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1

Determination of nitric oxide concentrations from sunrise E-region electron density measurements  

Microsoft Academic Search

Midlatitude sunrise electron density profiles have been analyzed in ; order to determine nitric oxide concentrations in the range 100-160 km. In ; general, the determinations are restricted to heights for which the ionization of ; nitric oxide by direct solar Lyman-$alpha$ radiation is the main contribution to ; the growth of the E region. The concentrations obtained are larger,

P. E. Monro; L. G. Smith

1975-01-01

2

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

PubMed Central

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 been shown to play a major role in health and disease. Pathophysiological conditions affect the cellular expression and localization of nitric oxide synthases, which in turn alter organ cross talk. In this study, we described the compartmentalization of nitric oxide in organs, cells and subcellular organelles, and how its localization relates to several relevant clinical conditions. Understanding the complexity of the compartmentalization of nitric oxide production and the implications of this compartmentalization in terms of cellular targets and downstream effects will eventually contribute toward the development of better strategies for treating or preventing pathological events associated with the increase, inhibition or mislocalization of nitric oxide production. PMID:20388537

Villanueva, Cleva; Giulivi, Cecilia

2010-01-01

3

Nitric Oxide Nanoparticle Technology  

PubMed Central

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

Englander, Laura

2010-01-01

4

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

Microsoft Academic Search

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

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

1995-01-01

5

Determination and Bioimaging Method for Nitric Oxide in Biological Specimens by Diaminofluorescein Fluorometry  

Microsoft Academic Search

A simple and sensitive assay and a cellular bioimaging method for nitric oxide (NO) were developed using a novel diaminofluorescein DAF-FM and its diacetate. DAF-FM is converted via an NO-specific mechanism to an intensely fluorescent triazole derivative. For the measurement of NO, the triazole derivative of DAF-FM was determined by reversed-phase high-performance liquid chromatography with fluorescence detection. In the presence

Yoshinori Itoh; Fu Hai Ma; Hanae Hoshi; Michiko Oka; Kumiko Noda; Yojiro Ukai; Hirotatsu Kojima; Tetsuo Nagano; Noboru Toda

2000-01-01

6

Nitric oxide neurotoxicity  

Microsoft Academic Search

Derangements in glutamate neurotransmission have been implicated in several neurodegenerative disorders including, stroke, epilepsy, Huntington's disease, Alzheimer's disease, and amyotrophic lateral sclerosis (ALS). Activation of the N-methyl-d-aspartate (NMDA) receptor subtype of glutamate receptors results in the influx of calcium which binds calmodulin and activates neuronal nitric oxide synthase (nNOS), to convent l-arginine to citrulline and nitric oxide (NO). NO has

Valina L. Dawson; Ted M. Dawson

1996-01-01

7

Exhaled nitric oxide.  

PubMed

Exhaled nitric oxide (FENO) is a noninvasive easily measurable biomarker that is proving to be an excellent surrogate for eosinophilic inflammation in the lungs of patients who have asthma. Although large-scale normative data are still awaited, preliminary studies have shown FENO to be helpful in diagnosing and assessing severity and control for asthma. FENO levels have also proven helpful in diagnosing and managing several other inflammatory lung diseases. PMID:17996576

Stewart, Lora; Katial, Rohit

2007-11-01

8

Nitric Oxide for Children  

Microsoft Academic Search

\\u000a The introduction of inhaled nitric oxide (iNO) for the treatment of hypoxemic respiratory failure in neonates ushered in a\\u000a new era in neonatal intensive care. This inhalational therapeutic redefined the medical management of the infant with persistent\\u000a pulmonary hypertension of the newborn (PPHN). With a selective pulmonary vasodilator in hand, a kinder, gentler approach to\\u000a ventilation was embraced in many

Judy L. Aschner; Candice D. Fike; Eric Austin; J. Donald Moore; Frederick E. Barr

9

[Nitric oxide metabolism].  

PubMed

Nitric oxide is an important mediator of physiological and pathological processes. It is a lipophilic molecule that contains a single unpaired electron which causes NO to be chemically reactive, and to function as a free radical with a short lifetime. NO can act by direct and indirect effects. Direct effects occur between NO and specific biological molecules whereas indirect effects are mediated by reactive nitrogen oxide species (RNOS) formed from the reaction of NO either with oxygen or superoxide. This review discusses the metabolic pathways of NO. PMID:17427511

Kowalczyk, Edward; Kopff, Anna; Kopff, Maria; B?aszczyk, Jan; Fija?kowski, Pawe?; Kowalski, Jan

2006-01-01

10

Nitric oxide signaling in plants.  

PubMed

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

Shapiro, Allan D

2005-01-01

11

[Nitric oxide--oxidant or antioxidant?].  

PubMed

Nitric oxide (NO), as a free radical, seems to be a potential antioxidant. It takes part in termination of lipid peroxidation reactions. It can be also an oxidant, particularly in indirect reactions with oxygen molecules or superoxide anion. PMID:16529066

Kowalczyk, Edward; Kopff, Anna; Kopff, Maria; Fija?kowski, Pawe?; B?aszczyk, Jan

2005-01-01

12

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

PubMed Central

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

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

2014-01-01

13

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

PubMed

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

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

2014-09-01

14

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

SciTech Connect

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

Jiang, Heng; Verovski, Valeri N.; Leonard, Wim; Law, Ka Lun; Vermeersch, Marieke; Storme, Guy; Van den Berge, Dirk; Gevaert, Thierry; Sermeus, Alexandra [Department of Radiotherapy, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels (Belgium)] [Department of Radiotherapy, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels (Belgium); De Ridder, Mark, E-mail: mark.deridder@uzbrussel.be [Department of Radiotherapy, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels (Belgium)

2013-03-01

15

Nitric oxide and cellular respiration  

Microsoft Academic Search

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

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

1999-01-01

16

Thermal Decomposition of Nitric Oxide  

Microsoft Academic Search

The decomposition of pure nitric oxide and of mixtures with nitrogen or helium was studied at T = 1170 to 1530°K in quartz vessels. Above about T = 1400°K, the reaction is homogeneous and cleanly second order in NO throughout the course of decomposition. A change in the surface to volume ratio leaves the rate unchanged as does the addition

Frederick Kaufman; John R. Kelso

1955-01-01

17

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

18

Nitric oxide: The wonder molecule  

Microsoft Academic Search

Nitric oxide, a newly discovered biological messenger molecule that is produced from different kinds of cells has diversified\\u000a and has significant effects on various pathological and physiological events ranging from the prevention of cancer and diabetes\\u000a mellitus to coronary artery disease (heart attack) and hypertension.

Kushal Chakraborty

2003-01-01

19

Determinants of aortic cyclic guanosine monophosphate in hypertension induced by chronic inhibition of nitric oxide synthase.  

PubMed Central

Nitric oxide (NO) and atrial natriuretic factor (ANF) cause vascular relaxation by generating cyclic guanosine monophosphate (cGMP) via activation of the soluble and particulate guanylate cyclases, respectively. The chronic effects of NG-nitro-L-arginine methyl ester (L-NAME), an L-arginine antagonist and NO synthase inhibitor, on the blood pressure and plasma and aortic cGMP levels of rats were tested. Wistar rats (n = 10 per group) were given doses of L-NAME (0, 1, 5, 10, 20, 50, and 100 mg/kg.d) by gavage twice a day for 4 wk. Chronic L-NAME induced a time- and dose-dependent increase in blood pressure. The total heart weight/body weight ratio did not change in any group, despite the hypertension. The plasma levels of cGMP did not change significantly in any group, and were correlated with the plasma ANF levels (r = 0.51, P less than 0.0001). Aortic cGMP decreased in negative correlation with increasing L-NAME from 0 to 10 mg/kg.d, culminating in a 10-fold drop arterial wall cGMP. The aortic cGMP content of rats in the four highest dose groups (from 10 to 100 mg/d) tended to increase slightly and was positively correlated with endogenous ANF (r = 0.48, P less than 0.002, n = 40). Intravenous L-arginine decreased arterial blood pressure and reversed the decline in aortic cGMP. Exogenous ANF and sodium nitroprusside both significantly increased aortic cGMP. Neither the arterial wall concentrations of cGMP-dependent kinase nor cAMP was changed by L-NAME. Thus, chronic blockade of NO synthase with L-NAME induces a dose-dependent increase in blood pressure and decrease in aortic cGMP. The in vivo basal aortic cGMP seems to be mainly dependent on NO synthase: soluble guanylate cyclase activity and to a minor extent on particulate guanylate cyclase activity. PMID:1379615

Arnal, J F; Warin, L; Michel, J B

1992-01-01

20

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

PubMed Central

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

Sestakova, Natalia; Puzserova, Angelika; Kluknavsky, Michal

2013-01-01

21

Relationship between Exhaled Nitric Oxide and Childhood Asthma  

Microsoft Academic Search

The purpose of the study was to determine if exhaled nitric oxide levels in children varied according to their asthmatic and atopic status. Exhaled nitric oxide was measured in a sample of 93 children at- tending the North West Lung Centre, Manchester, United Kingdom, for the clinical evaluation of a respiratory questionnaire being developed as a screening tool in general

TIMOTHY L. FRANK; ANIL ADISESH; ANTHONY C. PICKERING; JOHN F. J. MORRISON; TAMSIN WRIGHT; HELEN FRANCIS; ANGELA FLETCHER; PETER I. FRANK; PHILIP HANNAFORD

22

Nitric oxide mediates renal vasodilation during erythropoietin-induced polycythemia  

Microsoft Academic Search

Nitric oxide mediates renal vasodilation during erythropoietin-induced polycythemia. 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

Christopher S Wilcox; Xiaolin Deng; Avon H Doll; Harold Snellen; William J Welch

1993-01-01

23

Inflammatory Monocytes Determine Endothelial Nitric-oxide Synthase Uncoupling and Nitro-oxidative Stress Induced by Angiotensin II.  

PubMed

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

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

2014-10-01

24

Arginine metabolism: nitric oxide and beyond.  

PubMed Central

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

Wu, G; Morris, S M

1998-01-01

25

Nitric Oxide Activates Cyclooxygenase Enzymes  

Microsoft Academic Search

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

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

1993-01-01

26

Nitric oxide reburning with methane  

SciTech Connect

This paper deals with initial findings from the ongoing, three-year DOE program that began on 02/01/1995. The program involves computer simulation studies to aid in planning and conducting a series of experiments that will extend the knowledge of reburning process. The objective of this work is to find nitric oxide reduction effectiveness for various reburning fuels and identify both homogeneous and heterogeneous reaction mechanisms characterizing NO reduction.

Kumpaty, S.K. [Rust Coll., Holly Springs, MS (United States); Subramanian, K. [Subramanian (Kannikeswaran), Houston, TX (United States)

1996-12-31

27

Nitric oxide and the gut  

Microsoft Academic Search

Nitric oxide (NO) has been implicated as a modulator of blood flow, motility, electrolyte and water transport, and the function\\u000a of endothelial cells, platelets, mast cells, and macrophages within the digestive system. In addition, a number of reports\\u000a have demonstrated that NO possesses potent anti-inflammatory properties, whereas results from an equally impressive number\\u000a of studies suggest that NO may promote

David Jourd’heuil; Matthew B. Grisham; D. Neil Granger

1999-01-01

28

Nitric oxide and substance dependence  

Microsoft Academic Search

The free-radical gas nitric oxide (NO) plays an important role in a diverse range of physiological processes. It is synthesized from the precursor l-arginine by the enzyme NO synthase (NOS), which transforms l-arginine into NO and citrulline. This synthetic pathway exists in the central nervous system (CNS), and NO appears to be a messenger molecule in the CNS, fulfilling most

I. Tayfun Uzbay; Michael W. Oglesby

2001-01-01

29

Nitric oxide function in atherosclerosis  

PubMed Central

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

Matthys, K. E.

1997-01-01

30

Transport of nitric oxide by mean circulation and planetary waves  

SciTech Connect

The effects of the zonal mean circulation and planetary-wave winds on the distribution of nitric oxide in the 55-120 km height region is investigated. A time-dependent numerical model is used to investigate the interaction between planetary waves and the zonal mean circulation, and the effect of the circulation on the nitric oxide distribution is determined. The initial nitric oxide (NO) distribution is obtained by using a simple source/sink chemistry, vertical eddy diffusion, and advective transport by the zonal mean circulation. Changes in the initial NO distribution which result from the addition of planetary-wave winds are described. Planetary waves are found to induce a wave-like structure in the nitric oxide distribution which resembles the derived from observational data. Planetary waves can affect the nitric oxide concentration in two ways: first, through the wave-induced changes in the mean meridional circulation, and second, through the nitric oxide perturbation induced by wave winds themselves. The changes in total nitric oxide are due primarily to the zonal asymmetries in nitric oxide induced by the planetary waves. Implications of this result for explaining the winter anomaly are discussed.

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

1984-09-15

31

Macrophages produce nitric oxide at allograft sites.  

PubMed Central

OBJECTIVE: The current study was designed to determine which cytokines produced during an alloimmune response stimulate macrophage nitric oxide (.N = O) production at allograft sites. SUMMARY BACKGROUND DATA: Previous work has demonstrated that rat sponge matrix allograft infiltrating cells produce more .N = O on stimulation with alloantigen than syngeneic graft-infiltrating cells. Addition of NG-monomethyl-L-arginine (NMA), an inhibitor of .N = O synthesis, promotes allospecific cytolytic T-lymphocyte effector function. METHODS: Polyurethane sponges were implanted subcutaneously in recipient Lewis rats and injected with 10 x 10(6) ACl splenocytes. On various days after grafting, graft-infiltrating cells were harvested for in vitro study. Adherent macrophages from the graft infiltrating cell population were obtained by a 2- to 3-hour incubation to plastic dishes with subsequent washing to remove nonadherent cells. RESULTS: Stimulation of unseparated graft-infiltrating cell populations with lipopolysaccharide or interferon-tau resulted in enhanced .N = O synthesis by allograft infiltrating cells compared with syngeneic graft-infiltrating cells, early after grafting. Macrophages recovered from an allograft site spontaneously produce more .N = O than macrophages recovered from syngeneic grafts (p < 0.001). Significantly enhanced levels of .N = O were produced by allograft macrophages compared with syngeneic graft macrophages on stimulation with lipopolysaccharide or interferon-tau (p < or = 0.025). CONCLUSIONS: Nitric oxide appears to be produced in response to the local cytokines secreted by an ongoing rejection reaction. Nitric oxide serves under these circumstances to modulate the alloimmune response. PMID:8342995

Langrehr, J M; White, D A; Hoffman, R A; Simmons, R L

1993-01-01

32

Nanocarriers for Nitric Oxide Delivery  

PubMed Central

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

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

2011-01-01

33

Analytical Chemistry of Nitric Oxide  

PubMed Central

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

Hetrick, Evan M.

2013-01-01

34

UV Induced Oxidation of Nitric Oxide  

NASA Technical Reports Server (NTRS)

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

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

2007-01-01

35

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

NASA Technical Reports Server (NTRS)

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

Smith, Irwin D.; Dhooge, Patrick M.

1977-01-01

36

Nitric Oxide Activity in the Atherosclerotic Human Coronary Circulation  

Microsoft Academic Search

Objectives. We determined the activity of nitric oxide at rest and after acetylcholine in the atherosclerotic human coronary circulation.Background. Although responses to acetylcholine, an endothelium-dependent vasodilator, are abnormal in patients with coronary atherosclerosis, whether this reflects abnormal nitric oxide activity in humans in vivo has not been investigated previously.Methods. We investigated the effects of intracoronary l-NG-monomethyl arginine (l-NMMA), a specific

Arshed A Quyyumi; Nader Dakak; David Mulcahy; Neil P Andrews; Syed Husain; Julio A Panza; Richard O Cannon

1997-01-01

37

Nitric oxide measurement in chronic cough.  

PubMed

Chronic cough is a common symptom-based diagnostic challenge for primary care physicians and respiratory specialists. Measurement of exhaled nitric oxide is a convenient, reproducible, and inexpensive point-of-service test. It can simplify the evaluation process of chronic cough by providing information regarding the state of airway inflammation. If exhaled nitric oxide is elevated, this is predictive of a favorable response to inhaled corticosteroids. This has the effect of reducing empirical trials for cough-variant asthma or eosinophilic bronchitis. The inclusion of exhaled nitric oxide in the diagnostic approach to chronic cough should be considered. PMID:19809852

Lim, Kaiser G

2010-01-01

38

Calculated Effects of Nitric Oxide Flow Contamination on Scramjet Performance  

NASA Technical Reports Server (NTRS)

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

Fischer, Karen E.; Rock, Kenneth E.

1995-01-01

39

Nitric Oxide Synthases and Atrial Fibrillation  

PubMed Central

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

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

2012-01-01

40

Inducible Nitric Oxide Synthase - Time for Reappraisal  

Microsoft Academic Search

Inducible nitric oxide synthase (iNOS) is one of three key enzymes generating nitric oxide (NO) from the amino acid L-arginine. iNOS-derived NO plays an important role in numerous physiological and pathophysiological conditions, e.g. blood pressure regulation, inflammation, infection, and the onset and progression of malignant diseases. iNOS has been conjectured both as a marker and a therapeutic target in these

Philipp Lirk; Georg Hoffmann; Josef Rieder

2002-01-01

41

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

42

Amplified laser absorption - Detection of nitric oxide.  

NASA Technical Reports Server (NTRS)

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

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

1973-01-01

43

Nitric oxide in cancer metastasis.  

PubMed

Cancer metastasis is the spread and growth of tumor cells from the original neoplasm to further organs. This review analyzes the role of nitric oxide (NO), a signaling molecule, in the regulation of cancer formation, progression, and metastasis. The action of NO on cancer relies on multiple factors including cell type, metastasis stage, and organs involved. Various chemotherapy drugs cause cells to release NO, which in turn induces cytotoxic death of breast, liver, and skin tumors. However, NO has also been clinically connected to a poor cancer prognosis because of its role in angiogenesis and intravasation. This supports the claim that NO can be characterized as both pro-metastatic and anti-metastatic, depending on specific factors. The inhibition of cell proliferation and anti-apoptosis pathways by NO donors has been proposed as a novel therapy to various cancers. Studies suggest that NO-releasing non-steroidal anti-inflammatory drugs act on cancer cells in several ways that may make them ideal for cancer therapy. This review summarizes the biological significance of NO in each step of cancer metastasis, its controversial effects for cancer progression, and its therapeutic potential. PMID:25079686

Cheng, Huiwen; Wang, Lei; Mollica, Molly; Re, Anthony T; Wu, Shiyong; Zuo, Li

2014-10-10

44

Nitric oxide produced by endothelial nitric oxide synthase promotes diuresis  

PubMed Central

Extracellular fluid volume is highly regulated, at least in part, by peripheral resistance and renal function. Nitric oxide (NO) produced by NO synthase type 3 (NOS 3) in the nonrenal vasculature may promote fluid retention by reducing systemic vascular resistance and arterial pressure. In contrast, NO produced by renal NOS 3 promotes water excretion by reducing renal vascular resistance, increasing glomerular filtration, and inhibiting reabsorption along the nephron. Thus, the net effect of NO from NOS 3 on urinary volume (UV) is unclear. We hypothesized that NO produced by NOS 3 promotes water excretion primarily due to renal tubular effects. We gave conscious wild-type and NOS 3 ?/? mice an acute volume load and measured UV, blood pressure, plasma renin concentration (PRC), Na+, vasopressin, and urinary Na+ and creatinine concentrations. To give the acute volume load, we trained mice to drink a large volume of water while in metabolic cages. On the day of the experiment, water was replaced with 1% sucrose, and mice had access to it for 1 h. Volume intake was similar in both groups. Over 3 h, wild-type mice excreted 62 ± 10% of the volume load, but NOS 3 ?/? excreted only 42 ± 5% (P < 0.05). Blood pressure in NOS 3 ?/? was 118 ± 3 compared with 110 ± 2 mmHg in wild-type mice (P < 0.05), but it did not change following volume load in either strain. PRC, vasopressin, and glomerular filtration rate were similar between groups. Urinary Na+ excretion was 49.3 ± 7.0 in wild-type vs. 37.8 ± 6.4 ?mol/3 h in NOS 3 ?/? mice (P < 0.05). Bumetanide administration eliminated the difference in volume excretion between wild-type and NOS 3 ?/? mice. We conclude that 1) NO produced by NOS 3 promotes water and Na+ excretion and 2) the renal epithelial actions of NO produced by NOS 3 supersede the systemic and renal vascular actions. PMID:20147612

Perez-Rojas, Jazmin M.; Kassem, Kamal M.; Beierwaltes, William H.; Garvin, Jeffrey L.

2010-01-01

45

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

Microsoft Academic Search

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

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

1997-01-01

46

Nitric oxide synthase expression and effects of nitric oxide modulation on contractility of rat extraocular muscle  

Microsoft Academic Search

Extraocular muscles (EOMs) are special- ized skeletal muscles that are constantly active, gener- ate low levels of force for cross sectional area, have rapid contractile speeds, and are highly fatigue resis- tant. The neuronal isoform of nitric oxide synthase (nNOS) is concentrated at the sarcolemma of fast- twitch muscles fibers, and nitric oxide (NO) modulates contractility. This study evaluated nNOS

CHELLIAH R. RICHMONDS; HENRY J. KAMINSKI

2001-01-01

47

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

Microsoft Academic Search

The nitric oxide generating neurons of the nucleus accumbens exert a powerful influence over striatal function, in addition, these nitrergic inputs are in a position to regulate the dopaminergic and glutamatergic inputs on striatal projection neurons. It was the aim of this study to establish the source of the glutamatergic drive to nitric oxide synthase interneurons of the nucleus accumbens.

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

2005-01-01

48

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

49

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

Microsoft Academic Search

Purpose: Nitric oxide (NO), synthesized by the inducible nitric oxide synthase (iNOS), is known to inhibit metabolic oxygen consumption because of interference with mitochondrial respiratory activity. This study examined whether activation of iNOS (a) directly in tumor cells or (b) in bystander macrophages may improve radioresponse through sparing of oxygen. Methods and Materials: EMT-6 tumor cells and RAW 264.7 macrophages

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

2010-01-01

50

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

51

Nitric Oxide Formation by Meteoroids in the Upper Atmosphere  

NASA Technical Reports Server (NTRS)

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

Menees, Gene P.; Park, Chul

1976-01-01

52

Targeting of Nitric Oxide Synthase to Endothelial Cell Caveolae Via Palmitoylation: Implications for Nitric Oxide Signaling  

Microsoft Academic Search

The membrane association of endothelial nitric oxide synthase (eNOS) plays an important role in the biosynthesis of nitric oxice (NO) in vascular endothelium. Previously, we have shown that in cultured endothelial cells and in intact blood vessels, eNOS is found primarily in the perinuclear region of the cells and in discrete regions of the plasma membrane, suggesting trafficking of the

Guillermo Garcia-Cardena; Phil Oh; Jianwei Liu; Jan E. Schnitzer; William C. Sessa

1996-01-01

53

21 CFR 862.3080 - Breath nitric oxide test system.  

Code of Federal Regulations, 2010 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...

2010-04-01

54

21 CFR 862.3080 - Breath nitric oxide test system.  

...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...

2014-04-01

55

21 CFR 862.3080 - Breath nitric oxide test system.  

Code of Federal Regulations, 2012 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...

2012-04-01

56

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

57

Nitric oxide as a modulator of intestinal water and electrolyte transport.  

PubMed

The role of nitric oxide in intestinal fluid and electrolyte secretion depends upon whether the conditions under study are physiological or pathophysiological. In physiological conditions, endogenous nitric oxide seems to be a proabsorptive molecule, based on the findings that nitric oxide synthase inhibitors reverse net fluid absorption to net secretion in mice, rats, guinea pigs, rabbits, and dogs. This proabsorptive mode involves the enteric nervous system, the suppression of prostaglandin formation, and the opening of basolateral K+ channels. However, in some pathophysiological states nitric oxide synthase may be produced at higher concentrations that are capable of evoking net secretion. Thus nitric oxide synthase contributes to the diarrheal response in trinitrobenzene sulfonic acid-induced ileitis in guinea pigs and is the mediator of the laxative action of several intestinal secretagogues including castor oil, phenolphthalein, bisacodyl, magnesium sulfate, bile salts, senna, and cascara in the rat. Corresponding with the in vivo results, nitric oxide-donating compounds or nitric oxide itself stimulate chloride secretion in the guinea pig and rat intestine in vitro. Exceptions are the diarrhea produced by bacterial enterotoxins in the rat, in which nitric oxide seems to have a proabsorptive role, and the mouse ileum in vitro, in which nitric oxide-donating compounds produce a net proabsorptive effect on basal ion transport. Several endogenous secretagogues (substance P, 5-hydroxytryptamine, interleukin-1beta), which are important mediators of the inflammatory bowel diseases, act, at least in part, through the liberation of nitric oxide. Clinical studies have shown that nitric oxide is elevated in several inflammatory bowel diseases and other secretory conditions including ulcerative colitis, Crohn's disease, toxic megacolon, diverticulitis, infectious gastroenteritis, and infantile methemoglobinemia. However, the determination of nitric oxide in secretory diarrhea per se does not give conclusive information on the nitric oxide contribution to clinical secretory diarrhea. PMID:9724140

Izzo, A A; Mascolo, N; Capasso, F

1998-08-01

58

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

59

Mitochondria, nitric oxide, and cardiovascular dysfunction  

Microsoft Academic Search

Cardiovascular diseases encompass a wide spectrum of abnormalities with diverse etiologies. The molecular mechanisms underlying these disorders include a variety of responses such as changes in nitric oxide- (NO) dependent cell signaling and increased apoptosis. An interesting aspect that has received little or no attention is the role mitochondria may play in the vascular changes that occur in both atherosclerosis

Anup Ramachandran; Anna-Liisa Levonen; Paul S. Brookes; Erin Ceaser; Sruti Shiva; Maria Cecilia Barone; Victor Darley-Usmar

2002-01-01

60

Nitric oxide and gene regulation in plants  

Microsoft Academic Search

There is increasing evidence that nitric oxide (NO), which was first identified as a unique diffusible molecu- lar messenger in animals, plays an important role in diverse physiological processes in plants. Recent pro- gress that has deepened our understanding of NO signalling functions in plants, with special emphasis on defence signalling, is discussed here. Several stud- ies, based on plants

S. Grun; C. Lindermayr; S. Sell; J. Durner

2006-01-01

61

Effects of Nitric Oxide on Proprioceptive Signaling  

Microsoft Academic Search

We have analysed the effects of the neuromodulator nitric oxide (NO) on proprioceptive information processing by ascending intersegmental interneurons that form part of the local circuits within the terminal abdominal ganglion of the crayfish. NO modulates the synaptic inputs to ascending interneu- rons, enhancing the amplitude of class I interneurons and reducing the amplitude of class II interneurons. Repetitive proprioceptive

Hansjürgen Schuppe; Makoto Araki; Hitoshi Aonuma; Toshiki Nagayama; Philip L. Newland

2004-01-01

62

Nitric oxide in gastrointestinal health and disease  

Microsoft Academic Search

Nitric oxide is an intracellular and intercellular messenger with important functions in a number of physiologic and pathobiologic processes within gastroenterology and hepatology, including gastrointestinal tract motility, mucosal function, inflammatory responses, gastrointestinal malignancy, and blood flow regulation. Since the broad review of this topic in Gastroenterology more than 10 years ago, a number of advances have been made in the

Vijay Shah; Greg Lyford; Greg Gores; Gianrico Farrugia

2004-01-01

63

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

64

Nitric Oxide Acutely Inhibits Neuronal Energy Production  

Microsoft Academic Search

Disruption of mitochondrial respiration has been proposed as an action of nitric oxide (NO) responsible for its toxicity, but the effects of NO on the energetics of intact central neurons have not been reported. We examined the effects of NO on mito- chondrial function and energy metabolism in cultured hip- pocampal neurons. The application of NO from NO donors or

James R. Brorson; Paul T. Schumacker; He Zhang

1999-01-01

65

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

66

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

67

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

NASA Technical Reports Server (NTRS)

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

Cabell, Karen F.; Rock, Kenneth E.

2003-01-01

68

Equivalent-cone calculation of nitric oxide production rate during Space Shuttle re-entry  

NASA Technical Reports Server (NTRS)

The amount of nitric oxide likely to be produced in the shock layer around a Space Shuttle orbiter vehicle during its reentry is calculated at one point on the trajectory. An equivalent-cone is defined as one that produces the same amount of nitric oxide as the orbiter. The amounts of nitric oxide produced by the cone are calculated at points along the trajectory to determine their total and altitudinal distribution. The results show that about 14 tonne nitric oxide is produced at each entry, the peak occurring at 68 km altitude.

Park, C.; Rakich, J. V.

1980-01-01

69

Modulation of glutamine synthesis in cultured astrocytes by nitric oxide.  

PubMed

1. Previous results suggest that glutamine synthesis in brain could be modulated by nitric oxide. The aim of this work was to assess this possibility. 2. As glutamine synthetase in brain is located mainly in astrocytes, we used primary cultures of astrocytes to assess the effects of increasing or decreasing nitric oxide levels on glutamine synthesis in intact astrocytes. 3. Nitric oxide levels were decreased by adding nitroarginine, an inhibitor of nitric oxide synthase. To increase nitric oxide we used S-nitroso-N-acetylpenicillamine, a nitric oxide generating agent. 4. It is shown that S-nitroso-N-acetylpenicillamine decreases glutamine synthesis in intact astrocytes by approximately 40-50%. Nitroarginine increases glutamine synthesis slightly in intact astrocytes. 5. These results indicate that brain glutamine synthesis may be modulated in vivo by nitric oxide. PMID:9262869

Miñana, M D; Kosenko, E; Marcaida, G; Hermenegildo, C; Montoliu, C; Grisolía, S; Felipo, V

1997-08-01

70

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

NASA Technical Reports Server (NTRS)

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

Jachimowski, C. J.

1975-01-01

71

Increased nitric oxide levels as an early sign of premature aging in diabetes  

Microsoft Academic Search

The levels of different reactive species, especially those of nitric oxide and peroxynitrite, were determined in streptozotocin-induced diabetic rat tissues, before the development of histopathological damages. Significantly higher steady state free radical concentrations were found in the liver 3 weeks after the onset of diabetes compared to age-matched control groups. Increased nitric oxide levels in diabetic vasculature and kidney decreased

Krisztián Stadler; Veronika Jenei; Gábor von Bölcsházy; Anikó Somogyi; Judit Jakus

2003-01-01

72

Joule heating and nitric oxide in the thermosphere, 2 Charles A. Barth1  

E-print Network

Joule heating and nitric oxide in the thermosphere, 2 Charles A. Barth1 Received 14 April 2010 and higher. These gravity waves are produced by Joule heating that occurs at latitudes of 60° and higher of increased nitric oxide produced by Joule heating initiated gravity waves and to determine how often downflow

Bailey, Scott

73

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

SciTech Connect

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

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

2010-04-15

74

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

75

Nitric Oxide in Cardiovascular Biology and Pathophysiology  

Microsoft Academic Search

During the past 2 decades, our understanding of the role of endothelium-derived nitric oxide (NO) in maintaining cardiovascular\\u000a homeostasis has increased significantly. The physiologic synthesis, secretion, and function of NO form the basis for healthy\\u000a endothelial function. The endothelium is usually a quiescent monolayer of cells that lines the luminal surface of blood vessels\\u000a and the heart. Because of its

Marshall A. Corson

76

Endogenous nitric oxide generation in protoplast chloroplasts.  

PubMed

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

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

2013-01-01

77

Functional role of nitric oxide in plants  

Microsoft Academic Search

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

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

2010-01-01

78

Biological nitric oxide signalling: chemistry and terminology  

PubMed Central

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

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

2013-01-01

79

Pulsed EPR Determination of Distance between Heme Iron and FMN Centers in a Human Inducible Nitric Oxide Synthase  

PubMed Central

Mammalian NOS is a homodimeric flavo-hemoprotein that catalyzes the oxidation of l-arginine to NO. Regulation of NO biosynthesis by NOS is primarily through control of interdomain electron transfer (IET) processes in NOS catalysis. The IET from the FMN to heme domains is essential in the delivery of electrons required for O2 activation in the heme domain and the subsequent NO synthesis by NOS. The NOS output state for NO production is an IET-competent complex of the FMN-binding domain and heme domain, and thereby it facilitates the IET from the FMN to the catalytic heme site. The structure of the functional output state has not yet been determined. In the absence of crystal structure data for NOS holoenzyme, it is important to experimentally determine the Fe?FMN distance to provide a key calibration for computational docking studies and for the IET kinetics studies. Here we used the relaxation-induced dipolar modulation enhancement (RIDME) technique to measure the electron spin echo envelope modulation caused by the dipole interactions between paramagnetic FMN and heme iron centers in the [Fe(III)][FMNH•] form of a human iNOS oxygenase/FMN bi-domain construct. The FMNH•?Fe distance has been directly determined from the RIDME spectrum. This distance (18.8 ± 0.1 Å) is in excellent agreement with the IET rate constant measured by laser flash photolysis. PMID:20695464

Astashkin, Andrei V.; Elmore, Bradley O.; Fan, Weihong; Guillemette, J. Guy; Feng, Changjian

2010-01-01

80

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

81

Nitric oxide, oxidants, and protein tyrosine nitration  

Microsoft Academic Search

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

Rafael Radi

2004-01-01

82

Oxidative Stress, Nitric Oxide, and Diabetes  

PubMed Central

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

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

2010-01-01

83

Nitric Oxide: An Endogenous Modulator of Leukocyte Adhesion  

Microsoft Academic Search

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

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

1991-01-01

84

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

85

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

86

Structure–function studies on nitric oxide synthases  

Microsoft Academic Search

Nitric oxide synthase (NOS) catalyzes the oxidation of one l-arginine guanidinium N atom to nitric oxide (NO). NOS consists of a heme domain linked to a flavin mononucleotide (FMN)\\/flavin adenine dinucleotide (FAD) reductase that shuttles electrons from nicotinamide adenine dinucleotide phosphate (NADPH) to the heme. This review summarizes various aspects of NOS structure and function derived from crystal structures coupled

Huiying Li; Thomas L. Poulos

2005-01-01

87

Determination of tea polyphenols and caffeine in tea flowers (Camellia sinensis) and their hydroxyl radical scavenging and nitric oxide suppressing effects.  

PubMed

The native occurrence of tea polyphenols, namely, (-)-epicatechin, (+)-catechin, (-)-epigallocatechin 3-gallate, (-)-epicatechin, and (-)-epicatechin 3-gallate, and caffeine in tea flowers was assessed by an isocratic HPLC procedure. The levels of total catechins and caffeine were determined in tea flowers collected from 10 different species of Camellia sinensis. The results showed the levels of total catechin ranged from 10 to 38 mg/g, whereas the level of caffeine ranged from 3 to 8 mg/g. Levels of catechins and caffeine in tea leaves and various teas were also determined and ranged from 2 to 126 mg/g and from 23 to 49 mg/g, respectively. Both tea flower and tea leaf extracts exert their strong hydroxyl radical scavenging effects in the Fenton reaction system and nitric oxide suppressing effects in LPS-induced RAW 264.7 cells. Most tea flowers contain less caffeine, but comparable amounts of total catechins, compared to tea leaves and teas. The present study demonstrates that both tea flowers and tea leaves contain appreciable amounts of catechins and caffeine. It is likely that tea flowers might be useful for making alternative tea beverages. PMID:12568558

Lin, Yung-Sheng; Wu, Sang-Shung; Lin, Jen-Kun

2003-02-12

88

Inhaled nitric oxide in chronic obstructive lung disease  

SciTech Connect

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

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

1993-01-30

89

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

2013-07-01

90

Nitric oxide regulates vascular adaptive mitochondrial dynamics  

PubMed Central

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

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

2013-01-01

91

Nitric oxide scavenging by red cell microparticles.  

PubMed

Red cell microparticles form during the storage of red blood cells and in diseases associated with red cell breakdown and asplenia, including hemolytic anemias such as sickle cell disease. These small phospholipid vesicles that are derived from red blood cells have been implicated in the pathogenesis of transfusion of aged stored blood and hemolytic diseases, via activation of the hemostatic system and effects on nitric oxide (NO) bioavailability. Red cell microparticles react with the important signaling molecule NO almost as fast as cell-free hemoglobin, about 1000 times faster than red-cell-encapsulated hemoglobin. The degree to which this fast reaction with NO by red cell microparticles influences NO bioavailability depends on several factors that are explored here. In the context of stored blood preserved in ADSOL, we find that both cell-free hemoglobin and red cell microparticles increase as a function of duration of storage, and the proportion of extra erythrocytic hemoglobin in the red cell microparticle fraction is about 20% throughout storage. Normalized by hemoglobin concentration, the NO-scavenging ability of cell-free hemoglobin is slightly higher than that of red cell microparticles as determined by a chemiluminescence NO-scavenging assay. Computational simulations show that the degree to which red cell microparticles scavenge NO will depend substantially on whether they enter the cell-free zone next to the endothelial cells. Single-microvessel myography experiments performed under laminar flow conditions demonstrate that microparticles significantly enter the cell-free zone and inhibit acetylcholine, endothelial-dependent, and NO-dependent vasodilation. Taken together, these data suggest that as little as 5 ?M hemoglobin in red cell microparticles, an amount formed after the infusion of one unit of aged stored packed red blood cells, has the potential to reduce NO bioavailability and impair endothelial-dependent vasodilation. PMID:24051181

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

2013-12-01

92

Transport of Nitric Oxide by Perfluorocarbon Emulsion  

PubMed Central

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

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

2014-01-01

93

Role of nitric oxide in parasitic infections.  

PubMed Central

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

James, S L

1995-01-01

94

Systemic Nitric Oxide Production Rate during Hemodialysis and Its Relationship with Nitric Oxide-Related Factors  

Microsoft Academic Search

Background\\/Aims:Nitric oxide (NO) plays a key role in the regulation of vascular tone and controls both local and systemic hemodynamics. Here, we estimated systemic NO production rates of hemodialysis (HD) patients, based on the time course of plasma concentration of nitrate (an oxidative end product of NO) and investigated possible roles of NO-related factors. Methods: We measured plasma concentrations of

Seiichi Mochizuki; Jun-ichi Ono; Toyotaka Yada; Yasuo Ogasawara; Takehiro Miyasaka; Masumi Kimoto; Naoki Kashihara; Fumihiko Kajiya

2005-01-01

95

Dual labeling for simultaneous determination of nitric oxide, glutathione and cysteine in macrophage RAW264.7 cells by microchip electrophoresis with fluorescence detection.  

PubMed

A simple, rapid and efficient method based on microchip electrophoresis coupled with fluorescence detection (MCE-FLD) was developed for simultaneous determination of nitric oxide (NO), glutathione (GSH) and cysteine (Cys) using dual labeling strategy. Two highly reactive fluorogenic probes, 1,3,5,7-tetramethyl-8-(3',4'-diaminophenyl)-difluoroboradiaza-s-indacene (DAMBO) and 1,3,5,7-tetramethyl-8-phenyl-(2-maleimide)-difluoroboradiaza-s-indacene (TMPAB-o-M), were used for labeling NO and thiols, respectively, under physiological conditions. The rapid separation and sensitive detection of the derivatives were achieved on a glass microchip within 70s in a running buffer of 20mM H3Cit-Na2HPO4 solution (pH 7.4) containing 15% (v/v) acetonitrile at a separation voltage of 2400V. The limits of detection (S/N=3) for NO, GSH and Cys were 7.0, 3.0 and 2.0nM, respectively. The proposed method was validated by measuring intracellular levels of NO and biothiols in macrophage RAW264.7 cells. PMID:25069745

Tu, Feng-Qin; Zhang, Li-Yun; Guo, Xiao-Feng; Zhang, Zi-Xing; Wang, Hong; Zhang, Hua-Shan

2014-09-12

96

Nitric oxide reactions of bio-Inspired zinc and cobalt complexes  

E-print Network

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

Kozhukh, Julia, 1985-

2012-01-01

97

Plant Haemoglobins, Nitric Oxide and Hypoxic Stress  

PubMed Central

It is now known that there are several classes of haemoglobins in plants. A specialized class of haemoglobins, symbiotic haemoglobins, were discovered 62 years ago and are found only in nodules of plants capable of symbiotic nitrogen fixation. Plant haemoglobins, with properties distinct from symbiotic haemoglobins were discovered 18 years ago and are now believed to exist throughout the plant kingdom. They are expressed in different organs and tissues of both dicot and monocot plants. They are induced by hypoxic stress and by oversupply of certain nutrients. Most recently, truncated haemoglobins have been shown to also exist in plants. While hypoxic stress?induced haemoglobins are widespread in the plant kingdom, their function has not been elucidated. This review discusses the recent findings regarding the function of these haemoglobins in relation to adaptation to hypoxia in plants. We propose that nitric oxide is an important metabolite in hypoxic plant cells and that at least one of the functions of hypoxic stress?induced haemoglobins is to modulate nitric oxide levels in the cell. PMID:12509338

DORDAS, CHRISTOS; RIVOAL, JEAN; HILL, ROBERT D.

2003-01-01

98

Role of nitric oxide during rotavirus infection.  

PubMed

The pathophysiological mechanisms behind rotavirus-induced diarrhoea still remain incomplete. Current views suggest that the non-structural protein 4 (NSP4) of rotavirus and the enteric nervous system (ENS) participate in water secretion and diarrhoea. In the present work the role of nitric oxide (NO) in rotavirus infection and disease has been studied in vitro, mice and humans. Incubation of human intestinal epithelial cells (HT-29) with purified NSP4 but not with infectious virus produced NO2/NO3 accumulation in the incubation media. The NSP4-induced release of NO metabolites occurred within the first minutes after the addition of the toxin. Mice infected with murine rotavirus (strain EDIM) accumulated NO2/NO3 in the urine at the onset for diarrhoea. Following rotavirus infection, inducible nitric oxide synthetase (iNOS) mRNA was upregulated in ileum, but not in duodenum or jejunum of newborn pups within 5 days post-infection. A prospective clinical study including 46 children with acute rotavirus infection and age-matched controls concluded that rotavirus infection stimulates NO production during the course of the disease (P < 0.001). These observations identify NO as an important mediator of host responses during rotavirus infection. PMID:16721855

Rodríguez-Díaz, Jesús; Banasaz, Mahanez; Istrate, Claudia; Buesa, Javier; Lundgren, Ove; Espinoza, Felix; Sundqvist, Tommy; Rottenberg, Martin; Svensson, Lennart

2006-07-01

99

Adsorption and release of nitric oxide in metal organic frameworks  

US Patent & Trademark Office Database

Disclosed are metal organic frameworks that adsorb nitric oxide, NO-loaded metal organic frameworks, methods of preparing the NO-loaded metal organic frameworks, methods of releasing the nitric oxide into a solution or into air, and uses of the metal organic frameworks.

2013-07-16

100

Downregulation of Endothelial Constitutive Nitric Oxide Synthase Expression by Lipopolysaccharide  

Microsoft Academic Search

Lipopolysaccharide (LPS), a causal agent of sepsis, has been shown to induce systemic nitric oxide (NO) synthesis through complex mechanisms. However, the effect of LPS on endothelial cells is incompletely understood. To investigate the mechanism by which LPS influences the release of NO from endothelial cells, the effect of this compound on endothelial constitutive nitric oxide synthase (ecNOS) was studied

Jia-Ling Lu; Lorenz M. Schmiege; III; Lih Kuo; James C. Liao

1996-01-01

101

Nitric Oxide--Some Old and New Perspectives.  

ERIC Educational Resources Information Center

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

Ainscough, Eric W.; Brodie, Andrew M.

1995-01-01

102

Involvement and dual effects of nitric oxide in septic shock  

Microsoft Academic Search

Bacterial endotoxin (LPS) releases many mediators such as interleukins, tumour necrosis factor, oxygen free radicals, toxic eicosanoids, platelet activating factor, and nitric oxide (NO). LPS is a potent inducer of inducible nitric oxide synthase (iNOS). Large amounts of NO (made by iNOS) and peroxynitrite, among other factors, are responsible for the late phase of hypotension, vasoplegia, cellular suffocation, apoptosis, lactic

P. P. Wolkow

1998-01-01

103

Expired nitric oxide as a marker for childhood asthma  

Microsoft Academic Search

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

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

1997-01-01

104

STUDENT NITRIC OXIDE EXPLORER (SNOE) TELEMETRY AND FLIGHT SOFTWARE DESIGN  

E-print Network

1 STUDENT NITRIC OXIDE EXPLORER (SNOE) TELEMETRY AND FLIGHT SOFTWARE DESIGN Mark A. Salada the telemetry design and the flight software design for the Student Nitric Oxide Explorer (SNOE) satellite for the SNOE project sets forth a packetized telemetry data scheme based upon the recommendations

Bailey, Scott

105

Endothelial nitric oxide synthase: the Cinderella of inflammation?  

Microsoft Academic Search

A hallmark of inflammation is increased vascular permeability. Increases in vascular permeability and the migration of inflammatory cells are linked to complex interactions of inflammatory mediators with the vascular endothelium. Normally, endothelial nitric oxide synthase (eNOS) produces a tonic amount of nitric oxide (NO), which is responsible for the homeostasis between the endothelium and surrounding tissues. However, most agonists that

Giuseppe Cirino; Stefano Fiorucci; William C Sessa

2003-01-01

106

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

107

Ascaris haemoglobin is a nitric oxide-activated 'deoxygenase'.  

PubMed

The parasitic nematode Ascaris lumbricoides infects one billion people worldwide. Its perienteric fluid contains an octameric haemoglobin that binds oxygen nearly 25,000 times more tightly than does human haemoglobin. Despite numerous investigations, the biological function of this molecule has remained elusive. The distal haem pocket contains a metal, oxygen and thiol, all of which are known to be reactive with nitric oxide. Here we show that Ascaris haemoglobin enzymatically consumes oxygen in a reaction driven by nitric oxide, thus keeping the perienteric fluid hypoxic. The mechanism of this reaction involves unprecedented chemistry of a haem group, a thiol and nitric oxide. We propose that Ascaris haemoglobin functions as a 'deoxygenase', using nitric oxide to detoxify oxygen. The structural and functional adaptations of Ascaris haemoglobin suggest that the molecular evolution of haemoglobin can be rationalized by its nitric oxide related functions. PMID:10519555

Minning, D M; Gow, A J; Bonaventura, J; Braun, R; Dewhirst, M; Goldberg, D E; Stamler, J S

1999-09-30

108

Nitric oxide induces cell death in Taxus cells.  

PubMed

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

Pedroso; Magalhaes; Durzan

2000-08-22

109

Therapeutic approaches using nitric oxide in infants and children  

PubMed Central

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

Steinhorn, Robin H.

2011-01-01

110

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

E-print Network

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

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

2004-01-01

111

Direct determination of trace nitrogen dioxide by atmospheric pressure lonization mass spectrometry (APIMS) without conversion to nitric oxide  

Microsoft Academic Search

The aim of this study was to develop a new method for the determination of NO2 levels encountered in clinical settings as well as in environmental studies, using a bi-component atmospheric pressure ionization\\u000a mass spectrometry (APIMS). Hydrogen (1%) diluted in pure argon was ionized by corona discharge in the first ionization component.\\u000a Fifty ml of the analyte diluted in 250

Takaaki Kinoue; Satoshi Asai; Yukimoto Ishii; Koichi Ishikawa; Masashi Fujii; Kazuo Nakano; Keiji Hasumi

2000-01-01

112

Biochemical aspects of nitric oxide synthase feedback regulation by nitric oxide  

PubMed Central

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

Kopincova, Jana; Puzserova, Angelika; Bernatova, Iveta

2011-01-01

113

Direct determination of trace nitrogen dioxide by atmospheric pressure lonization mass spectrometry (APIMS) without conversion to nitric oxide.  

PubMed

The aim of this study was to develop a new method for the determination of NO(2) levels encountered in clinical settings as well as in environmental studies, using a bi-component atmospheric pressure ionization mass spectrometry (APIMS). Hydrogen (1%) diluted in pure argon was ionized by corona discharge in the first ionization component. Fifty ml of the analyte diluted in 250 ml of composite air or carbon dioxide (CO2) was introduced into the second ionization component and analyzed. When composite air was used as the sample carrier gas, NO in the analyte was oxygenated and there was an increase in the NO(2) content from that in the original analyte. However, when CO(2) was used as the sample carrier gas, the level of NO(2) in the analyte could be determined because CO(2) did not change the NO(2) content from that in the original analyte. A calibration curve with good linearity was obtained using the UG-410 APIMS system, with a regression equation of Y(%) = 5.513*10(-2) X (ppb) and a detection limit of 0.9 ppb. Since APIMS detects NO(2) direcdy within its system, the concentration of NO does not need to be measured. This system may be of great help in the accurate detection and determination of the concentration of low levels of NO(2) during inhaled NO therapy. PMID:21432192

Kinoue, T; Asai, S; Ishii, Y; Ishikawa, K; Fujii, M; Nakano, K; Hasumi, K

2000-10-01

114

Nitric oxide in skeletal muscle: inhibition of nitric oxide synthase inhibits walking speed in rats.  

PubMed

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, Ca(2+) dependence, and activity of NOS in human and rat skeletal muscle and (2) using a rat model, investigate the effect of chronic blockade of NOS on skeletal muscle structure and function. Our results showed that both human and rodent skeletal muscle had NOS activity. This NOS activity was similar to that of the endothelial and brain NOS isoforms in that it was calcium-dependent. However, Western blot analysis consistently showed that a polyclonal antibody raised against a peptide sequence of human inducible NOS (iNOS) reacted with a protein with a molecular weight (95 kDa) that was different from that of other NOS isoforms. RT-PCR analysis identified the mRNA expression of not only eNOS and bNOS but also iNOS in human and rat muscle. Inhibition of nitric oxide synthase in rats with N(omega)-nitro-L-arginine methyl ester (L-NAME) resulted in a progressive, severe reduction in walking speed (30-fold reduction in walking velocity at day 22, P < 0.001), muscle fiber cross-sectional area (40% reduction at day 22, P < 0.001), and muscle mass (40% reduction in dry weight at day 22, P < 0.01). Rats fed the same regimen of the enantiomer of L-NAME (d-NAME) had normal motor function, muscle fiber morphology, and muscle mass. Taken together, these results imply that there may be a novel nitric oxide synthase in muscle and that NO. generated from muscle may be important in muscle function. PMID:11384195

Wang, M X; Murrell, D F; Szabo, C; Warren, R F; Sarris, M; Murrell, G A

2001-06-01

115

Nitric oxide-releasing porous silicon nanoparticles  

PubMed Central

In this study, the ability of porous silicon nanoparticles (PSi NPs) to entrap and deliver nitric oxide (NO) as an effective antibacterial agent is tested against different Gram-positive and Gram-negative bacteria. NO was entrapped inside PSi NPs functionalized by means of the thermal hydrocarbonization (THC) process. Subsequent reduction of nitrite in the presence of d-glucose led to the production of large NO payloads without reducing the biocompatibility of the PSi NPs with mammalian cells. The resulting PSi NPs demonstrated sustained release of NO and showed remarkable antibacterial efficiency and anti-biofilm-forming properties. These results will set the stage to develop antimicrobial nanoparticle formulations for applications in chronic wound treatment. PMID:25114633

2014-01-01

116

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. PMID:22362384

Carpenter, Alexis W.; Schoenfisch, Mark H.

2012-01-01

117

Recent developments in nitric oxide donor drugs  

PubMed Central

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

Miller, M R; Megson, I L

2007-01-01

118

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. PMID:20169170

Muro, Antonio; Perez-Arellano, Jose-Luis

2010-01-01

119

Nitric Oxide Release Part I. Macromolecular Scaffolds  

PubMed Central

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

Riccio, Daniel A.; Schoenfisch, Mark H.

2012-01-01

120

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, >600 nm) 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 25 mM pH 6.50 borate buffer, DANPBO-H reacted with NO to give the corresponding triazole, DANPBO-H-T, at 35 °C for 20 min. 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 4 min on a C8 column and detected with fluorescence detection at excitation and emission wavelengths of 621 and 631 nm, 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

2013-11-15

121

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

PubMed Central

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

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

2014-01-01

122

Induction of hepatic Ito cell nitric oxide production after acute endotoxemia.  

PubMed

Nitric oxide is a highly reactive mediator released in the liver by hepatocytes, Kupffer cells and endothelial cells during endotoxin-induced inflammation. In this study we determined whether Ito cells also produce nitric oxide after exposure to endotoxin. For induction of endotoxemia, rats were injected intravenously with Escherichia coli lipopolysaccharide (2.5 mg/kg). Ito cells were isolated from the animals 48 hr later by means of in situ perfusion of the liver with protease and collagenase followed by purification on an arabinogalactan gradient. Ito cells from untreated and endotoxemic rats were found to produce low levels of nitric oxide in response to interferon-gamma. In both cell types, this response depended on L-arginine and was blocked by NG-monomethyl-L-arginine, a specific nitric oxide synthase inhibitor. Cells from rats treated with endotoxin produced significantly more nitric oxide than did cells from untreated animals; this was due, at least in part, to increased expression of protein for an inducible form of nitric oxide synthase. These cells also responded to stimulation with lipopolysaccharide in vitro, as well as the combination of interferon-gamma and lipopolysaccharide, which was synergistic in stimulating nitric oxide production. Tumor necrosis factor-alpha and macrophage colony-stimulating factor were also found to stimulate nitric oxide production by Ito cells from endotoxemic rats. In addition, in these cells, tumor necrosis factor-alpha synergized with interferon-gamma in inducing nitric oxide production. The combination of interferon-gamma and lipopolysaccharide was also found to inhibit Ito cell DNA synthesis, as measured on the basis of [3H]-thymidine uptake.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7527004

Helyar, L; Bundschuh, D S; Laskin, J D; Laskin, D L

1994-12-01

123

Nitric oxide: involvement in the effects of anesthetic agents.  

PubMed

There has been an explosive increase in the amount of interesting information about the physiologic and pathophysiologic roles of nitric oxide in cardiovascular, nervous, and immune systems. The possible involvement of the nitric oxide-cyclic guanosine monophosphate pathway in the effects of anesthetic agents has been the focus of many investigators. Relaxations of cerebral and peripheral arterial smooth muscle as well as increases in cerebral and other regional blood flows induced by anesthetic agents are mediated mainly via nitric oxide released from the endothelium and/or the nitrergic nerve and also via prostaglandin I2 or endothelium-derived hyperpolarizing factor. Preconditioning with volatile anesthetics protects against ischemia-reperfusion-induced myocardial dysfunction and cell death or neurotoxicity, possibly through nitric oxide release. Inhibition of nitric oxide synthase decreases the anesthetic requirement. Involvement of nitric oxide in the effects of volatile, intravenous, and local anesthetics differs. This review article includes a summary of information about the sites and mechanisms by which various anesthetic agents interact with the nitric oxide-cyclic guanosine monophosphate system. PMID:18073558

Toda, Noboru; Toda, Hiroshi; Hatano, Yoshio

2007-11-01

124

Role of Nitric Oxide in Neurodegeneration and Vulnerability of Neuronal Cells to Nitric Oxide Metabolites and Reactive Oxygen Species  

Microsoft Academic Search

\\u000a Nitric oxide (NO) is produced during the oxidative deamination catalyzed by nitric oxide synthase (NOS) that converts l-arginine to l-citrulline. NO can also be released chemically from a group of compounds called NO donors, such as sodium nitroprusside (SNP).\\u000a NO directly or through its metabolites is believed to be involved in several disorders, including Alzheimer’s disease (AD).\\u000a This chapter summarizes

Debomoy K. Lahiri; Chandramallika Ghosh; Jack T. Rogers; Stephen Bondy; Nigel H. Greig

125

Tetrahydrobiopterin alters superoxide and nitric oxide release in prehypertensive rats.  

PubMed Central

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

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

1998-01-01

126

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

NASA Astrophysics Data System (ADS)

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

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

2010-01-01

127

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

128

Nitric oxide and oxidative stress in cardiovascular aging.  

PubMed

The long-standing free radical theory of aging, which attributes cellular pathology to the relentless accumulation of reactive oxygen species (ROS), remains attractive but controversial. Emerging insights into the molecular interactions between ROS and reactive nitrogen species (RNS) such as nitric oxide suggest that, in biological systems, one effect of increased ROS is the disruption of protein S-nitrosylation, a ubiquitous posttranslational modification system. In this way, ROS may not only damage cells but also disrupt widespread signaling pathways. Here, we discuss this phenomenon in the context of the cardiovascular system and propose that ideas regarding oxidative stress and aging need to be reevaluated to take account of the balance between oxidative and nitrosative stress. PMID:15917507

Raju, Shubha V Y; Barouch, Lili A; Hare, Joshua M

2005-05-25

129

Prediction of nitric oxide concentrations during inflammation and carcinogenesis  

E-print Network

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

Chin, Melanie Pei-Heng

2010-01-01

130

Detecting and Understanding the Roles of Nitric Oxide in biology  

E-print Network

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

Tonzetich, Zachary J.

131

Racial Differences in Nitric Oxide-Dependent Vasorelaxation  

PubMed Central

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

Mata-Greenwood, Eugenia; Chen, Dong-Bao

2008-01-01

132

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

133

Nitric Oxide Myoglobin: Crystal Structure and Analysis of Ligand Geometry  

E-print Network

by stabilizing a water molecule in the deoxy heme pocket and lowers the dissociation rate constant by forming, the rate of nitric oxide dissociation from myoglobin increases tenfold. Proteins 30:352­356, 1998. 1998

Phillips, George N. Jr.

134

Hydrogen peroxide differentially modulates cardiac myocyte nitric oxide synthesis  

E-print Network

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

Sartoretto, Juliano

135

Controlled delivery of nitric oxide for cytotoxicity studies  

E-print Network

Endogenous synthesis of nitric oxide (NO) is essential for many physiological functions, including the immune defense. However, the sustained, high production of NO by immune cells (macrophages) that accompanies chronic ...

Wang, Chen, 1972-

2003-01-01

136

Endothelial nitric oxide synthase, vascular integrity and human exceptional longevity  

PubMed Central

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

2012-01-01

137

Hyperbaric oxygen upregulates cochlear constitutive nitric oxide synthase  

Microsoft Academic Search

Background  Hyperbaric oxygen therapy (HBOT) is a known adjuvant for treating ischemia-related inner ear diseases. Controversies still\\u000a exist in the role of HBOT in cochlear diseases. Few studies to date have investigated the cellular changes that occur in inner\\u000a ears after HBOT. Nitric oxide, which is synthesized by nitric oxide synthase (NOS), is an important signaling molecule in\\u000a cochlear physiology and

Chia-Der Lin; I-Hua Wei; Chih-Ho Lai; Te-Chun Hsia; Ming-Ching Kao; Ming-Hsui Tsai; Ching-Hsiang Wu; Mang-Hung Tsai

2011-01-01

138

Nitric oxide and teratogenesis: an update.  

PubMed

Nitric oxide (NO), generated by NO synthase (NOS) enzymes, is an important bioactive molecule involved in the regulation of several biological phenomena that are crucial for organogenesis, including gene expression, cell growth, matrix remolding, proliferation, differentiation and apoptosis. The expression of NOS isoforms in embryonic tissues is temporally and spatially regulated, and disruption of endogenous NO can lead to developmental defects. Maternal treatment with pan NOS inhibitors during early organogenesis caused severe malformations of the axial skeleton. In utero exposure during the fetal period induced limb reduction defects of vascular origin. Knock-out mice have been used to define the role of the various NOS isoforms on the origin of the abnormal development. Cardiovascular malformations, limb reduction defects, reduced growth and reduced survival have been observed in knock-out mice with targeted disruption of endothelial NOS (eNOS). Limited morphological changes were observed in mice lacking inducible NOS (iNOS) or neuronal NOS n(NOS). Results obtained with in vitro studies suggest that optimal levels of NO are required for neural tube closure. Disregulation of NO production was also recently proposed as a contributing mechanism in the origin of malformations associated with exposure to known environmental teratogens, such as valproic acid, thalidomide, copper deficiency, and diabetes. PMID:24502594

Tiboni, Gian Mario; Ponzano, Adalisa

2014-01-01

139

Nitric oxide and cancer: a review  

PubMed Central

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

2013-01-01

140

Nitric oxide modulates sensitivity to ABA.  

PubMed

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

Lozano-Juste, Jorge; León, José

2010-03-01

141

Vasculoprotective roles of neuronal nitric oxide synthase.  

PubMed

Nitric oxide (NO) has multiple important actions that contribute to the maintenance of vascular homeostasis. NO is synthesized by three different isoforms of NO synthase (NOS), all of which have been reported to be expressed in human atherosclerotic vascular lesions. Although the regulatory roles of endothelial NOS (eNOS) and inducible NOS (iNOS) on the development of atherosclerosis have been described, little is known about the role of neuronal NOS (nNOS). Here, we show that nNOS also exerts important vasculoprotective effects in vivo. In a carotid artery ligation model, nNOS gene-deficient (nNOS-KO) mice exhibited accelerated neointimal formation and constrictive vascular remodeling caused by blood flow disruption. In a rat balloon injury model, the selective inhibition of nNOS activity potently enhanced vasoconstrictor responses to a variety of calcium-mobilizing stimuli, suppressed tissue cGMP concentrations, a marker of vascular NO production, and exacerbated neointimal formation. In both models, nNOS was absent before injury and was up-regulated only after the injury, and was predominantly expressed in the neointima and medial smooth muscle cells. These results provide the first direct evidence that nNOS plays important roles in suppressing arteriosclerotic vascular lesion formation in vivo. PMID:12397095

Morishita, Tsuyoshi; Tsutsui, Masato; Shimokawa, Hiroaki; Horiuchi, Masataka; Tanimoto, Akihide; Suda, Osamu; Tasaki, Hiromi; Huang, Paul L; Sasaguri, Yasuyuki; Yanagihara, Nobuyuki; Nakashima, Yasuhide

2002-12-01

142

Panax ginseng pharmacology: a nitric oxide link?  

PubMed

Panax ginseng is used in traditional Chinese medicine to enhance stamina and capacity to cope with fatigue and physical stress. Major active components are the ginsenosides, which are mainly triterpenoid dammarane derivatives. The mechanisms of ginseng actions remain unclear, although there is an extensive literature that deals with effects on the CNS (memory, learning, and behavior), neuroendocrine function, carbohydrate and lipid metabolism, immune function, and the cardiovascular system. Reports are often contradictory, perhaps because the ginsenoside content of ginseng root or root extracts can differ, depending on the method of extraction, subsequent treatment, or even the season of its collection. Therefore, use of standardized, authentic ginseng root both in research and by the public is to be advocated. Several recent studies have suggested that the antioxidant and organ-protective actions of ginseng are linked to enhanced nitric oxide (NO) synthesis in endothelium of lung, heart, and kidney and in the corpus cavernosum. Enhanced NO synthesis thus could contribute to ginseng-associated vasodilatation and perhaps also to an aphrodisiac action of the root. Ginseng is sold in the U.S. as a food additive and thus need not meet specific safety and efficacy requirements of the Food and Drug Administration. Currently, such sales amount to over $300 million annually. As public use of ginseng continues to grow, it is important for this industry and Federal regulatory authorities to encourage efforts to study the efficacy of ginseng in humans by means of appropriately designed double-blind clinical studies. PMID:9296344

Gillis, C N

1997-07-01

143

Hemoglobin: A Nitric-Oxide Dioxygenase  

PubMed Central

Members of the hemoglobin superfamily efficiently catalyze nitric-oxide dioxygenation, and when paired with native electron donors, function as NO dioxygenases (NODs). Indeed, the NOD function has emerged as a more common and ancient function than the well-known role in O2 transport-storage. Novel hemoglobins possessing a NOD function continue to be discovered in diverse life forms. Unique hemoglobin structures evolved, in part, for catalysis with different electron donors. The mechanism of NOD catalysis by representative single domain hemoglobins and multidomain flavohemoglobin occurs through a multistep mechanism involving O2 migration to the heme pocket, O2 binding-reduction, NO migration, radical-radical coupling, O-atom rearrangement, nitrate release, and heme iron re-reduction. Unraveling the physiological functions of multiple NODs with varying expression in organisms and the complexity of NO as both a poison and signaling molecule remain grand challenges for the NO field. NOD knockout organisms and cells expressing recombinant NODs are helping to advance our understanding of NO actions in microbial infection, plant senescence, cancer, mitochondrial function, iron metabolism, and tissue O2 homeostasis. NOD inhibitors are being pursued for therapeutic applications as antibiotics and antitumor agents. Transgenic NOD-expressing plants, fish, algae, and microbes are being developed for agriculture, aquaculture, and industry. PMID:24278729

Gardner, Paul R.

2012-01-01

144

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

PubMed Central

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

2013-01-01

145

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...

146

Inducible Nitric Oxide Synthase Expression in Human Colorectal Cancer  

PubMed Central

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

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

2003-01-01

147

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

148

Discovery and development of neuronal nitric oxide synthase inhibitors  

Microsoft Academic Search

The role of neuronally derived nitric oxide (NO) in neurotransmission and neural injury remains an area of active investigation. NO generation has been postulated to be involved in the deleterious events surrounding ischemia\\/reperfusion injury either directly or via the production of more reactive oxidants such as peroxynitrite. In our search for novel therapeutics for the treatment of a variety of

David W Reif; Dennis J McCarthy; Ed Cregan; James E Macdonald

2000-01-01

149

Synthesis, nitric oxide release, and ?-glucosidase inhibition of nitric oxide donating apigenin and chrysin derivatives.  

PubMed

?-Glucosidase (AG) play crucial roles in the digestion of carbohydrates. Inhibitors of ?-glucosidase (AGIs) are promising candidates for the development of anti-diabetic drugs. Here, five series of apigenin and chrysin nitric oxide (NO)-donating derivatives were synthesised and evaluated for their AG inhibitory activity and NO releasing capacity in vitro. Except for 9a-c, twelve compounds showed remarkable inhibitory activity against ?-glucosidase, with potency being better than that of acarbose and 1-deoxynojirimycin. All organic nitrate derivatives released low concentrations of NO in the presence of l-cysteine. Structure activity relationship studies indicated that 5-OH, hydrophobic coupling chain, and carbonyl groups of the coupling chain could enhance the inhibitory activity. Apigenin and chrysin derivatives therefore represents a new class of promising compounds that can inhibit ?-glucosidase activity and supply moderate NO for preventing the development of diabetic complications. PMID:24508143

Wang, Qi-Qin; Cheng, Ning; Yi, Wen-Bing; Peng, Sheng-Ming; Zou, Xiao-Qing

2014-03-01

150

Nitric oxide and exercise in the horse.  

PubMed Central

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

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

1996-01-01

151

Hemorrhagic shock and nitric oxide release from erythrocytic nitric oxide synthase: A quantitative analysis  

PubMed Central

A large loss of blood during hemorrhage can result in profound shock, a state of hypotension associated with hemodynamic abnormalities. One of the hypotheses to account for this collapse of homeostasis is that the production of nitric oxide (NO), a gas molecule that dilates blood vessels, is significantly impaired during hemorrhage, resulting in a mismatch between O2 delivery and the metabolic activity in the tissues. NO can be released from multiple sources in the vasculature. Recent studies have shown that erythrocytes express functional endothelial nitric oxide synthase (NOS3), which potentially serves as an intraluminal NO source. NO delivery from this source is complex: Erythrocytes are not only NO producers but also act as potent sinks because of the high affinity of NO for hemoglobin. To test our hypothesis that the loss of erythrocytic NOS3 during hemorrhage contributes to NO deficiency-related shock, we have constructed a multicellular computational model that simulates NO production and transport to allow us to quantify the loss of NO under different hemorrhagic conditions. Our model shows that: (1) during mild hemorrhage and subsequent hemodilution (hematocrit >30%), NO from this intraluminal source is only slightly decreased in the vascular smooth muscle, but the NO level is significantly reduced under severe hemorrhagic conditions (hematocrit <30%); (2) whether a significant amount of NO from this source can be delivered to vascular smooth muscle is strongly dependent on the existence of a protective mechanism for NO delivery; (3) if the expression level of NOS3 on erythrocytes is similar to that on endothelial cells, we estimate ~13 pM NO at the vascular smooth muscle from this source when such a protective mechanism is involved. This study provides a basis for detailed studies to characterize the impairment of NO release pathways during hemorrhage and yield important insights for the development of resuscitation methods. PMID:19285090

Chen, Kejing; Pittman, Roland N.; Popel, Aleksander S.

2009-01-01

152

Environmental Exposures, Nitric Oxide Synthase Genes, and Exhaled Nitric Oxide in Asthmatic Children  

PubMed Central

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

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

2010-01-01

153

Kinetics of the reaction of nitric oxide with hydrogen  

NASA Technical Reports Server (NTRS)

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

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

1974-01-01

154

Pathogenic role of nitric oxide alterations in diabetic nephropathy.  

PubMed

Diabetic nephropathy is the most frequent cause of terminal renal failure, requiring renal replacement therapy. Although a number of factors may contribute to the development of renal disease in diabetes, the recent past has witnessed an explosive growth in literature pertaining to the role of nitric oxide in diabetic nephropathy. However, there are significant controversies in the findings of these studies partly because of the complex metabolic pathways involved in the generation and fate of nitric oxide in the diabetic kidney. The following discussion presents a critical and balanced review of the current understanding of this subject. PMID:16316597

Prabhakar, Sharma S

2005-12-01

155

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

E-print Network

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

Lim, Mi Hee

2006-01-01

156

Reciprocal regulation of cellular nitric oxide formation by nitric oxide synthase and nitrite reductases  

PubMed Central

Summary Our mini-review focuses on dual regulation of cellular nitric oxide (NO) signaling pathways by traditionally characterized enzymatic formation from L-arginine via the actions of NO synthases (NOS) and by enzymatic reduction of available cellular nitrite pools by a diverse class of cytosolic and mitochondrial nitrite reductases. Nitrite is a major metabolic product of NO and is found in all cell and tissue types that utilize NO signaling processes. Xanthine oxidoreductase (XOR) has been previously characterized as a housekeeping enzyme responsible for cellular uric acid formation via enzymatic conversion of hypoxanthine and xanthine. It has become apparent that XOR possesses multi-functional enzymatic activities outside the realm of xanthine metabolism and a small but significant literature also established a compelling functional association between administered sodium nitrite, XOR activation, and pharmacologically characterized NO transductive effects in positive cardiovascular function enhanced pulmonary perfusion, and protection against ischemia/reperfusion injury and hypoxic damage and oxidative stress. Similar positive vascular and cellular effects were observed to be functionally associated with mitochondrial aldehyde dehydrogenase and cytochrome c/cytochrome c oxidase. The profound implications of a reciprocal regulatory mechanism responsible for cytosolic and mitochondrial NO production are discussed below. PMID:21959625

Stefano, George B.; Kream, Richard M.

2011-01-01

157

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

PubMed Central

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

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

2014-01-01

158

Crystal structure of nitric oxide inhibited cytochrome c peroxidase  

SciTech Connect

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

Edwards, S.L.; Kraut, J. (Univ. of California, San Diego, La Jolla (USA)); Poulos, T.L. (Center for Advanced Research in Biotechnology, Rockville, MD (USA))

1988-10-18

159

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. PMID:19270016

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

160

Exhaled nitric oxide in occupational respiratory medicine and environmental health: state of art  

Microsoft Academic Search

Nitric oxide is a gas detectable in exhaled breath of humans and is recognized as a useful biomarker for asthma diagnosis and monitoring. Several studies have shown evidence of higher levels of exhaled nitric oxide in patients with respiratory diseases as compared to healthy population. The possibility of using exhaled nitric oxide measurement as a tool for the diagnosis and

Massimo Corradi; Petra Gergelova; Matteo Goldoni; Antonio Mutti

2011-01-01

161

Exhaled Nitric Oxide in Occupational Respiratory Medicine and Environmental Health: State of Art  

Microsoft Academic Search

Nitric oxide is a gas detectable in exhaled breath of humans and is recognized as a useful biomarker for asthma diagnosis and monitoring. Several studies have shown evidence of higher levels of exhaled nitric oxide in patients with respiratory diseases as compared with the healthy population. The possibility of using exhaled nitric oxide measurement as a tool for diagnosing and

Massimo Corradi; Petra Gergelova; Matteo Goldoni; Antonio Mutti

2011-01-01

162

Lasting beneficial effect of short-term inhaled nitric oxide on graft function after lung transplantation  

Microsoft Academic Search

The combination of ischemia and reperfusion after lung transplantation is characterized by endothelial damage, neutrophil sequestration, and decreased release of endothelial nitric oxide. Because nitric oxide has been shown to selectively dilate the pulmonary vasculature, abrogate neutrophil adherence, and restore endothelial dysfunction, we hypothesized that inhaled nitric oxide given for 4 hours during initial reperfusion might attenuate reperfusion injury in

Emile A. Bacha; Philippe Hervé; Shinya Murakami; Alain Chapelier; Guy-Michel Mazmanian; Vincent de Montpreville; Hélène Détruit; Jean-Marie Libert; Philippe Dartevelle

1996-01-01

163

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

164

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

E-print Network

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

George, Steven C.

165

Exhaled Nitric Oxide in Chronic Obstructive Pulmonary Disease  

Microsoft Academic Search

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

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

1998-01-01

166

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

167

Nitric oxide gamma and delta band emission at twilight  

NASA Technical Reports Server (NTRS)

Nitric oxide twilight emission above 140 km in the gamma- and delta-bands was observed with a rocket-borne spectrophotometer. The relative intensity of the two band systems indicates that the emission is produced predominantly by the chemiluminescent preassociation of oxygen and nitrogen atoms.

Feldman, P. D.; Takacs, P. Z.

1974-01-01

168

Surfactant and Inhaled Nitric Oxide in Acute Lung Injury  

Microsoft Academic Search

Pulmonary surfactant is routinely used in immature newborns for the prevention and treatment of respiratory distress syndrome (RDS). Inhaled nitric oxide (INO) is a new respiratory therapy, recently approved by the Food and Drug Administration, for selective pulmonary vasodilation in persistent pulmonary hypertension of the newborns (PPHN) and in hypoxic respiratory failure in neonates and infants. It is noteworthy that

B SUN

2000-01-01

169

Nitric oxide enhances de novo formation of endothelial gap junctions  

Microsoft Academic Search

Objective: Gap junctions (formed by connexins, Cx) are important for functional coordination of cells in the vascular wall. However, little is known about their physiological regulation in this tissue. We examined the effects of nitric oxide (NO), an important mediator of vasomotion, wound healing and angiogenesis, on the formation of gap junctions in endothelial cells (human umbilical vein endothelial cells,

Anke Hoffmann; Torsten Gloe; Ulrich Pohl; Stefan Zahler

2003-01-01

170

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

171

Nitric Oxide in Patients with Chronic Liver Diseases  

Microsoft Academic Search

Aim. Chronic liver disease (CLD) may be accompanied by portal hypertension (PHT). Nitric oxide (NO) system disturbances seem to play a key role in the pathogenesis of CLD and PHT. In this study we aim to assess if in chronic active hepatitis (CAH) and cirrhosis (CIR), CLD severity and etiology can be correlated with the serum level of NO metabolites.

Alina Elena Pârvu; Vasile Negrean; Luminiþa Ple; Angela Cosma; Anton Drãghici; Ana Uifãlean

172

Blood pressure response to hypoxia: role of nitric oxide synthase  

Microsoft Academic Search

BACKGROUND: Chronic exposure to hypobaric hypoxia has been shown to increase arterial pressure in genetically normal rats. The associated increase in blood pressure is unrelated to the hypoxia-induced erythrocytosis and persists indefinitely after restoration of normoxia. It is accompanied by a marked reduction in urinary excretion of nitric oxide metabolites (NOx) and is ameliorated by L-arginine supplementation. In view of

Cyril H. Barton; Zhenmin Ni; Nosratola D. Vaziri

2003-01-01

173

A global inventory of nitric oxide emissions from soils  

Microsoft Academic Search

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

Eric A. Davidson; Wendy Kingerlee

1997-01-01

174

Immunocytochemical localization of nitric oxide synthase in the mammalian retina  

E-print Network

Immunocytochemical localization of nitric oxide synthase in the mammalian retina In-Beom Kima , Eun, mouse, guinea pig, rabbit and cat retinae. Western blot analysis of retinal tissue extracts showed and rabbit retinae, two types of amacrine cells and a class of displaced amacrine cells were consistently NOS

Grzywacz, Norberto

175

Reaction of Coadsorbed Nitric Oxide and Nitrogen Atoms on Rh(111)  

Microsoft Academic Search

We have studied the reaction of nitrogen atoms (N) with nitric oxide molecules (NO) coadsorbed on a Rh(lll) catalyst in order to isolate the reaction of these two species as an elementary step (e.g., in the NO + CO reaction mechanism) and determine the products of that reaction. Electron beam dissociation of adsorbed NO was used to cleanly prepare N

D. N. Belton; C. L. Dimaggio; S. J. Schmieg; K. Y. S. Ng

1995-01-01

176

Amlodipine promotes kinin-mediated nitric oxide production in coronary microvessels of failing human hearts  

Microsoft Academic Search

Recently, we found that amlodipine can release nitric oxide (NO) from canine coronary microvessels, which raises the question of whether amlodipine can also promote coronary NO production in failing human hearts. The goal of this study was to define the effect of amlodipine on NO production in failing human hearts and to determine the role of kinins in the control

Xiaoping Zhang; Maryanne R Kichuk; Seema Mital; Mehmet Oz; Robert Michler; Alberto Nasjletti; Gabor Kaley; Thomas H Hintze

1999-01-01

177

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

178

Role of cardiovascular nitric oxide system in C-type natriuretic peptide effects  

Microsoft Academic Search

The aims were to evaluate the role of cardiovascular nitric oxide (NO)-system in C-type natriuretic peptide (CNP) actions and to investigate receptor types and signaling pathways involved in this interaction. Wistar rats were infused with saline or CNP. Mean arterial pressure (MAP) and nitrites and nitrates (NOx) excretion were determined. NO synthase (NOS) activity and NOS expression (Western blot) were

Rosana Elesgaray; Carolina Caniffi; Andrea Fellet; Cristina Arranz

2007-01-01

179

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

EPA Science Inventory

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

180

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

Microsoft Academic Search

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

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

1995-01-01

181

Spontaneous nitric oxide in hepatocyte monolayers and inhibition of compound-induced apoptosis  

Microsoft Academic Search

Primary cultures of hepatocytes are a widely used in vitro model for biochemical research. Following isolation, hepatocytes produce large amounts of nitric oxide (NO), which is known to have both pro- and anti-apoptotic effects in hepatocytes in vivo and in vitro. Previous work has not determined the effect of these increased levels of NO on the response of hepatocytes to

C. Dilworth; D. Bigot-Lasserre; R. Bars

2001-01-01

182

Hepatoprotective effect of endogenous nitric oxide during ischemia-reperfusion in the rat  

Microsoft Academic Search

The aim of this study was to evaluate the protective or deleterious effects of endogenous nitric oxide (NO) on liver cells during hepatic ischemia-reperfusion (IR) in the rat. Injury to hepatocytes and endothelial cells was evaluated by determining cytolysis-marker activity in plasma (alanine transaminase (ALT); aspartate transaminase (AST)) and plasma hyaluronic acid (HA) concentration. Clamping the hepatic pedicle for 45

Charles-Henry Cottart; Louis Do; Michel Vaubourdolle; Dominique Durand; Jean-Pierre Clot

1999-01-01

183

Role of Inducible Nitric Oxide Synthase in Resistance to Mycobacterium leprae in Mice  

Microsoft Academic Search

The manifestation of leprosy in humans is largely determined by host immunity to Mycobacterium leprae and is a model for immunoregulation in a human disease. However, animal models available for explora- tion of the leprosy spectrum are inadequate. This study explored M. leprae infection in mice deficient in inducible nitric oxide synthase, and this report describes elements resembling borderline tuberculoid

LINDA B. ADAMS; CHARLES K. JOB; JAMES L. KRAHENBUHL

2000-01-01

184

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

185

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

PubMed

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

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

1998-03-01

186

Practical nitric oxide measurement employing a nitric oxide-selective electrode  

NASA Astrophysics Data System (ADS)

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

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

1994-08-01

187

Effects of opioid (tramadol) treatment on testicular functions in adult male rats: The role of nitric oxide and oxidative stress.  

PubMed

Nowadays, tramadol hydrochloride is frequently used as a pain reliever, and for the treatment of premature ejaculation. Decreased semen quality was noted in chronic tramadol users. The present study aimed to elucidate the effects of tramadol on the testicular functions of adult male rats. A total of 40 albino adult male rats were divided into control and tramadol groups, with 20 rats for each group. Rats of the tramadol group were subcutaneously injected with 40 mg/kg three times per week for 8 weeks. The control group received normal saline 0.9%. Blood samples from each animal were obtained. Plasma levels of different biochemical substances were determined. Nitric oxide was measured in testicular tissue samples. Those samples together with epididymal tissue samples were processed for histopathological examination. Tramadol significantly reduced plasma levels of luteinizing hormone, follicle-stimulating hormone, testosterone and total cholesterol, but elevated prolactin and estradiol levels compared with the control group. In addition, tramadol increased the testicular levels of nitric oxide and lipid peroxidation, and decreased the anti-oxidant enzymes activities significantly compared with the control group. The tramadol group showed decreased sperm count and motility, and numbers of primary spermatocytes, rounded spermatid and Leydig cells. Immunohistochemical examinations showed that tramadol increased the expression of endothelial nitric oxide synthase in testicular tissues. The present study showed that tramadol treatment affects the testicular function of adult male rats, and these effects might be through the overproduction of nitric oxide and oxidative stress induced by this drug. PMID:24472030

Ahmed, Marwa A; Kurkar, Adel

2014-04-01

188

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

Microsoft Academic Search

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

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

2003-01-01

189

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

190

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

191

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. PMID:18060792

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

2008-01-01

192

Hypercholesterolemia decreases nitric oxide production by promoting the interaction of caveolin and endothelial nitric oxide synthase  

PubMed Central

Hypercholesterolemia is a central pathogenic factor of endothelial dysfunction caused in part by an impairment of endothelial nitric oxide (NO) production through mechanisms that remain poorly characterized. The activity of the endothelial isoform of NO synthase (eNOS) was recently shown to be modulated by its reciprocal interactions with the stimulatory Ca2+–calmodulin complex and the inhibitory protein caveolin. We examined whether hypercholesterolemia may reduce NO production through alteration of this regulatory equilibrium. Bovine aortic endothelial cells were cultured in the presence of serum obtained from normocholesterolemic (NC) or hypercholesterolemic (HC) human volunteers. Exposure of endothelial cells to the HC serum upregulated caveolin abundance without any measurable effect on eNOS protein levels. This effect of HC serum was associated with an impairment of basal NO release paralleled by an increase in inhibitory caveolin–eNOS complex formation. Similar treatment with HC serum significantly attenuated the NO production stimulated by the calcium ionophore A23187. Accordingly, higher calmodulin levels were required to disrupt the enhanced caveolin–eNOS heterocomplex from HC serum–treated cells. Finally, cell exposure to the low-density lipoprotein (LDL) fraction alone dose-dependently reproduced the inhibition of basal and stimulated NO release, as well as the upregulation of caveolin expression and its heterocomplex formation with eNOS, which were unaffected by cotreatment with antioxidants. Together, our data establish a new mechanism for the cholesterol-induced impairment of NO production through the modulation of caveolin abundance in endothelial cells, a mechanism that may participate in the pathogenesis of endothelial dysfunction and the proatherogenic effects of hypercholesterolemia. PMID:10079111

Feron, Olivier; Dessy, Chantal; Moniotte, Stephane; Desager, Jean-Pierre; Balligand, Jean-Luc

1999-01-01

193

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

PubMed

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

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

2013-11-30

194

Nitric Oxide and Epithelial Host Defense  

Microsoft Academic Search

This chapter describes a novel and potentially important mechanism for host defense of epithelial sufaces: the production\\u000a of reactive nitrogen oxides by the reduction of inorganic nitrate to nitrite and subsequent acidification. In addition, it\\u000a is clear that enzyme-derived NO from NOS provides antimicrobial oxides of nitrogen at mucosal surfaces in the respiratory\\u000a and gastrointestinal tracts. Whereas it is evident

Nigel Benjamin; Roelf Dykhuizen

195

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

196

Existence of nitric oxide synthase in rat hippocampal pyramidal cells.  

PubMed Central

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

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

1994-01-01

197

Nitric oxide in the upper stratosphere - Measurements and geophysical interpretation  

NASA Technical Reports Server (NTRS)

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

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

1983-01-01

198

Direct detection of radicals in intact soybean nodules: presence of nitric oxide-leghemoglobin complexes.  

PubMed

Electron paramagnetic resonance spectroscopy has been employed to examine the nature of the metal ions and radicals present in intact root nodules of soybean plants grown in the absence of nitrate. The spectra obtained from nodules of different ages using this non-invasive technique show dramatic differences, suggesting that there are both qualitative and quantitative changes in the metal ion and radical species present. A major component of the spectra obtained from young nodules is assigned to a complex (Lb-NO) of nitric oxide (NO.) with the heme protein leghemoglobin (Lb). This Lb-NO species, which has not been previously detected in intact root nodules of plants grown in the absence of nitrate, is thought to be formed by reaction of nitric oxide with iron(II) leghemoglobin. The nitric oxide may be generated from arginine via a nitric oxide synthase-like activity present in the nodules of the soybean plants, in a manner analogous to that recently described for Lupinus albus. This Lb-NO complex is present at lower concentrations in older nodules, and is almost completely absent from senescent nodules. Exposure of young and mature nodules to oxidant stress, in the form of hydrogen peroxide, results in changes in the EPR spectra, with the loss of the signals from the Lb-NO complex and appearance of absorptions similar to those from untreated senescent nodules. These results suggest that there are characteristic changes in both the metal ion complexes and radicals present in intact root nodules of different ages, and support the theory that nitric oxide and other radicals play a significant role in determining the nitrogen fixing activity of root nodules; the modulatory activity of NO. may involve regulation of gene activity. PMID:9626580

Mathieu, C; Moreau, S; Frendo, P; Puppo, A; Davies, M J

1998-05-01

199

In vivo detection of nitric oxide distribution in mice  

Microsoft Academic Search

This paper discusses in vivo detection of nitric oxide (NO) distribution in endotoxin-treated mice using L-band (1.1 GHz) electron paramagnetic resonance spectroscopy (EPR) in combination with the hydrophilic NO trapping complex: N-methyl-D-glucamine dithiocarbamate and iron (MGD-Fe). MGD-Fe-NO complex is found in the upper abdomen (liver region), lower abdomen (kidney and urinary bladder) and head region of ICR mice. Experiments with

Andrei M. Komarov

2002-01-01

200

Human Leptin Stimulates Systemic Nitric Oxide Production in the Rat  

Microsoft Academic Search

Objective: Apart from having an effect on energy balance, leptin is also involved in cardiovascular regulation and in the pathogenesis of obesity-associated hypertension. We investigated the effect of leptin on nitric oxide (NO) production.Research Methods and Procedures: Wistar rats were placed in metabolic cages, and urine was collected in 2-hour periods. After the control period, leptin (1 mg\\/kg intraperitoneal) was

Jerzy Beltowski; Gra?yna Wójcicka; Ewa Borkowska

2002-01-01

201

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

202

Regulation of cellular thiol redox status by nitric oxide  

Microsoft Academic Search

Nitric oxide (NO) is an important biological molecule that participates in a wide range of responses, including vasodilation,\\u000a platelet regulation, neurotransmission, and cytoxicity (1). NO’s most widely known and best understood mechanism of action\\u000a is through its interaction with the heme group in proteins such as soluble guanylate cyclase (1). In addition to heme iron,\\u000a NO has also been shown

Christine M. Padgett; A. Richard Whorton

1997-01-01

203

Nitric Oxide as an Alternative Electron Carrier During Oxygen Deprivation  

Microsoft Academic Search

Plant cells exposed to anaerobic stress generate copious amounts of the gaseous free radical nitric\\u000a oxide (NO). At this time, the concomitant expression of the ubiquitous class 1 plant hemoglobins establishes\\u000a one component of a soluble terminal NO dioxygenase system, which yields nitrate ions via reaction of\\u000a oxyhemoglobin with NO. Class 1 hemoglobin expression also enhances the cellular energy status,\\u000a redox status, and NO

Abir U. Igamberdiev; Kevin N. Baron; Robert D. Hill

204

Effects of Transition Metals on Nitric Oxide Synthase Catalysis  

Microsoft Academic Search

The biosynthesis of nitric oxide (NO) by the enzyme NO synthase (NOS) proceeds by the hydroxylation of L-arginine to form NG-hydroxy-L-arginine followed by the conversion of NG-hydroxy-L-arginine to L-citrulline and NO. The previously identified requirements of this relatively complicated reaction include several protein-bound cofactors: cytochrome P450-type heme, flavin mononucleotide (FMN), flavin adenine dinucleotide (FAD), and tetrahydrobiopterin (H4B). In addition to

Jason M. Perry; Michael A. Marletta

1998-01-01

205

Nitric oxide signaling in aluminum stress in plants  

Microsoft Academic Search

Nitric oxide (NO) is a ubiquitous signal molecule involved in multiple plant responses to environmental stress. In the recent\\u000a years, the regulating role of NO on heavy metal toxicity in plants is realized increasingly, but knowledge of NO in alleviating\\u000a aluminum (Al) toxicity is quite limited. In this article, NO homeostasis between its biosynthesis and elimination in plants\\u000a is presented.

Huyi He; Jie Zhan; Longfei He; Minghua Gu

206

A Community Study of Exhaled Nitric Oxide in Healthy Children  

Microsoft Academic Search

Exhaled nitric oxide (eNO) is elevated in patients with inflammatory pulmonary diseases and it has attracted increasing interest as a simple, noninvasive marker of airway inflammation. Little is known, however, about factors that might affect eNO in healthy subjects. We measured eNO in 157 healthy 7- to 13-yr-old children (mean 9.7 yr, 77 girls), with no history of respiratory tract

PETER J. FRANKLIN; ROSS TAPLIN; STEPHEN M. STICK

1999-01-01

207

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

208

Nitric oxide mediates chemoreceptor inhibition in the cat carotid body  

Microsoft Academic Search

Numerous studies have demonstrated that carotid sinus nerve fibers mediate a so-called “efferent” inhibition of carotid body chemoreceptors. However, the mechanism(s) underlying this phenomenon are not understood. Recently, it has been shown that an extensive plexus of nitric oxide synthase-containing carotid sinus nerve fibers innervate the carotid body, and that many fine, beaded fibers can be seen in close proximity

Z.-Z. Wang; L. J. Stensaas; B. G. Dinger; S. J. Fidone

1995-01-01

209

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

210

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

211

Nitric Oxide Production and Mitochondrial Dysfunction during Rat Thymocyte Apoptosis  

Microsoft Academic Search

Production of nitric oxide (NO) by mitochondrial membranes as methemoglobin formation sensitive to NG-methyl-l-arginine inhibition and mitochondrial O2 consumption in metabolic states 3 and 4 and the respiratory control (state 3\\/state 4) were measured at early stages of rat thymocyte apoptosis. Programmed cell death was induced by addition of methylprednisolone and etoposide to thymocyte suspensions. Increased NO production by mitochondrial

Juanita Bustamante; Geraldine Bersier; Marcia Romero; Romina Aron Badin; Alberto Boveris

2000-01-01

212

Arginine affects appetite via nitric oxide in ducks.  

PubMed

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

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

2014-08-01

213

The endocrine system in chronic nitric oxide deficiency.  

PubMed

The experimental model of chronic inhibition of nitric oxide (NO) production has proven to be a useful tool to study cardiovascular and renal lesions produced by this type of hypertension, which are similar to those found in human hypertension. It also offers a unique opportunity to study the interaction of NO with the humoral systems, known to have a role in the normal physiology of vascular tone and renal function. This review provides a thorough and updated analysis of the interactions of NO with the endocrine system. There is special focus on the main vasoactive factors, including the renin-angiotensin-aldosterone system, catecholamines, vasopressin, and endothelin among others. Recent discoveries of crosstalk between the endocrine system and NO are also reported. Study of these humoral interactions indicates that NO is a molecule with ubiquitous function and that its inhibition alters virtually to all other known regulatory systems. Thus, hypothyroidism attenuates the pressor effect of NO inhibitor N-nitro-L-arginine methyl ester, whereas hyperthyroidism aggravates the effects of NO synthesis inhibition; the sex hormone environment determines the blood pressure response to NO blockade; NO may play a homeostatic role against the prohypertensive effects of mineralocorticoids, thyroid hormones and insulin; and finally, NO deficiency affects not only blood pressure but also glucose and lipid homeostasis, mimicking the human metabolic syndrome X, suggesting that NO deficiency may be a link between metabolic and cardiovascular disease. PMID:17218720

Vargas, Félix; Moreno, Juan Manuel; Wangensteen, Rosemary; Rodríguez-Gómez, Isabel; García-Estañ, Joaquín

2007-01-01

214

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

PubMed

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

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

2014-12-01

215

Decoding Nitric Oxide Release Rates of Amine-Based Diazeniumdiolates  

PubMed Central

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

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

2013-01-01

216

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

Microsoft Academic Search

In this study, the design of a novel optical sensor that comprises surface plasmon resonance sensing chip and zinc oxide nano-film was proposed for the detection of nitric oxide gas. The electrical and optical properties of zinc oxide film vary in the presence of nitric oxide. This effect was utilized to prepare biochemical sensors with transduction based on surface plasmon

Wei-Yi Fenga; Nan-Fu Chiub; Hui-Hsin Lub; Hsueh-Ching Shihc; Dongfang Yangd; Chii-Wann Lina

2008-01-01

217

L-citrulline immunostaining identifies nitric oxide production sites within neurons  

NASA Technical Reports Server (NTRS)

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

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

2002-01-01

218

Effects of Aerobic Exercise on Uric Acid, Total Antioxidant Activity, Oxidative Stress, and Nitric Oxide in Human Saliva  

Microsoft Academic Search

The aim of this study was to determine the effect of aerobic exercise on uric acid (UA), total antioxidant activity (TAA), lipid hydroperoxides, and nitric oxide (NO) metabolites in human saliva. Twenty-four healthy male and female subjects were studied during a 10,000-m race. Saliva samples were collected 1 h before and immediately after exercise. The NO concentration was determined by

David González; Ramón Marquina; Norelis Rondón; Antonio J. Rodríguez-Malaver; Rafael Reyes

2008-01-01

219

A study on relationship of nitric oxide, oxidation, peroxidation, lipoperoxidation with chronic chole-cystitis.  

PubMed

AIM:To study relationship of injury induced by nitric oxide, oxidation, peroxidation,lipoperoxidation with chronic cholecystitis.METHODS:The values of plasma nitric oxide (P-NO), plasma vitamin C (P-VC), plasma vitamin E (P-VE), plasma beta-carotene (P-beta-CAR), plasma lipoperoxides (P-LPO), erythrocyte superoxide dismutase (E-SOD), erythrocyte catalase (E-CAT), erythrocyte glutathione peroxidase (E-GSH-Px) activities and erythrocyte lipoperoxides (E-LPO) level in 77 patients with chronic cholecystitis and 80 healthy control subjects were determined, differences of the above average values between the patient group and the control group and differences of the average values between preoperative and postoperative patients were analyzed and compared, linear regression and correlation of the disease course with the above determination values as well as the stepwise regression and correlation of the course with the values were analyzed.RESULTS:Compared with the control group, the average values of P-NO, P-LPO, E-LPO were significantly increased (P<0.01), and of P-VC, P-VE, P-beta-CAR, E-SOD, E-CAT and E-GSH-Px decreased (P <0.01) in the patient group. The analysis of the linear regression and correlation showed that with prolonging of the course, the values of P-NO, P-LPO and E-LPO in the patients were gradually ascended and the values of P-VC,P-VE, P-beta-CAR, E-SOD, E-CAT and E-GSH-Px descended (P<0.01). The analysis of the stepwise regression and correlation indicated that the correlation of the course with P-NO, P-VE and P-beta-CAR values was the closest. Compared with the preoperative patients, the average values of P-NO, P-LPO and E-LPO were significantly decreased (P <0.01) and the average values of P-VC, E-SOD, E-CAT and E-GSH-Px in postoperative patients increased (P <0.01) in postoperative patients. But there was no significant difference in the average values of P-VE, P-beta-CAR preoperative and postoperative patients.CONCLUSION:Chronic cholecystitis could induce the increase of nitric oxide, oxidation, peroxidation and lipoperoxidation. PMID:11819637

Zhou, Jun-Fu; Cai, Dong; Zhu, You-Gen; Yang, Jin-Lu; Peng, Cheng-Hong; Yu, Yang-Hai

2000-08-01

220

Protective role of exogenous nitric oxide against oxidative-stress induced by salt stress in barley ( Hordeum vulgare)  

Microsoft Academic Search

To probe into the potential of relieving the oxidative damage of salt stress, we investigated the protective role of nitric oxide on barley under salt stress. Salt stress resulted in increased ion leakage, lipid peroxidation and protein oxidation in barley leaves. Simultaneous treatments of barley leaves with 50?M sodium nitroprusside, a nitric oxide donor, alleviated the damage of salt stress,

Qiao-Yun Li; Hong-Bin Niu; Jun Yin; Meng-Ben Wang; Hong-Bo Shao; De-Zhi Deng; Xiao-Xia Chen; Jiang-Ping Ren; Yong-Chun Li

2008-01-01

221

The Function of Nitric Oxide in Wound Repair: Inhibition of Inducible Nitric Oxide-Synthase Severely Impairs Wound Reepithelialization  

Microsoft Academic Search

Recently, we demonstrated a large induction of inducible nitric oxide synthase (iNOS) during cutaneous wound repair. In this study, we established an in vivo model in mice to investigate the role of NO during the wound healing process. During excisional repair, mice were treated with L-N6-(1-iminoethyl)lysine (L-NIL), a selective inhibitor of iNOS enzymatic activity. Compared with control mice, L-NIL-treated animals

Birgit Stallmeyer; Heiko Kämpfer; Nicole Kolb; Josef Pfeilschifter; Stefan Frank

1999-01-01

222

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

223

Nitric-phosphoric acid oxidation of organic waste materials  

SciTech Connect

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

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

1995-11-01

224

REDUCTION OF NITRIC OXIDE WITH METAL SULFIDES  

EPA Science Inventory

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

225

Aerodynamic influences on nasal nitric oxide output measurements.  

PubMed

Nitric oxide (NO) concentration in aspirated nasal air is flow-dependent. Nasal NO outputs calculated from steady-state plateaux at flows < 1 l/min are substantially smaller than those at flows > 2 l/min. This study aimed to determine the differences in NO output as calculated from the NO concentration plateaux in aspirated nasal air, resulting from different aspiration flows. Nasal NO was determined by chemiluminescent analysis of air obtained from the nasal passages in series during velopharyngeal closure in 8 healthy adults (flows: 0.2-3.7 l/min) and 5 with symptomatic allergic rhinitis (flows: 0.2-3.7 l/min). Mean NO output in the healthy subjects was stable at approximately 315 nl/l/min at flows of 0.2-0.7 l/min, and increased to a second steady output level of approximately 400 nl/l/min (+28%, p < 0.0001) at more physiological flow rates of 2.7 l/min and higher. The symptomatic subjects had substantially higher NO output at all flows (p < 0.001) (709.3 nl/min at 3.7 l/min) than the non-allergic subjects. The flow dependency of the nasal NO output may be explained by failure at low flows for the air stream to penetrate the peripheral parts of the complex nasal passages, and by the presence of a laminar flow regime in which a marginal lamina would tend to insulate the main stream from the mucosa. Thus, previously reported NO outputs obtained at low flows may underestimate nasal NO output compared to output at higher and more physiological transnasal airflow rates, thus affecting interpretation of results. PMID:10445065

Djupesland, P G; Chatkin, J M; Qian, W; Cole, P; Zamel, N; McClean, P; Furlott, H; Haight, J S

1999-01-01

226

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. PMID:9456484

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

1997-01-01

227

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

228

A small amount of inhaled nitric oxide does not increase lung diffusing capacity  

Microsoft Academic Search

The aim of the present study was to determine: 1) whether 40-50 ppm nitric oxide (NO) increases diffusing capacity of the lung for NO (DL,NO) and carbon monoxide (DL,CO), membrane diffusing capacity for CO (Dm,CO) and pulmonary capillary blood volume (Vc); 2) the actual number of tests required to provide a reasonable estimate of DL,NO, DL,CO, Dm,CO and Vc; and

G. S. Zavorsky; J. M. Murias

2006-01-01

229

Atrial Natriuretic Peptide Modifies Arterial Blood Pressure Through Nitric Oxide Pathway in Rats  

Microsoft Academic Search

The aim of the present study was to determine the relationship between the hypotensive effect of the atrial natriuretic peptide (ANP) and the nitric oxide (NO) pathway. NG-nitro-L-arginine methyl ester bolus (L-NAME, 1 mg\\/kg) reverted the decrease in mean arterial pressure induced by ANP administration (5 mg\\/kg bolus and 0.2 mg z kg21 z min21 infusion), and the injection of

Monica P. Majowicz; Norberto A. Vidal; Ana M. Balaszczuk; Cristina T. Arranz

230

Plasma Nitric Oxide Products Correlate with Cardiac Index of Congenital Heart Disease  

Microsoft Academic Search

.   We wished to determine the relationship between circulating levels of nitric oxide (NO) and cardiac index (CI) in children\\u000a with congenital heart diseases. We measured the plasma levels of nitrate\\/nitrite (NO\\u000a x\\u000a ), the stable end products of NO production as well as tumor necrosis factor-? (TNF-?), atrial natriuretic peptide (ANP),\\u000a and brain natriuretic peptide in relation to various

J. Takaya; Y. Ikemoto; M. Teraguchi; S. Nogi; Y. Kobayashi

2000-01-01

231

Nitric oxide production in hypothalamus of 2-deoxy- d-glucose-treated and food deprived mice  

Microsoft Academic Search

Nitric oxide (NO) has been suggested to be involved in the regulation of food intake. In the present study, NO metabolite (nitrite and nitrate, NOx) levels in the hypothalamus were determined in hyperphagic mice. In normal mice, NOx levels were higher in the hypothalamus than those in frontal cortex. Although 2-deoxy-d-glucose (2-DG) is known to induce hyperphagia by inhibiting glucose

Jun Yamada; Hiroshi Hirose; Yumi Sugimoto

2002-01-01

232

Mechanism of impaired nitric oxide synthase activity in skeletal muscle of streptozotocin-induced diabetic rats  

Microsoft Academic Search

Aims\\/hypothesis. The aims of our study were to investigate whether nitric oxide synthase (NOS) activity is impaired in skeletal muscle of\\u000a insulin-deficient [Type I (insulin-dependent)] diabetic rats and if the case, to determine the mechanism of NOS dysregulation\\u000a in this disorder.¶Methods. Rats were rendered diabetic by streptozotocin injection (65 mg\\/kg, i. v.) and NOS activity and expression in gastrocnemius\\u000a muscles

M. Perreault; L. Dombrowski; A. Marette

2000-01-01

233

Long-term blockade of nitric oxide synthesis in rats modulates coronary capillary network remodeling  

Microsoft Academic Search

Long-term blockade of nitric oxide synthesis with N?-nitro-L-arginine methyl ester (L-NAME) induces cardiac perivascular fibrosis in rats. Its relationship to expression of angiogenic\\u000a growth factors and capillary network remodeling is not understood. This study was designed to determine whether capillary\\u000a proliferation and angiogenic growth factor regulation occur in response to L-NAME. Three groups of rats were studied: C, control;\\u000a L1,

Daisuke Goto; Satoshi Fujii; A. K. M. Tarikuz Zaman; Ichiro Sakuma; Ming Gao; Tomiyasu Koyama; John Mitchell; Janet Woodcock-Mitchell; Burton E. Sobel; Akira Kitabatake

1999-01-01

234

Shear Stress Regulates Endothelial Nitric-oxide Synthase Promoter Activity through Nuclear Factor B Binding  

Microsoft Academic Search

We have previously demonstrated that shear stress increases transcription of the endothelial nitric-oxide synthase (eNOS) by a pathway involving activation of the tyrosine kinase c-Src and extracellular signal-re- lated kinase 1\\/2 (ERK1\\/2). In the present study sought to determine the events downstream of this pathway. Shear stress activated a human eNOS promoter chlor- amphenicol acetyl-CoA transferase chimeric construct in a

Michael E. Davis; Isabella M. Grumbach; Tohru Fukai; Alexis Cutchins; David G. Harrison

2004-01-01

235

The role of nitric oxide in the pathophysiology of thromboembolic stroke in the rat  

Microsoft Academic Search

Although nitric oxide (NO) has been shown to play an important role in the pathophysiology of cerebral ischemia, its contribution to the pathogenesis of experimentally induced thromboembolic stroke is unknown. In this study, we pharmacologically manipulated NO levels in the acute post-thrombotic stage and determined the effects on behavior and histopathology. The following drugs were used: nitro-l-arginine-methyl ester (l-NAME), a

N. E Stagliano; W. D Dietrich; R Prado; E. J Green; R Busto

1997-01-01

236

Flow-dependency of exhaled nitric oxide in children with asthma and cystic fibrosis  

Microsoft Academic Search

The concentration of nitric oxide in exhaled air, a marker of airway\\u000a inflammation, depends critically on the flow of exhalation. Therefore, the\\u000a aim of this study was to determine the effect of varying the flow on\\u000a end-expiratory NO concentration and NO output in children with asthma or\\u000a cystic fibrosis (CF) and in healthy children. Nineteen children with\\u000a stable asthma, 10

A. Kroesbergen; Q. Jobsis; E. H. D. Bel; W. C. J. Hop; Jongste de J. C

1999-01-01

237

Conjugated linoleic acid improves blood pressure by increasing adiponectin and endothelial nitric oxide synthase activity  

Microsoft Academic Search

Conjugated linoleic acid (CLA) has been reported to reduce blood pressure in obese insulin-resistant rats, but its mechanism of action has not been identified. The objective of this study was to determine whether CLA isomers can reduce obesity-related hypertension in the fa\\/fa Zucker rat in relation to adiponectin production and endothelial nitric oxide synthase (eNOS) activation. Obese fa\\/fa Zucker rats

Vanessa DeClercq; Carla G. Taylor; Jeffrey Wigle; Brenda Wright; Leslee Tworek; Peter Zahradka

238

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

239

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

240

Induction and Regulation of Nitric Oxide Synthase in Airway Epithelial Cells by Respiratory Syncytial Virus  

Microsoft Academic Search

In this study, we evaluated the effects of respiratory syncytial virus (RSV) infection on nitric oxide (NO) production in human airway epithelial cells. In addition, we evaluated whether T-helper type 1 (Th1)- and Th2-type cytokines modulate the release of NO in re- sponse to RSV infection. To do this, we infected monolayers of A549 cells with RSV and determined nitrite

YACHU J. KAO; PEDRO A. PIEDRA; GARY L. LARSEN; GIUSEPPE N. COLASURDO

2001-01-01

241

Nitric Oxide Plasma Sources for Bio-Decontamination and Plasma Therapy  

NASA Astrophysics Data System (ADS)

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

Vasilets, Victor N.; Shekhter, Anatoly B.

242

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

PubMed Central

Catalytically active endothelial nitric oxide synthase (eNOS) is located on the Golgi complex and in the caveolae of endothelial cells (EC). Mislocalization of eNOS caused by mutation of the N-myristoylation or cysteine palmitoylation sites impairs production of stimulated nitric oxide (NO), suggesting that intracellular targeting is critical for optimal NO production. To investigate the molecular determinants of eNOS targeting in EC, we constructed eNOS–green fluorescent protein (GFP) chimeras to study its localization in living and fixed cells. The full-length eNOS–GFP fusion colocalized with a Golgi marker, mannosidase II, and retained catalytic activity compared to wild-type (WT) eNOS, suggesting that the GFP tag does not interfere with eNOS localization or function. Experiments with different size amino-terminal fusion partners coupled to GFP demonstrated that the first 35 amino acids of eNOS are sufficient to target GFP into the Golgi region of NIH 3T3 cells. Additionally, the unique (Gly-Leu)5 repeat located between the palmitoylation sites (Cys-15 and -26) of eNOS is necessary for its palmitoylation and thus localization, but not for N-myristoylation, membrane association, and NOS activity. The palmitoylation-deficient mutants displayed a more diffuse fluorescence pattern than did WT eNOS–GFP, but still were associated with intracellular membranes. Biochemical studies also showed that the palmitoylation-deficient mutants are associated with membranes as tightly as WT eNOS. Mutation of the N-myristoylation site Gly-2 (abolishing both N-myristoylation and palmitoylation) caused the GFP fusion protein to distribute throughout the cell as GFP alone, consistent with its primarily cytosolic nature in biochemical studies. Therefore, eNOS targets into the Golgi region of NIH 3T3 cells via the first 35 amino acids, including N-myristoylation and palmitoylation sites, and its overall membrane association requires N-myristoylation but not cysteine palmitoylation. These results suggest a novel role for fatty acylation in the specific compartmentalization of eNOS and most likely, for other dually acylated proteins, to the Golgi complex. PMID:9199168

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

1997-01-01

243

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

244

Dysfunctional nitric oxide signalling increases risk of myocardial infarction.  

PubMed

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

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

2013-12-19

245

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.

2008-02-01

246

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

PubMed Central

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

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

2013-01-01

247

Pterins inhibit nitric oxide synthase activity in rat alveolar macrophages.  

PubMed Central

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

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

1992-01-01

248

Nitric Oxide in Cerebral Vasospasm: Theories, Measurement, and Treatment  

PubMed Central

In recent decades, a large body of research has focused on the role of nitric oxide (NO) in the development of cerebral vasospasm (CV) following subarachnoid hemorrhage (SAH). Literature searches were therefore conducted regarding the role of NO in cerebral vasospasm, specifically focusing on NO donors, reactive nitrogen species, and peroxynitrite in manifestation of vasospasm. Based off the assessment of available evidence, two competing theories are reviewed regarding the role of NO in vasospasm. One school of thought describes a deficiency in NO due to scavenging by hemoglobin in the cisternal space, leading to an NO signaling deficit and vasospastic collapse. A second hypothesis focuses on the dysfunction of nitric oxide synthase, an enzyme that synthesizes NO, and subsequent generation of reactive nitrogen species. Both theories have strong experimental evidence behind them and hold promise for translation into clinical practice. Furthermore, NO donors show definitive promise for preventing vasospasm at the angiographic and clinical level. However, NO augmentation may also cause systemic hypotension and worsen vasospasm due to oxidative distress. Recent evidence indicates that targeting NOS dysfunction, for example, through erythropoietin or statin administration, also shows promise at preventing vasospasm and neurotoxicity. Ultimately, the role of NO in neurovascular disease is complex. Neither of these theories is mutually exclusive, and both should be considered for future research directions and treatment strategies. PMID:23878735

Siuta, Michael; Zuckerman, Scott L.; Mocco, J.

2013-01-01

249

Evidence that nitric oxide modulates food intake in mice  

SciTech Connect

Nitric oxide (NO) may be an intracellular modulator within the central nervous system. L-arginine, which results in NO synthesis, increased food intake in mice while the inhibitor of NO synthesis, L-N{sup G}-nitro arginine (L-NO Arg) inhibited food intake in food deprived mice. L-arginine, but not D-arginine, partially reverse the inhibitory effect of L-NO Arg on food intake. These findings suggest the possibility that NO may be a physiological modulator of food intake and that the possibility of exploring the utility of L-NO arg in the treatment of obesity should be explored.

Morley, J.E.; Flood, J.F. (St. Louis Univ., MO (United States))

1991-01-01

250

Flavanols, the Kuna, Cocoa Consumption, and Nitric Oxide  

PubMed Central

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

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

2013-01-01

251

The Moving Frontier in Nitric Oxide-Dependent Signaling  

NSDL National Science Digital Library

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

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

2004-11-02

252

Nitric oxide modulation as a therapeutic strategy in heart failure.  

PubMed

Nitric oxide (NO) is recognized as one of the most important cardiovascular signaling molecules, with multiple regulatory effects on myocardial and vascular tissue as well as on other tissues and organ systems. With the growth in understanding of the range and mechanisms of NO effects on the cardiovascular system, it is now possible to consider pharmaceutical interventions that directly target NO or key steps in NO effector pathways. This article reviews aspects of the cardiovascular effects of NO, abnormalities in NO regulation in heart failure, and clinical trials of drugs that target specific aspects of NO signaling pathways. PMID:22405665

Taylor, Anne L

2012-04-01

253

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

NASA Technical Reports Server (NTRS)

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

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

1986-01-01

254

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

255

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

NASA Technical Reports Server (NTRS)

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

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

1998-01-01

256

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

NASA Technical Reports Server (NTRS)

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

Reid, Ian A.

1994-01-01

257

Nitric Oxide Synthase: Non-Canonical Expression Patterns  

PubMed Central

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

Mattila, Joshua T.; Thomas, Anita C.

2014-01-01

258

Hyperbaric oxygen upregulates cochlear constitutive nitric oxide synthase  

PubMed Central

Background Hyperbaric oxygen therapy (HBOT) is a known adjuvant for treating ischemia-related inner ear diseases. Controversies still exist in the role of HBOT in cochlear diseases. Few studies to date have investigated the cellular changes that occur in inner ears after HBOT. Nitric oxide, which is synthesized by nitric oxide synthase (NOS), is an important signaling molecule in cochlear physiology and pathology. Here we investigated the effects of hyperbaric oxygen on eardrum morphology, cochlear function and expression of NOS isoforms in cochlear substructures after repetitive HBOT in guinea pigs. Results Minor changes in the eardrum were observed after repetitive HBOT, which did not result in a significant hearing threshold shift by tone burst auditory brainstem responses. A differential effect of HBOT on the expression of NOS isoforms was identified. Upregulation of constitutive NOS (nNOS and eNOS) was found in the substructures of the cochlea after HBOT, but inducible NOS was not found in normal or HBOT animals, as shown by immunohistochemistry. There was no obvious DNA fragmentation present in this HBOT animal model. Conclusions The present evidence indicates that the customary HBOT protocol may increase constitutive NOS expression but such upregulation did not cause cell death in the treated cochlea. The cochlear morphology and auditory function are consequently not changed through the protocol. PMID:21342510

2011-01-01

259

Inducible nitric oxide synthase--time for reappraisal.  

PubMed

Inducible nitric oxide synthase (iNOS) is one of three key enzymes generating nitric oxide (NO) from the amino acid L-arginine. iNOS-derived NO plays an important role in numerous physiological and pathophysiological conditions, e.g. blood pressure regulation, inflammation, infection, and the onset and progression of malignant diseases. iNOS has been conjectured both as a marker and a therapeutic target in these situations. iNOS is a mediator of unspecific host defence, central in the clearance of bacterial, viral, fungal and parasitic infections. However, excess production of NO appears to be linked to tissue damage and organ dysfunction, e.g. the hypotensive and vasoplegic state characteristic for septic shock. However, the use of iNOS-inhibitors in septic patients should be performed carefully with regard to the essential functions and properties of NO in blood pressure/blood flow regulation. Considering iNOS-derived NO as a multifactorial transmitter of tumorigenesis and tumor progression, it is tempting to speculate on therapeutical interference with iNOS activity, especially in tumors where metastatic activity, host denfence mechanisms and the level of differentiation seem to be correlated to iNOS expression. It is the aim of this review to provide basic insights into the NOS family of enzymes as well as their regulation. In the second part of the review, we will point out the pivotal roles NOS play in inflammation and neoplastic diseases. PMID:14561209

Lirk, Philipp; Hoffmann, Georg; Rieder, Josef

2002-03-01

260

Downregulation of endothelial constitutive nitric oxide synthase expression by lipopolysaccharide.  

PubMed

Lipopolysaccharide (LPS), a causal agent of sepsis, has been shown to induce systemic nitric oxide (NO) synthesis through complex mechanisms. However, the effect of LPS on endothelial cells is incompletely understood. To investigate the mechanism by which LPS influences the release of NO from endothelial cells, the effect of this compound on endothelial constitutive nitric oxide synthase (ecNOS) was studied in cultured bovine coronary venular endothelial cells. Western and Northern analyses showed that LPS decreased ecNOS expression at the protein and mRNA levels in a time-dependent and dose-responsive manner. Concurrent treatment of the endothelial cells with LPS and a transcription inhibitor, actinomycin D, resulted in decreased ecNOS mRNA within 8 hours. In contrast, treatment with actinomycin D had only a relatively insignificant effect on the ecNOS transcript level. This result suggests that the reduction of ecNOS by LPS resulted from an increased degradation rate of its transcript. PMID:8769085

Lu, J L; Schmiege, L M; Kuo, L; Liao, J C

1996-08-01

261

Endothelial nitric oxide synthase transgenic models of endothelial dysfunction  

PubMed Central

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

Atochin, Dmitriy N.; Huang, Paul L.

2010-01-01

262

Exploring vascular benefits of endothelium-derived nitric oxide.  

PubMed

Although the regulation of arterial blood flow has been a subject of intensive medical research, the precise circulatory mechanisms involved are still not fully understood. It has been increasingly recognized that the endothelium plays a vital role in regulating vascular tone, structure, and function. A seminal discovery was made with the identification of endothelium-derived relaxing factor, a key mediator of vasodilation, which was later identified as nitric oxide (NO). Nitric oxide is synthesized from the amino acid L-arginine in the endothelium. Decreased bioavailability of NO is associated with arterial stiffness, hypertension, atherosclerosis, and cardiovascular disease (CVD). Nebivolol is a novel beta-blocker that is highly selective for beta1-adrenergic receptors. Nebivolol also causes vasodilation through a mechanism involving endothelium-derived NO. In clinical studies in hypertensive subjects, nebivolol significantly improves vasodilator responses to endothelium-dependent agonists such as acetylcholine. In addition, nebivolol significantly reduces pulse wave velocity (PWV), a measure of arterial stiffness, whereas the beta-blocker atenolol has no effect on PWV. Because endothelial dysfunction and arterial stiffness play an integral part in the early atherosclerotic process and are associated with poor outcomes and increased mortality, independent of blood pressure, the ability of nebivolol to enhance release of endothelium-derived NO may have significant clinical implications for the use of this agent in the treatment of hypertension and CVD. PMID:16373196

Cockcroft, John R

2005-12-01

263

Exhaled nitric oxide in diagnosis and management of respiratory diseases  

PubMed Central

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

Abba, Abdullah A.

2009-01-01

264

Nitric oxide signaling contributes to ectopic orofacial neuropathic pain.  

PubMed

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

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

2013-12-01

265

Nitric oxide production and mitochondrial dysfunction during rat thymocyte apoptosis.  

PubMed

Production of nitric oxide (NO) by mitochondrial membranes as methemoglobin formation sensitive to N(G)-methyl-l-arginine inhibition and mitochondrial O(2) consumption in metabolic states 3 and 4 and the respiratory control (state 3/state 4) were measured at early stages of rat thymocyte apoptosis. Programmed cell death was induced by addition of methylprednisolone and etoposide to thymocyte suspensions. Increased NO production by mitochondrial membranes was observed after 30 min of methylprednisolone and etoposide addition and was accompanied by mitochondrial respiratory impairment as an early phenomenon in apoptotic thymocytes. The respiratory control in isolated mitochondria from untreated thymocytes was 4.2 +/- 0.2 and decreased to 3.1 +/- 0.2 and 1.9 +/- 0.3 after 1 h of methylprednisolone and etoposide treatment, respectively. The low mitochondrial respiratory control was accompanied by a marked decrease in GSH and cytochrome c content. Moreover, an inhibitory effect in the amount of apoptosis due to thymocyte pretreatment with N(G)-methyl-l-arginine and N(omega)-nitro-(l)-arginine (l-NNA), indicate that nitric oxide production is closely involved in the signaling of rat thymocyte apoptosis. PMID:10775408

Bustamante, J; Bersier, G; Romero, M; Badin, R A; Boveris, A

2000-04-15

266

Selective catalytic reduction (SCR) of nitric oxide (NO) with ammonia over vanadia-based and pillared interlayer clay-based catalysts  

E-print Network

. The experiments used a number of gas compositions to simulate different combustion gases. A Fourier transform infrared (FTIR) spectrometer was used to determine the concentrations of the product species. The major products were nitric oxide (NO), ammonia (NH 3...

Oh, Hyuk Jin

2004-09-30

267

Evidence for involvement of nitric oxide and GABAB receptors in MK-801- stimulated release of glutamate in rat prefrontal cortex  

PubMed Central

Systemic administration of NMDA receptor antagonists elevates extracellular glutamate within prefrontal cortex. The cognitive and behavioral effects of NMDA receptor blockade have direct relevance to symptoms of schizophrenia, and recent studies demonstrate an important role for nitric oxide and GABAB receptors in mediating the effects of NMDA receptor blockade on these behaviors. We sought to extend those observations by directly measuring the effects of nitric oxide and GABAB receptor mechanisms on MK-801-induced glutamate release in the prefrontal cortex. Systemic MK-801 injection (0.3 mg/kg) to male Sprague-Dawley rats significantly increased extracellular glutamate levels in prefrontal cortex, as determined by microdialysis. This effect was blocked by pretreatment with the nitric oxide synthase inhibitor L-NAME (60 mg/kg). Reverse dialysis of the nitric oxide donor SNAP (0.5 – 5 mM) directly into prefrontal cortex mimicked the effect of systemic MK-801, dose-dependently elevating cortical extracellular glutamate. The effect of MK-801 was also blocked by systemic treatment with the GABAB receptor agonist baclofen (5 mg/kg). In combination, these data suggest increased nitric oxide formation is necessary for NMDA antagonist-induced elevations of extracellular glutamate in the prefrontal cortex. Additionally, the data suggest GABAB receptor activation can modulate the NMDA antagonist-induced increase in cortical glutamate release. PMID:22579658

Roenker, Nicole L.; Gudelsky, Gary A.; Ahlbrand, Rebecca; Horn, Paul S.; Richtand, Neil M.

2012-01-01

268

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

Microsoft Academic Search

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

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

1998-01-01

269

Nitric oxide-mediated metabolic regulation during exercise: effects of training in health and cardiovascular disease  

Microsoft Academic Search

Accumulating data suggest that nitric oxide (NO) is important for both coronary and peripheral hemodynamic control and metabolic reg- ulation during exercise. Although still controversial, NO of endothelial origin may potentiate exercise- induced hyperemia. Mechanisms of release include both acetylcholine derived from the neuromuscular junction and elevation in vascular shear stress. A splice variant of neuronal nitric oxide synthase (NOS),

BRONWYN A. KINGWELL

2000-01-01

270

Xanthine oxidoreductase catalyses the reduction of nitrates and nitrite to nitric oxide under hypoxic conditions  

Microsoft Academic Search

Xanthine oxidoreductase (XOR) catalyses the reduction of the therapeutic organic nitrate, nitroglycerin (glyceryl trinitrate, GTN), as well as inorganic nitrate and nitrite, to nitric oxide (NO) under hypoxic conditions in the presence of NADH. Generation of nitric oxide is not detectable under normoxic conditions and is inhibited by the molybdenum site-specific inhibitors, oxypurinol and (?)BOF 4272. These enzymic reactions provide

Timothy M Millar; Cliff R Stevens; Nigel Benjamin; Robert Eisenthal; Roger Harrison; David R Blake

1998-01-01

271

The Effect of Nuclear Explosions on Stratospheric Nitric Oxide and Ozone  

Microsoft Academic Search

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

Harold Johnston; Garry Whitten; John Birks

1973-01-01

272

Effects of Nitric Oxide on the Horizontal Cell Network and Dopamine Release in the Carp Retina  

Microsoft Academic Search

In the teleost retina the intercellular messenger nitric oxide can be synthesized by several cell types including cone photoreceptors and H1 horizontal cells, indicating a modulatory role within the outer plexiform layer, the first stage of the visual information processing. Therefore, the aim of this study was to elucidate the effects of nitric oxide on the physiology of cone horizontal

MARK POTTEK; KONRAD SCHULTZ; RETO WEILER

1997-01-01

273

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

Microsoft Academic Search

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

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

1995-01-01

274

[The influence of geomagnetic variations on the formation of nitric oxide in exhaled air in human].  

PubMed

The content of nitric oxide in exhaled air in healthy persons has been studied. It was shown that nitric oxide in exhaled air is formed from saliva nitrite due to the nitrite reductase activity of mouth cavity microflora. A relationship between the nitric oxide level and age, arterial pressure, and geomagnetic field indices was established. It was shown that the level of nitric oxide diminishes with age. A negative correlation between the nitric oxide content in exhaled air and arterial pressure (systolic and diastolic) was found. It was assumed that nitric oxide from the mouth can penetrate into the lungs and then to the blood where it can influence the vessel tonus. It was shown that the negative relationship took place between nitric oxide level in the air and Ki-indices of geomagnetic field on the day of measurement or the day preceding the measurement. The data obtained suggest that nitric oxide is involved in processes causing infarcts and insults in periods of magnetic storms. PMID:17907415

Iamshanov, V A; Koshelevski?, V K

2007-01-01

275

Nitric Oxide Inhibits Metamorphosis in Larvae of Crepidula fornicata, the Slippershell Snail  

E-print Network

Nitric Oxide Inhibits Metamorphosis in Larvae of Crepidula fornicata, the Slippershell Snail JAN A metamorphosis in the marine gastropod Crepidula fornicata. Metamorphosis was stimulated by the nitric oxide) at concentrations of about 100­1000 mol l 1 and 50­200 mol l 1 , respectively. Metamorphosis was not, however

276

Altered messenger RNA expression of the neuronal nitric oxide synthase gene in infantile hypertrophic pyloric stenosis  

Microsoft Academic Search

Nitric oxide (NO) has been described as a mediator of smooth muscle relaxation in the mammalian gastrointestinal tract. The enzyme neuronal nitric oxide synthase (NOS) catalyzes the formation of NO. We examined the expression of the neuronal NOS gene at the messenger RNA (mRNA) level in pyloric smooth-muscle biopsy specimens from six patients with infantile hypertrophic pyloric stenosis (IHPS) using

T. Kusafuka; P. Puri

1997-01-01

277

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

Microsoft Academic Search

The objective of this study was to deter- mine the role of nitric oxide in muscle inflamma- tion, fiber necrosis, and apoptosis of inflammatory cells in vivo. The effects of nitric oxide synthase (NOS) inhibition on the concentrations of neutro- phils, ED11 and ED21 macrophages, apoptotic inflammatory cells, and necrotic muscle fibers in rats subjected to 10 days of hindlimb

Francis X. Pizza; Israel J. Hernandez; James G. Tidball

1998-01-01

278

Activation of renin synthesis is dependent on intact nitric oxide production  

Microsoft Academic Search

Activation of renin synthesis is dependent on intact nitric oxide production. The present study investigated whether or not nitric oxide (NO) synthesis mediates mechanisms regulating activation of renin formation. Studies were performed on afferent arterioles freshly isolated from the rat kidney. We have shown previously that this preparation is a useful model to study regulation of renin synthesis and secretion.

Pierre-Louis Tharaux; Jean-Claude Dussaule; Marie-Dominique Pauti; Yves Vassitch; Raymond Ardaillou; Christos Chatziantoniou

1997-01-01

279

Memory consolidation of Pavlovian fear conditioning requires nitric oxide signaling in the lateral amygdala  

E-print Network

Memory consolidation of Pavlovian fear conditioning requires nitric oxide signaling in the lateral Nitric oxide (NO) has been widely implicated in synaptic plasticity and memory formation. In studies of long-term potentiation (LTP), NO is thought to serve as a `retrograde messenger' that contributes

Schafe, Glenn

280

Regulation of Endothelial Nitric Oxide Synthase and Postnatal Angiogenesis by Rac1  

Microsoft Academic Search

Diminished bioavailability of nitric oxide is a hallmark of endothelial dysfunction and is associated with a broad spectrum of vascular disorders such as impaired angiogenesis. Because Rac1, a Rho family member, mediates cellular motility and generation of reactive oxygen species, it could be involved in the regulation of endothelial nitric oxide production. However, the pathophysiological consequences of postnatal endothelial Rac1

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

2010-01-01

281

Inhaled nitric oxide therapy in neonatal hypoxic respiratory failure: insights beyond primary outcomes  

Microsoft Academic Search

The Neonatal Research Network developed and initiated 3 multicenter randomized controlled clinical trials evaluating inhaled nitric oxide therapy. Additional projects evolved from these efforts including basic science research and observational investigations. This article provides a historical prospective of the Network’s investigations related to the diagnosis and management of neonatal hypoxic respiratory failure, especially those related to inhaled nitric oxide therapy.

Gregory M Sokol; Richard A Ehrenkranz

2003-01-01

282

Neuronal Nitric Oxide Synthase in the Canine Prostate: Aging, Sex Steroid, and Pathology Correlations  

Microsoft Academic Search

Nitric oxide synthase (NOS) is expressed in the pros- tate of various species, including humans. NOS catalyzes the pro- duction of nitric oxide (NO), which may function in prostatic smooth- muscle relaxation. To investigate further the role of NO in the pros- tate, we examined neuronal NOS expression in the aging canine prostate, after hormonal perturbation, and correlated these results

JULIE K. CRONE; ARTHUR L. BURNETF; SHELLY L. CHAMNESS; JOHN D. STRANDBERG; THOMAS S. K. CHANG

1998-01-01

283

Joule heating and nitric oxide in the thermosphere C. A. Barth,1  

E-print Network

Joule heating and nitric oxide in the thermosphere C. A. Barth,1 G. Lu,2 and R. G. Roble2 Received] The effect of Joule heating on the density of nitric oxide in the thermosphere was studied using observations Ionosphere Electrodynamics General Circulation Model for a Joule heating event that occurred on 25 September

Bailey, Scott

284

Regulation of Endothelial Nitric Oxide Synthase and Postnatal Angiogenesis by Rac1  

PubMed Central

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

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

2008-01-01

285

Photopromoted and Thermal Decomposition of Nitric Oxide by Metal Oxides.  

National Technical Information Service (NTIS)

This technical report summarizes research on decomposition of NOx by photopromoted and thermal solid-catalyzed decomposition of NO. Typical catalysts incorporated one or more metal oxides. Photopromotion of catalytic activity was observed with several cat...

E. Berman, J. Dong, N. N. Lichtin

1992-01-01

286

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

E-print Network

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

Wogan, Gerald N.

287

Human vascular smooth muscle cells inhibit platelet aggregation when incubated with glyceryl trinitrate: evidence for generation of nitric oxide.  

PubMed Central

1. The effect on platelet aggregation of glyceryl trinitrate in the presence of cultured vascular smooth muscle cells was determined turbidometrically. U46619 (a thromboxane mimetic) was used as agonist and experiments were performed in the presence of aspirin. Inorganic nitrite production from glyceryl trinitrate by vascular smooth muscle cells was also measured, to provide an indirect index of nitric oxide synthesis. 2. The combination of vascular smooth muscle cells together with glyceryl trinitrate, at concentrations that had little effect individually, profoundly inhibited platelet aggregation. 3. The inhibitory effect on platelet aggregation of vascular smooth muscle cells together with glyceryl trinitrate was markedly attenuated by haemoglobin, an inhibitor of nitric oxide. 4. These results show that vascular smooth muscle cells inhibit platelet aggregation when exposed to glycerol trinitrate and suggest that this is due to generation of nitric oxide from glyceryl trinitrate by vascular smooth muscle. PMID:1906768

Benjamin, N.; Dutton, J. A.; Ritter, J. M.

1991-01-01

288

ATMOS observations of nitric oxide in the mesosphere and lower thermosphere  

NASA Astrophysics Data System (ADS)

The nitric oxide density in the Earth's atmosphere between 50 and 130 km was measured by the ATMOS (Atmospheric Trace Molecule Spectroscopy) experiment onboard the Spacelab 3 mission on April 30, 1985 and May 1, 1985. Three observations were made at geographic latitudes of 35°N, 34°N, and 29°N which correspond to geomagnetic latitudes of 26°N, 44°N, and 39°N. The ATMOS measurements of nitric oxide in the thermosphere were compared to SME measurements made during the same time period. The two techniques agree within the geophysical variability of thermospheric nitric oxide. The observations show that during a geomagnetic storm there is a strong latitudinal gradient in the nitric oxide density in the lower thermosphere. Comparison of the observations with a one-dimensional time-dependent model shows that at midlatitudes, nitric oxide is transported downward from the thermosphere into the mesosphere as low as 70 km but not downward into the stratosphere.

Barth, Charles A.; Farmer, Crofton B.; Siskind, David E.; Perich, Jeffrey P.

1996-05-01

289

[Effect of nitric oxide on expression of apoptotic genes and HSP70 in Drosophila].  

PubMed

Abstract-Data on involvement of nitric oxide in apoptosis are contradictory. The balance between anti- and proapoptotic activities of nitric oxide depends on many factors, including its concentration in a tissue and interactions with other regulators of apoptosis. This paper describes the results of a series of experiments on the effect of nitric oxide donors and inhibitors as well as dNOS1 and dNOS4 transgenes on the apoptosis on drosophila LobRSV mutant strain and wild-type strain Oregon R. It has been shown that a high nitric oxide content in cells is able to inhibit antiapoptotic effect of HSP70 and stimulate apoptosis, possibly, via the grim-mediated apoptotic pathway. Moreover, long-term action of a high nitric oxide concentration during the entire development more efficiently stimulates the proapoptotic genes as compared with short-term action of this agent. PMID:22288105

Dzhansugurova, L B

2011-01-01

290

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

PubMed Central

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

Yuksel, Meral; Okur, Hacer Kuzu; Pelin, Zerrin; Ogunc, Ayliz Velioglu; Ozturk, Levent

2014-01-01

291

Protective role of nitric oxide during hydrogen peroxide-induced oxidative stress in tobacco plants  

Microsoft Academic Search

Nitric oxide, produced from exogenous NO donor, sodium nitroprusside, and hydrogen peroxide exerted antagonistic effects on\\u000a tobacco leaves at micromolar concentrations but induced synergistic effects at millimolar concentrations. During H2O2-induced oxidative stress, low concentrations of NO inhibited lipid peroxidation, counteracted the fragmentation of total\\u000a DNA, and prevented accumulation of soluble proteins in Nicotiana plumbaginifolia cells. When applied at high concentrations,

L. V. Dubovskaya; E. V. Kolesneva; D. M. Knyazev; I. D. Volotovskii

2007-01-01

292

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

PubMed Central

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

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

2014-01-01

293

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

Microsoft Academic Search

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

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

2010-01-01

294

Protective effect of exogenously applied nitric oxide on aluminum-induced oxidative stress in soybean plants  

Microsoft Academic Search

Aluminum (Al) toxicity promotes oxidative damage in plants, while nitric oxide (NO) may exert a beneficial effect on Al toxicity\\u000a condition in soybean. Pretreatment with NO donor sodium nitroprusside (SNP) before soybean exposure to Al significantly reduced\\u000a Al accumulation and MDA induction in the root apex. Pretreatment with SNP also increased the relative root elongation, chlorophyll\\u000a content, and activity of

M. Z. Cai; S. N. Zhang; F. M. Wang; N. Wang; S. Y. Xu

2011-01-01

295

Modeling nitric oxide emissions from biosolid amended soils  

NASA Astrophysics Data System (ADS)

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

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

296

Nitric oxide emissions from conventional vegetable fields in southeastern China  

NASA Astrophysics Data System (ADS)

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

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

297

Nitric oxide regulates the proliferation of chick embryo retina cells by a cyclic GMP-independent mechanism  

Microsoft Academic Search

Nitric oxide (NO) is an intercellular messenger involved in many physiological and pathological processes of vertebrate and invertebrate animal tissues. In the embryonic chick retina, nitric oxide synthase (NOS) activity and a system for l-arginine transport between neurons and glial cells were described, supporting the idea that nitric oxide is a critical molecule during retinal development. In the present work

Cristiane R. Magalhães; Renato E. S. Socodato; Roberto Paes-de-Carvalho

2006-01-01

298

Amplification of spinal nociceptive transmission depends on the generation of nitric oxide in normal and carrageenan rats  

Microsoft Academic Search

It has been proposed that nitric oxide (NO) is involved in the spinal transmission of nociceptive information, particularly following the development of peripheral inflammation. In this electrophysiological study the ability of the nitric oxide synthase inhibitor 7-nitro indazole (7-NI), which does not block endothelial nitric oxide in vivo, to inhibit the electrically evoked responses of dorsal horn neurones recorded in

Louise C Stanfa; Charu Misra; Anthony H Dickenson

1996-01-01

299

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

Microsoft Academic Search

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

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

1999-01-01

300

Oxidative Stress Modulates the Nitric Oxide Defense Promoted by Escherichia coli Flavorubredoxin  

PubMed Central

Mammalian cells of innate immunity respond to pathogen invasion by activating proteins that generate a burst of oxidative and nitrosative stress. Pathogens defend themselves from the toxic compounds by triggering a variety of detoxifying enzymes. Escherichia coli flavorubredoxin is a nitric oxide reductase that is expressed under nitrosative stress conditions. We report that in contrast to nitrosative stress alone, exposure to both nitrosative and oxidative stresses abolishes the expression of flavorubredoxin. Electron paramagnetic resonance (EPR) experiments showed that under these conditions, the iron center of the flavorubredoxin transcription activator NorR loses the ability to bind nitric oxide. Accordingly, triggering of the NorR ATPase activity, a requisite for flavorubredoxin activation, was impaired by treatment of the protein with the double stress. Studies of macrophages revealed that the contribution of flavorubredoxin to the survival of E. coli depends on the stage of macrophage infection and that the lack of protection observed at the early phase is related to inhibition of NorR activity by the oxidative burst. We propose that the time-dependent activation of flavorubredoxin contributes to the adaptation of E. coli to the different fluxes of hydrogen peroxide and nitric oxide to which the bacterium is subjected during the course of macrophage infection. PMID:22563051

Baptista, Joana M.; Justino, Marta C.; Melo, Ana M. P.; Teixeira, Miguel

2012-01-01

301

Effects of different resistance exercise protocols on nitric oxide, lipid peroxidation and creatine kinase activity in sedentary males  

Microsoft Academic Search

The purpose of this study was to determine the changes of oxi- dative response and exercise-induced muscle damage after two different resistance exercise protocols. Whether training with low or high intensity resistance programs cause alterations in the activities of lipid peroxidation, nitric oxide (NOx), and creatine kinase (CK) activity in human plasma was investigated. Twenty untrained males participated into this

Nevin Atalay Güzel; Serkan Hazar; Deniz Erbas

302

Dependency of Cortical Functional Hyperemia to Forepaw Stimulation on Epoxygenase and Nitric Oxide Synthase Activities in Rats  

Microsoft Academic Search

Individual inhibition of nitric oxide (NO) synthase and cytochrome P450 (CYP) epoxygenase activity attenuates cortical functional hyperemia evoked by whisker stimulation. The objectives of the present study were to determine (1) if administration of epoxygenase inhibitors attenuates cortical functional hyperemia by using a different modality of sensory activation (i.e., electrical stimulation of the rat forepaw), (2) if epoxygenase inhibition has

Xinqi Peng; Chenyang Zhang; Nabil J. Alkayed; David R. Harder; Raymond C. Koehler

2004-01-01

303

Immunohistochemical localization of nitric oxide synthase in rat anterior choroidal artery, stromal blood microvessels, and choroid plexus epithelial cells  

Microsoft Academic Search

Nitric oxide (NO) has recently been shown to regulate blood flow to choroid plexus, a specialized brain structure responsible for production of most of cerebrospinal fluid. In the present study, we used a specific polyclonal rabbit antibody against the neuronal isoform of NO synthase (NOS), a synthetic enzyme for NO, to determine the localization of NOS in the choroid plexus

Anne Y.-J. Lin; Joanna Szmydynger-Chodobska; Michael P. Rahman; Bernd Mayer; Paul R. Monfils; Conrad E. Johanson; Yow-Pin Lim; Stephanie Corsetti; Adam Chodobski

1996-01-01

304

Hemoglobin, nitric oxide and molecular mechanisms of hypoxic vasodilation.  

PubMed

The protected transport of nitric oxide (NO) by hemoglobin (Hb) links the metabolic activity of working tissue to the regulation of its local blood supply through hypoxic vasodilation. This physiologic mechanism is allosterically coupled to the O(2) saturation of Hb and involves the covalent binding of NO to a cysteine residue in the beta-chain of Hb (Cys beta93) to form S-nitrosohemoglobin (SNO-Hb). Subsequent S-transnitrosation, the transfer of NO groups to thiols on the RBC membrane and then in the plasma, preserves NO vasodilator activity for delivery to the vascular endothelium. This SNO-Hb paradigm provides insight into the respiratory cycle and a new therapeutic focus for diseases involving abnormal microcirculatory perfusion. In addition, the formation of S-nitrosothiols in other proteins may regulate an array of physiological functions. PMID:19781996

Allen, Barry W; Stamler, Jonathan S; Piantadosi, Claude A

2009-10-01

305

Nitric oxide counters ethylene effects on ripening fruits  

PubMed Central

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

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

2012-01-01

306

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

PubMed

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

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

2008-12-01

307

Natural Product Nitric Oxide Chemistry: New Activity of Old Medicines  

PubMed Central

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

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

2012-01-01

308

Exhaled Nitric Oxide: Sources of Error in Offline Measurement  

PubMed Central

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

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

2007-01-01

309

Antibacterial efficacy of exogenous nitric oxide on periodontal pathogens.  

PubMed

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

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

2014-11-01

310

Suppression of arthritis by an inhibitor of nitric oxide synthase  

PubMed Central

Nitric oxide (NO), a toxic radical gas produced during the metabolism of L-arginine by NO synthase (NOS), has been implicated as a mediator of immune and inflammatory responses. A single injection of streptococcal cell wall fragments (SCW) induces the accumulation of inflammatory cells within the synovial tissue and a cell-mediated immune response that leads destructive lesions. We show here that NO production is elevated in the inflamed joints of SCW-treated rats. Administration of NG-monomethyl-L-arginine, an inhibitor of NOS, profoundly reduced the synovial inflammation and tissue damage as measured by an articular index and reflected in the histopathology. These studies implicate the NO pathway in the pathogenesis of an inflammatory arthritis and demonstrate the ability of a NOS inhibitor to modulate the disease. PMID:7688035

1993-01-01

311

Hypoxic conditioning suppresses nitric oxide production upon myocardial reperfusion.  

PubMed

Physiologically modulated concentrations of nitric oxide (NO) are generally beneficial, but excessive NO can injure myocardium by producing cytotoxic peroxynitrite. Recently we reported that intermittent, normobaric hypoxia conditioning (IHC) produced robust cardioprotection against infarction and lethal arrhythmias in a canine model of coronary occlusion-reperfusion. This study tested the hypothesis that IHC suppresses myocardial nitric oxide synthase (NOS) activity and thereby dampens explosive, excessive NO formation upon reperfusion of occluded coronary arteries. Mongrel dogs were conditioned by a 20 d program of IHC (FIO(2) 9.5-10%; 5-10 min hypoxia/cycle, 5-8 cycles/d with intervening 4 min normoxia). One day later, ventricular myocardium was sampled for NOS activity assays, and immunoblot detection of the endothelial NOS isoform (eNOS). In separate experiments, myocardial nitrite (NO(2)(-)) release, an index of NO formation, was measured at baseline and during reperfusion following 1 h occlusion of the left anterior descending coronary artery (LAD). Values in IHC dogs were compared with respective values in non-conditioned, control dogs. IHC lowered left and right ventricular NOS activities by 60%, from 100-115 to 40-45 mU/g protein (P < 0.01), and decreased eNOS content by 30% (P < 0.05). IHC dampened cumulative NO(2)(-) release during the first 5 min reperfusion from 32 +/- 7 to 14 +/- 2 mumol/g (P < 0.05), but did not alter hyperemic LAD flow (15 +/- 2 vs. 13 +/- 2 ml/g). Thus, IHC suppressed myocardial NOS activity, eNOS content, and excessive NO formation upon reperfusion without compromising reactive hyperemia. Attenuation of the NOS/NO system may contribute to IHC-induced protection of myocardium from ischemia-reperfusion injury. PMID:18408142

Ryou, Myoung-Gwi; Sun, Jie; Oguayo, Kevin N; Manukhina, Eugenia B; Downey, H Fred; Mallet, Robert T

2008-06-01

312

Endothelial nitric oxide: protector of a healthy mind.  

PubMed

Endothelial nitric oxide (NO) is generated by constitutively active endothelial nitric oxide synthase (eNOS), an essential enzyme responsible for cardiovascular homeostasis. Historically, endothelial NO was first recognized as a major vasodilator involved in control of vasomotor function and local blood flow. In this review, our attention is focused on the emerging role of endothelial NO in linking cerebrovascular function with cognition. We will discuss the recognized ability of endothelial NO to modulate processing of amyloid precursor protein (APP), influence functional status of microglia, and affect cognitive function. Existing evidence suggests that the loss of NO in cultured human cerebrovascular endothelium causes increased expression of APP and ?-site APP-cleaving enzyme 1 (BACE1) thereby resulting in increased secretion of amyloid ? peptides (A?1-40 and A?1-42). Furthermore, increased expression of APP and BACE1 as well as increased production of A? peptides was detected in the cerebral microvasculature and brain tissue of eNOS-deficient mice. Since A? peptides are considered major cytotoxic molecules responsible for the pathogenesis of Alzheimer's disease, these observations support the concept that a loss of endothelial NO might significantly contribute to the initiation and progression of cognitive decline. In addition, genetic inactivation of eNOS causes activation of microglia and promotes a pro-inflammatory phenotype in the brain. Behavioural analysis revealed that eNOS-deficient mice exhibit impaired cognitive performance thereby indicating that selective loss of endothelial NO has a detrimental effect on the function of neuronal cells. Together with findings from prior studies demonstrating the ability of endothelial NO to affect synaptic plasticity, mitochondrial biogenesis, and function of neuronal progenitor cells, it is becoming apparent that the role of endothelial NO in the control of central nervous system function is very complex. We propose that endothelial NO represents the key molecule linking cerebrovascular and neuronal function. PMID:24357508

Katusic, Zvonimir S; Austin, Susan A

2014-04-01

313

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

PubMed Central

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

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

1998-01-01

314

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

PubMed Central

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

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

1997-01-01

315

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

PubMed Central

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

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

2014-01-01

316

Nitric Oxide and Peroxynitrite in Health and Disease  

PubMed Central

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

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

2008-01-01

317

Chronic exposure to aluminum impairs neuronal glutamate-nitric oxide-cyclic GMP pathway.  

PubMed

Humans are exposed to aluminum from environmental sources and therapeutic treatments. However, aluminum is neurotoxic and is considered a possible etiologic factor in Alzheimer's disease and other neurological disorders. The molecular mechanism of aluminum neurotoxicity is not understood. We tested the effects of aluminum on the glutamate-nitric oxide-cyclic GMP pathway in cultured neurons. Neurons were exposed to 50 microM aluminum in culture medium for short-term (4 h) or long-term (8-14 days) periods, or rats were prenatally exposed, i.e., 3.7% aluminum sulfate in the drinking water, during gestation. Chronic (but not short-term) exposure of neurons to aluminum decreased glutamate-induced activation of nitric oxide synthase by 38% and the formation of cyclic GMP by 77%. The formation of cyclic GMP induced by the nitric oxide-generating agent S-nitroso-N-acetylpenicillamine was reduced by 33%. In neurons from rats prenatally exposed to aluminum but not exposed to it during culture, glutamate-induced formation of cyclic GMP was inhibited by 81%, and activation of nitric oxide synthase was decreased by 85%. The formation of cyclic GMP induced by S-nitroso-N-acetylpenicillamine was not affected. These results indicate that chronic exposure to aluminum impairs glutamate-induced activation of nitric oxide synthase and nitric oxide-induced activation of guanylate cyclase. Impairment of the glutamate-nitric oxide-cyclic GMP pathway in neurons may contribute to aluminum neurotoxicity. PMID:9580158

Cucarella, C; Montoliu, C; Hermenegildo, C; Sáez, R; Manzo, L; Miñana, M D; Felipo, V

1998-04-01

318

The nitrate-nitrite-nitric oxide pathway: Its role in human exercise physiology  

Microsoft Academic Search

Nitric oxide (NO) is a potent signalling molecule that influences an array of physiological responses. It was traditionally assumed that NO was derived exclusively via the nitric oxide synthase (NOS) family of enzymes. This complex reaction requires a five electron oxidation of L-arginine and is contingent on the presence of numerous essential substrates (including O2) and co-factors. Recently an additional,

Stephen J. Bailey; Anni Vanhatalo; Paul G. Winyard; Andrew M. Jones

2012-01-01

319

The nitrate-nitrite-nitric oxide pathway: Its role in human exercise physiology  

Microsoft Academic Search

Nitric oxide (NO) is a potent signalling molecule that influences an array of physiological responses. It was traditionally assumed that NO was derived exclusively via the nitric oxide synthase (NOS) family of enzymes. This complex reaction requires a five electron oxidation of L-arginine and is contingent on the presence of numerous essential substrates (including O2) and co-factors. Recently an additional,

Stephen J. Bailey; Anni Vanhatalo; Paul G. Winyard; Andrew M. Jones

2011-01-01

320

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

PubMed Central

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

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

2013-01-01

321

Indium Tin Oxide Resistor-Based Nitric Oxide Microsensors  

NASA Technical Reports Server (NTRS)

A sensitive resistor-based NO microsensor, with a wide detection range and a low detection limit, has been developed. Semiconductor microfabrication techniques were used to create a sensor that has a simple, robust structure with a sensing area of 1.10 0.99 mm. A Pt interdigitated structure was used for the electrodes to maximize the sensor signal output. N-type semiconductor indium tin oxide (ITO) thin film was sputter-deposited as a sensing material on the electrode surface, and between the electrode fingers. Alumina substrate (250 m in thickness) was sequentially used for sensor fabrication. The resulting sensor was tested by applying a voltage across the two electrodes and measuring the resulting current. The sensor was tested at different concentrations of NO-containing gas at a range of temperatures. Preliminary results showed that the sensor had a relatively high sensitivity to NO at 450 C and 1 V. NO concentrations from ppm to ppb ranges were detected with the low limit of near 159 ppb. Lower NO concentrations are being tested. Two sensing mechanisms were involved in the NO gas detection at ppm level: adsorption and oxidation reactions, whereas at ppb level of NO, only one sensing mechanism of adsorption was involved. The NO microsensor has the advantages of high sensitivity, small size, simple batch fabrication, high sensor yield, low cost, and low power consumption due to its microsize. The resistor-based thin-film sensor is meant for detection of low concentrations of NO gas, mainly in the ppb or lower range, and is being developed concurrently with other sensor technology for multispecies detection. This development demonstrates that ITO is a sensitive sensing material for NO detection. It also provides crucial information for future selection of nanostructured and nanosized NO sensing materials, which are expected to be more sensitive and to consume less power.

Xu, Jennifer C.; Hunter, Gary W.; Gonzalez, Jose M., III; Liu, Chung-Chiun

2012-01-01

322

Nitric oxide synthase in the subfornical organ of Mongolian gerbil (Meriones unguiculatus), mouse and rat.  

PubMed

The present paper aims to contribute to the knowledge of the histophysiologic role of the subfornical organ. Using nicotinamide adenine dinucleotide phosphate diaphorase histochemistry (NADPH-diaporase) and nitric oxide synthase immunocytochemistry, we detected a high concentration of the neuronal isoform of nitric oxide synthase in neurons of the subfornical organ of the adult Mongolian gerbil (Meriones unguiculatus), mouse and rat. Our results suggest that neurons of the subfornical organ produce a considerable amount of nitric oxide which acts, not only as a neurotransmitter, but could also diffuse into cerebral blood vessels and cerebrospinal fluid. PMID:8607293

Krstic, R; Nicolas, D; Novier, A

1995-10-01

323

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

Microsoft Academic Search

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

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

1989-01-01

324

Nitric oxide releasing derivatives of tolfenamic acid with anti-inflammatory activity and safe gastrointestinal profile.  

PubMed

Tolfenamic acid esters with nitrooxyalcohols are synthesized. They are anti-inflammatory agents reducing carrageenan rat paw edema, with low gastrointestinal and general toxicity. In vitro, they are nitric oxide donors, inhibitors of lipoxygenase and cyclooxygenases. A two to three carbon chain between carboxylic and nitric ester groups seems optimal for activity. PMID:16185877

Ziakas, George N; Rekka, Eleni A; Gavalas, Antonios M; Eleftheriou, Phaedra T; Tsiakitzis, Karyofillis C; Kourounakis, Panos N

2005-12-01

325

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

NASA Technical Reports Server (NTRS)

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

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

1982-01-01

326

Cytotoxicity induced by grape seed proanthocyanidins: role of nitric oxide.  

PubMed

Grape seed proanthocyanidin extract (GPSE) at high doses has been shown to exhibit cytotoxicity that is associated with increased apoptotic cell death. Nitric oxide (NO), being a regulator of apoptosis, can be increased in production by the administration of GSPE. In a chick cardiomyocyte study, we demonstrated that high-dose (500 microg/ml) GSPE produces a significantly high level of NO that contributes to increased apoptotic cell death detected by propidium iodide and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining. It is also associated with the depletion of intracellular glutathione (GSH), probably due to increased consumption by NO with the formation of S-nitrosoglutathione. Co-treatment with L-NAME, a NO synthase inhibitor, results in reduction of NO and apoptotic cell death. The decline in reduced GSH/oxidized GSH (GSSG) ratio is also reversed. N-Acetylcysteine, a thiol compound that reacts directly with NO, can reduce the increased NO generation and reverse the decreased GSH/GSSG ratio, thereby attenuating the cytotoxicity induced by high-dose GSPE. Taken together, these results suggest that endogenous NO synthase (NOS) activation and excessive NO production play a key role in the pathogenesis of high-dose GSPE-induced cytotoxicity. PMID:16555001

Shao, Z H; Hsu, C W; Chang, W T; Waypa, G B; Li, J; Li, D; Li, C Q; Anderson, T; Qin, Y; Schumacker, P T; Becker, L B; Hoek, T L Vanden

2006-05-01

327

Nitric oxide production by the differentiating xylem of Zinnia elegans.  

PubMed

Nitric oxide (NO) is currently regarded as a signal molecule involved in plant cell differentiation and programmed cell death. Here, we investigated NO production in the differentiating xylem of Zinnia elegans by confocal laser scanning microscopy to answer the question of whether NO is produced during xylem differentiation. Results showed that NO production was mainly located in both phloem and xylem regardless of the cell differentiation status. However, there was evidence for a spatial NO gradient inversely related to the degree of xylem differentiation and a protoplastic NO burst was associated with the single cell layer of pro-differentiating thin-walled xylem cells. Confirmation of these results was obtained using trans-differentiating Z. elegans mesophyll cells. In this system, the scavenging of NO by means of 2-phenyl-4,4,5,5-tetramethyl imidazoline-1-oxyl-3-oxide (PTIO) inhibits tracheary element differentiation but increases cell viability. These results suggest that plant cells, which are just predetermined to irreversibly trans-differentiate in xylem elements, show a burst in NO production, this burst being sustained as long as secondary cell wall synthesis and cell autolysis are in progress. PMID:15720627

Gabaldón, Carlos; Gómez Ros, Laura V; Pedreño, María A; Ros Barceló, A

2005-01-01

328

Endothelial cell expression of haemoglobin ? regulates nitric oxide signalling.  

PubMed

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

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

2012-11-15

329

Oxidant stress—a major cause of reduced endothelial nitric oxide availability in cardiovascular disease  

Microsoft Academic Search

Common conditions predisposing to atherosclerosis, such as dyslipidemia, hypertension, diabetes, and smoking, are associated\\u000a with increased vascular production of reactive oxygen species (ROS). One of the major consequences of increased vascular ROS\\u000a production is a reduction of endothelial nitric oxide (NO) bioavailability. Importantly, endothelial NO not only produces\\u000a endothelium-dependent vasodilation but also has potent antiatherogenic properties, including inhibition of platelet

Ulf Landmesser; David G. Harrison; Helmut Drexler

2006-01-01

330

Adrenoreceptors and nitric oxide in the cardiovascular system  

PubMed Central

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

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

2013-01-01

331

Nitric oxide emissions from soils amended with municipal waste biosolids  

NASA Astrophysics Data System (ADS)

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

Roelle, Paul A.; Aneja, Viney P.

332

Association of expired nitric oxide with occupational particulate exposure.  

PubMed Central

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

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

2003-01-01

333

The biogenic emission potential of nitric oxide from sandy soils  

NASA Astrophysics Data System (ADS)

There are about 160.9 Mha of sandy land in China, about 17.6% of total Chinese area, which mainly distributed in 35°-50° N. The western Songnen Plain, which located in the semi-arid region of Northeastern China, is one of the main sandy soil distribution regions. The changes of land use in sandy soil are accompanied by changes in biogeochemical cycles of nutrients, particularly of the air-surface exchange of trace gases like nitric oxide. Our study, based on results obtained by a laboratory incubation technique, focuses on (a) NO production and consumption in sandy soils from two types of land use as function of soil temperature and soil moisture, and (b) The biogenic emission potential of nitric oxide from sandy soils in semi-arid region. At 25?C, average NO production (in terms of mass of N) was 0.016,and 0.013 ng kg-1s-1 in sandy soils from soybean land (SL) and man-made forest (MF), re¬spectively. NO consumption rate constant ranged from 0.26×10-6 to 7.28×10-6 m3 kg-1s-1. At 25?C and under optimum soil moisture conditions for NO production, the NO compensation point mixing ratio was about 266 and 161 ug m-3 (465,and 281 ppb) for soils of SL and MF, respectively. Statistically sound relationships have been observed between NO fluxes and soil moisture (optimum curves). NO fluxes also increased exponentially with soil temperature at any given soil moisture. The optimum soil moisture for which maximum NO flux was observed was independent of soil temperature. The maximum of NO flux potentials for SL and MF soils (at 25°C) were 59.6 and 36.5 ng m-2s-1 at water-filled pore space (%WFPS) of 26 and 24, respectively. The NO flux potential was about 2 times larger for cropland soil than for man-made forest soils, most likely due to fertilizer application to the cropland soils.

Yu, J. B.; Meixner, F. X.; Sun, Z. G.; Chen, X. B.; Mamtimin, B.

2009-04-01

334

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

PubMed Central

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

2012-01-01

335

Turn-on fluorescent probes for detecting nitric oxide in biology  

E-print Network

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

McQuade, Lindsey Elizabeth, 1981-

2010-01-01

336

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

E-print Network

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

Tennyson, Andrew Gregory

2008-01-01

337

Biochemistry of mobile zinc and nitric oxide revealed by fluorescent sensors  

E-print Network

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

Pluth, Michael D.

338

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

E-print Network

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

Pluth, Michael D.

339

Diffusion and reactions of nitric oxide, oxygen, and superoxide in cells and culture media  

E-print Network

As part of the non-specific immune response to infection, activated macrophages synthesize nitric oxide (NO) at relatively high rates, thereby creating local concentrations of NO that are toxic to the invading microorganisms. ...

Nalwaya, Nitesh, 1979-

2004-01-01

340

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

E-print Network

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

Pluth, Michael D.

341

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

E-print Network

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

Nizet, Victor

342

Short Communication The nitric oxide synthase inhibitor l-NAME suppresses androgen-induced  

E-print Network

Short Communication The nitric oxide synthase inhibitor l-NAME suppresses androgen-induced male anesthesia and each implanted with a Silastic tube (Helix Medical, 10 mm long, internal diameter 1.47 mm

Crews, David

343

In vitro investigation of the interaction between nitric oxide and cyclo-oxygenase activity in equine ventral colon smooth muscle.  

PubMed

The objective of this study was to determine if a correlation exists between the presence of nitric oxide and prostaglandin release in the equine ventral colon smooth muscle, since this relationship may accentuate the inflammatory process during intestinal injury. Tissue was collected from the ventral colon, cut into muscle strips oriented along the circular, longitudinal and taenial layers, and mounted in a tissue bath system. Samples of the bath fluid were collected before, following electrical field stimulation (EFS), and following EFS in the presence of L-NAME, a nitric oxide synthase inhibitor. Muscle strips were also obtained following systemic administration of a cyclo-oxygnease inhibitor and samples were collected using the previously described protocol. Concentrations of prostaglandins were determined in the fluid samples using an ELISA. Electrical field stimulated release of nitric oxide produced a significant increase in prostaglandin production which did not occur in the presence of L-NAME. Systemic administration of flunixin meglumine reduced prostaglandin levels at all sampling periods, although a small increase was present following EFS. The results of this study support the hypothesis that there is a correlation between the release of nitric oxide and the production of prostaglandins in the smooth muscle of the large colon. This association between nitric oxide and prostaglandin may act as an important regulatory mechanism for various physiological mechanisms, such as vascular smooth muscle tone, and may contribute to amplified tissue injury when the induced forms of both enzymes are activated during an inflammatory insult. This suggests that the use and development of COX2 and iNOS inhibitors may help attenuate the inflammatory response following intestinal injury. PMID:12358056

van Hoogmoed, L M; Harmon, F A; Stanley, S; White, J; Snyder, J

2002-07-01

344

Endothelin1Induced Constriction Inhibits Nitric-Oxide-Mediated Dilation in Isolated Rat Resistance Arteries  

Microsoft Academic Search

Vascular endothelial cells release dilatory compounds like nitric oxide and prostacyclin, as well as contractile factors like endothelin-1 (ET-1). We investigated the interaction of ET-1 with nitric-oxide-mediated dilation in cannulated pressurized (75 mm Hg) arterioles from rat cremaster muscle (180 ± 3 ?m). Arterioles constricted spontaneously to 101 ± 3 ?m, while ET-1 (0.4 nM)increased constriction to 78 ± 3

Erik N. T. P. Bakker; Peter J. W. van der Linden; Pieter Sipkema

1997-01-01

345

Role of nitric oxide in renal hemodynamic abnormalities of cyclosporin nephrotoxicity  

Microsoft Academic Search

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

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

1994-01-01

346

Self-administration of heroin produces alterations in the expression of inducible nitric oxide synthase  

Microsoft Academic Search

Nitric oxide plays a critical role in the immune response, and our studies have shown that heroin induces a reduction in the expression of iNOS, the enzyme responsible for nitric oxide production. The present study evaluated the effect of heroin self-administration on iNOS expression using a three-group design. Group one (self-administration) was trained to press a lever for i.v. administration

Ryan K. Lanier; Stephanie G. Ijames; Kelly A. Carrigan; Regina M. Carelli; Donald T. Lysle

2002-01-01

347

Nonspecific inhibition of nitric oxide synthesis evokes endothelin-dependent increases in myocardial contractility  

Microsoft Academic Search

The role of endogenous nitric oxide (NO) in modulating myocardial contractility is still unclear, in part because of unknown, secondary effects of blocking NO release. We hypothesized that the nonspecific inhibition of nitric oxide synthase (NOS) enhances endothelin-1 (ET-1) effects, which can play a role in ET-A receptor-dependent myocardial contractile responses. The myocardial contractility was estimated from the slope of

Miklós Czóbel; József Kaszaki; Gábor Molnár; Sándor Nagy; Mihály Boros

2009-01-01

348

Association of mitochondrial nitric oxide synthase activity with respiratory chain complex I  

PubMed Central

The present study shows that rat liver and brain mitochondrial nitric oxide synthase (mtNOS) are functionally associated with mitochondrial respiratory chain complex I. When complex I is activated, mtNOS exerts high activity and generates nitric oxide, whereas inactivation of complex I leads mtNOS to abandon its NOS activity. Functional association of mtNOS with complex I is potentially important in regulating mtNOS activity and mitochondrial functions. PMID:18036554

Parihar, Mordhwaj S.; Nazarewicz, Rafal R.; Kincaid, Erick; Bringold, Urs; Ghafourifar, Pedram

2008-01-01

349

Exercise training reverses age-induced inducible nitric oxide synthase upregulation  

E-print Network

an inflammatory response and may contribute to an exercise-induced rise of endogenous nitric oxide production. Similarly, acute exercise consisting of an incremental treadmill test followed by a continuous run until exhaustion at 110% of the individual anaerobic... an inflammatory response and may contribute to an exercise-induced rise of endogenous nitric oxide production. Similarly, acute exercise consisting of an incremental treadmill test followed by a continuous run until exhaustion at 110% of the individual anaerobic...

Song, Wook

2005-02-17

350

The catalytic reduction of nitric oxide with ammonia over tetraamminecopper (II) complexes  

E-print Network

that the ennanced catalytic activity of the NO-NH system in the presence of oxygen is directly 3 proportional to the amount of surface oxygen. The unusual activity profile of the reaction of nitric oxide with 23 ammonia over Cuy zeolites was first reported... of nitric oxide with ammonia over tetraamminecopper(II) complexes in aqueous solutions to compare this reaction environment with the parallel reac- tion over Cu(II) NaY zeolites. Zeolites are crystalline aluminosilicates which contain exchangeable...

Oates, Margaret Deron

2012-06-07

351

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

Microsoft Academic Search

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

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

2009-01-01

352

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

Microsoft Academic Search

Neuronal nitric oxide synthase was located in various organs of the goldfish by NADPH-diaphorase histochemistry and immunohistochemistry. Positive cells were detected throughout the digestive tract. A particularly dense plexus of nitric-oxide-synthase-containing fibers was present at the opening of the pneumatic duct into the esophagus and at the intestinal sphincter separating the esophagus and the intestinal bulb. The nitroxergic innervation was

Gerold Brüning; Katharina Hattwig; Bernd Mayer

1996-01-01

353

Estrogen downregulates neuronal nitric oxide synthase in rat anterior pituitary cells and GH 3 tumors  

Microsoft Academic Search

The anterior pituitary gland produces neuronal nitric oxide synthase (nNOS) and nitric oxide regulates secretion of various\\u000a anterior pituitary hormones. Estrogen has many functions in anterior pituitary cells including stimulation of prolectin (PRL)\\u000a cell proliferation and secretion of various anterior pituitary hormones. However, the role of estradiol-17? (E2) in regulating pituitary nNOS expression has not been previously examined. We studied

Xiang Qian; Long Jin; Ricardo V. Lloyd

1999-01-01

354

Nitric oxide synthases in infants and children with pulmonary hypertension and congenital heart disease  

Microsoft Academic Search

RATIONALE: Nitric oxide is an important regulator of vascular tone in the pulmonary circulation. Surgical correction of congenital heart disease limits pulmonary hypertension to a brief period. OBJECTIVES: The study has measured expression of endothelial (eNOS), inducible (iNOS), and neuronal nitric oxide synthase (nNOS) in the lungs from biopsies of infants with pulmonary hypertension secondary to cardiac abnormalities (n =

Thomas Hoehn; Brigitte Stiller; Allan R McPhaden; Roger M Wadsworth

2009-01-01

355

Ebselen and cytokine-induced nitric oxide synthase expression in insulin-producing cells  

Microsoft Academic Search

Interleukin-1 (IL-1) may be a mediator of ?-cell damage in insulin-dependent diabetes mellitus (IDDM). The IL-1 mechanism of action on insulin-producing cells probably includes activation of the transcription nuclear factor ?B (NF-?B), increased transcription of the inducible form of nitric oxide synthase (iNOS) and the subsequent production of nitric oxide (NO). Reactive oxygen intermediates, particularly H2O2, have been proposed as

Maria A. R. de-Mello; Malin Flodström; Décio L. Eizirik

1996-01-01

356

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

Microsoft Academic Search

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

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

1996-01-01

357

Exhaled nitric oxide in 4-year-old children: relationship with asthma and atopy  

Microsoft Academic Search

Airway inflammation is an early feature of asthma. Early detection and antiinflammatory\\u000atreatment may have important therapeutic impact. Exhaled nitric oxide is a noninvasive marker of airway inflammation. The current study investigated the association between exhaled nitric oxide and asthma, wheezing phenotypes, atopy and blood eosinophilia in a large group of 4-yr-old children from the general population.\\u000aAll children participated

J. E. Brussee; H. A. Smit; M. Kerkhof; L. P. Koopman; A. H. Wijga; D. S. Postma; J. Gerritsene; D. E. Grobbee; B. Brunekreef; J. C. de Jongste

2005-01-01

358

Malaria severity and human nitric oxide synthase type 2 (NOS2) promoter haplotypes  

Microsoft Academic Search

Nitric oxide (NO) mediates host resistance to severe malaria and other infectious diseases. NO production and mononuclear\\u000a cell expression of the NO producing enzyme-inducible nitric oxide synthase (NOS2) have been associated with protection from\\u000a severe falciparum malaria. The purpose of this study was to identify single nucleotide polymorphisms (SNPs) and haplotypes\\u000a in the NOS2 promoter, to identify associations of these

Marc C. Levesque; Maurine R. Hobbs; Charles W. O’Loughlin; Jennifer A. Chancellor; Youwei Chen; Ariana N. Tkachuk; Jennifer Booth; Kistie B. Patch; Sallie Allgood; Ann R. Pole; Carolyn A. Fernandez; Esther D. Mwaikambo; Theonest K. Mutabingwa; Michal Fried; Bess Sorensen; Patrick E. Duffy; Donald L. Granger; Nicholas M. Anstey; J. Brice Weinberg

2010-01-01

359

Inhaled nitric oxide and pentoxifylline in rat lung transplantation from non-heart-beating donors  

Microsoft Academic Search

Background: In non-heart-beating donor lung transplantation, postmortem warm ischemia poses a special challenge. Inhaled nitric oxide and pentoxifylline have been shown to attenuate ischemia-reperfusion injury after lung transplantation. We hypothesized that concomitant administration of inhaled nitric oxide and pentoxifylline would result in a synergistic effect on ischemia-reperfusion lung injury. Methods: Lungs were harvested from non-heart-beating donors after 30 minutes of

Shinya Murakami; Emile A. Bacha; Philippe Hervé; Hélène Détruit; Alain R. Chapelier; Philippe G. Dartevelle; Guy-Michel Mazmanian

1997-01-01

360

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

PubMed

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

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

2011-07-01

361

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

E-print Network

PATHOPHYSIOLOGY OF ENDOTOXIN: MICROVASCULAR DYSFUNCTION, AND THE ROLFS OF VEGF AND NITRIC OXIDE (NO) A Senior Honors Thesis bt MARK ANDREW NAFTANFL Submitted to the Olfice of Honors Programs A. Academic Scholarships Texas A&M University ln... PATHOPHYSIOLOGY OF ENDOTOXIN: MICROVASCULAR DYSFUNCTION, AND THE ROLFS OF VEGF AND NITRIC OXIDE (NO) A Senior Honors Thesis bt MARK ANDREW NAFTANFL Submitted to the Olfice of Honors Programs A. Academic Scholarships Texas A&M University ln...

Naftanel, Mark Andrew

2013-02-22

362

Gastric Stasis in Neuronal Nitric Oxide Synthase-Deficient Knockout Mice  

Microsoft Academic Search

Background & Aims: Nitric oxide (NO) is a major inhibitory neurotransmitter in the gut. This study aimed to identify the effect of chronic deprivation of NO derived from neuronal (nNOS) or endothelial (eNOS) nitric oxide synthase on gastric emptying. Methods: nNOS-deficient (knockout) mice were compared with wild-type mice for gastric size, fluoroscopic appearance after gavage of contrast, and histology of

2000-01-01

363

Nitric oxide synthase inhibition can initiate or prevent gut inflammation: Role of enzyme source  

Microsoft Academic Search

The role of nitric oxide in gut inflammation was evaluated by comparing the effects of selective or nonselective inhibitors of nitric oxide synthase (NOS). Aminoguanidine, a selective inducible NOS (iNOS) inhibitor, or NG-nitro-l-arginine methyl ester (l-NAME) were administered via the drinking water to normal guinea pigs or following induction of ileitis with trinitrobenzene sulfonic acid (TNBS 30 mg\\/kg). Aminoguanidine had

M. J. S. Miller; D. A. Clark

1994-01-01

364

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

PubMed

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

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

2014-11-01

365

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

PubMed

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

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

2004-10-01

366

Light-controlled nitric oxide delivering molecular assemblies.  

PubMed

The multiple roles nitric oxide (NO) plays as a bioregulatory, anticancer, antimicrobial and antioxidant agent has triggered an explosive interest in recent years in compounds able to deliver this diatomic radical for therapeutic purposes. A major issue associated with NO donors is the precise control of the NO release, which effect is highly concentration and flux dependent. Light represents a convenient non-invasive on/off trigger to deliver NO on demand since it allows the accurate control of site, timing and dosage. The assembling of NO photodonors through different approaches may lead to intriguing light-responsive molecular constructs including nanostructured films, polymers, gels, nanoparticles and molecular conjugates which exhibit promising potential in view of practical applications. This tutorial review illustrates the recent research from our and other laboratories towards the fabrication of these molecular assemblies, highlighting the logical design and the relevance in the biomedical field. Therefore, this review is aimed to be a source of inspiration for a wide range of scientists belonging to the chemical, materials science and biochemical communities, facing the common challenge of fabricating controllable NO dispensers. PMID:20556272

Sortino, Salvatore

2010-08-01

367

Nitric Oxide-Releasing S-Nitrosothiol-Modified Xerogels  

PubMed Central

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

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

2009-01-01

368

Photo-crosslinked Biodegradable Elastomers for Controlled Nitric Oxide Delivery  

PubMed Central

The delivery of nitric oxide (NO) has important applications in medicine, especially for procedures that involve the vasculature. We report photo-curable biodegradable poly(diol citrate) elastomers capable of slow release of NO. A methacrylated poly(diol citrate) macromonomer was prepared by polycondensation of citric acid with 1, 8-octanediol or 1, 12-dodecanediol followed by functionalization with 2-aminoethyl methacrylate. A miscible NO donor, diazeniumdiolated N, N-diethyldiethylenetriamine, was synthesized and incorporated into the polymer matrix. An elastomeric network was obtained via photo-polymerization of macromonomers upon UV irradiation within three minutes. Films and tubes of the NO-releasing crosslinked macromonomers exhibited strong tensile strength and radial compressive strength, respectively. They also exhibited cell compatibility and biodegradability in vitro. Sustained NO release under physiological conditions was achieved for at least one week. NO release enhanced the proliferation of human umbilical vein endothelial cells but inhibited the proliferation of human aortic smooth muscle cells. Photo-polymerizable NO-releasing materials provide a new approach for the localized and sustained delivery of NO to treat thrombosis and restenosis in the vasculature. PMID:24707352

Wang, Ying; Kibbe, Melina R.; Ameer, Guillermo A.

2013-01-01

369

Regulation of obesity and insulin resistance by nitric oxide.  

PubMed

Obesity is a risk factor for developing type 2 diabetes and cardiovascular disease and has quickly become a worldwide pandemic with few tangible and safe treatment options. Although it is generally accepted that the primary cause of obesity is energy imbalance, i.e., the calories consumed are greater than are utilized, understanding how caloric balance is regulated has proven a challenge. Many "distal" causes of obesity, such as the structural environment, occupation, and social influences, are exceedingly difficult to change or manipulate. Hence, molecular processes and pathways more proximal to the origins of obesity-those that directly regulate energy metabolism or caloric intake-seem to be more feasible targets for therapy. In particular, nitric oxide (NO) is emerging as a central regulator of energy metabolism and body composition. NO bioavailability is decreased in animal models of diet-induced obesity and in obese and insulin-resistant patients, and increasing NO output has remarkable effects on obesity and insulin resistance. This review discusses the role of NO in regulating adiposity and insulin sensitivity and places its modes of action into context with the known causes and consequences of metabolic disease. PMID:24878261

Sansbury, Brian E; Hill, Bradford G

2014-08-01

370

Heparin modulation on hepatic nitric oxide synthase in experimental steatohepatitis  

PubMed Central

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

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

2014-01-01

371

Nitric oxide controls nitrate and ammonium assimilation in Chlamydomonas reinhardtii.  

PubMed

Nitrate and ammonium are major inorganic nitrogen sources for plants and algae. These compounds are assimilated by means of finely regulated processes at transcriptional and post-translational levels. In Chlamydomonas, the expression of several genes involved in high-affinity ammonium (AMT1.1, AMT1.2) and nitrate transport (NRT2.1) as well as nitrate reduction (NIA1) are downregulated by ammonium through a nitric oxide (NO)-dependent mechanism. At the post-translational level, nitrate/nitrite uptake and nitrate reductase (NR) are also inhibited by ammonium, but the mechanisms implicated in this regulation are scarcely known. In this work, the effect of NO on nitrate assimilation and the high-affinity ammonium uptake was addressed. NO inhibited the high-affinity uptake of ammonium and nitrate/nitrite, as well as the NR activity, in a reversible form. In contrast, nitrite reductase and glutamine synthetase activities were not affected. The in vivo and in vitro studies suggested that NR enzyme is inhibited by NO in a mediated process that requires the cell integrity. These data highlight a role of NO in inorganic nitrogen assimilation and suggest that this signalling molecule is an important regulator for the first steps of the pathway. PMID:23918969

Sanz-Luque, Emanuel; Ocaña-Calahorro, Francisco; Llamas, Angel; Galvan, Aurora; Fernandez, Emilio

2013-08-01

372

Pulmonary vasodilation by inhaled nitric oxide after endothelial injury  

SciTech Connect

Inhaled nitric oxide gas (NO) has recently been shown to reverse experimentally induced pulmonary vasoconstriction. To examine the effect of free radical injury and methylene blue exposure on inhaled NO-induced pulmonary vasodilation the authors studied ventilated rabbit lungs perfused with Krebs solution containing 3% dextran and indomethacin. When NO gas (120 ppm) was added to the inhaled mixture for 3 min, the elevated pulmonary arterial perfusion pressure (Ppa) induced by the thromboxane analogue U-46619 was significantly reduced [8 [+-] 2 (SE) mmHg]. Acetylcholine similarly reduced Ppa (9 [+-] 1 mmHg). After free radical injury and methylene blue exposure, inhaled NO again produced significant vasodilation (5 [+-] 1 and 9 [+-] 2 mmHg, respectively), but acetylcholine resulted in an increase in Ppa ([minus]9 [+-] 3 and [minus]4 [+-] 1 mmHg, respectively). These data demonstrate that pulmonary vasodilation produced by inhaled NO is unaffected by free radical injury or methylene blue in the intact lung despite concomitant reversal of acetylcholine-induced vasodilation. 21 refs., 4 figs.

Rimar, S.; Gillis, C.N. (Yale Univ. School of Medicine, New Haven, CT (United States))

1992-11-01

373

Neuronal Nitric Oxide Synthase Contributes to the Regulation of Hematopoiesis  

PubMed Central

Nitric oxide (NO) signaling is important for the regulation of hematopoiesis. However, the role of individual NO synthase (NOS) isoforms is unclear. Our results indicate that the neuronal NOS isoform (nNOS) regulates hematopoiesis in vitro and in vivo. nNOS is expressed in adult bone marrow and fetal liver and is enriched in stromal cells. There is a strong correlation between expression of nNOS in a panel of stromal cell lines established from bone marrow and fetal liver and the ability of these cell lines to support hematopoietic stem cells; furthermore, NO donor can further increase this ability. The number of colonies generated in vitro from the bone marrow and spleen of nNOS-null mutants is increased relative to wild-type or inducible- or endothelial NOS knockout mice. These results describe a new role for nNOS beyond its action in the brain and muscle and suggest a model where nNOS, expressed in stromal cells, produces NO which acts as a paracrine regulator of hematopoietic stem cells. PMID:18091979

Krasnov, Peter; Michurina, Tatyana; Packer, Michael A; Stasiv, Yuri; Nakaya, Naoki; Moore, Kateri A; Drazan, Kenneth E; Enikolopov, Grigori

2008-01-01

374

Nitric oxide synthase, an essential factor in peripheral nerve regeneration.  

PubMed

Nitric oxide (NO) exerts both, pro-apoptotic and anti-apoptotic actions and appears to be acritical factor inneuronal degenerative and regenerative processes. NO is synthesized from L-arginine by NO synthase occurring in three isoforms of (neuronal, nNOS; endothelial, eNOS; inducible, iNOS). In a mice sciatic nerve model the regenerative outcome was assessed when the endogenous NO supply was deficient by knocking out the respective NOS isoform and compared to that of wild type mice after nerve transection. In nNOS knock-out mice a delay in regeneration, preceded by slowedWallerian degeneration and a disturbed pruning of uncontrolled sprouts, was observed. This was associated with a delayed recovery of sensory and motor function. Additionally, deficiency of nNOS led after nerve cut to a substantial loss of small and medium-sized dorsal root ganglia neurons, spinal cord interneurons and, to a lesser extent, spinal cord motor neurons. A lack of iNOS resulted in a delayed Wallerian degeneration and impaired regenerative outcome without consequences for neuronal survival. A lack of eNOS was well tolerated, although a delay in nerve revascularization was observed. Thus, after peripheral nerve lesion, regular NOS activity is essential for cell survival and recovery with reference to the nNOS isoform. PMID:14656046

Keilhoff, G; Fansa, H; Wolf, G

2003-09-01

375

Farnesoid X receptor regulates vascular reactivity through nitric oxide mechanism.  

PubMed

Farnesoid X receptor (FXR), a ligand-activated transcription factor and a member of nuclear receptor family, is not only highly expressed in the adrenal cortex, intestine, kidney and liver, but also has recently been found in the vasculature. However, the evidence on the roles of FXR in the vasculature is limited and whether FXR regulates vascular reactivity is poorly understood. In present study, we investigated the expression of FXR protein in rat vasculature by immunohistochemical method and tested the effects of FXR activation by chenodeoxycholic acid (CDCA) on thoracic aortic contraction and dilation. We also detected the level of nitrite/nitrate (NOx) and superoxide in the thoracic aortic segments. We found that FXR was expressed in rat carotid arteries, thoracic aorta, abdominal aorta and femoral arteries. FXR activation by CDCA significantly (P<0.01) inhibited the contractile responses of rat thoracic aorta rings to KCl and phenylephrine. The cumulative concentrations of CDCA caused a concentration-dependent relaxation, which could be partly impaired by L-NAME, an inhibitor of nitric oxide (NO) synthase. The NOx content in thoracic aorta significantly (P<0.01) increased when treated with CDCA. Meanwhile, the vascular redox status was not altered by high concentration of CDCA. The present study suggested that FXR regulated vascular reactivity through NO mechanism, which merits further attention. PMID:23070085

Zhang, R; Ran, H-H; Zhang, Y-X; Liu, P; Lu, C-Y; Xu, Q; Huang, Y

2012-08-01

376

REGULATION OF NITRIC OXIDE PRODUCTION IN HEALTH AND DISEASE  

PubMed Central

Purpose of review The purpose of this review is to highlight recent publications examining Nitric Oxide (NO) production in health and disease and its association with clinical nutrition and alterations in metabolism. Recent findings The role of the cofactor tetrahydrobiopterin (BH4) in NO production and its relation with arginine availability is indicated as an important explanation for the arginine paradox. This offers potential for NO regulation by dietary factors like arginine or its precursors and vitamin C. Because diets with a high saturated fat content induce high plasma fatty acid levels, endothelial NO production is often impaired due to a reduction in NOS3 phosphorylation. Increasing the arginine availability by arginine therapy or arginase inhibition was therefore proposed as a potential therapy to treat hypertension. Recent studies in septic patients and transgenic mice models found that inadequate de novo arginine production from citrulline reduces NO production. Citrulline supplementation may therefore be a novel therapeutic approach in conditions of arginine deficiency. Summary Both lack and excess of NO production in diseases can have various important implications in which dietary factors can play a modulating role. Future research is needed to expand our understanding of the regulation and adequate measurement of NO production at the organ level and by the different NOS isoforms, also in relation to clinical nutrition. PMID:19841582

Luiking, Yvette C.; Engelen, Marielle P.K.J.; Deutz, Nicolaas E.P.

2010-01-01

377

Concepts of neural nitric oxide-mediated transmission  

PubMed Central

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

Garthwaite, John

2008-01-01

378

Nitric oxide enhances Th9 cell differentiation and airway inflammation.  

PubMed

Th9 cells protect hosts against helminthic infection but also mediate allergic disease. Here we show that nitric oxide (NO) promotes Th9 cell polarization of murine and human CD4(+) T cells. NO de-represses the tumour suppressor gene p53 via nitrosylation of Mdm2. NO also increases p53-mediated IL-2 production, STAT5 phosphorylation and IRF4 expression, all essential for Th9 polarization. NO also increases the expression of TGF?R and IL-4R, pivotal to Th9 polarization. OVA-sensitized mice treated with an NO donor developed more severe airway inflammation. Transferred Th9 cells induced airway inflammation, which was exacerbated by NO and blocked by anti-IL-9 antibody. Nos2(-/-) mice had less Th9 cells and developed attenuated eosinophilia during OVA-induced airway inflammation compared with wild-type mice. Our data demonstrate that NO is an important endogenous inducer of Th9 cells and provide a hitherto unrecognized mechanism for NO-mediated airway inflammation via the expansion of Th9 cells. PMID:25099390

Niedbala, Wanda; Besnard, Anne-Gaelle; Nascimento, Daniele Carvalho; Donate, Paula Barbim; Sonego, Fabiane; Yip, Edwin; Guabiraba, Rodrigo; Chang, Hyun-Dong; Fukada, Sandra Y; Salmond, Robert J; Schmitt, Edgar; Bopp, Tobias; Ryffel, Bernhard; Liew, Foo Y

2014-01-01

379

Nitric oxide cycle in mammals and the cyclicity principle.  

PubMed

This paper continues a series of reports considering nitric oxide (NO) and its cyclic conversions in mammals. Numerous facts are summarized with the goal of developing a general concept that would allow the statement of the multiple effects of NO on various systems of living organisms in the form of a short and comprehensive law. The current state of biological aspects of NO research is analyzed in term of elucidation of possible role of these studies in the system of biological sciences. The general concept is based on a notion on cyclic conversions of NO and its metabolites. NO cycles in living organisms and nitrogen turnover in the biosphere and also the Bethe nitrogen-carbon cycle in star matter are considered. A hypothesis that the cyclic organization of processes in living organisms and the biosphere reflects the evolution of life is proposed: the development of physiological functions and metabolism are suggested to be closely related to space and evolution of the Earth as a planet of the Solar System. PMID:11970729

Reutov, V P

2002-03-01

380

Does nitric oxide play a role in orofacial pain transmission?  

PubMed

Although the synaptology, neural connectivity, and the roles played by nitric oxide (NO) and other neurotransmitters have been extensively studied in spinal pain, such information is rather scanty with respect to orofacial pain transmission. This paper presents the findings of several investigations carried out by the author and his colleagues on the roles of NO in orofacial pain transmission in male Wistar rats, using nicotinamide adenosine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry using light and electron microscopy; and NOS immunohistochemistry and immunofluorescence using both light and confocal laser scanning microscopy. The results revealed that (1) a complicated relation existed between the nitrergic axon terminals and dendrites in the caudal part of the spinal trigeminal nucleus (cSTN); (2) the nitrergic neuronal cells bodies were not projection neurons, but rather, local circuit neurons; (3) although the thalamus projecting neurons in the cSTN did not synthesize NO, they could be modulated by NO diffused from nitrergic neurons; (4) c-fos positive neurons in the superficial laminae of the cSTN, detected following subcutaneous injection of 0.5 ml of 4% formalin into the left lateral face of the rats, respond to the release of glutamate through activation of N-methyl-D-aspartate (NMDA), alpha-amine-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) and metabotropic glutamate (mGlu) receptors expressed by these c-fos neurons; and (5) NO might play a seemingly less important role than glutamate in neural transmission. PMID:12076972

Yeo, Jin-Fei

2002-05-01

381

Protective role of nitric oxide in ocular toxoplasmosis.  

PubMed Central

AIMS: To evaluate the role of nitric oxide (NO) in ocular involvement during systemic toxoplasmosis. METHODS: C57B1/6 mice were infected with Toxoplasma gondii strain ME49. The synthesis of NO was inhibited by an intraperitoneal injection of aminoguanidine every 8 hours, starting on the day of infection. Control infected mice received phosphate buffered saline vehicle alone. After 14 days, the ocular lesions were evaluated by histopathological examination. The expression of NO synthase induced in the spleen by toxoplasma infection was evaluated by immunostaining. The production of NO by the spleen cells of infected mice was measured by the colorimetric assay of Griess in the supernatant of cultures stimulated with toxoplasma antigen or concanavalin A. RESULTS: The inhibition of NO production in T gondii infected mice resulted in a marked increase in the symptoms of ocular inflammation. We observed a strong induction of NO synthase expression in the spleen of infected animals. In culture, the spleen cells from these mice produced high levels of NO in response to T gondii antigens. This elevation of NO synthesis was suppressed in the presence of aminoguanidine. CONCLUSION: This study indicates that NO plays a crucial role in the protection against T gondii infection as reflected by the severity of the ocular involvement. Images PMID:8795379

Hayashi, S.; Chan, C. C.; Gazzinelli, R. T.; Pham, N. T.; Cheung, M. K.; Roberge, F. G.

1996-01-01

382

S-Nitrosothiol-Modified Dendrimers as Nitric Oxide Delivery Vehicles  

PubMed Central

The synthesis and characterization of two generation-4 polyamidoamine (PAMAM) dendrimers with S-nitrosothiol exteriors are reported. The hyperbranched macromolecules were modified with either N-acetyl-D,L-penicillamine (NAP) or N-acetyl-L-cysteine (NACys) and analyzed via 1H and 13C-NMR, UV absorption spectroscopy, MALDI-TOF mass spectrometry, and size exclusion chromatography. Treatment of the dendritic thiols with nitrite solutions yielded the corresponding S-nitrosothiol nitric oxide (NO) donors (G4-SNAP, G4-NACysNO). Chemiluminescent NO detection demonstrated that the dendrimers were capable of storing ~2 ?mol NO·mg?1 when exposed to triggers of S-nitrosothiol decomposition (e.g., light and copper). The kinetics of NO-release were found to be highly dependent on the structure of the nitrosothiol (i.e., tertiary vs. primary) and exhibited similar NO-release characteristics to classical small molecule nitrosothiols reported in the literature. As demonstration of utility, the ability of G4-SNAP to inhibit thrombin-mediated platelet aggregation was assayed. At equivalent nitrosothiol concentrations (25 ?M), the G4-SNAP dendrimer resulted in a 62% inhibition of platelet aggregation, compared to only 17% for the small molecule NO donor. The multivalent NO storage, the dendritic effects exerted on nitrosothiol stability and reactivity, and the utility of dendrimers as drug delivery vehicles highlight the potential of these constructs as clinically useful S-nitrosothiol-based therapeutics. PMID:18247567

Stasko, Nathan A.; Fischer, Thomas H.

2013-01-01

383

Inaccuracies of nitric oxide measurement methods in biological media  

PubMed Central

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

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

2013-01-01

384

Neurovascular protection by ischaemic tolerance: role of nitric oxide  

PubMed Central

Abstract Nitric oxide (NO) has emerged as a key mediator in the mechanisms of ischaemic tolerance induced by a wide variety of preconditioning stimuli. NO is involved in the brain protection that develops either early (minutes–hours) or late (days–weeks) after the preconditioning stimulus. However, the sources of NO and the mechanisms underlying the protective effects differ substantially. While in early preconditioning NO is produced by the endothelial and neuronal isoform of NO synthase, in delayed preconditioning NO is synthesized by the inducible or ‘immunological’ isoform of NO synthase. Furthermore, in early preconditioning, NO acts through the canonical cGMP pathway, possibly through protein kinase G and opening of mitochondrial KATP channels. In late preconditioning, the protection is mediated by peroxynitrite formed by the reaction of NO with superoxide derived from the enzyme NADPH oxidase. The mechanisms by which peroxynitrite exerts its protective effect may include improvement of post-ischaemic cerebrovascular function, leading to enhancement of blood flow to the ischaemic territory, and expression of prosurvival genes resulting in cytoprotection. The evidence suggests that NO can engage highly effective and multifunctional prosurvival pathways, which could be exploited for the prevention and treatment of cerebrovascular pathologies. PMID:21746790

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

2011-01-01

385

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

NASA Astrophysics Data System (ADS)

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

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

2014-12-01

386

Effects of simulated microgravity on arterial nitric oxide synthase and nitrate and nitrite content  

NASA Technical Reports Server (NTRS)

The aim of the present work was to investigate the alterations in nitric oxide synthase (NOS) expression and nitrate and nitrite (NOx) content of different arteries from simulated microgravity rats. Male Wistar rats were randomly assigned to either a control group or simulated microgravity group. For simulating microgravity, animals were subjected to hindlimb unweighting (HU) for 20 days. Different arterial tissues were removed for determination of NOS expression and NOx. Western blotting was used to measure endothelial NOS (eNOS) and inducible NOS (iNOS) protein content. Total concentrations of NOx, stable metabolites of nitric oxide, were determined by the chemiluminescence method. Compared with controls, isolated vessels from simulated microgravity rats showed a significant increase in both eNOS and iNOS expression in carotid arteries and thoracic aorta and a significant decrease in eNOS and iNOS expression of mesenteric arteries. The eNOS and iNOS content of cerebral arteries, as well as that of femoral arteries, showed no differences between the two groups. Concerning NOx, vessels from HU rats showed an increase in cerebral arteries, a decrease in mesenteric arteries, and no change in carotid artery, femoral artery and thoracic aorta. These data indicated that there were differential alterations in NOS expression and NOx of different arteries after hindlimb unweighting. We suggest that these changes might represent both localized adaptations to differential body fluid redistribution and other factors independent of hemodynamic shifts during simulated microgravity.

Ma, Jin; Kahwaji, Chadi I.; Ni, Zhenmin; Vaziri, Nosratola D.; Purdy, Ralph E.

2003-01-01

387

Microarray analysis of nitric oxide responsive transcripts in Arabidopsis.  

PubMed

Nitric oxide (NO) is emerging as an important signalling molecule with diverse physiological functions in plants. In the current study, changes in gene expression in response to 0.1 mm and 1.0 mm sodium nitroprusside (SNP), a donor of NO, were studied in Arabidopsis using the whole genome ATH1 microarray, representing over 24,000 genes. We observed 342 up-regulated and 80 down-regulated genes in response to NO treatments. These included 126 novel genes with unknown functions. Most of these changes were specific to NO treatment, as we observed a reverse trend when the plants were treated with NO scavenger, 2-[4-carboxyphenyl]-4,4,5,5-tetramethylimidazoline-1-oxy-3-oxide (c-PTIO). Hierarchical clustering revealed 162 genes showing a dose-dependent increase in signal from 0.1 mm SNP to 1.0 mm SNP treatment. We observed the up-regulation of several genes encoding disease-resistance proteins, WRKY proteins, transcription factors, zinc finger proteins, glutathione S-transferases, ABC transporters, kinases and biosynthetic genes of ethylene, jasmonic acid, lignin and alkaloids. This report provides an insight into the molecular basis for the seemingly diverse biological functions of NO in plants. Interestingly, about 2.0% of the genes in Arabidopsis responded to NO treatment, about 10% of which were transcription factors. NO may also influence the plant's signal transduction network as indicated by the transcriptional activation of several protein kinases, including a mitogen-activated protein (MAP) kinase. We identified many genes previously not shown to be associated with NO responses in plants, and this is the first report of NO responsive genes based on a whole genome microarray. PMID:17134397

Parani, Madasamy; Rudrabhatla, Sairam; Myers, Rachel; Weirich, Heatherbea; Smith, Bruce; Leaman, Douglas W; Goldman, Stephen L

2004-07-01

388

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

NASA Technical Reports Server (NTRS)

The oxidative reaction of hexamethylbenzene (HMB) with nitric acid was studied, and the hitherto unknown polymethylbenzenepolycarboxylic acids were isolated: tetramethylphthalic anhydride, tetramethylisophthalic acid, 1,3,5-, 1,2,4- and 1,2,3-trimethylbenzenetricarboxylic acids. When HMB was warmed with 50% nitric acid at about 80 C, tetramethylphthalic anhydride and tetramethylisophthalic acid were initially produced. The continued reaction led to the production of trimethylbenzenetricarboxylic acids, but only slight amounts of dimethylbenzenetetracarboxylic acids were detected in the reaction mixture. Whereas tetramethylphthalic anydride and tetramethylisophthalic acid were obtained, pentamethylbenzoic acid, a possible precursor of them, was scarcely produced. On the other hand, a yellow material extracted with ether from the initial reaction mixture contained bis-(nitromethyl)prehnitene (CH3)4C6(CH2NO2)2, which was easily converted into the phthalic anhydride.

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

1986-01-01

389

Voltage-dependent anion channel-2 interaction with nitric oxide synthase enhances pulmonary artery endothelial cell nitric oxide production.  

PubMed

Increased pulmonary artery endothelial cell (PAEC) endothelium-dependent nitric oxide synthase (eNOS) activity mediates perinatal pulmonary vasodilation. Compromised eNOS activity is central to the pathogenesis of persistent pulmonary hypertension of the newborn (PPHN). Voltage-derived anion channel (VDAC)-1 was recently demonstrated to bind eNOS in the systemic circulation. We hypothesized that VDAC isoforms modulate eNOS activity in the pulmonary circulation, and that decreased VDAC expression contributes to PPHN. In PAECs derived from an ovine model of PPHN: (1) there is eNOS activity, but not expression; and (2) VDAC1 and -2 proteins are decreased. Immunocytochemistry, coimmunoprecipitation, and in situ proximity ligation assays in human PAECs (hPAECs) demonstrate binding between eNOS and both VDAC1 and -2, which increased upon stimulation with NO agonists. The ability of agonists to increase the eNOS/VDAC interaction was significantly blunted in hypertensive, compared with normotensive, ovine PAECs. Depletion of VDAC2, but not VDAC1, blocked the agonist-induced increase in eNOS activity in hPAECs. Overexpression of VDAC2 in hypertensive PAECs increased eNOS activity. Binding of VDAC2 enhances eNOS activity in the pulmonary circulation, and diminished VDAC2 constrains eNOS in PAECs derived from fetal lambs with chronic intrauterine pulmonary hypertension. We speculate that decreases in VDAC2 may contribute to the limited eNOS activity that characterizes pulmonary hypertension. PMID:22842492

Alvira, Cristina M; Umesh, Anita; Husted, Cristiana; Ying, Lihua; Hou, Yanli; Lyu, Shu-Chen; Nowak, Jeffrey; Cornfield, David N

2012-11-01

390

Voltage-Dependent Anion Channel-2 Interaction with Nitric Oxide Synthase Enhances Pulmonary Artery Endothelial Cell Nitric Oxide Production  

PubMed Central

Increased pulmonary artery endothelial cell (PAEC) endothelium-dependent nitric oxide synthase (eNOS) activity mediates perinatal pulmonary vasodilation. Compromised eNOS activity is central to the pathogenesis of persistent pulmonary hypertension of the newborn (PPHN). Voltage-derived anion channel (VDAC)-1 was recently demonstrated to bind eNOS in the systemic circulation. We hypothesized that VDAC isoforms modulate eNOS activity in the pulmonary circulation, and that decreased VDAC expression contributes to PPHN. In PAECs derived from an ovine model of PPHN: (1) there is eNOS activity, but not expression; and (2) VDAC1 and -2 proteins are decreased. Immunocytochemistry, coimmunoprecipitation, and in situ proximity ligation assays in human PAECs (hPAECs) demonstrate binding between eNOS and both VDAC1 and -2, which increased upon stimulation with NO agonists. The ability of agonists to increase the eNOS/VDAC interaction was significantly blunted in hypertensive, compared with normotensive, ovine PAECs. Depletion of VDAC2, but not VDAC1, blocked the agonist-induced increase in eNOS activity in hPAECs. Overexpression of VDAC2 in hypertensive PAECs increased eNOS activity. Binding of VDAC2 enhances eNOS activity in the pulmonary circulation, and diminished VDAC2 constrains eNOS in PAECs derived from fetal lambs with chronic intrauterine pulmonary hypertension. We speculate that decreases in VDAC2 may contribute to the limited eNOS activity that characterizes pulmonary hypertension. PMID:22842492

Alvira, Cristina M.; Umesh, Anita; Husted, Cristiana; Ying, Lihua; Hou, Yanli; Lyu, Shu-Chen; Nowak, Jeffrey

2012-01-01

391

Comparability of a hand-held nitric oxide analyser with online and offline chemiluminescence-based nitric oxide measurement.  

PubMed

Practicability is crucial for successful implementation of fractional exhaled nitric oxide (FeNO) measurement into asthma management. The study aimed at comparing a conventional chemiluminescence NO analyser (EcoMedics) with a hand-held device (NIOX MINO) and offline FeNO measurement using a commercially available system in an unselected cohort of children aged 6-16 yr. A secondary objective was to confirm FeNO stability over time in 15 samples from adult volunteers obtained using the offline system. Sixty-six children (mean +/- s.d. age 11.8 +/- 3.0 yr) underwent single breath FeNO measurement in triplets with each device. Offline collected FeNO was measured after offline breath collection into a Mylar balloon and subsequent analysis using the chemiluminescence NO analyser. Variability and between-method agreement were assessed, and stability over time within the Mylar balloons was tested by repeated hourly measurements. FeNO levels ranged from 2 to 113 p.p.b. Intra-class correlation was excellent (r = 0.98, p < 0.001 for each pair). Bland-Altman plots and back-transformation of logarithmic mean differences revealed fair agreement between methods. Stability over time was confirmed over 10 h both at room temperature and when stored under cooling conditions. FeNO values obtained using the chemiluminescence NO analyser, the portable NIOX MINO system and the offline collection technique show between-method agreement within clinically acceptable range. PMID:19682277

Schiller, Barbara; Hammer, Juerg; Barben, Juerg; Trachsel, Daniel

2009-11-01

392

Manganese-induced oxidative stress in two ontogenetic stages of chamomile and amelioration by nitric oxide.  

PubMed

Impact of manganese (Mn(2+)) excess (100, 500 and 1000 ?M over 7 days) on two ontogenetic stages (7-week-old plants and 7-day-old seedlings) of Matricaria chamomilla was compared. Mn excess depressed growth of seedlings (but not germination) and stimulated oxidative stress (ROS and lipid peroxidation) in both plants and seedlings. Growth inhibition could be evoked by higher Mn uptake and higher translocation factor in seedlings than in plants. Total thiols staining revealed elevation in almost all treatments. In 7-week-old plants, activity of peroxidases increased slightly and rather decreased under high Mn doses. Superoxide rather than hydrogen peroxide contributed to visualized ROS presence. Fluorescence of nitric oxide (NO) showed stimulation in plants but decrease in seedlings. Impact of exogenous nitric oxide donor (sodium nitroprusside/SNP) was therefore tested and results showed amelioration of 1000 ?M Mn-induced oxidative stress in seedlings (decrease in H2O2 and increase in NO content while antioxidative enzyme activities were variably affected) concomitantly with depleted Mn accumulation. It is concluded that NO participates in tolerance to Mn excess but negative effects of the highest SNP dose were also observed. Extensive fluorescence microscopy is also explanatively discussed. PMID:24388509

Ková?ik, Jozef; Babula, Petr; Hedbavny, Josef; Švec, Pavel

2014-02-01

393

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

PubMed

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

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

2000-08-01

394

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

PubMed Central

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

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

2013-01-01

395

Control of nitric oxide production by endogenous TGF-?1 and systemic nitric oxide in retinal pigment epithelial cells and peritoneal macrophages  

Microsoft Academic Search

Both in vivo and in vitro experiments demonstrate that transforming growth factor-ni (TGF4h) suppresses expression of the inducible form of nitric oxide synthase (iNOS). In this study, we examined the effects of exogenous and endo- genous TGF-?1 on retinal pigment epithelial (RPE) cells and resident peritoneal macrophages ex vivo using cells from TGF-?1 null (TGF-(?1\\

Yoram Vodovoz; John J. Letterio; Andrew G. Gemser; Anita B. Roberts; Janet Sparrow

396

Expression of nitric oxide synthases and effects ofl-arginine and l-NMMA on nitric oxide production and fluid transport in collagenous colitis  

Microsoft Academic Search

BACKGROUND AND AIMSLuminal nitric oxide (NO) is greatly increased in the colon of patients with collagenous and ulcerative colitis. To define the source and consequence of enhanced NO production we have studied expression of NO synthase (NOS) isoforms and nitrotyrosine in mucosal biopsies from these patients. In addition, effects on colonic fluid transfer caused by manipulating the substrate of NOS

A Perner; L Andresen; M Normark; B Fischer-Hansen; S Sørensen; J Eugen-Olsen; J Rask-Madsen

2001-01-01

397

Nitric oxide gas stimulates germination of dormant Arabidopsis seeds: use of a flow-through apparatus for delivery of nitric oxide  

Microsoft Academic Search

Nitric oxide (NO) is a gaseous free radical that reacts with O2 in air and aqueous solution. NO donors have been widely used to circumvent the difficulties inherent in working with a reactive gas, but NO donors do not deliver NO at a constant rate for prolonged periods of time. Furthermore, some of the most commonly used NO donors produce

Igor G. L. Libourel; Paul C. Bethke; Roberto De Michele; Russell L. Jones

2006-01-01

398

Fundamentals of nitric oxide formation in fossil fuel combustion  

Microsoft Academic Search

Combustion of fossil fuels in large stationary furnaces causes the emission of nitrogen oxides, a large fraction of which arise from the nitrogen-containing components in the fuel, producing a major pollution problem which is expected to increase severely in the future. The results reported in this paper are part of those obtained from a continuing study to determine the mechanism

T. J. Houser; M. E. McCarville; G. Zhou-Ying

1986-01-01

399

Endothelial nitric oxide synthase pathophysiology after nonocclusive common carotid artery thrombosis in rats.  

PubMed

Although vascular dysregulation has been documented in patients with extracranial vascular disease, transient ischemic attacks, and stroke, the pathomechanisms are poorly understood. To model thromboembolic stroke in rats, photochemically induced nonocclusive common carotid artery thrombosis (CCAT) was used to generate a platelet thrombus in the carotid artery of anesthetized rats. After CCAT, platelet aggregates break off the thrombus, travel to the distal cerebral vasculature, damage blood vessels, and cause small infarctions. The authors hypothesized that deficits in the endothelial nitric oxide synthase (eNOS) pathway may be responsible for vascular dysfunction after embolic stroke. To examine the functional status of the eNOS system, they measured eNOS-dependent dilation after CCAT by applying acetylcholine through a cranial window over the middle cerebral artery. The authors also measured eNOS mRNA and protein in the middle cerebral artery to determine whether functional changes were caused by alterations in expression. eNOS-dependent dilation was reduced at 6 hours, elevated at 24 hours, and returned to baseline 72 hours after CCAT. Endothelial nitric oxide synthase mRNA increased at 2 hours and was followed by a rise in protein 24 hours after CCAT. Changes in the eNOS system may account for some of the observed vascular deficits in patients with cerebrovascular disease. PMID:11973434

Danton, Gary H; Prado, Ricardo; Truettner, Jessie; Watson, Brant D; Dietrich, W Dalton

2002-05-01

400

Site of pulmonary vasodilation by inhaled nitric oxide in the perfused lung  

SciTech Connect

Site of pulmonary vasodilation by inhaled nitric oxide in the perfused lung. To determine the site of inhaled nitric oxide (NO)-induced pulmonary vasodilation, a double vascular occlusion technique was used with rabbit lungs ventilated and perfused at 20 ml/min with Krebs solution containing 3% dextran and 30 {mu}M indomethacin. Inhaled NO (120 ppm for 3% min) reduced pulmonary vasoconstriction produced by U-46619 infusion (0.5 -1.2 nmol/min), significantly decreasing total resistance (RT) [1,080 {plus_minus} 51 (SE) vs. 1,545 {plus_minus} 109 mmHg-min/l; P < 0.01]. Acetylcholine infusion (ACh; 2-5 nmol/min) and nitroglycerin (NTG; 0.35 {mu}mol) likewise decreased RT. Arterial resistance (Ra) was also significantly less with inhaled NO, ACh, and NTG compared with U-46619 alone. Venous resistance (Rv), however, was unchanged. When the direction of perfusion was reversed in the lung, inhaled NO, ACh, and NTG significantly decreased RT compared with U-46619 alone, and Rv was also reduced by all three agents. After electrolysis-induced acute lung injury, inhaled NO significantly reduced both RT and Ra compared with U-46619 alone, whereas Rv was unaffected. Our results demonstrate that inhaled NO gas affects primarily the arterial (precapillary) component of the pulmonary circulation but, under conditions of extreme venous constriction, may dilate the postcapillary component as well. 25 refs., 4 figs.

Rimar, S.; Gillis, C.N. [Yale Univ. School of Medicine, New Haven, CT (United States)

1995-05-01

401

Nitric oxide synthase in the enteric nervous system of the rainbow trout, Salmo gairdneri.  

PubMed

The distribution of nitric oxide synthase (NOS) was determined in the gastrointestinal tract of the rainbow trout, Salmo gairdneri. NOS immunoreactivity and the NADPH diaphorase histochemical reaction were co-localized in nerve cells in the myenteric ganglia. However, only about 60% of NADPH diaphorase-stained nerve cells in the vagus nerve trunks were immunoreactive for NOS. Reactive myenteric nerve cells were found throughout the gastrointestinal tract, comprising about 10-15% of all nerve cells. Reactive nerve cells and fibres appeared in the myenteric ganglia and nerve trunks. The circular muscle was innervated by reactive nerve fibres throughout the gastrointestinal tract. Some NOS-containing cell bodies were also in this layer. The submucous plexus contained reactive nerve fibres in each region of the gut; in the large intestine a few reactive nerve cell bodies were also seen in this plexus. The muscle in the mucosal folds of the large intestine was densely innervated. The observations suggest that nitric oxide is an enteric transmitter in teleost fish, as it is in mammals. PMID:7690579

Li, Z S; Furness, J B

1993-06-01

402

Borna disease virus P protein inhibits nitric oxide synthase gene expression in astrocytes  

SciTech Connect

Borna disease virus (BDV) is one of the potential infectious agents involved in the development of central nervous system (CNS) diseases. Neurons and astrocytes are the main targets of BDV infection, but little is known about the roles of BDV infection in the biological effects of astrocytes. Here we reported that BDV inhibits the activation of inducible nitric oxide synthase (iNOS) in murine astrocytes induced by bacterial LPS and PMA. To determine which protein of BDV is responsible for the regulation of iNOS expression, we co-transfected murine astrocytes with reporter plasmid iNOS-luciferase and plasmid expressing individual BDV proteins. Results from analyses of reporter activities revealed that only the phosphoprotein (P) of BDV had an inhibitory effect on the activation of iNOS. In addition, P protein inhibits nitric oxide production through regulating iNOS expression. We also reported that the nuclear factor kappa B (NF-{kappa}B) binding element, AP-1 recognition site, and interferon-stimulated response element (ISRE) on the iNOS promoter were involved in the repression of iNOS gene expression regulated by the P protein. Functional analysis indicated that sequences from amino acids 134 to 174 of the P protein are necessary for the regulation of iNOS. These data suggested that BDV may suppress signal transduction pathways, which resulted in the inhibition of iNOS activation in astrocytes.

Peng Guiqing [State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072 (China); Zhang Fengmin [College of Basic Medical Science, Harbin Medical University, Harbin 150081 (China); Zhang Qi; Wu Kailang; Zhu Fan [State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072 (China); Wu Jianguo [State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072 (China)], E-mail: jwu@edu.edu.cn

2007-09-30

403

Atorvastatin inhibits calcification and enhances nitric oxide synthase production in the hypercholesterolaemic aortic valve  

PubMed Central

Objective: To study in a rabbit model the expression of endothelial nitric oxide synthase (eNOS) in association with the development of calcification of the aortic valve, and to assess the effects of atorvastatin on eNOS expression, nitrite concentration, and aortic valve calcification. Methods: Rabbits (n ?=? 48) were treated for three months: 16, forming a control group, were fed a normal diet; 16 were fed a 0.5% (wt/wt) high cholesterol diet; and 16 were fed a 0.5% (wt/wt) cholesterol diet plus atorvastatin (2.5 mg/kg/day). The aortic valves were examined with eNOS immunostains and western blotting. Cholesterol and high sensitivity C reactive protein (hsCRP) concentrations were determined by standard assays. Serum nitrite concentrations were measured with a nitric oxide analyser. eNOS was localised by electron microscopy and immunogold labelling. Calcification in the aortic valve was evaluated by micro-computed tomography (CT). Results: Cholesterol, hsCRP, and aortic valve calcification were increased in the cholesterol fed compared with control animals. Atorvastatin inhibited calcification in the aortic valve as assessed by micro-CT. eNOS protein concentrations were unchanged in the control and cholesterol groups but increased in the atorvastatin treated group. Serum nitrite concentrations were decreased in the hypercholesterolaemic animals and increased in the group treated with atorvastatin. Conclusion: These data provide evidence that chronic experimental hypercholesterolaemia produces bone mineralisation in the aortic valve, which is inhibited by atorvastatin. PMID:15894785

Rajamannan, N M; Subramaniam, M; Stock, S R; Stone, N J; Springett, M; Ignatiev, K I; McConnell, J P; Singh, R J; Bonow, R O; Spelsberg, T C

2005-01-01

404

Open randomised controlled trial of inhaled nitric oxide and early dexamethasone in high risk preterm infants  

PubMed Central

AIM—To determine whether treatment with inhaled nitric oxide (NO) and/or dexamethasone reduces the incidence of chronic lung disease (CLD) and/or death in high risk preterm infants.?METHODS—Infants below 32 weeks of gestation were recruited at 96 hours of age if they were deemed to be at high risk of developing CLD. Infants were randomly assigned to one of four treatment groups using a factorial design: (1) 5-20 parts per million inhaled NO for 72 hours; (2) 0.5-1 mg/kg/day intravenous dexamethasone for 6 days; (3) both drugs together; (4) continued conventional management.?RESULTS—Forty two infants were randomised: 10 infants received inhaled NO alone; 11 dexamethasone alone; 10 both treatments; and 11 neither treatment. There was no difference in the combined incidence of CLD and/or death before discharge from hospital between either infants treated with inhaled NO and controls (RR 1.05, 95% CI 0.84-1.25), or those treated with dexamethasone and controls (RR 0.95, 95% CI 0.79-1.18).?CONCLUSIONS—At 96 hours of age, neither treatment with inhaled NO nor dexamethasone prevented CLD or death.?? Keywords: randomised controlled trial; nitric oxide; dexamethasone; chronic lung disease PMID:9462187

Subhedar, N; Ryan, S; Shaw, N

1997-01-01

405

Nitric Oxide Synthesis Is Increased in Cybrid Cells with m.3243A>G Mutation  

PubMed Central

Nitric oxide (NO) is a free radical and a signaling molecule in several pathways, produced by nitric oxide synthase (NOS) from the conversion of l-arginine to citrulline. Supplementation of l-arginine has been used to treat MELAS (mitochondrial encephalopathy with lactic acidosis and stroke like syndrome), a mitochondrial disease caused by the m.3243A>G mutation. Low levels of serum arginine and endothelium dysfunction have been reported in MELAS and this treatment may increase NO in endothelial cells and promote vasodilation, decreasing cerebral ischemia and strokes. Although clinical benefits have been reported, little is known about NO synthesis in MELAS. In this study we found that osteosarcoma derived cybrid cells with high levels of m.3243A>G had increased nitrite, an NO metabolite, and increased intracellular NO, demonstrated by an NO fluorescent probe (DAF-FM). Muscle vessels from patients with the same mutation had increased staining in NADPH diaphorase, suggestive of increased NOS. These results indicate increased production of NO in cells harboring the m.3243A>G, however no nitrated protein was detected by Western blotting. Further studies are necessary to clarify the exact mechanisms of l-arginine effect to determine the appropriate clinical use of this drug therapy. PMID:23263669

Gamba, Juliana; Gamba, Luana T.; Rodrigues, Gabriela S.; Kiyomoto, Beatriz H.; Moraes, Carlos T.; Tengan, Celia H.

2013-01-01

406

Temporal expression of hepatic inducible nitric oxide synthase in liver cirrhosis  

PubMed Central

AIM: Nitric oxide (NO) has been implicated in the pathogenesis of liver cirrhosis. We have found inducible nitric oxide synthase (iNOS) can be induced in hepatocytes of cirrhotic liver. This study further investigated the temporal expression and activity of hepatic iNOS in cirrhosis development. METHODS: Cirrhosis was induced in rats by chronic bile duct ligation (BDL). At different time points after the operation, samples were collected to examine NO concentration, liver function, and morphological changes. Hepatocytes were isolated for determination of iNOS mRNA, protein and enzymatic activity. RESULTS: Histological examination showed early cirrhosis 1-2 wk after BDL, with advanced cirrhosis at 3-4 wk. Bilirubin increased dramatically 3 d after BDL, but decreased by 47% on d 14. Three weeks after BDL, it elevated again. Systemic NO concentration did not increase significantly until 4 wk after BDL, when ascites developed. Hepatocyte iNOS mRNA expression was identified 3 d after BDL, and enhanced with time to 3 wk, but reduced thereafter. iNOS protein showed a similar pattern to mRNA expression. iNOS activity decreased from d 3 to d 7, but increased again thereafter till d 21. CONCLUSION: Hepatic iNOS can be induced in the early stage, which increases with time as cirrhosis develops. Its enzymatic activity is significantly correlated with protein expression and histological alterations of the liver, but not with systemic NO levels, nor with absolute values of liver function markers. PMID:15637745

Wei, Chang-Li; Hon, Wei-Min; Lee, Kang-Hoe; Khoo, Hoon-Eng

2005-01-01

407

Off-line exhaled nitric oxide measurements in children.  

PubMed

The concentration of exhaled nitric oxide (eNO) is a useful marker of asthmatic bronchial inflammation. eNO can now be measured away from the laboratory (off-line), even in children. Short exhalation maneuvers (8 sec) and small samples (1 L) of exhaled gas are probably sufficient in children, but more information is needed about the effect of different measurement conditions. As a preliminary step before conducting epidemiological studies in schoolchildren, we investigated the effects of expiratory flow, dead space, and expiratory time on eNO concentrations collected in 1-L mylar collection bags. We studied 101 cooperative subjects (62 males) aged 5-18 years (30 healthy volunteers, 51 asthmatics, and 20 children with various other respiratory diseases) in our pulmonary function laboratory. On-line and off-line eNO were compared in a single session, and analyzed with a Sievers NOA 280 nitric oxide analyzer. For both methods of collecting expired gas, subjects did a single exhalation without breath-holding against an expiratory pressure 10 cm H(2)O. We investigated the effects of expiratory flow, dead space, and exhalation time on eNO; we also compared on-line and off-line eNO measurements, and the repeatability of both techniques at a given flow rate. Expiratory flows of 58 mL/sec provided more reproducible data than lower flows (coefficient of repeatability 1.1 ppb for 58 mL/sec vs. 2.8 for 27 mL/sec vs. 5.7 for 18 mL/sec). eNO concentrations were about 25% higher in off-line than in on-line recordings if the initial 250 mL of exhaled gas were not eliminated, and 37% higher if exhalation lasted longer (16 sec vs. 8 sec). Eliminating 250 mL of dead space and shortening the filling time to 8 sec yielded off-line eNO values close to those on-line (geometric mean off-line eNO 14.4 ppb, 95% confidence interval: 12.2-17.0) vs. on-line eNO 13.8 ppb (95% confidence interval: 11.6-16.5). On-line and off-line results were highly correlated (r = 0.996, P = 0.000) and had similar coefficients of variation (on-line eNO 2.6%, off-line 2.8%). Neither agreement nor repeatability of eNO measurements were affected by disease status or baseline FEV(1) (% predicted values). Once standardized, the off-line eNO technique using 1-L gas collection bags will provide results similar to those recorded on-line. PMID:11477733

Barreto, M; Villa, M P; Martella, S; Falasca, C; Guglielmi, F; Pagani, J; Darder, M T; Ronchetti, R

2001-08-01

408

Nitric Oxide Directly Promotes Vascular Endothelial Insulin Transport  

PubMed Central

Insulin resistance strongly associates with decreased nitric oxide (NO) bioavailability and endothelial dysfunction. In the vasculature, NO mediates multiple processes that affect insulin delivery, including dilating both resistance and terminal arterioles in skeletal muscle in vivo. However, whether NO directly regulates vascular endothelial cell (EC) insulin uptake and its transendothelial transport (TET) is unknown. We report in this article that l-NG-nitro-l-arginine methyl ester (l-NAME) pretreatment blocked, whereas l-arginine and sodium nitroprusside (SNP) each enhanced, EC uptake of fluorescein isothiocyanate (FITC)-labeled insulin. SNP also partly or fully reversed the inhibition of EC insulin uptake caused by l-NAME, wortmannin, the Src inhibitor PP1, and tumor necrosis factor-?. In addition, SNP promoted [125I]TyrA14insulin TET by ?40%. Treatment with insulin with and without SNP did not affect EC cyclic guanosine monophosphate (cGMP) levels, and the cGMP analog 8-bromo-cGMP did not affect FITC-insulin uptake. In contrast, treatment with insulin and SNP significantly increased EC protein S-nitrosylation, the colocalization of S-nitrosothiol (S-NO) and protein-tyrosine phosphatase 1B (PTP1B), and Akt phosphorylation at Ser473 and inhibited PTP1B activity. Moreover, a high-fat diet significantly inhibited EC insulin-stimulated Akt phosphorylation and FITC-insulin uptake that was partially reversed by SNP in rats. Finally, inhibition of S-nitrosylation by knockdown of thioredoxin-interacting protein completely eliminated SNP-enhanced FITC-insulin uptake. We conclude that NO directly promotes EC insulin transport by enhancing protein S-nitrosylation. NO also inhibits PTP1B activity, thereby enhancing insulin signaling. PMID:23863813

Wang, Hong; Wang, Aileen X.; Aylor, Kevin; Barrett, Eugene J.

2013-01-01

409

?-Carotene As a Lipophilic Scavenger of Nitric Oxide.  

PubMed

The efficient bleaching following continuous bubbling of gaseous nitric oxide (NO(•)) to ?-carotene (?-Car) dissolved in n-hexane under anaerobic conditions results from an initial addition of two NO(•) followed by fragmentation coupled with further NO(•) addition as shown by mass spectrometry (MS). Density functional theory (DFT) calculations demonstrated that hydrogen atom transfer (HAT) and electron transfer (ET) from ?-Car to NO(•) are strongly energetically unfavorable in contrast to radical adduct formation (RAF) followed by degradation. The results indicated the lowest energy for addition of the first NO(•) at C7 with an activation free energy of ?G(?) = 74.40 kJ mol(-1) and a rate constant of 0.56 s(-1), followed by trans-addition of a second NO(•) at C8 with ?G(?) = 55.51 kJ mol(-1). MS confirmed the formation of a dinitrosyl-?-Car (596.6 m/z), and of a ?-Car fragment (400.4 m/z) formed by C7/C8 bond cleavage and suggested to be of importance for progression of bleaching. Up to eight reaction products with increasing mass of 28 m/z are assigned to continuous addition of NO(•) to the initially formed fragment forming nitroxides. Continuous wave photolysis of sodium nitroprusside (SNP) as a NO(•) source dissolved together with ?-Car in 4:1 (v/v) methanol:tetrahydrofuran gradually bleached ?-Car. Nanosecond laser flash photolysis at 355 nm followed by transient absorption spectroscopy showed a ?-Car derived intermediate with an absorption maximum around 420 nm in agreement with a prediction (425 nm) from time-dependent DFT (TDDFT) for the trans-C7,8 dinitrosyl adduct of ?-Car. The NO(•) adduct of ?-Car decays with a rate constant of ?10(7) s(-1) at 25 °C. PMID:25226353

Han, Rui-Min; Cheng, Hong; Feng, Ruopei; Li, Dan-Dan; Lai, Wenzhen; Zhang, Jian-Ping; Skibsted, Leif H

2014-10-01

410

Fluorinated Xerogel-Derived Microelectrodes for Amperometric Nitric Oxide Sensing  

PubMed Central

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

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

2009-01-01

411

Significant blood resistance to nitric oxide transfer in the lung  

PubMed Central

Lung diffusing capacity for nitric oxide (DlNO) is used to measure alveolar membrane conductance (DmNO), but disagreement remains as to whether DmNO = DlNO, and whether blood conductance (?NO) = ?. Our previous in vitro and in vivo studies suggested that ?NO < ?. We now show in a membrane oxygenator model perfused with whole blood that addition of a cell-free bovine hemoglobin (Hb) glutamer-200 solution increased diffusing capacity of the circuit (D) for NO (Dno) by 39%, D for carbon monoxide (Dco) by 24%, and the ratio of Dno to Dco by 12% (all P < 0.001). In three anesthetized dogs, DlNO and DlCO were measured by a rebreathing technique before and after three successive equal volume-exchange transfusions with bovine Hb glutamer-200 (10 ml/kg each, total exchange 30 ml/kg). At baseline, DlNO/DlCO = 4.5. After exchange transfusion, DlNO rose 57 ± 16% (mean ± SD, P = 0.02) and DlNO/DlCO = 7.1, whereas DlCO remained unchanged. Thus, in vitro and in vivo data directly demonstrate a finite ?NO. We conclude that the erythrocyte and/or its immediate environment imposes considerable resistance to alveolar-capillary NO uptake. DlNO is sensitive to dynamic hematological factors and is not a pure index of conductance of the alveolar tissue membrane. With successive exchange transfusion, the estimated in vivo ?NO [5.1 ml NO·(ml blood·min·Torr)?1] approached 4.5 ml NO·(ml blood·min·Torr)?1, which was derived from in vitro measurements by Carlsen and Comroe (J Gen Physiol 42: 83–107, 1958). Therefore, we suggest use of ?NO = 4.5 ml NO·(min·Torr·ml blood)?1 for calculation of DmNO and pulmonary capillary blood volume from DlNO and DlCO. PMID:20150569

Dunningham, Helen; Bottrill, Fiona; Vuylsteke, Alain; Yilmaz, Cuneyt; Dane, D. Merrill; Hsia, Connie C. W.

2010-01-01

412

Bronchodilator action of inhaled nitric oxide in guinea pigs.  

PubMed Central

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

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

1992-01-01

413

Nitric oxide and phytohormone interactions: current status and perspectives.  

PubMed

Nitric oxide (NO) is currently considered a ubiquitous signal in plant systems, playing significant roles in a wide range of responses to environmental and endogenous cues. During the signaling events leading to these plant responses, NO frequently interacts with plant hormones and other endogenous molecules, at times originating remarkably complex signaling cascades. Accumulating evidence indicates that virtually all major classes of plant hormones may influence, at least to some degree, the endogenous levels of NO. In addition, studies conducted during the induction of diverse plant responses have demonstrated that NO may also affect biosynthesis, catabolism/conjugation, transport, perception, and/or transduction of different phytohormones, such as auxins, gibberellins, cytokinins, abscisic acid, ethylene, salicylic acid, jasmonates, and brassinosteroids. Although still not completely elucidated, the mechanisms underlying the interaction between NO and plant hormones have recently been investigated in a number of species and plant responses. This review specifically focuses on the current knowledge of the mechanisms implicated in NO-phytohormone interactions during the regulation of developmental and metabolic plant events. The modifications triggered by NO on the transcription of genes encoding biosynthetic/degradative enzymes as well as proteins involved in the transport and signal transduction of distinct plant hormones will be contextualized during the control of developmental, metabolic, and defense responses in plants. Moreover, the direct post-translational modification of phytohormone biosynthetic enzymes and receptors through S-nitrosylation will also be discussed as a key mechanism for regulating plant physiological responses. Finally, some future perspectives toward a more complete understanding of NO-phytohormone interactions will also be presented and discussed. PMID:24130567

Freschi, Luciano

2013-01-01

414

Emission of nitric oxide from soil: laboratory vs. micrometeorological techniques  

NASA Astrophysics Data System (ADS)

High quality field measurements of the surface exchange of nitric oxide (NO) between soils and the atmosphere usually demand complex instrumentation and considerable power supplies. The latter often impedes such flux measurements at remote sites. However, soil samples could be taken everywhere, and consecutive parameterization of NO emission rates (derived from laboratory incubation of these soil samples) and up-scaling through independent data of soil properties (e.g. soil moisture, soil temperature, soil texture) is an effective alternative to quantify NO emission from soils, particularly from (very) remote sites. These laboratory derived NO emission rates have quite frequently verified through field measurements by the dynamic chamber technique. Here, we will present the first intercomparison between the laboratory and a micrometeorological (gradient) technique. In August 2006, the field experiment LIBRETTO (LIndenBerg REacTive Trace gas prOfiles) was carried out in cooperation with the German Meteorological Service (DWD) at the field site of the Richard Aßmann Observatory in Lindenberg. At 0.15 m and 2.0 m, concentrations of the trace gases O3, NO and NO2 were measured. Applying the modified Bowen ration technique to the measured concentration differences and the directly measured sensible heat flux (eddy covariance data from DWD) yielded the field surface fluxes of the trace gases (corrected for their flux divergence due to fast photochemical reactions during the vertical turbulent transport). Soil humidity and temperature in the top soil were measured at a separate plot at the field site. Mixed soil samples were taken in May 2008 at the LIBRETTO field site, air-dried, sieved (

Meixner, F. X.; Mayer, J.-C.; Bargsten, A.; Andreae, M. O.

2009-04-01

415

Nitric oxide and phytohormone interactions: current status and perspectives  

PubMed Central

Nitric oxide (NO) is currently considered a ubiquitous signal in plant systems, playing significant roles in a wide range of responses to environmental and endogenous cues. During the signaling events leading to these plant responses, NO frequently interacts with plant hormones and other endogenous molecules, at times originating remarkably complex signaling cascades. Accumulating evidence indicates that virtually all major classes of plant hormones may influence, at least to some degree, the endogenous levels of NO. In addition, studies conducted during the induction of diverse plant responses have demonstrated that NO may also affect biosynthesis, catabolism/conjugation, transport, perception, and/or transduction of different phytohormones, such as auxins, gibberellins, cytokinins, abscisic acid, ethylene, salicylic acid, jasmonates, and brassinosteroids. Although still not completely elucidated, the mechanisms underlying the interaction between NO and plant hormones have recently been investigated in a number of species and plant responses. This review specifically focuses on the current knowledge of the mechanisms implicated in NO–phytohormone interactions during the regulation of developmental and metabolic plant events. The modifications triggered by NO on the transcription of genes encoding biosynthetic/degradative enzymes as well as proteins involved in the transport and signal transduction of distinct plant hormones will be contextualized during the control of developmental, metabolic, and defense responses in plants. Moreover, the direct post-translational modification of phytohormone biosynthetic enzymes and receptors through S-nitrosylation will also be discussed as a key mechanism for regulating plant physiological responses. Finally, some future perspectives toward a more complete understanding of NO–phytohormone interactions will also be presented and discussed. PMID:24130567

Freschi, Luciano

2013-01-01

416

Production of Nitric Oxide within the Aplysia californica Nervous System  

PubMed Central

Nitric oxide (NO), an intercellular signaling molecule, helps coordinate neuronal network activity. Here we examine NO generation in the Aplysia californica central nervous system using 4,5-diaminofluorescein diacetate (DAF-2 DA), a fluorescent reagent that forms 4,5-diaminofluorescein triazole (DAF-2T) upon reaction with NO. Recognizing that other fluorescence products are formed within the biochemically complex intracellular environment, we validate the observed fluorescence as being from DAF-2T; using both capillary electrophoresis and mass spectrometry we confirm that DAF-2T is formed from tissues and cells exposed to DAF-2 DA. We observe three distinct subcellular distributions of fluorescence in neurons exposed to DAF-2 DA. The first shows uniform fluorescence inside the cell, with these cells being among previously confirmed NO synthase (NOS)-positive regions in the Aplysia cerebral ganglion. The second, seen inside buccal neurons, exhibits point sources of fluorescence, 1.5 ± 0.7 ?m in diameter. Interestingly, the number of fluorescence puncta increases when the tissue is preincubated with the NOS substrate l-arginine, and they disappear when cells are preexposed to the NOS inhibitor l-nitro-arginine methyl ester (l-NAME), demonstrating that the fluorescence is connected to NOS-dependent NO production. The third distribution type, seen in the R2 neuron, also exhibits fluorescent puncta but only on the cell surface. Fluorescence is also observed in the terminals of cultured bag cell neurons loaded with DAF-2 DA. Surprisingly, fluorescence at the R2 surface and bag cell neuron terminals is not modulated by l-arginine or l-NAME, suggesting that it has a source distinct from the buccal and cerebral ganglion DAF 2T-positive tissues. PMID:20532188

2009-01-01

417

The formation of nitric oxide donors from peroxynitrite.  

PubMed Central

1. Administration of peroxynitrite (ONOO-, 30-300 microM) caused relaxation of rabbit aortic strips superfused in series in a cascade. The compound responsible for this effect had a half-life greater than 20 s and could not therefore be either nitric oxide (NO) or ONOO- which have half-lives in the order of 1-2 s under these conditions. However the relaxation was inhibited by oxyhaemoglobin, suggesting the compound could be converted to NO in the vascular tissues or in the superfusate. 2. The products of the reactions between ONOO- and Krebs buffer containing 11 mM glucose, but not glucose-free Krebs buffer, caused relaxation of the bioassay tissues. These data suggest that stable NO donor(s) were formed from the reaction of ONOO- with glucose. We therefore prepared these NO donor(s) by the reaction of glucose solutions with ONOO- in order to characterize their ability to release NO. 3. These reaction product(s) caused relaxation in the cascade and inhibition of platelet aggregation. Both effects were dependent on the concentration of D-glucose, were equally effective if L-glucose was used as a reactant and were reversed by oxyhaemoglobin. 3. The products of the reaction between ONOO- and glucose or other biological molecules containing an alcohol functional group, such as fructose, glycerol, or glyceraldehyde, released NO in the presence of Cu2+and L-cysteine. 5. These results indicate that ONOO- reacts with sugars or other compounds containing an alcohol functional group(s) to form NO donors with the characteristics of organic nitrate/nitrites. This may represent a further detoxification pathway for ONOO- in vivo. PMID:8640338

Moro, M. A.; Darley-Usmar, V. M.; Lizasoain, I.; Su, Y.; Knowles, R. G.; Radomski, M. W.; Moncada, S.

1995-01-01

418

Oxygen tension limits nitric oxide synthesis by activated macrophages.  

PubMed Central

Previous studies have established that constitutive calcium-dependent ('low-output') nitric oxide synthase (NOS) is regulated by oxygen tension. We have investigated the role of oxygen tension in the synthesis of NO by the 'high-output' calcium-independent NOS in activated macrophages. Hypoxia increased macrophage NOS gene expression in the presence of one additional activator, such as lipopolysaccharide or interferon-gamma, but not in the presence of both. Hypoxia markedly reduced the synthesis of NO by activated macrophages (as measured by accumulation of nitrite and citrulline), such that, at 1% oxygen tension, NO accumulation was reduced by 80-90%. The apparent K(m) for oxygen calculated from cells exposed to a range of oxygen tensions was found to be 10.8%, or 137 microM, O(2) This value is considerably higher than the oxygen tension in tissues, and is virtually identical to that reported recently for purified recombinant macrophage NOS. The decrease in NO synthesis did not appear to be due to diminished arginine or cofactor availability, since arginine transport and NO synthesis during recovery in normoxia were normal. Analysis of NO synthesis during hypoxia as a function of extracellular arginine indicated that an altered V(max), but not K(m)(Arg), accounted for the observed decrease in NO synthesis. We conclude that oxygen tension regulates the synthesis of NO in macrophages by a mechanism similar to that described previously for the calcium-dependent low-output NOS. Our data suggest that oxygen tension may be an important physiological regulator of macrophage NO synthesis in vivo. PMID:10970783

McCormick, C C; Li, W P; Calero, M

2000-01-01

419

Nitric oxide-independent vasodilator rescues heme-oxidized soluble guanylate cyclase from proteasomal degradation.  

PubMed

Nitric oxide (NO) is an essential vasodilator. In vascular diseases, oxidative stress attenuates NO signaling by both chemical scavenging of free NO and oxidation and downregulation of its major intracellular receptor, the alphabeta heterodimeric heme-containing soluble guanylate cyclase (sGC). Oxidation can also induce loss of the heme of sGC, as well as the responsiveness of sGC to NO. sGC activators such as BAY 58-2667 bind to oxidized/heme-free sGC and reactivate the enzyme to exert disease-specific vasodilation. Here, we show that oxidation-induced downregulation of sGC protein extends to isolated blood vessels. Mechanistically, degradation was triggered through sGC ubiquitination and proteasomal degradation. The heme-binding site ligand BAY 58-2667 prevented sGC ubiquitination and stabilized both alpha and beta subunits. Collectively, our data establish oxidation-ubiquitination of sGC as a modulator of NO/cGMP signaling and point to a new mechanism of action for sGC activating vasodilators by stabilizing their receptor, oxidized/heme-free sGC. PMID:19478201

Meurer, Sabine; Pioch, Sylke; Pabst, Tatjana; Opitz, Nils; Schmidt, Peter M; Beckhaus, Tobias; Wagner, Kristina; Matt, Simone; Gegenbauer, Kristina; Geschka, Sandra; Karas, Michael; Stasch, Johannes-Peter; Schmidt, Harald H H W; Müller-Esterl, Werner

2009-07-01

420

Elevated Exhaled Nitric Oxide in Allergen-Provoked Asthma Is Associated with Airway Epithelial iNOS  

PubMed Central

Background Fractional exhaled nitric oxide is elevated in allergen-provoked asthma. The cellular and molecular source of the elevated fractional exhaled nitric oxide is, however, uncertain. Objective To investigate whether fractional exhaled nitric oxide is associated with increased airway epithelial inducible nitric oxide synthase (iNOS) in allergen-provoked asthma. Methods Fractional exhaled nitric oxide was measured in healthy controls (n?=?14) and allergic asthmatics (n?=?12), before and after bronchial provocation to birch pollen out of season. Bronchoscopy was performed before and 24 hours after allergen provocation. Bronchial biopsies and brush biopsies were processed for nitric oxide synthase activity staining with nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d), iNOS immunostaining, or gene expression analysis of iNOS by real-time PCR. NADPH-d and iNOS staining were quantified using automated morphometric analysis. Results Fractional exhaled nitric oxide and expression of iNOS mRNA were significantly higher in un-provoked asthmatics, compared to healthy controls. Allergic asthmatics exhibited a significant elevation of fractional exhaled nitric oxide after allergen provocation, as well as an accumulation of airway eosinophils. Moreover, nitric oxide synthase activity and expression of iNOS was significantly increased in the bronchial epithelium of asthmatics following allergen provocation. Fractional exhaled nitric oxide correlated with eosinophils and iNOS expression. Conclusion Higher fractional exhaled nitric oxide concentration among asthmatics is associated with elevated iNOS mRNA in the bronchial epithelium. Furthermore, our data demonstrates for the first time increased expression and activity of iNOS in the bronchial epithelium after allergen provocation, and thus provide a mechanistic explanation for elevated fractional exhaled nitric oxide in allergen-provoked asthma. PMID:24587191

Roos, Abraham B.; Mori, Michiko; Gronneberg, Reidar; Osterlund, Christina; Claesson, Hans-Erik; Wahlstrom, Jan; Grunewald, Johan; Eklund, Anders; Erjefalt, Jonas S.; Lundberg, Jon O.; Nord, Magnus

2014-01-01

421

Estrogen Receptor a and Endothelial Nitric Oxide Synthase Are Organized Into a Functional Signaling Module in Caveolae  

Microsoft Academic Search

Abstract—Estrogen causes nitric oxide (NO)-dependent vasodilation due to estrogen receptor (ER) a-mediated, nongenomic,activation of endothelial NO synthase (eNOS). The subcellular site of interaction between,ERa and eNOS was determined in studies of isolated endothelial cell plasma membranes. Estradiol (E 2 ,1 0 , mol\\/L) caused an increase in eNOS activity in plasma membranes in the absence of added calcium, calmodulin, or

Ken L. Chambliss; Ivan S. Yuhanna; Chieko Mineo; Pingsheng Liu; Zohre German; Todd S. Sherman; Michael E. Mendelsohn; Richard G. W. Anderson; Philip W. Shaul

2000-01-01

422

Nitric Oxide Inhibits Marek's Disease Virus Replication but Is Not the Single Decisive Factor in Interferon-?-Mediated Viral Inhibition  

Microsoft Academic Search

The purpose of this study was to determine to what extent nitric oxide (NO) may play a role in the antiviral-mediated effect of chicken IFN-? against the Marek's disease virus (MDV) RB-1B. NO-generating compounds S-nitroso-N-acetylpenicillamine (SNAP) and 3-morpholino-sydononimine (SIN-1) strongly inhibited RB-1B replication in chicken embryo fibroblasts (85%) in a dose-dependent manner. The addition of superoxide dismutase (SOD) did not

Aouatef Djeraba; Nelly Bernardet; Ginette Dambrine; Pascale Quéré

2000-01-01

423

Increased Expression of Inducible Nitric Oxide Synthase and Cyclooxygenase2 in Barrett's Esophagus and Associated Adenocarcinomas1  

Microsoft Academic Search

Barrett's esophagus is a premalignant condition arising in response to chronic reflux esophagitis. Inducible nitric oxide synthase (¡NOS;NOS-2) and cyclooxygenase-2 (COX-2) are mediators of inflammation and regu lators of epithelial cell growth. Expression levels of ¡NOS and COX-2 are high in colorectal adenomas and carcinomas, and COX-2 expression is elevated in gastric cancers. To determine the involvement of ¡NOSand COX-2

Keith T. Wilson; Sidong Fu; Kalathur S. Ramanujam; Stephen J. Meltzer

1998-01-01

424

Extracellular signal-regulated kinase (ERK) and nitric oxide synthase mediate intrathecal morphine-induced nociceptive behavior  

Microsoft Academic Search

Intrathecal (i.t.) administration of morphine at a high dose of 60nmol into the spinal lumbar space in mice produces a severe hindlimb scratching followed by biting and licking. Nitric oxide (NO) is thought to play an important role in signal transduction pathways that enhance nociceptive transmission in the spinal cord. The present study was designed to determine whether high-dose i.t.

Takaaki Komatsu; Chikai Sakurada; Mika Sasaki; Kengo Sanai; Minoru Tsuzuki; Giacinto Bagetta; Shinobu Sakurada; Tsukasa Sakurada

2007-01-01

425

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

Microsoft Academic Search

Background & Aims: Inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 are important regulators of mucosal inflammation and epithelial cell growth. To determine the role of iNOS and COX-2 in Helicobacter pylori–induced tissue injury, we compared their gene expression in H. pylori–induced gastritis with that in normal gastric mucosa and in non–H. pylori gastritis. Methods: In 43 patients, we assessed

Sidong Fu; Kalathur S. Ramanujam; Annie Wong; George T. Fantry; Cinthia B. Drachenberg; Stephen P. James; Stephen J. Meltzer; Keith T. Wilson

1999-01-01

426

Heparin And Nonanticoagulant Heparin Preserve Regional Myocardial Contractility After Ischemia-Reperfusion Injury: Role Of Nitric Oxide  

Microsoft Academic Search

Objectives: These studies were performed to determine the effect of heparin and nonanticoagulant heparin on myocardial function after ischemia-reperfusion and to further evaluate the role that the nitric oxide–cyclic guanosine monophosphate pathway plays in mediating the effect of heparin.Methods: Fifteen dogs were subjected to 15 minutes ischemia followed by 120 minutes reperfusion and pretreated with either saline solution, bovine heparin

Peter C. Kouretas; Adam K. Myers; Young D. Kim; Paul A. Cahill; Jeff L. Myers; Yi-Ning Wang; James V. Sitzmann; Robert B. Wallace; Robert L. Hannan

1998-01-01

427

Intrathecal administration of a new nitric oxide donor, NOC18, produces acute thermal hyperalgesia in the rat  

Microsoft Academic Search

A nitric oxide releasing compound, NOC-18, was injected intrathecally in order to determine the role of NO in spinal nociceptive mechanisms in rats. The nociceptive threshold was evaluated by the radiant heat tail-flick test. The effects of intrathecal injection of N-nitro-l-arginine methyl ester (l-NAME), an NO synthase inhibitor; methylene blue (MB), a soluble guanylate cyclase inhibitor and hemoglobin (Hb), an

Takaya Inoue; Takashi Mashimo; Satoshi Shibuta; Ikuto Yoshiya

1997-01-01

428

Intracellular Conversion of Environmental Nitrate and Nitrite to Nitric Oxide with Resulting Developmental Toxicity to the Crustacean Daphnia magna  

PubMed Central

Background Nitrate and nitrite (jointly referred to herein as NOx) are ubiquitous environmental contaminants to which aquatic organisms are at particularly high risk of exposure. We tested the hypothesis that NOx undergo intracellular conversion to the potent signaling molecule nitric oxide resulting in the disruption of endocrine-regulated processes. Methodology/Principal Findings These experiments were performed with insect cells (Drosophila S2) and whole organisms Daphnia magna. We first evaluated the ability of cells to convert nitrate (NO3?) and nitrite (NO2?) to nitric oxide using amperometric real-time nitric oxide detection. Both NO3? and NO2? were converted to nitric oxide in a substrate concentration-dependent manner. Further, nitric oxide trapping and fluorescent visualization studies revealed that perinatal daphnids readily convert NO2? to nitric oxide. Next, daphnids were continuously exposed to concentrations of the nitric oxide-donor sodium nitroprusside (positive control) and to concentrations of NO3? and NO2?. All three compounds interfered with normal embryo development and reduced daphnid fecundity. Developmental abnormalities were characteristic of those elicited by compounds that interfere with ecdysteroid signaling. However, no compelling evidence was generated to indicate that nitric oxide reduced ecdysteroid titers. Conclusions/Significance Results demonstrate that nitrite elicits developmental and reproductive toxicity at environmentally relevant concentrations due likely to its intracellular conversion to nitric oxide. PMID:20805993