of glucose, glycogen and fat in the insulin-sensitive tissues, and enhancing lipolysis in white adipocytes. Chronic effects of physiological levels of NO in vivo include stimulation of angiogenesis, blood flow, mitochondrial biogenesis, and brown adipocyte development. Modulation of NO-mediated pathways through dietary supplementation with L-arginine or its precursor L-citrulline may provide an effective, practical strategy to prevent and treat metabolic syndrome, including obesity, diabetes, and dyslipidemia in mammals, including humans. PMID:23553707

Dai, Zhaolai; Wu, Zhenlong; Yang, Ying; Wang, Junjun; Satterfield, M Carey; Meininger, Cynthia J; Bazer, Fuller W; Wu, Guoyao

2013-03-29

189

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

2010-11-09

190

Generation of Nitric Oxide by a Nitrite Reductase Activity of Xanthine Oxidase: A Potential Pathway for Nitric Oxide Formation in the Absence of Nitric Oxide Synthase Activity  

Microsoft Academic Search

Nitric oxide (NO) synthesis is now well-known to result from the oxidation of L-arginine by a family of NO synthases (NOS). However, under hypoxic conditions this mechanism of NO synthesis may be impaired and NO is formed by a NOS independent mechanism. This study was designed to examine the reduction of nitrite to NO by xanthine oxidase (XO) under hypoxia,

Zhi Zhang; Declan Naughton; Paul G. Winyard; Nigel Benjamin; David R. Blake; Martyn C. R. Symons

1998-01-01

191

Inhibition of nitric oxide synthase activity in cerebral cortical synaptosomes by nitric oxide donors: Evidence for feedback autoregulation  

Microsoft Academic Search

Despite evidence which supports a neurotransmitter-like role for nitric oxide (NO) in the CNS, relatively little is known regarding mechanisms which control NO formation within CNS neurons. In this study, isolated nerve endings (synaptosomes) from rat cerebral cortex were used to ascertain whether NO can autoregulate its own formation within neurons through feedback inhibition of the NO biosynthetic enzyme nitric

Thomas W. Vickroy; Wendi L. Malphurs

1995-01-01

192

Heteroaromatic Selective Inhibitors of Neuronal Nitric Oxide Synthase.  

National Technical Information Service (NTIS)

Compounds inhibiting neuronal nitric oxide synthase (nNOS) for potential treatment in neurodegenerative diseases, such as stroke, Alzheimer's disease, Parkinson's disease, Huntington's disease, such compounds of a formula.

H. Ji R. B. Silverman

2004-01-01

193

21 CFR 868.5165 - Nitric oxide administration apparatus.  

Code of Federal Regulations, 2013 CFR

...Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5165 Nitric oxide administration apparatus. (a) Identification....

2013-04-01

194

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); Keshore R. Bidasee (University of Nebraska Pharmacology); Hong Zeng (University of Nebraska Cellular and Integrative Physiology); PhD William G. Mayhan (University of Nebraska Cellular and Integrative Physiology)

2007-03-01

195

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.

2012-01-01

196

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.

2013-01-01

197

Role of nitric oxide during neurogenesis in the olfactory epithelium.  

PubMed

In mammals, neurogenesis continues during adulthood in restricted places of the nervous system, namely the subventricular zone, the dentate gyms and the olfactory epithelium. A dual role of the second messenger nitric oxide has been reported in such places, either promoting or inhibiting proliferation of neuronal precursors depending on the cellular signal implicated. In this review the regulation of adult olfactory epithelium neurogenesis by nitric oxide is discussed. PMID:17657340

Sulz, Lorena; Bacigalupo, Juan

2007-07-20

198

Iron deficiency suppresses ileal nitric oxide synthase activity  

Microsoft Academic Search

Intestinal motility disorders are more common in women of childbearing age who are prone to iron deficiency anemia. The neurotransmitters\\u000a nitric oxide (NO) and acetylcholine (ACh) play a key role in ileal smooth muscle relaxation and contraction, respectively.\\u000a Iron-containing heme is known to be a cofactor for nitric oxide synthase (NOS), the enzyme responsible for NO production.\\u000a Therefore we tested

Matthew I. Goldblatt; Seong-Ho Choi; Deborah A. Swartz-Basile; Atilla Nakeeb; Sushil K. Sarna; Henry A. Pitt

2001-01-01

199

Effect of Pressure on Burning Velocity of Nitric Oxide Flames  

Microsoft Academic Search

THE burning velocities of stoichiometric mixtures of hydrogen and nitric oxide, and of methane and nitric oxide have been measured by the Bunsen burner method over the pressure-range 0.2-40 atm. abs. An averaged burning velocity was obtained from the measurement of the total volume flow of gas and the total area of the flame front. The experimental technique was essentially

G. A. Mcd. Cummings

1958-01-01

200

Traumatic injury of the spinal cord and nitric oxide  

Microsoft Academic Search

In the current report, we summarize our findings related to the involvement of nitric oxide (NO) in the pathology of spinal cord trauma. We initially studied the distribution of nitric oxide synthase (NOS)-immunolabeled and\\/or nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd; which is highly colocalized with NOS)-stained somata and fibers in the spinal cord of the rabbit. Segmental and laminar distribution

Jozef Maršala; Judita Orendá?ová; Nadežda Luká?ová; Ivo Vanický

2007-01-01

201

Nitric oxide synthase distribution during implantation in the mouse  

Microsoft Academic Search

The peri-implantation period is a critical time during murine development. Although the importance of nitric oxide has been demonstrated during gestation, its role in implantation has not been fully defined. The aim of this study was to quantify (by Western blotting) two prominent nitric oxide synthase (NOS) isoforms, inducible (iNOS) and endothelial (eNOS) and localize all three forms (iNOS, eNOS,

T. L. Purcell; R. Given; K. Chwalisz; R. E. Garfield

1999-01-01

202

Insulin inhibits inducible nitric oxide synthase in skeletal muscle cells  

Microsoft Academic Search

Summary   Recent studies have shown that cytokines and endotoxins impair insulin-stimulated glucose transport by activating the expression\\u000a of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) production in skeletal muscle cells. In this study, we investigated\\u000a whether iNOS induction is modulated by insulin in L6 myocytes. Long term exposure of muscle cells to tumour necrosis factor-?\\u000a (TNF-?), interferon-? (IFN-?)

S. Bédard; B. Marcotte; A. Marette

1998-01-01

203

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

204

Detection of Nitric Oxide by Electron Paramagnetic Resonance Spectroscopy  

PubMed Central

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

Hogg, Neil

2010-01-01

205

The role of nitric oxide in cardiovascular diseases  

Microsoft Academic Search

Nitric oxide (NO) is a gaseous lipophilic free radical cellular messenger generated by three distinct isoforms of nitric oxide synthases (NOS), neuronal (nNOS), inducible (iNOS) and endothelial NOS (eNOS). NO plays an important role in the protection against the onset and progression of cardiovascular disease. Cardiovascular disease is associated with a number of different disorders including hypercholesterolaemia, hypertension and diabetes.

Khalid M. Naseem

2005-01-01

206

Ganoderma lucidum inhibits inducible nitric oxide synthase expression in macrophages  

Microsoft Academic Search

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

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

2005-01-01

207

iNOS-mediated nitric oxide production and its regulation  

Microsoft Academic Search

This review focuses on the production of nitric oxide (NO) by inducible nitric oxide synthase (iNOS) and its regulation under physiological and pathophysiological conditions. NO is an imporant biological mediator in the living organism that is synthesized from L-arginine using NADPH and molecular oxygen. However, the overproduction of NO which is catalyzed by iNOS, a soluble enzyme and active in

Fugen Aktan

2004-01-01

208

Involvement of nitric oxide in lipopolysaccharide induced anorexia  

Microsoft Academic Search

Treatment with the bacterial endotoxin lipopolysaccharide (LPS) is a commonly used model to induce disease-related anorexia. Following LPS treatment inducible nitric oxide synthase (iNOS) is expressed in the hypothalamic arcuate nucleus (ARC), where nitric oxide (NO) inhibits orexigenic neurons. Intracellular STAT signaling is triggered by inflammatory stimuli and has been linked to the transcriptional regulation of iNOS. We evaluated whether

Thomas Riediger; Caroline Cordani; Catarina Soares Potes; Thomas A. Lutz

2010-01-01

209

Nitric oxide induces cell death in Taxus cells  

Microsoft Academic Search

Sodium nitroprusside (SNP), a nitric oxide donor, or centrifugation at 150 times unit gravity, caused a nitric oxide burst in oocyte-derived Taxusbrevifolia 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

M. Cristina Pedroso; Jose R. Magalhaes; Don Durzan

2000-01-01

210

The Oxidation of Hydrazine by Nitric Acid  

SciTech Connect

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

Karraker, D.G.

2001-07-02

211

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

PubMed Central

Objective To determine the level of oxygen-nitrogen stress parameters in the pathogenesis of amebiasis. Methods Twenty-four acute intestinal amebiasis patients and 20 healthy controls were enrolled in the present study. Serum malondialdehyde and nitric oxide levels were determined spectrophotometrically. Results Serum malondialdehyde and nitric oxide levels were significantly higher in acute intestinal amebiasis patients than healthy controls (P<0.001). Conclusions These results suggest that oxidative and nitrosative stress may play a major role in tissue damage in acute intestinal amebiasis patients. Also these parameters can be used to supplement the conventional microscopic method for reliable diagnosis of intestinal amebiasis.

Nam?duru, ES; Tarakc?oglu, M; Nam?duru, M; Kocabas, R; Erbagc?, B; Meram, I; Karaoglan, I; Y?lmaz, N; Cekmen, M

2011-01-01

212

Deleterious effect of nitric oxide inhibition in chronic hepatopulmonary syndrome.  

PubMed

On the basis of limited experimental and clinical studies, increased activity of the vasodilatory nitric oxide-cyclic guanosine monophosphate pathway is considered to play a key role in the pathogenesis of hepatopulmonary syndrome. We report a 46-year-old woman with Child-Pugh class C cirrhosis and progressive dyspnoea for 12 months. Investigations revealed elevated circulating concentrations of nitric oxide metabolites and exhaled nitric oxide levels, an hyperdynamic circulation with low systemic vascular resistance and mean arterial pressure, a large right to left intrapulmonary shunt fraction on radiolabelled macroaggregated albumin perfusion scanning, positive contrast-enhanced echocardiography, reduced diffusion capacity of carbon monoxide, hypoxaemia and orthodeoxyia, all in keeping with severe hepatopulmonary syndrome. Sequential inhibition of the nitric oxide-cyclic guanosine monophosphate pathway using curcumin (diferuloylmethane), terlipressin and methylene blue was associated with substantial improvements in vascular tone and the hyperdynamic circulation. No improvement, however, in the intrapulmonary shunt was demonstrated. Both hypoxaemia and orthodeoxia were substantially, reproducibly and reversibly worsened with all three treatments. Our findings argue against the contention that intrapulmonary shunting and impairment in arterial oxygenation in hepatopulmonary syndrome are necessarily the consequence of on-going, nitric oxide-cyclic guanosine monophosphate-mediated vasodilatation, at least in the chronic stage, and, given the possibility of substantial worsening of pulmonary oxygen exchange, suggest that inhibition of the nitric oxide-cyclic guanosine monophosphate pathway should be avoided in this setting. PMID:17353701

Almeida, John A; Riordan, Stephen M; Liu, Jia; Galhenage, Sumedha; Kim, Robert; Bihari, David; Wegner, Eva A; Cranney, Gregory B; Thomas, Paul S

2007-04-01

213

(-)-epicatechin activation of endothelial cell endothelial nitric oxide synthase, nitric oxide, and related signaling pathways.  

PubMed

Recent reports indicate that (-)-epicatechin can exert cardioprotective actions, which may involve endothelial nitric oxide synthase (eNOS)-mediated nitric oxide production in endothelial cells. However, the mechanism by which (-)-epicatechin activates eNOS remains unclear. In this study, we proposed to identify the intracellular pathways involved in (-)-epicatechin-induced effects on eNOS, using human coronary artery endothelial cells in culture. Treatment of cells with (-)-epicatechin led to time- and dose-dependent effects that peaked at 10 minutes at 1 mumol/L. (-)-Epicatechin treatment activates eNOS via serine 633 and serine 1177 phosphorylation and threonine 495 dephosphorylation. Using specific inhibitors, we have established the participation of the phosphatidylinositol 3-kinase pathway in eNOS activation. (-)-Epicatechin induces eNOS uncoupling from caveolin-1 and its association with calmodulin-1, suggesting the involvement of intracellular calcium. These results allowed us to propose that (-)-epicatechin effects may be dependent on actions exerted at the cell membrane level. To test this hypothesis, cells were treated with the phospholipase C inhibitor U73122, which blocked (-)-epicatechin-induced eNOS activation. We also demonstrated inositol phosphate accumulation in (-)-epicatechin-treated cells. The inhibitory effects of the preincubation of cells with the calmodulin-dependent kinase II (CaMKII) inhibitor KN-93 indicate that (-)-epicatechin-induced eNOS activation is at least partially mediated via the Ca(2+)/CaMKII pathway. The (-)-epicatechin stereoisomer catechin was only partially able to stimulate nitric oxide production in cells. Together, these results strongly suggest the presence of a cell surface acceptor-effector for the cacao flavanol (-)-epicatechin, which may mediate its cardiovascular effects. PMID:20404222

Ramirez-Sanchez, Israel; Maya, Lisandro; Ceballos, Guillermo; Villarreal, Francisco

2010-04-19

214

Nitric oxide regulation of free radical- and enzyme-mediated lipid and lipoprotein oxidation.  

PubMed

The regulation of nonenzymatic and enzymatic lipid oxidation reactions by nitric oxide (.NO) is potent and pervasive and reveals novel non-cGMP-dependent reactivities for this free radical inflammatory and signal transduction mediator.NO and its metabolites stimulate and inhibit lipid peroxidation reactions, modulate enzymatically catalyzed lipid oxidation, complex with lipid-reactive metals, and alter proinflammatory gene expression. Through these mechanisms,.NO can regulate nonenzymatic lipid oxidation and the production of inflammatory and vasoactive eicosanoids by prostaglandin endoperoxide synthase and lipoxygenase. The accumulation of macrophages and oxidized low density lipoprotein within the vascular wall can also be modulated by.NO. A key determinant of the pro-oxidant versus oxidant-protective influences of.NO is the underlying oxidative status of tissue. When.NO is in excess of surrounding oxidants, lipid oxidation and monocyte margination into the vascular wall are attenuated, producing antiatherogenic effects. However, when endogenous tissue rates of oxidant production are accelerated or when tissue oxidant defenses become depleted,.NO gives rise to secondary oxidizing species that can increase membrane and lipoprotein lipid oxidation as well as foam cell formation in the vasculature, thus promoting proatherogenic effects. In summary,.NO is a multifaceted molecule capable of reacting via multiple pathways to modulate lipid oxidation reactions, thereby impacting on tissue inflammatory reactions. PMID:10894807

Bloodsworth, A; O'Donnell, V B; Freeman, B A

2000-07-01

215

Nitric oxide negatively regulates mammalian adult neurogenesis  

NASA Astrophysics Data System (ADS)

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

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

2003-08-01

216

Nitric oxide transport in an axisymmetric stenosis  

PubMed Central

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

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

2012-01-01

217

Gating NO release from nitric oxide synthase.  

PubMed

We have investigated the kinetics of NO escape from Geobacillus stearothermophilus nitric oxide synthase (gsNOS). Previous work indicated that NO release was gated at position 223 in mammalian enzymes; our kinetics experiments include mutants at that position along with measurements on the wild type enzyme. Employing stopped-flow UV-vis methods, reactions were triggered by mixing a reduced enzyme/N-hydroxy-l-arginine complex with an aerated buffer solution. NO release kinetics were obtained for wt NOS and three mutants (H134S, I223V, H134S/I223V). We have confirmed that wt gsNOS has the lowest NO release rate of known NOS enzymes, whether bacterial or mammalian. We also have found that steric clashes at positions 223 and 134 hinder NO escape, as judged by enhanced rates in the single mutants. The empirical rate of NO release from the gsNOS double mutant (H134/I223V) is nearly as rapid as that of the fastest mammalian enzymes, demonstrating that both positions 223 and 134 function as gates for escape of the product diatomic molecule. PMID:22148177

Whited, Charlotte A; Warren, Jeffrey J; Lavoie, Katherine D; Weinert, Emily E; Agapie, Theodor; Winkler, Jay R; Gray, Harry B

2011-12-07

218

Dipyridamole potentiates platelet inhibition by nitric oxide.  

PubMed

In a placebo-controlled double blind cross-over experiment the adenosine uptake inhibitor dipyridamole (400 mg/day) did not affect ex vivo platelet aggregation induced by collagen or adenosine-diphosphate (ADP) in an electronic whole blood aggregometer (WBA). Dipyridamole was also inactive in vitro, unless red blood cell injury was deliberately enhanced, thereby increasing the level of free adenine nucleotides. Since dipyridamole also inhibits cyclic guanosine monophosphate (GMP) phosphodiesterase (PDE), we used platelet rich plasma (PRP) to study its interaction with authentic and endothelium-derived nitric oxide (NO). The latter inhibits platelets by increasing cyclic GMP. Dipyridamole (1 to 30 microM), either alone or in combination with a subthreshold concentration of prostacyclin (PGI2), was inactive. However, when combined with a subthreshold concentration of NO, dipyridamole caused a concentration-dependent platelet suppression, which became more pronounced when PGI2 was present as well. It is concluded that dipyridamole could reduce the threshold for platelet suppression by NO through inhibition of cyclic GMP PDE. PMID:1746006

Bult, H; Fret, H R; Jordaens, F H; Herman, A G

1991-09-01

219

The nitric oxide reductase of Paracoccus denitrificans.  

PubMed Central

The nitric oxide (NO) reductase activity of the cytoplasmic membrane of Paracoccus denitrificans can be solubilized in dodecyl maltoside with good retention of activity. The solubilized enzyme lacks NADH-dependent activity, but can be assayed with isoascorbate plus 2,3,5,6-tetramethylphenylene-1,4-diamine as electron donor and with horse heart cytochrome c as mediator. Reduction of NO was measured with an amperomeric electrode. The solubilized enzyme could be separated from other electron-transport components, including the cytochrome bc1 complex and nitrite reductase, by several steps of chromatography. The purified enzyme had a specific activity of 11 mumols.min-1.mg of protein-1 and the Km(NO) was estimated as less than 10 microM. The enzyme formed N2O from NO with the expected stoichiometry. These observations support the view that NO reductase is a discrete enzyme that participates in the denitrification process. The enzyme contained both b- and c-type haems. The former was associated with a polypeptide of apparent molecular mass 37 kDa and the latter with a polypeptide of 18 kDa. Polypeptides of 29 and 45 kDa were also identified in the purified protein which showed variable behaviour on electrophoresis in polyacrylamide gels. Images Fig. 8.

Carr, G J; Ferguson, S J

1990-01-01

220

Nitric Oxide, Oxidative Stress and Inflammation in Pulmonary Arterial Hypertension  

PubMed Central

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

Crosswhite, Patrick; Sun, Zhongjie

2010-01-01

221

Chondrocyte apoptosis induced by nitric oxide.  

PubMed Central

Chondrocytes stimulated with IL-1 produce high levels of nitric oxide (NO), which inhibits proliferation induced by transforming growth factor-beta or serum. This study analyzes the role of NO and IL-1 in the induction of chondrocyte cell death. NO generated from sodium nitroprusside induced apoptosis in cultured chondrocytes as demonstrated by electron microscopy, 4',6-dianidino-2-phenylindole dihydrochloride staining, FACS analysis, and histochemical detection of DNA fragmentation. Similar results were obtained with two other NO donors, 3-morpholinosynonimide-hydrochloride and s-nitroso-N-acetyl-D-L-penicillamine. In contrast, oxygen radicals generated by hypoxanthine/xanthine oxidase caused necrosis but did not induce chondrocyte apoptosis. To analyze whether endogenously generated NO induces apoptosis, chondrocytes were stimulated with IL-1, but there was no evidence for apoptotic changes. Combinations of NO inducers such as IL-1, lipopolysaccharide, tumor necrosis factor, and interferon-gamma also failed to trigger apoptosis. IL-1-stimulated chondrocytes are known to produce oxygen radicals that react with NO to form products that can induce cell death in other systems. We thus tested IL-1 in combination with the oxygen radical scavengers N-acetyl cysteine, dimethyl sulfoxide, or 5,5'-dimetylpyrroline 1-oxide. Under these conditions IL-1 was able to induce apoptosis, which was inhibited in a dose-dependent manner by the NO synthase inhibitor N-monomethyl L-arginine. Conversely, endogenous oxygen radicals induced by inflammatory mediators caused necrosis under conditions in which the simultaneous production of NO was reduced. These results suggest that NO, but not oxygen radicals, is the primary inducer of apoptosis in human articular chondrocytes. Images Figure 1 Figure 2 Figure 4 Figure 7

Blanco, F. J.; Ochs, R. L.; Schwarz, H.; Lotz, M.

1995-01-01

222

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

223

Role of Inducible Nitric Oxide Synthase-Derived Nitric Oxide in Silica-Induced Pulmonary Inflammation and Fibrosis  

Microsoft Academic Search

Inhalation of crystalline silica can produce lung inflammation and fibrosis. Inducible nitric oxide synthase (iNOS)-derived nitric oxide (NO) is believed to be involved in silica-induced lung disease. To investigate the role of iNOS-derived NO in this disease, the responses of iNOS knockout (KO) versus C57Bl\\/6J wild-type (WT) mice to silica were compared. Male mice (8–10 wk old, mean body weight

Patti C. Zeidler; Ann Hubbs; Lori Battelli; Vincent Castranova

2004-01-01

224

Expression of nitric oxide synthase and effect of substrate manipulation of the nitric oxide pathway in mouse ovarian follicles  

Microsoft Academic Search

BACKGROUND: Nitric oxide (NO) is a cell messenger with multiple actions in different biological systems, impli- cated in the control of follicle and oocyte function. NO is formed from L-arginine by isoforms of nitric oxide synthase (NOS) via NG-hydroxy-L-arginine, with L-citrulline as a byproduct. This study aimed to show how modula- tion of NO by manipulating NOS substrates would affect

Leila M. Mitchell; C. Richard Kennedy; Geraldine M. Hartshorne; Coventry CV

2004-01-01

225

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

EPA Science Inventory

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

226

Nitric oxide-derived oxidants with a focus on peroxynitrite: molecular targets, cellular responses and therapeutic implications.  

PubMed

Nitric oxide participates in a wide array of physiological processes, ranging from neurotransmission to precursor of cytotoxic effector molecules of the immune system. Although nitric oxide is a mildly reactive intermediary, it can act as a precursor of strong oxidants under pathological conditions associated with oxidative stress including cardiovascular, inflammatory and neurodegenerative disorders. Peroxynitrite, the reaction product of nitric oxide with superoxide radicals, emerges as one of the principal players of nitric oxidederived toxicity due to its facile formation and ability to react with several critical cellular targets including, thiols, proteins, lipids and DNA. The extent of "nitroxidative stress" is determined by several factors, including the concentration and exposure time to this reactive species or its derived radicals and by the ability of the cell to face the oxidative challenge by means of its antioxidant defenses. The inflicted biomolecular damage can result on minimal and reversible changes to cell and tissue physiology, to alteration in bioenergetics, disruption of DNA integrity, mitochondrial dysfunction and even cell death. Although dissecting the free radical chemistry pathways responsible of cell/tissue disturbance of oxidative signaling and promotion of oxidative damage arising from nitric oxide-derived oxidants in a biological context is a vast endeavor, is an ineludible task in order to generate a rational therapeutic approach to modulate nitroxidative stress. Several redox-based pharmacological strategies with a collection of compounds with varying mechanisms of action have been tested at the cellular, preclinical and even clinical levels, and some novel and promising developments are underway. This review deals with key kinetic and biochemical aspects of nitric oxide-derived oxidant formation and reactions in biological systems, emphasizing the current evidence at the biochemical, cell/tissue and animal/human levels that support a pathophysiological role for peroxynitrite and related species in human pathology. In addition, a selection of available pharmacological tools will be discussed as an effort to rationalize antioxidant and/or redox-based therapeutic interventions in disease models. PMID:21933142

Calcerrada, P; Peluffo, G; Radi, R

2011-12-01

227

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

Microsoft Academic Search

BACKGROUND: Platelet-activating factor and nitric oxide may be involved in the initiation of human labour as inflammatory mediators. The aim of this study was to test whether platelet-activating factor and lipopolysaccharide were able to induce nitric oxide synthase expression and stimulate the production of nitric oxide in human fetal membrane explants in culture. METHODS: Fetal membranes were collected from Caesarean

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

2004-01-01

228

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

2009-09-12

229

Inducible Nitric Oxide Synthase Genetic Polymorphism and Risk of Asbestosis  

PubMed Central

Asbestos, a known occupational pollutant, may upregulate the activity of inducible nitric oxide synthase (iNOS) and thus the production of nitric oxide (NO). This study investigated whether iNOS?(CCTTT)n polymorphism is associated with an increased asbestosis risk in exposed workers. The study cohort consisted of 262 cases with asbestosis and 265 controls with no asbestos-related disease. For each subject the cumulative asbestos exposure data were available. The number of CCTTT repeats was determined following PCR amplification of the iNOS promoter region. Logistic regression was performed to estimate asbestosis risk. The OR of asbestosis was 1.20 (95%? CI = 0.85–1.69) for the LL genotype compared to the combined SL and SS genotypes and 1.26 (95% CI = 0.86–1.85) for the LL genotype compared to the SL genotype. The results of this study are borderline significant and suggest a possible role of iNOS?(CCTTT)n polymorphism in the risk of asbestosis; however, further studies are needed.

Franko, Alenka; Dodic-Fikfak, Metoda; Arneric, Niko; Dolzan, Vita

2011-01-01

230

Auxin and nitric oxide control indeterminate nodule formation  

PubMed Central

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

Pii, Youry; Crimi, Massimo; Cremonese, Giorgia; Spena, Angelo; Pandolfini, Tiziana

2007-01-01

231

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

232

Salt-induced hemodynamic regulation mediated by nitric oxide.  

PubMed

Excess daily salt intake impairs vasodilatation and enhances vasoconstriction, resulting in reduction of regional blood flow and elevation of blood pressure in healthy individuals and hypertensive patients with either salt sensitivity or not tested for salt sensitivity or not evaluated for salt sensitivity. The mechanism may involve decreased production of nitric oxide via endothelial nitric oxide synthase (eNOS), impaired bioavailability of nitric oxide, and elevated plasma levels of asymmetric dimethylarginine (ADMA). Experimental animals, irrespective of salt sensitivity, although less extensive in those with salt-resistance, fed a high-salt diet have deteriorated endothelial functions; the mechanisms involved include an impairment of eNOS activation, a decrease in eNOS expression, and an increase in oxidative stress and ADMA. The imbalance of interactions between nitric oxide and angiotensin II is also involved in salt sensitivity. Deficiency of nitric oxide formed via neuronal NOS and inducible NOS may contribute to salt-induced hypertension. Reduced daily salt intake, therefore, would be the most rational prophylactic measure against the development of hypertension. PMID:21150639

Toda, Noboru; Arakawa, Kikuo

2011-03-01

233

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.

Eldred, William D.; Blute, Todd A.

2006-01-01

234

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

235

The Nitric Acid Oxidation of Selected Alcohols and Ketones.  

ERIC Educational Resources Information Center

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

Field, Kurt W.; And Others

1985-01-01

236

Nitric oxide synthase and neuronal vulnerability in parkinson's disease  

Microsoft Academic Search

Parkinson's disease is characterized by a loss of dopaminergic neurons in the mesencephalon. Although the mechanism of this neuronal loss is still unknown, oxidative stress is very likely involved in the cascade of events leading to nerve cell death. Since nitric oxide could be involved in the production of free radicals, we analysed, using immunohistochemistry and histochemistry, the production systems

S. Hunot; F. Boissière; B. Faucheux; B. Brugg; A. Mouatt-Prigent; Y. Agid; E. C. Hirsch

1996-01-01

237

Inflammatory neurodegeneration mediated by nitric oxide, glutamate, and mitochondria  

Microsoft Academic Search

In inflammatory, infectious, ischemic, and neurodegenerative pathologies of th central nervous system (CNS) glia become “activated”\\u000a by inflammatory mediators, and express new proteins such as the inducible isoform of nitric oxide synthase (iNOS). Although\\u000a these activated glia have beneficial roles, in vitro they potently kill cocultured neurons, and there is increasing evidence\\u000a that they contribute to pathology in vivo. Nitric

Guy C. Brown; Anna Bal-Price

2003-01-01

238

Nitric oxide is involved in male sexual behavior of rats  

Microsoft Academic Search

In male rats, whether sexually experienced or sexually naive, the intraperitoneal administration of l-arginine (the natural substrate for nitric oxide synthase) (10, 25, 50 mg\\/kg) both increased the percentage of copulating in sexually naive rats and improved the indexes of sexual performance in sexually experienced rats, whereas the intraperitoneal administration of NG-nitro-l-arginine methyl ester (L-NAME) (a potent inhibitor of nitric

Augusta Benelli; Alfio Bertolini; Rosanna Poggioli; Elena Cavazzuti; Laura Calzà; Luciana Giardino; Rossana Arletti

1995-01-01

239

Nitric oxide is involved in male sexual behavior of rats.  

PubMed

In male rats, whether sexually experienced or sexually naive, the intraperitoneal administration of L-arginine (the natural substrate for nitric oxide synthase) (10, 25, 50 mg/kg) both increased the percentage of copulating in sexually naive rats and improved the indexes of sexual performance in sexually experienced rats, whereas the intraperitoneal administration of N(G)-nitro-L-arginine methyl ester (L-NAME) (a potent inhibitor of nitric oxide synthase) (10, 25, 50 mg/kg) had opposite effects. In contrast, after intracerebroventricular administration, L-arginine (25, 50, 100 microg/rat) had no effect - whether in naive or in experienced rats - whereas L-NAME completely prevented ejaculation in naive rats, at the dose of 100 microg/rat, but had no effect at all in experienced rats, up to the dose of 300 microg/rat. Finally, a direct relationship seems to exist between male copulatory performance and nitric oxide synthase activity in a discrete and defined brain area, the paraventricular nucleus of the hypothalamus: indeed, nitric oxide synthase mRNA expression in this nucleus in sexually potent rats is about twice that in sexually impotent rats. It is concluded that nitric oxide synthase is involved in the expression of male sexual activity, in spite of some inconsistencies that are hard to interpret. PMID:8750712

Benelli, A; Bertolini, A; Poggioli, R; Cavazzuti, E; Calza, L; Giardino, L; Arletti, R

1995-12-29

240

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

Microsoft Academic Search

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

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

1996-01-01

241

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

Microsoft Academic Search

Nitric oxide-derived oxidants such as nitrogen dioxide and peroxynitrite have been receiving increasing attention as mediators of nitric oxide toxicity. Indeed, nitrated and nitrosated compounds have been detected in biological fluids and tissues of healthy subjects and in higher yields in patients under inflammatory or infectious conditions as a consequence of nitric oxide overproduction. Among them, nitrated lipids have been

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

2005-01-01

242

Nitric oxide effect on coloncyte metabolism: Co-action of sulfides and peroxide  

Microsoft Academic Search

Luminal levels of nitric oxide\\/nitrite are high in colitis. Whether nitric oxide is injurious or protective to human colonocytes is unknown and the role of nitric oxide in the genesis of colitis unclear. The aims were to establish whether nitric oxide was injurious to oxidation of substrates (n-butyrate and D-glucose) in isolated human and rat colonocytes both alone and in

William E. Roediger; Wendy J. Babidge

2000-01-01

243

Redox interactions of nitric oxide with dopamine and its derivatives.  

PubMed

Nitric oxide (*NO) is a ubiquitous diffusible messenger in the central nervous system. *NO and derived nitrogen species may interact with catecholamines, thus, modifying not only its regulatory actions but also producing oxidants and free radicals that are likely to trigger toxic pathways in the nervous system. Oxidative pathways and chain oxidation reactions triggered by catecholamines may be broken by ascorbate and glutathione, of which there is ample supply in the brain. At the subcellular level, mitochondria and cytosolic dopamine storage vesicles are likely to provide site-specific settings for *NO and catecholamines interactions. Thus, a complex picture emerges in which the steady- state levels of the individual reactants, the rate constants of the reactions involved, the oxygen tension, and the compartmentalization of reactions determine the biological significance of the redox interactions between *NO and dopamine metabolism in the brain. The physiological relevance of *NO-driven chemical modifications of dopamine and its derivatives and the ensuing free radical production are discussed in connection with the neurodegeneration inherent in Parkinson's disease. PMID:15691585

Antunes, Fernando; Nunes, Carla; Laranjinha, João; Cadenas, Enrique

2005-03-15

244

Protective effects of pu-erh tea on LDL oxidation and nitric oxide generation in macrophage cells  

Microsoft Academic Search

Effects of water extract of pu-erh tea (WEPT) on low density of lipoprotein (LDL) oxidation and their regulation of nitric oxide in macrophage RAW 264.7 cells were determined. The results showed that WEPT significantly scavenged H2O2 in a concentration-dependent manner. In the range of 0–0.1mg\\/mL, the inhibitory action on LDL oxidation increased with increasing concentration of WEPT. In addition, WEPT

Bor-Sen Wang; Hui Mei Yu; Lee-Wen Chang; Wen-Jye Yen; Pin-Der Duh

2008-01-01

245

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

PubMed Central

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

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

2009-01-01

246

Melatonin inhibits visfatin-induced inducible nitric oxide synthase expression and nitric oxide production in macrophages.  

PubMed

Aberrant expression of inducible nitric oxide synthase (iNOS) in macrophages, which has been reported to be suppressed by melatonin, has an important contribution in the development of pathological inflammation. Visfatin, an adipokine, regulates the expression of various inflammatory factors, leading to inflammation; however, the influence of visfatin on iNOS-driven processes in macrophages is unclear. Here, we report the assessment of the role of visfatin in the regulation of iNOS gene expression in macrophages. Our data show that the levels of iNOS protein in peritoneal macrophages as well as nitric oxide (NO) in blood plasma were significantly lower after lipopolysaccharide treatment in visfatin(+/-) mice than those in the WT mice. In addition, visfatin increases iNOS mRNA and protein levels in RAW 264.7 cells, along with increasing production of NO. The enhancement of iNOS expression was prevented by treating the cells with inhibitors of the Janus kinase 2/signal transducers and activators of transcription 3 (JAK2/STAT3), nuclear factor (NF)-?B, extracellular signal-regulated kinase 1/2, and c-Jun N-terminal kinase pathways. Our results also show that visfatin-induced iNOS expression and NO production were significantly inhibited by melatonin, an effect that was closely associated with a reduction in phosphorylated JAK2/STAT3 levels and with the inhibition of p65 translocation into nucleus. In conclusion, our data show, for the first time, that melatonin suppresses visfatin-induced iNOS upregulation in macrophages by inhibiting the STAT3 and NF-?B pathways. Moreover, our data suggest that melatonin could be therapeutically useful for attenuating the development of visfatin-iNOS axis-associated diseases. PMID:23869429

Kang, Young-Soon; Kang, Yong-Gyu; Park, Hyun-Joo; Wee, Hee-Jun; Jang, Hye-Ock; Bae, Moon-Kyoung; Bae, Soo-Kyung

2013-07-22

247

Licofelone-nitric oxide donors as anticancer agents.  

PubMed

Five licofelone ([2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizin-5-yl]acetic acid) nitric oxide donor conjugates were developed by a parallel synthesis approach. The biological screening revealed that compounds with a propyl (6b), butyl (6c), or octyl (6d) chain between licofelone and the nitric oxide donor exhibited high antiproliferative potency at MCF-7 and MDA-MB-231 breast cancer as well as at HT-29 colon cancer cells. Moreover, 6b-d possessed at least 2-fold higher cytotoxicity at MDA-MB-231 cells than the parent compound licofelone although they showed less inhibitory activity at COX-1 and COX-2. A correlation between COX inhibition and growth inhibitory properties is not visible. However, the high levels of nitric oxide production of the compounds may result in their high cytotoxic activity. PMID:21681808

Liu, Wukun; Zhou, Jinpei; Liu, Yinglin; Liu, Haoran; Bensdorf, Kerstin; Guo, Cancheng; Gust, Ronald

2011-06-16

248

Direct evidence for nitric oxide formation from glyceryl trinitrate during incubation with intact bovine pulmonary artery.  

PubMed

It has been proposed that the mechanism of the vasodilator action of glyceryl trinitrate (GTN) involves biotransformation to nitric oxide. A sensitive chemiluminescence method for nitric oxide determination was used to test this hypothesis. In four experiments, bovine pulmonary artery (BPA) was incubated with GTN (0.1 mM) in Krebs' solution (2 mL) containing 30 mM KCl, and in anaerobic conditions using 95% Ar - 5% CO2, in a sealed micro-Fernbach flask (6.2-mL volume). After incubation for 2, 5, 10, or 20 min at 37 degrees C, 400-microL aliquots of headspace gas were removed and injected into a redox chemiluminescence detector. Nitric oxide formation was first measurable at 5 min (76 +/- 53 pmol/g wet wt. BPA), and increased with incubation time (174 +/- 46 pmol/g wet wt. BPA after 10 min and 310 +/- 67 pmol/g wet wt. BPA after 20 min). This is the first direct chemical measurement of nitric oxide formation during interaction of GTN with vascular smooth muscle. These data support the concept that GTN is a nitrovasodilator prodrug acting via the formation of nitric oxide. PMID:1521184

Marks, G S; McLaughlin, B E; Nakatsu, K; Brien, J F

1992-02-01

249

Exhaled nitric oxide (FENO) in non-pulmonary diseases.  

PubMed

Exhaled nitric oxide (F(E)NO) represents the only exhaled biomarker that has reached clinical practice even in primary care settings, due to the non-invasiveness of its assessment and ease of repeat measurements, even in patients with severe airflow obstruction. While F(E)NO has been suggested as a readily determined biomarker that can aid in the diagnosis and management of asthma, its potential role in pathophysiology of non-pulmonary diseases is less clear and therefore remains to be established. The purpose of the present review is to highlight the current literature investigating the use of F(E)NO in the diagnosis and management of non-pulmonary diseases. PMID:22549131

Bucca, Caterina; Cicolin, Alessandro; Guida, Giuseppe; Heffler, Enrico; Brussino, Luisa; Rolla, Giovanni

2012-05-02

250

Role of nitric oxide in the anticonvulsive effect of progesterone.  

PubMed

Described here is an investigation of the potential interaction of the nitric oxide signaling pathway with the anticonvulsant effects of progesterone. In ovariectomized Swiss mice, the threshold for seizures induced by intravenous infusion of pentylenetetrazole was determined after treatment with progesterone (25, 50, or 75 mg/kg, given subcutaneously 6h before seizure testing) or vehicle. Progesterone induced significant anticonvulsive activity at moderate (50 mg/kg) and high (75 mg/kg) doses. This effect of progesterone was abolished by the NO precursor compound L-arginine (200 mg/kg). Moreover, when subeffective doses of progesterone (25 mg/kg) and the NO synthase inhibitor N(omega)-nitro-L-arginine methyl ester (10 mg/kg) were injected, a strong anticonvulsant effect was observed. These findings suggest a potential role for NO signaling as an anticonvulsant target in females. PMID:18703162

Gholipour, Taha; Jabbarzadeh, Atieh; Riazi, Kiarash; Rasouli, Aylar; Nezami, Behtash Ghazi; Sharifzadeh, Mohammad; Dehpour, Ahmad Reza

2008-08-30

251

Concentration of nitric oxide metabolites in middle ear effusion.  

PubMed

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

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

2001-07-30

252

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

253

Nitric oxide as a potential biomarker in inflammatory bowel disease.  

PubMed

The aim of this study was to investigate changes in serum nitric oxide (NO) concentration in inflammatory bowel diseases (IBD) patients and its use as potential biomarker in differential diagnosis of ulcerative colitis (UC) and Crohn's disease (CD) and in disease activity assessment. In 60 patients of both genders - 30 with ulcerative colitis and 30 with Crohn's disease - and 30 controls serum nitric oxide concentration was determined by measuring nitrite concentration, a stable metabolic product of NO with oxygen. Conversion of nitrates (NO3-) to nitrites (NO2-) was done with elementary zinc. The nitrite concentration was determined by classic colorimetrical Griess reaction. Median serum NO concentration was statistically different (p=0,0005) between UC patients (15.25 µmol/L; 13.47 - 19.88 µmol/L), CD patients (14.54 µmol/L; 13.03 -16.32 µmol/L) and healthy controls (13.29 µmol/L; 12.40 - 13.92 µmol/L). When active UC and CD patients were compared with inactive UC and CD patients respectively a significant difference in serum NO level was found (p=0.0005). With a cut-off level of 17.39 µmol/L NO had a sensitivity of 100% and a specificity of 100% in discriminating between active and inactive UC patients. With cut-off value of 14.01 µmol/L serum NO level had a sensitivity of 88% and a specificity of 69% in distinguishing between patients with active CD and inactive CD. Serum NO concentration is a minimally invasive and rapid tool for discriminating between active and inactive IBD patients and could be used as useful biomarker in monitoring of disease activity in IBD patients. PMID:23448603

Avdagi?, Nesina; Za?iragi?, Asija; Babi?, Nermina; Huki?, Mirsada; Seremet, Mensura; Lepara, Orhan; Nakaš-I?indi?, Emina

2013-02-01

254

Stimulation of cardiac fatty acid oxidation by leptin is mediated by a nitric oxide–p38 MAPK-dependent mechanism  

Microsoft Academic Search

Leptin has previously been shown to stimulate fatty acid oxidation independent of AMP-activated protein kinase (AMPK). Nitric oxide and p38 mitogen activated protein kinase (MAPK) are known effectors of leptin signaling. The aim of the present study was to determine whether nitric oxide and p38 MAPK mediate the stimulation of leptin by MAPK. Hearts from male Sprague–Dawley rats were mounted

Vijay Sharma; Sally Mustafa; Natasha Patel; Richard Wambolt; Michael F. Allard; John H. McNeill

2009-01-01

255

Nitric oxide, S-Nitrosation, and endothelial permeability.  

PubMed

S-Nitrosation is rapidly emerging as a regulatory mechanism in vascular biology, with particular importance in the onset of hyperpermeability induced by pro-inflammatory agents. This review focuses on the role of endothelial nitric oxide synthase (eNOS)-derived nitric oxide (NO) in regulating S-Nitrosation of adherens junction proteins. We discuss evidence for translocation of eNOS, via caveolae, to the cytosol and analyze the significance of eNOS location for S-Nitrosation and onset of endothelial hyperpermeability to macromolecules. © 2013 IUBMB Life, 65(10):819-826, 2013. PMID:24078390

Durán, Walter N; Beuve, Annie V; Sánchez, Fabiola A

2013-09-17

256

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

National Technical Information Service (NTIS)

Research during recent years has established nitric oxide as a unique signaling molecule that plays important roles in the regulation of the cardiovascular, nervous, immune, and other systems. Nitric oxide has also been implicated in the control of the se...

I. A. Reid

1994-01-01

257

In vitro inducible nitric oxide synthesis inhibitory active constituents from Fraxinus rhynchophylla.  

PubMed

Bioassay-guided fractionation of an H2O extract of the barks of Fraxinus rhynchophylla has furnished two inducible nitric oxide synthase (iNOS) inhibitory compounds, ferulaldehyde (1) and scopoletin (3) together with a coumarin, fraxidin (2). Compounds 1 and 3 showed inhibition of nitric oxide (NO) synthesis in a dose-dependent manner by murine macrophage-like RAW 264.7 cells stimulated with interferon-gamma (IFN-gamma) plus lipopolysaccharide (LPS). The inhibition of NO synthesis of 1 was reflected in the decreased amount of iNOS protein, as determined by Western blotting. PMID:10575381

Kim, N Y; Pae, H O; Ko, Y S; Yoo, J C; Choi, B M; Jun, C D; Chung, H T; Inagaki, M; Higuchi, R; Kim, Y C

1999-10-01

258

Dynamic regulation of metabolism and respiration by endogenously produced nitric oxide protects against oxidative stress  

PubMed Central

One of the many biological functions of nitric oxide is the ability to protect cells from oxidative stress. To investigate the potential contribution of low steady state levels of nitric oxide generated by endothelial nitric oxide synthase (eNOS) and the mechanisms of protection against H2O2, spontaneously transformed human ECV304 cells, which normally do not express eNOS, were stably transfected with a green fluorescent-tagged eNOS cDNA. The eNOS-transfected cells were found to be resistant to injury and delayed death following a 2-h exposure to H2O2 (50–150 ?M). Inhibition of nitric oxide synthesis abolished the protective effect against H2O2 exposure. The ability of nitric oxide to protect cells depended on the presence of respiring mitochondria as ECV304+eNOS cells with diminished mitochondria respiration (??) are injured to the same extent as nontransfected ECV304 cells and recovery of mitochondrial respiration restores the ability of nitric oxide to protect against H2O2-induced death. Nitric oxide also found to have a profound effect in cell metabolism, because ECV304+eNOS cells had lower steady state levels of ATP and higher utilization of glucose via the glycolytic pathway than ECV304 cells. However, the protective effect of nitric oxide against H2O2 exposure is not reproduced in ECV304 cells after treatment with azide and oligomycin suggesting that the dynamic regulation of respiration by nitric oxide represent a critical and unrecognized primary line of defense against oxidative stress.

Paxinou, Evgenia; Weisse, Marie; Chen, Qiping; Souza, Jose M.; Hertkorn, Caryn; Selak, Mary; Daikhin, Evgueni; Yudkoff, Marc; Sowa, Grzegorz; Sessa, William C.; Ischiropoulos, Harry

2001-01-01

259

Neuroprotection by nitric oxide against hydroxyl radical-induced nigral neurotoxicity  

Microsoft Academic Search

We investigated the effects of nitric oxide on an in vitro and in vivo generation of hydroxyl radicals, and in vivo neurotoxicity caused by intranigral infusion of ferrous citrate in rats. The formation of hydroxyl radicals in vitro, without exogenous hydrogen peroxide, was dose-dependent. Some nitric oxide donors (e.g. sodium nitroprusside) stimulated, while others (nitroglycerin, diethylamine\\/nitric oxide, nitric oxide in

K. P Mohanakumar; I Hanbauer; C. C Chiueh

1998-01-01

260

Mitochondrial nitric oxide inhibits ATP synthesis Effect of free calcium in rat heart  

Microsoft Academic Search

Summary.  ?Nitric oxide is a small potentially toxic molecule and a diatomic free radical. We report the interaction of L-arginine,\\u000a oxygen and calcium with the synthesis of nitric oxide in heart mitochondria. Nitric oxide synthesis is increased in broken\\u000a rat heart mitochondria compared with intact and permeabilized mitochondria. Intact mitochondria subjected to hypoxia-reoxygenation\\u000a conditions accumulated nitric oxide that inhibits oxygen consumption

A. Saavedra-Molina; J. Ramírez-Emiliano; M. Clemente-Guerrero; V. Pérez-Vázquez; L. Aguilera-Aguirre; J. C. González-Hernández

2003-01-01

261

Pulmonary Nanoparticle Exposure Disrupts Systemic Microvascular Nitric Oxide Signaling  

PubMed Central

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

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

2009-01-01

262

Decoding the substrate supply to human neuronal nitric oxide synthase.  

PubMed

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

Simon, Alexandra; Karbach, Susanne; Habermeier, Alice; Closs, Ellen I

2013-07-09

263

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.

Habermeier, Alice; Closs, Ellen I.

2013-01-01

264

Neuronal Nitric Oxide Mediates Cerebral Vasodilatation during Acute Hypertension  

PubMed Central

Parasympathetic nerves from the pterygopalatine ganglia provide nitroxidergic innervation to forebrain cerebral blood vessels. Disruption of that innervation attenuates cerebral vasodilatation seen during acute hypertension as does systemic administration of a non-selective nitric oxide synthase (NOS) inhibitor. Although such studies suggest that nitric oxide (NO) released from parasympathetic nerves participates in vasodilatation of cerebral vessels during hypertension that hypothesis has not been tested with selective local inhibition of neuronal NOS (nNOS). We tested that hypothesis through these studies performed in anesthetized rats instrumented for continuous measurement of blood pressure, heart rate and pial arterial diameter through a cranial window. We sought to determine if the nNOS inhibitor propyl-L-arginine delivered directly to the outer surface of a pial artery would 1) attenuate changes in pial arterial diameter during acute hypertension and 2) block nNOS mediated dilator effects of N-methyl-D- Aspartate (NMDA) delivered into the window but 3) not block vasodilatation elicited by acetylcholine (ACh) and mediated by endothelial NOS dilator. Without the nNOS inhibitor arterial diameter abruptly increased 70 ± 15% when mean arterial pressure (MAP) reached 183 ± 3 mmHg while with nNOS inhibition diameter increased only 13 ± 10% (p<0.05) even when MAP reached 191 ± 4 (p>0.05). The nNOS inhibitor significantly attenuated vasodilatation induced by NMDA but not ACh delivered into the window. Thus, local nNOS inhibition attenuates breakthrough from autoregulation during hypertension as does complete interruption of the parasympathetic innervation of cerebral vessels. These findings further support the hypothesis that NO released from parasympathetic fibers contributes to cerebral vasodilatation during acute hypertension. Section: Regulatory Systems

Talman, William T.; Dragon, Deidre Nitschke

2007-01-01

265

Nitric Oxide as a Modulator of Intestinal Water and Electrolyte Transport  

Microsoft Academic Search

The role of nitric oxide in intestinal fluid andelectrolyte secretion depends upon whether theconditions under study are physiological orpathophysiological. In physiological conditions,endogenous nitric oxide seems to be a proabsorptive molecule,based on the findings that nitric oxide synthaseinhibitors reverse net fluid absorption to net secretionin mice, rats, guinea pigs, rabbits, and dogs. This proabsorptive mode involves the enteric nervoussystem, the suppression

Angelo A. Izzo; Nicola Mascolo; Francesco Capasso

1998-01-01

266

Inhaled nitric oxide is not a negative inotropic agent in a porcine model of pulmonary hypertension  

Microsoft Academic Search

Background: Reports of pulmonary edema complicating inhaled nitric oxide therapy in patients with chronic heart failure and pulmonary hypertension have raised the concern that inhaled nitric oxide may have negative inotropic effects. Methods and results: We investigated the effect of multiple doses of inhaled nitric oxide (20, 40 and 80 ppm) on left ventricular contractile state in 10 open-chest pigs.

Daniel J. Goldstein; David A. Dean; Arthur Smerling; Mehmet C. Oz; Daniel Burkhoff; Marc L. Dickstein

1997-01-01

267

Nitric oxide\\/guanylate cyclase pathways and flow in anterior segment perfusion  

Microsoft Academic Search

Background. The nitric oxide\\/guanylate cyclase pathway has been suggested to participate in the regulation of intraocular pressure. In the present study, the involvement of nitric oxide pathways on the outflow through the trabecular meshwork was assessed using pharmacological manipulation of the nitric oxide pathway. Methods. Anterior segments of human donor eyes were maintained in an organ culture perfusion system, and

Andrea Schneemann; Berlinde G. Dijkstra; Thomas J. van den Berg; Willem Kamphuis; Philip F. J. Hoyng

2002-01-01

268

Nitric Oxide Scavenging by Red Blood Cells as a Function of Hematocrit and Oxygenation  

Microsoft Academic Search

The reaction rate between nitric oxide and intraerythrocytic hemoglobin plays a major role in nitric oxide bioavailability and modulates homeostatic vascular function. It has previously been demonstrated that the encapsulation of hemoglobin in red blood cells restricts its ability to scavenge nitric oxide. This effect has been attributed to either factors intrinsic to the red blood cell such as a

Ivan Azarov; Kris T. Huang; Swati Basu; Mark T. Gladwin; Neil Hogg; Daniel B. Kim-Shapiro

2005-01-01

269

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

270

Nonsteroidal Anti-inflammatory Drugs Inhibit Expression of the Inducible Nitric Oxide Synthase Gene  

Microsoft Academic Search

Increased nitric oxide production is associated with acute and chronic inflammatory processes. Accordingly, we tested the hypothesis that the therapeutic action of nonsteroidal anti-inflammatory drugs could be attributed at least in part to inhibition of excess nitric oxide production. We report here that sodium salicylate, aspirin, ibuprofen, and indomethacin markedly inhibited the appearance of the inducible inflammatory nitric oxide synthase

E. E. Aeberhard; S. A. Henderson; N. S. Arabolos; J. M. Griscavage; F. E. Castro; C. T. Barrett; L. J. Ignarro

1995-01-01

271

Discovery of Some of the Biological Effects of Nitric Oxide and its Role in Cell Signaling  

Microsoft Academic Search

The role of nitric oxide in cellular signaling in the past 22 years has become one of the most rapidly growing areas in biology with more than 20,000 publications to date. Nitric oxide is a gas and free radical with an unshared electron that can regulate an ever-growing list of biological processes. In many instances nitric oxide mediates its biological

Ferid Murad

1999-01-01

272

Increased levels of nitric oxide derivatives in induced sputum in patients with asthma  

Microsoft Academic Search

Background: Nitric oxide (NO) plays an important role as an inflammatory mediator in the airways. However, because direct measurement of endogenous NO has been difficult in vivo, the exact pathologic roles of NO in human airway inflammation have remained unclear. Objective: This study was designed to determine whether NO may be harmful by amplifying allergic inflammation in asthmatic airways. Methods:

Hiroshi Kanazawa; Seiichi Shoji; Masashi Yamada; Tatsuo Fujii; Takashi Kawaguchi; Shinzoh Kudoh; Kazuto Hirata; Junichi Yoshikawa

1997-01-01

273

Nitric oxide synthase isoform expression in a porcine model of granulation tissue formation  

Microsoft Academic Search

Background. This study was designed to determine whether the nitric oxide (NO) pathway is involved in wound granulation tissue formation. Methods. A section of the pig abdominal wall (excluding the skin) was excised, creating an incisional hernia. The resulting defect was repaired with silicone sheeting in a manner that mimics a temporary abdominal wall closure. During the 14-day experimental period,

Jennifer S. Pollock; Whitney Webb; Dianne Callaway; Sathyanarayana; William O'Brien; Thomas R. Howdieshell

2001-01-01

274

Real?Time Detection of Nitric Oxide Isotopes in Lung Function Tests  

Microsoft Academic Search

In lung function tests, the determination of the pulmonary diffusing capacity (D) using the single?breath method is a commonly applied technique. The calculation of D is performed on the basis of accurate measurements of indicator gas concentrations. In this chapter, we demonstrate the appropriateness of the stable nitric oxide (NO) isotopes 14NO and 15NO in revealing reliable data of D.

H. Heller; R. Gäbler

2005-01-01

275

Role of Nitric Oxide in Lysis of Tumor Cells by Cytokine-activated Endothelial Cells  

Microsoft Academic Search

The purpose of these studies was to determine whether nitric oxide produced by cytokine-activated murine lung vascular endothelial cells plays a role in their lytic destruction of M-5076 reticulum cell sarcoma. Vascular endothelial cells harvested from perfused lungs of mice were adapted to grow in culture. Cloned lines ascertained to be of endothelial origin were incubated in vitro with interferon

Limin Li; Robert G. Kilbourn; James Adams; Isaiah J. Fidler

1991-01-01

276

C-type natriuretic peptide effects on cardiovascular nitric oxide system in spontaneously hypertensive rats  

Microsoft Academic Search

The aim was to study the effects of C-type natriuretic peptide (CNP) on mean arterial pressure (MAP) and the cardiovascular nitric oxide (NO) system in spontaneously hypertensive rats (SHR), and to investigate the signaling pathways involved in this interaction. SHR and WKY rats were infused with saline or CNP. MAP and nitrites and nitrates excretion (NOx) were determined. Catalytic NO

Carolina Caniffi; Rosana Elesgaray; Mariela Gironacci; Cristina Arranz

2010-01-01

277

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

278

Nitric oxide-dependent killing of Candida albicans by murine peritoneal cells during an experimental infection  

Microsoft Academic Search

The phagocytic and candidacidal activities of the peritoneal cells of Candida albicans-infected mice were studied 20 days following experimental infection. Both activities were enhanced during infection. The production of nitric oxide (NO) by the peritoneal cells of infected mice was determined, and an increase in the nitrite concentration in supernatants of peritoneal cell cultures was detected. The period of NO

Aitor Rementería; Roberto García-Tobalina; María Jesús Sevilla

1995-01-01

279

Proteomic identification of plant proteins probed by mammalian nitric oxide synthase antibodies  

Microsoft Academic Search

Several studies suggest that a mammalian-like nitric oxide synthase (NOS) exists in plants. Researchers have attempted to verify its presence using two approaches: (i) determination of NOS functional activity and (ii) probing with mammalian NOS antibodies. However, up to now, neither a NOS-like gene nor a protein has been found in plants. While there is still some controversy over whether

Yoki Kwok-Chu Butt; John Hon-Kei Lum; Samuel Chun-Lap Lo

2003-01-01

280

Superoxide Anion From the Adventitia of the Rat Thoracic Aorta Inactivates Nitric Oxide  

Microsoft Academic Search

The purpose of this study was to determine whether superoxide anion is produced endogenously in the rat aortic adventitia and whether sufficient superoxide anion is produced to interfere with the response of the rat aorta to nitric oxide. Relaxation was measured in rings of the rat thoracic aorta, which were oriented so that the adventitial or luminal surface could be

Hui Di Wang; Patrick J. Pagano; Yue Du; Antonio J. Cayatte; Mark T. Quinn; Peter Brecher; Richard A. Cohen

281

Endothelial, inducible and neuronal nitric oxide synthase in congenital pulmonary lymphangiectasis  

Microsoft Academic Search

Abnormal growth and development of lymphatic pulmonary structures leads to severe hypoxia in congenital pulmonary lymphangiectasis (CPL). This case study aims to determine the cellular source and topographical distribution of the nitric oxide synthases in CPL. It studies the post mortem tissue of a term newborn with the clinical course and histological findings of CPL and three controls without pulmonary

T. Hoehn; M. William; A. R. McPhaden; H. Stannigel; E. Mayatepek; R. M. Wadsworth

2006-01-01

282

Effects of estrogen on nitric oxide synthase and histological composition in the rabbit clitoris and vagina  

Microsoft Academic Search

We investigated the functional and histological changes after oophorectomy in the rabbit clitoris and vagina to determine the mechanism responsible for the development of arousal disorder in postmenopausal women. Twenty mature female New Zealand white rabbits were randomly divided into three groups: control; oophorectomy; and estrogen replacement after oophorectomy. We compared the nitric oxide synthase (NOS) activity and the degree

HN Yoon; WS Chung; YY Park; BS Shim; WS Han; SW Kwon

2001-01-01

283

Neurodevelopmental and medical outcomes of persistent pulmonary hypertension in term newborns treated with nitric oxide  

Microsoft Academic Search

Objective: To determine the medical and neurodevelopmental outcome of children with moderately severe persistent pulmonary hypertension of the newborn (PPHN) treated with or without inhaled nitric oxide (I-NO). Study design: Term infants with PPHN and a baseline oxygenation index of 24 ± 9 at study entry were randomly assigned to early treatment with placebo or initial doses of I-NO (5,

Paul H. Lipkin; Dennis Davidson; Lynn Spivak; Richard Straube; Jared Rhines; C. T. Chang

2002-01-01

284

Inhaled Nitric Oxide (iNO) Delivery with High-frequency Jet Ventilation (HFJV)  

Microsoft Academic Search

OBJECTIVE: To determine if nitric oxide (NO) therapy can be reliably administered during high-frequency jet ventilation (HFJV) using the INOvent delivery system.STUDY DESIGN: NO concentrations were measured just proximal to the endotracheal (ET) tube and at the distal tip of the ET tube during a bench evaluation. Measurements were taken over a wide range of airway pressure settings and NO

David R Platt; Doug Swanton; David Blackney

2003-01-01

285

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

286

Effects of Nitric Oxide Synthase Inhibition on Ciliary Blood Flow, Aqueous Production and Intraocular Pressure  

Microsoft Academic Search

A prior study found that inhibition of nitric oxide synthase with L-NAME causes a large, rapid decrease in IOP in anesthetized rabbits. In this follow-up study we sought to determine if this hypotensive effect was due to decreased aqueous production, possibly caused by ciliary vasoconstriction. Two protocols were performed in anesthetized rabbits. In the first protocol, mean arterial pressure (MAP)

J. W. Kiel; H. A. Reitsamer; J. S. Walker; F. W. Kiel

2001-01-01

287

The role of nitric oxide in diabetes-induced changes of morphine tolerance in rats  

Microsoft Academic Search

Several neuroendocrine complications including diabetes change the morphine antinociception and the development of tolerance to the drug. Morphine antinociception was reduced significantly in morphine tolerant diabetic rats compared to the non-diabetic animals. The exact mechanism of this effect is not known. This study was performed to determine the role of nitric oxide (NO) on morphine tolerance in diabetic state. Nociceptive

Khojasteh Joharchi; Masoumeh Jorjani

2007-01-01

288

Effect of exogenous nitric oxide on murine splenic immune response induced by Aggregatibacter actinomycetemcomitans lipopolysaccharide  

Microsoft Academic Search

The aim of this study was to determine the effect of exogenous nitric oxide (NO) on the induction of murine splenic immune response to Aggregatibacter actinomycetemcomitans lipopolysaccharide (LPS) in vitro. BALB\\/c mice were immunized with A. actinomycetemcomitans LPS and a control group was sham-immunized. Spleen cells were obtained, cultured and stimulated with A. actinomycetemcomitans LPS with or without the presence

W. Sosroseno; P. S. Bird; G. J. Seymour

2009-01-01

289

Lineshapes of Ionizing Stark Resonances in Rydberg States of Helium and Nitric Oxide  

Microsoft Academic Search

High resolution laser spectroscopy is used to study the Stark effect in helium and nitric oxide. The energies, widths, intensities and shapes of resonances in helium above the classical ionization threshold are measured for a wide range of field values. The high resolution of the lasers combined with careful design of the electric field plates allow accurate determination of the

Andre Nussenzweig

1989-01-01

290

Elevated Nitric Oxide Production in Children with Malarial Anemia: Hemozoin-Induced Nitric Oxide Synthase Type 2 Transcripts and Nitric Oxide in Blood Mononuclear Cells  

Microsoft Academic Search

Experiments outlined here investigate the role of nitric oxide (NO) in the pathogenesis of Plasmodium falciparum-induced malarial anemia (MA). The results show that ex vivo and in vitro NO synthase (NOS) activity in peripheral blood mononuclear cells (PBMCs) is significantly elevated in children with MA and inversely associated with hemoglobin levels. Additional experiments using PBMCs from non-malaria-exposed donors demonstrate that

Christopher C. Keller; Peter G. Kremsner; James B. Hittner; Mary A. Misukonis; J. Brice Weinberg; Douglas J. Perkins

2004-01-01

291

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

292

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

PubMed

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

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

2010-12-01

293

Nitric Oxide Inhibits HIV1 Replication in Human Astrocytoma Cells  

Microsoft Academic Search

Astroglial cells represent a target for HIV infection in the central nervous system. In astrocytes, HIV infection is poorly productive, being characterized by a persistent state of viral latency. However, activation of the nuclear factor NF-?B and its binding to HIV long terminal repeat (LTR) can induce HIV replication. Moreover, nitric oxide (NO) can affect NF-?B activation in glial cells.

Tiziana Persichini; Marco Colasanti; Maurizio Fraziano; Vittorio Colizzi; Paolo Ascenzi; Giuliana M. Lauro

1999-01-01

294

Diazeniumdiolated carbamates: A novel class of nitric oxide donors  

PubMed Central

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

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

2012-01-01

295

Human–bacteria nitric oxide cycles in HIV1 infection  

Microsoft Academic Search

The human intestinal tract harbors a complex microbiotic environment containing commensal bacteria and immunocompetent mucosal cells. There is considerable communication between the bacteria and host cells through dietary constituents and metabolic cycles. We propose that in the pathogenesis of acquired immunodeficiency syndrome (AIDS), the human immunodeficiency virus-1 (HIV-1) triggers a change in a coupled transorganism (human–bacteria) nitric oxide interchange cycle,

H. Zhang; D. Boring; H. Haverkos

2002-01-01

296

Potential genotoxicity of chronically elevated nitric oxide: A review  

Microsoft Academic Search

Several human cancers are associated with chronic bacterial, viral and parasitic infections. Nitric oxide, which is a short-lived free radical produced by many types of cells for a number of important physiological functions, is elevated in these infections. Long-term exposure to elevated NO · cells could have potential genotoxic effects on hosts. There are at least three mechanisms by which

Rui Hai Liu; Joseph H. Hotchkiss

1995-01-01

297

Exogenous Nitric Oxide and Bubble Formation in Divers  

Microsoft Academic Search

ABSTRACT DUJIC ´ ,Z ? ., I. PALADA, Z. VALIC, D. DUPLAN)IC ´ , A. OBAD, U. WISLKFF, and A. O. BRUBAKK. Exogenous Nitric Oxide and Bubble Formation in Divers. Med. Sci. Sports Exerc., Vol. 38, No. 8, pp. 1432Y 1435, 2006. Purpose: Prevention of bubble formation is a central goal in standard decompression,procedures. Previously we have shown,that exercise 20Y

IVAN PALADA; ZORAN VALIC; ANTE OBAD; ALF O. BRUBAKK

2006-01-01

298

Nitric Oxide Inhalation During Exercise in Chronic Obstructive Pulmonary Disease  

Microsoft Academic Search

Patients with chronic obstructive pulmonary disease (COPD) may develop hypoxemia and pulmonary hypertension when exercising. To investigate whether inhaled nitric oxide (NO), a selective pulmo- nary vasodilator, modifies the changes induced by exercise in pulmonary hemodynamics and gas ex- change in COPD, we studied nine patients (FEV 1 5 39 6 2% predicted), at rest and at submaximal ex- ercise,

NÚRIA ROGER; JOAN A. BARBERÀ; JOSEP ROCA; IRENE ROVIRA; FEDERICO P. GÓMEZ; ROBERT RODRIGUEZ-ROISIN

1997-01-01

299

Combustion hazard of mixing ammonia with nitric oxide  

Microsoft Academic Search

Premixed ammonia\\/nitric oxide flame was simulated using the Lindstedt 1994 and Miller–Bowman 1989 reaction mechanisms in CHEMKIN. The predicted laminar burning velocities compared well with limited measured values in the literature. The effects of unburnt mixture temperature and pressure on laminar burning velocity, flammability limits, adiabatic flame temperature and species profiles were studied. The unburnt mixture temperature had a positive

Rui Liu; David S.-K. Ting; M. David Checkel

2003-01-01

300

Increased nitric oxide production by neutrophils in bronchial asthma  

Microsoft Academic Search

This study was designed to assess the production of nitric oxide (NO) by neutrophils in bronchial asthma. Thirty asthmatic patients (ten each of mild, moderate and severe asthma) and ten healthy controls were included in the study. Neutrophils from peripheral venous blood were stimulated with latex, and production of nitrite (an NO metabolise) and L-citrulline (a co-product of NO) was

G. Ramesh; S. K. Jindal; N. K. Ganguly; V. Dhawan

2001-01-01

301

Nitric oxide production during exercise in chronic heart failure  

Microsoft Academic Search

In chronic heart failure (CHF), the ventilatory response is increased compared with normal. This response is, in part, caused by reduced perfusion to ventilated lung. Nitric oxide (NO) is a potent vasodilator and may have an important role in pulmonary vasodilatation during exercise. NO is present in exhaled air. The amount of NO in exhaled air, when breathing NO-free compressed

Hitoshi Adachi; Paul H. Nguyen; Romualdo Belardinelli; Dodie Hunter; Tyler Jung; Karlman Wasserman

1997-01-01

302

Thermospheric nitric oxide infrared emissions measured by CRISTA  

Microsoft Academic Search

In November 1994 the CRISTA (Cryogenic Infrared Spectrometers and Telescopes of the Atmosphere) experiment measured mid and far infrared spectra from the Earth limb. One of the spectral channels covered the 5.3 ?m (?v = 1) band of nitric oxide. A first analysis of the data of this channel is presented. Large enhancements of the 5.3 ?m band radiances were

K. U Grossmann; M. Kaufmann; K. Vollmann

1997-01-01

303

Altered interleukin 12 and nitric oxide levels in recurrrent miscarriage  

Microsoft Academic Search

The causes of recurrent miscarriage are not fully understood. Recent studies have suggested that whilst a TH 2 type immune response may be associated with a healthy pregnancy, miscarriage may be associated with a TH 1 type response. Serum levels of nitric oxide (NO) and Interleukin 12 (IL 12) were measured in; healthy non-pregnant women; healthy pregnant women; women suffering

Rhoda Wilson; Iain McInnes; Bernard Leung; James H McKillop; James J Walker

1997-01-01

304

Is estradiol cardioprotection a nitric oxide-mediated effect?  

Microsoft Academic Search

BACKGROUND: Estradiol exerts a number of biological effects that support extensive observational data suggesting a protective role for estrogen in cardiovascular disease prevention. These include effects on lipid and carbohydrate metabolism, coagulation\\/fibrinolysis as well as a possible effect on vascular reactivity. It has been proposed that this might be mediated by vascular endothelial nitric oxide (NO) production. Accordingly, we designed

A. C. Duncan; J. R. Petrie; M. J. Brosnan; A. M. Devlin; R. A. Bass; D. S. Charnock-Jones; J. M. C. Connell; A. F. Dominiczak; M. A. Lumsden

2002-01-01

305

Role of nitric oxide in placental vascular development and function  

Microsoft Academic Search

Nitric oxide (NO) is one of the most pleiotropic signaling molecules at systemic and cellular levels, participating in vascular tone regulation, cellular respiration, proliferation, apoptosis and gene expression. Indeed NO actively participates in trophoblast invasion, placental development and represents the main vasodilator in this tissue. Despite the large number of studies addressing the role of NO in the placenta, its

B. J. Krause; M. A. Hanson; P. Casanello

2011-01-01

306

Inhaled nitric oxide in term and preterm infants  

Microsoft Academic Search

Nitric oxide (NO) is a gas that has potent vasodilator properties. It can be administered via inhalation in situations where NO production is impaired and results in vasodilatation of the pulmonary capillaries. In term infants, the administration of inhaled NO, at a dose of 20 parts per million, may reduce the need for extracorporeal membrane oxygenation by reducing pulmonary vascular

K Sekar

2006-01-01

307

Low energy electron attachment to clusters of nitric oxide  

SciTech Connect

The attachment of low energy (9--80 meV) electrons to clusters of nitric oxide (NO) has been studied by means of Rydberg electron transfer (RET) from selected [ital nd] states of rubidium ([ital n]=15--40). The product negative ions have stoichiometry (NO)[sup [minus

Carman, H.S. Jr. (Chemical Physics Section, Health Sciences Research Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831-6125 (United States))

1994-02-15

308

Nitric Oxide: Cytotoxicity versus Cytoprotection— How, Why, When, and Where?  

Microsoft Academic Search

Nitric oxide (NO) has been found to play an important role as a signal molecule in many parts of the organism as well as a cytotoxic effector molecule of the nonspecific immune response. It appears paradoxical that NO on one side acts as a physiological intercellular messenger and on the other side may display cytotoxic activityin vivo.To make things even

Klaus-D. Kröncke; Karin Fehsel; Victoria Kolb-Bachofen

1997-01-01

309

Direct scavenging of nitric oxide and superoxide by green tea  

Microsoft Academic Search

In the present study, we investigated the free radical scavenging effects of green tea extract and green tea tannin mixture and its components using a nitric oxide (NO) and superoxide (O2?) generating system in vitro. Green tea extract showed direct scavenging activity against NO and O2? and green tea tannin mixture, at the same concentration, showed high scavenging activity. Comparison

T Nakagawa; T Yokozawa

2002-01-01

310

Nitric oxide and the regulation of gene expression  

Microsoft Academic Search

During the past 15 years, nitric oxide (NO) and NO synthases have become an important research topic in cellular and molecular biology. NO is produced by many if not all mammalian cells and fulfils a broad spectrum of signaling functions in physiological and pathophysiological processes. In this review, recent advances in our understanding of the mechanisms by which NO regulates

Christian Bogdan

2001-01-01

311

Regulation of Nitric Oxide Production by Stimulated Rat Kupffer Cells  

Microsoft Academic Search

Macrophages have been described to release nitric oxide (NO) as a cytotoxic radical. This highly unstable substance is as well known as endothelium-derived relaxing factor produced by vascular endothelial cells. Because of its cytotoxic activity the synthesis of NO by rat Kupffer cells, the liver macrophages, upon stimulation with endotoxin (lipopolysaccharide; LPS) and tumor necrosis factor-? (TNF-?) in combination with

T. Gaillard; A. Mülsch; R. Busse; H. Klein; K. Decker

1991-01-01

312

Astrocytic nitric oxide triggers tau hyperphosphorylation in hippocampal neurons.  

PubMed

Production of nitric oxide (NO) by glial cells has been proposed to mediate cytotoxic effects on neighboring neurons. Although extensive genetic data implicate the beta amyloid peptide (Abeta) in the neurodegenerative cascade of Alzheimer's disease (AD), the molecular mechanisms underlying its effects on neurons and glia and the relationship between glial activation and neuronal death are not well understood. In AD, Abeta is sufficient to induce glial activation and promote the generation of inflammatory mediators including NO. We examined whether Abeta stimulated astrocytes to express nitric oxide synthase and produce NO. Also, we investigated whether astrocytic NO contributes to degenerative changes occurring in co-cocultured hippocampal neurons. We found that the treatment of rat hippocampal astrocyte cultures with Abeta(25-35) fragment up-regulated the mRNA and protein levels of both the inducible and neuronal forms of nitric oxide synthase (iNOS and nNOS, respectively) and increased the production of nitric oxide. Remarkably, hippocampal neurons co-cultured with astrocytes, previously stimulated with Abeta, displayed hyperphosphorylation of the microtubule-associated protein tau. This effect was attenuated by iNOS inhibitors, suggesting the role of overproduction of NO by reactive astrocytes in AD pathogenesis. PMID:15341183

Saez, T Estefanía; Pehar, Mariana; Vargas, Marcelo; Barbeito, Luis; Maccioni, Ricardo B

313

The role of nitric oxide in vascular disease  

Microsoft Academic Search

The discovery that the vascular endothelium can generate a free radical, nitric oxide (NO), that alters the function of vascular smooth muscle, revolutionized vascular biology. Endothelial damage and the loss of NO function is at the root of peripheral vascular disease.NO is also an important signalling molecule in many other biological systems, but this contribution will focus specifically on the

Karen Stuart-Smith

2004-01-01

314

Role of nitric oxide in genotoxicity: Implication for carcinogenesis  

Microsoft Academic Search

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

Emanuela Felley-Bosco

1998-01-01

315

Stress-related diseases - a potential role for nitric oxide  

Microsoft Academic Search

Summary Nitric oxide (NO) is involved in stress physiology and stress-related disease processes. Like stress, NO seems to be capable of principally exerting either beneficial or deleterious effects. The actual distinction depends on a multitude of factors. Moreover, NO counteracts norepi- nephrine (NE) activity and sympathetic responsivity. Thus, NO and the stress (patho)physiol- ogy are closely connected and molecular mechanisms

Tobias Esch; George B. Stefano; Gregory L. Fricchione; Herbert Benson

2002-01-01

316

Nitric Oxide Is Protective in Listeric Meningoencephalitis of Rats  

Microsoft Academic Search

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

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

2001-01-01

317

Nitric oxide: a newly discovered function on wound healing  

Microsoft Academic Search

Wound healing impairment represents a particularly challenging clinical problem to which no efficacious treatment regimens currently exist. The factors ensuring appropriate intercellular communication during wound repair are not completely understood. Although protein-type mediators are well-established players in this process, emerging evidence from both animal and human studies indicates that nitric oxide (NO) plays a key role in wound repair. The

Jian-dong Luo; Alex F Chen

2005-01-01

318

Nitric oxide (NO) synthase immunoreactivity in the starfish Marthasterias glacialis  

Microsoft Academic Search

The neuroendocrine system of the starfish Marthasterias glacialis was investigated immunocytochemically using antisera specific for rat neuronal, bovine aortic endothelial, and mouse macrophage, nitric oxide (NO) synthases. Immunoreactivity was detected only with the antibodies specific for the neural enzyme, in the ectoneural and hyponeural tissues of the radial nerve cords and in the basiepithelial plexus and endocrine cells of the

A. Martínez; V. Riveros-Moreno; J. M. Polak; S. Moncada; P. Sesma

1994-01-01

319

Inducible Nitric Oxide Synthase Mediates Bone Loss in Ovariectomized Mice  

Microsoft Academic Search

Several clinical studies have shown that bone loss may be attributed to osteoclast recruitment induced by mediators of inflammation. In different experimental paradigms we have recently demonstrated that estrogen exhibits antiinflamma- tory activity by preventing the induction of inducible nitric oxide synthase (iNOS) and other components of the inflam- matory reaction. To verify whether this could explain the estrogen-dependent blockade

SALVATORE CUZZOCREA; EMANUELA MAZZON; LAURA DUGO; TIZIANA GENOVESE; ROSANNA DI PAOLA; ZAIRA RUGGERI; ELISABETTA VEGETO; ACHILLE P. CAPUTI; DOMENICO PUZZOLO; ADRIANA MAGGI

2003-01-01

320

A NITRIC OXIDE SYNTHASE IN STREPTOMYCES TURGIDISCABIES AFFECTS THAXTOMIN BIOSYNTHESIS  

Technology Transfer Automated Retrieval System (TEKTRAN)

We have identified a gene, strNOS, in the plant pathogen Streptomyces turgidiscabies, homologous to nitric oxide synthases (NOSs) from Bacillus halodurans and iNOSOX, an inducible murine NOS. strNOS is conserved among plant pathogenic streptomycetes and is on a mobilizable pathogenicity island, upst...

321

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

322

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

SciTech Connect

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

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

2007-03-15

323

Involvement of the nitric oxide pathway in the anticonvulsant effect of tramadol on pentylenetetrazole-induced seizures in mice  

Microsoft Academic Search

In the present study, the effects of tramadol on pentylenetetrazole (PTZ)-induced seizures and involvement of nitric oxide (NO) were assessed in mice. To determine the threshold for clonic seizures, PTZ was administered intravenously. Tramadol was administered intraperitoneally (0.5–50mg\\/kg) 30minutes prior to induction of seizures. The effects of the nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 0.5, 1, 5,

Ali Lesani; Mehrak Javadi-Paydar; Tina Kabiri Khodadad; Alaleh Asghari-Roodsari; Mahyar Shirkhodaei; Abbas Norouzi; Ahmad Reza Dehpour

2010-01-01

324

Gene Transfer of Endothelial Nitric Oxide Synthase to the Penis Augments Erectile Responses in the Aged Rat  

Microsoft Academic Search

Nitric oxide (NO), a mediator involved in penile erection, is synthesized by the nitric oxide synthase (NOS) family of enzymes. It has been shown that NOS activity decreases with age. To determine whether adenoviral-mediated overexpression of endothelial NOS (eNOS) could enhance erectile responses, we administered a recombinant adenovirus containing the eNOS gene (AdCMVeNOS) into the corpora cavernosum of the aged

H. C. Champion; T. J. Bjvalacqua; A. L. Hyman; L. J. Ignarro; W. J. G. Hellstrom; P. J. Kadowitz

1999-01-01

325

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

326

Nitric Oxide – A Product of Plant Nitrogen Metabolism  

Microsoft Academic Search

Nitric oxide is an intermediate product of inorganic nitrogen assimilation. In plants, it can be\\u000a formed either by reducing inorganic nitrogen by the nitrite-dependent pathway or by oxidation of organic\\u000a nitrogen by the arginine-dependent pathway. Both pathways require adequate nitrogen supply to the plant\\u000a and may not operate under nitrogen deficiency. However, the pathways are differently regulated in relation\\u000a to

Christine Stöhr

327

Process for combined control of mercury and nitric oxide.  

SciTech Connect

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

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

1999-11-03

328

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

NASA Astrophysics Data System (ADS)

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

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

1994-08-01

329

Dihydrofolate reductase protects endothelial nitric oxide synthase from uncoupling in tetrahydrobiopterin deficiency  

Microsoft Academic Search

Tetrahydrobiopterin (BH4) is a required cofactor for the synthesis of NO by endothelial nitric oxide synthase (eNOS), and endothelial BH4 bioavailability is a critical factor in regulating the balance between NO and superoxide production (eNOS coupling). Biosynthesis of BH4 is determined by the activity of GTP-cyclohydrolase I (GTPCH). However, BH4 levels may also be influenced by oxidation, forming 7,8-dihydrobiopterin (BH2),

Mark J. Crabtree; Ashley B. Hale; Keith M. Channon

2011-01-01

330

Nitric oxide as a cellular antioxidant: A little goes a long way  

Microsoft Academic Search

Nitric oxide (NO S ) is an effective chain-breaking antioxidant in free radical-mediated lipid oxidation (LPO). It reacts rapidly with peroxyl radicals as a sacrificial chain-terminating antioxidant. The goal of this work was to determine the minimum threshold concentration of NO S required to inhibit Fe 2+ -induced cellular lipid peroxidation. Using oxygen consumption as a measure of LPO, we

Stephen G. Hummel; Anthony J. Fischer; Sean M. Martin; Freya Q. Schafer; Garry R. Buettner

2005-01-01

331

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.

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

2004-01-01

332

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

333

Portal hypertension triggers local activation of inducible nitric oxide synthase gene in colonic mucosa.  

PubMed

Recently a new clinical entity "portal hypertensive colopathy" has been reported. It involves vascular abnormalities and bleeding. Because nitric oxide may mediate these changes, we studied whether portal hypertension affects nitric oxide synthase in portal hypertensive colonic mucosa. In portal hypertensive and sham-operated rats the following studies were done: (1) colonic mucosal blood flow, (2) quantitative histologic examination, (3) reverse transcription-polymerase chain reaction for nitric oxide synthase mRNA, (4) nitric oxide synthase activity assay, and (5) immunostaining for nitric oxide synthase. In portal hypertensive rats, colonic mucosal blood flow and the number of submucosal veins were significantly increased in comparison to sham-operated rats. The mRNA expression and enzyme activity for inducible nitric oxide synthase (but not constitutive nitric oxide synthase) were significantly increased in portal hypertensive rats. Fluorescence signal intensity for inducible nitric oxide synthase in endothelia of mucosal and submucosal veins was significantly higher in portal hypertensive rats than in sham-operated rats. Portal hypertension activates inducible nitric oxide synthase gene and protein in colonic mucosal vessels. The excess of nitric oxide generated by overexpressed inducible nitric oxide synthase may play an important role in the development of vascular and hemodynamic abnormalities characterizing portal hypertensive colopathy. PMID:9834352

Ohta, M; Kaviani, A; Tarnawski, A S; Itani, R; Sugimachi, K; Sarfeh, I J

334

Alterations in Nitric Oxide Synthase in the Aged CNS  

PubMed Central

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

Jung, Junyang; Na, Changhyun; Huh, Youngbuhm

2012-01-01

335

Nitric Oxide Release Part III. Measurement and Reporting  

PubMed Central

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

Coneski, Peter N.; Schoenfisch, Mark H.

2012-01-01

336

Phenolic compounds from plants as nitric oxide production inhibitors.  

PubMed

Nitric oxide (NO) is a diatomic free radical produced from L-arginine by constitutive and inducible nitric oxide synthase (cNOS and iNOS) in numerous mammalian cells and tissues. Nitric oxide (NO), superoxide (O2-) and their reaction product peroxynitrite (ONOO-) may be generated in excess during the host response against viral and antibacterial infections and contribute to some pathogenesis by promoting oxidative stress, tissue injury and, even, cancer. Oxidative damage, caused by action of free radicals, may initiate and promote the progression of a number of chronic diseases, including cancer, cardiovascular diseases, Alzheimer's disease, diabetes and inflammation. The mechanism of inflammation injury is attributed, in part, to release of reactive oxygen species from activated neutrophils and macrophages. ROS propagate inflammation by stimulating release of mediators such as NO and cytokines. The interest of the research is motivated by the current need to find new substances of natural origin which have demonstrated effectiveness in the described fields of application and low degree of toxicity for humans. Natural products provide a vast pool of NO inhibitors that can possibly be developed into clinical products. This article reviews some plenolic secondary metabolites from plants with NO inhibitory properties and their structure-activity relationship studies that can be focused for drug development programs. PMID:21291370

Conforti, F; Menichini, F

2011-01-01

337

The role of glutathione in the transport and catabolism of nitric oxide  

Microsoft Academic Search

Nitric oxide acts as a neuronal and vascular messenger implying diffusion through intracellular environments containing 5–10 mM glutathione. Nitric oxide reacts with glutathione under aerobic conditions generating S-nitrosoglutathione (GSNO). GSNO reacts with glutathione (k = 8.3 × 10?3 M?1 · s?1) to generate nitrous oxide and glutathione disulfide (GSSG). Anaerobically, glutathione reacts with nitric oxide generating nitrous oxide and GSSG

Neil Hogg; Ravinder J. Singh; B. Kalyanaraman

1996-01-01

338

Mediated electrochemical oxidation process: Electrooxidation of cerium(III) to cerium(IV) in nitric acid medium and a study on phenol degradation by cerium(IV) oxidant  

Microsoft Academic Search

Cerium(III) in nitric acid medium was oxidized electrochemically using a flow type electrochemical cell fabricated in our laboratory. The variation of applied cell current, temperature and the concentration of the electrolyte were studied to determine the oxidation efficiency of Ce(III) in the electrochemical cell. The conversion yield of cerium(IV) in nitric acid was 97% in a short duration of 90min.

Subramanian Balaji; Sang Joon Chung; Ramesh Thiruvenkatachari; Il Shik Moon

2007-01-01

339

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

PubMed Central

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

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

2008-01-01

340

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

PubMed Central

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

Bhatia, R. P.; Dhawan, Shikha; Khanna, H. D.; Dash, Amitabh

2010-01-01

341

Histochemical Localization of Nitric Oxide Neurons in the Hypothalamus: Association with Gonadotropin-Releasing Hormone Neurons and Co-Localization with N-Methyl-D-Aspartate Receptors  

Microsoft Academic Search

The neurotransmitter glutamate plays an important role in the control of gonadotropin releasing hormone (GnRH) secretion. Recent evidence suggests that the novel transmitter nitric oxide may also play a role in controlling GnRH release and may be an important mediator of glutamate effects. To explore the role of nitric oxide in these events, the present study determined the distribution of

Ganapathy K. Bhat; Virendra B. Mahesh; Charisee A. Lamar; Ling Ping; Kripamoy Aguan; Darrell W. Brann

1995-01-01

342

Mechanistic study of the selective catalytic reduction of nitric oxide with methane over yttrium oxide  

SciTech Connect

The catalytic activity of nanocrystalline Group IIIB metal oxides for the reduction of nitric oxide with methane was shown to be comparable to that of Co-ZSM-5. The mechanism of selective catalytic reduction of nitric oxide with methane in excess oxygen was examined over nanocrystalline yttrium oxide. A series of heterogeneous and homogeneous reaction steps was proposed to account for the observed trends in catalytic properties. Methyl radicals generated at the catalyst surface desorb into the gas phase, where they react with nitric oxide to form nitrosomethane. Nitrosomethane then decomposes in a series of homogeneous and heterogeneous reactions to produce nitrogen and nitrous oxide. Evidence for gas-phase reaction of methyl radicals with nitric oxide was found in the adsorption studies of nitric oxide on yttrium oxide, the presence of ethane and ethene in the reactor effluent, catalytic studies involving nitrosomethane and nitromethane, as well as the successful prediction of methane selectivities based on a homogeneous reaction mechanism for methyl radical consumption. The proposed pathway for nitrogen production was supported by the observation of hydrogen cyanide under certain operating conditions, as well as adsorbed NCO species detected by infrared spectroscopy.

Fokema, M.D.; Ying, J.Y.

2000-05-15

343

Nitric oxide inhibits prooxidant actions of uric acid during copper-mediated LDL oxidation  

Microsoft Academic Search

Interactions between uric acid and physiologically relevant fluxes of nitric oxide (NO) during copper-mediated low-density lipoprotein (LDL) oxidation were evaluated. In the absence of NO, a dual pro- and antioxidant action of uric acid was evident: low concentrations of uric acid enhanced lipid oxidation and ?-tocopherol consumption, while its protective role was observed at higher concentrations. The prooxidant effects of

Silvia M Sanguinetti; Carlos Batthyány; Andrés Trostchansky; Horacio Botti; Graciela I López; Regina L. W Wikinski; Homero Rubbo; Laura E Schreier

2004-01-01

344

Induction of platelet formation from megakaryocytoid cells by nitric oxide.  

PubMed

Although the growth factors that regulate megakaryocytopoiesis are well known, the molecular determinants of platelet formation from mature megakaryocytes remain poorly understood. Morphological changes in megakaryocytes associated with platelet formation and removal of senescent megakaryocytes are suggestive of an apoptotic process. Previously, we have established that nitric oxide (NO) can induce apoptosis in megakaryocytoid cell lines. To determine whether there is an association between NO-induced apoptosis and platelet production, we exposed Meg-01 cells to S-nitrosoglutathione (GSNO) with or without thrombopoeitin (TPO) pretreatment and used flow cytometry and electron microscopy to assess platelet-sized particle formation. Meg-01 cells treated with TPO alone produced few platelet-sized particles (<3% of total counts), whereas treatment with GSNO alone produced a significant percentage of platelet-sized particles (22 +/- 4% of total counts); when combined with TPO pretreatment, however, GSNO led to a marked increase in platelet-sized particle production (48 +/- 3% of total counts). Electron microscopy confirmed that Meg-01 cells treated with TPO and GSNO yielded platelet-sized particles with morphological features specific for platelet forms. The platelet-sized particle population appears to be functional, because addition of calcium, fibrinogen, and thrombin receptor-activating peptide led to aggregation. These results demonstrate that NO facilitates platelet production, thereby establishing the essential role of NO in megakaryocyte development and thrombopoiesis. PMID:11734646

Battinelli, E; Willoughby, S R; Foxall, T; Valeri, C R; Loscalzo, J

2001-12-01

345

Induction of platelet formation from megakaryocytoid cells by nitric oxide  

PubMed Central

Although the growth factors that regulate megakaryocytopoiesis are well known, the molecular determinants of platelet formation from mature megakaryocytes remain poorly understood. Morphological changes in megakaryocytes associated with platelet formation and removal of senescent megakaryocytes are suggestive of an apoptotic process. Previously, we have established that nitric oxide (NO) can induce apoptosis in megakaryocytoid cell lines. To determine whether there is an association between NO-induced apoptosis and platelet production, we exposed Meg-01 cells to S-nitrosoglutathione (GSNO) with or without thrombopoeitin (TPO) pretreatment and used flow cytometry and electron microscopy to assess platelet-sized particle formation. Meg-01 cells treated with TPO alone produced few platelet-sized particles (<3% of total counts), whereas treatment with GSNO alone produced a significant percentage of platelet-sized particles (22 ± 4% of total counts); when combined with TPO pretreatment, however, GSNO led to a marked increase in platelet-sized particle production (48 ± 3% of total counts). Electron microscopy confirmed that Meg-01 cells treated with TPO and GSNO yielded platelet-sized particles with morphological features specific for platelet forms. The platelet-sized particle population appears to be functional, because addition of calcium, fibrinogen, and thrombin receptor-activating peptide led to aggregation. These results demonstrate that NO facilitates platelet production, thereby establishing the essential role of NO in megakaryocyte development and thrombopoiesis.

Battinelli, Elisabeth; Willoughby, Scott R.; Foxall, Thomas; Valeri, C. Robert; Loscalzo, Joseph

2001-01-01

346

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.

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

2012-01-01

347

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.

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

348

Antenatal insults modify newborn olfactory function by nitric oxide produced from neuronal nitric oxide synthase.  

PubMed

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

2012-07-24

349

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

PubMed

No study has evaluated the correlation between different expression of nitric oxide synthase (NOS) isoforms in nasal epithelial cells and nasal NO (nNO) level in primary ciliary dyskinesia (PCD). Gene expression of endothelial (NOS3) and inducible NOS (NOS2) and their correlation with nNO level, ciliary function and morphology were studied in patients with PCD or secondary ciliary dyskinesia (SCD). NOS3 gene polymorphisms were studied in blood leukocytes. A total of 212 subjects were studied (48 with PCD, 161 with SCD and three normal subjects). nNO level correlated with mean ciliary beat frequency (p = 0.044; r = 0.174). The lower the nNO level the higher was the percentage of immotile cilia (p<0.001; r = -0.375). A significant positive correlation between NOS2 gene expression and nNO levels was demonstrated in all children (p = 0.001; r = 0.428), and this correlation was confirmed in patients with PCD (p = 0.019; r = 0.484). NOS2 gene expression was lower in PCD than in SCD (p = 0.04). The NOS3 isoform correlated with missing central microtubules (p = 0.048; r = 0.447). nNO levels were higher in PCD subjects with the NOS3 thymidine 894 mutation, and this was associated with a higher ciliary beat frequency (p = 0.045). These results demonstrate a relationship between nNO level, NOS mRNA expression and ciliary beat frequency. PMID:21273388

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

2011-01-27

350

[Vasodilatator testing with nitric oxide (bronchial control treatment system--BCTS) in patients with pulmonary hypertension].  

PubMed

Nitric oxide (NO) is one of the most important mediators produced in the human organism. It participates in the regulation of blood vessel lumens, activation of leucocytes and platelet; it is a mediator in the nervous system and in inflammation reactions. It was proved that in cases of patients with pulmonary hypertension, a decreased secretion of nitric oxide and an increased synthesis of endothelin-1 is observed. Therefore, in case of patients with pulmonary hypertension the exogenous, inhaled nitric oxide (iNO) is applied. It is added to the respiratory mixture and it passes through the alveolar-capillary barrier to the smooth muscle cells where it activates a guanyle cyclase, similarly to the physiologically produced nitric oxide. It was proved that it decreases pulmonary vascular resistance (PVR) and pulmonary artery pressure (PAP). Inhaled nitric oxide is applied for treatment purposes to patients after cardiosurgical operations, mainly heart transplantation and correction of valvular defects with accompanying pulmonary hypertension, as well as after implantation of the left ventricular assist device in order to relieve the right chamber. In case of patients qualified for cardiosurgical operations with the accompanying pulmonary hypertension as well as in case of patients with the arterial pulmonary hypertension a diagnostical test using iNO is carried out in order to determine further course of therapeutical treatment. The application of the new method of iNO administration by the BCTS (Bronchial Control Treatment System) method allows for a precise administration of accurately determined doses of iNO and its full utilisation through addition to the respiratory mixture in the initial phase of inspiration. The risk of side effects is also decreased; so far no influence on the circulatory system or an increase of the level of methemoglobin was observed. PMID:15724676

Podolec, Piotr; Ka?nica-Wiatr, Magdalena; Podolec, Zygmunt; Krochin, Marek; Wilko?ek, Piotr; Przyby?owski, Piotr; Wierzbicki, Karol; Sadowski, Jerzy; Zmudka, Krzysztof; Tracz, Wies?awa

2004-01-01

351

Modulation by nitric oxide of rat brain GABAA receptors.  

PubMed

The effect of nitric oxide (NO) on the function of GABAA receptors was studied in two different rat brain neuron populations. Cerebral cortex neuronal GABAA receptors were studied by preparing microsacs and evaluating 36Cl- accumulation. Whether nitric oxide was provided by sodium nitroprusside (SNP) or by the metabolic precursor precursor arginine there was a 15-25% reduction in the Vmax for GABA-stimulated 36Cl- accumulation. The arginine effect could be reversed by the NO synthase (NOS) inhibitor N omega-nitro-L-arginine. GABAA receptor mediated Cl- currents were studied in rat cerebellar granule cells by whole-cell patch clamp. S-Nitroso-N-acetylpenicillamine (SNAP), sodium nitroprusside and L-arginine reduced the Cl- current elicited by 10 microM GABA. The L-arginine effect was reversible upon its washing out. This circumstance indicates that NO produced by endogenous NOS can inhibit GABAA receptor function in cerebellar granule cells. PMID:7535408

Zarri, I; Bucossi, G; Cupello, A; Rapallino, M V; Robello, M

1994-10-24

352

Nitric oxide in the upper stratosphere - Measurements and geophysical interpretation  

NASA Astrophysics Data System (ADS)

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.

1983-12-01

353

Arginine and Nitric Oxide Pathways in Obesity-Associated Asthma  

PubMed Central

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

Holguin, Fernando

2013-01-01

354

Nitrite and Nitric Oxide Metabolism in Peripheral Artery Disease  

PubMed Central

Peripheral Artery Disease (PAD) represents a burgeoning form of cardiovascular disease associated with significant clinical morbidity and increased 5 year cardiovascular disease mortality. It is characterized by impaired blood flow to the lower extremities, claudication pain and severe exercise intolerance. Pathophysiological factors contributing to PAD include atherosclerosis, endothelial cell dysfunction, and defective nitric oxide metabolite physiology and biochemistry that collectively lead to intermittent or chronic tissue ischemia. Recent work from our laboratories is revealing that nitrite/nitrate anion and nitric oxide metabolism plays an important role in modulating functional and pathophysiological responses during this disease. In this review, we discuss experimental and clinical findings demonstrating that nitrite anion acts to ameliorate numerous pathophysiological events associated with PAD and chronic tissue ischemia. We also highlight future directions for this promising line of therapy.

Allen, Jason D.; Giordano, Tony; Kevil, Christopher G.

2012-01-01

355

Bactericidal efficacy of nitric oxide-releasing silica nanoparticles  

PubMed Central

The utility of nitric oxide (NO)-releasing silica nanoparticles as a novel antibacterial is demonstrated against Pseudomonas aeruginosa. Nitric oxide-releasing nanoparticles were prepared via co-condensation of tetraalkoxysilane with aminoalkoxysilane modified with diazeniumdiolate NO donors, allowing for the storage of large NO payloads. Comparison of the bactericidal efficacy of the NO-releasing nanoparticles to 1-[2-(carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolate (PROLI/NO), a small molecule NO donor, demonstrated enhanced bactericidal efficacy of nanoparticle-derived NO and reduced cytotoxicity to healthy cells (mammalian fibroblasts). Confocal microscopy revealed that fluorescently-labeled NO-releasing nanoparticles associated with the bacteria, providing rationale for the enhanced bactericidal efficacy of the nanoparticles. Intracellular NO concentrations were measurable when the NO was delivered from nanoparticles as opposed to PROLI/NO. Collectively, these results demonstrate the advantage of delivering NO via nanoparticles for antimicrobial applications.

Hetrick, Evan M.; Shin, Jae Ho; Stasko, Nathan A.; Johnson, C. Bryce; Wespe, Daniel A.; Holmuhamedov, Ekhson; Schoenfisch, Mark H.

2013-01-01

356

Nitric Oxide-Donor SNAP Induces Xenopus Eggs Activation  

PubMed Central

Nitric oxide (NO) is identified as a signaling molecule involved in many cellular or physiological functions including meiotic maturation and parthenogenetic activation of mammalian oocytes. We observed that nitric oxide donor SNAP was potent to induce parthenogenetic activation in Xenopus eggs. NO-scavenger CPTIO impaired the effects of SNAP, providing evidence for the effects of the latter to be specific upon NO release. In Xenopus eggs, SNAP treatment induced pigment rearrangement, pronucleus formation and exocytosis of cortical granules. At a biochemical level, SNAP exposure lead to MAPK and Rsk inactivation within 30 minutes whereas MPF remained active, in contrast to calcium ionophore control where MPF activity dropped rapidly. MAPK inactivation could be correlated to pronuclear envelope reformation observed. In SNAP-treated eggs, a strong increase in intracellular calcium level was observed. NO effects were impaired in calcium-free or calcium limited medium, suggesting that that parthenogenetic activation of Xenopus oocytes with a NO donor was mainly calcium-dependent.

Jeseta, Michal; Marin, Matthieu; Tichovska, Hana; Melicharova, Petra; Cailliau-Maggio, Katia; Martoriati, Alain; Lescuyer-Rousseau, Arlette; Beaujois, Remy; Petr, Jaroslav; Sedmikova, Marketa; Bodart, Jean-Francois

2012-01-01

357

The role of nitric oxide in prostaglandin biology; update  

PubMed Central

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

Kim, Sangwon F.

2011-01-01

358

ENDOTHELIAL NITRIC OXIDE (NO) AND ITS PATHOPHYSIOLOGIC REGULATION  

PubMed Central

Nitric oxide (NO) is a gaseous lipophilic free radical generated by three distinct isoforms of nitric oxide synthases (NOS), type 1 or neuronal (nNOS), type 2 or inducible (iNOS) and type 3 or endothelial NOS (eNOS). Expression of eNOS is altered in many types of cardiovascular disease, such as atherosclerosis, diabetes and hypertension. The ubiquitous chaperone heat shock protein 90 (hsp90) associates with NOS and is important for its proper folding and function. Current studies point toward a therapeutic potential by modulating hsp90-NOS association in various vascular diseases. Here we review the transcriptional regulation of endothelial NOS and factors affecting eNOS activity and function, as well as the important vascular pathologies associated with altered NOS function, focusing on the regulatory role of hsp90 and other factors in NO-associated pathogenesis of these diseases.

Chatterjee, A.; Catravas, J.D.

2008-01-01

359

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

NASA Astrophysics Data System (ADS)

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

Kim-Shapiro, Daniel

2007-11-01

360

Nitric oxide synthase-derived plasma nitrite predicts exercise capacity  

PubMed Central

Background Nitrite is the main oxidation product of nitric oxide (NO) in plasma. It sensitively reflects changes in endothelial NO synthase (eNOS) activity under fasting conditions and serves as an endocrine NO donor, contributing to the regulation of blood flow through reaction with haemoglobin. As NO is necessary to maintain an adequate vascular response to the increased demands of blood flow, it is believed to be important for vasodilation induced by exercise. Objective To investigate whether the capacity of the vasculature to produce nitrite is associated with exercise performance. Design With the use of chemiluminescence detection, nitrite concentrations in 55 healthy subjects (mean (SEM) age 40 (2) years; 22 men) were studied before and after an exercise test, and endothelial function was determined by measuring flow?mediated dilation of the brachial artery using high?resolution ultrasound. In a subset of subjects, the NOS inhibitor, NG?monomethyl?l?arginine, was applied to elucidate the effect of eNOS on changes in nitrite. Results Exercise significantly (p<0.001) increased plasma nitrite from 97 (6) to 125 (8)?nM. The relative increase in plasma nitrite was related to flow?mediated dilation (6.1 (0.3)%; r?=?0.36; p?=?0.01). NG?Monomethyl?l?arginine blocked increases in nitrite. Post?exercise nitrite concentration correlated with exercise performance, as determined by maximally reached stress power (r?=?0.37; p<0.007), and inversely with age. Multivariate analysis showed that both age and post?exercise nitrite concentration were independent predictors of stress endurance and power. Conclusion The results suggest a role for plasma nitrite in the adaptation of haemodynamics during exercise. An impaired increase in plasma nitrite may limit exercise capacity.

Rassaf, Tienush; Lauer, Thomas; Heiss, Christian; Balzer, Jan; Mangold, Sarah; Leyendecker, Thorsten; Rottler, Jessica; Drexhage, Christine; Meyer, Christian; Kelm, Malte

2007-01-01

361

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

PubMed Central

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

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

2004-01-01

362

Lethal Mycobacterium Bovis Bacillus Calmette Guérin Infection in Nitric Oxide Synthase 2Deficient Mice: Cell-Mediated Immunity Requires Nitric Oxide Synthase 2  

Microsoft Academic Search

The role of nitric oxide (NO) in Mycobacterium bovis Bacillus Calmette Guérin (BCG) infection was investigated using nitric oxide synthase 2 (nos2)-deficient mice, because NO plays a pivotal protective role in M. tuberculosis infection. We demonstrate that nos2-deficient mice were unable to eliminate BCG and succumbed within 8 to 12 weeks to BCG infection (106 CFU) with cachexia and pneumonia,

Irene Garcia; Reto Guler; Dominique Vesin; Maria L Olleros; Pierre Vassalli; Yolande Chvatchko; Muazzam Jacobs; Bernhard Ryffel

2000-01-01

363

Estrogen Up-Regulates Inducible Nitric Oxide Synthase, Nitric Oxide, and Cyclooxygenase2 in Splenocytes Activated with T Cell Stimulants: Role of Interferon  

Microsoft Academic Search

Estrogen is implicated in many autoimmune diseases and is a robust immunomodulator. For example, it regulates inter- feron (IFN)-, a cytokine believed to up-regulate inducible nitric oxide synthase (iNOS). A notable gap in the literature is a lack of information on the regulation of nitric oxide in im- mune tissues by estrogen. We now show that activation of splenocytes with

Ebru Karpuzoglu; Jillian B. Fenaux; Rebecca A. Phillips; Andrea J. Lengi; Francois Elvinger; S. Ansar Ahmed

2005-01-01

364

Nitric oxide education survey – Use of a Delphi survey to produce guidelines for training neonatal nurses to work with inhaled nitric oxide  

Microsoft Academic Search

The pulmonary vasodilator nitric oxide is potentially dangerous for both patients and staff. There is however little published guidance about appropriate training for staff. This study used the Delphi survey technique to identify consensus opinion, amongst a group of experts, on how best to train neonatal nurses to work safely and effectively with nitric oxide. The consensus was used to

Paul Cornick

2006-01-01

365

Induction of Nitric Oxide Synthase Expression by Vibrio vulnificus Cytolysin  

Microsoft Academic Search

The pore-forming cytolysin of Vibrio vulnificus (VVC) causes severe hypotension and vasodilatation in vivo. Under the condition of bacterial sepsis, large amounts of nitric oxide (NO) produced by inducible NO synthase (iNOS) can contribute to host-induced tissue damage causing hypotension and septic shock. In this study, we investigated the effect of purified VVC on NO production in mouse peritoneal macrophages.

Mi-Kyung Kang; Eun-Chung Jhee; Bon-Sun Koo; Jeong-Yeh Yang; Byung-Hyun Park; Jong-Suk Kim; Hye-Won Rho; Hyung-Rho Kim; Jin-Woo Park

2002-01-01

366

Bidirectional Regulation of Osteoclast Function by Nitric Oxide Synthase Isoforms  

Microsoft Academic Search

Nitric oxide (NO) produces rapid osteoclast detachment and contraction in vitro, and this effect is accompanied by a profound inhibition of bone resorption. Work by others has confirmed these findings in vivo: inhibition of NO synthase [NOS; L-arginine, NADPH: oxygen oxidoreductase (NO-forming), EC 1.14.13.39] in normal rats is followed by increased bone resorption reflected by a marked loss in bone

M. L. Brandi; M. Hukkanen; T. Umeda; N. Moradi-Bidhendi; S. Bianchi; S. S. Gross; J. M. Polak; I. MacIntyre

1995-01-01

367

Nitric oxide production: an easily measurable condition index for vertebrates  

Microsoft Academic Search

Nitric oxide (NO) is a multifunctional signalling molecule, acting as a vasodilator, neurotransmitter, and modulator of inflammatory\\u000a processes. It also participates in killing parasites, virus-infected cells, and tumor cells by formation of peroxynitrite,\\u000a one of the most important initiators of the free radical damage. Uncontrolled production of NO can lead to nitrosative stress,\\u000a causing damages to proteins and DNA and

Elin Sild; Peeter Hõrak

2009-01-01

368

Nitric oxide detection in turbulent premixed methane\\/air flames  

Microsoft Academic Search

Investigations of the nitric oxide formation mechanisms of turbulent premixed methane\\/air flames, with regard to turbulence properties and equivalence ratio, are presented. An atmospheric burner with perforated turbulence generating grids allowed the realization of different turbulent flow conditions (Re=8.5×103–1.7×104, u?\\/sL=0.8–8.0), which were measured by PIV. Planar LIF was used to detect the OH radical (as a tracer for the flame

K. Herrmann; K. Boulouchos

2005-01-01

369

Superequilibrium and thermal nitric oxide formation in turbulent diffusion flames  

Microsoft Academic Search

Measurements and modeling of the formation of superequilibrium radicals and nitric oxide in atmospheric pressure turbulent jet diffusion flames are presented which quantify the influence of superequilibrium on thermal NO\\/sub x\\/ formation. Variation of fuel gas compositions (CO\\/Hâ\\/Nâ, CO\\/Hâ\\/COâ, and CO\\/Hâ\\/Ar) permits partial separation of chemical and fluid mechanical effects. Superequilibrium OH radical concentrations are measured by single-pulse laser saturated

M. C. Drake; S. M. Correa; R. W. Pitz; W. Shyy; C. P. Fenimore

1987-01-01

370

Glycosylated PROLI/NO Derivatives as Nitric Oxide Prodrugs  

PubMed Central

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

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

2009-01-01

371

Nitric Oxide in Exhaled Air: Relevance in Inflammatory Lung Disease  

Microsoft Academic Search

\\u000a Nitric oxide (NO) is produced by many cells within the respiratory tract and endogenous NO may play an important signalling\\u000a role in the physiological control of airway function and in the pathophysiology of airway diseases [1–3]. All three isoforms of NO synthase (NOS) exist within the respiratory tract [4–6]. The endothelial constitutive isoform (eNOS) is localised to bronchial endothelial cells

Peter J. Barnes; Sergei A. Kharitonov

372

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.

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

2013-01-01

373

Effect of nitric oxide on rat adrenal zona fasciculata steroidogenesis  

Microsoft Academic Search

The present study was designed to investigate the role of nitric oxide (NO) in the regulation of adreno- cortical function. DiVerent NO donors, such as sodium nitroprusside (SNP), S-nitroso-l-acetyl penicillamine, diethylamine\\/NO complex sodium salt and diethylene- triamine NO adduct, significantly decreased cortico- sterone production both in unstimulated and in corticotropin-stimulated zona fasciculata adrenal cells, in a dose-dependent manner. The eVect

C B Cymeryng; L A Dad; E J Podesta

1998-01-01

374

Nitric Oxide: Monotherapy or Sensitiser to Conventional Cancer Treatments?  

Microsoft Academic Search

\\u000a Nitric oxide is a small molecule with enormous untapped potential in cancer therapy. It is involved in regulating many of\\u000a the pathways that define the malignant phenotype, and its expression within tumours has now been shown to affect the growth\\u000a of tumours and their response to conventional therapies. NO has clear anticancer potential as a single agent in colon, liver

David G. Hirst; Tracy Robson

375

Hepatic and splanchnic nitric oxide activity in patients with cirrhosis  

Microsoft Academic Search

BACKGROUNDIn animal models of cirrhosis, altered activity of nitric oxide (NO) has been implicated in the pathogenesis of increased intrahepatic portal vascular resistance and abnormal mesenteric vasodilatation.AIMSTo investigate NO activity in the liver and splanchnic vascular bed of patients with cirrhosis.METHODSActivity of the calcium dependent constitutive and calcium independent inducible isoforms of NO synthase (cNOS and iNOS, respectively) was assayed

A I Sarela; F M A Mihaimeed; J J Batten; B R Davidson; R T Mathie

1999-01-01

376

Endothelial Nitric Oxide Synthase Gene Polymorphism and Acute Myocardial Infarction  

Microsoft Academic Search

Recently a point mutation of guanine to thymine at nucleotide position 1917 in the endothelial nitric oxide synthase (eNOS) gene has been reported to be associated with coronary artery spasm. In addition, a significant association of the 4a\\/b polymorphism in intron 4 of the eNOS gene with coronary artery disease has been reported. However, the implications of these polymorphisms with

Kiyoshi Hibi; Tomoaki Ishigami; Kouichi Tamura; Shunsaku Mizushima; Nobuo Nyui; Takayuki Fujita; Hisao Ochiai; Masami Kosuge; Yasujirou Watanabe; Yuzuru Yoshii; Minoru Kihara; Kazuo Kimura; Masao Ishii; Satoshi Umemura

2010-01-01

377

Role of nitric oxide in liver ischemia and reperfusion injury  

Microsoft Academic Search

The present study was designed to assess the role of endothelial cell and inducible nitric oxide synthase (eNOS, iNOS)-derived NO in ischemia\\/reperfusion (I\\/R)-induced pro-inflammatory cytokine expression and tissue injury in a murine model of hepatic I\\/R. Forty-five min of partial hepatic ischemia and 3 h of reperfusion resulted in a significant increase in liver injury as assessed by serum alanine

Ian N. Hines; Shigeyuki Kawachi; Hirohisa Harada; Kevin P. Pavlick; Jason M. Hoffman; Sulaiman Bharwani; Robert E. Wolf; Matthew B. Grisham

2002-01-01

378

Nitric oxide in autoimmune disease: cytotoxic or regulatory mediator?  

Microsoft Academic Search

Nitric oxide (NO) is released locally during inflammatory autoimmune diseases and is believed to contribute to tissue destruction. However, recent studies are not fully consistent with such a simple role for NO. Here, Hubert Kolb and Victoria Kolb-Bachofen discuss data that suggest a role for NO in autoimmune diseases as an important regulator of the T helper 1 (Th1)\\/Th2 balance.

Hubert Kolb; Victoria Kolb-Bachofen

1998-01-01

379

Nitric oxide, cell death and increased taxol recovery  

Microsoft Academic Search

Genes for plant nitric oxide synthase (NOS) now help explain how NO is produced from nitrate, nitrite, and\\/or L-arginine in the culture medium and in cells. Evidence is presented that under aseptic conditions; plant NOS activity, NO bursts, and cell death (apoptosis) are important factors in the recovery of taxol (paclitaxel) from cell suspensions of several Taxus sp. Cell-suspension responses

Don J. DURZAN

2005-01-01

380

The dual effect of a nitric oxide donor in nociception  

Microsoft Academic Search

Low intrathecal (i.t.) doses of the nitric oxide (NO)-donor 3-morpholinosydnonimine (SIN-1) (0.1–2.0 ?g\\/10 ?l) reduced, while higher doses had no effect (5 or 100 ?g\\/10 ?l.) or increased (10 and 20 ?g\\/10 ?l) the mechanical allodynia induced by chronic ligature of the sciatic nerve in rats. SIN-1 (0.1–100 ?g\\/10 ?l; i.t.) produced only antinociceptive effect in the rat tail flick

Angela M. Sousa; Wiliam A. Prado

2001-01-01

381

Induction of nitric oxide synthase by traumatic brain injury  

Microsoft Academic Search

We investigated the dynamic induction\\/expression of inducible nitric oxide synthase (iNOS) using human brains made available through death by traumatic brain injury (TBI). Astrocytes, microglia, and neutrophils were identified in tissue using immunohistochemical staining with antibodies against glial fibrillary acidic protein (GFAP), MHC class II antigen, and neutrophil elastase, respectively. The localization of iNOS protein in each of these cell

Yoshiyuki Orihara; Kazuya Ikematsu; Ryouichi Tsuda; Ichiro Nakasono

2001-01-01

382

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

383

Nitric oxide and MPP + -induced hydroxyl radical generation  

Microsoft Academic Search

Summary.  Although neuroprotective effect of nitric oxide (NO) is discussed, NO has a role of pathogenesis of cellular injury. NO is\\u000a synthesized from L-arginine by NO synthase (NOS). NO contributes to the extracellular potassium-ion concentration ([K+]o)-induced hydroxyl radical (•OH) generation. Cytotoxic free radicals such as peroxinitrite (ONOO?) and •OH may also be implicated in NO-mediated cell injury. NO activation was induced

T. Obata

2006-01-01

384

Ageing-related role of nitric oxide in the brain  

Microsoft Academic Search

Production of nitric oxide (NO) in the cell is catalysed by NO synthase (NOS), which using L-arginine and oxygen as substrates, synthesies NO. Normally cells express neuronal and\\/or endothelial NOS (nNOS and eNOS, respectively) producing nanomolar NO. Under inflammatory conditions cells express inducible NOS (iNOS), which, once expressed, produces micromolar NO. Since micromolar NO could elicit damage to cells, iNOS

Sofia Mariotto; Massimo Miscusi; Tiziana Persichini; Marco Colasanti; Hisanori Suzuki

2005-01-01

385

The Akt kinase signals directly to endothelial nitric oxide synthase  

Microsoft Academic Search

Endothelial nitric oxide synthase (eNOS) is an important modulator of angiogenesis and vascular tone [1]. It is stimulated by treatment of endothelial cells in a phosphatidylinositol 3-kinase (PI 3-kinase)-dependent fashion by insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF) [2,3] and is activated by phosphorylation at Ser1177 in the sequence RIRTQS1177F (in the single-letter amino acid code) [4].

B. J. Michell; J. E. Griffiths; K. I. Mitchelhill; I. Rodriguez-Crespo; T. Tiganis; S. Bozinovski; P. R. Ortiz de Montellano; B. E. Kemp; R. B. Pearson

1999-01-01

386

Skeletal muscle inflammation and nitric oxide in patients with COPD  

Microsoft Academic Search

In chronic obstructive pulmonary disease (COPD) the presence of systemic inflammation has been associated with peripheral muscle abnormalities and weight loss. To study whether inflammatory factors are important in these processes, the present study compared the skeletal muscle levels of nitrite, nitrate, nitrotyrosine, neuronal, endothelial and inducible nitric oxide synthases (nNOS, eNOS, and iNOS, respectively), and inflammatory markers (tumour necrosis

M. Montes de Oca; S. H. Torres; A. Mata; N. Hernandez; C. Talamo

2005-01-01

387

Inducible nitric oxide synthase expression in human cerebral infarcts  

Microsoft Academic Search

The inducible or “immunological” isoform of nitric oxide synthase (iNOS) is induced in many cell types by inflammatory stimuli\\u000a and synthesizes toxic amounts of NO. In rodent models of focal cerebral ischemia, iNOS is expressed in neutrophils invading\\u000a the injured brain and in local blood vessels. Studies with iNOS inhibitors and iNOS null mice indicate that NO produced by\\u000a iNOS

Colleen Forster; H. Brent Clark; M. Elizabeth Ross; Constantino Iadecola

1999-01-01

388

Nitric Oxide and TNF? Effects in Experimental Autoimmune Encephalomyelitis Demyelination  

Microsoft Academic Search

The involvement of inducible nitric oxide synthase (iNOS), which plays various roles in the progression of autoimmune diseases, was studied in iNOS knockout (KO) mice and wild-type (WT) controls with respect to experimental autoimmune encephalomyelitis (EAE). The iNOS (KO) mice presented a less severe form of the disease than the WT control mice. Although the levels of TNF? decreased in

Alessandro S. Farias; Cristiane de la Hoz; Fabiano R. Castro; Elaine C. Oliveira; Jose R. Ribeiro dos Reis; João S. Silva; Francesco Langone; Leonilda M. B. Santos

2007-01-01

389

Nitric oxide: state of the art in drug design.  

PubMed

Since the great discovery of Furchgott, Ignarro and Murad in the late 90's, nitric oxide (NO) is considered one of the most versatile endogenous molecules, which is involved in important signaling biochemistry pathways of the human body. Thus, it is directly related to pathological processes and its over- or low-production is able to cause damage in systems that are involved. By using certain functional groups present in molecules that already have potential therapeutic value, hybrid compounds, by means of inclusion of NO-donors (e.g., ester nitrates, furoxans, benzofuroxans, NONOates, S-nitrosothiols, metal complexes), can be generated that have a NO release benefit along with maintaining the activity of the native drug. This approach has proved to be useful in many spheres of Medicinal Chemistry, such as cardiovascular, inflammatory, bacterial, fungal, viral, parasitic, ocular diseases and cancer. Potent and selective nitric oxide synthase inhibitors are being designed, mainly through enzyme structure based process, however, due to high homology between the isoforms, these studies have proved to be very difficult. The objective of the research is to achieve a balance between the release of therapeutic amounts of NO, especially in specific site of action, and maintaining the native drug activity. The search for new and effective NO-donor hybrid drugs, as well as selective nitric oxide synthase inhibitors, is an important focus in modern drug design in order to manipulate biochemical pathways involving NO that influence many dysfunctions of the human organism. PMID:22335514

Serafim, R A M; Primi, M C; Trossini, G H G; Ferreira, E I

2012-01-01

390

The abundance of nitric oxide in molecular clouds  

NASA Astrophysics Data System (ADS)

The detection of two rotational transitions of nitric oxide in six molecular clouds - at two oppositions in the dark cloud L134N and in five giant clouds, OMC1, W51, SgrB2, SgrA + 20 km/s and +50 km/s clouds - is reported. In the dark cloud L134N, the NO column density is about equal to that of (C-18)O, resulting in abundance relative to H2 of about 2 x 10 exp -7. This contrasts with the case of TMC1, where nitric oxide is less abundant than (C-18)O by at least a factor of two. Nitric oxide is mainly produced in the reaction N+OH yields NO+H and mainly destroyed by N+NO yields N2+O. A quantum chemical study of the first reaction indicates that it proceeds with no activation barrier. Steady state chemical models reproduce satisfactorily the observed abundances of NO, and of nitrogen hydrides in the dark cloud L134N, provided that none of the above reactions has an activation barrier.

Gerin, M.; Viala, Y.; Pauzat, F.; Ellinger, Y.

1992-12-01

391

Cerebral blood flow regulation by nitric oxide in Alzheimer's disease.  

PubMed

Cerebral hypoperfusion due to impaired bioavailability of nitric oxide (NO) synthesized by endothelial nitric oxide synthase and neuronal nitric oxide synthase leads to cognitive decline and neurodegeneration in Alzheimer's disease (AD). Risk factors for endothelial dysfunction, such as inadequate lifestyle, cardiovascular/metabolic diseases, and aging, evokes cerebral hypoperfusion, impaired autoregulation, and increased production of amyloid-? peptides (A?) in association with vasculogenic memory loss and dementia. Decrease in parasympathetic nitrergic nerve activity also plays a role in cerebral hypoperfusion. A? is a functional obstacle to NO-mediated vasodilatation; therefore, it decreases cerebral blood flow. Generation of reactive oxygen species by A? is a major action in promoting NO degradation. Effective strategies for the prophylaxis or treatment of AD includes acetylcholinesterase inhibitors, drugs acting on the NO-cyclic GMP signaling pathway, antioxidants, peroxisome proliferator-activated receptor ?-agonists, and hydroxymethylglutaryl-CoA reductase inhibitors. Here our hypothesis about the mechanisms underlying the actions of acetylcholinesterase inhibitors in relation to NO-mediated cerebral blood flow is presented. Future detailed analyses of the relationship between cerebral blood flow regulation by constitutive NO and cognitive decline/neurodegeneration will provide clues for developing novel prophylactic measures and therapeutic means to alleviate AD. PMID:22810094

Toda, Noboru; Okamura, Tomio

2012-01-01

392

[Nitric oxide and reflectory regulation of blood circulation in rats].  

PubMed

In acute experiments on anaesthetized with urethane normotensive rats we studied the ways of participation of nitric oxide (NO) in reflector control of the cardiovascular system by the medullary neurons within n.tractus solitarii (NTS), dorsal nucleus of the vagus nerve (DNV), n. ambiguus (AMB), and the lateral reticular nucleus (LRN). Modulations of the activities of neuronal NO-synthase (nNOS) in the populations of the cardiovascular neurons within the medullary nuclei which are involved in the reflector cardiovascular control were induced by intramedullary injections of sodium nitroprusside as NO donor, L-arginine as NO precursor, L-NNA as an inhibitor of NOS, as well as by intraperetoneal injections of 7-nitroindazol (nNOS inhibitor). We have determined that stimulation of nNOS activity in the populations of the medullary neurons resulted in both remarkable shifts in the SAP level and in inhibiting the chemoreceptor reflector responses. After preliminary inhibiting nNOS chemoreceptor reflexes induced by epinephrine were found to be enhanced in most experiments. PMID:14509925

Shapoval, L M; Mo?benko, O O; Sahach, V F; Pobiha?lo, L S; Dmytrenko, O V

2003-01-01

393

Nitric oxide mediates renal vasodilation during erythropoietin-induced polycythemia.  

PubMed

The renal blood flow (RBF) of patients with polycythemia rubra vera is increased despite the high hematocrit (Hct) which elevates the whole blood viscosity. Since blood viscosity determines the shear force on the endothelium which is a major stimulus to nitric oxide (NO) release, we investigated the hypothesis that renal vasodilation during erythropoietin-induced erythrocytosis is mediated by the L-arginine-NO pathway. Groups of Sprague-Dawley rats received thrice weekly injections of erythropoietin (E) for two to five weeks; responses were contrasted with normal rats (N) which received sham injections. The first group was studied after five weeks of erythropoietin injections which led to sharp increases in Hct (E: 72 +/- 3 vs. N: 44 +/- 1%) and mean arterial pressure (MAP: 126 +/- 3 vs. 107 +/- 3 mm Hg). These rats had an elevated basal RBF whether measured by the clearance and renal extraction of PAH or by a transit-time renal blood flow meter. Subsequent groups were studied after two to three weeks of erythropoietin which raised the Hct more modestly to 59 +/- 2%. In this group, the basal MAP was similar in E and N rats. Graded doses of the NO synthase inhibitor, N omega-monomethyl-L-arginine (L-NMA) led to a steeper rise in MAP in E than N; at the highest doses, the MAP had increased by 36 +/- 2 in E and 23 +/- 3 mm Hg in N (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8377385

Wilcox, C S; Deng, X; Doll, A H; Snellen, H; Welch, W J

1993-08-01

394

Nitric oxide modulation of quantal secretion in chick ciliary ganglia.  

PubMed Central

1. Long-term potentiation of quantal secretion was studied at ciliary ganglion synapses of post-hatched birds following tetanic stimulation of the oculomotor nerve and the effects of nitric oxide (NO) on quantal secretion were determined. 2. Tetanic stimulation of the oculomotor nerve at 30 Hz for 20 s at room temperature increased the amplitude of the excitatory postsynaptic potential (EPSP) by about 100%; 1-2 min after the tetanus the EPSP declined exponentially with a time constant of about 10 min (long-term potentiation; LTP). LTP was due to an increase in the quantal content of the EPSP not to a change in quantal size. 3. A component of LTP was shown to be due to the release of NO in the ganglion, as blocking the synthesis of NO with L-arginine methyl ester decreased the potentiation by 70%. 4. Exogenous application of NO using sodium nitroprusside increased the amplitude of the EPSP by more than 30% due to an increase in the quantal content of the EPSP. 5. Both 8-bromo-cGMP and 8-bromo-cAMP increased the quantal content of the EPSP by more than 44% without changing the quantal size. 6. The results suggest that endogenous NO is involved in either the initiation or maintenance phase of LTP. This may occur through an increase in quantal secretion consequent on the action of an elevated cGMP increasing cAMP.

Lin, Y Q; Bennett, M R

1994-01-01

395

Nitric Oxide Diffusion Rate is Reduced in the Aortic Wall?  

PubMed Central

Endogenous nitric oxide (NO) plays important physiological roles in the body. As a small diatomic molecule, NO has been assumed to freely diffuse in tissues with a diffusion rate similar to that in water. However, this assumption has not been tested experimentally. In this study, a modified Clark-type NO electrode attached with a customized aorta holder was used to directly measure the flux of NO diffusion across the aortic wall at 37°C. Experiments were carefully designed for accurate measurements of the apparent NO diffusion coefficient D and the partition coefficient ? in the aortic wall. A mathematical model was presented for analyzing experimental data. It was determined that ? = 1.15 ± 0.11 and D = 848 ± 45 ?m2/s (n = 12). The NO diffusion coefficient in the aortic wall is nearly fourfold smaller than the reported diffusion coefficient in solution at 37°C, indicating that NO diffusion in the vascular wall is no longer free, but markedly dependent on the environment in the tissue where these NO molecules are. These results imply that the NO diffusion rate in the vascular wall may be upregulated and downregulated by certain physiological and/or pathophysiological processes affecting the composition of tissues.

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

2008-01-01

396

Reduction of nitric oxide by hydroxylamine. 1. Kinetics and mechanism  

SciTech Connect

The reaction of nitric oxide with hydroxylamine conforms to the rate law -dP/sub NO//dt = k/sub 2/(NH/sub 2/O/sup -/)P/sub NO/ in the pH range 7.29-13.14, confirming the rate-determining abstraction of an N-bound H atom by NO. Measured kinetic quantities: k/sub 2/ = 6.68 x 10/sup -3/ M/sup -1/ s/sup -1/ at 25/sup 0/C; ..delta.. H double dagger = 29.6 kJ mol/sup -1/; ..delta.. S double dagger = -189 J K/sup -1/ mol/sup -1/. Thermodynamic values have been obtained for the pK/sub a/ of NH/sub 2/OH at several temperatures; ..delta.. H of dissociation = 55.29 kJ mol/sup -1/. The presence of trace amounts of O/sub 2/ in the NO-NH/sub 2/OH reaction system catalyzes the reaction and leads to a reduced molar product ratio n/sub N/sub 2/O/, effects that are ascribed at least in part to reactive N/sub 2/O/sub 3/. The difference in reactivity between the NO/sup -/ intermediate formed in this reaction and that produced in trioxodinitrate decomposition is discussed.

Bonner, F.T.; Wang, N.Y.

1986-05-21

397

Neuronal nitric oxide synthase and dystrophin-deficient muscular dystrophy.  

PubMed Central

Neuronal nitric oxide synthase (nNOS) in fast-twitch skeletal muscle fibers is primarily particulate in contrast to its greater solubility in brain. Immunohistochemistry shows nNOS localized to the sarcolemma, with enrichment at force transmitting sites, the myotendinous junctions, and costameres. Because this distribution is similar to dystrophin, we determined if nNOS expression was affected by the loss of dystrophin. Significant nNOS immunoreactivity and enzyme activity was absent in skeletal muscle tissues from patients with Duchenne muscular dystrophy. Similarly, in dystrophin-deficient skeletal muscles from mdx mice both soluble and particulate nNOS was greatly reduced compared with C57 control mice. nNOS mRNA was also reduced in mdx muscle in contrast to mRNA levels for a dystrophin binding protein, alpha 1-syntrophin. nNOS levels increased dramatically from 2 to 52 weeks of age in C57 skeletal muscle, which may indicate a physiological role for NO in aging-related processes. Biochemical purification readily dissociates nNOS from the dystrophin-glycoprotein complex. Thus, nNOS is not an integral component of the dystrophin-glycoprotein complex and is not simply another dystrophin-associated protein since the expression of both nNOS mRNA and protein is affected by dystrophin expression. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4

Chang, W J; Iannaccone, S T; Lau, K S; Masters, B S; McCabe, T J; McMillan, K; Padre, R C; Spencer, M J; Tidball, J G; Stull, J T

1996-01-01

398

Decoding nitric oxide release rates of amine-based diazeniumdiolates.  

PubMed

Amine-based diazeniumdiolates (NONOates) have garnered widespread use as nitric oxide (NO) donors, and their potential for nitroxyl (HNO) release has more recently been realized. While NO release rates can vary significantly with the type of amine, half-lives of seconds to days under physiological conditions, there is as yet no way to determine a priori the NO or HNO production rates of a given species, and no discernible trends have manifested other than that secondary amines produce only NO (i.e., no HNO). As a step to understanding these complex systems, here we describe a procedure for modeling amine-based NONOates in water solvent that provides an excellent correlation (R(2) = 0.94) between experimentally measured dissociation rates of seven secondary amine species and their computed NO release activation energies. The significant difference in behavior of NONOates in the gas and solvent phases is also rigorously demonstrated via explicit additions of quantum mechanical water molecules. The presented results suggest that the as-yet unsynthesized simplest amine-based NONOate, the diazeniumdiolated ammonia anion [H2N-N(O)?NO(-)], could serve as an unperturbed HNO donor. These results provide a step forward toward the accurate modeling of general NO and/or HNO donors as well as for the identification of tailored prodrug candidates. PMID:23834533

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

2013-07-23

399

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

1. 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'. 2. 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 N (G)-nitro-L-arginine methyl ester (L-NAME, 100 mg x kg(-1)) and the NO donor sodium nitroprusside (NP, 5.1 +/- 2.0 microg x kg(-1) x 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. 3. 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. 4. 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, D S; Powlson, A S; Giussani, D A

2001-12-01

400

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.

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

2001-01-01

401

Effects of melatonin on testicular tissue nitric oxide level and antioxidant enzyme activities in experimentally induced left varicocele  

Microsoft Academic Search

OBJECTIVES: The pathophysiology of the testicular damage in varicocele have not been completely understood. There are several studies concerning the effects of increased seminal reactive oxygen species (ROS) and the role of nitric oxide (NO) in infertile patients with varicocele and antioxidants have been used successfully to decrease oxidative stress in testis. In this study, we determined the effects of

Atilla Semercioz; Rahmi Onur; Sezai Ogras; Irfan Orhan

402

Third phase formation in nitric acid extraction by n-octyl(phenyl)-n,n-diisobutylcarbamoylmethylphosphine oxide  

SciTech Connect

The third phase formation was studied as a function of n-octyl(phenyl)-N,N-diisobutylcarbamoylmethylphosphine oxide (CMPO) and tri-n-butyl phosphate (TBP) concentrations and temperature in the extraction of nitric acid. The concentration fractions of CMPO and TBP in the second and the third phases were determined by gas chromatography. Both CMPO and TBP were found to be enriched in the third phase. The concentrations of nitric acid in the second and the third phases relatively agreed with the calculated concentrations based on the extraction equilibrium constants of nitric acid by CMPO and TBP. The extraction of Np with the third phase formation was also discussed. 21 refs., 4 figs., 3 tabs.

Nagasaki, S.; Wisnubroto, D.S.; Enokida, Y.; Suzuki, A. (Univ. of Tokyo (Japan))

1994-03-01

403

Haptoglobin polymorphism affects nitric oxide bioavailability in preeclampsia.  

PubMed

Studies showed elevated cell-free hemoglobin (Hb) in preeclampsia (PE), and Hb reacts with nitric oxide (NO), decreasing its bioavailability. Haptoglobin (Hp) is a polymorphic protein (Hp1-1, Hp2-1 and Hp2-2) that binds Hb to form a complex that is removed from circulation, thus preventing Hb-driven oxidative stress and NO scavenging. Hp protein products differ in biochemical and biophysical properties, which reflects on the Hb-Hp complex clearance rate. We hypothesized that Hp phenotypes modulate NO bioavailability by influencing NO consumption in PE. We studied 92 PE subjects and 105 normal pregnant women (NP). Hp genotypes were determined using real-time PCR. To assess NO bioavailability, we measured plasma nitrite using an ozone-based chemiluminescence assay. Plasma Hb and Hp were assessed with commercial immunoassays. A NO consumption assay was used to measure NO consumption. We found no differences in Hp genotype frequencies between PE and NP groups. Hp genotypes had no effects on plasma heme levels, NO consumption and plasma nitrite in NP. However, in PE, Hp2-1 and Hp2-2 were associated with higher plasma heme levels (48 and 55% higher, respectively; P<0.05), increased NO consumption (42 and 44% more, respectively; P<0.05) and lower plasma nitrite (39% less for Hp2-2; P<0.05) compared with Hp1-1. These findings indicate that although Hp genotype does not affect the risk of PE, Hp1-1 genotype may exert a protective role in PE by reducing NO scavenging, whereas Hp2-1 and Hp2-2 further may aggravate PE by reducing NO bioavailability. PMID:23223086

Sertório, J T; Lacchini, R; Amaral, L M; Palei, A C T; Cavalli, R C; Sandrim, V C; Duarte, G; Tanus-Santos, J E

2012-12-06

404

Nitric oxide induces transcriptional activation of the nitric oxide-tolerant alternative oxidase in Arabidopsis suspension cells  

Microsoft Academic Search

Nitric oxide (NO) is a double-edged sword - it can be either beneficial and activate defence responses in plants and animals or, together with reactive oxygen species, it can kill not only the pathogen but also the host. A prime target of NO is the cytochrome c-dependent respiration. Only plants possess alternative-pathway respiration with alternative oxidase (AOX) as a terminal

Xi Huang; Uta von Rad; Jörg Durner

2002-01-01

405

Nitric Oxide Synthase Generates Superoxide and Nitric Oxide in Arginine-Depleted Cells Leading to Peroxynitrite-Mediated Cellular Injury  

Microsoft Academic Search

Besides synthesizing nitric oxide (NO), purified neuronal NO synthase (nNOS) can produce superoxide (\\\\cdotO2-) at lower L-Arg concentrations. By using electron paramagnetic resonance spin-trapping techniques, we monitored NO and \\\\cdotO2- formation in nNOS-transfected human kidney 293 cells. In control transfected cells, the Ca2+ ionophore A23187 triggered NO generation but no \\\\cdotO2- was seen. With cells in L-Arg-free medium, we observed

Yong Xia; Valina L. Dawson; Ted M. Dawson; Solomon H. Snyder; Jay L. Zweier

1996-01-01

406

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

Microsoft Academic Search

The objective of this study was to elucidate the nitric oxide–forming reactions of the iron-N-methyl-d-glucamine dithiocarbamate (Fe-MGD) complex from the nitrogen-containing compound hydroxyurea. The Fe2+(MGD)2 complex is commonly used in electron paramagnetic resonance (EPR) spectroscopic detection of NO both in vivo and in vitro. The reaction of Fe2+(MGD)2 with NO yields the resultant NO-Fe2+(DETC)2 complex, which has a characteristic triplet

Koichiro Tsuchiya; Jin-Jie Jiang; Masanori Yoshizumi; Toshiaki Tamaki; Hitoshi Houchi; Kazuo Minakuchi; Kenji Fukuzawa; Ronald P. Mason

1999-01-01

407

Activation of Inducible Nitric Oxide Synthase Results in Nitric Oxide-mediated Radiosensitization of Hypoxie EMT6 Tumor Cells1  

Microsoft Academic Search

EMT-6 cells treated for 16 h with 1-10 units\\/ml IFN-y showed a gradual activation ofinducible nitric oxide synthase (¡NOS) in Western and Northern blots, a simultaneous raise in NO output, and an increase in hypoxic cell radiosensitivity almost to the level of aerobic cells. Both the NO signal and radioseasitization were counteracted by the NO scavenger oxyhemoglobin, by the specific

Marleen Y. Janssens; Dirk L. Van den Berge; Valeri N. Verovski; Christinne Monsaert; Guy A. Storme

1998-01-01

408

Neuronal (Type I) Nitric Oxide Synthase Regulates Nuclear Factor kappa B Activity and Immunologic (Type II) Nitric Oxide Synthase Expression  

Microsoft Academic Search

Nitric oxide subserves diverse physiologic roles in the nervous system. NO is produced from at least three different NO synthase (NOS) isoforms: neuronal NOS (nNOS), endothelial NOS, and immunologic NOS (iNOS). We show that nNOS is the predominant isoform constitutively expressed in glia. NO derived from nNOS in glia inhibits the transcription factor nuclear factor kappa B (NFkappa B) as

Hitoshi Togashi; Masayuki Sasaki; Elliot Frohman; Eichi Taira; Rajiv R. Ratan; Ted M. Dawson; Valina L. Dawson

1997-01-01

409

L-Arginine Availability Is Not Limiting for Nitric Oxide Generation from Recombinant Endothelial Nitric Oxide Synthase  

Microsoft Academic Search

L-Arginine (L-Arg) may be limiting for inducible nitric oxide synthase (NOS) activity and under certain circumstances, such as increased concentrations of a NOS inhibitor, may also be limiting for endothelial NOS activity. It is unknown if L-Arg is limiting for recombinant eNOS activity in the vascular wall after adenoviral mediated gene transfer. Our aim was to examine, if L-Arg is

Tibor Mohacsi; Geza Mozes; Jun’ichi Sato; Peter Gloviczki; Zvonimir Katusic; Timothy O’Brien

1999-01-01

410

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

Microsoft Academic Search

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

Toshio Obata; Yasumitsu Yamanaka

2001-01-01

411

Nitric oxide decreases cytokine-induced endothelial activation. Nitric oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokines.  

PubMed

To test the hypothesis that nitric oxide (NO) limits endothelial activation, we treated cytokine-stimulated human saphenous vein endothelial cells with several NO donors and assessed their effects on the inducible expression of vascular cell adhesion molecule-1 (VCAM-1). In a concentration-dependent manner, NO inhibited interleukin (IL)-1 alpha-stimulated VCAM-1 expression by 35-55% as determined by cell surface enzyme immunoassays and flow cytometry. This inhibition was paralleled by reduced monocyte adhesion to endothelial monolayers in nonstatic assays, was unaffected by cGMP analogues, and was quantitatively similar after stimulation by either IL-1 alpha, IL-1 beta, IL-4, tumor necrosis factor (TNF alpha), or bacterial lipopolysaccharide. NO also decreased the endothelial expression of other leukocyte adhesion molecules (E-selectin and to a lesser extent, intercellular adhesion molecule-1) and secretable cytokines (IL-6 and IL-8). Inhibition of endogenous NO production by L-N-monomethyl-arginine also induced the expression of VCAM-1, but did not augment cytokine-induced VCAM-1 expression. Nuclear run-on assays, transfection studies using various VCAM-1 promoter reporter gene constructs, and electrophoretic mobility shift assays indicated that NO represses VCAM-1 gene transcription, in part, by inhibiting NF-kappa B. We propose that NO's ability to limit endothelial activation and inhibit monocyte adhesion may contribute to some of its antiatherogenic and antiinflammatory properties within the vessel wall. PMID:7542286

De Caterina, R; Libby, P; Peng, H B; Thannickal, V J; Rajavashisth, T B; Gimbrone, M A; Shin, W S; Liao, J K

1995-07-01

412

Nitric Oxide Has Differential Effects on Currents in Different Subsets of Manduca sexta Antennal Lobe Neurons  

PubMed Central

Nitric oxide has been shown to regulate many biological systems including olfaction. In the moth olfactory system nitric oxide is produced in the antennal lobe in response to odor stimulation and has complex effects on the activity of both projection neurons and local interneurons. To examine the cell autonomous effects of nitric oxide on these cells, we used patch-clamp recording in conjunction with pharmacological manipulation of nitric oxide to test the hypothesis that nitric oxide differentially regulates the channel properties of these different antennal lobe neuron subsets. We found that nitric oxide caused increasing inward currents in a subset of projection neurons while the effects on local neurons were variable but consistent within identifiable morphological subtypes.

Higgins, Mark; Miller, Michael; Nighorn, Alan

2012-01-01

413

Gas-Phase Oxidation of Nitric Oxide: Chemical Kinetics and Rate Constant  

Microsoft Academic Search

Inhaled nitric oxide (NO) is gaining popularity as a selective pulmonary vasodilator. Because of the potential toxicity of NO and its oxidizing product nitrogen dioxide (NO2), any system for the delivery of inhaled NO must aim at predictable and reproducible levels of NO and at as low concentrations of NO2 as possible. This review describes the chemical kinetics and rate

Hirokazu Tsukahara; Takanobu Ishida; Mitsufumi Mayumi

1999-01-01

414

Interactions between nitric oxide and lipid oxidation pathways: implications for vascular disease.  

PubMed

Nitric oxide ((.)NO) signaling pathways and lipid oxidation reactions are of central importance in both the maintenance of vascular homeostasis and the progression of vascular disease. Because both of these pathways involve free radical species that can also react together at extremely fast rates, convergent interactions between these pathways are expected. Biochemical and cell biology studies have defined multiple interactions of (.)NO with oxidizing lipids that could lead to either vascular protection or potentiation of inflammatory vascular injury. For example, low levels of (.)NO generated by endothelial nitric oxide synthase can terminate propagating lipid radicals and inhibit lipoxygenases, reactions that would be protective. Alternatively, if generated at elevated levels, for example, after inducible nitric oxide synthase expression in inflammation, (.)NO can be converted to prooxidant species, such as peroxynitrite (ONOO(-)) and nitrogen dioxide ((.)NO(2)), that can potentiate inflammatory injury to vascular cells. Finally, both enzymatic and nonenzymatic lipid oxidation reactions can influence (.)NO bioactivity by directly scavenging (.)NO or altering the induction and catalytic activity of nitric oxide synthase enzymes. In this review, we summarize the biochemical interactions between (.)NO and lipid oxidation reactions and discuss the recognized and potential roles of these reactions in the vasculature. PMID:11139468

O'Donnell, V B; Freeman, B A

2001-01-19

415

Different expression patterns of nitric oxide synthase isozymes in various gynecological cancers  

Microsoft Academic Search

The expression of nitric oxide synthase (NOS) in human gynecological cancers, including ovarian cancers, uterocervical cancers,\\u000a and endometrial cancers for example, was examined by the reverse transcriptase\\/polymerase chain reaction, coupled with Southern\\u000a hybridization and by immunohistochemistry. Nitric oxide synthase II (NOS II), an inducible form, was expressed in more than\\u000a 90% of the cancers. Nitric oxide synthase I (NOS I),

Rieko Hamaoka; Yuji Yaginuma; Tomoaki Takahashi; Junichi Fujii; Masahiko Koizumi; Han Geuk Seo; Yutaka Hatanaka; Kaoru Hashizume; Kunio Ii; Jun-ichiro Miyagawa; Toshiaki Hanafusa; Yuji Matsuzawa; Mutsuo Ishikawa; Naoyuki Taniguchi

1999-01-01

416

Nitric oxide for the evaluation and treatment of pulmonary hypertension in congenital heart disease.  

PubMed Central

The use of inhaled nitric oxide as a selective pulmonary vasodilator has expanded to include patients with congenital heart disease and pulmonary hypertension. The therapeutic and diagnostic roles of inhaled nitric oxide offer additional alternatives and benefits to these patients with pulmonary hypertension, particularly in the postoperative setting. This article reviews the background, mechanism of action, toxicities, and current clinical applications of inhaled nitric oxide in the child with congenital heart disease and pulmonary hypertension.

Kovalchin, J P; Mott, A R; Rosen, K L; Feltes, T F

1997-01-01

417

Nitric Oxide is an Important Mediator for Tumoricidal Activity In vivo  

Microsoft Academic Search

When cultured in vitro, peritoneal macrophages, obtained from mice previously inoculated with bacillus Calmette-Guerin, release nitric oxide, which is cytostatic and\\/or cytolytic for tumor cells. However, it is not known whether nitric oxide has antitumor effects in vivo. Here we demonstrate that nitric oxide is an important mediator of host resistance to syngeneic and xenogeneic ovarian tumor grafts in C3HeB\\/FeJ

Robin Farias-Eisner; Michael P. Sherman; Ernesto Aeberhard; Gautam Chaudhuri

1994-01-01

418

Hypoxia-Induced Generation of Nitric Oxide Free Radicals in Cerebral Cortex of Newborn Guinea Pigs  

Microsoft Academic Search

Previous studies have shown that brain tissue hypoxia results in increased N-methyl-D-aspartate (NMDA) receptor activation and receptor-mediated increase in intracellular calcium which may activate Ca++-dependent nitric oxide synthase (NOS). The present study tested the hypothesis that tissue hypoxia will induce generation of nitric oxide (NO) free radicals in cerebral cortex of newborn guinea pigs. Nitric oxide free radical generation was

Om Prakash Mishra; Santina Zanelli; S. Tsuyoshi Ohnishi; Maria Delivoria-Papadopoulos

2000-01-01

419

Functional Expression of Three Isoforms of Human Nitric Oxide Synthase in Baculovirus-Infected Insect Cells  

Microsoft Academic Search

Complementary DNAs encoding three human isoforms (neuronal, inducible, and endothelial) of nitric oxide synthase were cloned into the baculovirus expression vector pVL1392\\/1393. Transfection of Sf-9 insect cells with the recombinant baculovirus resulted in the expression of high levels of nitric oxide synthases. The expressed proteins of neuronal and inducible nitric oxide synthase were predominantly soluble, whereas the endothelial enzyme was

M. Nakane; J. S. Pollock; V. Klinghofer; F. Basha; P. A. Marsden; A. Hokari; T. Ogura; H. Esumi; G. W. Carter

1995-01-01

420

Nitric oxide interacts with the cAMP pathway to modulate capacitation of human spermatozoa  

Microsoft Academic Search

This study aimed to demonstrate nitric oxide production by human spermatozoa and to characterize the interaction between nitric oxide and cAMP-related pathway in the control of human sperm capacitation and protein tyrosine phosphorylation. Spermatozoa were incubated in Tyrode’s medium with or without bovine serum albumin (BSA), and nitric oxide was measured with the spin trap sodium N-methyl-D-glucamine dithiocarbamate. Under noncapacitating

Maria Belén Herrero; Suvro Chatterjee; Linda Lefièvre; Eve de Lamirande; Claude Gagnon

2000-01-01

421

The reduction potential of nitric oxide (NO) and its importance to NO biochemistry  

Microsoft Academic Search

A potential of about -0.8 (±0.2) V (at 1 M versus normal hydrogen electrode) for the reduction of nitric oxide (NO) to its one-electron reduced species, nitroxyl anion (3NO-) has been determined by a combination of quantum mechanical calculations, cyclic voltammetry measurements, and chemical reduction experiments. This value is in accord with some, but not the most commonly accepted, previous

Michael D. Bartberger; Wei Liu; Eleonora Ford; Katrina M. Miranda; Christopher Switzer; Jon M. Fukuto; Patrick J. Farmer; David A. Wink; Kendall N. Houk

2002-01-01

422

Expression of endothelial nitric oxide synthase in the ovine ovary throughout the estrous cycle  

Microsoft Academic Search

This study was conducted to evaluate the expression of endothelial nitric oxide synthase (eNOS) in ovarian follicles and corpora lutea (CL) throughout the estrous cycle in sheep. Three experiments were conducted to (1) immunolocalize eNOS protein, (2) determine expression of mRNA for eNOS and its receptor guanylate cyclase 1 soluble b3 (GUCY1B3), and (3) co-localize eNOS and vascular endothelial growth

Anna T Grazul-Bilska; Chainarong Navanukraw; Mary Lynn Johnson; Daniel A Arnold; Lawrence P Reynolds; Dale A Redmer

2006-01-01

423

Role of nitric oxide in renal tubular apoptosis of unilateral ureteral obstruction  

Microsoft Academic Search

Role of nitric oxide in renal tubular apoptosis of unilateral ureteral obstruction.BackgroundThe obstructed kidney in unilateral ureteral obstruction (UUO) is characterized by renal atrophy and tissue loss, which is mediated by renal tubular apoptosis. We sought to determine whether NO is involved in renal tubular apoptosis in vitro and in vivo.MethodsRat renal tubular epithelial cells (NRK-52E) were subjected to mechanical

Akira Miyajima; Jie Chen; Dix P. Poppas; E. Darracott Vaughan; Diane Felsen

2001-01-01

424

Increased Serum Nitric Oxide Concentration After Bariatric Surgery—A Potential Mechanism for Cardiovascular Benefit  

Microsoft Academic Search

Background  It is believed that endothelial dysfunction associated with obesity contributes to reduced vascular production of nitric oxide\\u000a (NO). Weight reduction after bariatric surgery is known to decrease the risk of cardiovascular disease. The purpose of this\\u000a study was to determine whether bariatric surgery leads to improvement of metabolic markers of endothelial function: serum\\u000a NO and its precursor (arginine) concentrations in

Tomasz Sledzinski; Maciej Sledzinski; Ryszard Tomasz Smolenski; Julian Swierczynski

2010-01-01

425

Role of Nitric Oxide in Pathogenesis of Herpes Simplex Virus Encephalitis in Rats  

Microsoft Academic Search

The role of nitric oxide (NO) in the pathogenesis of viral encephalitis was investigated by using an experimental model of herpes simplex virus type 1 (HSV-1) encephalitis in Lewis rats. The expression of inducible NO synthase (iNOS) mRNA determined by Northern blotting was observed first in the olfactory bulb and the brain stem on day 5 after intranasal inoculation of

Shigemoto Fujii; Takaaki Akaike; Hiroshi Maeda

1999-01-01

426

Laser-saturated fluorescence of nitric oxide and chemiluminescence measurements in premixed ethanol flames  

Microsoft Academic Search

In this study, nitric oxide laser-saturated fluorescence (LSF) measurements were acquired from premixed ethanol flames at atmospheric pressure in a burner. NO-LSF experimental profiles for fuel-rich premixed ethanol flames ( = 1.34 and = 1.66) were determined through the excitation\\/detection scheme of the Q(26.5) rotational line in the A²{sup +} - X² (0,0) vibronic band and (0,1) emission band. A

Carla S. T. Marques; Luiz G. Barreta; Maria E. Sbampato; Alberto M. dos Santos

2010-01-01

427

Laser induced fluorescence measurements and modeling of nitric oxide in high-pressure premixed flames  

Microsoft Academic Search

Laser-induced fluorescence (LIF) has been applied to the quantitative measurement of nitric oxide (NO) in premixed, laminar, high-pressure flames. Their chemistry was also studied using three current kinetics schemes to determine the predictive capabilities of each mechanism with respect to NO concentrations. The flames studied were low-temperature (1600 less than T less than 1850K) C2H6\\/O2\\/N2 and C2H6\\/O2\\/N2 flames, and high

John R. Reisel; Normand M. Laurendeau

1994-01-01

428

Laser-saturated fluorescence of nitric oxide and chemiluminescence measurements in premixed ethanol flames  

Microsoft Academic Search

In this study, nitric oxide laser-saturated fluorescence (LSF) measurements were acquired from premixed ethanol flames at atmospheric pressure in a burner. NO-LSF experimental profiles for fuel-rich premixed ethanol flames (?=1.34 and ?=1.66) were determined through the excitation\\/detection scheme of the Q2(26.5) rotational line in the A2?+?X2? (0,0) vibronic band and ?(0,1) emission band. A calibration procedure by NO doping into

Carla S. T. Marques; Luiz G. Barreta; Maria E. Sbampato; Alberto M. dos Santos

2010-01-01

429

Kinetic model of the inhibition of respiration by endogenous nitric oxide in intact cells  

Microsoft Academic Search

Nitric oxide (NO) inhibits mitochondrial respiration by decreasing the apparent affinity of cytochrome c oxidase (CcO) for oxygen. Using iNOS-transfected HEK 293 cells to achieve regulated intracellular NO production, we determined NO and O2 concentrations and mitochondrial O2 consumption by high-resolution respirometry over a range of O2 concentrations down to nanomolar. Inhibition of respiration by NO was reversible, and complete

Enara Aguirre; Félix Rodríguez-Juárez; Andrea Bellelli; Erich Gnaiger; Susana Cadenas

2010-01-01

430

Involvement of nitric oxide in granisetron improving effect on scopolamine-induced memory impairment in mice  

Microsoft Academic Search

Granisetron, a serotonin 5-HT3 receptor antagonist, widely used as an antiemetic drug following chemotherapy, has been found to improve learning and memory. In this study, effects of granisetron on spatial recognition memory and fear memory and the involvement of nitric oxide (NO) have been determined in a Y-maze and passive avoidance test. Granisetron (3, 10mg\\/kg, intraperitoneally) was administered to scopolamine-induced

Mehrak Javadi-Paydar; Marjan Zakeri; Abbas Norouzi; Hossein Rastegar; Naser Mirazi; Ahmad Reza Dehpour

431

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

432

Purification of a Distinctive Form of Endotoxin-Induced Nitric Oxide Synthase from Rat Liver  

Microsoft Academic Search

An endotoxin-induced form of nitric oxide synthase (EC 1.14.23) was purified to homogeneity from rat liver by sequential anion-exchange chromatography and affinity chromatography using 2',5'-ADP-Sepharose. The enzyme has a subunit molecular mass of 135 kDa as determined by SDS\\/PAGE, a maximum specific activity of 462 nmol of citrulline formed from arginine per min per mg, and a K_m for arginine

Tom Evans; Adam Carpenter; Jonathan Cohen

1992-01-01

433

Nitric Oxide Impairs Normoxic Degradation of HIF-1  by Inhibition of Prolyl Hydroxylases  

Microsoft Academic Search

Hypoxia inducible factor-1 (HIF-1) is the master regulator of metabolic adaptation to hypoxia. It is appreciated that HIF-1 accumulation is achieved under normoxic conditions by e.g., nitric oxide. We determined molecular mechanisms of HIF-1 accumulation under the impact of S-nitrosoglutathione (GSNO). In human embryonic kidney cells GSNO provoked nuclear accu- mulation of HIF-1. This appeared unrelated to gene transcription and

Eric Metzen; Jie Zhou; Wolfgang Jelkmann; Joachim Fandrey; Bernhard Brun

2003-01-01

434

Contribution of nitric oxide to the blood pressure and arterial responses to exercise in humans  

Microsoft Academic Search

An exaggerated blood pressure (BP) response to exercise predicts future cardiovascular risk. The mechanisms underlying exercise-induced hypertension remain unclear, although endothelial dysfunction and elevated arterial stiffness may contribute. Given the association between reductions in nitric oxide (NO) and vascular dysfunction, we sought to determine whether acute inhibition of NO synthase with NG-monomethyl-L-arginine (L-NMMA) would lead to exaggerated BP responses to

R Campbell; J P Fisher; J E Sharman; B J McDonnell; M P Frenneaux

2011-01-01

435

Exhaled nitric oxide in a population-based study of Southern California Schoolchildren  

Microsoft Academic Search

BACKGROUND: Determinants of exhaled nitric oxide (FeNO) need to be understood better to maximize the value of FeNO measurement in clinical practice and research. Our aim was to identify significant predictors of FeNO in an initial cross-sectional survey of southern California schoolchildren, part of a larger longitudinal study of asthma incidence. METHODS: During one school year, we measured FeNO at

William S Linn; Edward B Rappaport; Kiros T Berhane; Tracy M Bastain; Edward L Avol; Frank D Gilliland

2009-01-01

436

The Roles of Atomic Oxygen and Nitric Oxide in Low Temperature Plasmas  

NASA Astrophysics Data System (ADS)

Nitric oxide, NO, and oxygen, O, concentrations have been experimentally measured using one-photon and two-photon laser induced fluorescence, respectively, as a function of time after a nanosecond pulsed plasma discharge. The relative behavior of these two species is fundamentally different than that predicted using the extended Zeldovich Mechanism. A plasma chemistry kinetic model sensitivity analysis has been conducted to determine the dominate reactions involved. The spectra, concentrations, and kinetic modeling predictions will be discussed.

Bowman, Sherrie S.; Burnette, David; Adamovich, Igor V.; Lempert, Walter R.

2013-06-01

437

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

438

Inhaled nitric oxide in acute respiratory failure: Dose-response curves  

Microsoft Academic Search

Objective: To determine the dose-response curve of inhaled nitric oxide (NO) in terms of pulmonary vasodilation and improvement in PaO2 in adults with severe acute respiratory failure. Design: Prospective randomized study. Setting: A 14-bed ICU in a teaching hospital. Patients: 6 critically ill patients with severe acute respira- tory failure (lung injury severity score >__ 2.5) and pulmo- nary hypertension.

L. Puybasset; J. J. Rouby; E. Mourgeon; T. E. Stewart; P. Cluzel; M. Arthaud; P. Poète; L. Bodin; A. M. Korinek; P. Viars

1994-01-01

439

Evidence for a Difference in Nitric Oxide Biosynthesis Between Healthy Women and Men  

Microsoft Academic Search

There is indirect evidence for a gender difference in nitric oxide (NO) synthesis from vascular endothelium. The aim of the present study was to determine NO production more directly in healthy women and men by the measurement of 15N nitrate excreted in urine after the intravenous administration of L-(15N)2-guanidino arginine. Twenty-four healthy volunteers (13 men aged 22 to 40 years

Pablo Forte; Barry J. Kneale; Eric Milne; Phil J. Chowienczyk; Atholl Johnston; Nigel Benjamin; James M. Ritter

2010-01-01

440

Inducible nitric oxide synthase-deficient mice have enhanced leukocyte-endothelium interactions in endotoxemia  

Microsoft Academic Search

Nitric oxide (NO) from constitutive NO synthase (NOS) has been postulated to be a ho- meostatic regulator of leukocyte-endothelial cell in- teractions. By contrast, the inducible NO synthase (iNOS) isoform has been invoked as a potential pathogenic enzyme in numerous inflammatory dis- eases. The objective of this study was to determine whether the iNOS isoform is also capable of func-

MICHAEL J. HICKEY; A. SHARKEY; ELAINE G. SIHOTA; PAUL H. REINHARDT; JOHN D. MACMICKING; CARL NATHAN

441

Association Capacity of Ribose Bis(Thiosemicarbazonato)Copper(II) with Nitric Oxide  

Microsoft Academic Search

The stability constant for copper(II) complex with ribose bis(thiosemicarbazone) (log K=18.46±0.15) was determined from UV-Vis data using LETAGROP program. Its interaction with nitric oxide was studied by spectroscopic and electrochemical techniques. This interaction was observed in the UV-Vis spectra as a shoulder around 350 nm and an isosbestic point at 420 nm. The corresponding equilibrium constant was calculated and the

Talkmore Ngarivhume; Alicia Díaz; Roberto Cao; Mayreli Ortiz; Iliana Sánchez

2005-01-01

442

OH-radical-type reactive oxygen species derived from superoxide and nitric oxide: a sensitive method for their determination and differentiation.  

PubMed

Reactive oxygen species are involved in many diseases where the radical species OH, peroxynitrite and the non-radical, hypochlorous acid, play an outstanding role. The formation of OH-type oxidants is essentially confined to a few types of reactions. The most prominent ones are the one-electron reduction of hydrogen peroxide by F2+ or Cu+ -ions (Fenton-type reactions), reaction of hypochlorite with superoxide and finally formation and decay of peroxynitrite (ONOOH), formed from superoxide and NO. In this communication we wish to report on a simple model system allowing to differentiate between these ROS: ethene formation from ACC is only detectable in the presence of hypochlorite (v. Kruedener et al, 1995) and not detectable with Fenton-type oxidants or SIN-1 (3-morpholinosydonimine, a peroxynitrite generator by releasing sequentially superoxide and NO) at 10 microM concentrations. On the other hand, ethene formation from KMB is negligible in the presence of hypochlorite but proceeds rapidly with Fenton-type oxidants (4 microM H2O2; 4 microM Fe2+) as well as with 1 microM SIN-1. Stimulation of Fenton-type oxidants and not of SIN-1 by EDTA and characteristic patterns of inhibition by SOD, catalases, hemoglobin and uric acid allow a differentiation between these two potential precursors of OH-radicals. Synthetic ONOOH shows different reaction kinetics as compared to SIN-1. Inhibition of ONOOH-dependent ethene formation by different compounds occurs more or less "random" indicating an unspecific influence of proteins and also small molecules. Comparison of the individual inhibition types of several selected compounds allows a differential analysis as to the generation pathway of the final oxidants, OH- radical or peroxynitrite. PMID:9462930

Hippeli, S; Rohnert, U; Koske, D; Elstner, E F

443

Role of exhaled nitric oxide as a predictor of atopy  

PubMed Central

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

2013-01-01

444

Theoretical investigation of nitric oxide interaction with aluminum phthalocyanine.  

PubMed

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 delivery agents we carried out a quantum mechanical study of the interaction of NO with aluminum phthalocyanine (AlPc) at B3LYP/6-31G* level. The calculation results show clearly that the complexation of NO with AlPc depends on the latter's oxidation state. NO is more strongly bonded to AlPc in the reduced state (-33.77 kcal/mol) than in the oxidized state (-4.96 kcal/mol). By applying the Fukui function and analysis of the Frontier molecular orbital, it was possible to explain the situation within which nitric oxide interacts with AlPc. PMID:21342778

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

2010-11-03

445

The nitric oxide response in plant-associated endosymbiotic bacteria.  

PubMed

Nitric oxide (NO) is a gaseous signalling molecule which becomes very toxic due to its ability to react with multiple cellular targets in biological systems. Bacterial cells protect against NO through the expression of enzymes that detoxify this molecule by oxidizing it to nitrate or reducing it to nitrous oxide or ammonia. These enzymes are haemoglobins, c-type nitric oxide reductase, flavorubredoxins and the cytochrome c respiratory nitrite reductase. Expression of the genes encoding these enzymes is controlled by NO-sensitive regulatory proteins. The production of NO in rhizobia-legume symbiosis has been demonstrated recently. In functioning nodules, NO acts as a potent inhibitor of nitrogenase enzymes. These observations have led to the question of how rhizobia overcome the toxicity of NO. Several studies on the NO response have been undertaken in two non-dentrifying rhizobial species, Sinorhizobium meliloti and Rhizobium etli, and in a denitrifying species, Bradyrhizobium japonicum. In the present mini-review, current knowledge of the NO response in those legume-associated endosymbiotic bacteria is summarized. PMID:22103544

Cabrera, Juan J; Sánchez, Cristina; Gates, Andrew J; Bedmar, Eulogio J; Mesa, Socorro; Richardson, David J; Delgado, María J

2011-12-01

446

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

SciTech Connect

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

Quick, E.E.

1980-03-01

447

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

SciTech Connect

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

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

1988-11-29

448

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

PubMed

The nitric oxide synthase-catalyzed conversion of L-arginine to L-citrulline and nitric oxide is known to be the sum of two partial reactions: oxygenation of arginine to N-hydroxyarginine, followed by oxygenation of N-hydroxyarginine to citrulline and nitric oxide. Whereas the conversion of N-hydroxyarginine to citrulline and nitric oxide has been the subject of a number of studies, the oxygenation of arginine to N-hydroxyarginine has received little attention. Here we show that substrate amounts of rat cerebellar nitric oxide synthase, in the absence of added NADPH, catalyze the conversion of arginine to N-hydroxyarginine as the dominant product. The product appears not to be tightly bound to the enzyme. A maximum of 0.16 mol of N-hydroxyarginine/mol of nitric oxide synthase subunit was formed. The reaction requires oxygen and the addition of Ca2+/calmodulin and is stimulated 3-fold by tetrahydrobiopterin. Upon addition of NADPH, citrulline is formed exclusively. Conversion of N-hydroxyarginine to citrulline, like the first partial reaction, requires Ca2+/calmodulin and is stimulated by tetrahydrobiopterin but differs from the first partial reaction in being completely dependent upon addition of NADPH. These results indicate that brain nitric oxide synthase contains an endogenous reductant that can support oxygenation of arginine but not of N-hydroxyarginine. The reductant is not NADPH, since the amount of nitric oxide synthase-bound NADPH is appreciably less than the amount required for N-hydroxyarginine synthesis. Possible candidates for this role are discussed in relation to proposed mechanisms of action of nitric oxide synthase. PMID:7530247

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

1995-01-27

449

Molecular Dynamics Simulations Reveal Proton Transfer Pathways in Cytochrome C-Dependent Nitric Oxide Reductase  

PubMed Central

Nitric oxide reductases (NORs) are membrane proteins that catalyze the reduction of nitric oxide (NO) to nitrous oxide (N2O), which is a critical step of the nitrate respiration process in denitrifying bacteria. Using the recently determined first crystal structure of the cytochrome c-dependent NOR (cNOR) [Hino T, Matsumoto Y, Nagano S, Sugimoto H, Fukumori Y, et al. (2010) Structural basis of biological N2O generation by bacterial nitric oxide reductase. Science 330: 1666–70.], we performed extensive all-atom molecular dynamics (MD) simulations of cNOR within an explicit membrane/solvent environment to fully characterize water distribution and dynamics as well as hydrogen-bonded networks inside the protein, yielding the atomic details of functionally important proton channels. Simulations reveal two possible proton transfer pathways leading from the periplasm to the active site, while no pathways from the cytoplasmic side were found, consistently with the experimental observations that cNOR is not a proton pump. One of the pathways, which was newly identified in the MD simulation, is blocked in the crystal structure and requires small structural rearrangements to allow for water channel formation. That pathway is equivalent to the functional periplasmic cavity postulated in cbb3 oxidase, which illustrates that the two enzymes share some elements of the proton transfer mechanisms and confirms a close evolutionary relation between NORs and C-type oxidases. Several mechanisms of the critical proton transfer steps near the catalytic center are proposed.

Pisliakov, Andrei V.; Hino, Tomoya; Shiro, Yoshitsugu; Sugita, Yuji

2012-01-01

450

Molecular dynamics simulations reveal proton transfer pathways in cytochrome C-dependent nitric oxide reductase.  

PubMed

Nitric oxide reductases (NORs) are membrane proteins that catalyze the reduction of nitric oxide (NO) to nitrous oxide (N(2)O), which is a critical step of the nitrate respiration process in denitrifying bacteria. Using the recently determined first crystal structure of the cytochrome c-dependent NOR (cNOR) [Hino T, Matsumoto Y, Nagano S, Sugimoto H, Fukumori Y, et al. (2010) Structural basis of biological N2O generation by bacterial nitric oxide reductase. Science 330: 1666-70.], we performed extensive all-atom molecular dynamics (MD) simulations of cNOR within an explicit membrane/solvent environment to fully characterize water distribution and dynamics as well as hydrogen-bonded networks inside the protein, yielding the atomic details of functionally important proton channels. Simulations reveal two possible proton transfer pathways leading from the periplasm to the active site, while no pathways from the cytoplasmic side were found, consistently with the experimental observations that cNOR is not a proton pump. One of the pathways, which was newly identified in the MD simulation, is blocked in the crystal structure and requires small structural rearrangements to allow for water channel formation. That pathway is equivalent to the functional periplasmic cavity postulated in cbb(3) oxidase, which illustrates that the two enzymes share some elements of the proton transfer mechanisms and confirms a close evolutionary relation between NORs and C-type oxidases. Several mechanisms of the critical proton transfer steps near the catalytic center are proposed. PMID:22956904

Pisliakov, Andrei V; Hino, Tomoya; Shiro, Yoshitsugu; Sugita, Yuji

2012-08-30

451

Salicylate inhibits LDL oxidation initiated by superoxide\\/nitric oxide radicals  

Microsoft Academic Search

Simultaneously produced superoxide\\/nitric oxide radicals (O??2\\/NO?) could form peroxynitrite (OONO?) which has been found to cause atherogenic, i.e. oxidative modification of LDL. Aromatic hydroxylation and nitration of the aspirin metabolite salicylate by OONO? has been reported. Therefore we tested if salicylate may be able to protect LDL from oxidation by O??2\\/NO? by scavenging the OONO? reactive decomposition products. When LDL

Marcela Hermann; Stylianos Kapiotis; Roland Hofbauer; Markus Exner; Christian Seelos; Irmtraud Held; Bernhard Gmeiner

1999-01-01

452

Nitric Oxide Regulation of Free Radical and Enzyme-Mediated Lipid and Lipoprotein Oxidation  

Microsoft Academic Search

Abstract—The regulation of nonenzymatic,and enzymatic,lipid oxidation reactions by nitric oxide ( zNO) is potent and pervasive and reveals novel non? cGMP-dependent reactivities for this free radical inflammatory,and signal transduction mediator. zNO and its metabolites stimulate and inhibit lipid peroxidation reactions, modulate enzymatically catalyzed lipid oxidation, complex with lipid-reactive metals, and alter proinflammatory gene expression. Through these mechanisms, zNO can regulate

Allison Bloodsworth; Valerie B. O'Donnell; Bruce A. Freeman

453

Oxidative stress disrupts nitric oxide synthase activation in liver endothelial cells  

Microsoft Academic Search

Oxidative stress may mediate vascular disruption associated with a loss of endothelial nitric oxide synthase (eNOS) activity and a hypersensitivity to the constrictor effects of endothelin-1 (ET-1). We hypothesize that this is due, in part, to uncoupling of ETB receptors from eNOS activation. Thus, we tested whether oxidative stress (OS) affects liver vascular relaxation by reducing basal and ET-1-induced NO

Amel Karaa; Walid S. Kamoun; Mark G. Clemens

2005-01-01

454

Phenylpropanoid ester from Zingiber officinale and their inhibitory effects on the production of nitric oxide.  

PubMed

A new phenylpropanoid ester mixture, (E)-geranylferulic acid (1a) and (Z)-geranylferulic acid (1b), along with 13 known compounds, [6]-gingerol (2), [8]-gingerol (3), [10]-gingerdione (4), 1-dehydro-[6]-gingerdione (5), 1-dehydro-[8]-gingerdione (6), [6]-paradol (7), [8]-paradol (8), [6]-gingeroldiacetate (9), 6-hydroxy-[6]-shogaol (10), galanolactone (11), trans-®-sesquiphellandrol (12), trans-sesquipiperitol (13), and 4?,5?-dihydroxybisabola-2,10-diene (14) were isolated from ethanol extract of Zingiber officinale. Their structures were determined based on the spectroscopic (1D, 2D-NMR and MS) and chemical evidence. All of the isolates were evaluated for their potential to inhibit LPS-induced production of nitric oxide in murine macrophage RAW264.7 cells. Compounds 1-12 were found to inhibit nitric oxide production with IC(50) values ranging from 5.5 to 28.5 ?M. PMID:22370785

Hong, Seong Su; Oh, Joa Sub

2012-02-28

455

Osmotic swelling induces p75 neurotrophin receptor (p75NTR) expression via nitric oxide.  

PubMed

Brain injuries by physical trauma, epileptic seizures, or microbial infection upset the osmotic homeostasis resulting in cell swelling (cerebral edema), inflammation, and apoptosis. Expression of the neurotrophin receptor p75NTR is increased in the injured tissue and axon regeneration is repressed by the Nogo receptor using p75NTR as the signal transducer. Hence, p75NTR seems central to the injury response and we wished to determine the signals that regulate its expression. Here, we demonstrate that tonicity mediated cell swelling rapidly activates transcription of the endogenous p75NTR gene and of a p75NTR promoter-reporter gene in various cell types. Transcription activation is independent of de novo protein synthesis and requires the activities of phospholipase C, protein kinase C, and nitric-oxide synthase. Hence, p75NTR is a nitric oxide effector gene regulated by osmotic swelling, thereby providing a strategy for therapeutic intervention to modulate p75NTR functions following injury. PMID:12821676

Peterson, Suzanne; Bogenmann, Emil

2003-06-23

456

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

NASA Astrophysics Data System (ADS)

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

Balaban, Alexandru T.; Seitz, William

2003-06-01

457

The role of nitric oxide in low level light therapy  

NASA Astrophysics Data System (ADS)

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

Hamblin, Michael R.

2008-03-01

458

Exhaled nitric oxide from lung periphery is increased in COPD.  

PubMed

Single constant flow exhaled nitric oxide (eNO) cannot distinguish between the sources of NO. The present study measured eNO at multiple expired flows (MEFeNO) to partition NO into alveolar (Calv,NO) and bronchial (Jaw,NO) fractions to investigate peripheral lung contribution to eNO in chronic obstructive lung disease (COPD). MEFeNO were made in 81 subjects including 18 nonsmokers, 16 smokers and 47 COPD patients of different severity by the classification of the Global Initiative for Chronic Obstructive Lung Disease (GOLD): 0 (n = 14), 1 (n = 7), 2 (n = 11), 3 (n = 8) and 4 (n = 7). COPD severity was correlated with an increased Calv,NO regardless of the patient's smoking habit or current treatment. The levels of Calv,NO (in ppb) were 1.4+/-0.09 in nonsmokers, 2.1+/-0.1 in smokers categorised as GOLD stage 0 (smokers-GOLD0), 3.3+/-0.18 in GOLD1-2 and 3.4+/-0.1 in GOLD3-4. Jaw,NO levels (pL x s(-1)) were higher in nonsmokers than smokers-GOLD0 (716.2+/-33.3 versus 464.7+/-41.8), GOLD3-4 (609.4+/-71). Diffusion of NO in the airways (Daw,NO pL x ppb(-1) s(-1)) was higher (p<0.05) in GOLD3-4 than in nonsmokers (15+/-1.2 versus 11+/-0.5) and smokers-GOLD0 (11.6+/-0.5). MEFeNO measurements were reproducible, free from day-to-day and diurnal variation and were not affected by bronchodilators. In conclusion, chronic obstructive pulmonary disease is associated with elevated alveolar nitric oxide. Measurements of nitric oxide at multiple expired flows may be useful in monitoring inflammation and progression of chronic obstructive pulmonary disease, and the response to anti-inflammatory treatment. PMID:15994389

Brindicci, C; Ito, K; Resta, O; Pride, N B; Barnes, P J; Kharitonov, S A

2005-07-01

459

Optimization models for determining nitric acid equilibria in supercritical water  

Microsoft Academic Search

Optimization models are developed to determine equilibrium constants for dissociation, redox and disproportionation reactions involving nitric and nitrous acid, NO2, NO, N2O, NO ? 3 , and oxygen in supercritical water at temperatures of 380 and 4008C and at pressures of 276-414 bar. A constrained nonlinear programming (NLP) model of moderate size is developed to estimate equilibrium constants and extinction

Kirk J. Ziegler; Leon Lasdon; Keith P. Johnston

460

Effects of nitric oxide and nitrogen dioxide on bacterial growth.  

PubMed

The effects of low concentrations of nitric oxide (NO) and nitrogen dioxide (NO2) on actively dividing cultures of Staphylococcus aureus, Micrococcus luteus, Micrococcus roseus, Serratia marcescens, Bacillus subtilis, Bacillus circulans, Bacillus megaterium, and Bacillus cereus were studied. Fresh cultures of each organism were incubated for 24 h at 25 degrees C on both nutrient agar and mineral salts glucose agar plates under atmospheres containing various low concentrations of NO in air (0 to 1.9 ppm [0 to 2.0 micrograms/g of air]), NO2 in air (0 to 5.5 ppm [0 to 8.8 micrograms/g of air]), or NO and NO2 in air. Bacteria grown under air only were used as controls. After incubation, the colonies that developed on the plates were counted. None of the bacteria tested was affected by NO or NO2 at the indicated concentrations while growing on nutrient agar. Serratia marcescens, B. circulans, B. subtilis, B. megaterium, and B. cereus grown on mineral salts glucose agar were not significantly affected by NO or NO2. Low concentrations (0 to 1.9 ppm) of NO were bacteriostatic to log-phase cultures of M. roseus, M. luteus, and Staphylococcus aureus grown on mineral salts glucose agar. Bacteriostatic activity over a 24-h interval was maximal at an initial NO concentration of 1 ppm. Appreciable amounts of NO2 were produced in 24 h at initial NO concentrations greater than 1 ppm. These results suggest that NO2 may reduce the bacteriostatic activity of NO. Low concentrations (0 to 5.5 ppm) of NO2 in air did not affect any of the bacteria tested. At these low concentrations, NO affected bacterial growth, although NO2, NO2-, and NO3- did not. In addition, it was determined that the bacteriostatic activity observed in this study was not due to an increase in the acidity of the medium. PMID:6351744

Mancinelli, R L; McKay, C P

1983-07-01