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Sample records for nitric oxide homeostasis

  1. Nitric oxide and plant iron homeostasis.

    PubMed

    Buet, Agustina; Simontacchi, Marcela

    2015-03-01

    Like all living organisms, plants demand iron (Fe) for important biochemical and metabolic processes. Internal imbalances, as a consequence of insufficient or excess Fe in the environment, lead to growth restriction and affect crop yield. Knowledge of signals and factors affecting each step in Fe uptake from the soil and distribution (long-distance transport, remobilization from old to young leaves, and storage in seeds) is necessary to improve our understanding of plant mineral nutrition. In this context, the role of nitric oxide (NO) is discussed as a key player in maintaining Fe homeostasis through its cross talk with hormones, ferritin, and frataxin and the ability to form nitrosyl-iron complexes.

  2. Metagenomic analysis of nitrate-reducing bacteria in the oral cavity: implications for nitric oxide homeostasis.

    PubMed

    Hyde, Embriette R; Andrade, Fernando; Vaksman, Zalman; Parthasarathy, Kavitha; Jiang, Hong; Parthasarathy, Deepa K; Torregrossa, Ashley C; Tribble, Gena; Kaplan, Heidi B; Petrosino, Joseph F; Bryan, Nathan S

    2014-01-01

    The microbiota of the human lower intestinal tract helps maintain healthy host physiology, for example through nutrient acquisition and bile acid recycling, but specific positive contributions of the oral microbiota to host health are not well established. Nitric oxide (NO) homeostasis is crucial to mammalian physiology. The recently described entero-salivary nitrate-nitrite-nitric oxide pathway has been shown to provide bioactive NO from dietary nitrate sources. Interestingly, this pathway is dependent upon oral nitrate-reducing bacteria, since humans lack this enzyme activity. This pathway appears to represent a newly recognized symbiosis between oral nitrate-reducing bacteria and their human hosts in which the bacteria provide nitrite and nitric oxide from nitrate reduction. Here we measure the nitrate-reducing capacity of tongue-scraping samples from six healthy human volunteers, and analyze metagenomes of the bacterial communities to identify bacteria contributing to nitrate reduction. We identified 14 candidate species, seven of which were not previously believed to contribute to nitrate reduction. We cultivated isolates of four candidate species in single- and mixed-species biofilms, revealing that they have substantial nitrate- and nitrite-reduction capabilities. Colonization by specific oral bacteria may thus contribute to host NO homeostasis by providing nitrite and nitric oxide. Conversely, the lack of specific nitrate-reducing communities may disrupt the nitrate-nitrite-nitric oxide pathway and lead to a state of NO insufficiency. These findings may also provide mechanistic evidence for the oral systemic link. Our results provide a possible new therapeutic target and paradigm for NO restoration in humans by specific oral bacteria.

  3. Nitric oxide plays a role in stem cell niche homeostasis through its interaction with auxin.

    PubMed

    Sanz, Luis; Fernández-Marcos, María; Modrego, Abelardo; Lewis, Daniel R; Muday, Gloria K; Pollmann, Stephan; Dueñas, Montserrat; Santos-Buelga, Celestino; Lorenzo, Oscar

    2014-12-01

    Nitric oxide (NO) is a unique reactive nitrogen molecule with an array of signaling functions that modulates plant developmental processes and stress responses. To explore the mechanisms by which NO modulates root development, we used a pharmacological approach and NO-deficient mutants to unravel the role of NO in establishing auxin distribution patterns necessary for stem cell niche homeostasis. Using the NO synthase inhibitor and Arabidopsis (Arabidopsis thaliana) NO biosynthesis mutants (nitric oxide-associated1 [noa1], nitrate reductase1 [nia1] and nia2, and nia1 nia2 noa1), we show that depletion of NO in noa1 reduces primary root elongation and increases flavonol accumulation consistent with elevated reactive oxygen species levels. The elevated flavonols are required for the growth effect, because the transparent testa4 mutation reverses the noa1 mutant root elongation phenotype. In addition, noa1 and nia1 nia2 noa1 NO-deficient mutant roots display small root meristems with abnormal divisions. Concomitantly, auxin biosynthesis, transport, and signaling are perturbed. We further show that NO accumulates in cortex/endodermis stem cells and their precursor cells. In endodermal and cortical cells, the noa1 mutant acts synergistically to the effect of the wuschel-related homeobox5 mutation on the proximal meristem, suggesting that NO could play an important role in regulating stem cell decisions, which has been reported in animals. © 2014 American Society of Plant Biologists. All Rights Reserved.

  4. Nitric oxide and frataxin: two players contributing to maintain cellular iron homeostasis

    PubMed Central

    Ramirez, Leonor; Zabaleta, Eduardo Julián; Lamattina, Lorenzo

    2010-01-01

    Background Nitric oxide (NO) is a signalling and physiologically active molecule in animals, plants and bacteria. The specificity of the molecular mechanism(s) involved in transducing the NO signal within and between cells and tissues is still poorly understood. NO has been shown to be an emerging and potent signal molecule in plant growth, development and stress physiology. The NO donor S-nitrosoglutathion (GSNO) was shown to be a biologically active compound in plants and a candidate for NO storage and/or mobilization between plant tissues and cells. NO has been implicated as a central component in maintaining iron bioavailavility in plants. Scope and Conclusions Iron is an essential nutrient for almost all organisms. This review presents an overview of the functions of NO in iron metabolism in animals and discusses how NO production constitutes a key response in plant iron sensing and availability. In plants, NO drives downstream responses to both iron deficiency and iron overload. NO-mediated improvement of iron nutrition in plants growing under iron-deficient conditions represents a powerful tool to cope with soils displaying low iron availability. An interconversion between different redox forms based on the iron and NO status of the plant cells might be the core of a metabolic process driving plant iron homeostasis. Frataxin, a recently identified protein in plants, plays an important role in mitochondria biogenesis and in maintaining mitochondrial iron homeostasis. Evidence regarding the interaction between frataxin, NO and iron from analysis of frataxin knock-down Arabidopsis thaliana mutants is reviewed and discussed. PMID:19556267

  5. Ethylene and nitric oxide are involved in maintaining ion homeostasis in Arabidopsis callus under salt stress.

    PubMed

    Wang, Huahua; Liang, Xiaolei; Wan, Qi; Wang, Xiaomin; Bi, Yurong

    2009-07-01

    In the present study, the role of ethylene in nitric oxide (NO)-mediated protection by modulating ion homeostasis in Arabidopsis callus under salt stress was investigated. Results showed that the ethylene-insensitive mutant etr1-3 was more sensitive to salt stress than the wild type (WT). Under 100 mM NaCl, etr1-3 callus displayed a greater electrolyte leakage and Na(+)/K(+) ratio but a lower plasma membrane (PM) H(+)-ATPase activity compared to WT callus. Application of exogenous 1-aminocyclopropane-1-carboxylic acid (ACC, an ethylene precursor) or sodium nitroprusside (SNP, a NO donor) alleviated NaCl-induced injury by maintaining a lower Na(+)/K(+) ratio and an increased PM H(+)-ATPase activity in WT callus but not in etr1-3 callus. The SNP actions in NaCl stress were attenuated by a specific NO scavenger or an ethylene biosynthesis inhibitor in WT callus. Under 100 mM NaCl, the NO accumulation and ethylene emission appeared at early time, and NO production greatly stimulated ethylene emission in WT callus. In addition, ethylene induced the expression of PM H(+)-ATPase genes under salt stress. The recovery experiment showed that NaCl-induced injury was reversible, as signaled by the similar recovery of Na(+)/K(+) ratio and PM H(+)-ATPase activity in WT callus. Taken together, the results indicate that ethylene and NO cooperate in stimulating PM H(+)-ATPase activity to modulate ion homeostasis for salt tolerance, and ethylene may be a part of the downstream signal molecular in NO action.

  6. [Nitric oxide].

    PubMed

    Rovira, I

    1995-01-01

    Nitric oxide was identified as the relaxing factor derived from the endothelium in 1987. Nitric oxide synthesis allows the vascular system to maintain a state of vasodilation, thereby regulating arterial pressure. Nitric oxide is also found in platelets, where it inhibits adhesion and aggregation; in the immune system, where it is responsible for the cytotoxic action of macrophages; and in the nervous system, where it acts as neurotransmitter. A deficit in endogenous synthesis of nitric oxide contributes to such conditions as essential arterial hypertension, pulmonary hypertension and heart disease. An excess of nitrous oxide induced by endotoxins and cytokinins, meanwhile, is believed to be responsible for hypotension in septic shock and for hyperdynamic circulatory state in cirrhosis of the liver. Nitric oxide has also been implicated in the rejection of transplanted organs and in cell damage after reperfusion. Inhaled nitrous oxide gas reduces pulmonary hypertension without triggering systemic hypotension in both experimental and clinical conditions. It also produces selective vasodilation when used to ventilate specific pulmonary areas, thereby improving the ventilation/perfusion ratio and, hence, oxygenation. Nitric oxide inhalation is effective in pulmonary hypertension-coincident with chronic obstructive lung disease, in persistent neonatal pulmonary hypertension and in pulmonary hypertension with congenital or acquired heart disease. Likewise, it reduces intrapulmonary shunt in acute respiratory failure and improves gas exchange. Under experimental conditions nitric oxide acts as a bronchodilator, although it seems to be less effective for this purpose in clinical use.(ABSTRACT TRUNCATED AT 250 WORDS)

  7. Nitric oxide

    Integrated Risk Information System (IRIS)

    Nitric oxide ; CASRN 10102 - 43 - 9 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Ef

  8. [Interrupted alcohol treatment and liver: free radical homeostasis, nitric oxide, adaptive mechanisms].

    PubMed

    Miskevich, D A; Borodinskiĭ, A N; Petushok, N E; Konovalenko, O V; Lelevich, V V

    2006-01-01

    Alcohol administration can result in liver damage. Reactive oxygen species (ROS), nitric oxide (NO) and their interaction are crucial factors in this process. The aim of work was to investigate, free radical state and mechanisms of adaptation of the antioxidant system (AOS) to stress, caused by interrupted alcohol intake. Repeated cycles of alcoholization caused an imbalance between production and utilization of various ROS. This imbalance was due to impairments in the system superoxide dismutase/catalase. Nevertheless, in most experimental groups there was clear reduction of lipid peroxidation (LPO) products evaluated by thiobarbituric acid reactive substances. This might be attributed to the antioxidant effect of NO. However, there was an increased level of transaminases in blood plasma. After 28 days of this experimental scheme all the parameters studied normalized.

  9. Nitric oxide, nitrosyl iron complexes, ferritin and frataxin: a well equipped team to preserve plant iron homeostasis.

    PubMed

    Ramirez, Leonor; Simontacchi, Marcela; Murgia, Irene; Zabaleta, Eduardo; Lamattina, Lorenzo

    2011-11-01

    Iron is a key element in plant nutrition. Iron deficiency as well as iron overload results in serious metabolic disorders that affect photosynthesis, respiration and general plant fitness with direct consequences on crop production. More than 25% of the cultivable land possesses low iron availability due to high pH (calcareous soils). Plant biologists are challenged by this concern and aimed to find new avenues to ameliorate plant responses and keep iron homeostasis under control even at wide range of iron availability in various soils. For this purpose, detailed knowledge of iron uptake, transport, storage and interactions with cellular compounds will help to construct a more complete picture of its role as essential nutrient. In this review, we summarize and describe the recent findings involving four central players involved in keeping cellular iron homeostasis in plants: nitric oxide, ferritin, frataxin and nitrosyl iron complexes. We attempt to highlight the interactions among these actors in different scenarios occurring under iron deficiency or iron overload, and discuss their counteracting and/or coordinating actions leading to the control of iron homeostasis.

  10. Hepatitis B virus X protein regulates hepatic glucose homeostasis via activation of inducible nitric oxide synthase.

    PubMed

    Shin, Hye-Jun; Park, Young-Ho; Kim, Sun-Uk; Moon, Hyung-Bae; Park, Do Sim; Han, Ying-Hao; Lee, Chul-Ho; Lee, Dong-Seok; Song, In-Sung; Lee, Dae Ho; Kim, Minhye; Kim, Nam-Soon; Kim, Dae-Ghon; Kim, Jin-Man; Kim, Sang-Keun; Kim, Yo Na; Kim, Su Sung; Choi, Cheol Soo; Kim, Young-Bum; Yu, Dae-Yeul

    2011-08-26

    Dysregulation of liver functions leads to insulin resistance causing type 2 diabetes mellitus and is often found in chronic liver diseases. However, the mechanisms of hepatic dysfunction leading to hepatic metabolic disorder are still poorly understood in chronic liver diseases. The current work investigated the role of hepatitis B virus X protein (HBx) in regulating glucose metabolism. We studied HBx-overexpressing (HBxTg) mice and HBxTg mice lacking inducible nitric oxide synthase (iNOS). Here we show that gene expressions of the key gluconeogenic enzymes were significantly increased in HepG2 cells expressing HBx (HepG2-HBx) and in non-tumor liver tissues of hepatitis B virus patients with high levels of HBx expression. In the liver of HBxTg mice, the expressions of gluconeogenic genes were also elevated, leading to hyperglycemia by increasing hepatic glucose production. However, this effect was insufficient to cause systemic insulin resistance. Importantly, the actions of HBx on hepatic glucose metabolism are thought to be mediated via iNOS signaling, as evidenced by the fact that deficiency of iNOS restored HBx-induced hyperglycemia by suppressing the gene expression of gluconeogenic enzymes. Treatment of HepG2-HBx cells with nitric oxide (NO) caused a significant increase in the expression of gluconeogenic genes, but JNK1 inhibition was completely normalized. Furthermore, hyperactivation of JNK1 in the liver of HBxTg mice was also suppressed in the absence of iNOS, indicating the critical role for JNK in the mutual regulation of HBx- and iNOS-mediated glucose metabolism. These findings establish a novel mechanism of HBx-driven hepatic metabolic disorder that is modulated by iNOS-mediated activation of JNK.

  11. The role of nitric oxide in pre-synaptic plasticity and homeostasis

    PubMed Central

    Hardingham, Neil; Dachtler, James; Fox, Kevin

    2013-01-01

    Since the observation that nitric oxide (NO) can act as an intercellular messenger in the brain, the past 25 years have witnessed the steady accumulation of evidence that it acts pre-synaptically at both glutamatergic and GABAergic synapses to alter release-probability in synaptic plasticity. NO does so by acting on the synaptic machinery involved in transmitter release and, in a coordinated fashion, on vesicular recycling mechanisms. In this review, we examine the body of evidence for NO acting as a retrograde factor at synapses, and the evidence from in vivo and in vitro studies that specifically establish NOS1 (neuronal nitric oxide synthase) as the important isoform of NO synthase in this process. The NOS1 isoform is found at two very different locations and at two different spatial scales both in the cortex and hippocampus. On the one hand it is located diffusely in the cytoplasm of a small population of GABAergic neurons and on the other hand the alpha isoform is located discretely at the post-synaptic density (PSD) in spines of pyramidal cells. The present evidence is that the number of NOS1 molecules that exist at the PSD are so low that a spine can only give rise to modest concentrations of NO and therefore only exert a very local action. The NO receptor guanylate cyclase is located both pre- and post-synaptically and this suggests a role for NO in the coordination of local pre- and post-synaptic function during plasticity at individual synapses. Recent evidence shows that NOS1 is also located post-synaptic to GABAergic synapses and plays a pre-synaptic role in GABAergic plasticity as well as glutamatergic plasticity. Studies on the function of NO in plasticity at the cellular level are corroborated by evidence that NO is also involved in experience-dependent plasticity in the cerebral cortex. PMID:24198758

  12. Nitric Oxide Plays a Role in Stem Cell Niche Homeostasis through Its Interaction with Auxin1[W][OPEN

    PubMed Central

    Sanz, Luis; Fernández-Marcos, María; Modrego, Abelardo; Lewis, Daniel R.; Pollmann, Stephan

    2014-01-01

    Nitric oxide (NO) is a unique reactive nitrogen molecule with an array of signaling functions that modulates plant developmental processes and stress responses. To explore the mechanisms by which NO modulates root development, we used a pharmacological approach and NO-deficient mutants to unravel the role of NO in establishing auxin distribution patterns necessary for stem cell niche homeostasis. Using the NO synthase inhibitor and Arabidopsis (Arabidopsis thaliana) NO biosynthesis mutants (nitric oxide-associated1 [noa1], nitrate reductase1 [nia1] and nia2, and nia1 nia2 noa1), we show that depletion of NO in noa1 reduces primary root elongation and increases flavonol accumulation consistent with elevated reactive oxygen species levels. The elevated flavonols are required for the growth effect, because the transparent testa4 mutation reverses the noa1 mutant root elongation phenotype. In addition, noa1 and nia1 nia2 noa1 NO-deficient mutant roots display small root meristems with abnormal divisions. Concomitantly, auxin biosynthesis, transport, and signaling are perturbed. We further show that NO accumulates in cortex/endodermis stem cells and their precursor cells. In endodermal and cortical cells, the noa1 mutant acts synergistically to the effect of the wuschel-related homeobox5 mutation on the proximal meristem, suggesting that NO could play an important role in regulating stem cell decisions, which has been reported in animals. PMID:25315603

  13. Hydrogen Sulfide Regulates Ca2+ Homeostasis Mediated by Concomitantly Produced Nitric Oxide via a Novel Synergistic Pathway in Exocrine Pancreas

    PubMed Central

    Moustafa, Amira

    2014-01-01

    Abstract Aim: The present study was designed to explore the effects of hydrogen sulfide (H2S) on Ca2+ homeostasis in rat pancreatic acini. Results: Sodium hydrosulfide (NaHS; an H2S donor) induced a biphasic increase in the intracellular Ca2+ concentration ([Ca2+]i) in a dose-dependent manner. The NaHS-induced [Ca2+]i elevation persisted with an EC50 of 73.3 μM in the absence of extracellular Ca2+ but was abolished by thapsigargin, indicating that both Ca2+ entry and Ca2+ release contributed to the increase. The [Ca2+]i increase was markedly inhibited in the presence of NG-monomethyl L-arginine or 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO), and diaminofluorescein-2/diaminofluorescein-2 triazole (DAF-2/DAF-2T) fluorometry demonstrated that nitric oxide (NO) was also produced by H2S in a dose-dependent manner with an EC50 of 64.8 μM, indicating that NO was involved in the H2S effect. The H2S-induced [Ca2+]i increase was inhibited by pretreatment with U73122, xestospongin C, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, KT5823, and GP2A, indicating that phospholipase C (PLC), the inositol 1,4,5-trisphosphate (IP3) receptor, soluble guanylate cyclase (sGC), protein kinase G (PKG), and Gq-protein play roles as intermediate components in the H2S-triggered intracellular signaling. Innovation: To our knowledge, our study is the first one highlighting the effect of H2S on intracellular Ca2+ dynamics in pancreatic acinar cells. Moreover, a novel cascade was presumed to function via the synergistic interaction between H2S and NO. Conclusion: We conclude that H2S affects [Ca2+]i homeostasis that is mediated by H2S-evoked NO production via an endothelial nitric oxide synthase (eNOS)-NO-sGC-cyclic guanosine monophosphate-PKG-Gq-protein-PLC-IP3 pathway to induce Ca2+ release, and this pathway is identical to the one we recently proposed for a sole effect of NO and the two gaseous molecules synergistically function to regulate Ca2+ homeostasis

  14. Chlorine gas exposure disrupts nitric oxide homeostasis in the pulmonary vasculature

    PubMed Central

    Honavar, Jaideep; Bradley, Eddie; Bradley, Kelley; Oh, Joo Yeun; Vallejo, Matthew O.; Kelley, Eric E.; Cantu-Medellin, Nadiezhda; Doran, Stephen; Dell’italia, Louis J.; Matalon, Sadis; Patel, Rakesh P.

    2014-01-01

    Exposure to chlorine (Cl2) gas during industrial accidents or chemical warfare leads to significant airway and distal lung epithelial injury that continues post exposure. While lung epithelial injury is prevalent, relatively little is known about whether Cl2 gas also promotes injury to the pulmonary vasculature. To determine this, rats were subjected to a sub-lethal Cl2 gas exposure (400ppm, 30min) and then brought back to room air. Pulmonary arteries (PA) were isolated from rats at various times post-exposure and contractile (phenylephrine) and nitric oxide (NO)-dependent vasodilation (acetylcholine and mahmanonoate) responses measured ex-vivo. PA contractility did not change, however significant inhibition of NO-dependent vasodilation was observed that was maximal at 24–48 hours post exposure. Superoxide dismutase restored NO-dependent vasodilation suggesting a role for increased superoxide formation. This was supported by ~2-fold increase in superoxide formation (measured using 2-hydroethidine oxidation to 2-OH-E+) from PA isolated from Cl2 exposed rats. We next measured PA pressures in anesthetized rats. Surprisingly, PA pressures were significantly (~4mmHg) lower in rats that had been exposed to Cl2 gas 24 hours earlier suggesting that deficit in NO-signaling observed in isolated PA experiments did not manifest as increased PA pressures in vivo. Administration of the iNOS selective inhibitor 1400W, restored PA pressures to normal in Cl2 exposed, but not control rats suggesting that any deficit in NO-signaling due to increased superoxide formation in the PA, is offset by increased NO-formation from iNOS. These data indicate that disruption of endogenous NO-signaling mechanisms that maintain PA tone is an important aspect of post-Cl2 gas exposure toxicity. PMID:24769334

  15. Carbon monoxide enhances the chilling tolerance of recalcitrant Baccaurea ramiflora seeds via nitric oxide-mediated glutathione homeostasis.

    PubMed

    Bai, Xue-gui; Chen, Jin-hui; Kong, Xiang-xiang; Todd, Christopher D; Yang, Yong-ping; Hu, Xiang-yang; Li, De-zhu

    2012-08-15

    Both carbon monoxide (CO) and nitric oxide (NO) play fundamental roles in plant responses to environmental stress. Glutathione (GSH) homeostasis through the glutathione-ascorbate cycle regulates the cellular redox status and protects the plant from damage due to reactive oxygen species (ROS) or reactive nitrogen species (RNS). Most recalcitrant seeds are sensitive to chilling stress, but the roles of and cross talk among CO, NO, ROS, and GSH in recalcitrant seeds under low temperature are not well understood. Here, we report that the germination of recalcitrant Baccaurea ramiflora seeds shows sensitivity to chilling stress, but application of exogenous CO or NO markedly increased GSH accumulation, enhanced the activities of antioxidant enzymes involved in the glutathione-ascorbate cycle, decreased the content of H(2)O(2) and RNS, and improved the tolerance of seeds to low-temperature stress. Compared to orthodox seeds such as maize, only transient accumulation of CO and NO was induced and only a moderate increase in GSH was shown in the recalcitrant B. ramiflora seeds. Exogenous CO or NO treatment further increased the GSH accumulation and S-nitrosoglutathione reductase (GSNOR) activity in B. ramiflora seeds under chilling stress. In contrast, suppressing CO or NO generation, removing GSH, or blocking GSNOR activity resulted in increases in ROS and RNS and impaired the germination of CO- or NO-induced seeds under chilling stress. Based on these results, we propose that CO acts as a novel regulator to improve the tolerance of recalcitrant seeds to low temperatures through NO-mediated glutathione homeostasis. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Shedding light on NO homeostasis: Light as a key regulator of glutathione and nitric oxide metabolisms during seedling deetiolation.

    PubMed

    Zuccarelli, Rafael; Coelho, Aline C P; Peres, Lazaro E P; Freschi, Luciano

    2017-01-18

    Despite the significant impacts of light on nitric oxide (NO) levels in plants, the mechanism underlying the influence of this environmental factor on NO metabolism remains poorly understood. A critical mechanism controlling NO levels in plant cells relies on the S-nitrosylation of glutathione (GSH), giving rise to S-nitrosoglutathione (GSNO), which can be either stored or degraded depending on the cellular context. Here, we demonstrate that a strict balance is maintained between NO generation and scavenging during tomato (Solanum lycopersicum) seedling deetiolation. Given the absence of accurate methods in the literature to estimate NO scavenging in planta, we first developed a simple, robust system to continuously monitor the global in vivo NO scavenging by plant tissues. Then, using photomorphogenic tomato mutants, we demonstrated that the light-evoked de-etiolation is associated with a dramatic rise in NO content followed by a progressive increment in NO scavenging capacity of the tissues. Light-driven increments in NO scavenging rates coincided with pronounced rises in S-nitrosothiol content and GSNO reductase (GSNOR) activity, thereby suggesting that GSNO formation and subsequent removal via GSNOR might be key for controlling NO levels during seedling deetiolation. Accordingly, treatments with thiol-blocking compounds further indicated that thiol nitrosylation might be critically involved in the NO scavenging mechanism responsible for maintaining NO homeostasis during deetiolation. The impacts of both light and NO on the transcriptional profile of glutathione metabolic genes also revealed an independent but coordinated action of these signals on the regulation of key components of glutathione and GSNO metabolisms. Altogether, these data indicated that GSNO formation and subsequent removal might facilitate maintaining NO homeostasis during light-driven seedling deetiolation.

  17. Nitric oxide and cardiovascular system.

    PubMed

    Cengel, Atiye; Sahinarslan, Asife

    2006-12-01

    Endothelium has many important functions including the control of blood-tissue permeability and vascular tonus, regulation of vascular surface properties for homeostasis and inflammation. Nitric oxide is the chief molecule in regulation of endothelial functions. Nitric oxide deficiency, which is also known as endothelial dysfunction, is the first step for the occurrence of many disease states in cardiovascular system including heart failure, hypertension, dyslipidemia, insulin resistance, diabetes mellitus, hyperhomocysteinemia and smoking. This review deals with the importance of nitric oxide for cardiovascular system. It also includes the latest improvements in the diagnosis and treatment of endothelial dysfunction.

  18. Hydrogen sulfide enhances salt tolerance through nitric oxide-mediated maintenance of ion homeostasis in barley seedling roots

    PubMed Central

    Chen, Juan; Wang, Wen-Hua; Wu, Fei-Hua; He, En-Ming; Liu, Xiang; Shangguan, Zhou-Ping; Zheng, Hai-Lei

    2015-01-01

    Hydrogen sulfide (H2S) and nitric oxide (NO) are emerging as messenger molecules involved in the modulation of plant physiological processes. Here, we investigated a signalling network involving H2S and NO in salt tolerance pathway of barley. NaHS, a donor of H2S, at a low concentration of either 50 or 100 μM, had significant rescue effects on the 150 mM NaCl-induced inhibition of plant growth and modulated the K+/Na+ balance by decreasing the net K+ efflux and increasing the gene expression of an inward-rectifying potassium channel (HvAKT1) and a high-affinity K+ uptake system (HvHAK4). H2S and NO maintained the lower Na+ content in the cytoplast by increasing the amount of PM H+-ATPase, the transcriptional levels of PM H+-ATPase (HvHA1) and Na+/H+ antiporter (HvSOS1). H2S and NO modulated Na+ compartmentation into the vacuoles with up-regulation of the transcriptional levels of vacuolar Na+/H+ antiporter (HvVNHX2) and H+-ATPase subunit β (HvVHA-β) and increased in the protein expression of vacuolar Na+/H+ antiporter (NHE1). H2S mimicked the effect of sodium nitroprusside (SNP) by increasing NO production, whereas the function was quenched with the addition of NO scavenger. These results indicated that H2S increased salt tolerance by maintaining ion homeostasis, which were mediated by the NO signal. PMID:26213372

  19. Nitric oxide signaling in plants.

    PubMed

    Shapiro, Allan D

    2005-01-01

    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.

  20. Nitric oxide enhancement strategies.

    PubMed

    Bryan, Nathan S

    2015-08-01

    It is becoming increasingly clear that many diseases are characterized or associated with perturbations in nitric oxide (NO) production/signaling. Therapeutics or strategies designed to restore normal NO homeostasis will likely have broad application and utility. This highly complex and multistep pathway for NO production and subsequent target activation provides many steps in the endogenous pathway that may be useful targets for drug development for cardiovascular disease, antimicrobial, cancer, wound healing, etc. This article will summarize known strategies that are currently available or in development for enhancing NO production or availability in the human body. Each strategy will be discussed including exogenous sources of NO, use of precursors to promote NO production and downstream pathways affected by NO production with advantages and disadvantages highlighted for each. Development of NO-based therapeutics is and will continue to be a major focus of biotech, academia as well as pharmaceutical companies. Application of safe and effective strategies will certainly transform health and disease.

  1. A nitric oxide regulated small RNA controls expression of genes involved in redox homeostasis in Bacillus subtilis.

    PubMed

    Durand, Sylvain; Braun, Frédérique; Lioliou, Efthimia; Romilly, Cédric; Helfer, Anne-Catherine; Kuhn, Laurianne; Quittot, Noé; Nicolas, Pierre; Romby, Pascale; Condon, Ciarán

    2015-02-01

    RsaE is the only known trans-acting small regulatory RNA (sRNA) besides the ubiquitous 6S RNA that is conserved between the human pathogen Staphylococcus aureus and the soil-dwelling Firmicute Bacillus subtilis. Although a number of RsaE targets are known in S. aureus, neither the environmental signals that lead to its expression nor its physiological role are known. Here we show that expression of the B. subtilis homolog of RsaE is regulated by the presence of nitric oxide (NO) in the cellular milieu. Control of expression by NO is dependent on the ResDE two-component system in B. subtilis and we determined that the same is true in S. aureus. Transcriptome and proteome analyses revealed that many genes with functions related to oxidative stress and oxidation-reduction reactions were up-regulated in a B. subtilis strain lacking this sRNA. We have thus renamed it RoxS. The prediction of RoxS-dependent mRNA targets also suggested a significant enrichment for mRNAs related to respiration and electron transfer. Among the potential direct mRNA targets, we have validated the ppnKB mRNA, encoding an NAD+/NADH kinase, both in vivo and in vitro. RoxS controls both translation initiation and the stability of this transcript, in the latter case via two independent pathways implicating RNase Y and RNase III. Furthermore, RNase Y intervenes at an additional level by processing the 5' end of the RoxS sRNA removing about 20 nucleotides. Processing of RoxS allows it to interact more efficiently with a second target, the sucCD mRNA, encoding succinyl-CoA synthase, thus expanding the repertoire of targets recognized by this sRNA.

  2. A Nitric Oxide Regulated Small RNA Controls Expression of Genes Involved in Redox Homeostasis in Bacillus subtilis

    PubMed Central

    Durand, Sylvain; Braun, Frédérique; Lioliou, Efthimia; Romilly, Cédric; Helfer, Anne-Catherine; Kuhn, Laurianne; Quittot, Noé; Nicolas, Pierre; Romby, Pascale; Condon, Ciarán

    2015-01-01

    RsaE is the only known trans-acting small regulatory RNA (sRNA) besides the ubiquitous 6S RNA that is conserved between the human pathogen Staphylococcus aureus and the soil-dwelling Firmicute Bacillus subtilis. Although a number of RsaE targets are known in S. aureus, neither the environmental signals that lead to its expression nor its physiological role are known. Here we show that expression of the B. subtilis homolog of RsaE is regulated by the presence of nitric oxide (NO) in the cellular milieu. Control of expression by NO is dependent on the ResDE two-component system in B. subtilis and we determined that the same is true in S. aureus. Transcriptome and proteome analyses revealed that many genes with functions related to oxidative stress and oxidation-reduction reactions were up-regulated in a B. subtilis strain lacking this sRNA. We have thus renamed it RoxS. The prediction of RoxS-dependent mRNA targets also suggested a significant enrichment for mRNAs related to respiration and electron transfer. Among the potential direct mRNA targets, we have validated the ppnKB mRNA, encoding an NAD+/NADH kinase, both in vivo and in vitro. RoxS controls both translation initiation and the stability of this transcript, in the latter case via two independent pathways implicating RNase Y and RNase III. Furthermore, RNase Y intervenes at an additional level by processing the 5′ end of the RoxS sRNA removing about 20 nucleotides. Processing of RoxS allows it to interact more efficiently with a second target, the sucCD mRNA, encoding succinyl-CoA synthase, thus expanding the repertoire of targets recognized by this sRNA. PMID:25643072

  3. Nitric Oxide Synthases and Atrial Fibrillation

    PubMed Central

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

    2012-01-01

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

  4. Delphinidin, an active compound of red wine, inhibits endothelial cell apoptosis via nitric oxide pathway and regulation of calcium homeostasis.

    PubMed

    Martin, Sophie; Giannone, Grégory; Andriantsitohaina, Ramaroson; Martinez, M Carmen

    2003-07-01

    1. Epidemiological studies have suggested that moderate consumption of natural dietary polyphenolic compounds might reduce the risk of cardiovascular disease and also protect against cancer. The present study investigates the effects of delphinidin, an anthocyanin present in red wine, on bovine aortic endothelial cells apoptosis. 2. Based on flow cytometry, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling analysis and detection of mitochondrial cytochrome c release, we show that delphinidin (10(-2) g l(-1)) alone had no effect either on necrosis or on apoptosis, but it significantly reduced apoptosis elicited by actinomycin D (1 micro g ml(-1), 24 h) and 7beta-hydroxycholesterol (10 micro g ml(-1), 18 h). 3. The protective effect of delphinidin was abolished by inhibitors of nitric oxide-synthase (NOS) (L-NA, 100 micro M and SMT, 100 micro M), guanylyl cyclase (ODQ, 100 micro M) and MAP kinase (PD98059, 30 micro M). 4. Western blot analysis and protein detection by confocal microscopy demonstrate that the antiapoptotic effect of delphinidin was associated with an increased endothelial NOS expression mediated by a MAP kinase pathway. 5. Finally, delphinidin alone had no effect on cytosolic-free calcium ([Ca(2+)](i)), but normalized the changes in [Ca(2+)](i) produced by actinomycin D towards the control values, suggesting that the antiapoptotic effect of delphinidin is associated with the maintenance of [Ca(2+)](i) in the physiological range. 6. All of the observed effects of delphinidin may preserve endothelium integrity, the alteration of which lead to pathologies including cardiovascular diseases, such as atherosclerosis, and is often associated with cancers. In conclusion, the protective effect of delphinidin against endothelial cell apoptosis contributes to understand the potential benefits of a consumption rich in polyphenols.

  5. Altered carnitine homeostasis is associated with decreased mitochondrial function and altered nitric oxide signaling in lambs with pulmonary hypertension

    PubMed Central

    Sharma, Shruti; Sud, Neetu; Wiseman, Dean A.; Carter, A. Lee; Kumar, Sanjiv; Hou, Yali; Rau, Thomas; Wilham, Jason; Harmon, Cynthia; Oishi, Peter; Fineman, Jeffrey R.; Black, Stephen M.

    2008-01-01

    Utilizing aortopulmonary vascular graft placement in the fetal lamb, we have developed a model (shunt) of pulmonary hypertension that mimics congenital heart disease with increased pulmonary blood flow. Our previous studies have identified a progressive development of endothelial dysfunction in shunt lambs that is dependent, at least in part, on decreased nitric oxide (NO) signaling. The purpose of this study was to evaluate the possible role of a disruption in carnitine metabolism in shunt lambs and to determine the effect on NO signaling. Our data indicate that at 2 wk of age, shunt lambs have significantly reduced expression (P < 0.05) of the key enzymes in carnitine metabolism: carnitine palmitoyltransferases 1 and 2 as well as carnitine acetyltransferase (CrAT). In addition, we found that CrAT activity was inhibited due to increased nitration. Furthermore, free carnitine levels were significantly decreased whereas acylcarnitine levels were significantly higher in shunt lambs (P < 0.05). We also found that alterations in carnitine metabolism resulted in mitochondrial dysfunction, since shunt lambs had significantly decreased pyruvate, increased lactate, and a reduced pyruvate/lactate ratio. In pulmonary arterial endothelial cells cultured from juvenile lambs, we found that mild uncoupling of the mitochondria led to a decrease in cellular ATP levels and a reduction in both endothelial NO synthase-heat shock protein 90 (eNOS-HSP90) interactions and NO signaling. Similarly, in shunt lambs we found a loss of eNOS-HSP90 interactions that correlated with a progressive decrease in NO signaling. Our data suggest that mitochondrial dysfunction may play a role in the development of endothelial dysfunction and pulmonary hypertension and increased pulmonary blood flow. PMID:18024721

  6. Nitric oxide enhancement strategies

    PubMed Central

    Bryan, Nathan S

    2015-01-01

    It is becoming increasingly clear that many diseases are characterized or associated with perturbations in nitric oxide (NO) production/signaling. Therapeutics or strategies designed to restore normal NO homeostasis will likely have broad application and utility. This highly complex and multistep pathway for NO production and subsequent target activation provides many steps in the endogenous pathway that may be useful targets for drug development for cardiovascular disease, antimicrobial, cancer, wound healing, etc. This article will summarize known strategies that are currently available or in development for enhancing NO production or availability in the human body. Each strategy will be discussed including exogenous sources of NO, use of precursors to promote NO production and downstream pathways affected by NO production with advantages and disadvantages highlighted for each. Development of NO-based therapeutics is and will continue to be a major focus of biotech, academia as well as pharmaceutical companies. Application of safe and effective strategies will certainly transform health and disease. PMID:28031863

  7. Carbon monoxide enhances salt tolerance by nitric oxide-mediated maintenance of ion homeostasis and up-regulation of antioxidant defence in wheat seedling roots.

    PubMed

    Xie, Yanjie; Ling, Tengfang; Han, Yi; Liu, Kaili; Zheng, Qingsong; Huang, Liqin; Yuan, Xingxing; He, Ziyi; Hu, Bing; Fang, Lei; Shen, Zhenguo; Yang, Qing; Shen, Wenbiao

    2008-12-01

    Salt stress induced an increase in endogenous carbon monoxide (CO) production and the activity of the CO synthetic enzyme haem oxygenase (HO) in wheat seedling roots. In addition, a 50% CO aqueous solution, applied daily, not only resulted in the enhancement of CO release, but led to a significant reversal in dry weight (DW) and water loss caused by 150 mm NaCl treatment, which was mimicked by the application of two nitric oxide (NO) donors sodium nitroprusside (SNP) and diethylenetriamine NO adduct (DETA/NO). Further analyses showed that CO, as well as SNP, apparently up-regulated H(+)-pump and antioxidant enzyme activities or related transcripts, thus resulting in the increase of K/Na ratio and the alleviation of oxidative damage. Whereas, the CO/NO scavenger haemoglobin (Hb), NO scavenger or synthetic inhibitor methylene blue (MB) or N(G)-nitro-l-arginine methyl ester hydrochloride (l-NAME) differentially blocked these effects. Furthermore, CO was able to mimic the effect of SNP by strongly increasing NO release in the root tips, whereas the CO-induced NO signal was quenched by the addition of l-NAME or cPTIO, the specific scavenger of NO. The results suggested that CO might confer an increased tolerance to salinity stress by maintaining ion homeostasis and enhancing antioxidant system parameters in wheat seedling roots, both of which were partially mediated by NO signal.

  8. Nitric oxide in the airways.

    PubMed

    Scadding, Glenis

    2007-08-01

    This review briefly explains the basic facts about nitric oxide, which is entering clinical practice as a measure of lower airways inflammation and is likely also to be employed in otorhinolaryngological practice. These include the validity of nasal nitric oxide in diagnosing primary ciliary dyskinesia and in monitoring the response to chronic rhinosinusitis therapy. The nasal nitric oxide value combined with a humming manoeuvre, which increases the passage of nitric oxide from the sinuses to the nose if the ostiomeatal complex is patent, could reduce the need for computed tomography scans. The link between nitric oxide production and ciliary beating requires further exploration. Therapeutic adjustments to nitric oxide production are under investigation. Nitric oxide is likely to prove highly relevant to airways defence, as well as being an inflammatory mediator. Nasal nitric oxide probably explains some of the benefit of nasal rather than mouth breathing.

  9. Bacterial nitric oxide synthases.

    PubMed

    Crane, Brian R; Sudhamsu, Jawahar; Patel, Bhumit A

    2010-01-01

    Nitric oxide synthases (NOSs) are multidomain metalloproteins first identified in mammals as being responsible for the synthesis of the wide-spread signaling and protective agent nitric oxide (NO). Over the past 10 years, prokaryotic proteins that are homologous to animal NOSs have been identified and characterized, both in terms of enzymology and biological function. Despite some interesting differences in cofactor utilization and redox partners, the bacterial enzymes are in many ways similar to their mammalian NOS (mNOS) counterparts and, as such, have provided insight into the structural and catalytic properties of the NOS family. In particular, spectroscopic studies of thermostable bacterial NOSs have revealed key oxyheme intermediates involved in the oxidation of substrate L-arginine (Arg) to product NO. The biological functions of some bacterial NOSs have only more recently come to light. These studies disclose new roles for NO in biology, such as taking part in toxin biosynthesis, protection against oxidative stress, and regulation of recovery from radiation damage.

  10. Nitric oxide neurotoxicity.

    PubMed

    Dawson, V L; Dawson, T M

    1996-06-01

    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 many roles in the central nervous system as a messenger molecule, however, when generated in excess NO can be neurotoxic. Excess NO is in part responsible for glutamate neurotoxicity in primary neuronal cell culture and in animal models of stroke. It is likely that most of the neurotoxic actions of NO are mediated by peroxynitrite (ONOO-), the reaction product from NO and superoxide anion. In pathologic conditions, peroxynitrite and oxygen free radicals can be generated in excess of a cell antioxidant capacity resulting in severe damage to cellular constituents including proteins, DNA and lipids. The inherent biochemical and physiological characteristics of the brain, including high lipid concentrations and energy requirements, make it particularly susceptible to free radical and oxidant mediated insult. Increasing evidence indicates that many neurologic disorders may have components of free radical and oxidative stress induced injury.

  11. Demystified … Nitric oxide

    PubMed Central

    Stuart-Smith, K

    2002-01-01

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

  12. Detection of nitric oxide pollution

    NASA Technical Reports Server (NTRS)

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

    1973-01-01

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

  13. Nitric oxide signaling in yeast.

    PubMed

    Astuti, Rika Indri; Nasuno, Ryo; Takagi, Hiroshi

    2016-11-01

    As a cellular signaling molecule, nitric oxide (NO) is widely conserved from microorganisms, such as bacteria, yeasts, and fungi, to higher eukaryotes including plants and mammals. NO is mainly produced by NO synthase (NOS) or nitrite reductase (NIR) activity. There are several NO detoxification systems, including NO dioxygenase (NOD) and S-nitrosoglutathione reductase (GSNOR). NO homeostasis based on the balance between NO synthesis and degradation is important for the regulation of its physiological functions because an excess level of NO causes nitrosative stress due to the high reactivity of NO and NO-derived compounds. In yeast, NO may be involved in stress responses, but NO and its signaling have been poorly understood due to the lack of mammalian NOS orthologs in the genome. Even though the activities of NOS and NIR have been observed in yeast cells, the gene encoding NOS and the NO production mechanism catalyzed by NIR remain unclear. On the other hand, yeast cells employ NOD and GSNOR to maintain an intracellular redox balance following endogenous NO production, exogenous NO treatment, or environmental stresses. This article reviews NO metabolism (synthesis, degradation) and its regulation in yeast. The physiological roles of NO in yeast, including the oxidative stress response, are also discussed here. Such investigations into NO signaling are essential for understanding the NO-dependent genetic and physiological modulations. In addition to being responsible for the pathology and pharmacology of various degenerative diseases, NO signaling may be a potential target for the construction and engineering of industrial yeast strains.

  14. Nitric oxide and cancer

    PubMed Central

    Muntané, Jordi; la Mata, Manuel De

    2010-01-01

    Nitric oxide (NO) is a lipophilic, highly diffusible and short-lived physiological messenger which regulates a variety of important physiological responses including vasodilation, respiration, cell migration, immune response and apoptosis. NO is synthesized by three differentially gene-encoded NO synthase (NOS) in mammals: neuronal NOS (nNOS or NOS-1), inducible NOS (iNOS or NOS-2) and endothelial NOS (eNOS or NOS-3). All isoforms of NOS catalyze the reaction of L-arginine, NADPH and oxygen to NO, L-citrulline and NADP. NO may exert its cellular action by cGMP-dependent as well as by cGMP-independent pathways including postranslational modifications in cysteine (S-nitrosylation or S-nitrosation) and tyrosine (nitration) residues, mixed disulfide formation (S-nitrosoglutathione or GSNO) or promoting further oxidation protein stages which have been related to altered protein function and gene transcription, genotoxic lesions, alteration of cell-cycle check points, apoptosis and DNA repair. NO sensitizes tumor cells to chemotherapeutic compounds. The expression of NOS-2 and NOS-3 has been found to be increased in a variety of human cancers. The multiple actions of NO in the tumor environment is related to heterogeneous cell responses with particular attention in the regulation of the stress response mediated by the hypoxia inducible factor-1 and p53 generally leading to growth arrest, apoptosis or adaptation. PMID:21161018

  15. 49 CFR 173.337 - Nitric oxide.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 2 2013-10-01 2013-10-01 false Nitric oxide. 173.337 Section 173.337... SHIPMENTS AND PACKAGINGS Gases; Preparation and Packaging § 173.337 Nitric oxide. (a) Nitric oxide must be... valve and valve seat that will not deteriorate in contact with nitric oxide. Cylinders or valves may...

  16. 49 CFR 173.337 - Nitric oxide.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 2 2014-10-01 2014-10-01 false Nitric oxide. 173.337 Section 173.337... SHIPMENTS AND PACKAGINGS Gases; Preparation and Packaging § 173.337 Nitric oxide. (a) Nitric oxide must be... valve and valve seat that will not deteriorate in contact with nitric oxide. Cylinders or valves may...

  17. 49 CFR 173.337 - Nitric oxide.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 2 2011-10-01 2011-10-01 false Nitric oxide. 173.337 Section 173.337... SHIPMENTS AND PACKAGINGS Gases; Preparation and Packaging § 173.337 Nitric oxide. (a) Nitric oxide must be... valve and valve seat that will not deteriorate in contact with nitric oxide. Cylinders or valves may...

  18. 49 CFR 173.337 - Nitric oxide.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 2 2012-10-01 2012-10-01 false Nitric oxide. 173.337 Section 173.337... SHIPMENTS AND PACKAGINGS Gases; Preparation and Packaging § 173.337 Nitric oxide. (a) Nitric oxide must be... valve and valve seat that will not deteriorate in contact with nitric oxide. Cylinders or valves may...

  19. Nitric oxide in shock.

    PubMed

    Cauwels, A

    2007-09-01

    Refractory hypotension with end-organ hypoperfusion and failure is an ominous feature of shock. Distributive shock is caused by severe infections (septic shock) or severe systemic allergic reactions (anaphylactic shock). In 1986, it was concluded that nitric oxide (NO) is the endothelium-derived relaxing factor that had been discovered 6 years earlier. Since then, NO has been shown to be important for the physiological and pathological control of vascular tone. Nevertheless, although inhibition of NO synthesis restores blood pressure, NO synthase (NOS) inhibition cannot improve outcome, on the contrary. This implies that NO acts as a double-edged sword during septic shock. Consequently, the focus has shifted towards selective inducible NOS (iNOS) inhibitors. The contribution of NO to anaphylactic shock seems to be more straightforward, as NOS inhibition abrogates shock in conscious mice. Surprisingly, however, this shock-inducing NO is not produced by the inducible iNOS, but by the so-called constitutive enzyme endothelial NOS. This review summarizes the contribution of NO to septic and anaphylactic shock. Although NOS inhibition may be promising for the treatment of anaphylactic shock, the failure of a phase III trial indicates that other approaches are required for the successful treatment of septic shock. Amongst these, high hopes are set for selective iNOS inhibitors. But it might also be necessary to shift gears and focus on downstream cardiovascular targets of NO or on other vasodilating phenomena.

  20. Chemiluminescence of nitric oxide

    NASA Technical Reports Server (NTRS)

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

    1981-01-01

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

  1. Nitric oxide in the pulmonary vasculature.

    PubMed

    Coggins, Matthew P; Bloch, Kenneth D

    2007-09-01

    Homeostasis in the pulmonary vasculature is maintained by the actions of vasoactive compounds, including nitric oxide (NO). NO is critical for normal development of the pulmonary vasculature and continues to mediate normal vasoregulation in adulthood. Loss of NO bioavailability is one component of the endothelial dysfunction and vascular pathology found in pulmonary hypertension (PH). A broad research effort continues to expand our understanding of the control of NO production and NO signaling and has generated novel theories on the importance of pulmonary NO production in the control of the systemic vasculature. This understanding has led to exciting developments in our ability to treat PH, including inhaled NO and phosphodiesterase inhibitors, and to several promising directions for future therapies using nitric oxide-donor compounds, stimulators of soluble guanylate cyclase, progenitor cells expressing NO synthase (NOS), and NOS gene manipulation.

  2. Proteomic analysis of human bladder epithelial cells by 2D blue native SDS-PAGE reveals TCDD-induced alterations of calcium and iron homeostasis possibly mediated by nitric oxide.

    PubMed

    Verma, Nisha; Pink, Mario; Petrat, Frank; Rettenmeier, Albert W; Schmitz-Spanke, Simone

    2015-01-02

    A proteomic analysis of the interaction among multiprotein complexes involved in 2,3,7,8-dibenzo-p-dioxin (TCDD)-mediated toxicity in urinary bladder epithelial RT4 cells was performed using two-dimensional blue native SDS-PAGE (2D BN/SDS-PAGE). To enrich the protein complexes, unexposed and TCDD-exposed cells were fractionated. BN/SDS-PAGE of the resulting fractions led to an effective separation of proteins and protein complexes of various origins, including cell membrane, mitochondria, and other intracellular compartments. Major differences between the proteome of control and exposed cells involved the alteration of many calcium-regulated proteins (calmodulin, protein S100-A2, annexin A5, annexin A10, gelsolin isoform b) and iron-regulated proteins (ferritin, heme-binding protein 2, transferrin). On the basis of these findings, the intracellular calcium concentration was determined, revealing a significant increase after 24 h of exposure to TCDD. Moreover, the concentration of the labile iron pool (LIP) was also significantly elevated in TCDD-exposed cells. This increase was strongly inhibited by the calmodulin (CaM) antagonist W-7, which pointed toward a possible interaction between iron and calcium signaling. Because nitric oxide (NO) production was significantly enhanced in TCDD-exposed cells and was also inhibited by W-7, we hypothesize that alterations in calcium and iron homeostasis upon exposure to TCDD may be linked through NO generated by CaM-activated nitric oxide synthase. In our model, we propose that NO produced upon TCDD exposure interacts with the iron centers of iron-regulatory proteins (IRPs) that modulate the alteration of ferritin and transferrin, resulting in an augmented cellular LIP and, hence, increased toxicity.

  3. Ethylene and nitric oxide involvement in the up-regulation of key genes related to iron acquisition and homeostasis in Arabidopsis.

    PubMed

    García, María J; Lucena, Carlos; Romera, Francisco J; Alcántara, Esteban; Pérez-Vicente, Rafael

    2010-09-01

    In a previous work it was shown that ethylene participates in the up-regulation of several Fe acquisition genes of Arabidopsis, such as AtFIT, AtFRO2, and AtIRT1. In this work the relationship between ethylene and Fe-related genes in Arabidopsis has been looked at in more depth. Genes induced by Fe deficiency regulated by ethylene were searched for. For this, studies were conducted, using microarray analysis and reverse transcription-PCR (RT-PCR), to determine which of the genes up-regulated by Fe deficiency are simultaneously suppressed by two different ethylene inhibitors (cobalt and silver thiosulphate), assessing their regulation by ethylene in additional experiments. In a complementary experiment, it was determined that the Fe-related genes up-regulated by ethylene were also responsive to nitric oxide (NO). Further studies were performed to analyse whether Fe deficiency up-regulates the expression of genes involved in ethylene biosynthesis [S-adenosylmethionine synthetase, 1-aminocyclopropane-1-carboxylate (ACC) synthase, and ACC oxidase genes] and signalling (AtETR1, AtCTR1, AtEIN2, AtEIN3, AtEIL1, and AtEIL3). The results obtained show that both ethylene and NO are involved in the up-regulation of many important Fe-regulated genes of Arabidopsis, such as AtFIT, AtbHLH38, AtbHLH39, AtFRO2, AtIRT1, AtNAS1, AtNAS2, AtFRD3, AtMYB72, and others. In addition, the results show that Fe deficiency up-regulates genes involved in both ethylene synthesis (AtSAM1, AtSAM2, AtACS4, AtACS6, AtACS9, AtACO1, and AtACO2) and signalling (AtETR1, AtCTR1, AtEIN2, AtEIN3, AtEIL1, and AtEIL3) in the roots.

  4. [Nitric oxide production in plants].

    PubMed

    Małolepsza, Urszula

    2007-01-01

    There are still many controversial observations and opinions on the cellular/subcellular localization and sources of endogenous nitric oxide synthesis in plant cells. NO can be produced in plants by non-enzymatic and enzymatic systems depending on plant species, organ or tissue as well as on physiological state of the plant and changing environmental conditions. The best documented reactions in plant that contribute to NO production are NO production from nitrite as a substrate by cytosolic (cNR) and membrane bound (PM-NR) nitrate reductases (NR), and NO production by several arginine-dependent nitric oxide synthase-like activities (NOS). The latest papers indicate that mitochondria are an important source of arginine- and nitrite-dependent NO production in plants. There are other potential enzymatic sources of NO in plants including xanthine oxidoreductase, peroxidase, cytochrome P450.

  5. Nitric oxide reburning with methane

    SciTech Connect

    Kumpaty, S.K.; Subramanian, K.

    1996-12-31

    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.

  6. Nitric oxide and airway reactivity.

    PubMed

    Strapkova, A; Nosalova, G

    2001-01-01

    Nitric oxide is a neurotransmitter of the inhibitory nonadrenergic noncholinergic mediation in the respiratory system. Its participation in the regulation of airways functions is determined by its level in the organism. We examined participation of nitric oxide in the changes of the airway reactivity evoked by toluene exposure as the source of the free radicals. The changes of nitric oxide level in the organism were evoked by administration of its indirect donor isosorbide dinitrate. Thiol groups were provided by administration of antioxidative mucolytic N-acetylcysteine. Used drugs--isosorbide dinitrate (5 mg/kg b.w.) and N-acetylcysteine (300 mg/kg b.w.) were administered intraperitoneally or by inhalation 30 minutes before each exposure to the toluene vapours. The control group was not treated with drugs. After toluene exposure (2 hours in each of 3 consecutive days) tracheal and lung strips smooth muscle reactivity to histamine was observed under in "in vitro" conditions. The administration of isosorbide dinitrate decreased especially the lung strip smooth muscle reactivity to histamine. We revealed more expressive effect of the pretreatment with intraperitoneally administered isosorbide dinitrate in the comparison with inhalation. Simultaneous pretreatment with N-acetylcysteine intensified beneficial effect of isosorbide dinitrate probably by increasing of the intracellullary level of thiols. In our experimental conditions possible participation of nitric oxide in changes of airways smooth muscle reactivity after exposure to the toluene follows from results, as well as the importance of thiol groups for the activity of its indirect donors. (Fig. 6, Tab. 3, Ref. 35.)

  7. Nitric Oxide Production in Plants

    PubMed Central

    Planchet, Elisabeth

    2006-01-01

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

  8. Nitric oxide and the common cold.

    PubMed

    Proud, David

    2005-02-01

    The common cold is a clinical syndrome triggered by a variety of viral pathogens, but rhinoviruses are the most frequent cause. Complications of such infections include sinusitis, otitis media, and exacerbations of asthma and chronic obstructive lung disease. There is growing interest in host innate defence responses that may regulate the severity of viral responses. We will review recent evidence that nitric oxide is an important contributor to the host response during colds. Infection of human airway epithelial cells with human rhinovirus has been shown to lead to the increased expression of inducible nitric oxide synthase both in vitro and in vivo. This increase in epithelial inducible nitric oxide synthase correlates with increased levels of nitric oxide in exhaled air. Importantly, nitric oxide can inhibit human rhinovirus-induced epithelial expression of several pro-inflammatory cytokines and can inhibit viral replication in epithelial cells in vitro. Moreover, nitric oxide can modulate several signal transduction pathways that are associated with cytokine generation. Nitric oxide can also nitrosylate viral proteases and can interact with the immune system. Consistent with these observations, pilot studies have indicated that the increased generation of nitric oxide during rhinovirus infections is associated with fewer symptoms and more rapid viral clearance. Further studies are warranted to evaluate the role of nitric oxide in colds and to determine whether the administration of nitric oxide donor compounds could be a viable therapeutic approach for viral exacerbations of airway diseases.

  9. The emerging multifaceted roles of nitric oxide.

    PubMed Central

    Kuo, P C; Schroeder, R A

    1995-01-01

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

  10. Nitric oxide: a challenge to chiropractic

    PubMed Central

    Morgan, Lon

    2000-01-01

    The 1998 Nobel Prize in Physiology or Medicine recognized the biological significance of nitric oxide. Nitric oxide is derived from the amino acid arginine. It is intimately involved with circulatory vessel dilation where, for example, it protects against heart attacks, and is the basis for new medications such as Sildenafil (Viagra). Nitric oxide acts as a neurotransmitter and can modulate many neurological reactions. The immune system uses nitric oxide to destroy pathogens by interfering with key enzymes. Nitric oxide is responsible for both osteoclastic and osteoblastic responses in bone and is a key player in the degenerative aspects of arthritis. The process of apoptosis employs nitric oxide in the orderly removal of unneeded cells. There is clear evidence that major signaling and control mechanisms exist in the body apart from the nervous system. Chiropractic is thus faced with the challenge of how to incorporate this new knowledge which conflicts with traditional chiropractic concepts.

  11. Nitric oxide in marine photosynthetic organisms.

    PubMed

    Kumar, Amit; Castellano, Immacolata; Patti, Francesco Paolo; Palumbo, Anna; Buia, Maria Cristina

    2015-05-01

    Nitric oxide is a versatile and powerful signaling molecule in plants. However, most of our understanding stems from studies on terrestrial plants and very little is known about marine autotrophs. This review summarizes current knowledge about the source of nitric oxide synthesis in marine photosynthetic organisms and its role in various physiological processes under normal and stress conditions. The interactions of nitric oxide with other stress signals and cross talk among secondary messengers are also highlighted.

  12. The nitric oxide producing reactions of hydroxyurea.

    PubMed

    King, S Bruce

    2003-03-01

    Hydroxyurea is used to treat a variety of cancers and sickle cell disease. Despite this widespread use, a complete mechanistic understanding of the beneficial actions of this compound remains to be understood. Hydroxyurea inhibits ribonucleotide reductase and increases the levels of fetal hemoglobin, which explains a portion of the effects of this drug. Administration of hydroxyurea to patients results in a significant increase in levels of iron nitrosyl hemoglobin, nitrite and nitrate suggesting the in vivo metabolism of hydroxyurea to nitric oxide. Formation of nitric oxide from hydroxyurea may explain a portion of the observed effects of hydroxyurea treatment. At the present, the mechanism or mechanisms of nitric oxide release, the identity of the in vivo oxidant and the site of metabolism remain to be identified. Chemical oxidation of hydroxyurea produces nitric oxide and nitroxyl, the one-electron reduced form of nitric oxide. These oxidative pathways generally proceed through the nitroxide radical (2) or C-nitrosoformamide (3). Biological oxidants, including both iron and copper containing enzymes and proteins, also convert hydroxyurea to nitric oxide or its decomposition products in vitro and these reactions also occur through these intermediates. A number of other reactions of hydroxyurea including the reaction with ribonucleotide reductase and irradiation demonstrate the potential to release nitric oxide and should be further investigated. Gaining an understanding of the metabolism of hydroxyurea to nitric oxide will provide valuable information towards the treatment of these disorders and may lead to the development of better therapeutic agents.

  13. Study of Atmospheric Nitric Oxide

    NASA Technical Reports Server (NTRS)

    Dalgarno, A.

    1998-01-01

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

  14. Novel effects of nitric oxide

    NASA Technical Reports Server (NTRS)

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

    2001-01-01

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

  15. [Nitric oxide in dengue pathology].

    PubMed

    Rodriguez-Ortega, M

    1998-01-01

    Nitric oxide (NO) is a multifunctional molecule that is involved in citotoxic as well as citoprotective processes, it's synthesis is highly regulated by the cell because an alteration in NO production is associated with a variety of pathologies, such as Septic, Anaphylactic and Hemorrhagic Shock. The clinical feature of dengue virus infection has a spectrum that goes from mild, dengue fever, to a severe disease, dengue hemorrhagic fever/dengue shock. Here, some evidences are discussed that links NO with the pathology of the severe disease cause by dengue virus.

  16. The basics about nitric oxide.

    PubMed

    Bruckdorfer, Richard

    2005-01-01

    Nitric oxide is a gas and a free radical which is now recognised to have very important physiological roles. It is synthesised enzymatically from the amino acid L-arginine in a number of tissues using the three isoforms of nitric oxide synthase, one of which is inducible and can form much large amounts of NO. NO is important in the endothelium-dependent regulation of blood flow and pressure as well as inhibiting the activation of blood platelets. NO is recognised as a neurotransmitter at least in certain types of nerves. Along with other free radicals, NO is also important in the primary defence mechanisms against attack by micro-organisms. NO has a close interaction with iron-containing proteins and binds to haem. By this process NO activates a haem-containing enzyme called soluble guanylyl cyclase which is activated a thousand fold to produce the signalling molecule cyclic GMP. This has many effects at the molecular level to set in train the pathways which propagate the diverse physiological actions of NO. Although this pathway through cyclic GMP is important, this is by no means the only mechanism by which NO influences the activities of the cell. These alternative pathways depend on modification of the structure of enzymes and structural proteins in several different ways. Most of these modifications result from the actions of NO with other free radicals such as oxygen and superoxide anions to produce reactive oxidants. The oxidants modify the proteins by, among others, nitrosation and nitration of proteins of thiol groups and aromatic amino acids respectively. These changes introduce potential new subtleties to the effects on NO on cellular function which are only now being explored. Protein modifications by NO are even more evident in many inflammatory disorders and may account, at least to some extent, to the pathology seen in these conditions.

  17. Oxidative stress, nitric oxide, and diabetes.

    PubMed

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

    2010-01-01

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

  18. Oxidative Stress, Nitric Oxide, and Diabetes

    PubMed Central

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

    2010-01-01

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

  19. Nitric oxide fumigation for postharvest pest control

    USDA-ARS?s Scientific Manuscript database

    Nitric oxide fumigation is effective against all arthropod pests at various life stages tested. Nine insect pests at various life stages and bulb mites were subjected to nitric oxide fumigation treatments under ultralow oxygen conditions of =50 ppm O2 in 1.9L glass jars as fumigation chambers. The ...

  20. Two Dimensional Polymer That Generates Nitric Oxide.

    DOEpatents

    McDonald, William F.; Koren, Amy B.

    2005-10-04

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

  1. UV Induced Oxidation of Nitric Oxide

    NASA Technical Reports Server (NTRS)

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

    2007-01-01

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

  2. Analytical Chemistry of Nitric Oxide

    PubMed Central

    Hetrick, Evan M.

    2013-01-01

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

  3. Nanocarriers for Nitric Oxide Delivery

    PubMed Central

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

    2011-01-01

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

  4. Analytical chemistry of nitric oxide.

    PubMed

    Hetrick, Evan M; Schoenfisch, Mark H

    2009-01-01

    Nitric oxide (NO) is the focus of intense research primarily because of its wide-ranging biological and physiological actions. To understand its origin, activity, and regulation, accurate and precise measurement techniques are needed. 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 the picomolar-to-micromolar range in physiological milieus, 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 a focus on the underlying mechanism of each technique and on approaches that have been coupled with modern analytical measurement tools to create novel NO sensors.

  5. Nitric oxide and virus infection

    PubMed Central

    Akaike, T; Maeda, H

    2000-01-01

    Nitric oxide (NO) has complex and diverse functions in physiological and pathophysiological phenomena. The mechanisms of many events induced by NO are now well defined, so that a fundamental understanding of NO biology is almost established. Accumulated evidence suggests that NO and oxygen radicals such as superoxide are key molecules in the pathogenesis of various infectious diseases. NO biosynthesis, particularly through expression of an inducible NO synthase (iNOS), occurs in a variety of microbial infections. Although antimicrobial activity of NO is appreciated for bacteria and protozoa, NO has opposing effects in virus infections such as influenza virus pneumonia and certain other neurotropic virus infections. iNOS produces an excessive amount of NO for long periods, which allows generation of a highly reactive nitrogen oxide species, peroxynitrite, via a radical coupling reaction of NO with superoxide. Thus, peroxynitrite causes oxidative tissue injury through potent oxidation and nitration reactions of various biomolecules. NO also appears to affect a host's immune response, with immunopathological consequences. For example, overproduction of NO in virus infections in mice is reported to suppress type 1 helper T-cell-dependent immune responses, leading to type 2 helper T-cell-biased immunological host responses. Thus, NO may be a host response modulator rather than a simple antiviral agent. The unique biological properties of NO are further illustrated by our recent data suggesting that viral mutation and evolution may be accelerated by NO-induced oxidative stress. Here, we discuss these multiple roles of NO in pathogenesis of virus infections as related to both non-specific inflammatory responses and immunological host reactions modulated by NO during infections in vivo. PMID:11106932

  6. Nitric Oxide Synthases in Heart Failure

    PubMed Central

    Carnicer, Ricardo; Crabtree, Mark J.; Sivakumaran, Vidhya

    2013-01-01

    Abstract Significance: The regulation of myocardial function by constitutive nitric oxide synthases (NOS) is important for the maintenance of myocardial Ca2+ homeostasis, relaxation and distensibility, and protection from arrhythmia and abnormal stress stimuli. However, sustained insults such as diabetes, hypertension, hemodynamic overload, and atrial fibrillation lead to dysfunctional NOS activity with superoxide produced instead of NO and worse pathophysiology. Recent Advances: Major strides in understanding the role of normal and abnormal constitutive NOS in the heart have revealed molecular targets by which NO modulates myocyte function and morphology, the role and nature of post-translational modifications of NOS, and factors controlling nitroso-redox balance. Localized and differential signaling from NOS1 (neuronal) versus NOS3 (endothelial) isoforms are being identified, as are methods to restore NOS function in heart disease. Critical Issues: Abnormal NOS signaling plays a key role in many cardiac disorders, while targeted modulation may potentially reverse this pathogenic source of oxidative stress. Future Directions: Improvements in the clinical translation of potent modulators of NOS function/dysfunction may ultimately provide a powerful new treatment for many hearts diseases that are fueled by nitroso-redox imbalance. Antioxid. Redox Signal. 18, 1078–1099. PMID:22871241

  7. Sampling nitric oxide from combustion gases.

    NASA Technical Reports Server (NTRS)

    England, C.; Houseman, J.; Teixeira, D. P.

    1973-01-01

    Experimental study of several sampling tube and probe material compositions and designs aimed at preventing nitric oxide reduction when sampling nitric oxide from combustion gases. A 250,000 Btu/h furnace fired with technical grade methane was used for testing the sampling probes over a wide range of air-fuel mixtures. The results obtained include the finding that the use of stainless steel in probes creates inaccuracies in near-stoichiometric and fuel-rich sampling in hydrocarbon flames. For very fuel-rich flames, water cooling is needed even in quartz probes to prevent significant reduction of nitric oxide.-

  8. Distribution of nitric oxide in cardiovascular system.

    PubMed

    Mesáros, S; Grunfeld, S

    1997-01-01

    We report here the in vitro measurements of nitric oxide in the cardiovascular system using a porphyrinic sensor specific for NO. Nitric oxide concentrations were measured directly in different parts of the heart and also in different arteries and veins, ranging from 100 microm to 5 mm in diameter. Highest NO. concentrations were found in the heart and particularly in the areas of aortic and pulmonary valves. The NO. concentration in the arteries was higher than in the veins. A clearcut positive correlation was obtained by plotting the vessel diameter and production of nitric oxide.

  9. 21 CFR 868.2380 - Nitric oxide analyzer.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Nitric oxide analyzer. 868.2380 Section 868.2380...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2380 Nitric oxide analyzer. (a) Identification. The nitric oxide analyzer is a device intended to measure the concentration of nitric oxide...

  10. 21 CFR 868.2380 - Nitric oxide analyzer.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Nitric oxide analyzer. 868.2380 Section 868.2380...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2380 Nitric oxide analyzer. (a) Identification. The nitric oxide analyzer is a device intended to measure the concentration of nitric oxide...

  11. 21 CFR 868.2380 - Nitric oxide analyzer.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Nitric oxide analyzer. 868.2380 Section 868.2380...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2380 Nitric oxide analyzer. (a) Identification. The nitric oxide analyzer is a device intended to measure the concentration of nitric oxide...

  12. 21 CFR 868.2380 - Nitric oxide analyzer.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Nitric oxide analyzer. 868.2380 Section 868.2380...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2380 Nitric oxide analyzer. (a) Identification. The nitric oxide analyzer is a device intended to measure the concentration of nitric oxide...

  13. 21 CFR 868.5165 - Nitric oxide administration apparatus.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Nitric oxide administration apparatus. 868.5165... apparatus. (a) Identification. The nitric oxide administration apparatus is a device used to add nitric oxide to gases that are to be breathed by a patient. The nitric oxide administration apparatus is to...

  14. 21 CFR 868.5165 - Nitric oxide administration apparatus.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Nitric oxide administration apparatus. 868.5165... apparatus. (a) Identification. The nitric oxide administration apparatus is a device used to add nitric oxide to gases that are to be breathed by a patient. The nitric oxide administration apparatus is to...

  15. Anticonvulsant drugs, oxidative stress and nitric oxide.

    PubMed

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

    2011-01-01

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

  16. Nitric oxide production by Tunguska meteor

    NASA Technical Reports Server (NTRS)

    Park, C.

    1978-01-01

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

  17. Inducible nitric oxide synthase in the myocard.

    PubMed

    Buchwalow, I B; Schulze, W; Karczewski, P; Kostic, M M; Wallukat, G; Morwinski, R; Krause, E G; Müller, J; Paul, M; Slezak, J; Luft, F C; Haller, H

    2001-01-01

    Recognition of significance of nitric oxide synthases (NOS) in cardiovascular regulations has led to intensive research and development of therapies focused on NOS as potential therapeutic targets. However, the NOS isoform profile of cardiac tissue and subcellular localization of NOS isoforms remain a matter of debate. The aim of this study was to investigate the localization of an inducible NOS isoform (NOS2) in cardiomyocytes. Employing a novel immunocytochemical technique of a catalyzed reporter deposition system with tyramide and electron microscopical immunocytochemistry complemented with Western blotting and RT-PCR, we detected NOS2 both in rat neonatal and adult cultured cardiomyocytes and in the normal myocard of adult rats as well as in the human myocard of patients with dilative cardiomyopathy. NOS2 was targeted predominantly to a particulate component of the cardiomyocyte--along contractile fibers, in the plasma membrane including T-tubules, as well as in the nuclear envelope, mitochondria and Golgi complex. Our results point to an involvement of NOS2 in maintaining cardiac homeostasis and contradict to the notion that NOS2 is expressed in cardiac tissue only in response to various physiological and pathogenic factors. NOS2 targeting to mitochondria and contractile fibers suggests a relationship of NO with contractile function and energy production in the cardiac muscle.

  18. Hemoglobin: A Nitric-Oxide Dioxygenase

    PubMed Central

    Gardner, Paul R.

    2012-01-01

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

  19. Nitric oxide synthase in tiger salamander retina.

    PubMed

    Kurenni, D E; Thurlow, G A; Turner, R W; Moroz, L L; Sharkey, K A; Barnes, S

    1995-10-23

    Previous studies have indicated that nitric oxide, a labile freely diffusible biological messenger synthesized by nitric oxide synthase, may modulate light transduction and signal transmission in the retina. In the present work, the large size of retinal cells in tiger salamander (Ambystoma tigrinum) allowed the utilization of nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase histochemistry and nitric oxide synthase immunocytochemistry to delineate the cell-specific intracellular localization of nitric oxide synthase. NADPH-diaphorase activity was highly concentrated in the outer retina, in rod and cone inner segment ellipsoids, and between and adjacent to the photoreceptor cell bodies in the outer nuclear layer. Examination of enzymatically isolated retinal cells indicated that outer nuclear layer NADPH-diaphorase activity was localized to the distal processes of the retinal glial (Müller) cells and to putative bipolar cell Landolt clubs. Less intense NADPH-diaphorase activity was seen in the photoreceptor inner segment myoid region, in a small number of inner nuclear layer cells, in cap-like configurations at the distal poles of cells in the ganglion cell layer and surrounding ganglion cell layer somata, and in punctate form within both plexiform layers, the pigment epithelium, and the optic nerve. Nitric oxide synthase-like immunoreactivity was similarly localized, but was also concentrated along a thin sublamina centered within the inner plexiform layer. The potential for nitric oxide generation at multiple retinal sites suggests that this molecule may play a number of roles in the processing of visual information in the retina.

  20. [Nitric oxide and lipid peroxidation].

    PubMed

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

    1995-01-01

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

  1. [Retinal ischemia and nitric oxide].

    PubMed

    Neroev, V V; Arkhipova, M M

    2003-01-01

    Retinal ischemia is the main chain in the pathogenesis of vascular diseases of the eye. It was established that nitric oxide (NO) plays the key role in the development of ischemia. Recent understanding of the NO role, as a universal regulator of the cellular and tissue metabolism, is presented. The authors' and published data were used to design a scheme of pathogenesis of retinal ischemia with regard for the NO role. NO can produce both positive and negative effects depending on a stage of the process, NO concentration and on a number of other factors if they are present. Initial stages of hypoxia/ischemia are accompanied by an activation of all forms of NO-synthases (NOS) caused by the influence of biologically active substances (cytokines, prostaglandins, serotonin, bradykinin, glycolisis suboxide products etc.). The activation of inducible NOS, which synthesize a bigger quantity of NO possessing a direct cytotoxic action and contributing to the production of highly toxic radical of peroxinitrit, is in the focus of attention. The damage of cellular structures due to free-radical processes leads to the development of endothelial, macrophage and thrombocyte malfunctions, which manifest itself through a reduced activity of endothelial NOS and through disruption of NO-dependent processes (vasospasm, an increased aggregation of platelets and a reduced fibrinolytic activity). A sharp reduction of NO synthesis substrate (L-arginine) is observed in patients with retinal ischemia. The aggravation of ischemia causes a decrease of NO synthesis due to an exhaustion of L-arginine and its intensified consumption in the course of free-radical processes. The use of NO-inhibitors and of NO-donors at different stages of retinal ischemia prevents the development of neovascularization and proliferation.

  2. Nitric oxide, inducible nitric oxide synthase and inflammation in veterinary medicine.

    PubMed

    Hunter, Robert P

    2002-12-01

    Inflammation is a process consisting of a complex of cytological and chemical reactions which occur in and around affected blood vessels and adjacent tissues in response to an injury caused by a physical, chemical or biological insult. Much work has been performed in the past several years investigating inducible nitric oxide synthase (NOS, EC 1.14.13.39) and nitric oxide in inflammation. This has resulted in a rapid increase in knowledge about iNOS and nitric oxide. Nitric oxide formation from inducible NOS is regulated by numerous inflammatory mediators, often with contradictory effects, depending upon the type and duration of the inflammatory insult. Equine medicine appears to have benefited the most from the increased interest in this small, inflammatory mediator. Most of the information on nitric oxide in traditional veterinary species has been produced using models or naturally occurring inflammatory diseases of this species.

  3. Neural mechanisms in nitric-oxide-deficient hypertension

    NASA Technical Reports Server (NTRS)

    Sander, M.; Victor, R. G.; Blomqvist, C. G. (Principal Investigator)

    1999-01-01

    Nitric oxide is hypothesized to be an inhibitory modulator of central sympathetic nervous outflow, and deficient neuronal nitric oxide production to cause sympathetic overactivity, which then contributes to nitric-oxide-deficient hypertension. The biochemical and neuroanatomical basis for this concept revolves around nitric oxide modulation of glutamatergic neurotransmission within brainstem vasomotor centers. The functional consequence of neuronal nitric oxide in blood pressure regulation is, however, marked by an apparent conflict in the literature. On one hand, conscious animal studies using sympathetic blockade suggest a significant role for neuronal nitric oxide deficiency in the development of nitric-oxide-deficient hypertension, and on the other hand, there is evidence against such a role derived from 'knock-out' mice lacking nitric-oxide synthase 1, the major source of neuronal nitric oxide.

  4. Neural mechanisms in nitric-oxide-deficient hypertension

    NASA Technical Reports Server (NTRS)

    Sander, M.; Victor, R. G.; Blomqvist, C. G. (Principal Investigator)

    1999-01-01

    Nitric oxide is hypothesized to be an inhibitory modulator of central sympathetic nervous outflow, and deficient neuronal nitric oxide production to cause sympathetic overactivity, which then contributes to nitric-oxide-deficient hypertension. The biochemical and neuroanatomical basis for this concept revolves around nitric oxide modulation of glutamatergic neurotransmission within brainstem vasomotor centers. The functional consequence of neuronal nitric oxide in blood pressure regulation is, however, marked by an apparent conflict in the literature. On one hand, conscious animal studies using sympathetic blockade suggest a significant role for neuronal nitric oxide deficiency in the development of nitric-oxide-deficient hypertension, and on the other hand, there is evidence against such a role derived from 'knock-out' mice lacking nitric-oxide synthase 1, the major source of neuronal nitric oxide.

  5. Nitric oxide inhibition of human sperm motility.

    PubMed

    Weinberg, J B; Doty, E; Bonaventura, J; Haney, A F

    1995-08-01

    To determine the effect of nitric oxide (NO) on sperm motility in vitro. Normal human sperm separated by centrifugation through a discontinuous Percoll gradient and subsequent swim-up were incubated for up to 24 hours with NO donors, with and without the known NO quencher hemoglobin, as well as with agents that raise intracellular cyclic 3',5'-guanosine monophosphate (cGMP). Sperm respiration was determined by a tetrazolium-formazan spectrophotometric assay. Andrology laboratory. Absolute sperm motility and respiration. Sperm incubated with the NO donors 1 mM nitroprusside, 100 to 125 microM 3-morpholinosydnonimine, and 25 to 125 microM pure nitric oxide gas dissolved in buffer were inhibited in motility in a dose-dependent fashion. The inhibition could be reversed by the NO quencher hemoglobin. Agents that raise cellular cGMP (dibutyryl cGMP or 8-bromo-cGMP) did not inhibit motility. Nitric oxide inhibited sperm respiration, as measured by the tetrazolium-formazan assay. Nitric oxide reduces sperm motility, possibly by a mechanism involving inhibition of cellular respiration independent of an elevation of intracellular cGMP. Nitric oxide elaborated in the female or male genital tract in vivo could adversely influence sperm function and fertility.

  6. Oxidative Stress and Autophagy in Cardiovascular Homeostasis

    PubMed Central

    Morales, Cyndi R.; Pedrozo, Zully; Lavandero, Sergio

    2014-01-01

    Abstract Significance: Autophagy is an evolutionarily ancient process of intracellular protein and organelle recycling required to maintain cellular homeostasis in the face of a wide variety of stresses. Dysregulation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) leads to oxidative damage. Both autophagy and ROS/RNS serve pathological or adaptive roles within cardiomyocytes, depending on the context. Recent Advances: ROS/RNS and autophagy communicate with each other via both transcriptional and post-translational events. This cross talk, in turn, regulates the structural integrity of cardiomyocytes, promotes proteostasis, and reduces inflammation, events critical to disease pathogenesis. Critical Issues: Dysregulation of either autophagy or redox state has been implicated in many cardiovascular diseases. Cardiomyocytes are rich in mitochondria, which make them particularly sensitive to oxidative damage. Maintenance of mitochondrial homeostasis and elimination of defective mitochondria are each critical to the maintenance of redox homeostasis. Future Directions: The complex interplay between autophagy and oxidative stress underlies a wide range of physiological and pathological events and its elucidation holds promise of potential clinical applicability. Antioxid. Redox Signal. 20, 507–518. PMID:23641894

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

    PubMed Central

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

    2009-01-01

    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

  8. Hemorrhagic shock and nitric oxide release from erythrocytic nitric oxide synthase: a quantitative analysis.

    PubMed

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

    2009-06-01

    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 O(2) 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 approximately 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.

  9. Nitric Oxide's Involvement in the Spectrum of Psychotic Disorders.

    PubMed

    Maia-de-Oliveira, João Paulo; Kandratavicius, Ludmyla; Nunes, Emerson Arcoverde; Machado-de-Sousa, João Paulo; Hallak, Jaime E; Dursun, Serdar Murat

    2016-01-01

    Recent findings suggest that dopaminergic abnormalities found in psychotic disorders may be secondary to nitric oxide dysfunctions. Nitric oxide seems to influence glutamatergic and dopaminergic neurotransmission, both of which have been associated with psychosis. To search and review published works which examined the influence of nitric oxide in psychotic disorders subjects. The research was executed in the on-line collections of Pubmed and ISI Web of Science. The key aspects utilized were "Psychotic Disorders AND Nitric Oxide", "Psychosis AND Nitric Oxide","Schizotypal Personality Disorder AND Nitric Oxide", "Delusional Disorder AND Nitric Oxide", "Brief Psychotic Disorder AND Nitric Oxide", "Schizophreniform Disorder AND Nitric Oxide", "Schizoaffective Disorder AND Nitric Oxide", and "Schizophrenia AND Nitric Oxide". Empirical works utilizing human subjects, published in the last 10 years, in English language were included. Initially, the search yielded a total of 95 studies. Then, 39 were elected according to the inclusion requirements. The selected articles were divided into five groups: biochemical studies (n=15; 38.5%), genetic studies (n=11; 28.2%), postmortem studies (n=6; 15.4%), clinical trials (n=6; 15.4%), and case reports (n=1; 2.5%). The studies evaluated only schizophrenic or schizoaffective disorder subjects. The great majority of them found evidence of nitric oxide dysfunctions in psychosis. The results of the review strengthen the idea that nitric oxide has a key participation in psychotic disorders and deserves deeper investigation as a target for future pharmacological intervention.

  10. The role of Bradyrhizobium japonicum nitric oxide reductase in nitric oxide detoxification in soya bean root nodules.

    PubMed

    Meakin, G E; Jepson, B J N; Richardson, D J; Bedmar, E J; Delgado, M J

    2006-02-01

    The identification of nitric oxide-bound leghaemoglobin within soya bean nodules has led to the question of how Bradyrhizobium japonicum bacteroids overcome the toxicity of this nitric oxide. It has previously been shown that one candidate for nitric oxide detoxification, the respiratory nitric oxide reductase, is expressed in soya bean nodules from plants supplied with nitrate. In this paper, the role of this enzyme in nitric oxide detoxification is assessed and discussion is provided on other possible B. japonicum nitric oxide detoxification systems.

  11. Nitric oxide signaling in aluminum stress in plants.

    PubMed

    He, Huyi; Zhan, Jie; He, Longfei; Gu, Minghua

    2012-07-01

    Nitric oxide (NO) is a ubiquitous signal molecule involved in multiple plant responses to environmental stress. In the recent years, the regulating role of NO on heavy metal toxicity in plants is realized increasingly, but knowledge of NO in alleviating aluminum (Al) toxicity is quite limited. In this article, NO homeostasis between its biosynthesis and elimination in plants is presented. Some genes involved in NO/Al network and their expressions are also introduced. Furthermore, the role of NO in Al toxicity and the functions in Al tolerance are discussed. It is proposed that Al toxicity may disrupt NO homeostasis, leading to endogenous NO concentration being lower than required for root elongation in plants. There are many evidences that pointed out that the exogenous NO treatments improve Al tolerance in plants through activating antioxidative capacity to eliminate reactive oxygen species. Most of the work with respect to NO regulating pathways and functions still has to be done in the future.

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

    PubMed Central

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

    1995-01-01

    Recent studies have suggested that nitric oxide (NO.), the product of nitric oxide synthase in inflammatory cells, may play a part in tissue injury and inflammation through its oxidative metabolism. In this study the colonic generation of oxides of nitrogen (NOx) and nitric oxide synthase activity was determined in ulcerative colitis and Crohn's disease. Colonic biopsy specimens were obtained from inflammatory bowel disease patients and from normal controls. Mucosal explants were cultured in vitro for 24 hours and NOx generation was determined. Nitric oxide synthase activity was monitored by the conversion of [3H]-L-arginine to citrulline. Median NOx generation by inflamed colonic mucosa of patients with active ulcerative colitis and Crohn's colitis was 4.2- and 8.1-fold respectively higher than that by normal human colonic mucosa. In ulcerative colitis and Crohn's colitis nitric oxide synthase activity was 10.0- and 3.8-fold respectively higher than in normal subjects. Colonic NOx generation is significantly decreased by methylprednisolone and ketotifen. The decrease in NOx generation by cultured colonic mucosa induced by methylprednisolone suggests that NO synthase activity is induced during the culture and the steroid effect may contribute to its therapeutic effect. Enhanced colonic NOx generation by stimulated nitric oxide synthase activity in ulcerative colitis and Crohn's disease may contribute to tissue injury. PMID:7541008

  13. Role of exhaled nitric oxide in asthma.

    PubMed

    Yates, D H

    2001-04-01

    Nitric oxide (NO), an evanescent atmospheric gas, has recently been discovered to be an important biological mediator in animals and humans. Nitric oxide plays a key role within the lung in the modulation of a wide variety of functions including pulmonary vascular tone, nonadrenergic non-cholinergic (NANC) transmission and modification of the inflammatory response. Asthma is characterized by chronic airway inflammation and increased synthesis of NO and other highly reactive and toxic substances (reactive oxygen species). Pro- inflammatory cytokines such as TNFalpha and IL-1beta are secreted in asthma and result in inflammatory cell recruitment, but also induce calcium- and calmodulin-independent nitric oxide synthases (iNOS) and perpetuate the inflammatory response within the airways. Nitric oxide is released by several pulmonary cells including epithelial cells, eosinophils and macrophages, and NO has been shown to be increased in conditions associated with airway inflammation, such as asthma and viral infections. Nitric oxide can be measured in the expired air of several species, and exhaled NO can now be rapidly and easily measured by the use of chemiluminescence analysers in humans. Exhaled NO is increased in steroid-naive asthmatic subjects and during an asthma exacerbation, although it returns to baseline levels with appropriate anti-inflammatory treatment, and such measurements have been proposed as a simple non-invasive method of measuring airway inflammation in asthma. Here the chemical and biological properties of NO are briefly discussed, followed by a summary of the methodological considerations relevant to the measurement of exhaled NO and its role in lung diseases including asthma. The origin of exhaled NO is considered, and brief mention made of other potential markers of airway inflammation or oxidant stress in exhaled breath.

  14. Neuronal Nitric Oxide Synthase in Vascular Physiology and Diseases

    PubMed Central

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

    2016-01-01

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

  15. BIOGENIC NITRIC OXIDE EMISSIONS FROM CROPLAND SOILS

    EPA Science Inventory

    Emissions of nitric oxide (NO) were determined during late spring and summer 1995 and the spring of 1996 from four agricultural soils on which four different crops were grown. These agricultural soils were located at four different sites throughout North Carolina. Emission rates ...

  16. Arginine metabolism: nitric oxide and beyond.

    PubMed Central

    Wu, G; Morris, S M

    1998-01-01

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

  17. BIOGENIC NITRIC OXIDE EMISSIONS FROM CROPLAND SOILS

    EPA Science Inventory

    Emissions of nitric oxide (NO) were determined during late spring and summer 1995 and the spring of 1996 from four agricultural soils on which four different crops were grown. These agricultural soils were located at four different sites throughout North Carolina. Emission rates ...

  18. Nitric oxide. Novel biology with clinical relevance.

    PubMed Central

    Billiar, T R

    1995-01-01

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

  19. Nitric oxide-releasing ruthenium nanoparticles.

    PubMed

    Ho, Chi-Ming; Liao, Kai-Jun; Lok, Chun-Nam; Che, Chi-Ming

    2011-10-14

    Nitric oxide-releasing ruthenium nanoparticles were synthesized by the reaction of alkanethiolate-protected ruthenium nanoparticles with tert-butyl nitrite ((t)BuONO), and their water-soluble derivatives are able to deliver NO to proteins such as reduced myoglobin upon light irradiation in aqueous media.

  20. 21 CFR 868.5165 - Nitric oxide administration apparatus.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Nitric oxide administration apparatus. 868.5165... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5165 Nitric oxide administration apparatus. (a) Identification. The nitric oxide administration apparatus is a device used to add...

  1. 21 CFR 868.5165 - Nitric oxide administration apparatus.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Nitric oxide administration apparatus. 868.5165... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5165 Nitric oxide administration apparatus. (a) Identification. The nitric oxide administration apparatus is a device used to add...

  2. 21 CFR 868.5165 - Nitric oxide administration apparatus.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Nitric oxide administration apparatus. 868.5165... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5165 Nitric oxide administration apparatus. (a) Identification. The nitric oxide administration apparatus is a device used to add...

  3. Nitric oxide methods in seed biology.

    PubMed

    Bethke, Paul C; Libourel, Igor G L; Vitecek, Jan; Jones, Russell L

    2011-01-01

    The ubiquitous signaling molecule nitric oxide (NO) plays an important role in seed biology. Experiments with this biologically important gas require special provisions because NO in aerobic environments is readily converted into other oxides of nitrogen. In this chapter, we describe methods for the application of NO as a gas, and through the use of NO-donor compounds. We included information on the removal or reduction of NO with NO scavengers. Methods for detecting NO using NO-reactive fluorescent probes, and an apparatus incorporating an oxidizer column are also described.

  4. A selective nanosensing probe for nitric oxide

    NASA Astrophysics Data System (ADS)

    Gouma, P. I.; Kalyanasundaram, K.

    2008-12-01

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

  5. Endothelial nitric oxide synthase in the microcirculation

    PubMed Central

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

    2015-01-01

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

  6. Endothelial nitric oxide synthase in the microcirculation.

    PubMed

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

    2015-12-01

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

  7. Nitric oxide and obstructive sleep apnea.

    PubMed

    Weiss, J Woodrow; Liu, Yuzhen; Li, Xianghong; Ji, En-sheng

    2012-11-15

    Obstructive sleep apnea is a common disease, affecting 16% of the working age population. Although sleep apnea has a well-established connection to daytime sleepiness presumably mediated through repetitive sleep disruption, some other consequences are less well understood. Clinical, epidemiological, and physiological investigations have demonstrated a connection between sleep apnea and daytime hypertension. The elevation of arterial pressure is evident during waking, when patients are not hypoxic, and is mediated by sustained sympathoexcitation and by altered peripheral vascular reactivity. This review summarizes data suggesting that both the sympathoexcitation and the altered vascular reactivity are, at least in part, a consequence of reduced expression of nitric oxide synthase, in neural tissue and in endothelium. Reduced nitric oxide generation in central and peripheral sites of sympathoregulation and in endothelium together may, in part, explain the elevations in waking pressures observed in sleep apnea patients. Copyright © 2012 Elsevier B.V. All rights reserved.

  8. Inducible nitric oxide synthase: Good or bad?

    PubMed

    Lind, Maggie; Hayes, Alan; Caprnda, Martin; Petrovic, Daniel; Rodrigo, Luis; Kruzliak, Peter; Zulli, Anthony

    2017-09-01

    Nitric oxide synthases (NOS) are a family of isoforms responsible for the synthesis of the potent dilator nitric oxide (NO). Expression of inducible NOS (iNOS) occurs in conditions of inflammation, and produces large amounts of NO. In pathological conditions iNOS is regarded as a harmful enzyme and is proposed to be a major contributor to diseases of the cardiovascular system such as atherosclerosis. In this review, we address the notion that iNOS is a detrimental enzyme in disease and discuss its potentially beneficial roles. Additionally, we describe other molecules associated with iNOS in diseases such as atherosclerosis, and current research on therapeutic inhibitors tested to reduced pathology associated with cardiovascular diseases (CVD). Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  9. Nitric oxide, malnutrition and chronic renal failure.

    PubMed

    Brunini, Tatiana M C; Moss, Monique B; Siqueira, Mariana A S; Santos, Sérgio F F; Lugon, Jocemir R; Mendes-Ribeiro, Antônio C

    2007-04-01

    The conditionally essential amino acid L-arginine is the substrate for nitric oxide (NO) synthesis, a key second messenger involved in physiological functions including endothelium-dependent vascular relaxation and inhibition of platelet adhesion and aggregation. Extracellular L-arginine transport seems to be essential for the production of NO by the action of NO synthases (NOS), even when the intracellular levels of L-arginine are available in excess (L-arginine paradox). Chronic renal failure (CRF) is a complex clinical condition associated with accelerated atherosclerosis and thrombosis leading to cardiovascular events. Various studies document that markers of malnutrition and inflammation, such as low body mass index (BMI), C-reactive protein (CRP) and interleukin-6 (IL-6), are strong independent predictors of cardiovascular mortality in patients with end-stage renal disease (ESRD). There is considerable literature demonstrating that a disturbance in the nitric oxide control mechanism plays a role in mediating the haemodynamic and haemostatic disorders present in CRF. Endogenous analogues of L-arginine, ADMA and L-NMMA, which can inhibit NO synthesis and L-arginine transport, are increased whilst L-arginine is reduced in plasma from all stages of CRF patients. In this context, the uptake of L-arginine in blood cells is increased in undialysed CRF patients and in patients treated by CAPD and haemodialysis. In platelets obtained from haemodialysis patients, the activation of L-arginine transport and NO production was limited to well-nourished patients. Impairment in nitric oxide bioactivity, coupled with malnutrition and inflammation, may contribute to increased incidence of atherothrombotic events in CRF. This article summarizes the current knowledge of L-arginine-nitric oxide pathway and malnutrition in CRF and briefly describes possible therapeutic interventions.

  10. Endogenous nitric oxide generation in protoplast chloroplasts.

    PubMed

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

    2013-01-01

    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 μM nitric oxide synthase inhibitors [L-NNA, Nω-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 μM) 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.

  11. Nitric Oxide in Mammary Tumor Progression

    DTIC Science & Technology

    1998-07-01

    smaller level TIMP-3. This indicated that invasion stimulating effects of endogenous NO are, at least in part , mediated by downregulation TIMP-2 and...vasculature: Inhibition retards tumor growth in vivo. In: Moncada S, Feelisch M, Busse R, Higgs EA (eds) Biology of Nitric Oxide. Part 4: Enzymology...useful in treating certain human cancers either as single agents or as a part of combination therapies. I. Introduction duction of proliferation

  12. Killing of Plasmodium falciparum in vitro by nitric oxide derivatives.

    PubMed Central

    Rockett, K A; Awburn, M M; Cowden, W B; Clark, I A

    1991-01-01

    We have investigated the in vitro susceptibility of the human malaria parasite Plasmodium falciparum to killing by nitric oxide and related molecules. A saturated solution of nitric oxide did not inhibit parasite growth, but two oxidation products of nitric oxide (nitrite and nitrate ions) were toxic to the parasite in millimolar concentrations. Nitrosothiol derivatives of cysteine and glutathione were found to be about a thousand times more active (50% growth inhibitory concentration, approximately 40 microM) than nitrite. PMID:1879941

  13. Nitric oxide and thiol groups.

    PubMed

    Gaston, B

    1999-05-05

    S-Nitroso(sy)lation reactions have recently been appreciated to regulate protein function and mediate 'nitrosative' stress. S-Nitrosothiols (SNOs) have been identified in a variety of tissues, and represent a novel class of signaling molecules which may act independently of homolytic cleavage to NO - and, indeed, in a stereoselective fashion - or be metabolized to other bioactive nitrogen oxides. It is now appreciated that sulfur-NO interactions have critical physiological relevance to mammalian neurotransmission, ion channel function, intracellular signaling and antimicrobial defense. These reactions are promising targets for the development of new medical therapies.

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

    PubMed Central

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

    2012-01-01

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

  15. [Nitric oxide and the kidneys].

    PubMed

    Dzúrik, R; Spustová, V

    2001-02-01

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

  16. Development of sensors for nitric oxide

    SciTech Connect

    Glazier, S.A.

    1994-12-31

    The importance of nitric oxide (NO) in mammalian systems has recently been recognized. Interest in NO stems from the discovery of its role in several processes. Firstly, NO is found to be an endothelium-derived relaxing factor. Release of NO by endothelial cells lining blood vessels causes the surrounding smooth muscle of the vessel walls to relax. Secondly, it is known to inhibit the aggregation and adhesion of platelets in blood vessels. Thirdly, NO is believed to be formed by activated macrophage cells to assist in killing foreign cells. Lastly, NO acts in the brain both as a feedback messenger from post- to presynaptic nerve cells and as a conventional neurotransmitter affecting cells other than presynaptic nerve cells. In addition to these roles, it is likely that NO is involved in other processes given its reactivity and potential presence in all mammalian cells. Measurement of NO flux within biological systems is a challenging problem as NO is generated in the nanomolar to micromolar range and is subject to rapid oxidation. The three most common assay techniques for NO in biological systems include: (a) electron paramagnetic resonance detection, (b) hemoglobin oxidation, and (c) chemiluminescence detection with ozone. The authors have initiated research on the construction of a hemoglobin-based, fiber-optic sensor for the detection of nitric oxide in biological systems and progress toward this goal will be presented.

  17. Reduction of nitric oxide emissions from a combustor

    SciTech Connect

    Craig, R.A.; Pritchard, H.O.

    1980-05-27

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

  18. Nitric oxide control of lower genitourinary tract functions: a review.

    PubMed

    Burnett, A L

    1995-06-01

    It is apparent that evolving concepts of the regulatory basis for functions in the pelvis must take into account the role exerted by nitric oxide. A recently characterized messenger molecule, nitric oxide has been associated with numerous physiologic processes. Intense investigations of this molecule have extended its importance to several genitourinary functions. Penile erection, micturition, peristalsis of the male excurrent duct system, contractile properties of the prostate, and lumbosacral spinal cord neurotransmission are all functions that may transpire under some degree of control by nitric oxide. Impotence, urinary obstruction, or ejaculatory problems, in turn, may represent alterations of nitric oxide production or action. The strategic manipulation of nitric oxide or its mechanism of action, possibly by pharmacologic means, may restore or produce desired functional effects. These possibilities, therefore, suggest that the advancing knowledge of nitric oxide in the genitourinary tract may be of enormous clinical value in the future.

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

    PubMed

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

    2013-03-01

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

  20. Enhanced gastric nitric oxide synthase activity in duodenal ulcer patients.

    PubMed Central

    Rachmilewitz, D; Karmeli, F; Eliakim, R; Stalnikowicz, R; Ackerman, Z; Amir, G; Stamler, J S

    1994-01-01

    Nitric oxide, the product of nitric oxide synthase in inflammatory cells, may have a role in tissue injury through its oxidative metabolism. Nitric oxide may have a role in the pathogenesis of duodenal ulcer and may be one of the mechanisms responsible for the association between gastric infection with Helicobacter pylori and peptic disease. In this study, calcium independent nitric oxide synthase activity was detected in human gastric mucosa suggesting expression of the inducible isoform. In 17 duodenal ulcer patients gastric antral and fundic nitric oxide synthase activity was found to be two and 1.5-fold respectively higher than its activity in the antrum and fundus of 14 normal subjects (p < 0.05). H pylori was detected in the antrum of 15 of 17 duodenal ulcer patients and only in 7 of 14 of the control subjects. Antral nitric oxide synthase activity in H pylori positive duodenal ulcer patients was twofold higher than in H pylori positive normal subjects (p < 0.05). In duodenal ulcer patients antral and fundic nitric oxide synthase activity resumed normal values after induction of ulcer healing with ranitidine. Eradication of H pylori did not further affect gastric nitric oxide synthase activity. These findings suggest that in duodenal ulcer patients stimulated gastric mucosal nitric oxide synthase activity, though independent of the H pylori state, may contribute to the pathogenesis of the disease. PMID:7525417

  1. Measuring nasal nitric oxide in allergic rhinitis patients.

    PubMed

    Nesic, V S; Djordjevic, V Z; Tomic-Spiric, V; Dudvarski, Z R; Soldatovic, I A; Arsovic, N A

    2016-11-01

    This study aimed to compare two sampling methods for nasal nitric oxide in healthy individuals and allergic rhinitis patients, and to examine the within-subject reliability of nasal nitric oxide measurement. The study included 23 allergic rhinitis patients without concomitant asthma and 10 healthy individuals. For all participants, nitric oxide levels were measured non-invasively from the lungs through the mouth (i.e. the oral fractional exhaled nitric oxide) and the nose. Nasal nitric oxide was measured by two different methods: (1) nasal aspiration via one nostril during breath holding and (2) single-breath quiet exhalation against resistance through a tight facemask (i.e. the nasal fractional exhaled nitric oxide). Compared with healthy participants, allergic rhinitis patients had significantly higher average oral and nasal nitric oxide levels. All methods of nitric oxide measurement had excellent reliability. Nasal nitric oxide measurement is a useful and reliable clinical tool for diagnosing allergic rhinitis in patients without asthma in an out-patient setting.

  2. Inhaled nitric oxide in chronic obstructive lung disease

    SciTech Connect

    Tiihonen, J.; Hakola, P.; Paanila, J.; Turtiainen . Dept. of Forensic Psychiatry)

    1993-01-30

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

  3. Processes regulating nitric oxide emissions from soils.

    PubMed

    Pilegaard, Kim

    2013-07-05

    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.

  4. New concepts in vascular nitric oxide signaling.

    PubMed

    Oeckler, R A; Wolin, M S

    2000-09-01

    Low levels of nitric oxide (NO) control the activities of guanylate cyclase and mitochondrial respiration. Increasing NO levels interact with multiple signaling systems through the formation of peroxynitrite and other oxidation products. Signaling mechanisms linked to NO participate in the prevention of acute responses such as vasoconstriction, thrombosis and the recruitment of inflammatory cells. In contrast, processes related to vascular remodeling, and responses to injury that are associated with the progression and adaptation to disease processes, are not as well understood. Many of the opposing processes involved in these adaptations may originate from the diverse signaling mechanisms that NO and its oxidized products can regulate in a cell-specific manner in the vessel wall.

  5. Processes regulating nitric oxide emissions from soils

    PubMed Central

    Pilegaard, Kim

    2013-01-01

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

  6. Regulatory effects of anesthetics on nitric oxide.

    PubMed

    Fan, Wenguo; Liu, Qin; Zhu, Xiao; Wu, Zhi; Li, Dongpei; Huang, Fang; He, Hongwen

    2016-04-15

    Nitric oxide (NO) is a free radical gas in the biological system, which is produced by nitric oxide synthase (NOS) family. NO acts as a biological mediator and plays important roles in different systems in humans. The NO/NOS system exerts a broad spectrum of signaling functions involved in vasodilation, inflammation, oxidative stress, cardioprotection and neuroprotection. It has been demonstrated that intravenous and volatile anesthetics (such as propofol, ketamine, midazolam, isoflurane, sevoflurane, and desflurane, etc.) modulate NO production through multiple mechanisms that may influence physiological and pathophysiological processes. This review focuses on the effects of different anesthetics on NO/NOS regulation in different disease conditions. Possible cellular mechanisms and intermediate role of NO/NOS in anesthetic-mediated organ protection are also discussed. It would be interesting to clarify the impact of anesthetics on NO/NOS regulation. This review gives an overview of the effects of different anesthetics on NO/NOS regulation and function in different physiologic and pathophysiologic states.

  7. Nitric oxide in liver inflammation and regeneration.

    PubMed

    Martin-Sanz, Paloma; Hortelano, Sonsoles; Callejas, Nuria A; Goren, Nora; Casado, Marta; Zeini, Miriam; Boscá, Lisardo

    2002-12-01

    Hepatocytes express and release inflammatory mediators after challenge with bacterial cell wall molecules and proinflammatory cytokines. Nitric oxide synthase-2 (NOS-2) is expressed under these conditions and the high-output NO synthesis that follows contributes to the inflammatory response in this tissue and participates in the onset of several hepatopathies. However, in the course of liver regeneration, for example, after partial hepatectomy, NOS-2 is expressed at moderate levels and contributes to inhibit apoptosis and to favor progression in the cell cycle until the organ size and function are restored. The mechanisms involved in the regulation of NOS-2 expression under these conditions are revised.

  8. Nitric oxide as a surgical adjuvant.

    PubMed

    Krausz, Aimee; Friedman, Adam J

    2015-08-01

    Advances in surgical technology have allowed for previously unconsidered therapeutic interventions. However, the complexity and invasiveness of surgical procedures are not without adverse consequences. Nitric oxide's fundamental role in a host of physiological processes, including angiogenesis, wound and bone healing, thromboresistance, smooth muscle relaxation and inflammation makes it a significant player in accelerating wound healing and mitigating the inflammation of ischemia reperfusion injury common to surgical procedures. In addition, the therapeutic properties of NO have been harnessed for the prophylactic treatment of implant infection and graft failure. In this article, we will discuss the mechanism by which NO mediates these processes, and its perioperative translational applications.

  9. Effect of premixing on nitric oxide formation

    NASA Technical Reports Server (NTRS)

    Anderson, D. N.

    1973-01-01

    Emissions from a simple 10-cm (4-in.) diameter tube combustor burning a premixed, gaseous propane/air mixture were measured. Inlet conditions included a temperature of 590 K (600 F), pressure of 5.5 atm, and reference velocity of 23 m/s (75 ft/s) for a range of equivalence ratios from the lean limit to slightly richer than stoichiometric. A nitric oxide emission index of 1 g NO2/kg fuel was measured for an equivalence ratio of 0.57.

  10. Nitric oxide and oxidative stress in placental explant cultures.

    PubMed

    Goncalves, Juvic M; Casart, Ysabel C; Camejo, María I

    2016-01-01

    Placental explant culture, and cellular cytolysis and cellular differentiation have been previously studied. However, oxidative stress and nitric oxide profiles have not been evaluated in these systems. The aim of this study was to determine the release of lipid peroxidation and nitric oxide from placental explants cultured over a seven day period. Placental explants were maintained for seven days in culture and the medium was changed every 24 hours. The response was assessed in terms of syncytiotrophoblast differentiation (human chorionic gonadotropin, hCG), cellular cytolysis (lactate dehydrogenase, LDH), oxidative stress (thiobarbituric acid reactive substances, TBARS), and nitric oxide (NO). Levels of hCG increased progressively from day two to attain its highest level on days four and five after which it decreased gradually. In contrast, the levels of LDH, TBARS, and NO were elevated in the early days of placental culture when new syncytiotrophoblast from cytotrophoblast were forming and also in the last days of culture when tissue was declining. In conclusion, the levels of NO and lipid peroxidation follow a pattern similar to LDH and contrary to hCG. Future placental explant studies to evaluate oxidative stress and NO should consider the physiological changes inherent during the time of culture.

  11. Mitochondrial dysfunction associated with nitric oxide pathways in glutamate neurotoxicity.

    PubMed

    Manucha, Walter

    Multiple mechanisms underlying glutamate-induced neurotoxicity have recently been discussed. Likewise, a clear deregulation of the mitochondrial respiratory mechanism has been described in patients with neurodegeneration, oxidative stress, and inflammation. This article highlights nitric oxide, an atypical neurotransmitter synthesized and released on demand by the post-synaptic neurons, and has many important implications for nerve cell survival and differentiation. Consequently, synaptogenesis, synapse elimination, and neurotransmitter release, are nitric oxide-modulated. Interesting, an emergent role of nitric oxide pathways has been discussed as regards neurotoxicity from glutamate-induced apoptosis. These findings suggest that nitric oxide pathways modulation could prevent oxidative damage to neurons through apoptosis inhibition. This review aims to highlight the emergent aspects of nitric oxide-mediated signaling in the brain, and how they can be related to neurotoxicity, as well as the development of neurodegenerative diseases development.

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  14. Vascular nitric oxide: Beyond eNOS.

    PubMed

    Zhao, Yingzi; Vanhoutte, Paul M; Leung, Susan W S

    2015-10-01

    As the first discovered gaseous signaling molecule, nitric oxide (NO) affects a number of cellular processes, including those involving vascular cells. This brief review summarizes the contribution of NO to the regulation of vascular tone and its sources in the blood vessel wall. NO regulates the degree of contraction of vascular smooth muscle cells mainly by stimulating soluble guanylyl cyclase (sGC) to produce cyclic guanosine monophosphate (cGMP), although cGMP-independent signaling [S-nitrosylation of target proteins, activation of sarco/endoplasmic reticulum calcium ATPase (SERCA) or production of cyclic inosine monophosphate (cIMP)] also can be involved. In the blood vessel wall, NO is produced mainly from l-arginine by the enzyme endothelial nitric oxide synthase (eNOS) but it can also be released non-enzymatically from S-nitrosothiols or from nitrate/nitrite. Dysfunction in the production and/or the bioavailability of NO characterizes endothelial dysfunction, which is associated with cardiovascular diseases such as hypertension and atherosclerosis.

  15. Nitric oxide may mediate nipple erection.

    PubMed

    Tezer, Murat; Ozluk, Yasemin; Sanli, Oner; Asoglu, Oktar; Kadioglu, Ates

    2012-01-01

    The nipple is a specialized structure that can become erect by cold, sexual arousal, breast-feeding, or other tactile stimulations, which can induce the milk ejection reflex and sexual arousal because of intense sensory innervation. The studies that have been conducted thus far to identify the mechanism of nipple erection (NE) are not sufficient. It has been stated that NE occurs via activation of the sympathetic nervous system and smooth muscle contraction. The purposes of this study were to investigate the existence of nitric oxide synthase (NOS) in the nipple-areola complex (NAC) to explain the NE mechanism. Considering that smooth muscle relaxation might be effective in NE, endothelial and neuronal NOS expression and localization were investigated via immunohistochemical methods on sagittal sections from 17 human NACs. The results of this study indicate that eNOS is expressed in the vascular endothelium, ductal epithelium, and smooth muscles, whereas nNOS is expressed in the neural fibers, smooth muscles, ductal epithelium, and vascular endothelium in the NAC. Sinusoidal spaces with endothelial layers similar to those found in penile cavernosal tissue are not found in the NAC. Various mediators are known to affect the function of the NAC smooth muscles; however, this study demonstrates that enzymes (eNOS and nNOS) that synthesize nitric oxide are expressed in the NAC.

  16. Nitric oxide synthase in the pineal gland.

    PubMed

    López-Figueroa, M O; Møller, M

    1996-10-01

    The recent discovery of nitric oxide (NO) as a biological messenger molecule with unique characteristics has opened a new field in pineal research. This free radical gas is synthesized by the enzyme nitric oxide synthase (NOS) from L-arginine. The activation of adrenoreceptors in the membrane of the pinealocytes mediates the increase in NO through a mechanism that involves G proteins. In the pinealocyte, NO stimulates guanylyl cyclase resulting in an increased intracellular content of cGMP. The role of cGMP in pineal metabolism, however, is still enigmatic. Using enzyme histochemistry and immunohistochemistry, the presence of NOS has been confirmed in the pineal gland of some species. In the rat and especially in the sheep, NOS is located in nerve fibres innervating the gland. These nerve fibres also contain the neuropeptides vasoactive intestinal peptide (VIP) and peptide histidine isoleucine (PHI), and are probably of parasympathetic origin. In cell cultures and tissue sections NOS immunoreactivity has been shown to be present in pinealocytes of the rat and bovine but not in the sheep. Finally, NOS is also present in the endothelial cells of the blood vessels of the pineal gland. Accordingly, in the mammalian pineal gland, NO is synthesized in both presynaptic nerve fibers and pinealocytes, as well as in blood vessels. However, the anatomical location of NO synthesis varies considerably among species. NO released in the pineal gland, might influence both the pineal metabolism and the blood flow of the gland.

  17. Nitric oxide from a "green" perspective.

    PubMed

    Corpas, Francisco J; Barroso, Juan B

    2015-02-15

    The molecule nitric oxide (NO) which is involved in practically all biochemical and physiological plant processes has become a subject for plant research. However, there remain many unanswered questions concerning how, where and when this molecule is enzymatically generated in higher plants. This mini-review aims to provide an overview of NO in plants for those readers unfamiliar with this field of research. The review will therefore discuss the importance of NO in higher plants at the physiological and biochemical levels, its involvement in designated nitro-oxidative stresses in response to adverse abiotic and biotic environmental conditions, NO emission/uptake from plants, beneficial plant-microbial interactions, and its potential application in the biotechnological fields of agriculture and food nutrition.

  18. Melatonin and its precursors scavenge nitric oxide

    SciTech Connect

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

    1998-12-01

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

  19. Nitric oxide rescues thalidomide mediated teratogenicity

    PubMed Central

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

    2012-01-01

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

  20. Nitric oxide accumulation is required to protect against iron-mediated oxidative stress in frataxin-deficient Arabidopsis plants.

    PubMed

    Martin, Mariana; Colman, María José Rodríguez; Gómez-Casati, Diego F; Lamattina, Lorenzo; Zabaleta, Eduardo Julián

    2009-02-04

    Frataxin is a mitochondrial protein that is conserved throughout evolution. In yeast and mammals, frataxin is essential for cellular iron (Fe) homeostasis and survival during oxidative stress. In plants, frataxin deficiency causes increased reactive oxygen species (ROS) production and high sensitivity to oxidative stress. In this work we show that a knock-down T-DNA frataxin-deficient mutant of Arabidopsis thaliana (atfh-1) contains increased total and organellar Fe levels. Frataxin deficiency leads also to nitric oxide (NO) accumulation in both, atfh-1 roots and frataxin null mutant yeast. Abnormally high NO production might be part of the defence mechanism against Fe-mediated oxidative stress.

  1. Nitrate, nitrite and nitric oxide reductases: from the last universal common ancestor to modern bacterial pathogens.

    PubMed

    Vázquez-Torres, Andrés; Bäumler, Andreas J

    2016-02-01

    The electrochemical gradient that ensues from the enzymatic activity of cytochromes such as nitrate reductase, nitric oxide reductase, and quinol oxidase contributes to the bioenergetics of the bacterial cell. Reduction of nitrogen oxides by bacterial pathogens can, however, be uncoupled from proton translocation and biosynthesis of ATP or NH4(+), but still linked to quinol and NADH oxidation. Ancestral nitric oxide reductases, as well as cytochrome c oxidases and quinol bo oxidases evolved from the former, are capable of binding and detoxifying nitric oxide to nitrous oxide. The NO-metabolizing activity associated with these cytochromes can be a sizable source of antinitrosative defense in bacteria during their associations with host cells. Nitrosylation of terminal cytochromes arrests respiration, reprograms bacterial metabolism, stimulates antioxidant defenses and alters antibiotic cytotoxicity. Collectively, the bioenergetics and regulation of redox homeostasis that accompanies the utilization of nitrogen oxides and detoxification of nitric oxide by cytochromes of the electron transport chain increases fitness of many Gram-positive and -negative pathogens during their associations with invertebrate and vertebrate hosts.

  2. Nitrate, nitrite and nitric oxide reductases: from the last universal common ancestor to modern bacterial pathogens

    PubMed Central

    Vázquez-Torres, Andrés; Bäumler, Andreas

    2016-01-01

    The electrochemical gradient that ensues from the enzymatic activity of cytochromes such as nitrate reductase, nitric oxide reductase, and quinol oxidase contributes to the bioenergetics of the bacterial cell. Reduction of nitrogen oxides by bacterial pathogens can, however, be uncoupled from proton translocation and biosynthesis of ATP or NH4+, but still linked to quinol and NADH oxidation. Ancestral nitric oxide reductases, as well as cytochrome coxidases and quinol bo oxidases evolved from the former, are capable of binding and detoxifying nitric oxide to nitrous oxide. The NO-metabolizing activity associated with these cytochromes can be a sizable source of antinitrosative defense in bacteria during their associations with host cells. Nitrosylation of terminal cytochromes arrests respiration, reprograms bacterial metabolism, stimulates antioxidant defenses and alters antibiotic cytotoxicity. Collectively, the bioenergetics and regulation of redox homeostasis that accompanies the utilization of nitrogen oxides and detoxification of nitric oxide by cytochromes of the electron transport chain increases fitness of many Gram-positive and –negative pathogens during their associations with invertebrate and vertebrate hosts. PMID:26426528

  3. Critical Role of the Nitric Oxide/Reactive Oxygen Species Balance in Endothelial Progenitor Dysfunction

    PubMed Central

    Fleissner, Felix

    2011-01-01

    Abstract Endothelial injury and dysfunction are critical events in the pathogenesis of cardiovascular disease. During these processes, an impaired balance of nitric oxide bioavailability and oxidative stress is mechanistically involved. Circulating angiogenic cells (including early and late outgrowth endothelial progenitor cells (EPC)) contribute to formation of new blood vessels, neovascularization, and homeostasis of the vasculature, and are highly sensitive for misbalance between NO and oxidative stress. We here review the role of the endothelial nitric oxide synthase and oxidative stress producing enzyme systems in EPC during cardiovascular disease. We also focus on the underlying molecular mechanisms and potential emerging drug- and gene-based therapeutic strategies to improve EPC function in cardiovascular diseased patients. Antioxid. Redox Signal. 15, 933–948. PMID:20712407

  4. Nitric Oxide--Some Old and New Perspectives.

    ERIC Educational Resources Information Center

    Ainscough, Eric W.; Brodie, Andrew M.

    1995-01-01

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

  5. 21 CFR 868.2380 - Nitric oxide analyzer.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Nitric oxide analyzer. 868.2380 Section 868.2380 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2380 Nitric oxide analyzer....

  6. Nitric Oxide--Some Old and New Perspectives.

    ERIC Educational Resources Information Center

    Ainscough, Eric W.; Brodie, Andrew M.

    1995-01-01

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

  7. The Iron-Catalyzed Oxidation of Hydrazine by Nitric Acid

    SciTech Connect

    Karraker, D.G.

    2001-07-17

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

  8. Nitric Oxide Modulators: An Emerging Class of Medicinal Agents

    PubMed Central

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

    2012-01-01

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

  9. Nitric oxide protects endothelium from cadmium mediated leakiness.

    PubMed

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

    2013-05-01

    Cadmium targets the vascular endothelium causing endothelial dysfunction and leakiness of endothelial barrier. Nitric oxide plays a major role in mediating endothelial functions including angiogenesis, migration and permeability. The present study investigates the nitric oxide effects on cadmium induced endothelial leakiness. Results of ex vivo and in vitro permeability assays showed that even a sub-lethal dose of cadmium chloride (1 µM) was sufficient to induce leakiness of endothelial cells. Cadmium drastically altered the actin polymerisation pattern and membrane tension of these cells compared to controls. Addition of nitric oxide donor Spermine NONOate (SP) significantly blunted cadmium-mediated effects and recover endothelial cells integrity. Cadmium-induced cytoskeletal rearrangements and membrane leakiness are associated with the low nitric oxide availability and high reactive oxygen species generation. In brief, we show the protective role of nitric oxide against cadmium-mediated endothelial leakiness. © 2013 International Federation for Cell Biology.

  10. Reduction of nitric oxide emissions from a combustor

    NASA Technical Reports Server (NTRS)

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

    1980-01-01

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

  11. Sickle cell disease and nitric oxide: A paradigm shift?

    PubMed Central

    Mack, A. Kyle; Kato, Gregory J.

    2008-01-01

    Traditionally the pathophysiology of sickle cell disease is thought to result from the polymerization of hemoglobin S in red cells, under hypoxic conditions, resulting in the occlusion of blood vessels. Adhesion of cells to the venular endothelium also appears to play a role. Recent studies have also suggested that in addition to the polymerization of hemoglobin S in the red blood cell, a deficiency of the endogenous vasodilator, nitric oxide may be involved. Hemoglobin released as a result of hemolysis rapidly consumes nitric oxide resulting in a whole program of events that inhibit blood flow. Therapies directed at decreasing the destruction of nitric oxide, increasing the production of nitric oxide, or amplifying the nitric oxide response may prove beneficial. PMID:16517208

  12. Plant pathogenic Streptomyces species produce nitric oxide synthase-derived nitric oxide in response to host signals

    USDA-ARS?s Scientific Manuscript database

    Nitric oxide (NO) is a potent intercellular signal for defense, development and metabolism in animals and plants. In mammals, highly regulated nitric oxide synthases (NOSs) generate NO. NOS homologs exist in some prokaryotes, but direct evidence for NO production by these proteins has been lacking...

  13. Production of nitric oxide and expression of inducible nitric oxide synthase in ovarian cystic tumors.

    PubMed

    Nomelini, Rosekeila Simões; de Abreu Ribeiro, Lívia Carolina; Tavares-Murta, Beatriz Martins; Adad, Sheila Jorge; Murta, Eddie Fernando Candido

    2008-01-01

    Tumor sections from nonneoplastic (n = 15), benign (n = 28), and malignant ovarian tumors (n = 20) were obtained from 63 women. Immunohistochemistry of the tumor sections demonstrated that inducible nitric oxide synthase (iNOS) expression was increased in ovarian cancer samples compared to nonneoplastic or benign tumor samples. Using the Griess method, nitric oxide (NO) metabolite levels were also found to be elevated in malignant tumor samples compared to benign tumor samples (P < .05). For stage I ovarian cancer, intracystic NO levels >80 microM were more frequent than NO levels <80 microM, and iNOS expression in well-differentiated carcinomas was greater than in moderately/poorly differentiated carcinomas (P < .05). These data suggest an important role for NO in ovarian carcinogenesis.

  14. Production of Nitric Oxide and Expression of Inducible Nitric Oxide Synthase in Ovarian Cystic Tumors

    PubMed Central

    Nomelini, Rosekeila Simões; Ribeiro, Lívia Carolina de Abreu; Tavares-Murta, Beatriz Martins; Adad, Sheila Jorge; Murta, Eddie Fernando Candido

    2008-01-01

    Tumor sections from nonneoplastic (n = 15), benign (n = 28), and malignant ovarian tumors (n = 20) were obtained from 63 women. Immunohistochemistry of the tumor sections demonstrated that inducible nitric oxide synthase (iNOS) expression was increased in ovarian cancer samples compared to nonneoplastic or benign tumor samples. Using the Griess method, nitric oxide (NO) metabolite levels were also found to be elevated in malignant tumor samples compared to benign tumor samples (P < .05). For stage I ovarian cancer, intracystic NO levels >80 μM were more frequent than NO levels <80 μM, and iNOS expression in well-differentiated carcinomas was greater than in moderately/poorly differentiated carcinomas (P < .05). These data suggest an important role for NO in ovarian carcinogenesis. PMID:19132106

  15. Combination of nitric oxide therapy, anti-oxidative therapy, low level laser therapy, plasma rich platelet therapy and stem cell therapy as a novel therapeutic application to manage the pain and treat many clinical conditions

    NASA Astrophysics Data System (ADS)

    Halasa, Salaheldin; Dickinson, Eva

    2014-02-01

    From hypertension to diabetes, cancer to HIV, stroke to memory loss and learning disorders to septic shock, male impotence to tuberculosis, there is probably no pathological condition where nitric oxide does not play an important role. Nitric oxide is an analgesic, immune-modulator, vasodilator, anti-apoptotic, growth modulator, angiogenetic, anti-thrombotic, anti-inflammatory and neuro-modulator. Because of the above actions of nitric oxide, many clinical conditions associated with abnormal Nitric oxide (NO) production and bioavailability. Our novel therapeutic approach is to restore the homeostasis of nitric oxide and replace the lost cells by combining nitric oxide therapy, anti-oxidative therapy, low level laser therapy, plasma rich platelet therapy and stem cell therapy.

  16. Nitric oxide-releasing porous silicon nanoparticles

    NASA Astrophysics Data System (ADS)

    Kafshgari, Morteza Hasanzadeh; Cavallaro, Alex; Delalat, Bahman; Harding, Frances J.; McInnes, Steven JP; Mäkilä, Ermei; Salonen, Jarno; Vasilev, Krasimir; Voelcker, Nicolas H.

    2014-07-01

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

  17. Nitric oxide signalling via cytoskeleton in plants.

    PubMed

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

    2011-11-01

    Nitric oxide (NO) in plant cell mediates processes of growth and development starting from seed germination to pollination, as well as biotic and abiotic stress tolerance. However, proper understanding of the molecular mechanisms of NO signalling in plants has just begun to emerge. Accumulated evidence suggests that in eukaryotic cells NO regulates functions of proteins by their post-translational modifications, namely tyrosine nitration and S-nitrosylation. Among the candidates for NO-downstream effectors are cytoskeletal proteins because of their involvement in many processes regulated by NO. This review discusses new insights in plant NO signalling focused mainly on the involvement of cytoskeleton components into NO-cascades. Herein, examples of NO-related post-translational modifications of cytoskeletal proteins, and also indirect NO impact, are discussed. Special attention is paid to plant α-tubulin tyrosine nitration as an emerging topic in plant NO research.

  18. Nitric oxide-releasing porous silicon nanoparticles

    PubMed Central

    2014-01-01

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

  19. Humming greatly increases nasal nitric oxide.

    PubMed

    Weitzberg, Eddie; Lundberg, Jon O N

    2002-07-15

    The paranasal sinuses are major producers of nitric oxide (NO). We hypothesized that oscillating airflow produced by humming would enhance sinus ventilation and thereby increase nasal NO levels. Ten healthy subjects took part in the study. Nasal NO was measured with a chemiluminescence technique during humming and quiet single-breath exhalations at a fixed flow rate. NO increased 15-fold during humming compared with quiet exhalation. In a two-compartment model of the nose and sinus, oscillating airflow caused a dramatic increase in gas exchange between the cavities. Obstruction of the sinus ostium is a central event in the pathogenesis of sinusitis. Nasal NO measurements during humming may be a useful noninvasive test of sinus NO production and ostial patency. In addition, any therapeutic effects of the improved sinus ventilation caused by humming should be investigated.

  20. Nitric Oxide Release Part I. Macromolecular Scaffolds

    PubMed Central

    Riccio, Daniel A.; Schoenfisch, Mark H.

    2012-01-01

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

  1. Nitric oxide and mitochondria in metabolic syndrome

    PubMed Central

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

    2015-01-01

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

  2. Nitric oxide and hyperoxic acute lung injury

    PubMed Central

    Liu, Wen-wu; Han, Cui-hong; Zhang, Pei-xi; Zheng, Juan; Liu, Kan; Sun, Xue-jun

    2016-01-01

    Hyperoxic acute lung injury (HALI) refers to the damage to the lungs secondary to exposure to elevated oxygen partial pressure. HALI has been a concern in clinical practice with the development of deep diving and the use of normobaric as well as hyperbaric oxygen in clinical practice. Although the pathogenesis of HALI has been extensively studied, the findings are still controversial. Nitric oxide (NO) is an intercellular messenger and has been considered as a signaling molecule involved in many physiological and pathological processes. Although the role of NO in the occurrence and development of pulmonary diseases including HALI has been extensively studied, the findings on the role of NO in HALI are conflicting. Moreover, inhalation of NO has been approved as a therapeutic strategy for several diseases. In this paper, we briefly summarize the role of NO in the pathogenesis of HALI and the therapeutic potential of inhaled NO in HALI. PMID:27867474

  3. Recent developments in nitric oxide donor drugs

    PubMed Central

    Miller, M R; Megson, I L

    2007-01-01

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

  4. Superhydrophobic nitric oxide-releasing xerogels.

    PubMed

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

    2014-08-01

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

  5. Nitric Oxide Signaling in the Microcirculation

    PubMed Central

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

    2013-01-01

    Several apparent paradoxes are evident when one compares mathematical predictions from models of nitric oxide (NO) diffusion and convection in vasculature structures with experimental measurements of NO (or related metabolites) in animal and human studies. Values for NO predicted from mathematical models are generally much lower than in vivo NO values reported in the literature for experiments, specifically with NO microelectrodes positioned at perivascular locations next to different sizes of blood vessels in the microcirculation and NO electrodes inserted into a wide range of tissues supplied by the microcirculation of each specific organ system under investigation. There continues to be uncertainty about the roles of NO scavenging by hemoglobin versus a storage function that may conserve NO, and other signaling targets for NO need to be considered. This review describes model predictions and relevant experimental data with respect to several signaling pathways in the microcirculation that involve NO. PMID:22196161

  6. Role of nitric oxide in thermotolerance

    PubMed Central

    Xuan, Yi; Zhou, Shuo; Wang, Lei; Jiang, Haijun

    2010-01-01

    A tCaM3 is a key factor in heat shock (HS) signal transduction. Nitric oxide (NO) is believed to mediate a variety of resistant reactions against environmental factors. Our experiments indicate that under heat stress NO induces thermotolerance. In order to do so, NO is signal molecule acting upstream of AtCaM3, stimulating the DNA-binding activity of HS transcription factors as well as the accumulation of heat shock proteins. As a novel HS signaling molecule, NO signal pathway is little known and several unexpected results are emerging. Herein we are discussing them and conclude that in order to obtain a more profound understanding of this new role of NO, detailed research will be needed in the future. PMID:21057186

  7. An intercomparison of nitric oxide measurement techniques

    NASA Technical Reports Server (NTRS)

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

    1985-01-01

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

  8. Nitric oxide generating/releasing materials

    PubMed Central

    Liang, Hongying; Nacharaju, Parimala; Friedman, Adam; Friedman, Joel M

    2015-01-01

    Harnessing the impressive therapeutic potential of Nitric oxide (NO) remains an ongoing challenge. This paper describes several of the current strategies both with respect to the underlying chemistry and physics and to the applications where they have shown promise. Included in this overview are molecular systems such as NONOates that release NO through chemical reactions and delivery vehicles such as nanoparticles that can generate, store, transport and deliver NO and related bioactive forms of NO such as nitrosothiols. Although there has been much positive movement, it is clear that we are only at the early stages of knowing how to precisely produce, transport and deliver to targeted sites therapeutic levels of NO and related molecules. PMID:26855790

  9. Nitric oxide, human diseases and the herbal products that affect the nitric oxide signalling pathway.

    PubMed

    Achike, Francis I; Kwan, Chiu-Yin

    2003-09-01

    1. Nitric oxide (NO) is formed enzymatically from l-arginine in the presence of nitric oxide synthase (NOS). Nitric oxide is generated constitutively in endothelial cells via sheer stress and blood-borne substances. Nitric oxide is also generated constitutively in neuronal cells and serves as a neurotransmitter and neuromodulator in non-adrenergic, non-cholinergic nerve endings. Furthermore, NO can also be formed via enzyme induction in many tissues in the presence of cytokines. 2. The ubiquitous presence of NO in the living body suggests that NO plays an important role in the maintenance of health. Being a free radical with vasodilatory properties, NO exerts dual effects on tissues and cells in various biological systems. At low concentrations, NO can dilate the blood vessels and improve the circulation, but at high concentrations it can cause circulatory shock and induce cell death. Thus, diseases can arise in the presence of the extreme ends of the physiological concentrations of NO. 3. The NO signalling pathway has, in recent years, become a target for new drug development. The high level of flavonoids, catechins, tannins and other polyphenolic compounds present in vegetables, fruits, soy, tea and even red wine (from grapes) is believed to contribute to their beneficial health effects. Some of these compounds induce NO formation from the endothelial cells to improve circulation and some suppress the induction of inducible NOS in inflammation and infection. 4. Many botanical medicinal herbs and drugs derived from these herbs have been shown to have effects on the NO signalling pathway. For example, the saponins from ginseng, ginsenosides, have been shown to relax blood vessels (probably contributing to the antifatigue and blood pressure-lowering effects of ginseng) and corpus cavernosum (thus, for the treatment of men suffering from erectile dysfunction; however, the legendary aphrodisiac effect of ginseng may be an overstatement). Many plant extracts or

  10. Nitric oxide synthesis and signalling in plants.

    PubMed

    Wilson, Ian D; Neill, Steven J; Hancock, John T

    2008-05-01

    As with all organisms, plants must respond to a plethora of external environmental cues. Individual plant cells must also perceive and respond to a wide range of internal signals. It is now well-accepted that nitric oxide (NO) is a component of the repertoire of signals that a plant uses to both thrive and survive. Recent experimental data have shown, or at least implicated, the involvement of NO in reproductive processes, control of development and in the regulation of physiological responses such as stomatal closure. However, although studies concerning NO synthesis and signalling in animals are well-advanced, in plants there are still fundamental questions concerning how NO is produced and used that need to be answered. For example, there is a range of potential NO-generating enzymes in plants, but no obvious plant nitric oxide synthase (NOS) homolog has yet been identified. Some studies have shown the importance of NOS-like enzymes in mediating NO responses in plants, while other studies suggest that the enzyme nitrate reductase (NR) is more important. Still, more published work suggests the involvement of completely different enzymes in plant NO synthesis. Similarly, it is not always clear how NO mediates its responses. Although it appears that in plants, as in animals, NO can lead to an increase in the signal cGMP which leads to altered ion channel activity and gene expression, it is not understood how this actually occurs. NO is a relatively reactive compound, and it is not always easy to study. Furthermore, its biological activity needs to be considered in conjunction with that of other compounds such as reactive oxygen species (ROS) which can have a profound effect on both its accumulation and function. In this paper, we will review the present understanding of how NO is produced in plants, how it is removed when its signal is no longer required and how it may be both perceived and acted upon.

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

    PubMed

    Kakizawa, Sho; Yamazawa, Toshiko; Iino, Masamitsu

    2013-01-01

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

  12. Inducible nitric oxide synthase as a possible target in hypertension.

    PubMed

    Oliveira-Paula, Gustavo H; Lacchini, Riccardo; Tanus-Santos, Jose E

    2014-02-01

    Nitric oxide (NO) is an important vasodilator produced by vascular endothelium. Its enzymatic formation is derived from three different synthases: neuronal (nNOS), endothelial (eNOS) and inducible (iNOS) synthases. While relatively small amounts of NO produced by eNOS are important to cardiovascular homeostasis, high NO levels produced associated with iNOS activity may have detrimental consequences to the cardiovascular system and contribute to hypertension. In this article, we reviewed current literature and found mounting evidence indicating that increased iNOS expression and activity contribute to the pathogenesis of hypertension and its complications. Excessive amounts of NO produced by iNOS up-regulation can react with superoxide anions forming peroxynitrite, thereby promoting nitrosative stress and endothelial dysfunction. In addition, abnormal iNOS activity can up-regulate arginase activity, allowing it to compete with eNOS for L-arginine, thereby resulting in reduced NO bioavailability. This may also lead to eNOS uncoupling with enhanced production of superoxide anions instead of NO. All these alterations mediated by iNOS apparently contribute to hypertension and its complications. We also reviewed current evidence showing the effects of iNOS inhibitors on different animal models of hypertension. iNOS inhibition apparently exerts antihypertensive effects, decreases oxidative and nitrosative stress, and improves vascular function. Together, these studies highlight the possibility that iNOS is a potential pharmacological target in hypertension.

  13. Nitrogen oxide cycle regulates nitric oxide levels and bacterial cell signaling

    PubMed Central

    Sasaki, Yasuyuki; Oguchi, Haruka; Kobayashi, Takuya; Kusama, Shinichiro; Sugiura, Ryo; Moriya, Kenta; Hirata, Takuya; Yukioka, Yuriya; Takaya, Naoki; Yajima, Shunsuke; Ito, Shinsaku; Okada, Kiyoshi; Ohsawa, Kanju; Ikeda, Haruo; Takano, Hideaki; Ueda, Kenji; Shoun, Hirofumi

    2016-01-01

    Nitric oxide (NO) signaling controls various metabolic pathways in bacteria and higher eukaryotes. Cellular enzymes synthesize and detoxify NO; however, a mechanism that controls its cellular homeostasis has not been identified. Here, we found a nitrogen oxide cycle involving nitrate reductase (Nar) and the NO dioxygenase flavohemoglobin (Fhb), that facilitate inter-conversion of nitrate, nitrite, and NO in the actinobacterium Streptomyces coelicolor. This cycle regulates cellular NO levels, bacterial antibiotic production, and morphological differentiation. NO down-regulates Nar and up-regulates Fhb gene expression via the NO-dependent transcriptional factors DevSR and NsrR, respectively, which are involved in the auto-regulation mechanism of intracellular NO levels. Nitrite generated by the NO cycles induces gene expression in neighboring cells, indicating an additional role of the cycle as a producer of a transmittable inter-cellular communication molecule. PMID:26912114

  14. Analytical techniques for assaying nitric oxide bioactivity.

    PubMed

    Jiang, Hong; Parthasarathy, Deepa; Torregrossa, Ashley C; Mian, Asad; Bryan, Nathan S

    2012-06-18

    Nitric oxide (NO) is a diatomic free radical that is extremely short lived in biological systems (less than 1 second in circulating blood). NO may be considered one of the most important signaling molecules produced in our body, regulating essential functions including but not limited to regulation of blood pressure, immune response and neural communication. Therefore its accurate detection and quantification in biological matrices is critical to understanding the role of NO in health and disease. With such a short physiological half life of NO, alternative strategies for the detection of reaction products of NO biochemistry have been developed. The quantification of relevant NO metabolites in multiple biological compartments provides valuable information with regards to in vivo NO production, bioavailability and metabolism. Simply sampling a single compartment such as blood or plasma may not always provide an accurate assessment of whole body NO status, particularly in tissues. The ability to compare blood with select tissues in experimental animals will help bridge the gap between basic science and clinical medicine as far as diagnostic and prognostic utility of NO biomarkers in health and disease. Therefore, extrapolation of plasma or blood NO status to specific tissues of interest is no longer a valid approach. As a result, methods continue to be developed and validated which allow the detection and quantification of NO and NO-related products/metabolites in multiple compartments of experimental animals in vivo. The established paradigm of NO biochemistry from production by NO synthases to activation of soluble guanylyl cyclase (sGC) to eventual oxidation to nitrite (NO(2)(-)) and nitrate (NO(3)(-)) may only represent part of NO's effects in vivo. The interaction of NO and NO-derived metabolites with protein thiols, secondary amines, and metals to form S-nitrosothiols (RSNOs), N-nitrosamines (RNNOs), and nitrosyl-heme respectively represent c

  15. Targeting Nitric Oxide with Natural Derived Compounds as a Therapeutic Strategy in Vascular Diseases.

    PubMed

    Forte, Maurizio; Conti, Valeria; Damato, Antonio; Ambrosio, Mariateresa; Puca, Annibale A; Sciarretta, Sebastiano; Frati, Giacomo; Vecchione, Carmine; Carrizzo, Albino

    2016-01-01

    Within the family of endogenous gasotransmitters, nitric oxide (NO) is the smallest gaseous intercellular messenger involved in the modulation of several processes, such as blood flow and platelet aggregation control, essential to maintain vascular homeostasis. NO is produced by nitric oxide synthases (NOS) and its effects are mediated by cGMP-dependent or cGMP-independent mechanisms. Growing evidence suggests a crosstalk between the NO signaling and the occurrence of oxidative stress in the onset and progression of vascular diseases, such as hypertension, heart failure, ischemia, and stroke. For these reasons, NO is considered as an emerging molecular target for developing therapeutic strategies for cardio- and cerebrovascular pathologies. Several natural derived compounds, such as polyphenols, are now proposed as modulators of NO-mediated pathways. The aim of this review is to highlight the experimental evidence on the involvement of nitric oxide in vascular homeostasis focusing on the therapeutic potential of targeting NO with some natural compounds in patients with vascular diseases.

  16. Targeting Nitric Oxide with Natural Derived Compounds as a Therapeutic Strategy in Vascular Diseases

    PubMed Central

    Forte, Maurizio; Damato, Antonio; Ambrosio, Mariateresa; Puca, Annibale A.; Sciarretta, Sebastiano; Frati, Giacomo; Vecchione, Carmine

    2016-01-01

    Within the family of endogenous gasotransmitters, nitric oxide (NO) is the smallest gaseous intercellular messenger involved in the modulation of several processes, such as blood flow and platelet aggregation control, essential to maintain vascular homeostasis. NO is produced by nitric oxide synthases (NOS) and its effects are mediated by cGMP-dependent or cGMP-independent mechanisms. Growing evidence suggests a crosstalk between the NO signaling and the occurrence of oxidative stress in the onset and progression of vascular diseases, such as hypertension, heart failure, ischemia, and stroke. For these reasons, NO is considered as an emerging molecular target for developing therapeutic strategies for cardio- and cerebrovascular pathologies. Several natural derived compounds, such as polyphenols, are now proposed as modulators of NO-mediated pathways. The aim of this review is to highlight the experimental evidence on the involvement of nitric oxide in vascular homeostasis focusing on the therapeutic potential of targeting NO with some natural compounds in patients with vascular diseases. PMID:27651855

  17. Nitric oxide scavengers differentially inhibit ammonia oxidation in ammonia-oxidizing archaea and bacteria.

    PubMed

    Sauder, Laura A; Ross, Ashley A; Neufeld, Josh D

    2016-04-01

    Differential inhibitors are important for measuring the relative contributions of microbial groups, such as ammonia-oxidizing bacteria (AOB) and ammonia-oxidizing archaea (AOA), to biogeochemical processes in environmental samples. In particular, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (PTIO) represents a nitric oxide scavenger used for the specific inhibition of AOA, implicating nitric oxide as an intermediate of thaumarchaeotal ammonia oxidation. This study investigated four alternative nitric oxide scavengers for their ability to differentially inhibit AOA and AOB in comparison to PTIO. Caffeic acid, curcumin, methylene blue hydrate and trolox were tested onNitrosopumilus maritimus, two unpublished AOA representatives (AOA-6f and AOA-G6) as well as the AOB representative Nitrosomonas europaea All four scavengers inhibited ammonia oxidation by AOA at lower concentrations than for AOB. In particular, differential inhibition of AOA and AOB by caffeic acid (100 μM) and methylene blue hydrate (3 μM) was comparable to carboxy-PTIO (100 μM) in pure and enrichment culture incubations. However, when added to aquarium sponge biofilm microcosms, both scavengers were unable to inhibit ammonia oxidation consistently, likely due to degradation of the inhibitors themselves. This study provides evidence that a variety of nitric oxide scavengers result in differential inhibition of ammonia oxidation in AOA and AOB, and provides support to the proposed role of nitric oxide as a key intermediate in the thaumarchaeotal ammonia oxidation pathway.

  18. The oral microbiome and nitric oxide homoeostasis.

    PubMed

    Hezel, M P; Weitzberg, E

    2015-01-01

    The tiny radical nitric oxide (NO) participates in a vast number of physiological functions including vasodilation, nerve transmission, host defence and cellular energetics. Classically produced by a family of specific enzymes, NO synthases (NOSs), NO signals via reactions with other radicals or transition metals. An alternative pathway for the generation of NO is the nitrate-nitrite-NO pathway in which the inorganic anions nitrate (NO(3)(-)) and nitrite (NO(2)(-)) are reduced to NO and other reactive nitrogen intermediates. Nitrate and nitrite are oxidation products from NOS-dependent NO generation but also constituents in our diet, mainly in leafy green vegetables. Irrespective of origin, active uptake of circulating nitrate in the salivary glands, excretion in saliva and subsequent reduction to nitrite by oral commensal bacteria are all necessary steps for further NO generation. This central role of the oral cavity in regulating NO generation from nitrate presents a new and intriguing aspect of the human microbiome in health and disease. In this review, we present recent advances in our understanding of the nitrate-nitrite-NO pathway and specifically highlight the importance of the oral cavity as a hub for its function. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Biomimetic and microbial reduction of nitric oxide

    SciTech Connect

    Potter, W.T.; Le, U.; Ronda, S.

    1995-12-31

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

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

    PubMed

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

    2014-09-01

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

  1. Nitric oxide signalling: insect brains and photocytes.

    PubMed

    Trimmer, Barry A; Aprille, June; Modica-Napolitano, Josephine

    2004-01-01

    The success of insects arises partly from extraordinary biochemical and physiological specializations. For example, most species lack glutathione peroxidase, glutathione reductase and respiratory-gas transport proteins and thus allow oxygen to diffuse directly into cells. To counter the increased potential for oxidative damage, insect tissues rely on the indirect protection of the thioredoxin reductase pathway to maintain redox homoeostasis. Such specializations must impact on the control of reactive oxygen species and free radicals such as the signalling molecule NO. This chapter focuses on NO signalling in the insect central nervous system and in the light-producing lantern of the firefly. It is shown that neural NO production is coupled to both muscarinic and nicotinic acetylcholine receptors. The NO-mediated increase in cGMP evokes changes in spike activity of neurons controlling the gut and body wall musculature. In addition, maps of NO-producing and -responsive neurons make insects useful models for establishing the range and specificity of NO's actions in the central nervous system. The firefly lantern also provides insight into the interplay of tissue anatomy and cellular biochemistry in NO signalling. In the lantern, nitric oxide synthase is expressed in tracheal end cells that are interposed between neuron terminals and photocytes. Exogenous NO can activate light production and NO scavengers block evoked flashes. NO inhibits respiration in isolated lantern mitochondria and this can be reversed by bright light. It is proposed that NO controls flashes by transiently inhibiting oxygen consumption and permitting direct oxidation of activated luciferin. It is possible that light production itself contributes to the restoration of mitochondrial activity and consequent cessation of the flash.

  2. The Oxidation of Hydrazine by Nitric Acid

    SciTech Connect

    Karraker, D.G.

    2001-07-02

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

  3. 21 CFR 862.3080 - Breath nitric oxide test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

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

  4. 21 CFR 862.3080 - Breath nitric oxide test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

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

  5. 21 CFR 862.3080 - Breath nitric oxide test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

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

  6. 21 CFR 862.3080 - Breath nitric oxide test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

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

  7. 21 CFR 862.3080 - Breath nitric oxide test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

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

    NASA Technical Reports Server (NTRS)

    Fischer, Karen E.; Rock, Kenneth E.

    1995-01-01

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

  9. Detection of nitric oxide by electron paramagnetic resonance spectroscopy.

    PubMed

    Hogg, Neil

    2010-07-15

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

  10. Nitric Oxide Inhibits Coxiella burnetii Replication and Parasitophorous Vacuole Maturation

    PubMed Central

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

    2002-01-01

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

  11. Measurements of nitric oxide after a nuclear burst

    NASA Technical Reports Server (NTRS)

    Mcghan, M.; Shaw, A.; Megill, L. R.; Sedlacek, W.; Guthals, P. R.; Fowler, M. M.

    1981-01-01

    Measurements of ozone and nitric oxide in a nuclear cloud 7 days after the explosion are reported. No measurable increase above ambient density of either ozone or nitric oxide was found. Results from a chemistry model of the cloud do not agree with the measurement unless 'nonstandard' assumptions are made with regard to the operating chemical processes. A number of possible explanations of the results are discussed.

  12. Nitric oxide is required for tactile learning in Octopus vulgaris.

    PubMed

    Robertson, J D; Bonaventura, J; Kohm, A P

    1994-06-22

    Nitric oxide, produced by nitric oxide synthase in brain tissue, is essential for several different kinds of learning in vertebrates. We present the first evidence that it is also essential for learning in an invertebrate. Intramuscular injections of an inhibitor of the enzyme completely block touch learning in Octopus vulgaris. Eight control animals learned a touch paradigm, but none of eight synthase-inhibited ones learned it.

  13. Nitric oxide donors for cardiovascular implant applications.

    PubMed

    Naghavi, Noora; de Mel, Achala; Alavijeh, Omid Sadeghi; Cousins, Brian G; Seifalian, Alexander M

    2013-01-14

    In an era of increased cardiovascular disease burden in the ageing population, there is great demand for devices that come in to contact with the blood such as heart valves, stents, and bypass grafts that offer life saving treatments. Nitric oxide (NO) elution from healthy endothelial tissue that lines the vessels maintains haemostasis throughout the vasculature. Surgical devices that release NO are desirable treatment options and N-diazeniumdiolates and S-nitrosothiols are recognized as preferred donor molecules. There is a keen interest to investigate newer methods by which NO donors can be retained within biomaterials so that their release and kinetic profiles can be optimized. A range of polymeric scaffolds incorporating microparticles and nanomaterials are presenting solutions to current challenges, and have been investigated in a range of clinical applications. This review outlines the application of NO donors for cardiovascular therapy using biomaterials that release NO locally to prevent thrombosis and intimal hyperplasia (IH) and enhance endothelialization in the fabrication of next generation cardiovascular device technology.

  14. Nitric oxide negatively regulates mammalian adult neurogenesis

    NASA Astrophysics Data System (ADS)

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

    2003-08-01

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

  15. Nitric oxide transport in an axisymmetric stenosis.

    PubMed

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

    2012-10-07

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

  16. Nasal nitric oxide in unilateral sinus disease

    PubMed Central

    Fu, Chia-Hsiang; Tseng, Hsiao-Jung; Huang, Chi-Che; Chang, Po-Hung; Chen, Yi-Wei; Lee, Ta-Jen

    2017-01-01

    Unilateral sinus disease (USD) can sometimes be difficult to accurately diagnose before surgery. The application of nasal nitric oxide (nNO) for USD diagnosis and its surgical outcome in USD has not been reported in the literature. We prospectively enrolled sixty-six USD patients who underwent endoscopic sinus surgery for fungal rhinosinusitis (n = 19), chronic rhinosinusitis (CRS) without nasal polyps (n = 13), CRS with nasal polyps (n = 12) and sinonasal mass lesions (n = 22). nNO levels were measured preoperatively and at three and six months postoperatively. Correlations between nNO levels and potential clinical parameters, type of disease, disease severity, and disease-related quality of life (QOL) were assessed. Unlike bilateral CRS, in USD, nNO levels did not correlate with disease severity or postoperative QOL improvements. Except for fungus group, there were no differences in nNO levels between lesion and non-lesion sides in all the other groups. nNO levels on both sides were significantly elevated six months postoperatively in all groups. Fungal rhinosinusitis patients had the lowest preoperative nNO levels, and a cutoff of 239.3 ppb had the best sensitivity (79.0%) and specificity (87.2%) for preoperative diagnosis. While preoperative nNO levels cannot serve as an alternative marker for disease severity of USD, they were lower in fungal rhinosinusitis patients than in other USD patients and may be useful for more accurate diagnosis prior to surgery. PMID:28199369

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

    PubMed

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

    2016-09-09

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

  18. Effects of nitric oxide in mucociliary transport.

    PubMed

    Blanco, Eleonora Elisia Abra; Pinge, Marli Cardoso Martins; Andrade Neto, Otavio André; Pessoa, Nathália Gardin

    2009-01-01

    The airways are made up of ciliated epithelium which secretes mucous, protecting the respiratory tract from particles inhaled during breathing. Its is paramount to understand the physiology and the mechanisms involved in mucociliary activity. Literature suggests that Nitric oxide (NO), especially the one produced by iNOS expression, maintains the mucociliary function and the immune defense of the nasal cavity. to assess NO participation and the enzymatic pathways in the production of NO and mucociliary transport, using constructive and inductive NO synthetase inhibitors, L-NAME and aminoguanidine, respectively. frog palates were prepared and immersed in ringer (control), L-NAME or aminoguanidine solutions. The palates were immersed in these solutions for four periods of 15 minutes. Mucociliary transport measures were carried out before and after each exposure. control palates maintained stable their transportation speed. L-NAME increased, while aminoguanidine reduced mucous transportation velocity. unspecific cNOS block with L-NAME and relatively specific iNOS block with aminoguanidine results leads us to propose that depending on the pathway, the NO can increase or reduce mucociliary transport in frog palates.

  19. Nitric oxide and teratogenesis: an update.

    PubMed

    Tiboni, Gian Mario; Ponzano, Adalisa

    2014-01-01

    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.

  20. Modulation of nitric oxide bioavailability by erythrocytes

    NASA Astrophysics Data System (ADS)

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

    2001-09-01

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

  1. Structures of human constitutive nitric oxide synthases

    PubMed Central

    Li, Huiying; Jamal, Joumana; Plaza, Carla; Pineda, Stephanie Hai; Chreifi, Georges; Jing, Qing; Cinelli, Maris A.; Silverman, Richard B.; Poulos, Thomas L.

    2014-01-01

    Mammals produce three isoforms of nitric oxide synthase (NOS): neuronal NOS (nNOS), inducible NOS (iNOS) and endothelial NOS (eNOS). The overproduction of NO by nNOS is associated with a number of neurodegenerative disorders; therefore, a desirable therapeutic goal is the design of drugs that target nNOS but not the other isoforms. Crystallography, coupled with computational approaches and medicinal chemistry, has played a critical role in developing highly selective nNOS inhibitors that exhibit exceptional neuroprotective properties. For historic reasons, crystallography has focused on rat nNOS and bovine eNOS because these were available in high quality; thus, their structures have been used in structure–activity–relationship studies. Although these constitutive NOSs share more than 90% sequence identity across mammalian species for each NOS isoform, inhibitor-binding studies revealed that subtle differences near the heme active site in the same NOS isoform across species still impact enzyme–inhibitor interactions. Therefore, structures of the human constitutive NOSs are indispensible. Here, the first structure of human neuronal NOS at 2.03 Å resolution is reported and a different crystal form of human endothelial NOS is reported at 1.73 Å resolution. PMID:25286850

  2. Nitric oxide reduces seed dormancy in Arabidopsis.

    PubMed

    Bethke, Paul C; Libourel, Igor G L; Jones, Russell L

    2006-01-01

    Dormancy is a property of many mature seeds, and experimentation over the past century has identified numerous chemical treatments that will reduce seed dormancy. Nitrogen-containing compounds including nitrate, nitrite, and cyanide break seed dormancy in a range of species. Experiments are described here that were carried out to further our understanding of the mechanism whereby these and other compounds, such as the nitric oxide (NO) donor sodium nitroprusside (SNP), bring about a reduction in seed dormancy of Arabidopsis thaliana. A simple method was devised for applying the products of SNP photolysis through the gas phase. Using this approach it was shown that SNP, as well as potassium ferricyanide (Fe(III)CN) and potassium ferrocyanide (Fe(II)CN), reduced dormancy of Arabidopsis seeds by generating cyanide (CN). The effects of potassium cyanide (KCN) on dormant seeds were tested and it was confirmed that cyanide vapours were sufficient to break Arabidopsis seed dormancy. Nitrate and nitrite also reduced Arabidopsis seed dormancy and resulted in substantial rates of germination. The effects of CN, nitrite, and nitrate on dormancy were prevented by the NO scavenger c-PTIO. It was confirmed that NO plays a role in reducing seed dormancy by using purified NO gas, and a model to explain how nitrogen-containing compounds may break dormancy in Arabidopsis is presented.

  3. Airborne intercomparison of nitric oxide measurement techniques

    NASA Technical Reports Server (NTRS)

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

    1987-01-01

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

  4. Nitric oxide modulates sensitivity to ABA

    PubMed Central

    Lozano-Juste, Jorge

    2010-01-01

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

  5. Nitric oxide transport in an axisymmetric stenosis

    PubMed Central

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

    2012-01-01

    To test the hypothesis that disturbed flow can impede the transport of nitric oxide (NO) in the artery and hence induce atherogenesis, we used a lumen–wall model of an idealized arterial stenosis with NO produced at the blood vessel–wall interface to study the transport of NO in the stenosis. Blood flows in the lumen and through the arterial wall were simulated by Navier–Stokes equations and Darcy's Law, respectively. Meanwhile, the transport of NO in the lumen and the transport of NO within the arterial wall were modelled by advection–diffusion reaction equations. Coupling of fluid dynamics at the endothelium was achieved by the Kedem–Katchalsky equations. The results showed that both the hydraulic conductivity of the endothelium and the non-Newtonian viscous behaviour of blood had little effect on the distribution of NO. However, the blood flow rate, stenosis severity, red blood cells (RBCs), RBC-free layer and NO production rate at the blood vessel–wall interface could significantly affect the transport of NO. The theoretical study revealed that the transport of NO was significantly hindered in the disturbed flow region distal to the stenosis. The reduced NO concentration in the disturbed flow region might play an important role in the localized genesis and development of atherosclerosis. PMID:22593099

  6. Differential Modulation of Nitric Oxide Synthases in Aging: Therapeutic Opportunities

    PubMed Central

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

    2012-01-01

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

  7. The endocrine system in chronic nitric oxide deficiency.

    PubMed

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

    2007-01-01

    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.

  8. Morphine stimulates nitric oxide release in human mitochondria.

    PubMed

    Stefano, George B; Mantione, Kirk J; Capellan, Lismary; Casares, Federico M; Challenger, Sean; Ramin, Rohina; Samuel, Joshua M; Snyder, Christopher; Kream, Richard M

    2015-10-01

    The expression of morphine by plants, invertebrate, and vertebrate cells and organ systems, strongly indicates a high level of evolutionary conservation of morphine and related morphinan alkaloids as required for life. The prototype catecholamine, dopamine, serves as an essential chemical intermediate in morphine biosynthesis, both in plants and animals. We surmise that, before the emergence of specialized plant and animal cells/organ systems, primordial multi-potential cell types required selective mechanisms to limit their responsiveness to environmental cues. Accordingly, cellular systems that emerged with the potential for recruitment of the free radical gas nitric oxide (NO) as a multi-faceted autocrine/paracrine signaling molecule, were provided with extremely positive evolutionary advantages. Endogenous morphinergic signaling, in concert with NO-coupled signaling systems, has evolved as an autocrine/paracrine regulator of metabolic homeostasis, energy metabolism, mitochondrial respiration and energy production. Basic physiological processes involving morphinergic/NO-coupled regulation of mitochondrial function, with special emphasis on the cardiovascular system, are critical to all organismic survival. Key to this concept may be the phenomenon of mitochondrial enslavement in eukaryotic evolution via endogenous morphine.

  9. Nitric oxide in adaptation to altitude.

    PubMed

    Beall, Cynthia M; Laskowski, Daniel; Erzurum, Serpil C

    2012-04-01

    This review summarizes published information on the levels of nitric oxide gas (NO) in the lungs and NO-derived liquid-phase molecules in the acclimatization of visitors newly arrived at altitudes of 2500 m or more and adaptation of populations whose ancestors arrived thousands of years ago. Studies of acutely exposed visitors to high altitude focus on the first 24-48 h with just a few extending to days or weeks. Among healthy visitors, NO levels in the lung, plasma, and/or red blood cells fell within 2h, but then returned toward baseline or slightly higher by 48 h and increased above baseline by 5 days. Among visitors ill with high-altitude pulmonary edema at the time of the study or in the past, NO levels were lower than those of their healthy counterparts. As for highland populations, Tibetans had NO levels in the lung, plasma, and red blood cells that were at least double and in some cases orders of magnitude greater than other populations regardless of altitude. Red blood cell-associated nitrogen oxides were more than 200 times higher. Other highland populations had generally higher levels although not to the degree shown by Tibetans. Overall, responses of those acclimatized and those presumed to be adapted are in the same direction, although the Tibetans have much larger responses. Missing are long-term data on lowlanders at altitude showing how similar they become to the Tibetan phenotype. Also missing are data on Tibetans at low altitude to see the extent to which their phenotype is a response to the immediate environment or expressed constitutively. The mechanisms causing the visitors' and the Tibetans' high levels of NO and NO-derived molecules at altitude remain unknown. Limited data suggest processes including hypoxic upregulation of NO synthase gene expression, hemoglobin-NO reactions, and genetic variation. Gains in understanding will require integrating appropriate methods and measurement techniques with indicators of adaptive function under hypoxic

  10. Nitric oxide in adaptation to altitude

    PubMed Central

    Laskowski, Daniel; Erzurum, Serpil C.

    2012-01-01

    This review summarizes published information on levels of nitric oxide gas (NO) in the lungs and NO-derived liquid phase molecules in the acclimatization of visitors newly arrived at altitudes of 2500m or more and adaptation of populations whose ancestors arrived thousands of years ago. Studies of acutely exposed visitors to high altitude focus on the first 24–48 hours with just a few extending to days or weeks. Among healthy visitors, NO levels in the lung, plasma and/or red blood cells fell within three hours, but then returned toward baseline or slightly higher by 48 hours, and increased above baseline by 5 days. Among visitors ill with high-altitude pulmonary edema at the time of the study or in the past, NO levels were lower than their healthy counterparts. As for highland populations, Tibetans had NO levels in the lung, plasma and red blood cells that were at least double and in some cases orders of magnitude greater than other populations regardless of altitude. Red blood cell associated nitrogen oxides were more than two hundred times higher. Other highland populations had generally higher levels although not to the degree showed by Tibetans. Overall, responses of those acclimatized and those presumed to be adapted are in the same direction although the Tibetans have much larger responses. Missing are long-term data on lowlanders at altitude showing how similar they become to the Tibetan phenotype. Also missing are data on Tibetans at low altitude to see the extent to which their phenotype is a response to the immediate environment or expressed constitutively. The mechanisms causing the visitors’ and the Tibetans’ high levels of NO and NO-derived molecules at altitude remain unknown. Limited data suggest processes including hypoxic upregulation of NO synthase gene expression, hemoglobin-NO reactions and genetic variation. Gains in understanding will require integrating appropriate methods and measurement techniques with indicators of adaptive function

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

    PubMed Central

    Popova, Taissia G.; Teunis, Allison; Vaseghi, Haley; Zhou, Weidong; Espina, Virginia; Liotta, Lance A.; Popov, Serguei G.

    2015-01-01

    Nitric oxide (NO) is a key physiological regulator in eukaryotic and prokaryotic organisms. It can cause a variety of biological effects by reacting with its targets or/and indirectly inducing oxidative stress. NO can also be produced by bacteria including the pathogenic Bacillus anthracis; however, its role in the infectious process only begins to emerge. NO incapacitates macrophages by S-nitrosylating the intracellular proteins and protects B. anthracis from oxidative stress. It is also implicated in the formation of toxic peroxynitrite. In this study we further assessed the effects of B. anthracis NO produced by the NO synthase (bNOS) on bacterial metabolism and host cells in experiments with the bNOS knockout Sterne strain. The mutation abrogated accumulation of nitrite and nitrate as tracer products of NO in the culture medium and markedly attenuated growth in both aerobic and microaerobic conditions. The regulatory role of NO was also suggested by the abnormally high rate of nitrate denitrification by the mutant in the presence of oxygen. Anaerobic regulation mediated by NO was reflected in reduced fermentation of glucose by the mutant correlating with the reduced toxicity of bacteria toward host cells in culture. The toxic effect of NO required permeabilization of the target cells as well as the activity of fermentation-derived metabolite in the conditions of reduced pH. The host cells demonstrated increased phosphorylation of major survivor protein kinase AKT correlating with reduced toxicity of the mutant in comparison with Sterne. Our global proteomic analysis of lymph from the lymph nodes of infected mice harboring bacteria revealed numerous changes in the pattern and levels of proteins associated with the activity of bNOS influencing key cell physiological processes relevant to energy metabolism, growth, signal transduction, stress response, septic shock, and homeostasis. This is the first in vivo observation of the bacterial NO effect on the lymphatic

  12. Nitric oxide production and nitric oxide synthase immunoreactivity in Naegleria fowleri.

    PubMed

    Rojas-Hernández, Saúl; Rodríguez-Monroy, Marco A; Moreno-Fierros, Leticia; Jarillo-Luna, Adriana; Carrasco-Yepez, Marisela; Miliar-García, Angel; Campos-Rodríguez, Rafael

    2007-07-01

    Free-living ameba Naegleria fowleri produces an acute and fatal infectious disease called primary amebic meningoencephalitis (PAM), whose pathophysiological mechanism is largely unknown. The aim of this study was to investigate the role of nitric oxide (NO) in PAM. Although NO has a cytotoxic effect on various parasites, it is produced by others as part of the pathology, as is the case with Entamoeba histolytica. To test for the production of NO, we analyzed whether antibodies against mammalian NO synthase isoforms (neuronal, inducible, and endothelial) presented immunoreactivity to N. fowleri proteins. We found that the trophozoites produced NO in vitro. The Western blot results, which showed N. fowleri trophozoites, contained proteins that share epitopes with the three described mammalian NOS, but have relative molecular weights different than those described in the literature, suggesting that N. fowleri may contain undescribed NOS isoforms. Moreover, we found that trophozoites reacted to the NOS2 antibody, in amebic cultures as well as in the mouse brain infected with N. fowleri, suggesting that nitric oxide may participate in the pathogenesis of PAM. Further research aimed at determining whether N. fowleri contains active novel NOS isoforms could lead to the design of new therapies against this parasite.

  13. Nitric oxide-dependent penile erection in mice lacking neuronal nitric oxide synthase.

    PubMed Central

    Burnett, A. L.; Nelson, R. J.; Calvin, D. C.; Liu, J. X.; Demas, G. E.; Klein, S. L.; Kriegsfeld, L. J.; Dawson, V. L.; Dawson, T. M.; Snyder, S. H.

    1996-01-01

    BACKGROUND: Nitric oxide (NO) has been implicated as a mediator of penile erection, because the neuronal isoform of NO synthase (NOS) is localized to the penile innervation and NOS inhibitors selectively block erections. NO can also be formed by two other NOS isoforms derived from distinct genes, inducible NOS (iNOS) and endothelial NOS (eNOS). To clarify the source of NO in penile function, we have examined mice with targeted deletion of the nNOS gene (nNOS- mice). MATERIALS AND METHODS: Mating behavior, electrophysiologically induced penile erection, isolated erectile tissue isometric tension, and eNOS localization by immunohistochemistry and Western blot were performed on nNOS- mice and wild-type controls. RESULTS: Both intact animal penile erections and isolated erectile tissue function are maintained in nNOS mice, in agreement with demonstrated normal sexual behaviors, but is stereospecifically blocked by the NOS inhibitor, L-nitroarginine methyl ester (L-NAME). eNOS is abundantly present in endothelium of penile vasculature and sinusoidal endothelium within the corpora cavemosa, with levels that are significantly higher in nNOS- mice than in wild-type controls. CONCLUSIONS: eNOS mediates NO-dependent penile erection in nNOS- animals and normal penile erection. These data clarify the role of nitric oxide in penile erection and may have implications for therapeutic agents with selective effects on NOS isoforms. Images FIG. 2 FIG. 3 FIG. 5 PMID:8784782

  14. Nitric oxide-dependent penile erection in mice lacking neuronal nitric oxide synthase.

    PubMed

    Burnett, A L; Nelson, R J; Calvin, D C; Liu, J X; Demas, G E; Klein, S L; Kriegsfeld, L J; Dawson, V L; Dawson, T M; Snyder, S H

    1996-05-01

    Nitric oxide (NO) has been implicated as a mediator of penile erection, because the neuronal isoform of NO synthase (NOS) is localized to the penile innervation and NOS inhibitors selectively block erections. NO can also be formed by two other NOS isoforms derived from distinct genes, inducible NOS (iNOS) and endothelial NOS (eNOS). To clarify the source of NO in penile function, we have examined mice with targeted deletion of the nNOS gene (nNOS- mice). Mating behavior, electrophysiologically induced penile erection, isolated erectile tissue isometric tension, and eNOS localization by immunohistochemistry and Western blot were performed on nNOS- mice and wild-type controls. Both intact animal penile erections and isolated erectile tissue function are maintained in nNOS mice, in agreement with demonstrated normal sexual behaviors, but is stereospecifically blocked by the NOS inhibitor, L-nitroarginine methyl ester (L-NAME). eNOS is abundantly present in endothelium of penile vasculature and sinusoidal endothelium within the corpora cavemosa, with levels that are significantly higher in nNOS- mice than in wild-type controls. eNOS mediates NO-dependent penile erection in nNOS- animals and normal penile erection. These data clarify the role of nitric oxide in penile erection and may have implications for therapeutic agents with selective effects on NOS isoforms.

  15. Osmotic swelling induces p75 neurotrophin receptor (p75NTR) expression via nitric oxide.

    PubMed

    Peterson, Suzanne; Bogenmann, Emil

    2003-09-05

    Brain injuries by physical trauma, epileptic seizures, or microbial infection upset the osmotic homeostasis resulting in cell swelling (cerebral edema), inflammation, and apoptosis. Expression of the neurotrophin receptor p75NTR is increased in the injured tissue and axon regeneration is repressed by the Nogo receptor using p75NTR as the signal transducer. Hence, p75NTR seems central to the injury response and we wished to determine the signals that regulate its expression. Here, we demonstrate that tonicity mediated cell swelling rapidly activates transcription of the endogenous p75NTR gene and of a p75NTR promoter-reporter gene in various cell types. Transcription activation is independent of de novo protein synthesis and requires the activities of phospholipase C, protein kinase C, and nitric-oxide synthase. Hence, p75NTR is a nitric oxide effector gene regulated by osmotic swelling, thereby providing a strategy for therapeutic intervention to modulate p75NTR functions following injury.

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

    PubMed

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

    2009-11-15

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

  17. 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...

  18. Nitric oxide synthases: structure, function and inhibition.

    PubMed Central

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

    2001-01-01

    This review concentrates on advances in nitric oxide synthase (NOS) structure, function and inhibition made in the last seven years, during which time substantial advances have been made in our understanding of this enzyme family. There is now information on the enzyme structure at all levels from primary (amino acid sequence) to quaternary (dimerization, association with other proteins) structure. The crystal structures of the oxygenase domains of inducible NOS (iNOS) and vascular endothelial NOS (eNOS) allow us to interpret other information in the context of this important part of the enzyme, with its binding sites for iron protoporphyrin IX (haem), biopterin, L-arginine, and the many inhibitors which interact with them. The exact nature of the NOS reaction, its mechanism and its products continue to be sources of controversy. The role of the biopterin cofactor is now becoming clearer, with emerging data implicating one-electron redox cycling as well as the multiple allosteric effects on enzyme activity. Regulation of the NOSs has been described at all levels from gene transcription to covalent modification and allosteric regulation of the enzyme itself. A wide range of NOS inhibitors have been discussed, interacting with the enzyme in diverse ways in terms of site and mechanism of inhibition, time-dependence and selectivity for individual isoforms, although there are many pitfalls and misunderstandings of these aspects. Highly selective inhibitors of iNOS versus eNOS and neuronal NOS have been identified and some of these have potential in the treatment of a range of inflammatory and other conditions in which iNOS has been implicated. PMID:11463332

  19. Nitric oxide and the paranasal sinuses.

    PubMed

    Lundberg, Jon O

    2008-11-01

    The discovery within the paranasal sinuses for the production of nitric oxide (NO) has altered the traditional explanations of sinus physiology. This review article reports the ongoing investigation of sinus physiology beginning with the discovery of NO gas production in the paranasal sinuses that occurred in 1995, and the impact that finding has had both in the basic science and clinical arenas. It was shown that healthy paranasal sinus epithelium expresses an inducible NO synthase that continuously generates large amounts of NO, a pluripotent gaseous messenger with potent vasodilating, and antimicrobial activity. This NO can be measured noninvasively in nasally exhaled breath. The role of NO in the sinuses is likely to enhance local host defense mechanisms via direct inhibition of pathogen growth and stimulation of mucociliary activity. The NO concentration in a healthy sinus exceeds those that are needed for antibacterial effects in vitro. In patients with primary ciliary dyskinesia (PCD) and in cystic fibrosis, nasal NO is extremely low. This defect NO generation likely contributes to the great susceptibility to chronic sinusitis in these patients. In addition, the low-nasal NO is of diagnostic value especially in PCD, where nasal NO is very low or absent. Intriguingly, NO gas from the nose and sinuses is inhaled with every breath and reaches the lungs in a more diluted form to enhance pulmonary oxygen uptake via local vasodilation. In this sense NO may be regarded as an "aerocrine" hormone that is produced in the nose and sinuses and transported to a distal site of action with every inhalation. Copyright 2008 Wiley-Liss, Inc.

  20. Nitric oxide scavenging by red cell microparticles.

    PubMed

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

    2013-12-01

    Red cell microparticles form during the storage of red blood cells and in diseases associated with red cell breakdown and asplenia, including hemolytic anemias such as sickle cell disease. These small phospholipid vesicles that are derived from red blood cells have been implicated in the pathogenesis of transfusion of aged stored blood and hemolytic diseases, via activation of the hemostatic system and effects on nitric oxide (NO) bioavailability. Red cell microparticles react with the important signaling molecule NO almost as fast as cell-free hemoglobin, about 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 μM 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.

  1. Transnitrosylation: A Factor in Nitric Oxide-Mediated Penile Erection.

    PubMed

    Musicki, Biljana; Lagoda, Gwen; Goetz, Tabitha; La Favor, Justin D; Burnett, Arthur L

    2016-05-01

    Nitric oxide (NO) signaling can be mediated not only through classic 3',5'-cyclic guanosine monophosphate but also through S-nitrosylation. However, the impact of S-nitrosylation on erectile function and in NO regulation and oxidative stress in the penis remains poorly understood. To characterize the role of S-nitrosoglutathione reductase (GSNOR), a major regulator of S-nitrosylation homeostasis, on erection physiology and on endothelial NO synthase (eNOS) function and oxidative-nitrosative stress in the penis. Adult GSNOR-deficient and wild-type (WT) mice were used. Erectile function was assessed in response to electrical stimulation of the cavernous nerve. Total NO in penile homogenates was measured by Griess reaction. Protein S-nitrosylation, eNOS phosphorylation on Ser-1177 (positive regulatory site), eNOS uncoupling, and markers of oxidative stress (4-hydroxy-2-nonenal, malondialdehyde, and nitrotyrosine) in the penis were measured by western blot. Erectile function, eNOS function, and oxidative stress in the penis of GSNOR-deficient mice. Erectile function was intact in GSNOR-deficient mice. Total S-nitrosylated proteins were increased (P < .05) in the GSNOR(-/-) compared with WT mouse penis. Although eNOS phosphorylation on Ser-1177 did not differ between the GSNOR(-/-) and WT mouse penises at baseline, electrical stimulation of the cavernous nerve increased (P < .05) phosphorylated eNOS in the WT mouse penis but failed to increase phosphorylated eNOS in the GSNOR(-/-) mouse penis. Total NO production was decreased (P < .05), whereas eNOS uncoupling, 4-hydroxy-2-nonenal, malondialdehyde, and nitrotyrosine were increased (P < .05) in the GSNOR-deficient mouse penis compared with the WT mouse penis. Transnitrosylation mechanisms play an important role in regulating NO bioactivity in the penis. Deficiency of GSNOR leads to eNOS dysfunction and increased oxidative damage, suggesting that homeostatic eNOS function in the penis is governed by transnitrosylation

  2. Nitric oxide–mediated regulation of ferroportin-1 controls macrophage iron homeostasis and immune function in Salmonella infection

    PubMed Central

    Nairz, Manfred; Schleicher, Ulrike; Schroll, Andrea; Sonnweber, Thomas; Theurl, Igor; Ludwiczek, Susanne; Talasz, Heribert; Brandacher, Gerald; Moser, Patrizia L.; Muckenthaler, Martina U.; Fang, Ferric C.; Bogdan, Christian

    2013-01-01

    Nitric oxide (NO) generated by inducible NO synthase 2 (NOS2) affects cellular iron homeostasis, but the underlying molecular mechanisms and implications for NOS2-dependent pathogen control are incompletely understood. In this study, we found that NO up-regulated the expression of ferroportin-1 (Fpn1), the major cellular iron exporter, in mouse and human cells. Nos2−/− macrophages displayed increased iron content due to reduced Fpn1 expression and allowed for an enhanced iron acquisition by the intracellular bacterium Salmonella typhimurium. Nos2 gene disruption or inhibition of NOS2 activity led to an accumulation of iron in the spleen and splenic macrophages. Lack of NO formation resulted in impaired nuclear factor erythroid 2-related factor-2 (Nrf2) expression, resulting in reduced Fpn1 transcription and diminished cellular iron egress. After infection of Nos2−/− macrophages or mice with S. typhimurium, the increased iron accumulation was paralleled by a reduced cytokine (TNF, IL-12, and IFN-γ) expression and impaired pathogen control, all of which were restored upon administration of the iron chelator deferasirox or hyperexpression of Fpn1 or Nrf2. Thus, the accumulation of iron in Nos2−/− macrophages counteracts a proinflammatory host immune response, and the protective effect of NO appears to partially result from its ability to prevent iron overload in macrophages PMID:23630227

  3. Vascular aging: Chronic oxidative stress and impairment of redox signaling—consequences for vascular homeostasis and disease

    PubMed Central

    Bachschmid, Markus M.; Schildknecht, Stefan; Matsui, Reiko; Zee, Rebecca; Haeussler, Dagmar; Cohen, Richard A.; Pimental, David; van der Loo, Bernd

    2013-01-01

    Characteristic morphological and molecular alterations such as vessel wall thickening and reduction of nitric oxide occur in the aging vasculature leading to the gradual loss of vascular homeostasis. Consequently, the risk of developing acute and chronic cardiovascular diseases increases with age. Current research of the underlying molecular mechanisms of endothelial function demonstrates a duality of reactive oxygen and nitrogen species in contributing to vascular homeostasis or leading to detrimental effects when formed in excess. Furthermore, changes in function and redox status of vascular smooth muscle cells contribute to age-related vascular remodeling. The age-dependent increase in free radical formation causes deterioration of the nitric oxide signaling cascade, alters and activates prostaglandin metabolism, and promotes novel oxidative posttranslational protein modifications that interfere with vascular and cell signaling pathways. As a result, vascular dysfunction manifests. Compensatory mechanisms are initially activated to cope with age-induced oxidative stress, but become futile, which results in irreversible oxidative modifications of biological macromolecules. These findings support the ‘free radical theory of aging’ but also show that reactive oxygen and nitrogen species are essential signaling molecules, regulating vascular homeostasis. PMID:22380696

  4. Postponed effect of neostigmine on oxidative homeostasis

    PubMed Central

    2014-01-01

    Cholinesterases are enzymes able to hydrolyze the neurotransmitter acetylcholine and thus to terminate transmission. Once the enzymes are inhibited, excitotoxicity can appear in the adjacent cells. It is well known that oxidative stress is involved in the toxicity of cholinesterase inhibitors. Commonly, stress follows inhibition of cholinesterases and disappears shortly afterwards. In the present experiment, it was decided to test the impact of an inhibitor, neostigmine, on oxidative stress in BALB/c mice after a longer interval. The animals were sacrificed three days after onset of the experiment and spleens and livers were collected. Reduced glutathione (GSH), glutathione reductase (GR), glutathione S-transferase (GST), thiobarbituric acid reactive substances (TBARS), ferric reducing antioxidant power (FRAP), caspase-3 and activity of acetylcholinesterase (AChE) were assayed. The tested markers were not altered with exceptions of FRAP. The FRAP values indicate accumulation of low molecular weight antioxidants in the examined organs. The role of low molecular weight antioxidants in the toxicity of AChE inhibitors is discussed. PMID:26109890

  5. Nitric oxide functions as a signal in plant disease resistance.

    PubMed

    Delledonne, M; Xia, Y; Dixon, R A; Lamb, C

    1998-08-06

    Recognition of an avirulent pathogen triggers the rapid production of the reactive oxygen intermediates superoxide (O2-) and hydrogen peroxide (H2O2). This oxidative burst drives crosslinking of the cell wall, induces several plant genes involved in cellular protection and defence, and is necessary for the initiation of host cell death in the hypersensitive disease-resistance response. However, this burst is not enough to support a strong disease-resistance response. Here we show that nitric oxide, which acts as a signal in the immune, nervous and vascular systems, potentiates the induction of hypersensitive cell death in soybean cells by reactive oxygen intermediates and functions independently of such intermediates to induce genes for the synthesis of protective natural products. Moreover, inhibitors of nitric oxide synthesis compromise the hypersensitive disease-resistance response of Arabidopsis leaves to Pseudomonas syringae, promoting disease and bacterial growth. We conclude that nitric oxide plays a key role in disease resistance in plants.

  6. Pharmacological therapies, lifestyle choices and nitric oxide deficiency: a perfect storm.

    PubMed

    Bryan, Nathan S

    2012-12-01

    Over the past 10 years, despite a slight increase in life expectancy and a decrease in all causes of deaths, the percentage of the US population with heart disease, cancer, diabetes, hypertension and obesity has increased. So even though Americans are living longer, they are plagued by increasing incidences of morbidities. This trend is also reflective of the global population, where 17.3 million people died from cardiovascular disease in 2008, and an estimated 23.6 million are expected to die from this disease in 2030. Whereas access to medical care and management of certain diseases has improved, it is clear that the incidence and treatment of chronic disease has not kept pace. The discovery of nitric oxide (NO) production in the human body is a relatively new advancement of modern medicine. Unfortunately, NO is still not at the forefront of therapy. In the clinical setting, there are no standard laboratory diagnostics for NO status and no prescription therapies to safely and effectively restore NO homeostasis, despite being recognized as the earliest indicator for a number of different chronic diseases. This review will reveal how many modern therapies and western lifestyles actually lead to a decrease in NO homeostasis in patients, from pediatrics to geriatrics. The findings outlined here highlight why nitric oxide homeostasis should be accounted for and considered in the treatment of patients and in the development of new therapies. Understanding NO homeostasis in each patient and how treatments and procedures affect NO homeostasis should allow for better medical care and improved outcomes. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Nitric Oxide Generating Polymeric Coatings for Subcutaneous Glucose Sensors

    DTIC Science & Technology

    2008-10-14

    required to fabricate implantable amperometric glucose sensors with outer polymeric coatings that slowly generate low levels of nitric oxide (NO...is aimed at exploring and optimizing the chemistries required to fabricate implantable amperometric glucose sensors with outer polymeric films that...34 Oral Presentation, The Tenth World Congress on Biosensors , May 16, 2008, Shanghai, China. -J. Yang, J. L. Welby, M. E. Meyerhoff, “Generic Nitric

  8. The Nitric Acid Oxidation of Selected Alcohols and Ketones.

    ERIC Educational Resources Information Center

    Field, Kurt W.; And Others

    1985-01-01

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

  9. Nitric Oxide Formation by Meteoroids in the Upper Atmosphere

    NASA Technical Reports Server (NTRS)

    Menees, Gene P.; Park, Chul

    1976-01-01

    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.

  10. Nitric Oxide in Astrocyte-Neuron Signaling

    SciTech Connect

    Li, Nianzhen

    2002-01-01

    Astrocytes, a subtype of glial cell, have recently been shown to exhibit Ca2+ elevations in response to neurotransmitters. A Ca2+ elevation can propagate to adjacent astrocytes as a Ca2+ wave, which allows an astrocyte to communicate with its neighbors. Additionally, glutamate can be released from astrocytes via a Ca2+-dependent mechanism, thus modulating neuronal activity and synaptic transmission. In this dissertation, the author investigated the roles of another endogenous signal, nitric oxide (NO), in astrocyte-neuron signaling. First the author tested if NO is generated during astrocytic Ca2+ signaling by imaging NO in purified murine cortical astrocyte cultures. Physiological concentrations of a natural messenger, ATP, caused a Ca2+-dependent NO production. To test the roles of NO in astrocytic Ca2+ signaling, the author applied NO to astrocyte cultures via addition of a NO donor, S-nitrosol-N-acetylpenicillamine (SNAP). NO induced an influx of external Ca2+, possibly through store-operated Ca2+ channels. The NO-induced Ca2+ signaling is cGMP-independent since 8-Br-cGMP, an agonistic analog of cGMP, did not induce a detectable Ca2+ change. The consequence of this NO-induced Ca2+ influx was assessed by simultaneously monitoring of cytosolic and internal store Ca2+ using fluorescent Ca2+ indicators x-rhod-1 and mag-fluo-4. Blockage of NO signaling with the NO scavenger PTIO significantly reduced the refilling percentage of internal stores following ATP-induced Ca2+ release, suggesting that NO modulates internal store refilling. Furthermore, locally photo-release of NO to a single astrocyte led to a Ca2+ elevation in the stimulated astrocyte and a subsequent Ca2+ wave to neighbors. Finally, the author tested the role of NO inglutamate-mediated astrocyte-neuron signaling by

  11. Light activated nitric oxide releasing materials

    NASA Astrophysics Data System (ADS)

    Muizzi Casanas, Dayana Andreina

    The ability to control the location and dosage of biologically active molecules inside the human body can be critical to maximizing effective treatment of cardiovascular diseases like angina. The current standard of treatment relies on the metabolism of organonitrate drugs into nitric oxide (NO), which are not specific, and also show problems with densitization with long-term use. There is a need then to create a treatment method that gives targeted release of NO. Metal-nitrosyl (M-NO) complexes can be used for delivery of NO since the release of NO can be controlled with light. However, the NO-releasing drug must be activated with red light to ensure maximum penetration of light through tissue. However, the release of NO from M-NO complexes with red-light activation is a significant challenge since the energy required to break the metal-NO bond is usually larger than the energy provided by red light. The goal of this project was to create red- sensitive, NO-releasing materials based on Ru-salen-nitrosyl compounds. Our approach was to first modify Ru salen complexes to sensitize the photochemistry for release of NO after red light irradiation. Next, we pursued polymerization of the Ru-salen complexes. We report the synthesis and quantitative photochemical characterization of a series of ruthenium salen nitrosyl complexes. These complexes were modified by incorporating electron donating groups in the salen ligand structure at key locations to increase electron density on the Ru. Complexes with either an --OH or --OCH3 substituent showed an improvement in the quantum yield of release of NO upon blue light irradiation compared to the unmodified salen. These --OH and --OCH3 complexes were also sensitized for NO release after red light activation, however the red-sensitive complexes were unstable and showed ligand substitution on the order of minutes. The substituted complexes remained sensitive for NO release, but only after blue light irradiation. The Ru

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

    PubMed Central

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

    2000-01-01

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

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

    PubMed

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

    2000-10-15

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

  14. The nitric oxide/cyclic GMP pathway: a potential major regulator of cochlear physiology.

    PubMed

    Fessenden, J D; Schacht, J

    1998-04-01

    The nitric oxide (NO)/cyclic guanosine monophosphate (GMP) pathway is now recognized as a major regulatory system in cell physiology and tissue homeostasis. This pathway may control processes as diverse as muscle relaxation, gut peristalsis, neurotransmission and hormonal secretion. It is also involved in the development and function of sensory systems such as vision and olfaction. This review will detail the NO/cyclic GMP pathway, evaluate studies in the auditory system and discuss its potential participation in cochlear blood flow, supporting cell physiology and excitotoxicity.

  15. Sleep-disordered breathing children: Measurement of nasal nitric oxide and fractional exhaled nitric oxide.

    PubMed

    Huang, Y; Zou, Y; Mai, F; Zhang, X; Liu, Y; Lin, X

    2016-03-01

    To assess the clinical significance of nasal nitric oxide (nNO) and fractional exhaled nitric oxide (FeNO) concentrations in children with sleep-disordered breathing (SDB). Enrolled in this study were 30 children with SDB and 15 healthy children. The nNO and FeNO concentrations were measured noninvasively using a NIOX MINO system (Aerocrine AB, Solna, Sweden). SPSS statistics 20.0 software (IBM SPSS statistics 20.0, Armonk, NY, USA) was used to analyze the data. The median (25th and 75th percentiles) nNO concentration of SDB children measured in parts per billion (ppb) was 111.0 (44.0; 349.0) ppb; FeNO concentration of SDB children was 12.0 (9.8; 14.0) ppb. The nNO concentration of healthy children was 52.0 (22.0; 139.0) ppb; FeNO concentration of healthy children was 12.0 (10.0; 16.0) ppb. Compared to healthy children, nNO concentration was significantly higher in children with SDB (Z = -2.215, P = 0.027). Correlation analysis showed that SDB children's nNO concentration directly correlated with apnea-hypopnea index (AHI; r = 0.429, P = 0.018), and inversely correlated with nadir oxygen saturation (SaO2; r = -0.482, P = 0.007). No other polysomnographic parameters significantly correlated with nNO concentration. Our data suggest that nNO concentration might be useful for diagnosis and evaluation of disease severity in SDB children. Furthermore, these results suggest that nNO concentration has a greater prognostic value than FeNO concentration.

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

    PubMed Central

    Anderson, J. H.

    1965-01-01

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

  17. Nitric Oxide Bioavailability in Obstructive Sleep Apnea: Interplay of Asymmetric Dimethylarginine and Free Radicals.

    PubMed

    Badran, Mohammad; Golbidi, Saeid; Ayas, Najib; Laher, Ismail

    2015-01-01

    Obstructive sleep apnea (OSA) occurs in 2% of middle-aged women and 4% of middle-aged men and is considered an independent risk factor for cerebrovascular and cardiovascular diseases. Nitric oxide (NO) is an important endothelium derived vasodilating substance that plays a critical role in maintaining vascular homeostasis. Low levels of NO are associated with impaired endothelial function. Asymmetric dimethylarginine (ADMA), an analogue of L-arginine, is a naturally occurring product of metabolism found in the human circulation. Elevated levels of ADMA inhibit NO synthesis while oxidative stress decreases its bioavailability, so impairing endothelial function and promoting atherosclerosis. Several clinical trials report increased oxidative stress and ADMA levels in patients with OSA. This review discusses the role of oxidative stress and increased ADMA levels in cardiovascular disease resulting from OSA.

  18. [Nitric oxide and electrogenic metals (Ca, Na, K) in epidermal cells].

    PubMed

    Petukhov, V I; Baumane, L K; Dmitriev, E V; Vanin, A F

    2015-01-01

    Using atomic emission spectrometry and EPR analysis metal-ligand homeostasis (MLH) has been studied in epidermal cells of 954 liquidators of the Chernobyl accident and 947 healthy individuals. A possible association of the redox status with the quantitative changes in the MLH, which could be used as discriminators of oxidative/nitrosative stress, attracts special interest. Characteristic features of oxidative stress mainly related to electrogenic metals (Ca, K, Na), were found not only among the liquidators examined, but also in some healthy individuals (18.1%); this suggests the presence of oxidative/nitrosative stress of non-radiation origin. Correlation between intracellular production of nitric oxide (NO) with quantitative changes in the electrogenic metals may indicate the possible involvement of NO in the generation of an electric potential of the cell.

  19. Nitric oxide and changes of iron metabolism in exercise.

    PubMed

    Qian, Zhong Ming

    2002-11-01

    Accumulated data imply that exercise itself might not lead to a true iron deficiency or 'sport anaemia' in a healthy athlete who has adequate iron intake. The higher prevalence of iron deficiency anaemia in younger female athletes might be not due to exercise itself, but probably results from dietary choices, inadequate iron intake and menstruation. These factors can also induce iron deficiency or anaemia in the general population. However, exercise does affect iron metabolism, leading to low or sub-optimal iron status. The underlying mechanism is unknown. In this review, recent advances in the study of the effect of exercise on iron metabolism and nitric oxide, and the relationship between nitric oxide and iron status in exercise are discussed. A hypothesis that increased production of nitric oxide might contribute to sub-optimal iron status in exercise is proposed.

  20. Parameters controlling nitric oxide emissions from gas turbine combustors

    NASA Technical Reports Server (NTRS)

    Heywood, J. B.; Mikus, T.

    1973-01-01

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

  1. Nitric oxide formation by meteoroids in the upper atmosphere

    NASA Technical Reports Server (NTRS)

    Menees, G. P.; Park, C.

    1974-01-01

    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, its radius 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 is found to occur between 90- and 100-km altitude, the total annual rate being around 40 million kg.

  2. Nitric Oxide-Releasing Biomaterials for Biomedical Applications.

    PubMed

    Zhou, Xin; Zhang, Jimin; Feng, Guowei; Shen, Jie; Kong, Deling; Zhao, Qiang

    2016-01-01

    Nitric oxide (NO), as an essential signaling molecule, participates in various physiological processes such as cardiovascular homeostasis, neuronal transmission, immunomodulation, and tumor growth. The multiple role of NO in physiology and pathophysiology has triggered a massive interest in the strategies of delivering exogenous NO for biomedical applications. Hence, different kinds of NO prodrugs have been developed up to date, including diazeniumdiolates, S-nitrosothiol, metal-nitrosyl, nitrobenzene, and so on. However, the clinical application of these low molecular weight NO donors has been restricted due to the problems of burst release, low payloads, and untargeted delivery. The delivery of NO by biomaterialbased carrier offers a beneficial strategy to realize the controlled and sustained delivery of NO to the targeted tissues or organs. In detail, NO-donor prodrugs have been attached and loaded to diverse biomaterials to fabricate nanoparticles, hydrogels, and coating platforms by means of physical, chemical, or supramolecular techniques. These NO-releasing biomaterials hold promise for a number of biomedical applications ranging from therapy of the ischemic disease and several types of cancer to cardiovascular devices and wound dressing. First, surface coating with NO-releasing biomaterials could mimic the physiological function of vascular endothelium, therefore promoting vascularization and improving the patency of cardiovascular implants. Next, because NO also mediates many important processes that take place after cutaneous injury, NO-releasing biomaterials could serve as ideal wound dressing to accelerate tissue regeneration. Finally, biomaterials enable localized delivery of high dose of NO to tumors in a sustained manner, thus generating potent tumoricidal effect. In this review, we will summarize the progress of different NO-releasing biomaterials, and highlight their biomedical applications with a hope to inspire new perspectives in the area of

  3. Enhanced biogenic emissions of nitric oxide and nitrous oxide following surface biomass burning

    Treesearch

    Iris C. Anderson; Joel S. Levine; Mark A. Poth; Philip J. Riggan

    1988-01-01

    Recent measurements indicate significantly enhanced biogenic soil emissions of both nitric oxide (NO) and nitrous oxide (N2O) following surface burning. These enhanced fluxes persisted for at least 6 months following the burn. Simultaneous measurements indicate enhanced levels of...

  4. Relationship between exhaled nitric oxide and childhood asthma.

    PubMed

    Frank, T L; Adisesh, A; Pickering, A C; Morrison, J F; Wright, T; Francis, H; Fletcher, A; Frank, P I; Hannaford, P

    1998-10-01

    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 attending the North West Lung Centre, Manchester, United Kingdom, for the clinical evaluation of a respiratory questionnaire being developed as a screening tool in general practice. The clinical assessment included full lung function, skin prick testing, and exercise challenge. Children were said to be asthmatic either by consensus decision of three independent consultant pediatricians, who reviewed all the clinical results except the nitric oxide measurements, or by positive exercise test. Atopic asthmatic children had higher geometric mean exhaled nitric oxide levels (consensus decision, 12.5 ppb [parts per billion] 95% CI, 8.3 to 18. 8; positive exercise test, 12.2 ppb 95% CI, 7.6 to 19.7) than did nonatopic asthmatic children (3.2 ppb 95% CI, 2.3 to 4.6; 3.2 ppb 95% CI, 2.0 to 5.0), atopic nonasthmatic children (3.8 ppb 95% CI, 2. 7 to 5.5; 5.7 ppb 95% CI, 4.1 to 8.0), or nonatopic nonasthmatic children (3.4 ppb 95% CI, 2.8 to 4.1; 3.5 ppb 95% CI, 3.0 to 4.1). Thus, exhaled nitric oxide was raised in atopic asthmatics but not in nonatopic asthmatics, and these nonatopic asthmatics had levels of exhaled nitric oxide similar to those of the nonasthmatics whether atopic or not.

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

    PubMed Central

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

    2013-01-01

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

  6. Role of Carnitine Acetyl Transferase in Regulation of Nitric Oxide Signaling in Pulmonary Arterial Endothelial Cells

    PubMed Central

    Sharma, Shruti; Sun, Xutong; Agarwal, Saurabh; Rafikov, Ruslan; Dasarathy, Sridevi; Kumar, Sanjiv; Black, Stephen M.

    2013-01-01

    Congenital heart defects with increased pulmonary blood flow (PBF) result in pulmonary endothelial dysfunction that is dependent, at least in part, on decreases in nitric oxide (NO) signaling. Utilizing a lamb model with left-to-right shunting of blood and increased PBF that mimics the human disease, we have recently shown that a disruption in carnitine homeostasis, due to a decreased carnitine acetyl transferase (CrAT) activity, correlates with decreased bioavailable NO. Thus, we undertook this study to test the hypothesis that the CrAT enzyme plays a major role in regulating NO signaling through its effect on mitochondrial function. We utilized the siRNA gene knockdown approach to mimic the effect of decreased CrAT activity in pulmonary arterial endothelial cells (PAEC). Our data indicate that silencing the CrAT gene disrupted cellular carnitine homeostasis, reduced the expression of mitochondrial superoxide dismutase-and resulted in an increase in oxidative stress within the mitochondrion. CrAT gene silencing also disrupted mitochondrial bioenergetics resulting in reduced ATP generation and decreased NO signaling secondary to a reduction in eNOS/Hsp90 interactions. Thus, this study links the disruption of carnitine homeostasis to the loss of NO signaling observed in children with CHD. Preserving carnitine homeostasis may have important clinical implications that warrant further investigation. PMID:23344032

  7. Recent Advances on Nitric Oxide in the Upper Airways.

    PubMed

    Maniscalco, Mauro; Bianco, Andrea; Mazzarella, Gennaro; Motta, Andrea

    2016-01-01

    Exhaled nitric oxide (NO) originates from the upper airways, and takes action, to varying extents, in regulation, protection and defense, as well as in noxious processes. Nitric oxide retains important functions in a wide range of physiological and pathophysiological processes of the human body, including vaso-regulation, antimicrobial activity, neurotransmission and respiration. This review article reports the ongoing investigations regarding the source, biology and relevance of NO within upper respiratory tract. In addition, we discuss the role of NO, originating from nasal and paranasal sinuses, in inflammatory disorders such as allergic rhinitis, sinusitis, primary ciliary dyskinesia, and cystic fibrosis.

  8. Nitric oxide emission from pulverized coal blend flames

    SciTech Connect

    Kopparthi, V.; Gollahalli, S.R.

    1995-09-01

    An experimental study of the nitric oxide emission from pulverized blended coal flames as a function of blending mass ratio is presented. Coals of three ranks (anthracite, bituminous, and lignite), and of the same rank (bituminous), but of different origin (Oklahoma and Wyoming mines), were used as fuels. Also, their blends (anthracite-bituminous, anthracite-lignite, lignite-bituminous, and Oklahoma-Wyoming coals) at mass ratios of 20:80, 40:60, 60:40, and 80:20 were studied. Correlations of nitric oxide emission index (mass/unit energy release) with blend mass ratio are presented.

  9. Use of inhaled nitric oxide in preterm infants.

    PubMed

    Kumar, Praveen

    2014-01-01

    Nitric oxide, an important signaling molecule with multiple regulatory effects throughout the body, is an important tool for the treatment of full-term and late-preterm infants with persistent pulmonary hypertension of the newborn and hypoxemic respiratory failure. Several randomized controlled trials have evaluated its role in the management of preterm infants ≤ 34 weeks' gestational age with varying results. The purpose of this clinical report is to summarize the existing evidence for the use of inhaled nitric oxide in preterm infants and provide guidance regarding its use in this population.

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

    PubMed

    Gradoni, L; Ascenzi, P

    2004-06-01

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

  11. Nitric oxide mediates low magnesium inhibition of osteoblast-like cell proliferation.

    PubMed

    Leidi, Marzia; Dellera, Federica; Mariotti, Massimo; Banfi, Giuseppe; Crapanzano, Calogero; Albisetti, Walter; Maier, Jeanette A M

    2012-10-01

    An adequate intake of magnesium (Mg) is important for bone cell activity and contributes to the prevention of osteoporosis. Because (a) Mg is mitogenic for osteoblasts and (b) reduction of osteoblast proliferation is detected in osteoporosis, we investigated the influence of different concentrations of extracellular Mg on osteoblast-like SaOS-2 cell behavior. We found that low Mg inhibited SaOS-2 cell proliferation by increasing the release of nitric oxide through the up-regulation of inducible nitric oxide synthase (iNOS). Indeed, both pharmacological inhibition with the iNOS inhibitor l-N(6)-(iminoethyl)-lysine-HCl and genetic silencing of iNOS by small interfering RNA restored the normal proliferation rate of the cells. Because a moderate induction of nitric oxide is sufficient to potentiate bone resorption and a relative deficiency in osteoblast proliferation can result in their inadequate activity, we conclude that maintaining Mg homeostasis is relevant to ensure osteoblast function and, therefore, to prevent osteoporosis.

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

    PubMed

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

    2010-12-01

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

  13. Estimates of nitric oxide production for lifting spacecraft reentry

    NASA Technical Reports Server (NTRS)

    Park, C.

    1971-01-01

    The amount of nitric oxide which may be produced by heating of air during an atmospheric reentry of a lifting spacecraft is estimated by three different methods. Two assume nitrogen fixation by the process of sudden freezing, and the third is a computer calculation using chemical rate equations.

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

    USDA-ARS?s Scientific Manuscript database

    There is a great demand for safe and effective alternative fumigants to replace methyl bromide and other toxic fumigants for pest control. Nitric oxide, a common signal molecule in biological systems, was found to be effective and safe to control insects under ultralow oxygen conditions. Fumigatio...

  15. Nitric oxide emissions from a central California dairy

    USDA-ARS?s Scientific Manuscript database

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

  16. Arginine, citrulline and nitric oxide metabolism in sepsis

    USDA-ARS?s Scientific Manuscript database

    Arginine has vasodilatory effects, via its conversion by nitric oxide (NO) synthase into NO, and immunomodulatory actions that play important roles in sepsis. Protein breakdown affects arginine availability, and the release of asymmetric dimethylarginine, an inhibitor of NO synthase, may therefore a...

  17. Substituted 2-aminopyridines as inhibitors of nitric oxide synthases.

    PubMed

    Hagmann, W K; Caldwell, C G; Chen, P; Durette, P L; Esser, C K; Lanza, T J; Kopka, I E; Guthikonda, R; Shah, S K; MacCoss, M; Chabin, R M; Fletcher, D; Grant, S K; Green, B G; Humes, J L; Kelly, T M; Luell, S; Meurer, R; Moore, V; Pacholok, S G; Pavia, T; Williams, H R; Wong, K K

    2000-09-04

    A series of substituted 2-aminopyridines was prepared and evaluated as inhibitors of human nitric oxide synthases (NOS). 4,6-Disubstitution enhanced both potency and specificity for the inducible NOS with the most potent compound having an IC50 of 28 nM.

  18. The levels of nitric oxide in megaloblastic anemia.

    PubMed

    Erkurt, Mehmet Ali; Aydoğdu, İsmet; Bayraktar, Nihayet; Kuku, İrfan; Kuku, İrfan; Kaya, Emin

    2009-12-05

    The purpose of this study was to investigate the relationship between nitric oxide degradation products (nitrate and nitrite) levels and megaloblastic anemia which is treated with cyalocobalamin. A total of 30 patients with megaloblastic anemia (16 Male, 14 Female) were included in the study. Cyanocobalamin was administered (1.000 µg/day intramuscularly) until the reticulocyte crisis occurred to the normal range. The control group consisted of 30 healthy subjects (15 Male, 15 Female). Nitric oxide levels were measured before treatment and compared with the values obtained during peak reticulocyte count. Plasma direct nitrite, total nitrite and nitrate levels were 24,86±3,87, 60.56±7,01 and 36,02±5,24 in before treatment versus 15,48±3,05, 38,92±6,44 and 22,77±6,04 μmol/dl in after treatment, respectively. Plasma direct nitrite, total nitrite and nitrate levels were significantly lower in after treatment compared with the before treatment (p<0.001). Nitric oxide levels are seen to increase in megaloblastic anemia. This study suggested that abnormalities in the nitric oxide levels in megaloblastic anemia are restored by vitamin B12 replacement therapy.

  19. Apple fruit responses following exposure to nitric oxide

    USDA-ARS?s Scientific Manuscript database

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

  20. Nitric oxide inhibition sustains vasopressin-induced vasoconstriction.

    PubMed Central

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

    1995-01-01

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

  1. Modulation of nitric-oxide synthase by nicotine.

    PubMed

    Tonnessen, B H; Severson, S R; Hurt, R D; Miller, V M

    2000-11-01

    Effects of nicotine on arterial endothelium-dependent relaxations mediated by nitric oxide are controversial. Experiments were designed to test the hypothesis that nicotine can directly alter activity of endothelial nitric-oxide synthase (eNOS). NOS from aortic endothelial cells of untreated dogs and recombinant eNOS, neuronal NOS, and inducible NOS were used for these experiments. NOS activity was determined as conversion of L-[(3)H]arginine to L-[(3)H]citrulline in the absence or presence of nicotine (10(-7)-10(-3) M) in vitro. In separate assays, concentrations of cofactors NADPH, FAD, and tetrahydrobioprotein were reduced by half to assess for possible interaction with nicotine. With enzyme from aortic endothelial cells, total and calcium-dependent accumulation of citrulline increased by 30% in the presence of 10(-5) M nicotine. Nicotine dose dependently also increased citrulline accumulation by recombinant eNOS and neuronal NOS but not inducible NOS. Effects of nicotine on accumulation of citrulline by isolated eNOS and recombinant eNOS were further modulated by changes in the concentration of NADPH in the incubation solution. Our data demonstrate a significant effect of nicotine on eNOS-mediated citrulline accumulation. These results suggest that effects of nicotine on production of nitric oxide may depend on NADPH or oxygen radical interactions with NOS and thus may explain, in part, inconsistent findings of changes in production of endothelium-derived nitric oxide with nicotine administration.

  2. Cross sections for electron collisions with nitric oxide

    SciTech Connect

    Itikawa, Yukikazu

    2016-09-15

    Cross section data are reviewed for electron collisions with nitric oxide. Collision processes considered are total scattering, elastic scattering, momentum transfer, excitations of rotational, vibrational, and electronic states, ionization, and dissociative electron attachment. After a survey of the literature (up to the end of 2015), recommended values of the cross section are determined, as far as possible.

  3. Nitric oxide determination by amperometric carbon fiber microelectrode.

    PubMed

    Katrlík, Jaroslav; Zálesáková, Pavlína

    2002-05-15

    Nitric oxide (NO) amperometric microsensor was prepared by the modification of bare carbon fiber electrode by Nafion and cellulose acetate (CA). Detection limit, response time, reproducibility and influence of some possible interferences (nitrite, nitrate, arginine) were tested and evaluated. This sensor was used for in vitro determination of NO release from fresh porcine aorta induced by calcium ionophore A23187 (CI).

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

    PubMed Central

    Kucera, I

    1992-01-01

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

  5. Influence of basal nitric oxide secretion on cardiac function in man.

    PubMed Central

    Clarkson, P B; Lim, P O; MacDonald, T M

    1995-01-01

    1. Nitric oxide is recognised as an important biological mediator, which is thought to be involved in cardiovascular homeostasis. The purpose of this study was to investigate the effects of basal nitric oxide synthesis on cardiac function in man, by blocking nitric oxide synthesis with NG-monomethyl-L-arginine (L-NMMA). 2. Eight normal volunteers were studied on two separate occasions. Measurements of heart rate, blood pressure and echocardiographic indices of left ventricular systolic and diastolic function were made at baseline on each day and every 20 min during incremental infusion of L-NMMA (0.1, 0.2, 0.5, 1.0 and 2.0 mg kg-1 h-1) or placebo. 3. A trend towards reduction in heart rate was observed with L-NMMA infusion although this did not reach statistical significance, whereas significant increases in both systolic blood pressure (at 2.0 mg kg-1 h-1) and systemic vascular resistance index (at 0.5 mg kg-1 h-1) were seen. 4. L-NMMA infusion caused significant reductions in stroke distance and cardiac index, although there was no change in the ratio of end systolic wall stress/end systolic volume index (an afterload independent index of left ventricular systolic performance). 5. The isovolumic relaxation time significantly increased with L-NMMA infusion, together with a significant reduction in the 'E' wave flow velocity integral. Reductions in both peak E/A ratio and E/A flow velocity integral ratio were also seen, although these failed to reach statistical significance. 6. In conclusion, the basal generation of nitric oxide in man appears to maintain a vasodilated state, and modifies left ventricular diastolic filling parameters. PMID:8554930

  6. Production of nitric oxide using a microwave plasma torch and its application to fungal cell differentiation

    NASA Astrophysics Data System (ADS)

    Na, Young Ho; Kumar, Naresh; Kang, Min-Ho; Cho, Guang Sup; Choi, Eun Ha; Park, Gyungsoon; Uhm, Han Sup

    2015-03-01

    The generation of nitric oxide by a microwave plasma torch is proposed for its application to cell differentiation. A microwave plasma torch was developed based on basic kinetic theory. The analytical theory indicates that nitric oxide density is nearly proportional to oxygen molecular density and that the high-temperature flame is an effective means of generating nitric oxide. Experimental data pertaining to nitric oxide production are presented in terms of the oxygen input in units of cubic centimeters per minute. The apparent length of the torch flame increases as the oxygen input increases. The various levels of nitric oxide are observed depending on the flow rate of nitrogen gas, the mole fraction of oxygen gas, and the microwave power. In order to evaluate the potential of nitric oxide as an activator of cell differentiation, we applied nitric oxide generated from the microwave plasma torch to a model microbial cell (Neurospora crassa: non-pathogenic fungus). Germination and hyphal differentiation of fungal cells were not dramatically changed but there was a significant increase in spore formation after treatment with nitric oxide. In addition, the expression level of a sporulation related gene acon-3 was significantly elevated after 24 h upon nitric oxide treatment. Increase in the level of nitric oxide, nitrite and nitrate in water after nitric oxide treatment seems to be responsible for activation of fungal sporulation. Our results suggest that nitric oxide generated by plasma can be used as a possible activator of cell differentiation and development.

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

    PubMed Central

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

    2004-01-01

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

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

    PubMed

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

    1998-03-01

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

  9. Inhaled nitric oxide augments nitric oxide transport on sickle cell hemoglobin without affecting oxygen affinity

    PubMed Central

    Gladwin, Mark T.; Schechter, Alan N.; Shelhamer, James H.; Pannell, Lewis K.; Conway, Deirdre A.; Hrinczenko, Borys W.; Nichols, James S.; Pease-Fye, Margaret E.; Noguchi, Constance T.; Rodgers, Griffin P.; Ognibene, Frederick P.

    1999-01-01

    Nitric oxide (NO) inhalation has been reported to increase the oxygen affinity of sickle cell erythrocytes. Also, proposed allosteric mechanisms for hemoglobin, based on S-nitrosation of β-chain cysteine 93, raise the possibilty of altering the pathophysiology of sickle cell disease by inhibiting polymerization or by increasing NO delivery to the tissue. We studied the effects of a 2-hour treatment, using varying concentrations of inhaled NO. Oxygen affinity, as measured by P50, did not respond to inhaled NO, either in controls or in individuals with sickle cell disease. At baseline, the arterial and venous levels of nitrosylated hemoglobin were not significantly different, but NO inhalation led to a dose-dependent increase in mean nitrosylated hemoglobin, and at the highest dosage, a significant arterial-venous difference emerged. The levels of nitrosylated hemoglobin are too low to affect overall hemoglobin oxygen affinity, but augmented NO transport to the microvasculature seems a promising strategy for improving microvascular perfusion. PMID:10510334

  10. Nitric oxide synthase in acute alteration of nitric oxide levels after subarachnoid hemorrhage.

    PubMed

    Sehba, Fatima A; Chereshnev, Igor; Maayani, Saul; Friedrich, Victor; Bederson, Joshua B

    2004-09-01

    Subarachnoid hemorrhage (SAH) is associated with acute decreases and subsequent recovery of cerebral nitric oxide (NO) levels, but the mechanisms of these alterations are not known. In this study, we measured NO synthase (NOS) protein and kinetics to determine its involvement in the alterations of cerebral NO levels after SAH. The endovascular rat model of SAH was used. The number of NOS-1 (neuronal) and NOS-2 (inducible)-positive cells (0-96 h) was determined by counting immunoreactive cells in 8-microm cryostat sections. The tissue content of active NOS and its kinetic parameters were studied with an enzymatic l-citrulline assay. The number of NOS-1-positive cells increased between 1 and 3 hours after SAH, decreased to and below control values at 6 and 72 hours after SAH, and increased to control values 96 hours after SAH. The number of NOS-2-positive cells increased 1 hour after SAH, decreased to control values at 24 hours, and increased above control values 96 hours after SAH. The Michaelis-Menten kinetic parameters (V(max), K(m), slope) of NOS remained unchanged at 10 and 90 minutes after SAH. NOS-1 and -2 proteins undergo a triphasic alteration after SAH, whereas the amount of active NOS and its kinetic parameters remain unchanged during the first 90 minutes after SAH. Depletion of NOS is not involved in the acute alterations of cerebral NO levels after SAH.

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

    NASA Astrophysics Data System (ADS)

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

    1994-08-01

    An NO-selective electrode was developed as an easily applicable tool for a real-time nitric oxide (NO) measurement. The working electrode (0.2 mm diam) was made from Pt/Ir alloy coated with a three-layered membrane. The counterelectrode was made from a carbon fiber. When a stable NO donor, S-nitroso-N-acetyl-dl-penicillamine, was applied, the electrode current increased in a dose-dependent fashion. The current and calculated NO concentration showed a linear relationship in the range from 0.2 nM (S/N=1) to 1 μM 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 μM NG-monomethyl-L-arginine, an inhibitor of NO synthase. Thus, this NO-selective electrode is applicable to real-time NO assay in biological systems.

  12. Inhaled nitric oxide in premature infants: effect on tracheal aspirate and plasma nitric oxide metabolites

    PubMed Central

    Posencheg, M A; Gow, A J; Truog, W E; Ballard, R A; Cnaan, A; Golombek, S G; Ballard, P L

    2010-01-01

    Objective: Inhaled nitric oxide (iNO) is a potential new therapy for prevention of bronchopulmonary dysplasia and brain injury in premature infants. This study examined dose-related effects of iNO on NO metabolites as evidence of NO delivery. Study Design: A subset of 102 premature infants in the NO CLD trial, receiving 24 days of iNO (20 p.p.m. decreasing to 2 p.p.m.) or placebo, were analyzed. Tracheal aspirate (TA) and plasma samples collected at enrollment and at intervals during study gas were analyzed for NO metabolites. Result: iNO treatment increased NO metabolites in TA at 20 and 10 p.p.m. (1.7- to 2.3-fold vs control) and in plasma at 20, 10, and 5 p.p.m. (1.6- to 2.3-fold). In post hoc analysis, treated infants with lower metabolite levels at entry had an improved clinical outcome. Conclusion: iNO causes dose-related increases in NO metabolites in the circulation as well as lung fluid, as evidenced by TA analysis, showing NO delivery to these compartments. PMID:19812581

  13. Nitric oxide and pH modulation in gynaecological cancer.

    PubMed

    Sanhueza, Carlos; Araos, Joaquín; Naranjo, Luciano; Barros, Eric; Subiabre, Mario; Toledo, Fernando; Gutiérrez, Jaime; Chiarello, Delia I; Pardo, Fabián; Leiva, Andrea; Sobrevia, Luis

    2016-12-01

    Nitric oxide plays several roles in cellular physiology, including control of the vascular tone and defence against pathogen infection. Neuronal, inducible and endothelial nitric oxide synthase (NOS) isoforms synthesize nitric oxide. Cells generate acid and base equivalents, whose physiological intracellular concentrations are kept due to membrane transport systems, including Na(+) /H(+) exchangers and Na(+) /HCO3(-) transporters, thus maintaining a physiological pH at the intracellular (~7.0) and extracellular (~7.4) medium. In several pathologies, including cancer, cells are exposed to an extracellular acidic microenvironment, and the role for these membrane transport mechanisms in this phenomenon is likely. As altered NOS expression and activity is seen in cancer cells and because this gas promotes a glycolytic phenotype leading to extracellular acidosis in gynaecological cancer cells, a pro-inflammatory microenvironment increasing inducible NOS expression in this cell type is feasible. However, whether abnormal control of intracellular and extracellular pH by cancer cells regards with their ability to synthesize or respond to nitric oxide is unknown. We, here, discuss a potential link between pH alterations, pH controlling membrane transport systems and NOS function. We propose a potential association between inducible NOS induction and Na(+) /H(+) exchanger expression and activity in human ovary cancer. A potentiation between nitric oxide generation and the maintenance of a low extracellular pH (i.e. acidic) is proposed to establish a sequence of events in ovarian cancer cells, thus preserving a pro-proliferative acidic tumour extracellular microenvironment. We suggest that pharmacological therapeutic targeting of Na(+) /H(+) exchangers and inducible NOS may have benefits in human epithelial ovarian cancer.

  14. Nitric oxide influences blood flow distribution in renovascular hypertension.

    PubMed

    Sigmon, D H; Beierwaltes, W H

    1994-01-01

    Endothelium-derived nitric oxide contributes to the regulation of regional blood flow. Inhibition of endothelium-derived nitric oxide synthesis increases blood pressure and vascular resistance. Using the substrate antagonist N omega-nitro-L-arginine-methyl ester to block endothelium-derived nitric oxide synthesis, we tested the hypothesis that, in two-kidney, one clip renovascular hypertension, endothelium-derived nitric oxide plays an increased role in maintaining blood flow to the nonclipped kidney and other visceral organs compared with normotensive controls. This could be due to increased vascular shear stress, a primary stimulus for endothelium-derived nitric oxide synthesis, after the onset of hypertension. In hypertensive rats with mild renal artery stenosis, basal renal blood flow normalized by kidney weight was similar in the nonclipped and clipped kidneys. Basal blood pressure of controls was 98 +/- 2 mm Hg compared with 145 +/- 3 mm Hg in the two-kidney, one clip hypertensive rats. N omega-nitro-L-arginine-methyl ester increased blood pressure by 20 +/- 2 and 43 +/- 3 mm Hg in control and hypertensive rats, respectively. Compared with normotensive controls, basal resistance was higher in all organ beds in the hypertensive rats including brain, heart, intestine, and kidney. With the exception of the renal circulation, the increase in vascular resistance after N omega-nitro-L-arginine-methyl ester was greater in hypertensive rats compared with normotensive controls. In the hypertensive rats, N omega-nitro-L-arginine-methyl ester caused a similar increase in vascular resistance in both the nonclipped and clipped kidneys, and this was not different from normotensive controls.(ABSTRACT TRUNCATED AT 250 WORDS)

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

    PubMed Central

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

    2008-01-01

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

  16. Process for combined control of mercury and nitric oxide.

    SciTech Connect

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

    1999-11-03

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

  17. Arginase regulates red blood cell nitric oxide synthase and export of cardioprotective nitric oxide bioactivity.

    PubMed

    Yang, Jiangning; Gonon, Adrian T; Sjöquist, Per-Ove; Lundberg, Jon O; Pernow, John

    2013-09-10

    The theory that red blood cells (RBCs) generate and release nitric oxide (NO)-like bioactivity has gained considerable interest. However, it remains unclear whether it can be produced by endothelial NO synthase (eNOS), which is present in RBCs, and whether NO can escape scavenging by hemoglobin. The aim of this study was to test the hypothesis that arginase reciprocally controls NO formation in RBCs by competition with eNOS for their common substrate arginine and that RBC-derived NO is functionally active following arginase blockade. We show that rodent and human RBCs contain functional arginase 1 and that pharmacological inhibition of arginase increases export of eNOS-derived nitrogen oxides from RBCs under basal conditions. The functional importance was tested in an ex vivo model of myocardial ischemia-reperfusion injury. Inhibitors of arginase significantly improved postischemic functional recovery in rat hearts if administered in whole blood or with RBCs in plasma. By contrast, arginase inhibition did not improve postischemic recovery when administered with buffer solution or plasma alone. The protective effect of arginase inhibition was lost in the presence of a NOS inhibitor. Moreover, hearts from eNOS(-/-) mice were protected when the arginase inhibitor was given with blood from wild-type donors. In contrast, when hearts from wild-type mice were given blood from eNOS(-/-) mice, the arginase inhibitor failed to protect against ischemia-reperfusion. These results strongly support the notion that RBCs contain functional eNOS and release NO-like bioactivity. This process is under tight control by arginase 1 and is of functional importance during ischemia-reperfusion.

  18. Nitric oxide synthase-dependent nitric oxide production is associated with salt tolerance in Arabidopsis.

    PubMed

    Zhao, Min-Gui; Tian, Qiu-Ying; Zhang, Wen-Hao

    2007-05-01

    Nitric oxide (NO) has emerged as a key molecule involved in many physiological processes in plants. To characterize roles of NO in tolerance of Arabidopsis (Arabidopsis thaliana) to salt stress, effect of NaCl on Arabidopsis wild-type and mutant (Atnoa1) plants with an impaired in vivo NO synthase (NOS) activity and a reduced endogenous NO level was investigated. Atnoa1 mutant plants displayed a greater Na+ to K+ ratio in shoots than wild-type plants due to enhanced accumulation of Na+ and reduced accumulation of K+ when exposed to NaCl. Germination of Atnoa1 seeds was more sensitive to NaCl than that of wild-type seeds, and wild-type plants exhibited higher survival rates than Atnoa1 plants when grown under salt stress. Atnoa1 plants had higher levels of hydrogen peroxide than wild-type plants under both control and salt stress, suggesting that Atnoa1 is more vulnerable to salt and oxidative stress than wild-type plants. Treatments of wild-type plants with NOS inhibitor and NO scavenger reduced endogenous NO levels and enhanced NaCl-induced increase in Na+ to K+ ratio. Exposure of wild-type plants to NaCl inhibited NOS activity and reduced quantity of NOA1 protein, leading to a decrease in endogenous NO levels measured by NO-specific fluorescent probe. Treatment of Atnoa1 plants with NO donor sodium nitroprusside attenuated the NaCl-induced increase in Na+ to K+ ratio. Therefore, these findings provide direct evidence to support that disruption of NOS-dependent NO production is associated with salt tolerance in Arabidopsis.

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

    PubMed Central

    Grisham, Matthew B.

    1995-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    1994-08-01

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

  1. Alterations in Nitric Oxide Synthase in the Aged CNS

    PubMed Central

    Jung, Junyang; Na, Changhyun; Huh, Youngbuhm

    2012-01-01

    Aging is associated with neuronal loss, gross weight reduction of the brain, and glial proliferation in the cortex, all of which lead to functional changes in the brain. It is known that oxidative stress is a critical factor in the pathogenesis of aging; additionally, growing evidence suggests that excessive nitric oxide (NO) production contributes to the aging process. However, it is still unclear how NO plays a role in the aging process. This paper describes age-related changes in the activity of NADPH-diaphorase (NADPH-d), a marker for neurons containing nitric oxide synthase (NOS), in many CNS regions. Understanding these changes may provide a novel perspective in identifying the aging mechanism. PMID:22829960

  2. Phenolic compounds from plants as nitric oxide production inhibitors.

    PubMed

    Conforti, F; Menichini, F

    2011-01-01

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

  3. Nitric oxide in prepubertal rat ovary contribution of the ganglionic nitric oxide synthase system via superior ovarian nerve.

    PubMed

    Casais, Marilina; Delgado, Silvia Marcela; Vallcaneras, Sandra; Sosa, Zulema; Rastrilla, Ana María

    2007-02-01

    Both peripheral innervation and nitric oxide (NO) participate in ovarian steroidogenesis. Considering the existence of the nitric oxide/ nitric oxide synthase system in the peripheral neural system and in the ovary, the aim of this work was to analyze if the liberation of NO in the ovarian compartment of prepubertal rats is of ovarian and/or ganglionic origin. The analysis is carried out from a physiological point of view using the experimental coeliac ganglion--Superior Ovarian Nerve--ovary model with and without ganglionic cholinergic stimulus Acetylcholine (Ach) 10(-6) M. Non selective and selective inhibitors of the synthase nitric oxide enzyme were added to the ovarian and ganglionic compartment, and the liberation of nitrites (soluble metabolite of the nitric oxide) in the ovarian incubation liquid was measured. We found that the non-selective inhibitor L-nitro-arginina methyl ester (L-NAME) in the ovarian compartment decreased the liberation of nitrites, and that Aminoguanidine (AG) in two concentrations in a non-dose dependent form provoked the same effect. The addition of Ach in ganglion magnified the effect of the inhibitors of the NOS enzyme. The most relevant results after the addition of inhibitors in ganglion were obtained with AG 400 and 800 microM. The inhibition was made evident with and without the joint action of Ach in ganglion. These data suggest that the greatest production of NO in the ovarian compartment comes from the ovary, mainly the iNOS isoform, though the coeliac ganglion also contributes through the superior ovarian nerve but with less quantity.

  4. Effects of the nitric oxide donor, DEA/NO on cortical spreading depression.

    PubMed

    Wang, M; Obrenovitch, T P; Urenjak, J

    2003-06-01

    Cortical spreading depression (CSD) is a transient disruption of local ionic homeostasis that may promote migraine attacks and the progression of stroke lesions. We reported previously that the local inhibition of nitric oxide (NO) synthesis with Nomega-nitro-L-arginine methyl ester (L-NAME) delayed markedly the initiation of the recovery of ionic homeostasis from CSD. Here we describe a novel method for selective, controlled generation of exogenous NO in a functioning brain region. It is based on microdialysis perfusion of the NO donor, 2-(N,N-diethylamino)-diazenolate-2-oxide (DEA/NO). As DEA/NO does not generate NO at alkaline pH, and as the brain has a strong acid-base buffering capacity, DEA/NO was perfused in a medium adjusted at alkaline (but unbuffered) pH. Without DEA/NO, such a microdialysis perfusion medium did not alter CSD. DEA/NO (1, 10 and 100 microM) had little effect on CSD by itself, but it reversed in a concentration-dependent manner the effects of NOS inhibition by 1 mM L-NAME. These data demonstrate that increased formation of endogenous NO associated with CSD is critical for subsequent, rapid recovery of cellular ionic homeostasis. In this case, the molecular targets for NO may be located either on brain cells to suppress mechanisms directly involved in CSD genesis, or on local blood vessels to couple flow to the increased energy demand associated with CSD.

  5. Hypergravity upregulates renal inducible nitric oxide synthase expression and nitric oxide production

    PubMed Central

    Yoon, Gun; Oh, Choong Sik; Kim, Hyun-Soo

    2016-01-01

    Exposure to hypergravity severely decreases renal blood flow, potentially causing renal dysfunction. Nitric oxide (NO), which is endogenously synthesized by inducible NO synthase (iNOS), plays an important role in the regulation of renal function. The purpose of this study was to examine the effect of hypergravity exposure on the production of NO in kidneys. To determine whether hypergravity induces renal hypoxia and alters renal iNOS expression and NO production, mice were exposed to short-term hypergravity at +3Gz for 1 h. The time course of iNOS mRNA expression, hypoxia-inducible factor (HIF)-1α expression, and NO production was examined. Renal HIF-1α levels were significantly elevated immediately after centrifugation, and this increase was sustained for 3 h post-exposure. iNOS mRNA levels were also significantly increased immediately after exposure and were maintained during the reoxygenation period. Immunohistochemical staining for iNOS revealed that the cortical tubular epithelium exhibited moderate to strong cytoplasmic iNOS immunoreactivity immediately after hypergravity exposure and during the reoxygenation period. The time course of NO production was similar to that of iNOS expression. Our results suggest that both hypoxia and reoxygenation might be involved in the upregulation of HIF-1α in the kidneys of mice exposed to hypergravity. Significant increases in renocortical iNOS expression immediately after centrifugation and during the reoxygenation period suggest that iNOS expression induced by hypergravity exposure might play a protective role against hypoxia/reoxygenation injury in the renal cortex. Further investigations are necessary to clarify the role of iNOS and NO in kidneys exposed to hypergravity. PMID:27174912

  6. Characterization of exhaled nitric oxide: introducing a new reproducible method for nasal nitric oxide measurements.

    PubMed

    Palm, J P; Graf, P; Lundberg, J O; Alving, K

    2000-08-01

    Nitric oxide (NO) is present in the human nasal airways and has been suggested to originate primarily from the paranasal sinuses. The aim of this study was to establish a new and reproducible method for measurement of nasal NO. Through repeated single-breath measurements the intra- and inter-individual variations of NO levels in nasally (into a tightly fitting mask covering the nose) and orally exhaled air were determined in healthy humans. Variations due to the methods used were investigated. The contribution of oral NO to the nasal exhalations by introducing a mouthwash procedure was also studied. This study shows distinct individual values of NO in nasally and orally exhaled air of healthy humans. Some diurnal variability was also found with a rise in NO in nasally and orally exhaled air over the day, but no, or little, day-to-day variability when comparing the results from separate mornings. There was no correlation between NO levels in nasally and orally exhaled air, whereas there was a strong correlation between NO levels in air exhaled through the left and right nostril. The levels of NO in air exhaled at 0.17 L x s(-1) through either nostril separately were higher than in air exhaled at the same flow rate through both nostrils simultaneously. After the introduction of a mouthwash procedure the level of NO in orally, but not nasally exhaled air was reduced. To conclude the method using nasal exhalation into a nose mask is highly reproducible. It is also suggested that subtracting the level of NO in orally exhaled air, after mouthwash, from that in nasally exhaled air, would adequately reflect nasal NO levels.

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

    PubMed Central

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

    2012-01-01

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

  8. Influence of atmospheric nitric oxide concentration on the measurement of nitric oxide in exhaled air

    PubMed Central

    Corradi, M.; Pelizzoni, A.; Majori, M.; Cuomo, A.; Munari, E. d.; Pesci, A.

    1998-01-01

    BACKGROUND—Measurement of nitric oxide (NO) in exhaled air shows promise as a non-invasive method of detecting lung inflammation. However, variable concentrations of NO are measured in environmental air. The aim of this study was to verify a possible relationship between exhaled NO and atmospheric NO values during high atmospheric NO days.
METHOD—Exhaled air from 78 healthy non-smokers of mean age 35.3 years was examined for the presence of NO using a chemiluminescence NO analyser and NO levels were expressed as part per billion (ppb). The exhaled air from all the subjects was collected into a single bag and into two sequential bags. Before each test atmospheric NO was measured.
RESULTS—The mean (SE) concentration of exhaled NO collected into the single bag was 17.1 (0.6) ppb while the mean values of exhaled NO in bags 1 and 2 were 16.7 (1.3) ppb and 13.8 (1.2) ppb, respectively. The atmospheric NO concentrations registered before each test varied from 0.4 to 71 ppb. There was a significant correlation between exhaled NO in the single bag and atmospheric NO (r = 0.38,p = 0.001). The atmospheric NO concentration also correlated with exhaled NO both in bag 1 (r = 0.44, p = 0.0001) and in bag 2 (r= 0.42, p = 0.0001). These correlations disappeared with atmospheric NO concentrations lower than 35ppb.
CONCLUSIONS—These results indicate a relationship between atmospheric NO and NO levels measured in exhaled air, therefore exhaled NO should not be measured on very high atmospheric NO days.

 PMID:9828854

  9. Endothelial nitric oxide synthase activation and nitric oxide function: new light through old windows.

    PubMed

    Bird, Ian M

    2011-09-01

    The principle mechanisms operating at the level of endothelial nitric oxide synthase (eNOS) itself to control its activity are phosphorylation, the auto-regulatory properties of the protein itself, and Ca(2)(+)/calmodulin binding. It is now clear that activation of eNOS is greatest when phosphorylation of certain serine and threonine residues is accompanied by elevation of cytosolic [Ca2+](i). While eNOS also contains an autoinhibitory loop, Rafikov et al. (2011) present the evidence for a newly identified 'flexible arm' that operates in response to redox state. Boeldt et al. (2011) also review the evidence that changes in the nature of endothelial Ca(2)(+) signaling itself in different physiologic states can extend both the amplitude and duration of NO output, and a failure to change these responses in pregnancy is associated with preeclampsia. The change in Ca(2)(+) signaling is mediated through altering capacitative entry mechanisms inherent in the cell, and so many agonist responses using this mechanism are altered. The term 'adaptive cell signaling' is also introduced for the first time to describe this phenomenon. Finally NO is classically regarded as a regulator of vascular function, but NO has other actions. One proposed role is regulation of steroid biosynthesis but the physiologic relevance was unclear. Ducsay & Myers (2011) now present new evidence that NO may provide the adrenal with a mechanism to regulate cortisol output according to exposure to hypoxia. One thing all three of these reviews show is that even after several decades of study into NO biosynthesis and function, there are clearly still many things left to discover.

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

    PubMed

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

    2007-08-01

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

  11. Was nitric oxide the first deep electron sink?

    PubMed

    Ducluzeau, Anne-Lise; van Lis, Robert; Duval, Simon; Schoepp-Cothenet, Barbara; Russell, Michael J; Nitschke, Wolfgang

    2009-01-01

    Evolutionary histories of enzymes involved in chemiosmotic energy conversion indicate that a strongly oxidizing substrate was available to the last universal common ancestor before the divergence of Bacteria and Archaea. According to palaeogeochemical evidence, O(2) was not present beyond trace amounts on the early Earth. Based on recent phylogenetic, enzymatic and geochemical results, we propose that, in the earliest Archaean, nitric oxide (NO) and its derivatives nitrate and nitrite served as strongly oxidizing substrates driving the evolution of a bioenergetic pathway related to modern dissimilatory denitrification. Aerobic respiration emerged later from within this ancestral pathway via adaptation of the enzyme NO reductase to its new substrate, dioxygen.

  12. Nitric oxide ameliorates the damaging effects of oxidative stress induced by iron deficiency in cyanobacterium Anabaena 7120.

    PubMed

    Kaushik, Manish Singh; Srivastava, Meenakshi; Srivastava, Alka; Singh, Anumeha; Mishra, Arun Kumar

    2016-11-01

    In cyanobacterium Anabaena 7120, iron deficiency leads to oxidative stress with unavoidable consequences. Nitric oxide reduces pigment damage and supported the growth of Anabaena 7120 in iron-deficient conditions. Elevation in nitric oxide accumulation and reduced superoxide radical production justified the role of nitric oxide in alleviating oxidative stress in iron deficiency. Increased activities of antioxidative enzymes and higher levels of ROS scavengers (ascorbate, glutathione and thiol) in iron deficiency were also observed in the presence of nitric oxide. Nitric oxide also supported the membrane integrity of Anabaena cells and reduces protein and DNA damage caused by oxidative stress induced by iron deficiency. Results suggested that nitric oxide alleviates the damaging effects of oxidative stress induced by iron deficiency in cyanobacterium Anabaena 7120.

  13. Expression and Activity of Nitric Oxide Synthase Isoforms in Methamphetamine-Induced Striatal Dopamine Toxicity

    PubMed Central

    Friend, Danielle M.; Son, Jong H.; Keefe, Kristen A.

    2013-01-01

    Nitric oxide is implicated in methamphetamine (METH)-induced neurotoxicity; however, the source of the nitric oxide has not been identified. Previous work has also revealed that animals with partial dopamine loss induced by a neurotoxic regimen of methamphetamine fail to exhibit further decreases in striatal dopamine when re-exposed to methamphetamine 7–30 days later. The current study examined nitric oxide synthase expression and activity and protein nitration in striata of animals administered saline or neurotoxic regimens of methamphetamine at postnatal days 60 and/or 90, resulting in four treatment groups: Saline:Saline, METH:Saline, Saline:METH, and METH:METH. Acute administration of methamphetamine on postnatal day 90 (Saline:METH and METH:METH) increased nitric oxide production, as evidenced by increased protein nitration. Methamphetamine did not, however, change the expression of endothelial or inducible isoforms of nitric oxide synthase, nor did it change the number of cells positive for neuronal nitric oxide synthase mRNA expression or the amount of neuronal nitric oxide synthase mRNA per cell. However, nitric oxide synthase activity in striatal interneurons was increased in the Saline:METH and METH:METH animals. These data suggest that increased nitric oxide production after a neurotoxic regimen of methamphetamine results from increased nitric oxide synthase activity, rather than an induction of mRNA, and that constitutively expressed neuronal nitric oxide synthase is the most likely source of nitric oxide after methamphetamine administration. Of interest, animals rendered resistant to further methamphetamine-induced dopamine depletions still show equivalent degrees of methamphetamine-induced nitric oxide production, suggesting that nitric oxide production alone in response to methamphetamine is not sufficient to induce acute neurotoxic injury. PMID:23230214

  14. Refractory Oxide Coatings on Titanium for Nitric Acid Applications

    NASA Astrophysics Data System (ADS)

    Ravi Shankar, A.; Kamachi Mudali, U.

    2014-07-01

    Tantalum and Niobium have good corrosion resistance in nitric acid as well as in molten chloride salt medium encountered in spent fuel nuclear reprocessing plants. Commercially, pure Ti (Cp-Ti) exhibits good corrosion resistance in nitric acid medium; however, in vapor condensates of nitric acid, significant corrosion was observed. In the present study, a thermochemical diffusion method was pursued to coat Ta2O5, Nb2O5, and Ta2O5 + Nb2O5 on Ti to improve the corrosion resistance and enhance the life of critical components in reprocessing plants. The coated samples were characterized by XRD, SEM, EDX, profilometry, micro-scratch test, and ASTM A262 Practice-C test in 65 pct boiling nitric acid. The SEM micrograph of the coated samples showed that uniform dense coating containing Ta2O5 and/or Nb2O5 was formed. XRD patterns indicated the formation of TiO2, Ta2O5/Nb2O5, and mixed oxide/solid solution phase on coated Ti samples. ASTM A262 Practice-C test revealed reproducible outstanding corrosion resistance of Ta2O5-coated sample in comparison to Nb2O5- and Ta2O5 + Nb2O5-coated sample. The hardness of the Ta2O5-coated Cp-Ti sample was found to be twice that of uncoated Cp-Ti. The SEM and XRD results confirmed the presence of protective oxide layer (Ta2O5, rutile TiO2, and mixed phase) on coated sample which improved the corrosion resistance remarkably in boiling liquid phase of nitric acid compared to uncoated Cp-Ti and Ti-5Ta-1.8Nb alloy. Three phase corrosion test conducted on Ta2O5-coated samples in boiling 11.5 M nitric acid showed poor corrosion resistance in vapor and condensate phases of nitric acid due to poor adhesion of the coating. The adhesive strength of the coated samples needs to be optimized in order to improve the corrosion resistance in vapor and condensate phases of nitric acid.

  15. Uncoupled Cardiac Nitric Oxide Synthase Mediates Diastolic Dysfunction

    PubMed Central

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

    2010-01-01

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

  16. Nitric oxide synthase in plants: Where do we stand?

    PubMed

    Santolini, Jérôme; André, François; Jeandroz, Sylvain; Wendehenne, David

    2017-02-28

    Over the past twenty years, nitric oxide (NO) has emerged as an important player in various plant physiological processes. Although many advances in the understanding of NO functions have been made, the question of how NO is produced in plants is still challenging. It is now generally accepted that the endogenous production of NO is mainly accomplished through the reduction of nitrite via both enzymatic and non-enzymatic mechanisms which remain to be fully characterized. Furthermore, experimental arguments in favour of the existence of plant nitric oxide synthase (NOS)-like enzymes have been reported. However, recent investigations revealed that land plants do not possess animal NOS-like enzymes while few algal species do. Phylogenetic and structural analyses reveals interesting features specific to algal NOS-like proteins.

  17. Efficacy of inhaled nitric oxide in preterm neonates.

    PubMed

    Love, Lauren E; Bradshaw, Wanda T

    2012-02-01

    Over the past 20 years, the recognition of nitric oxide (NO) as an endothelial-derived vasodilator has led to remarkable advances in vascular biology awareness. The signaling molecule NO, produced by NO synthase, is a molecule that is widespread in the body and important in multiple organ systems. Soon after its discovery, investigators found NO to be a potent pulmonary vasodilator in term neonates. Nitric oxide has come to perform a key function in neonatal therapy and management since its identification, especially in those with respiratory failure. It is conventionally used in the neonatal population for the treatment of persistent pulmonary hypertension, resulting in hypoxic respiratory failure of the term or near-term newborn. Inhaled NO has been successful in acutely improving oxygenation and in reducing the need for extracorporeal membrane oxygenation treatment. In recent years, the efficacy of inhaled NO for the prevention of pulmonary disability as well as its neuroprotective capabilities in preterm infants has been explored.

  18. Nitric oxide-donor SNAP induces Xenopus eggs activation.

    PubMed

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

    2012-01-01

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

  19. Exogenous nitric oxide activates the endothelial glucocorticoid receptor.

    PubMed

    Ji, Julie Y; Diamond, Scott L

    2004-05-21

    This study investigated the effect of exogenous nitric oxide (NO) on endothelial glucocorticoid receptor (GR) function. The NO donor diethylenetriamine NONOate (DETA, 50-500microM) caused concentration dependent nuclear localization of transfected chimeric green fluorescent protein GFP-GR and elevated expression of secreted alkaline phosphatase (SEAP) from a glucocorticoid response element (GRE) promoter construct in bovine aortic endothelial cells. Other weaker NO donors (S-nitroso-N-acetylpenicillamine and spermine NONOate) failed to induce GFP-GR nuclear localization, but all the NO donors activated GRE-SEAP expression, a response unaffected by the antioxidant N-acetyl-L-cysteine. Overall, exogenous NO from high concentration donors can directly activate GR, suggesting a potential feedback mechanism for NO to regulate endothelial inducible nitric oxide synthase (iNOS) expression.

  20. Nitric oxide dioxygenase: An enzymic function for flavohemoglobin

    PubMed Central

    Gardner, Paul R.; Gardner, Anne M.; Martin, Lori A.; Salzman, Andrew L.

    1998-01-01

    Nitric oxide (NO•) is a toxin, and various life forms appear to have evolved strategies for its detoxification. NO•-resistant mutants of Escherichia coli were isolated that rapidly consumed NO•. An NO•-converting activity was reconstituted in extracts that required NADPH, FAD, and O2, was cyanide-sensitive, and produced NO3−. This nitric oxide dioxygenase (NOD) contained 19 of 20 N-terminal amino acids identical to those of the E. coli flavohemoglobin. Furthermore, NOD activity was produced by the flavohemoglobin gene and was inducible by NO•. Flavohemoglobin/NOD-deficient mutants were also sensitive to growth inhibition by gaseous NO•. The results identify a function for the evolutionarily conserved flavohemoglobins and, moreover, suggest that NO• detoxification may be a more ancient function for the widely distributed hemoglobins, and associated methemoglobin reductases, than dioxygen transport and storage. PMID:9724711

  1. Bactericidal efficacy of nitric oxide-releasing silica nanoparticles

    PubMed Central

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

    2013-01-01

    The utility of nitric oxide (NO)-releasing silica nanoparticles as a novel antibacterial is demonstrated against Pseudomonas aeruginosa. Nitric oxide-releasing nanoparticles were prepared via co-condensation of tetraalkoxysilane with aminoalkoxysilane modified with diazeniumdiolate NO donors, allowing for the storage of large NO payloads. Comparison of the bactericidal efficacy of the NO-releasing nanoparticles to 1-[2-(carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolate (PROLI/NO), a small molecule NO donor, demonstrated enhanced bactericidal efficacy of nanoparticle-derived NO and reduced cytotoxicity to healthy cells (mammalian fibroblasts). Confocal microscopy revealed that fluorescently-labeled NO-releasing nanoparticles associated with the bacteria, providing rationale for the enhanced bactericidal efficacy of the nanoparticles. Intracellular NO concentrations were measurable when the NO was delivered from nanoparticles as opposed to PROLI/NO. Collectively, these results demonstrate the advantage of delivering NO via nanoparticles for antimicrobial applications. PMID:19206623

  2. Nitric oxide: considerations for the treatment of ischemic stroke

    PubMed Central

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

    2012-01-01

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

  3. Nitric oxide in the upper stratosphere - Measurements and geophysical interpretation

    NASA Technical Reports Server (NTRS)

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

    1983-01-01

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

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

    PubMed Central

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

    1994-01-01

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

  5. Diazeniumdiolated carbamates: A novel class of nitric oxide donors

    PubMed Central

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

    2012-01-01

    We report an indirect method for synthesis of previously inaccessible diazeniumdiolated carbamates. Synthesis involves use of previously reported triisopropylsilyloxymethylated isopropylamine diazeniumdiolate (TOM-ylated IPA/NO). These novel diazeniumdiolated carbamate prodrugs upon activation release nitric oxide (NO) similar to their secondary amine counterparts. They are also efficient sources of intracellular NO. These prodrugs may have potential applications as therapeutic NO-donors. PMID:22356735

  6. Regulation of nitric oxide synthesis by dimethylarginine dimethylaminohydrolase.

    PubMed Central

    MacAllister, R. J.; Parry, H.; Kimoto, M.; Ogawa, T.; Russell, R. J.; Hodson, H.; Whitley, G. S.; Vallance, P.

    1996-01-01

    1. Dimethylarginine dimethylaminohydrolase (DDAH), an enzyme that metabolizes the endogenous nitric oxide synthase inhibitors NG-monomethyl-arginine and NG,NG-dimethy-L-arginine to citrulline, was identified by Western blotting in rat and human tissue homogenates. 2. S-2-amino-4(3-methylguanidino)butanoic acid (4124W) inhibited the metabolism of [14C]-NG-monomethyl-L-arginine to [14C]-citrulline by rat liver homogenates (IC50 416 +/- 66 microM; n = 9), human cultured endothelial cells (IC50 250 +/- 34 microM; n = 9) and isolated purified dimethylarginine dimethylaminohydrolase. 3. Addition of 4124W to culture medium increased the accumulation of endogenously-generated NG,NG-dimethy-L-arginine in the supernatant of human cultured endothelial cells from 3.1 +/- 0.3 to 5 +/- 0.7 microM (n = 15; P < 0.005). 4. 4124W (1 microM - 1 mM) had no direct effect on endothelial nitric oxide synthase activity but caused endothelium-dependent contraction of rat aortic rings (1 mM 4124W increased tone by 81.5 +/- 9.6% of that caused by phenylephrine 100 nM). This effect was reversed by L-arginine (100 microM). 4124W reversed endothelium-dependent relaxation of human saphenous vein (19.2 +/- 6.7% reversal of bradykinin-induced relaxation at 1 mM 4124W). 5. These data suggest that inhibition of dimethylarginine dimethylaminohydrolase increases the intracellular contraction of NG,NG-dimethyl-L-arginine sufficiently to inhibit nitric oxide synthesis. Inhibiting the activity of DDAH may provide an alternative mechanism for inhibition of nitric oxide synthases and changes in the activity of DDAH could contribute to pathophysiological alterations in NO generation. Images Figure 1 Figure 2 Figure 3 PMID:8982498

  7. Application of a Nitric Oxide Sensor in Biomedicine

    PubMed Central

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

    2014-01-01

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

  8. Nitric oxide: a physiologic mediator of penile erection.

    PubMed

    Burnett, A L; Lowenstein, C J; Bredt, D S; Chang, T S; Snyder, S H

    1992-07-17

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

  9. Nitric oxide production in plants: facts and fictions.

    PubMed

    Planchet, Elisabeth; Kaiser, Werner M

    2006-03-01

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

  10. Tuning the nitric oxide release from CPO-27 MOFs.

    PubMed

    Cattaneo, Damiano; Warrender, Stewart J; Duncan, Morven J; Kelsall, Christopher J; Doherty, Mary K; Whitfield, Phillip D; Megson, Ian L; Morris, Russell E

    2016-02-13

    Nitric oxide (NO) storage and release measurements have been recorded for Ni-doped CPO-27 (Mg) and CPO-27 (Zn), and the biological effect of the released NO was assessed in porcine coronary artery relaxation tests. The results indicate that the doping strategy leads to increased levels of NO storage and delivery compared to the parent materials and that the NO dosage and biological response can be tuned via this approach to suit the requirements of particular applications.

  11. [Recommendations for inhaled nitric oxide treatment in the newborn diseases].

    PubMed

    2001-09-01

    The recommendations in this document highlight current indications for inhaled nitric oxide (iNO) treatment in the newborn by clearly differentiating between those that are supported by scientific evidence and those for which evidence is still lacking. However, the use of this treatment in preterm infants and in those with congenital heart disease has not yet been scientifically approved. We discuss the methodology, dosage and adverse effects of iNO administration, as well as the reasons for its ineffectiveness.

  12. [Recommendations for inhaled nitric oxide treatment in the newborn].

    PubMed

    Figueras Aloy, J; Castillo Salinas, F; Elorza Fernández, D; Sánchez-Luna, M; Pérez Rodríguez, J

    2006-03-01

    The recommendations in this document describe the current indications for inhaled nitric oxide (iNO) treatment in the newborn and clearly distinguish between those supported by scientific evidence and those for which evidence is still lacking, such as its use in preterm infants. The methodology for iNO administration, its dosage and the main secondary effects are discussed, and the reasons for lack of response to this treatment are analyzed.

  13. The response of thermospheric nitric oxide to an auroral storm

    SciTech Connect

    Siskind, D.E.

    1988-01-01

    The response of thermospheric nitric oxide (NO) to the auroral storm of September 19, 1984 is analyzed. Measurements of nitric oxide from the Solar Mesosphere Explorer (SME) ultraviolet spectrometer are compared with the calculations of a one-dimensional photochemical model of the lower thermosphere. The NCAR Thermospheric General Circulation Model (TGCM) is used to calculate the response of the background neutral atmosphere to auroral forcings such as Joule and particle heating. The output of the TGCM is used as input to the photochemical model. The time history of the auroral energy input is assessed using particle data from the NOAA 6 and 7 satellites. The SME NO measurements were made from 100 km to 140 km along two orbital tracks: one over the United States and one over Europe. The observations show a factor of 3 increase in NO at auroral latitudes for both orbits as a result of the storm. Nitric oxide at mid-latitudes also increased by a factor of 3 but only over the United States. Calculations of the mid-latitude NO response show that temperature increases which result from Joule heating lead to NO enhancements. A larger response is initially seen for altitudes greater than 120 km.

  14. Defective nitric oxide production by alveolar macrophages during Pneumocystis pneumonia.

    PubMed

    Lasbury, Mark E; Liao, Chung-Ping; Hage, Chadi A; Durant, Pamela J; Tschang, Dennis; Wang, Shao-Hung; Zhang, Chen; Lee, Chao-Hung

    2011-04-01

    The effect of nitric oxide (NO) on Pneumocystis (Pc) organisms, the role of NO in the defense against infection with Pc, and the production of NO by alveolar macrophages (AMs) during Pneumocystis pneumonia (PCP) were investigated. The results indicate that NO was toxic to Pc organisms and inhibited their proliferation in culture. When the production of NO was inhibited by intraperitoneal injection of rats with the nitric oxide synthase inhibitor L-N(5)-(1-iminoethyl) ornithine, progression of Pc infection in immunocompetent rats was enhanced. Concentrations of NO in bronchoalveolar lavage fluids from immunosuppressed, Pc-infected rats and mice were greatly reduced, compared with those from uninfected animals, and AMs from these animals were defective in NO production. However, inducible nitric oxide synthase (iNOS) mRNA and protein concentrations were high in AMs from Pc-infected rats and mice. Immunoblot analysis showed that iNOS in AMs from Pc-infected rats existed primarily as a monomer, but the homo-dimerization of iNOS monomers was required for the production of NO. When iNOS dimerization cofactors, including calmodulin, were added to macrophage lysates, iNOS dimerization increased, whereas incubation of the same lysates with all cofactors except calmodulin did not rescue iNOS dimer formation. These data suggest that NO is important in the defense against Pc infection, but that the production of NO in AMs during PCP is defective because of the reduced dimerization of iNOS.

  15. [Measurement of exhaled nitric oxide in healthy Chinese].

    PubMed

    Zhang, Luo; Luo, Xue-rui; Liu, Cheng-yao; Zhao, Yan; Han, De-min

    2009-04-01

    To obtain the normal values of nitric oxide (NO) exhaled through nose and mouth in healthy Chinese adults by measuring exhaled NO and analyzing the influencing factors. Eighty healthy Chinese adults were recruited, including 20 males and 60 females. The age ranged from 18 to 44 years old. Chemiluminescence analyzer (NIOX) was used to obtain the values of exhaled NO through nose and mouth. The relativity between NO and gender, age, height, body mass index, time, ambient NO were analyzed with Multiple linear regression and correlation. Exhaled NO values were (17+/-8)x10(-9) and correlated significantly with height. Regression equation: Y (exhaled nitric oxide)=-58.524+0.457X (height, cm), t=-2.985, P<0.01. Transnasal NO values were (819+/-211)x10(-9) and correlated significantly with age and gender. Regression equation: Y (nasal nitric oxide)=760.245+9.417X1(age)-111.222X2(gender), t=5.188, P<0.01. Exhaled NO normal values were 17x10(-9) and Transnasal NO normal values were 819x10(-9). Exhaled NO correlated positively with height. Transnasal NO correlated positively with age and negatively with gender.

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

    PubMed Central

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

    2015-01-01

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

  17. Cytokine and nitric oxide production following severe envenomation.

    PubMed

    Petricevich, Vera L

    2004-09-01

    Venom is a complex mixture of many substances such as toxins, enzymes, growth factor activators, and inhibitors are particularly responsible for the deleterious effects of cells. These constituents interact in the body with a large number of proteins and receptors, and this interaction determines the eventual inflammatory effect of the compounds. Envenomation by bees, scorpions, snakes, spiders and wasps involves the activation of the inflammatory response with the release and activation of pro-inflammatory cytokines and other mediators, such as nitric oxide. Recently, a battery of cytokines produced by activated T cells or macrophages have been added to in envenomations. Cytokines are important for the interactions between cells in the immune and inflammatory responses. Although the pathophysiology of envenomation is not fully understood, venom and immune responses are known to trigger the release of cytokines and nitric oxide. The cytokines initiate a cascade of events that lead to illness behaviors such as fever, anorexia, and, as well as a host of physiologic events such as activation of vasodilation, hypotension and increased nitric oxide production. Accumulating evidence indicates that these cytokines play important roles in mediating cell recruitment and activation necessary for inflammation and the repair of tissue damage. A better understanding of the involvement of the inflammatory system in different envenoming syndromes may have future therapeutic benefits.

  18. Evaluation of oxidative stress and nitric oxide levels in patients with oral cavity cancer.

    PubMed

    Beevi, S Syed Sultan; Rasheed, A Muzib Hassanal; Geetha, A

    2004-07-01

    The aim of this study was to evaluate the magnitude of oxidative stress and levels of nitric oxide in patients with oral cavity cancer by analyzing the levels of lipid peroxidation products, antioxidants and nitric oxide products. This prospective study was conducted on 15 patients with biopsy proven squamous cell cancer of the oral cavity with clinical stage III/IV and an equal number of age and sex matched healthy subjects. The levels of lipid peroxidation products, antioxidants and nitric oxide products were determined by colorimetric methods. Lipid peroxidation products like lipid hydroperoxide (LHP) and malondialdehyde (MDA) and nitric oxide products like nitrite (NO(2)(-)), nitrate (NO(3)(-)) and total nitrite (TNO(2)(-)) were significantly elevated, whereas enzymatic and non-enzymatic antioxidants were significantly lowered in oral cavity cancer patients when compared to normal healthy subjects. Enhanced lipid peroxidation with concomitant decrease in antioxidants is indicative of oxidative stress that provides evidence of the relationship between lipid peroxidation and oral cavity cancer. Increased nitric oxide production represents a general mechanism in its pathogenesis.

  19. Basal nitric oxide production is enhanced by hydraulic pressure in cultured human trabecular cells

    PubMed Central

    Matsuo, T.

    2000-01-01

    BACKGROUND/AIMS—Nitric oxide donors reduce intraocular pressure. Human trabecular cells in culture were examined for their nitric oxide production in response to hydraulic pressure.
METHODS—Human trabecular cells were cultured from trabeculum tissue fragments excised during trabeculectomy and exposed to hydraulic pressure change in a culture flask connected to a glass syringe. The pressure was exerted by automatic infusion of the piston of the syringe and monitored by a pressure gauge. The intracellular nitric oxide level was measured in real time with a nitric oxide binding fluorescent dye, diaminofluorescein-2.
RESULTS—Intracellular nitric oxide levels in cultured trabecular cells showed spontaneous fluctuation during 400 seconds of observation. Peak levels of intracellular nitric oxide were significantly higher at hydraulic pressure of 30, 40, and 50 mm Hg, compared with 0 and 25 mm Hg (p<0.0001, one way ANOVA, and p<0.05, Tukey-Kramer test). The fluctuation was completely abolished by the presence of N-methyl-L-arginine (L-NMMA), a nitric oxide synthase inhibitor. The cultured trabecular cells were shown by immunohistochemistry to express brain nitric oxide synthase (bNOS).
CONCLUSION—Higher levels of hydraulic pressure enhanced basal production of nitric oxide in human trabecular cells. Nitric oxide would be a physiological mediator in the regulation of intraocular pressure.

 PMID:10837391

  20. Nitric oxide regulation of calcitonin gene-related peptide gene expression in rat trigeminal ganglia neurons

    PubMed Central

    Bellamy, Jamie; Bowen, Elizabeth J.; Russo, Andrew F.; Durham, Paul L.

    2006-01-01

    Calcitonin gene-related peptide (CGRP) and nitric oxide are involved in the underlying pathophysiology of migraine and other diseases involving neurogenic inflammation. We have tested the hypothesis that nitric oxide might trigger signaling mechanisms within the trigeminal ganglia neurons that would coordinately stimulate CGRP synthesis and release. Treatment of primary trigeminal ganglia cultures with nitric oxide donors caused a greater than four-fold increase in CGRP release compared with unstimulated cultures. Similarly, CGRP promoter activity was also stimulated by nitric oxide donors and overexpression of inducible nitric oxide synthase (iNOS). Cotreatment with the antimigraine drug sumatriptan greatly repressed nitric oxide stimulation of CGRP promoter activity and secretion. Somewhat surprisingly, the mechanisms of nitric oxide stimulation of CGRP secretion did not require cGMP or PI3-kinase signaling pathways, but rather, nitric oxide action required extracellular calcium and likely involves T-type calcium channels. Furthermore, nitric oxide was shown to increase expression of the active forms of the mitogen-activated protein kinases Jun amino-terminal kinase and p38 but not extracellular signal-related kinase in trigeminal neurons. In summary, our results provide new insight into the cellular mechanisms by which nitric oxide induces CGRP synthesis and secretion from trigeminal neurons. PMID:16630053

  1. Effects of nitric oxide on magnocellular neurons of the supraoptic nucleus involve multiple mechanisms

    PubMed Central

    da Silva, M.P.; Cedraz-Mercez, P.L.; Varanda, W.A.

    2014-01-01

    Physiological evidence indicates that the supraoptic nucleus (SON) is an important region for integrating information related to homeostasis of body fluids. Located bilaterally to the optic chiasm, this nucleus is composed of magnocellular neurosecretory cells (MNCs) responsible for the synthesis and release of vasopressin and oxytocin to the neurohypophysis. At the cellular level, the control of vasopressin and oxytocin release is directly linked to the firing frequency of MNCs. In general, we can say that the excitability of these cells can be controlled via two distinct mechanisms: 1) the intrinsic membrane properties of the MNCs themselves and 2) synaptic input from circumventricular organs that contain osmosensitive neurons. It has also been demonstrated that MNCs are sensitive to osmotic stimuli in the physiological range. Therefore, the study of their intrinsic membrane properties became imperative to explain the osmosensitivity of MNCs. In addition to this, the discovery that several neurotransmitters and neuropeptides can modulate their electrical activity greatly increased our knowledge about the role played by the MNCs in fluid homeostasis. In particular, nitric oxide (NO) may be an important player in fluid balance homeostasis, because it has been demonstrated that the enzyme responsible for its production has an increased activity following a hypertonic stimulation of the system. At the cellular level, NO has been shown to change the electrical excitability of MNCs. Therefore, in this review, we focus on some important points concerning nitrergic modulation of the neuroendocrine system, particularly the effects of NO on the SON. PMID:24519124

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

    PubMed

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

    2014-11-01

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

  3. Extracellular nitric oxide signaling in the hamster biological clock.

    PubMed

    Plano, Santiago A; Agostino, Patricia V; Golombek, Diego A

    2007-11-27

    Nocturnal light pulses induce phase shifts in circadian rhythms and activate cFos expression in the suprachiasmatic nuclei (SCN). We have studied the role of nitric oxide (NO) in the intercellular communication within the dorsal and ventral portions of the SCN in Syrian hamsters. Administration of the NO scavenger 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide blocked photic phase advances in a dose-dependent manner and inhibited light-induced cFos-ir, without affecting light-induced circadian phase delays. These results suggest that NO may act as an intercellular messenger in the SCN, mediating light-induced phase advances.

  4. L-citrulline immunostaining identifies nitric oxide production sites within neurons.

    PubMed

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

    2002-01-01

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

  5. L-citrulline immunostaining identifies nitric oxide production sites within neurons

    NASA Technical Reports Server (NTRS)

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

    2002-01-01

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

  6. Inhibition of in vivo leishmanicidal mechanisms by tempol: nitric oxide down-regulation and oxidant scavenging.

    PubMed

    Linares, Edlaine; Giorgio, Selma; Augusto, Ohara

    2008-04-15

    Tempol (4-hydroxy-2,2,6,6-tetramethyl-1-piperidinyloxy) has long been known to protect experimental animals from the injury associated with oxidative and inflammatory conditions. In the latter case, a parallel decrease in tissue protein nitration levels has been observed. Protein nitration represents a shift in nitric oxide actions from physiological to pathophysiological and potentially damaging pathways involving its derived oxidants such as nitrogen dioxide and peroxynitrite. In infectious diseases, protein tyrosine nitration of tissues and cells has been taken as evidence for the involvement of nitric oxide-derived oxidants in microbicidal mechanisms. To examine whether tempol inhibits the microbicidal action of macrophages, we investigated its effects on Leishmania amazonensis infection in vitro (RAW 264.7 murine macrophages) and in vivo (C57Bl/6 mice). Tempol was administered in the drinking water at 2 mM throughout the experiments and shown to reach infected footpads as the nitroxide plus the hydroxylamine derivative by EPR analysis. At the time of maximum infection (6 weeks), tempol increased footpad lesion size (120%) and parasite burden (150%). In lesion extracts, tempol decreased overall nitric oxide products and expression of inducible nitric oxide synthase to about 80% of the levels in control animals. Nitric oxide-derived products produced by radical mechanisms, such as 3-nitrotyrosine and nitrosothiol, decreased to about 40% of the levels in control mice. The results indicate that tempol worsened L. amazonensis infection by a dual mechanism involving down-regulation of iNOS expression and scavenging of nitric oxide-derived oxidants. Thus, the development of therapeutic strategies based on nitroxides should take into account the potential risk of altering host resistance to parasite infection.

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

    SciTech Connect

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

    2015-03-13

    As the core structure of flavonoids, flavone has been proved to possess anticancer effects. Flavone's growth inhibitory functions are related to NO. NO is synthesized by nitric oxide synthase (NOS), and generally increased in a variety of cancer cells. NO regulates multiple cellular responses by S-nitrosylation. In this study, we explored flavone-induced regulations on nitric oxide (NO)-related cellular processes in breast cancer cells. Our results showed that, flavone suppresses breast cancer cell proliferation and induces apoptosis. Flavone restrains NO synthesis by does-dependent inhibiting NOS enzymatic activity. The decrease of NO generation was detected by fluorescence microscopy and flow cytometry. Flavone-induced inhibitory effect on NOS activity is dependent on intact cell structure. For the NO-induced protein modification, flavone treatment significantly down-regulated protein S-nitrosylation, which was detected by “Biotin-switch” method. The present study provides a novel, NO-related mechanism for the anticancer function of flavone. - Highlights: • Flavone inhibits proliferation and induces apoptosis in MCF-7 cells. • Flavone decreases nitric oxide production by inhibiting NOS enzymatic activity in breast cancer cells. • Flavone down-regulates protein S-nitrosylation.

  8. Correction of hypertension by normalization of endothelial levels of fibroblast growth factor and nitric oxide synthase in spontaneously hypertensive rats.

    PubMed Central

    Cuevas, P; García-Calvo, M; Carceller, F; Reimers, D; Zazo, M; Cuevas, B; Muñoz-Willery, I; Martínez-Coso, V; Lamas, S; Giménez-Gallego, G

    1996-01-01

    Acidic and basic fibroblast growth factors (FGFs) share a wide range of diverse biological activities. To date, low levels of FGF have not been correlated with a pathophysiologic state. We report that blood vessels of spontaneously hypertensive rats are shown to be associated with a marked decrement in endothelial basic FGF content. This decrement correlates both with hypertension and with a decrease in the endothelial content of nitric oxide synthase. Restoration of FGF to physiological levels in the vascular wall, either by systemic administration or by in vivo gene transfer, significantly augmented the number of endothelial cells with positive immunostaining for nitric oxide synthase, corrected hypertension, and ameliorated endothelial-dependent responses to vasoconstrictors. These results suggest an important role for FGFs in blood pressure homeostasis and open new avenues for the understanding of the etiology and treatment of hypertension. Images Fig. 2 Fig. 4 PMID:8876251

  9. Correction of Hypertension by Normalization of Endothelial Levels of Fibroblast Growth Factor and Nitric Oxide Synthase in Spontaneously Hypertensive Rats

    NASA Astrophysics Data System (ADS)

    Cuevas, Pedro; Garcia-Calvo, Margarita; Carceller, Fernando; Reimers, Diana; Zazo, Mercedes; Cuevas, Begona; Munoz-Willery, Isabel; Martinez-Coso, Victoria; Lamas, Santiago; Gimenez-Gallego, Guillermo

    1996-10-01

    Acidic and basic fibroblast growth factors (FGFs) share a wide range of diverse biological activities. To date, low levels of FGF have not been correlated with a pathophysiologic state. We report that blood vessels of spontaneously hypertensive rats are shown to be associated with a marked decrement in endothelial basic FGF content. This decrement correlates both with hypertension and with a decrease in the endothelial content of nitric oxide synthase. restoration of FGF to physiological levels in the vascular wall, either by systemic administration or by in vivo gene transfer, significantly augmented the number of endothelial cells with positive immunostaining for nitric oxide synthase, corrected hypertension, and ameliorated endothelial-dependent responses to vasoconstrictors. These results suggest an important role for FGFs in blood pressure homeostasis and open new avenues for the understanding of the etiology and treatment of hypertension.

  10. Correction of hypertension by normalization of endothelial levels of fibroblast growth factor and nitric oxide synthase in spontaneously hypertensive rats.

    PubMed

    Cuevas, P; García-Calvo, M; Carceller, F; Reimers, D; Zazo, M; Cuevas, B; Muñoz-Willery, I; Martínez-Coso, V; Lamas, S; Giménez-Gallego, G

    1996-10-15

    Acidic and basic fibroblast growth factors (FGFs) share a wide range of diverse biological activities. To date, low levels of FGF have not been correlated with a pathophysiologic state. We report that blood vessels of spontaneously hypertensive rats are shown to be associated with a marked decrement in endothelial basic FGF content. This decrement correlates both with hypertension and with a decrease in the endothelial content of nitric oxide synthase. Restoration of FGF to physiological levels in the vascular wall, either by systemic administration or by in vivo gene transfer, significantly augmented the number of endothelial cells with positive immunostaining for nitric oxide synthase, corrected hypertension, and ameliorated endothelial-dependent responses to vasoconstrictors. These results suggest an important role for FGFs in blood pressure homeostasis and open new avenues for the understanding of the etiology and treatment of hypertension.

  11. How the location of superoxide generation influences the β-cell response to nitric oxide.

    PubMed

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

    2015-03-20

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

  12. Endothelial nitric oxide synthase: From biochemistry and gene structure to clinical implications of NOS3 polymorphisms.

    PubMed

    Oliveira-Paula, Gustavo H; Lacchini, Riccardo; Tanus-Santos, Jose E

    2016-01-10

    Nitric oxide (NO) is an important vasodilator with a well-established role in cardiovascular homeostasis. While mediator is synthesized from L-arginine by neuronal, endothelial, and inducible nitric oxide synthases (NOS1,NOS3 and NOS2 respectively), NOS3 is the most important isoform for NO formation in the cardiovascular system. NOS3 is a dimeric enzyme whose expression and activity are regulated at transcriptional, posttranscriptional,and posttranslational levels. The NOS3 gene, which encodes NOS3, exhibits a number of polymorphic sites including single nucleotide polymorphisms (SNPs), variable number of tandem repeats (VNTRs), microsatellites, and insertions/deletions. Some NOS3 polymorphisms show functional effects on NOS3 expression or activity, thereby affecting NO formation. Interestingly, many studies have evaluated the effects of functional NOS3 polymorphisms on disease susceptibility and drug responses. Moreover, some studies have investigated how NOS3 haplotypes may impact endogenous NO formation and disease susceptibility. In this article,we carried out a comprehensive review to provide a basic understanding of biochemical mechanisms involved in NOS3 regulation and how genetic variations in NOS3 may translate into relevant clinical and pharmacogenetic implications.

  13. Nitric oxide, interorganelle communication, and energy flow: a novel route to slow aging

    PubMed Central

    Valerio, Alessandra; Nisoli, Enzo

    2015-01-01

    The mitochondrial lifecycle (mitochondrial biogenesis, dynamics, and removal by mitophagy) is carefully orchestrated to ensure the efficient generation of cellular energy and to maintain reactive oxygen species (ROS) production within an optimal range for cellular health. Based on latest research, these processes largely depend on mitochondrial interactions with other cell organelles, so that the ER- and peroxisome-mitochondrial connections might intervene in the control of cellular energy flow. Damaged organelles are cleared by autophagic mechanisms to assure the quality and proper function of the intracellular organelle pool. Nitric oxide (NO) generated through the endothelial nitric oxide synthase (eNOS) acts a gas signaling mediator to promote mitochondrial biogenesis and bioenergetics, with a favorable impact in diverse chronic diseases of the elderly. Obesity, diabetes and aging share common pathophysiological mechanisms, including mitochondrial impairment and dysfunctional eNOS. Here we review the evidences that eNOS-dependent mitochondrial biogenesis and quality control, and possibly the complex interplay among cellular organelles, may be affected by metabolic diseases and the aging processes, contributing to reduce healthspan and lifespan. Drugs or nutrients able to sustain the eNOS-NO generating system might contribute to maintain organelle homeostasis and represent novel preventive and/or therapeutic approaches to chronic age-related diseases. PMID:25705617

  14. Post-Translational Modification of Constitutive Nitric Oxide Synthase in the Penis

    PubMed Central

    Musicki, Biljana; Ross, Ashley E.; Champion, Hunter C.; Burnett, Arthur L.; Bivalacqua, Trinity J.

    2009-01-01

    Erectile dysfunction (ED) is a common men's health problem characterized by the consistent inability to sustain an erection sufficient for sexual intercourse. Basic science research on erectile physiology has been devoted to investigating the pathogenesis of ED and has led to the conclusion that ED is predominately a disease of vascular origin and/or neurogenic dysfunction. The constitutive forms of nitric oxide synthase [NOS; endothelial NOS (eNOS) and neuronal NOS (nNOS)] are important enzymes involved in the production of nitric oxide (NO) and thus regulate penile vascular homeostasis. Given the impact of endothelial- and neuronal-derived NO in penile vascular biology, a great deal of research over the past decade has focused on the role of NO synthesis from the endothelium and nitrergic nerve terminal in normal erectile physiology as well as in disease states. Loss of the functional integrity of the endothelium and subsequent endothelial dysfunction plays an integral role in the occurrence of ED. Therefore, molecular mechanisms involved in dysregulation of these NOS isoforms in the development of ED are essential to discovering the pathogenesis of ED in various disease states. This communication reviews the role of eNOS and nNOS in erectile physiology and discusses the alterations in eNOS and nNOS via post-translation modification in various vascular diseases of the penis. PMID:19342700

  15. Nitric oxide. A general review about the different roles of this innocent radical.

    PubMed

    Gentiloni Silveri, N; Mazzone, M; Portale, G; Carbone, L

    2001-06-01

    Nitric oxide, a short half-life radical, is highly reactive, and it is involved in many biological processes, such as vascular homeostasis, neurotransmission, and inflammation, defined as a sequence of events which can be simplified as follows: vasodilatation, alteration of vascular permeability, emigration of leucocytes from vessels, migration of leucocytes into the sites of tissutal damages or inflammation, activation of leucocyte mechanisms. This review has a double purpose: 1) to provide a comprehensive table of cell types that produce NO, together with the effects of agents used to study iNOS regulation; 2) to investigate the role of NO in different human systems. The different relations between NO and cytokines, the heart, infectious diseases, inflammatory diseases, brain cells and, lastly, gastrointestinal diseases are examined.

  16. Role of nitric oxide and hydrogen peroxide during the salt resistance response.

    PubMed

    Zhang, Feng; Wang, Yuping; Wang, Di

    2007-11-01

    Ion homeostasis is essential for plant cell resistance to salt stress. Under salt stress, to avoid cellular damage and nutrient deficiency, plant cells need to maintain adequate K nutrition and a favorable K to Na ratio in the cytosol. Recent observations revealed that both nitric oxide (NO) and hydrogen peroxide (H(2)O(2)) act as signaling molecules to regulate K to Na ratio in calluses from Populus euphratica under salt stress. Evidence indicated that NO mediating H(2)O(2) causes salt resistance via the action of plasma membrane H(+)-ATPase but that activity of plasma membrane NADPH oxidase is dependent on NO. Our study demonstrated the signaling transduction pathway. In this addendum, we proposed a testable hypothesis for NO function in regulation of H(2)O(2) mediating salt resistance.

  17. S-nitrosothiols regulate nitric oxide production and storage in plants through the nitrogen assimilation pathway

    PubMed Central

    Frungillo, Lucas; Skelly, Michael J.; Loake, Gary J.; Spoel, Steven H.; Salgado, Ione

    2014-01-01

    Nitrogen assimilation plays a vital role in plant metabolism. Assimilation of nitrate, the primary source of nitrogen in soil, is linked to generation of the redox signal nitric oxide (NO). An important mechanism by which NO regulates plant development and stress responses is through S-nitrosylation, i.e. covalent attachment of NO to cysteines to form S-nitrosothiols (SNO). Despite the importance of nitrogen assimilation and NO signalling, it remains largely unknown how these pathways are interconnected. Here we show that SNO signalling suppresses both nitrate uptake and reduction by transporters and reductases, respectively, to fine-tune nitrate homeostasis. Moreover, NO derived from nitrate assimilation suppresses the redox enzyme S-nitrosoglutathione Reductase 1 (GSNOR1) by S-nitrosylation, preventing scavenging of S-nitrosoglutathione, a major cellular bio-reservoir of NO. Hence, our data demonstrates that (S)NO controls its own generation and scavenging by modulating nitrate assimilation and GSNOR1 activity. PMID:25384398

  18. The pivotal role of nitric oxide: effects on the nervous and immune systems.

    PubMed

    Banuls, Celia; Rocha, Milagros; Rovira-Llopis, Susana; Falcon, Rosa; Castello, Raquel; Herance, Jose R; Polo, Miriam; Blas-Garcia, Ana; Hernandez-Mijares, Antonio; Victor, Victor M

    2014-01-01

    Nitric oxide (NO) has an important role in physiological and pathological processes in general, and in particular plays a homeostatic role in the nervous and immune systems. The many different physiological functions of NO include those of a mediator of blood vessel dilation, neurotransmitter, neuromodulator and inductor of mitochondrial biogenesis. In addition, NO can transform into highly reactive and harmful molecules producing an impairment of the DNA, lipids or proteins, and thus altering their function. This dual action of NO, by which it plays an important role in homeostasis and aids the development of pathological processes, makes this molecule an interesting target for medical therapies, especially with respect to the nervous and immune systems. This review describes the multiple roles of NO played out in the nervous and immune systems during different physiological and pathophysiological processes.

  19. Polymer-Based Nitric Oxide Therapies: Recent Insights for Biomedical Applications

    PubMed Central

    Jen, Michele C.; Serrano, María C.; van Lith, Robert

    2014-01-01

    Since the discovery of nitric oxide (NO) in the 1980s, this cellular messenger has been shown to participate in diverse biological processes such as cardiovascular homeostasis, immune response, wound healing, bone metabolism, and neurotransmission. Its beneficial effects have prompted increased research in the past two decades, with a focus on the development of materials that can locally release NO. However, significant limitations arise when applying these materials to biomedical applications. This Feature Article focuses on the development of NO-releasing and NO-generating polymeric materials (2006–2011) with emphasis on recent in vivo applications. Results are compared and discussed in terms of NO dose, release kinetics, and biological effects, in order to provide a foundation to design and evaluate new NO therapies. PMID:25067935

  20. S-nitrosothiols regulate nitric oxide production and storage in plants through the nitrogen assimilation pathway.

    PubMed

    Frungillo, Lucas; Skelly, Michael J; Loake, Gary J; Spoel, Steven H; Salgado, Ione

    2014-11-11

    Nitrogen assimilation plays a vital role in plant metabolism. Assimilation of nitrate, the primary source of nitrogen in soil, is linked to the generation of the redox signal nitric oxide (NO). An important mechanism by which NO regulates plant development and stress responses is through S-nitrosylation, that is, covalent attachment of NO to cysteine residues to form S-nitrosothiols (SNO). Despite the importance of nitrogen assimilation and NO signalling, it remains largely unknown how these pathways are interconnected. Here we show that SNO signalling suppresses both nitrate uptake and reduction by transporters and reductases, respectively, to fine tune nitrate homeostasis. Moreover, NO derived from nitrate assimilation suppresses the redox enzyme S-nitrosoglutathione Reductase 1 (GSNOR1) by S-nitrosylation, preventing scavenging of S-nitrosoglutathione, a major cellular bio-reservoir of NO. Hence, our data demonstrates that (S)NO controls its own generation and scavenging by modulating nitrate assimilation and GSNOR1 activity.

  1. Modulation of nitric oxide synthase activity in macrophages

    PubMed Central

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

    1995-01-01

    L-Arginine is converted to the highly reactive and unstable nitric oxide (NO) and L-citrulline by an enzyme named nitric oxide synthase (NOS). NO decomposes into other nitrogen oxides such as nitrite (NO2-) and nitrate (NO2-), and in the presence of superoxide anion to the potent oxidizing agent peroxynitrite (ONOO−). Activated rodent macrophages are capable of expressing an inducible form of this enzyme (iNOS) in response to appropriate stimuli, i.e., lipopolysaccharide (LPS) and interferon-γ (IFNγ). Other cytokines can modulate the induction of NO biosynthesis in macrophages. NO is a major effector molecule of the anti-microbial and cytotoxic activity of rodent macrophages against certain micro-organisms and tumour cells, respectively. The NO synthesizing pathway has been demonstrated in human monocytes and other cells, but its role in host defence seems to be accessory. A delicate functional balance between microbial stimuli, host-derived cytokines and hormones in the microenvironment regulates iNOS expression. This review will focus mainly on the known and proposed mechanisms of the regulation of iNOS induction, and on agents that can modulate NO release once the active enzyme has been expressed in the macrophage. PMID:18475620

  2. The nitric oxide response in plant-associated endosymbiotic bacteria.

    PubMed

    Cabrera, Juan J; Sánchez, Cristina; Gates, Andrew J; Bedmar, Eulogio J; Mesa, Socorro; Richardson, David J; Delgado, María J

    2011-12-01

    Nitric oxide (NO) is a gaseous signalling molecule which becomes very toxic due to its ability to react with multiple cellular targets in biological systems. Bacterial cells protect against NO through the expression of enzymes that detoxify this molecule by oxidizing it to nitrate or reducing it to nitrous oxide or ammonia. These enzymes are haemoglobins, c-type nitric oxide reductase, flavorubredoxins and the cytochrome c respiratory nitrite reductase. Expression of the genes encoding these enzymes is controlled by NO-sensitive regulatory proteins. The production of NO in rhizobia-legume symbiosis has been demonstrated recently. In functioning nodules, NO acts as a potent inhibitor of nitrogenase enzymes. These observations have led to the question of how rhizobia overcome the toxicity of NO. Several studies on the NO response have been undertaken in two non-dentrifying rhizobial species, Sinorhizobium meliloti and Rhizobium etli, and in a denitrifying species, Bradyrhizobium japonicum. In the present mini-review, current knowledge of the NO response in those legume-associated endosymbiotic bacteria is summarized.

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

    NASA Astrophysics Data System (ADS)

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

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

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

    NASA Technical Reports Server (NTRS)

    Cabell, Karen F.; Rock, Kenneth E.

    2003-01-01

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

  5. Nitric oxide-releasing polymer incorporated ointment for cutaneous wound healing.

    PubMed

    Kang, Youngnam; Kim, Jihoon; Lee, Yeong Mi; Im, Sooseok; Park, Hansoo; Kim, Won Jong

    2015-12-28

    This work demonstrates the development of nitric oxide-releasing ointment and its potential on efficient wound healing. Nitric oxide-releasing polymer was successfully synthesized, which is composed of biocompatible Pluronic F127, branched polyethylenimine and 1-substituted diazen-1-ium-1,2-diolates. The synthesized nitric oxide-releasing polymer was incorporated into the PEG-based ointment which not only facilitated nitric oxide release in a slow manner, but also served as a moisturizer to enhance the wound healing. As compared to control groups, the nitric oxide-releasing ointment showed the accelerated wound closure with enhanced re-epithelialization, collagen deposition, and blood vessel formation in vivo. Therefore, this nitric oxide-based ointment presents the promising potential for the efficient strategy to heal the cutaneous wound.

  6. Nitrite-nitric oxide control of mitochondrial respiration at the frontier of anoxia.

    PubMed

    Benamar, Abdelilah; Rolletschek, Hardy; Borisjuk, Ljudmilla; Avelange-Macherel, Marie-Hélène; Curien, Gilles; Mostefai, H Ahmed; Andriantsitohaina, Ramaroson; Macherel, David

    2008-10-01

    Actively respiring animal and plant tissues experience hypoxia because of mitochondrial O(2) consumption. Controlling oxygen balance is a critical issue that involves in mammals hypoxia-inducible factor (HIF) mediated transcriptional regulation, cytochrome oxidase (COX) subunit adjustment and nitric oxide (NO) as a mediator in vasodilatation and oxygen homeostasis. In plants, NO, mainly derived from nitrite, is also an important signalling molecule. We describe here a mechanism by which mitochondrial respiration is adjusted to prevent a tissue to reach anoxia. During pea seed germination, the internal atmosphere was strongly hypoxic due to very active mitochondrial respiration. There was no sign of fermentation, suggesting a down-regulation of O(2) consumption near anoxia. Mitochondria were found to finely regulate their surrounding O(2) level through a nitrite-dependent NO production, which was ascertained using electron paramagnetic resonance (EPR) spin trapping of NO within membranes. At low O(2), nitrite is reduced into NO, likely at complex III, and in turn reversibly inhibits COX, provoking a rise to a higher steady state level of oxygen. Since NO can be re-oxidized into nitrite chemically or by COX, a nitrite-NO pool is maintained, preventing mitochondrial anoxia. Such an evolutionarily conserved mechanism should have an important role for oxygen homeostasis in tissues undergoing hypoxia.

  7. Caspase-mediated apoptosis in neuronal excitotoxicity triggered by nitric oxide.

    PubMed Central

    Leist, M.; Volbracht, C.; Kühnle, S.; Fava, E.; Ferrando-May, E.; Nicotera, P.

    1997-01-01

    BACKGROUND: Excitotoxicity and excess generation of nitric oxide (NO) are believed to be fundamental mechanisms in many acute and chronic neurodegenerative disorders. Disturbance of Ca2+ homeostasis and protein nitration/nitrosylation are key features in such conditions. Recently, a family of proteases collectively known as caspases has been implicated as common executor of a variety of death signals. In addition, overactivation of poly-(ADP-ribose) polymerase (PARP) has been observed in neuronal excitotoxicity. We therefore designed this study to investigate whether triggering of caspase activity and/or activation of PARP played a role in cerebellar granule cell (CGC) apoptosis elicited by peroxynitrite (ONOO-) or NO donors. MATERIALS AND METHODS: CGC from wild-type or PARP -/- mice were exposed to various nitric oxide donors. Caspase activation and its implications for membrane alterations, Ca2+ homeostasis, intracellular proteolysis, chromatin degradation, and cell death were investigated. RESULTS: CGC exposed to NO donors undergo apoptosis, which is mediated by excess synaptic release of excitotoxic mediators. This excitotoxic mechanism differs from direct NO toxicity in some other neuronal populations and does not involve PARP activation. Inhibition of caspases with different peptide substrates prevented cell death and the related features, including intracellular proteolysis, chromatin breakdown, and translocation of phosphatidylserine to the outer surface of the cell membrane. Increased Ca2+ influx following N-methyl-D-aspartate (NMDA) receptor (NMDA-R) activation was not inhibited by caspase inhibitors. CONCLUSIONS: In CGC, NO donors elicit apoptosis by a mechanism involving excitotoxic mediators, Ca2+ overload, and subsequent activation of caspases. Images Fig. 4 FIG. 5 FIG. 6 FIG. 7 PMID:9407551

  8. Increased brain nitric oxide levels following ethanol administration.

    PubMed

    Finnerty, Niall; O'Riordan, Saidhbhe L; Klamer, Daniel; Lowry, John; Pålsson, Erik

    2015-05-01

    Nitric oxide is a ubiquitous messenger molecule, which at elevated concentrations has been implicated in the pathogenesis of several neurological disorders. Its role in oxidative stress, attributed in particular to the formation of peroxynitrite, proceeds through its high affinity for the superoxide radical. Alcoholism has recently been associated with the induction of oxidative stress, which is generally defined as a shift in equilibrium between pro-oxidant and anti-oxidant species in the direction of the former. Furthermore, its primary metabolite acetaldehyde, has been extensively associated with oxidative damage related toxic effects following alcohol ingestion. The principal objective of this study was the application of long term in vivo electrochemistry (LIVE) to investigate the effect of ethanol (0.125, 0.5 and 2.0 g kg(-1)) and acetaldehyde (12.5, 50 and 200 mg kg(-1)) on NO levels in the nucleus accumbens of freely moving rats. Systemic administrations of ethanol and acetaldehyde resulted in a dose-dependent increases in NO levels, albeit with very differing time courses. Subsequent to this the effect on accumbal NO levels, of subjecting the animal to different drug combinations, was also elucidated. The nitric oxide synthase inhibitor L-NAME (20 mg kg(-1)) and acetaldehyde sequestering agent D-penicillamine (50 mg kg(-1)) both attenuated the increase in NO levels following ethanol (1 g kg(-1)) administration. Conversely, the alcohol dehydrogenase inhibitor 4-methylpyrazole (25 mg kg(-1)) and catalase inhibitor sodium azide (10 mg kg(-1)) potentiated the increase in NO levels following ethanol administration. Finally, dual inhibition of aldehyde dehydrogenase and catalase by cyanamide (25 mg kg(-1)) caused an attenuation of ethanol effects on NO levels. Taken together these data highlight a robust increase in brain NO levels following systemic alcohol administration which is dependent on NO synthase activity and may involve both alcohol- and acetaldehyde

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

    PubMed Central

    Hall, Catherine N; Attwell, David

    2008-01-01

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

  10. Cross-Regulation between N Metabolism and Nitric Oxide (NO) Signaling during Plant Immunity.

    PubMed

    Thalineau, Elise; Truong, Hoai-Nam; Berger, Antoine; Fournier, Carine; Boscari, Alexandre; Wendehenne, David; Jeandroz, Sylvain

    2016-01-01

    Plants are sessile organisms that have evolved a complex immune system which helps them cope with pathogen attacks. However, the capacity of a plant to mobilize different defense responses is strongly affected by its physiological status. Nitrogen (N) is a major nutrient that can play an important role in plant immunity by increasing or decreasing plant resistance to pathogens. Although no general rule can be drawn about the effect of N availability and quality on the fate of plant/pathogen interactions, plants' capacity to acquire, assimilate, allocate N, and maintain amino acid homeostasis appears to partly mediate the effects of N on plant defense. Nitric oxide (NO), one of the products of N metabolism, plays an important role in plant immunity signaling. NO is generated in part through Nitrate Reductase (NR), a key enzyme involved in nitrate assimilation, and its production depends on levels of nitrate/nitrite, NR substrate/product, as well as on L-arginine and polyamine levels. Cross-regulation between NO signaling and N supply/metabolism has been evidenced. NO production can be affected by N supply, and conversely NO appears to regulate nitrate transport and assimilation. Based on this knowledge, we hypothesized that N availability partly controls plant resistance to pathogens by controlling NO homeostasis. Using the Medicago truncatula/Aphanomyces euteiches pathosystem, we showed that NO homeostasis is important for resistance to this oomycete and that N availability impacts NO homeostasis by affecting S-nitrosothiol (SNO) levels and S-nitrosoglutathione reductase activity in roots. These results could therefore explain the increased resistance we noted in N-deprived as compared to N-replete M. truncatula seedlings. They open onto new perspectives for the studies of N/plant defense interactions.

  11. Cross-Regulation between N Metabolism and Nitric Oxide (NO) Signaling during Plant Immunity

    PubMed Central

    Thalineau, Elise; Truong, Hoai-Nam; Berger, Antoine; Fournier, Carine; Boscari, Alexandre; Wendehenne, David; Jeandroz, Sylvain

    2016-01-01

    Plants are sessile organisms that have evolved a complex immune system which helps them cope with pathogen attacks. However, the capacity of a plant to mobilize different defense responses is strongly affected by its physiological status. Nitrogen (N) is a major nutrient that can play an important role in plant immunity by increasing or decreasing plant resistance to pathogens. Although no general rule can be drawn about the effect of N availability and quality on the fate of plant/pathogen interactions, plants’ capacity to acquire, assimilate, allocate N, and maintain amino acid homeostasis appears to partly mediate the effects of N on plant defense. Nitric oxide (NO), one of the products of N metabolism, plays an important role in plant immunity signaling. NO is generated in part through Nitrate Reductase (NR), a key enzyme involved in nitrate assimilation, and its production depends on levels of nitrate/nitrite, NR substrate/product, as well as on L-arginine and polyamine levels. Cross-regulation between NO signaling and N supply/metabolism has been evidenced. NO production can be affected by N supply, and conversely NO appears to regulate nitrate transport and assimilation. Based on this knowledge, we hypothesized that N availability partly controls plant resistance to pathogens by controlling NO homeostasis. Using the Medicago truncatula/Aphanomyces euteiches pathosystem, we showed that NO homeostasis is important for resistance to this oomycete and that N availability impacts NO homeostasis by affecting S-nitrosothiol (SNO) levels and S-nitrosoglutathione reductase activity in roots. These results could therefore explain the increased resistance we noted in N-deprived as compared to N-replete M. truncatula seedlings. They open onto new perspectives for the studies of N/plant defense interactions. PMID:27092169

  12. Reduction Rates for Higher Americium Oxidation States in Nitric Acid

    SciTech Connect

    Grimes, Travis Shane; Mincher, Bruce Jay; Schmitt, Nicholas C

    2015-09-30

    The stability of hexavalent americium was measured using multiple americium concentrations and nitric acid concentrations after contact with the strong oxidant sodium bismuthate. Contrary to our hypotheses Am(VI) was not reduced faster at higher americium concentrations, and the reduction was only zero-order at short time scales. Attempts to model the reduction kinetics using zero order kinetic models showed Am(VI) reduction in nitric acid is more complex than the autoreduction processes reported by others in perchloric acid. The classical zero-order reduction of Am(VI) was found here only for short times on the order of a few hours. We did show that the rate of Am(V) production was less than the rate of Am(VI) reduction, indicating that some Am(VI) undergoes two electron-reduction to Am(IV). We also monitored the Am(VI) reduction in contact with the organic diluent dodecane. A direct comparison of these results with those in the absence of the organic diluent showed the reduction rates for Am(VI) were not statistically different for both systems. Additional americium oxidations conducted in the presence of Ce(IV)/Ce(III) ions showed that Am(VI) is reduced without the typical growth of Am(V) observed in the systems sans Ce ion. This was an interesting result which suggests a potential new reduction/oxidation pathway for Am in the presence of Ce; however, these results were very preliminary, and will require additional experiments to understand the mechanism by which this occurs. Overall, these studies have shown that hexavalent americium is fundamentally stable enough in nitric acid to run a separations process. However, the complicated nature of the reduction pathways based on the system components is far from being rigorously understood.

  13. Modulation of Lung Function by Increased Nitric Oxide Production

    PubMed Central

    Yadav, Ram Lochan; Yadav, Prakash Kumar

    2017-01-01

    Introduction Cigarette smoking reduces endogenous Nitric Oxide (NO) production by reducing Nitric Oxide Synthase (NOS) activity, which is one of the probable reason for increased rate of pulmonary diseases in smokers. Nitric oxide/oxygen blends are used in critical care to promote capillary and pulmonary dilation to treat several pulmonary vascular diseases. Among several supplements, the highest NOS activation has been proved for garlic with its unique mechanism of action. Aim To investigate the effect of dietary supplementation of NO producing garlic on pulmonary function of smokers. Materials and Methods The study was conducted on 40 healthy non-smoker (Group A) and 40 chronic smoker (Group B) males with matched age, height and weight. The pulmonary function tests- Forced Vital Capacity (FVC), Forced Expiratory Volume in one second (FEV1), FEV1/FVC ratio and Peak Expiratory Flow Rate (PEFR) were performed in non-smokers (Group A), smokers (Group B) and smokers after supplementation of approximately 4 gm of raw garlic (2 garlic cloves) per day for three months (Group C). Endogenous NO production was studied in smokers before and after garlic supplementation and in non-smokers without supplementation. The data obtained were compared between the groups using unpaired student’s t-test. The p-value considered significant at <0.05. Results Our results showed that FVC, FEV1, FEV1/FVC ratio and PEFR were reduced significantly along with a significant decreased NOS activity among smokers (Group B) when compared with non-smokers (Group A). Garlic supplementation significantly improved the pulmonary function tests in Group C in comparison to Group B by increasing NOS activity. Conclusion Dietary supplementation of garlic, which might be by increasing NOS activity, has significantly improved pulmonary functions in smokers. PMID:28764150

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

    PubMed

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

    2013-12-19

    Myocardial infarction, a leading cause of death in the Western world, usually occurs when the fibrous cap overlying an atherosclerotic plaque in a coronary artery ruptures. The resulting exposure of blood to the atherosclerotic material then triggers thrombus formation, which occludes the artery. The importance of genetic predisposition to coronary artery disease and myocardial infarction is best documented by the predictive value of a positive family history. Next-generation sequencing in families with several affected individuals has revolutionized mutation identification. Here we report the segregation of two private, heterozygous mutations in two functionally related genes, GUCY1A3 (p.Leu163Phefs*24) and CCT7 (p.Ser525Leu), in an extended myocardial infarction family. GUCY1A3 encodes the α1 subunit of soluble guanylyl cyclase (α1-sGC), and CCT7 encodes CCTη, 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 α1-sGC as well as β1-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 α1-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.

  15. Daily exhaled nitric oxide measurements and asthma exacerbations in children.

    PubMed

    van der Valk, R J P; Baraldi, E; Stern, G; Frey, U; de Jongste, J C

    2012-02-01

    Fractional exhaled Nitric Oxide (FeNO) is a biomarker for eosinophilic airway inflammation and can be measured at home on a daily basis. A short-term increase in FeNO may indicate a higher risk of future asthma exacerbations. To assess changes in FeNO before and after asthma exacerbations compared to a stable control period. A post hoc analysis was performed on daily FeNO measurements over 30 weeks in children with asthma (n = 77). Moderate exacerbations were defined by an increase in symptom scores and severe exacerbations by prescription of prednisone. Individual mean and maximum FeNO, the variability of FeNO assessed by the coefficient of variation (CV), and slopes of FeNO in time were all quantified in 3-week blocks. Cross-correlation of FeNO with symptoms and autocorrelation of FeNO were assessed in relation to exacerbations and examined as predictors for exacerbations compared to reference periods using logistic regression. Fractional exhaled nitric oxide could be assessed in relation to 25 moderate and 12 severe exacerbations. The CV, slope, cross-correlation, and autocorrelation of daily FeNO increased before moderate exacerbations. Increases in slope were also randomly seen in 19% of 2-week blocks of children without exacerbations. At least 3-5 FeNO measurements in the 3 weeks before an exacerbation were needed to calculate a slope that could predict moderate exacerbations. No specific pattern of FeNO was seen before severe exacerbations. Fractional exhaled nitric oxide monitoring revealed changes in FeNO prior to moderate exacerbations. Whether this can be used to prevent loss of asthma control should be further explored. © 2011 John Wiley & Sons A/S.

  16. The role of nitric oxide in low level light therapy

    NASA Astrophysics Data System (ADS)

    Hamblin, Michael R.

    2008-02-01

    The use of low levels of visible or near infrared light for reducing pain, inflammation and edema, promoting healing of wounds, deeper tissues and nerves, and preventing tissue damage by reducing cellular apoptosis has been known for almost forty years since the invention of lasers. Despite many reports of positive findings from experiments conducted in vitro, in animal models and in randomized controlled clinical trials, LLLT remains controversial. Firstly the biochemical mechanisms underlying the positive effects are incompletely understood, and secondly the complexity of choosing amongst a large number of illumination parameters has led to the publication of a number of negative studies as well as many positive ones. This review will focus on the role of nitric oxide in the cellular and tissue effects of LLLT. Red and near-IR light is primarily absorbed by cytochrome c oxidase (unit four in the mitochondrial respiratory chain). Nitric oxide produced in the mitochondria can inhibit respiration by binding to cytochrome c oxidase and competitively displacing oxygen, especially in stressed or hypoxic cells. If light absorption displaced the nitric oxide and thus allowed the cytochrome c oxidase to recover and cellular respiration to resume, this would explain many of the observations made in LLLT. Why the effect is only seen in hypoxic, stressed or damaged cells or tissues? How the effects can keep working for some time (hours or days) postillumination? Why increased NO concentrations are sometimes measured in cell culture or in animals? How blood flow can be increased? Why angiogenesis is sometimes increased after LLLT in vivo?

  17. Role of nitric oxide in coronary vasomotion during handgrip exercise.

    PubMed

    Nishikawa, Y; Kanki, H; Ogawa, S

    1997-11-01

    Endothelium-dependent modulation of coronary vasomotion during increased sympathetic tone remains unclear in normal and atherosclerotic human coronory arteries. We evaluated the role of endothelium-derived nitric oxide in vasomotion during isometric exercise in normal subjects (n = 7) and in patients with coronary artery disease (CAD) (n = 10). Coronary blood flow and epicardial coronary artery diameter to the handgrip test were measured before and after intracoronary administration of 100 micromol/min of N(G)-monomethyl L-arginine (L-NMMA). Heart rate and aortic blood pressure increased during handgrip test. Handgrip test caused a significant dilation in the diameter of the epicardial coronary artery in normal subjects (9.9% +/- 3.9%, mean +/- SD) and in the diameter of smooth segments of patients with CAD (5% +/- 3.7%, p < 0.05 vs normal subjects). In contrast, the diameter of irregular segments in patients with CAD decreased during handgrip test (-9.8 +/- 3.9%). After L-NMMA, the epicardial coronary artery significantly increased during handgrip test compared with before L-NMMA in normal subjects. L-NMMA did not have any effect on handgrip test induced vasodilation in the smooth segments and vasoconstriction in the irregular segments in the patients with CAD. Handgrip test-induced increases in coronary blood flow did not change after L-NMMA in both groups. Nitric oxide does not play a major role in HNG-induced vasodilation in epicardial and microcirculatory vessels in normal human coronary circulation. Although the decreased release in nitric oxide may modulate the abnormal response of the epicardial coronary artery to handgrip test, this does not explain the paradoxic constrictive response from the depressed but still dilatory response in the patients with CAD.

  18. Methods of nitric oxide detection in plants: a commentary.

    PubMed

    Mur, Luis A J; Mandon, Julien; Cristescu, Simona M; Harren, Frans J M; Prats, Elena

    2011-11-01

    Over the last decade nitric oxide (NO) has been shown to influence a range of processes in plants. However, when, where and even if NO production occurs is controversial in several physiological scenarios in plants. This arises from a series of causes: (a) doubts have arisen over the specificity of widely used 4,5-diaminofluorescein diacetate (DAF-2DA)/4-amino-5-methylamino-2,7-difluorofluorescein (DAF-FM) dyes for NO, (b) no plant nitric oxide synthase (NOS) has been cloned, so that the validity of using mammalian NOS inhibitors to demonstrate that NO is being measured is debatable, (c) the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-l-oxyl-3-oxide (cPTIO) needs to be used with caution, and (d) some discrepancies between assays for in planta measurements and another based on sampling NO from the gas phase have been reported. This review will outline some commonly used methods to determine NO, attempt to reconcile differing results obtained by different laboratories and suggest appropriate approaches to unequivocally demonstrate the production of NO.

  19. Cancer Cell Metabolism and the Modulating Effects of Nitric Oxide

    PubMed Central

    Chang, Ching-Fang; Diers, Anne R.; Hogg, Neil

    2016-01-01

    Altered metabolic phenotype has been recognized as a hallmark of tumor cells for many years, but this aspect of the cancer phenotype has come into greater focus in recent years. NOS2 (inducible nitric oxide synthase of iNOS) has been implicated as a component in many aggressive tumor phenotypes, including melanoma, glioblastoma and breast cancer. Nitric oxide has been well established as a modulator of cellular bioenergetics pathways, in many ways similar to the alteration of cellular metabolism observed in aggressive tumors. In this review we attempt to bring these concepts together with the general hypothesis that one function of NOS2 and NO in cancer is to modulate metabolic processes to facilitate increased tumor aggression. There are many mechanisms by which NO can modulate tumor metabolism, including direct inhibition of respiration, alterations in mitochondrial mass, oxidative inhibition of bioenergetic enzymes, and the stimulation of secondary signaling pathways. Here we review metabolic alterations in the context of cancer cells and discuss the role of NO as a potential mediator of these changes. PMID:25464273

  20. Elucidating nitric oxide synthase domain interactions by molecular dynamics.

    PubMed

    Hollingsworth, Scott A; Holden, Jeffrey K; Li, Huiying; Poulos, Thomas L

    2016-02-01

    Nitric oxide synthase (NOS) is a multidomain enzyme that catalyzes the production of nitric oxide (NO) by oxidizing L-Arg to NO and L-citrulline. NO production requires multiple interdomain electron transfer steps between the flavin mononucleotide (FMN) and heme domain. Specifically, NADPH-derived electrons are transferred to the heme-containing oxygenase domain via the flavin adenine dinucleotide (FAD) and FMN containing reductase domains. While crystal structures are available for both the reductase and oxygenase domains of NOS, to date there is no atomic level structural information on domain interactions required for the final FMN-to-heme electron transfer step. Here, we evaluate a model of this final electron transfer step for the heme-FMN-calmodulin NOS complex based on the recent biophysical studies using a 105-ns molecular dynamics trajectory. The resulting equilibrated complex structure is very stable and provides a detailed prediction of interdomain contacts required for stabilizing the NOS output state. The resulting equilibrated complex model agrees well with previous experimental work and provides a detailed working model of the final NOS electron transfer step required for NO biosynthesis.

  1. Mitochondrial nitric oxide metabolism in rat muscle during endotoxemia.

    PubMed

    Alvarez, Silvia; Boveris, Alberto

    2004-11-01

    In this study, heart and diaphragm mitochondria produced 0.69 and 0.77 nmol nitric oxide (NO)/min mg protein, rates that account for 67 and 24% of maximal cellular NO production, respectively. Endotoxemia and septic shock occur with an exacerbated inflammatory response that damages tissue mitochondria. Skeletal muscle seems to be one of the main target organs in septic shock, showing an increased NO production and early oxidative stress. The kinetic properties of mitochondrial nitric oxide synthase (mtNOS) of heart and diaphragm were determined. For diaphragm, the KM values for O2 and L-Arg were 4.6 and 37 microM and for heart were 3.3 and 36 microM. The optimal pH for mtNOS activity was 6.5 for diaphragm and 7.0 for heart. A marked increase in mtNOS activity was observed in endotoxemic rats, 90% in diaphragm and 30% in heart. Diaphragm and heart mitochondrial O2*- and H2O2 production were 2- to 3-fold increased during endotoxemia and Mn-SOD activity showed a 2-fold increase in treated animals, whereas catalase activity was unchanged. One of the current hypotheses for the molecular mechanisms underlying the complex condition of septic shock is that the enhanced NO production by mtNOS leads to excessive peroxynitrite production and protein nitration in the mitochondrial matrix, causing mitochondrial dysfunction and contractile failure.

  2. Characteristics of the nitric oxide synthase-catalyzed conversion of arginine to N-hydroxyarginine, the first oxygenation step in the enzymic synthesis of nitric oxide.

    PubMed

    Campos, K L; Giovanelli, J; Kaufman, S

    1995-01-27

    The nitric oxide synthase-catalyzed conversion of L-arginine to L-citrulline and nitric oxide is known to be the sum of two partial reactions: oxygenation of arginine to N-hydroxyarginine, followed by oxygenation of N-hydroxyarginine to citrulline and nitric oxide. Whereas the conversion of N-hydroxyarginine to citrulline and nitric oxide has been the subject of a number of studies, the oxygenation of arginine to N-hydroxyarginine has received little attention. Here we show that substrate amounts of rat cerebellar nitric oxide synthase, in the absence of added NADPH, catalyze the conversion of arginine to N-hydroxyarginine as the dominant product. The product appears not to be tightly bound to the enzyme. A maximum of 0.16 mol of N-hydroxyarginine/mol of nitric oxide synthase subunit was formed. The reaction requires oxygen and the addition of Ca2+/calmodulin and is stimulated 3-fold by tetrahydrobiopterin. Upon addition of NADPH, citrulline is formed exclusively. Conversion of N-hydroxyarginine to citrulline, like the first partial reaction, requires Ca2+/calmodulin and is stimulated by tetrahydrobiopterin but differs from the first partial reaction in being completely dependent upon addition of NADPH. These results indicate that brain nitric oxide synthase contains an endogenous reductant that can support oxygenation of arginine but not of N-hydroxyarginine. The reductant is not NADPH, since the amount of nitric oxide synthase-bound NADPH is appreciably less than the amount required for N-hydroxyarginine synthesis. Possible candidates for this role are discussed in relation to proposed mechanisms of action of nitric oxide synthase.

  3. Application of nitric oxide measurements in clinical conditions beyond asthma

    PubMed Central

    Malinovschi, Andrei; Ludviksdottir, Dora; Tufvesson, Ellen; Rolla, Giovanni; Bjermer, Leif; Alving, Kjell; Diamant, Zuzana

    2015-01-01

    Fractional exhaled nitric oxide (FeNO) is a convenient, non-invasive method for the assessment of active, mainly Th2-driven, airway inflammation, which is sensitive to treatment with standard anti-inflammatory therapy. Consequently, FeNO serves as a valued tool to aid diagnosis and monitoring in several asthma phenotypes. More recently, FeNO has been evaluated in several other respiratory, infectious, and/or immunological conditions. In this short review, we provide an overview of several clinical studies and discuss the status of potential applications of NO measurements in clinical conditions beyond asthma. PMID:26672962

  4. [Nitric oxide is a major player in plant immune system].

    PubMed

    Koen, Emmanuel; Lamotte, Olivier; Besson-Bard, Angélique; Bourque, Stéphane; Nicolas-Francès, Valérie; Jeandroz, Sylvain; Wendehenne, David

    2013-03-01

    In animals, nitric oxide (NO) functions as a ubiquitous signaling molecule involved in diverse physiological processes such as immunity. Recent studies provided evidence that plants challenged by pathogenic microorganisms also produce NO. The emerging picture is that NO functions as a signal in plant immunity and executes part of its effects through posttranslational protein modifications. Notably, the characterization of S-nitrosylated proteins provided insights into the molecular mechanisms by which NO exerts its activities. Based on these findings, it appears that NO is involved in both the activation and the negative control of the signaling pathways related to plant immunity.

  5. Nitric oxide and reactive oxygen species in plant biotic interactions.

    PubMed

    Scheler, Claudia; Durner, Jörg; Astier, Jeremy

    2013-08-01

    Nitric oxide (NO) and reactive oxygen species (ROS) are important signaling molecules in plants. Recent progress has been made in defining their role during plant biotic interactions. Over the last decade, their function in disease resistance has been highlighted and focused a lot of investigations. Moreover, NO and ROS have recently emerged as important players of defense responses after herbivore attacks. Besides their role in plant adaptive response development, NO and ROS have been demonstrated to be involved in symbiotic interactions between plants and microorganisms. Here we review recent data concerning these three sides of NO and ROS functions in plant biotic interactions.

  6. Electrochemical Detection of Nitric Oxide in Plant Cell Suspensions.

    PubMed

    Griveau, Sophie; Besson-Bard, Angélique; Bedioui, Fethi; Wendehenne, David

    2016-01-01

    Nitric oxide is a hydrophobic radical acting as a physiological mediator in plants. Because of its unique properties, the detection of NO in plant tissues and cell suspensions remains a challenge. For this purpose, several techniques are used, each having certain advantages and limitations such as interferences with other species, questionable sensitivity, and/or selectivity or ex situ measurement. Here we describe a very attractive approach for tracking NO in plant cell suspensions using a NO-sensitive homemade platinum/iridium-based electrochemical microsensor. This method constitutes the absolute real-time proof of the production of free NO in physiological conditions.

  7. Nitric oxide signaling in plant responses to abiotic stresses.

    PubMed

    Qiao, Weihua; Fan, Liu-Min

    2008-10-01

    Nitric oxide (NO) plays important roles in diverse physiological processes in plants. NO can provoke both beneficial and harmful effects, which depend on the concentration and location of NO in plant cells. This review is focused on NO synthesis and the functions of NO in plant responses to abiotic environmental stresses. Abiotic stresses mostly induce NO production in plants. NO alleviates the harmfulness of reactive oxygen species, and reacts with other target molecules, and regulates the expression of stress responsive genes under various stress conditions.

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

    PubMed Central

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

    2016-01-01

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

  9. Multi-reference calculations of nitric oxide dimer

    NASA Astrophysics Data System (ADS)

    Taguchi, Naoki; Mochizuki, Yuji; Ishikawa, Takeshi; Tanaka, Kiyoshi

    2008-01-01

    The nitric oxide dimer, (NO) 2, has been known as an archetype with severe near-degeneracy because of the weak N-N bonding. We thus performed a series of multi-reference calculations of fourth-order coupled pair approximation (MRCPA4) and configuration interaction (MRCI). For the ground state, the molecular structure of cis form was optimized by these calculations. The MRCPA4 geometry was favorably compared with the recent experimental data, indicating the importance of higher excitations. Low-lying singlet excited states were also addressed. Through these calculations, the intrinsic MR character of this system was illustrated.

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

    PubMed

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

    2015-01-01

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

  11. Nitric oxide donor-mediated killing of bioluminescent Escherichia coli.

    PubMed Central

    Virta, M; Karp, M; Vuorinen, P

    1994-01-01

    The antimicrobial activities of two nitric oxide-releasing compounds against Escherichia coli were investigated by using recombinant E. coli cloned with a luciferase gene from Pyrophorus plagiophthalamus. Since luciferase uses intracellular ATP to generate visible light which can be measured from living cells in real time, we wanted to compare the extent to which cell viability parallels light emission. Results from luminescence measurements and CFU counts were in good agreement, and the decrease in light emission was shown to provide a rapid and more sensitive indication of cytotoxicity. PMID:7695261

  12. An appraisal of techniques for administration of gaseous nitric oxide.

    PubMed

    Tibballs, J; Hochmann, M; Carter, B; Osborne, A

    1993-12-01

    Gaseous nitric oxide (NO) is a potent selective pulmonary vasodilator. When mixed with O2 for more than 10-15 minutes it forms toxic amounts of nitrogen dioxide (NO2). We describe two techniques to administer 20 parts per million (ppm) during mechanical ventilation. A technique using flows of NO and O2 at low pressure to drive a Siemens Servo 900C ventilator provided a constant inspired concentration of NO. Another technique in which NO was added to the inspiratory limb of a Siemens Servo 900C ventilator driven by high pressure oxygen provided a highly variable concentration (9-53 ppm) of inspired NO.

  13. New regulatory, signaling pathways, and sources of nitric oxide.

    PubMed

    Pluta, Ryszard M

    2011-01-01

    Discovered in 1980 by the late Robert F. Furchgott, endothelium-derived relaxing factor, nitric oxide (NO), has been in the forefront of vascular research for several decades. What was originally a narrow approach, has been significantly widened due to major advances in understanding the chemical and biological properties of NO as well as its signaling pathways and discovering new sources of this notorious free radical gas. In this review, recent discoveries regarding NO and their implications on therapy for delayed cerebral vasospasm are presented.

  14. Nitric oxide affects plant mitochondrial functionality in vivo.

    PubMed

    Zottini, Michela; Formentin, Elide; Scattolin, Michela; Carimi, Francesco; Lo Schiavo, Fiorella; Terzi, Mario

    2002-03-27

    In this report, we show that nitric oxide affects mitochondrial functionality in plant cells and reduces total cell respiration due to strong inhibition of the cytochrome pathway. The residual respiration depends on the alternative pathway and novel synthesis of alternative oxidase occurs. These modifications are associated with depolarisation of the mitochondrial membrane potential and release of cytochrome c from mitochondria, suggesting a conserved signalling pathway in plants and animals. This signal cascade is triggered at the mitochondrial level and induces about 20% of cell death. In order to achieve a higher level of cell death, the addition of H(2)O(2) is necessary.

  15. H2S regulation of nitric oxide metabolism

    PubMed Central

    Kolluru, Gopi K.; Yuan, Shuai; Shen, Xinggui; Kevil, Christopher G.

    2015-01-01

    Nitric oxide (NO) and hydrogen sulfide (H2S) are two major gaseous signaling molecules that regulate diverse physiological functions. Recent publications indicate the regulatory role of H2S on NO metabolism. In this chapter, we discuss the latest findings on H2S-NO interactions through formation of novel chemical derivatives, and experimental approaches to study these adducts. This chapter also addresses potential H2S interference on various NO detection techniques, along with precautions for analyzing biological samples from various sources. This information will facilitate critical evaluation and clearer insight into H2S regulation of NO signaling and its influence on various physiological functions. PMID:25725527

  16. The redox interplay between nitrite and nitric oxide: From the gut to the brain☆

    PubMed Central

    Pereira, Cassilda; Ferreira, Nuno R.; Rocha, Bárbara S.; Barbosa, Rui M.; Laranjinha, João

    2013-01-01

    The reversible redox conversion of nitrite and nitric oxide (•NO) in a physiological setting is now widely accepted. Nitrite has long been identified as a stable intermediate of •NO oxidation but several lines of evidence support the reduction of nitrite to nitric oxide in vivo. In the gut, this notion implies that nitrate from dietary sources fuels the longstanding production of nitrite in the oral cavity followed by univalent reduction to •NO in the stomach. Once formed, •NO boosts a network of reactions, including the production of higher nitrogen oxides that may have a physiological impact via the post-translational modification of proteins and lipids. Dietary compounds, such as polyphenols, and different prandial states (secreting specific gastric mediators) modulate the outcome of these reactions. The gut has unusual characteristics that modulate nitrite and •NO redox interplay: (1) wide range of pH (neutral vs acidic) and oxygen tension (c.a. 70 Torr in the stomach and nearly anoxic in the colon), (2) variable lumen content and (3) highly developed enteric nervous system (sensitive to •NO and dietary compounds, such as glutamate). The redox interplay of nitrite and •NO might also participate in the regulation of brain homeostasis upon neuronal glutamatergic stimulation in a process facilitated by ascorbate and a localized and transient decrease of oxygen tension. In a way reminiscent of that occurring in the stomach, a nitrite/•NO/ascorbate redox interplay in the brain at glutamatergic synapses, contributing to local •NO increase, may impact on •NO-mediated process. We here discuss the implications of the redox conversion of nitrite to •NO in the gut, how nitrite-derived •NO may signal from the digestive to the central nervous system, influencing brain function, as well as a putative ascorbate-driven nitrite/NO pathway occurring in the brain. PMID:24024161

  17. Molecular mechanisms of neuronal nitric oxide synthase in cardiac function and pathophysiology

    PubMed Central

    Zhang, Yin Hua; Jin, Chun Zi; Jang, Ji Hyun; Wang, Yue

    2014-01-01

    Neuronal nitric oxide synthase (nNOS or NOS1) is the major endogenous source of myocardial nitric oxide (NO), which facilitates cardiac relaxation and modulates contraction. In the healthy heart it regulates intracellular Ca2+, signalling pathways and oxidative homeostasis and is upregulated from early phases upon pathogenic insult. nNOS plays pivotal roles in protecting the myocardium from increased oxidative stress, systolic/diastolic dysfunction, adverse structural remodelling and arrhythmias in the failing heart. Here, we show that the downstream target proteins of nNOS and underlying post-transcriptional modifications are shifted during disease progression from Ca2+-handling proteins [e.g. PKA-dependent phospholamban phosphorylation (PLN-Ser16)] in the healthy heart to cGMP/PKG-dependent PLN-Ser16 with acute angiotensin II (Ang II) treatment. In early hypertension, nNOS-derived NO is involved in increases of cGMP/PKG-dependent troponin I (TnI-Ser23/24) and cardiac myosin binding protein C (cMBP-C-Ser273). However, nNOS-derived NO is shown to increase S-nitrosylation of various Ca2+-handling proteins in failing myocardium. The spatial compartmentation of nNOS and its translocation for diverse binding partners in the diseased heart or various nNOS splicing variants and regulation in response to pathological stress may be responsible for varied underlying mechanisms and functions. In this review, we endeavour to outline recent advances in knowledge of the molecular mechanisms mediating the functions of nNOS in the myocardium in both normal and diseased hearts. Insights into nNOS gene regulation in various tissues are discussed. Overall, nNOS is an important cardiac protector in the diseased heart. The dynamic localization and various mediating mechanisms of nNOS ensure that it is able to regulate functions effectively in the heart under stress. PMID:24756636

  18. Real-time visualization of distinct nitric oxide generation of nitric oxide synthase isoforms in single cells.

    PubMed

    Eroglu, Emrah; Hallström, Seth; Bischof, Helmut; Opelt, Marissa; Schmidt, Kurt; Mayer, Bernd; Waldeck-Weiermair, Markus; Graier, Wolfgang F; Malli, Roland

    2017-09-04

    The members of the nitric oxide synthase (NOS) family, eNOS, nNOS and iNOS, are well-characterized enzymes. However, due to the lack of suitable direct NO sensors, little is known about the kinetic properties of cellular NO generation by the different nitric oxide synthase isoenzymes. Very recently, we developed a novel class of fluorescent protein-based NO-probes, the geNOps, which allow real-time measurement of cellular NO generation and fluctuation. By applying these genetic NO biosensors to nNOS-, eNOS- and iNOS-expressing HEK293 cells we were able to characterize the respective NO dynamics in single cells that exhibited identical Ca(2+) signaling as comparable activator of nNOS and eNOS. Our data demonstrate that upon Ca(2+) mobilization nNOS-derived NO signals occur instantly and strictly follow the Ca(2+) elevation while NO release by eNOS occurs gradually and sustained. To detect high NO levels in cells expressing iNOS, a new ratiometric probe based on two fluorescent proteins was developed. This novel geNOp variant allows the measurement of the high NO levels in cells expressing iNOS. Moreover, we used this probe to study the L-arginine-dependency of NO generation by iNOS on the level of single cells. Our experiments highlight that the geNOps technology is suitable to detect obvious differences in the kinetics, amplitude and substrate-dependence of cellular NO signals-derived from all three nitric oxide synthase isoforms. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Nitric Oxide Donors as Neuroprotective Agents after an Ischemic Stroke-Related Inflammatory Reaction

    PubMed Central

    Rojas-Mayorquín, Argelia E.; Ortuño-Sahagún, Daniel

    2013-01-01

    Cerebral ischemia initiates a cascade of detrimental events including glutamate-associated excitotoxicity, intracellular calcium accumulation, formation of Reactive oxygen species (ROS), membrane lipid degradation, and DNA damage, which lead to the disruption of cellular homeostasis and structural damage of ischemic brain tissue. Cerebral ischemia also triggers acute inflammation, which exacerbates primary brain damage. Therefore, reducing oxidative stress (OS) and downregulating the inflammatory response are options that merit consideration as potential therapeutic targets for ischemic stroke. Consequently, agents capable of modulating both elements will constitute promising therapeutic solutions because clinically effective neuroprotectants have not yet been discovered and no specific therapy for stroke is available to date. Because of their ability to modulate both oxidative stress and the inflammatory response, much attention has been focused on the role of nitric oxide donors (NOD) as neuroprotective agents in the pathophysiology of cerebral ischemia-reperfusion injury. Given their short therapeutic window, NOD appears to be appropriate for use during neurosurgical procedures involving transient arterial occlusions, or in very early treatment of acute ischemic stroke, and also possibly as complementary treatment for neurodegenerative diseases such as Parkinson or Alzheimer, where oxidative stress is an important promoter of damage. In the present paper, we focus on the role of NOD as possible neuroprotective therapeutic agents for ischemia/reperfusion treatment. PMID:23691263

  20. Nitric oxide donors as neuroprotective agents after an ischemic stroke-related inflammatory reaction.

    PubMed

    Godínez-Rubí, Marisol; Rojas-Mayorquín, Argelia E; Ortuño-Sahagún, Daniel

    2013-01-01

    Cerebral ischemia initiates a cascade of detrimental events including glutamate-associated excitotoxicity, intracellular calcium accumulation, formation of Reactive oxygen species (ROS), membrane lipid degradation, and DNA damage, which lead to the disruption of cellular homeostasis and structural damage of ischemic brain tissue. Cerebral ischemia also triggers acute inflammation, which exacerbates primary brain damage. Therefore, reducing oxidative stress (OS) and downregulating the inflammatory response are options that merit consideration as potential therapeutic targets for ischemic stroke. Consequently, agents capable of modulating both elements will constitute promising therapeutic solutions because clinically effective neuroprotectants have not yet been discovered and no specific therapy for stroke is available to date. Because of their ability to modulate both oxidative stress and the inflammatory response, much attention has been focused on the role of nitric oxide donors (NOD) as neuroprotective agents in the pathophysiology of cerebral ischemia-reperfusion injury. Given their short therapeutic window, NOD appears to be appropriate for use during neurosurgical procedures involving transient arterial occlusions, or in very early treatment of acute ischemic stroke, and also possibly as complementary treatment for neurodegenerative diseases such as Parkinson or Alzheimer, where oxidative stress is an important promoter of damage. In the present paper, we focus on the role of NOD as possible neuroprotective therapeutic agents for ischemia/reperfusion treatment.

  1. Reactions of nitric oxide with tree and fungal laccase.

    PubMed

    Martin, C T; Morse, R H; Kanne, R M; Gray, H B; Malmström, B G; Chan, S I

    1981-09-01

    The reactions of nitric oxide (NO) with the oxidized and reduced forms of fungal and tree laccase, as well as with tree laccase depleted in type 2 copper, are reported. The products of the reactions were determined by NMR and mass spectroscopy, whereas the oxidation states of the enzymes were monitored by EPR and optical spectroscopy. All three copper sites in fungal laccase are reduced by NO. In addition, NO forms a specific complex with the reduced type 2 copper. NO similarly reduces all of the copper sites in tree laccase, but it also oxidizes the reduced sites produced by ascorbate or NO reduction. A catalytic cycle is set up in which N2O, NO2-, and various forms of the enzyme are produced. On freezing of fully reduced tree laccase in the presence of NO, the type 1 copper becomes reoxidized. This reaction does not occur with the enzyme depleted in type 2 copper, suggesting that it involves intramolecular electron transfer from the type 1 copper to NO bound to the type 2 copper. When the half-oxidized tree laccase is formed in the presence of NO, a population of molecules exists which exhibits a type 3 EPR signal. A triplet EPR signal is also seen in the same preparation and is attributed to a population of the enzyme molecules in which NO is bound to the reduced copper of a half-oxidized type 3 copper site.

  2. Uncoupled cardiac nitric oxide synthase mediates diastolic dysfunction.

    PubMed

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

    2010-02-02

    Heart failure with preserved ejection fraction is 1 consequence of hypertension and is caused by impaired cardiac diastolic relaxation. Nitric oxide (NO) is a known modulator of cardiac relaxation. Hypertension can lead to a reduction in vascular NO, in part because NO synthase (NOS) becomes uncoupled when oxidative depletion of its cofactor tetrahydrobiopterin (BH(4)) occurs. Similar events may occur in the heart that lead to uncoupled NOS and diastolic dysfunction. In a hypertensive mouse model, diastolic dysfunction was accompanied by cardiac oxidation, a reduction in cardiac BH(4), and uncoupled NOS. Compared with sham-operated animals, male mice with unilateral nephrectomy, with subcutaneous implantation of a controlled-release deoxycorticosterone acetate pellet, and given 1% saline to drink were mildly hypertensive and had diastolic dysfunction in the absence of systolic dysfunction or cardiac hypertrophy. The hypertensive mouse hearts showed increased oxidized biopterins, NOS-dependent superoxide production, reduced NO production, and dephosphorylated phospholamban. Feeding hypertensive mice BH(4) (5 mg/d), but not treating with hydralazine or tetrahydroneopterin, improved cardiac BH(4) stores, phosphorylated phospholamban levels, and diastolic dysfunction. Isolated cardiomyocyte experiments revealed impaired relaxation that was normalized with short-term BH(4) treatment. Targeted cardiac overexpression of angiotensin-converting enzyme also resulted in cardiac oxidation, NOS uncoupling, and diastolic dysfunction in the absence of hypertension. Cardiac oxidation, independently of vascular changes, can lead to uncoupled cardiac NOS and diastolic dysfunction. BH(4) may represent a possible treatment for diastolic dysfunction.

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

    NASA Technical Reports Server (NTRS)

    Reid, Ian A.

    1994-01-01

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

  4. Nasal nitric oxide is dependent on sinus obstruction in allergic rhinitis.

    PubMed

    Suojalehto, Hille; Vehmas, Tapio; Lindström, Irmeli; Kennedy, David W; Kilpeläinen, Maritta; Plosila, Tuomas; Savukoski, Sauli; Sipilä, Jukka; Varpula, Matti; Wolff, Henrik; Alenius, Harri; Toskala, Elina

    2014-06-01

    The aim of this study was to evaluate the associations between nasal nitric oxide and nasal symptoms, sinus opacification, and markers of allergic inflammation in allergic and in nonallergic rhinitis while taking into account the effect of sinus obstruction. We studied 175 young adult subjects divided into three groups: 1) allergic rhinitis, 2) nonallergic rhinitis, and 3) controls. We measured nasal nitric oxide using the breath-holding method and exhaled nitric oxide and scored semiquantitatively nasal computed tomography scans for opacification and obstruction. We also assessed the visual analogue scores of nasal symptoms, eosinophil count, and interleukin-13 mRNA levels in nasal biopsies. The level of nasal nitric oxide correlated with exhaled nitric oxide (r = 0.377, P < .001). In allergic rhinitis, nasal nitric oxide was elevated when compared to the controls, and an inverse correlation existed between the nasal nitric oxide level and sinus ostial obstruction (r = -0.272, P = .013). In nonallergic rhinitis, the level of nasal nitric oxide was similar to that of the controls. In allergic rhinitis, nasal nitric oxide correlated positively with the opacification score (r = 0.250, P = .033) and the nasal eosinophil count (r = 0.293, P = .030) of patients without a marked sinus ostial obstruction. Sinus ostial obstruction lowers the level of nasal nitric oxide and reduces its value as an indicator of allergic mucosal inflammation. A high nasal nitric oxide level may be a useful marker of eosinophilic inflammation in the nasal cavity and indicate the absence of marked sinus ostial obstruction. 3b. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

  5. Nitric oxide is necessary for visual learning in Octopus vulgaris.

    PubMed

    Robertson, J D; Bonaventura, J; Kohm, A; Hiscat, M

    1996-12-22

    We recently reported that inhibition of nitric oxide synthase (NOS) in Octopus vulgaris by intramuscular injections of an analog of L-arginine, N-omega-nitro-L-arginine methyl ester (L-NAME), blocked touch learning in Octopus vulgaris. The inactive enantiomorph (D-NAME), which had no effect on learning, was used for control. We now report that essentially the same procedures block visual learning in this animal. We used a visual paradigm in which the octopus was trained to respond positively to a smooth black plastic ball 2.5 cm diameter and negatively to a similar white ball, or vice versa. One set of eight animals was trained to the black ball positive, and another set of six to the white ball positive. Each set was trained at different times by two different trainers. We found that a 1 h pretreatment with the nitric oxide synthase inhibitor L-NAME blocks visual learning in Octopus vulgaris in both sets of animals.

  6. Antioxidant and nitric oxide inhibition activities of Thai medicinal plants.

    PubMed

    Makchuchit, Sunita; Itharat, Arunporn; Tewtrakul, Supinya

    2010-12-01

    Nineteen Thai medicinal plants used in Thai traditional medicine preparation to treat colds, asthma and fever were studied for their antioxidant and NO inhibitory activities. Three extracts were obtained from each plant. First extract obtained by macerating the plant part in 95% ethanol (Et) residue was boiled in water, where water extract (EW) was obtained. The third extract (HW) was obtained by boiling each plant in water similar to that of Thai traditional medicine practice. These extracts were tested for their antioxidant activity using DPPH assay, and anti-inflammatory activity by determination of inhibitory activity on lipopolysaccharide (LPS) induced nitric oxide (NO) production in RAW 264.7 cell lines using Griess reagent. Results indicated that Et, EW and HW of Syzygium aromaticum showed the highest antioxidant activity (EC50 = 6.56, 4.73 and 5.30 microg/ml, respectively). Et of Atractylodes lancea exhibited the most potent inhibitory activity on lipopolysaccharide (LPS) induced nitric oxide (NO) production in RAW 264.7 cells, with IC50 value of 9.70 microg/ml, followed by Et of Angelica sinensis and Cuminum cyminum (IC50 = 12.52 and 13.56 microg/ml, respectively) but water extract (EW, HW) of all plants were apparently inactive. These results of anti-inflammatory activity of these plants correspond with the traditional use for fever; cold, allergic-related diseases and inflammatory-related diseases.

  7. Effects of nitric oxide on stem cell therapy.

    PubMed

    Wang, Wuchen; Lee, Yugyung; Lee, Chi H

    2015-12-01

    The use of stem cells as a research tool and a therapeutic vehicle has demonstrated their great potential in the treatment of various diseases. With unveiling of nitric oxide synthase (NOS) universally present at various levels in nearly all types of body tissues, the potential therapeutic implication of nitric oxide (NO) has been magnified, and thus scientists have explored new treatment strategies involved with stem cells and NO against various diseases. As the functionality of NO encompasses cardiovascular, neuronal and immune systems, NO is involved in stem cell differentiation, epigenetic regulation and immune suppression. Stem cells trigger cellular responses to external signals on the basis of both NO specific pathways and concerted action with endogenous compounds including stem cell regulators. As potency and interaction of NO with stem cells generally depend on the concentrations of NO and the presence of the cofactors at the active site, the suitable carriers for NO delivery is integral for exerting maximal efficacy of stem cells. The innovative utilization of NO functionality and involved mechanisms would invariably alter the paradigm of therapeutic application of stem cells. Future prospects in NO-involved stem cell research which promises to enhance drug discovery efforts by opening new era to improve drug efficacy, reduce drug toxicity and understand disease mechanisms and pathways, were also addressed.

  8. Nitric oxide and cellular immunity in experimental cutaneous leishmaniasis.

    PubMed

    Díaz, N L; Fernández, M; Figueira, E; Ramírez, R; Monsalve, I B; Tapia, F J

    2003-05-01

    We examined the local and systemic production of nitric oxide (NO) and the pattern of cytokine during the course of Leishmania mexicana infection in susceptible BALB/c and resistant C57BL/6 mice. NO derivatives were measured in serum, and the expression of inducible nitric oxide synthase (iNOS), interferon (IFN-gamma), interleukin (IL-4) and epidermal Langerhans cells (LC) was measured in the lesions by immunohistology. Circulating NO concentrations, iNOS+ cell density, IFN-gamma+ Th1 cells and CD205+ Langerhans cells were higher in early lesions of resistant C57BL/6 mice. In contrast, susceptible BALB/c mice developed chronic and progressive lesions with a predominance of IL-4+ Th2 cells. In both susceptible and resistant mice, lesion size and lymph node volume followed a similar course. The early local and systemic production of NO in resistant mice may be related with the premature production of IFN-gamma observed, contributing to the resolution of the lesion.

  9. Compartmentalized nitric oxide signaling in the resistance vasculature

    PubMed Central

    Mutchler, Stephanie M.; Straub, Adam C.

    2015-01-01

    Nitric oxide (NO) was first described as a bioactive molecule through its ability to stimulate soluble guanylate cyclase, but the revelation that NO was the endothelium derived relaxation factor drove the field to its modern state. The wealth of research conducted over the past 30 years has provided us with a picture of how diverse NO signaling can be within the vascular wall, going beyond simple vasodilation to include such roles as signaling through protein S-nitrosation. This expanded view of NO’s actions requires highly regulated and compartmentalized production. Importantly, resistance arteries house multiple proteins involved in the production and transduction of NO allowing for efficient movement of the molecule to regulate vascular tone and reactivity. In this review, we focus on the many mechanisms regulating NO production and signaling action in the vascular wall, with a focus on the control of endothelial nitric oxide synthase (eNOS), the enzyme responsible for synthesizing most of the NO within these confines. We also explore how cross talk between the endothelium and smooth muscle in the microcirculation can modulate NO signaling, illustrating that this one small molecule has the capability to produce a plethora of responses. PMID:26028569

  10. Applications of plasma sources for nitric oxide medicine

    NASA Astrophysics Data System (ADS)

    Vasilets, Victor; Shekhter, Anatoly; Pekshev, Alexander

    2013-09-01

    Nitric oxide (NO) has important roles in the function of many tissues and organs. Wound healing processes are always accompanying by the increase of nitric oxide concentration in wound tissue. These facts suggest a possible therapeutic use of various NO donors for the acceleration of the wound healing and treatment of other diseases. Our previous studies indicated that gaseous NO flow produced by air-plasma generators acts beneficially on the wound healing. This beneficial effect could be caused by the mechanism involving peroxynitrite as an intermediate. As a result of mobilization of various antioxidant reactions more endogenous NO molecules become available as signaling molecules. to regulate the metabolic processes in wound tissue. In this paper different air plasma sources generated therapeutic concentrations of NO are discussed. The concentration of NO and other therapeutically important gas products are estimated by thermodynamic simulation. Synergy effects of NO with other plasma components are discussed as a factor enhancing therapeutic results. Some new medical application of plasma devices are presented. Advanced Plasma Therapies Inc.

  11. Nitric oxide-dependent hypotensive effects of wax gourd juice.

    PubMed

    Nakashima, Miki; Shigekuni, Yukiko; Obi, Takeshi; Shiraishi, Mitsuya; Miyamoto, Atsushi; Yamasaki, Hideo; Etoh, Takeomi; Iwai, Sumio

    2011-11-18

    The wax gourd (Benincasa hispida (Thunb) Cong.) is a long-season vegetable that has been used in traditional Chinese medicine to treat high blood pressure. However, precise details of its effect and the mechanism of action involved are still lacking. Ten-fold-condensed wax gourd juice was used for the experiments. We measured (1) blood pressure of anesthetized normal Wistar rats in vivo, (2) isolated rat aortic contraction and relaxation, and (3) nitric oxide production from cultured porcine endothelial cells. The rats mentioned had not been treated with the investigational medicine. Intravenous injection of the juice produced a dose-dependent decrease in blood pressure. Treatment with the juice induced concentration-dependent relaxation of isolated rat aortic rings that had been precontracted with noradrenaline. The relaxation induced by the juice was strongly inhibited by treatment with the nitric oxide (NO) synthase inhibitor N(G)-nitro-l-arginine methyl ester hydrochloride (l-NAME) or endothelial denudation. Treatment with the juice produced NO from cultured porcine aortic endothelial cells. This NO production was significantly inhibited by l-NAME. The present findings suggest that wax gourd juice exerts a hypotensive effect via endothelium-dependent vasodilation. The main endothelium-derived relaxing factor involved might be NO. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

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

    PubMed Central

    Hickok, Jason R.; Thomas, Douglas D.

    2013-01-01

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

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

    PubMed

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

    2003-08-01

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

  14. Nitric Oxide Is Protective in Listeric Meningoencephalitis of Rats

    PubMed Central

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

    2001-01-01

    The bacterium Listeria monocytogenes causes meningoencephalitis in humans. In rodents, listeriosis is associated with granulomatous lesions in the liver and the spleen, but not with meningoencephalitis. Here, infant rats were infected intracisternally to generate experimental listeric meningoencephalitis. Dose-dependent effects of intracisternal inoculation with L. monocytogenes on survival and activity were noted; 104 L. monocytogenes organisms induced a self-limiting brain infection. Bacteria invaded the basal meninges, chorioid plexus and ependyme, spread to subependymal tissue and hippocampus, and disappeared by day 7. This was paralleled by recruitment and subsequent disappearance of macrophages expressing inducible nitric oxide synthase (iNOS) and nitrotyrosine accumulation, an indication of nitric oxide (NO⋅) production. Treatment with the spin-trapping agent α-phenyl-tert-butyl nitrone (PBN) dramatically increased mortality and led to bacterial numbers in the brain 2 orders of magnitude higher than in control animals. Treatment with the selective iNOS inhibitor l-N6-(1-iminoethyl)-lysine (L-NIL) increased mortality to a similar extent and led to 1 order of magnitude higher bacterial counts in the brain, compared with controls. The numbers of bacteria that spread to the spleen and liver did not significantly differ among L-NIL-treated, PBN-treated, and control animals. Thus, the infant rat brain is able to mobilize powerful antilisterial mechanisms, and both reactive oxygen and NO⋅ contribute to Listeria growth control. PMID:11349080

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

    PubMed

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

    2015-04-01

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

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

    PubMed Central

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

    2007-01-01

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

  17. Role of nitric oxide in the epileptogenesis of EL mice.

    PubMed

    Murashima, Y L; Yoshii, M; Suzuki, J

    2000-01-01

    To understand the role of nitric oxide (NO) in the regulation of seizures, we measured the extracellular levels of the NO metabolites nitrite and nitrate as indices of NO generation in the parietal cortex, hippocampus, and temporal cortex of EL mice. Furthermore, alterations of neuronal, endothelial, and inducible nitric oxide synthetase (nNOS, eNOS, and iNOS, respectively) were observed to correlate them with epileptogenesis. EL mice of 20 weeks and 30 weeks of age (before and after the establishment of epileptogenesis, respectively) were used. Nitrite was quantified using the specific absorbancy of diazo dye. NOS isoenzymes (nNOS, iNOS, and eNOS) were also investigated in the hippocampus during development until mice were 30 weeks old. Samples (total protein, 8.33 to 8.43 microg) were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and identified by immunoblotting. EL mice that experienced repetitive seizures showed a remarkable increase in nitrite in the hippocampus at 30 weeks of age compared with EL mice that had no experience of seizures. nNOS and iNOS were major and minor components, respectively, and both increased in parallel with the development of epileptogenesis. eNOS was not detectable. Excess iNOS (and subsequent increase in harmful NO) and deficient eNOS (and subsequent decrease in NO identified as an endothelium-derived relaxing factor) may work together to form a focus complex.

  18. Nitric Oxide Signaling in Hypergravity-Induced Neuronal Plasticity

    NASA Technical Reports Server (NTRS)

    Holstein, Gay R.

    2003-01-01

    The goal of this research project was to identify the neurons and circuits in the vestibular nuclei and nucleus prepositus hypoglossi that utilize nitric oxide (NO) for intercellular signaling during gravity-induced plasticity. This objective was pursued using histochemical and immunocytochemical approaches to localize NO-producing neurons and characterize the fine morphology of the cells in ground-based studies of normal rats, rats adapted to hypergravity, and rats adapted to hypergravity and then re-adapted to the 1G environment. NO-producing neurons were identified and studied using four methodologies: i) immunocytochemistry employing polyclonal antibodies directed against neuronal nitric oxide synthase (nNOS), to provide an indication of the capacity of a cell for NO production; ii) immunocytochemistry employing a monoclonal antibody directed against L-citrulline, to provide an indirect index of the enzyme's activity; iii) histochemistry based on the NADPH-diaphorase reaction, for fuI1 cytological visualization of neurons; and iv) double immunofluorescence to co-localize nNOS and L-citrulline in individual vestibular nuclei (VN) and neurons.

  19. Nasal nitric oxide is a marker of poor asthma control.

    PubMed

    Heffler, Enrico; Pizzimenti, Stefano; Badiu, Iuliana; Guida, Giuseppe; Ricciardolo, Fabio Luigi Massimo; Bucca, Caterina; Rolla, Giovanni

    2013-06-01

    Asthma control, evaluated by symptoms, exacerbations rate and lung function may be greatly influenced by comorbidities, particularly chronic rhinosinusitis (CRS). Measurement of nasal nitric oxide (nNO) is a simple way to assess the severity of CRS. We aimed to analyze the relationship between asthma control and nasal NO. All patients with moderate-to-severe asthma on regular follow-up at our Outpatients' Clinic between November 2009 and April 2010 were included into the study. All patients were evaluated for asthma control by asthma control questionnaire (ACQ) and comorbidities (rhinitis, chronic rhinosinusitis with (CRSwNP) or without nasal polyps, obesity). Exhaled nitric oxide and nNO were obtained in all patients. Eighty-two patients were enrolled (mean age: 48 years, range: 21-80; 42 females). According to ACQ, 53 patients (64.6%) reported controlled asthma. Patients with uncontrolled asthma had lower nNO and higher prevalence of CRSwNP, with a significant correlation between nNO and ACQ. nNO is a biomarker negatively related to asthma control. As low nNO values were associated to CRSwNP, our results indicate that asthma control is highly influenced by this comorbidity.

  20. Nitric oxide synthase in experimental autoimmune myocarditis dysfunction.

    PubMed

    Goren, N; Leiros, C P; Sterin-Borda, L; Borda, E

    1998-11-01

    This study reports the expression of inducible nitric oxide synthase (NOS) in heart from autoimmune myocarditis mice associated with an alteration in their contractile behavior. By mean of the production of [U-14C]citrulline from [U-14C]arginine and immunoblot assay, the expression of iNOS was demonstrated in autoimmune atria that was normally absent. The iNOS activity decreased with administration of dexamethasone and in mice treated with monoclonal anti-interferon-gamma antibody (anti-IFN-gamma mAb). The inhibitors of protein kinase C activity (staurosporine) but not calcium/calmodulin (trifluoperazine) attenuated the iNOS activity. Moreover, autoimmune atria presented contractile alterations (lower values of dF/dt than control). The in vivo treatment with inhibitors of NOS activity or anti-IFN-gamma mAb or dexamethasone improved the contractile activity of autoimmune atria with no change in the contractility of normal atria. The results suggest that the infiltrative cells in myocarditis heart have a potential role in cardiac dysfunction by production of IFN-gamma and subsequent expression of iNOS, that in turn alter the contractile behavior of the heart. The data indicate that cytokines induced activation of L-arginine nitric oxide pathway in myocarditis atria leading to contractile dysfunction.

  1. Nitric oxide heme interactions in nitrophorin from Cimex lectularius

    NASA Astrophysics Data System (ADS)

    Christmann, R.; Auerbach, H.; Berry, R. E.; Walker, F. A.; Schünemann, V.

    2016-12-01

    The nitrophorin from the bedbug Cimex lectularius (cNP) is a nitric oxide (NO) carrying protein. Like the nitrophorins (rNPs) from the kissing bug Rhodnius prolixus, cNP forms a stable heme Fe(III)-NO complex, where the NO can be stored reversibly for a long period of time. In both cases, the NPs are found in the salivary glands of blood-sucking bugs. The insects use the nitrophorins to transport the NO to the victim's tissues, resulting in vasodilation and reduced blood coagulation. However, the structure of cNP is significantly different to those of the rNPs from Rhodnius prolixus. Furthermore, the cNP can bind a second NO molecule to the proximal heme cysteine when present at higher concentrations. High field Mössbauer spectroscopy on 57Fe enriched cNP complexed with NO shows reduction of the heme iron and formation of a ferrous nitric oxide (Fe(II)-NO) complex. Density functional theory calculations reproduce the experimental Mössbauer parameters and confirm this observation.

  2. Implications of glial nitric oxide in neurodegenerative diseases

    PubMed Central

    Yuste, Jose Enrique; Tarragon, Ernesto; Campuzano, Carmen María; Ros-Bernal, Francisco

    2015-01-01

    Nitric oxide (NO) is a pleiotropic janus-faced molecule synthesized by nitric oxide synthases (NOS) which plays a critical role in a number of physiological and pathological processes in humans. The physiological roles of NO depend on its local concentrations, as well as its availability and the nature of downstream target molecules. Its double-edged sword action has been linked to neurodegenerative disorders. Excessive NO production, as the evoked by inflammatory signals, has been identified as one of the major causative reasons for the pathogenesis of several neurodegenerative diseases. Moreover, excessive NO synthesis under neuroinflammation leads to the formation of reactive nitrogen species and neuronal cell death. There is an intimate relation between microglial activation, NO and neuroinflammation in the human brain. The role of NO in neuroinflammation has been defined in animal models where this neurotransmitter can modulate the inflammatory process acting on key regulatory pathways, such as those associated with excitotoxicity processes induced by glutamate accumulation and microglial activation. Activated glia express inducible NOS and produce NO that triggers calcium mobilization from the endoplasmic reticulum, activating the release of vesicular glutamate from astroglial cells resulting in neuronal death. This change in microglia potentially contributes to the increased age-associated susceptibility and neurodegeneration. In the current review, information is provided about the role of NO, glial activation and age-related processes in the central nervous system (CNS) that may be helpful in the isolation of new therapeutic targets for aging and neurodegenerative diseases. PMID:26347610

  3. Mitochondrial nitric oxide synthase regulates mitochondrial matrix pH.

    PubMed

    Ghafourifar, P; Richter, C

    1999-01-01

    Nitric oxide (nitrogen monoxide, NO) exerts a wide profile of its biological activities via regulation of respiration and respiration-dependent functions. The presence of nitric oxide synthase (NOS) in mitochondria (mtNOS) was recently reported by us (Ghafourifar and Richter, FEBS Lett. 418, 291-296, 1997) and others (Giulivi et al., J. Biol. Chem. 273, 11038-11043, 1998). Here we report that NO, provided by an NO donor as well as by mtNOS stimulation, regulates mitochondrial matrix pH, transmembrane potential and Ca2+ buffering capacity. Exogenously-added NO causes a dose-dependent matrix acidification. Also mtNOS stimulation, induced by loading mitochondria with Ca2+, causes mitochondrial matrix acidification and a drop in mitochondrial transmembrane potential. Inhibition of mtNOS's basal activity causes mitochondrial matrix alkalinization and provides a resistance to the sudden drop of mitochondrial transmembrane potential induced by mitochondrial Ca2+ uptake. We conclude that mtNOS plays a critical role in regulating mitochondrial delta(pH).

  4. Antiviral effect of nitric oxide during Japanese encephalitis virus infection

    PubMed Central

    Saxena, Shailendra K; Singh, Aditi; Mathur, Asha

    2000-01-01

    The ability of Japanese encephalitis virus (JEV) and JEV-induced macrophage derived neutrophil chemotactic factor (MDF) to produce nitric oxide (NO), and the possible antiviral effect of NO during JEV infection, was investigated. Splenic macrophages of JEV infected mice produced maximum NO in vivo at day 7 post infection, and in vitro at 24 h after JEV stimulation. MDF-induced NO production was dose dependent and maximal at 60 min after MDF treatment. The response was sensitive to anti-MDF antibody treatment and the nitric oxide synthase inhibitor NG-monomethyl-l-arginine (L-NMMA). Pretreatment of mice with L-NMMA increased the mortality to 100% in JEV infected mice in vivo and inhibited NO production in vitro, while MDF stimulated macrophages inhibited virus replication with high levels of NO production. MDF treatment increased the survival rate of JEV infected mice. The findings thus demonstrate that MDF induces production of NO during JEV infection, which has an antiviral effect. This may be one of the important mechanisms of natural immunity in controlling the initial stages of JEV infection. PMID:10762444

  5. Expression of inducible nitric oxide in human lung epithelial cells.

    PubMed

    Robbins, R A; Barnes, P J; Springall, D R; Warren, J B; Kwon, O J; Buttery, L D; Wilson, A J; Geller, D A; Polak, J M

    1994-08-30

    Nitric oxide (NO) is increased in the exhaled air of subjects with several airway disorders. To determine if cytokines could stimulate epithelial cells accounting for the increased NO, the capacity of the proinflammatory cytokines (cytomix: tumor necrosis factor-alpha, interleukin-1 beta, and interferon-gamma) to increase inducible nitric oxide synthase (iNOS) was investigated in A549 and primary cultures of human bronchial epithelial cells. Cytomix induced a time-dependent increase in nitrite levels in culture supernatant fluids (p < 0.05). Increased numbers of cells stained for iNOS and increased iNOS mRNA was detected in the cytokine-stimulated cells compared to control (p < 0.05). Dexamethasone diminished the cytokine-induced increase in nitrite, iNOS by immunocytochemistry, and iNOS mRNA. These data demonstrate that cytokines, such as those released by mononuclear cells, can induce lung epithelial iNOS expression and NO release, and that this is attenuated by dexamethasone.

  6. Involvement of nitric oxide in learning & memory processes

    PubMed Central

    Paul, Vanaja; Ekambaram, Perumal

    2011-01-01

    Nitric oxide (NO), synthesized from the amino acid, L-arginine by nitric oxide synthase (NOS) has received attention as a neurotransmitter in the brain. NO has been found to induce cognitive behaviour in experimental animals. In order to show evidence for the involvement of NO in learning and memory processes, the reports indicating the effects of its precursor, donors, and inhibitors of its synthesis in mammals, birds, fishes and invertebrates have been reviewed. Further, learning and memory impairment occurring in man and animals due to defective NO activity in the brain due to pathological conditions such as epilepsy, stress, diabetes and side effects of therapeutic agents and reversal of this condition by L-arginine and NO donors have been included. In addition, the reports that indicate ageing-induced impairment of cognition that is known to occur in Alzheimer's disease due to deposition of the toxic protein, beta amyloid and the effect of L-arginine and NO donors in preventing dementia in these patients have been reviewed. PMID:21623030

  7. Diurnal variation of nitric oxide in the upper stratosphere

    NASA Technical Reports Server (NTRS)

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

    1990-01-01

    Two recent measurements of the temporal variation of nitric oxide at constant altitude near 40 km are reported. The observations were made at float altitude with a balloon-borne chemiluminescence detector together with in situ ozone measurements. The first measurement was made at 44 N on September 17, 1987, at an altitude of 40 km from before sunrise until 1000 LT. The second observation was made at the same latitude on June 18, 1988, at 39 km from 0800 to 1230 LT. At an altitude of 40 km, nitric oxide was observed to start increasing very rapidly at sunrise when the solar zenith angle reached about 95 deg. After the rapid initial buildup, the rate of NO increase stabilized for 3 hours at about 1.2 ppbv/hour. Near 1100 LT at 39 km in summer, the NO mixing ratio was observed to become nearly constant. These features of the diurnal variation of NO are in accord with the temporal variation expected from a time-dependent zero-dimensional photochemical model.

  8. Hyperbaric oxygen upregulates cochlear constitutive nitric oxide synthase

    PubMed Central

    2011-01-01

    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

  9. Endomorphin-suppressed nitric oxide release from mice peritoneal macrophages.

    PubMed

    Balog, Tihomir; Sarić, Ana; Sobocanec, Sandra; Kusić, Borka; Marotti, Tatjana

    2010-02-01

    Endomorphins are newly discovered mu-opioid receptor selective immunocompetent opioid peptides. Endomorphin 1 is predominantly distributed in brain, while endomorphin 2 is widely allocated in the spinal cord. Lately, endomorphins have been investigated as modulators of reactive oxygen and nitrogen species. Nitric oxide is short lived radical involved in various biological processes such as regulation of blood vessel contraction, inflammation, neurotransmission and apoptosis. The aim of this work was to investigate the in vivo effects of endomorphins on nitric oxide release and NOS 2 isoenzyme upregulation in mice peritoneal macrophages additionally challenged ex vivo with lipopolysaccharide. The results showed that endomorphin 1 or endomorphin 2 in vitro did not change NO release from peritoneal mouse macrophages during a 48 h incubation period. On the other hand in vivo endomorphins had suppressive effect on NO release as well as on NOS 2 and IL-1 protein concentration. The most of suppressive effect in vivo of both endomorphins was blocked with 30 min pretreatment with mu-receptor selective antagonist beta-FNA, which proved involvement of opioid receptor pathway in suppressive effects of endomorphins.

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

    PubMed Central

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

    2002-01-01

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

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

    PubMed Central

    2011-01-01

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

  12. Therapeutic role of nitric oxide as emerging molecule.

    PubMed

    Kumar, Sahil; Singh, Rajesh K; Bhardwaj, T R

    2017-01-01

    NO has many physiological roles; in inflammation, pain, rheumatoid arthritis, immune system, gastroprotection, as antioxidant and reported to be a free radical scavenger.Intensive research on the biological functions of NO and other reactive nitrogen oxide species demands exogenous sources of NO donors as research tools and pharmaceuticals. Since the mid-1980s, the development of new NO donors has offered several advantages over theprevious NO donors, such as spontaneous release of NO, donation of NO under controlled rates, and even the targeting of NO to certain tissues. Nitric oxide releasing derivatives of conventional NSAIDs have been synthesized not only to avoid gastrotoxicity, but also for making them fit for topical delivery, targeting them to brain and increase their analgesic and anti-inflammatory activity. "Hybrid nitrates" have vital role in different like NSAIDs, Anti-platelet, Antileukemic, Glaucoma, Antihypertensive, Antimalarial etc.

  13. Nitric Oxide-Releasing Dendrimers as Antibacterial Agents

    PubMed Central

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

    2012-01-01

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

  14. Catalytic reduction of nitric oxide by the siderophore ferrioxamine B

    SciTech Connect

    Smith, S.R.; Thorp, H.H.

    1995-12-01

    The reduction of nitrogen oxides by transition metal complexes has been an area of intense research due to importance in the environment and physiology. We present a unique catalytic system in which the iron siderophore ferrioxamine B (E{sub l/2}(Fe(III/II))=-0.76 V v SSCE) facilitate, the reduction of nitric oxide at potentials as low as -0.6 V v. SSCE. The reduction proceeds through a rapidly formed iron-containing intermediate that can be observed in the visible spectrum. This absorbance exhibits a strong 1000 cm{sup -1} catalytic cycle. progression at room temperature. This species is the resting state of the catalytic cycle. The differential binding constant of the siderophore ligand for Fe(III) over Fe(II) provides part of the driving force in the catalytic cycle.

  15. Endothelial dihydrofolate reductase: critical for nitric oxide bioavailability and role in angiotensin II uncoupling of endothelial nitric oxide synthase.

    PubMed

    Chalupsky, Karel; Cai, Hua

    2005-06-21

    Recent studies demonstrate that oxidative inactivation of tetrahydrobiopterin (H4B) may cause uncoupling of endothelial nitric oxide synthase (eNOS) to produce superoxide (O2*-). H4B was found recyclable from its oxidized form by dihydrofolate reductase (DHFR) in several cell types. Functionality of the endothelial DHFR, however, remains completely unknown. Here we present findings that specific inhibition of endothelial DHFR by RNA interference markedly reduced endothelial H4B and nitric oxide (NO.) bioavailability. Furthermore, angiotensin II (100 nmol/liter for 24 h) caused a H4B deficiency that was mediated by H2O2-dependent down-regulation of DHFR. This response was associated with a significant increase in endothelial O2*- production, which was abolished by eNOS inhibitor N-nitro-L-arginine-methyl ester or H2O2 scavenger polyethylene glycol-conjugated catalase, strongly suggesting H2O2-dependent eNOS uncoupling. Rapid and transient activation of endothelial NAD(P)H oxidases was responsible for the initial burst production of O2* (Rac1 inhibitor NSC 23766 but not an N-nitro-L-arginine-methyl ester-attenuated ESR O2*- signal at 30 min) in response to angiotensin II, preceding a second peak in O2*- production at 24 h that predominantly depended on uncoupled eNOS. Overexpression of DHFR restored NO. production and diminished eNOS production of O2*- in angiotensin II-stimulated cells. In conclusion, these data represent evidence that DHFR is critical for H4B and NO. bioavailability in the endothelium. Endothelial NAD(P)H oxidase-derived H2O2 down-regulates DHFR expression in response to angiotensin II, resulting in H4B deficiency and uncoupling of eNOS. This signaling cascade may represent a universal mechanism underlying eNOS dysfunction under pathophysiological conditions associated with oxidant stress.

  16. Electron Paramagnetic Resonance Characterization of Tetrahydrobiopterin Radical Formation in Bacterial Nitric Oxide Synthase Compared to Mammalian Nitric Oxide Synthase

    PubMed Central

    Brunel, Albane; Santolini, Jérôme; Dorlet, Pierre

    2012-01-01

    H4B is an essential catalytic cofactor of the mNOSs. It acts as an electron donor and activates the ferrous heme-oxygen complex intermediate during Arg oxidation (first step) and NOHA oxidation (second step) leading to nitric oxide and citrulline as final products. However, its role as a proton donor is still debated. Furthermore, its exact involvement has never been explored for other NOSs such as NOS-like proteins from bacteria. This article proposes a comparative study of the role of H4B between iNOS and bsNOS. In this work, we have used freeze-quench to stop the arginine and NOHA oxidation reactions and trap reaction intermediates. We have characterized these intermediates using multifrequency electron paramagnetic resonance. For the first time, to our knowledge, we report a radical formation for a nonmammalian NOS. The results indicate that bsNOS, like iNOS, has the capacity to generate a pterin radical during Arg oxidation. Our current electron paramagnetic resonance data suggest that this radical is protonated indicating that H4B may not transfer any proton. In the 2nd step, the radical trapped for iNOS is also suggested to be protonated as in the 1st step, whereas it was not possible to trap a radical for the bsNOS 2nd step. Our data highlight potential differences for the catalytic mechanism of NOHA oxidation between mammalian and bacterial NOSs. PMID:22828337

  17. Hemoglobin Effects on Nitric Oxide Mediated Hypoxic Vasodilation.

    PubMed

    Rong, Zimei; Cooper, Chris E

    2016-01-01

    The brain responds to hypoxia with an increase in cerebral blood flow (CBF). However, such an increase is generally believed to start only after the oxygen tension decreases to a certain threshold level. Although many mechanisms (different vasodilator and different generation and metabolism mechanisms of the vasodilator) have been proposed at the molecular level, none of them has gained universal acceptance. Nitric oxide (NO) has been proposed to play a central role in the regulation of oxygen supply since it is a vasodilator whose production and metabolism are both oxygen dependent. We have used a computational model that simulates blood flow and oxygen metabolism in the brain (BRAINSIGNALS) to test mechanism by which NO may elucidate hypoxic vasodilation. The first model proposed that NO was produced by the enzyme nitric oxide synthase (NOS) and metabolized by the mitochondrial enzyme cytochrome c oxidase (CCO). NO production declined with decreasing oxygen concentration given that oxygen is a substrate for nitric oxide synthase (NOS). However, this was balanced by NO metabolism by CCO, which also declined with decreasing oxygen concentration. However, the NOS effect was dominant; the resulting model profiles of hypoxic vasodilation only approximated the experimental curves when an unfeasibly low K m for oxygen for NOS was input into the model. We therefore modified the model such that NO generation was via the nitrite reductase activity of deoxyhemoglobin instead of NOS, whilst keeping the metabolism of NO by CCO the same. NO production increased with decreasing oxygen concentration, leading to an improved reproduction of the experimental CBF versus PaO2 curve. However, the threshold phenomenon was not perfectly reproduced. In this present work, we incorporated a wider variety of oxygen dependent and independent NO production and removal mechanisms. We found that the addition of NO removal via oxidation to nitrate mediated by oxyhemoglobin resulted in the

  18. Nitric-oxide supplementation for treatment of long-term complications in argininosuccinic aciduria

    USDA-ARS?s Scientific Manuscript database

    Argininosuccinate lyase (ASL) is required for the synthesis and channeling of L-arginine to nitric oxide synthase (NOS) for nitric oxide (NO) production. Congenital ASL deficiency causes argininosuccinic aciduria (ASA), the second most common urea cycle disorder, and leads to deficiency of both urea...

  19. Nitric oxide pathways in circular muscle of the rat jejunum before and after small bowel transplantation.

    PubMed

    Balsiger, B M; Duenes, J A; Ohtani, N; Shibata, C; Farrugia, G; Anding, W J; Sarr, M G

    2000-01-01

    Previous studies suggest that nitric oxide synthase is upregulated after small bowel transplantation which may have implications in enteric dysfunction after small bowel transplantation. The aim of this study was to determine the role of nitric oxide in nonadrenergic, noncholinergic inhibitory function after small bowel transplantation in rat jejunal circular muscle. The following four groups of rats (n = >/=8 rats per group) were studied: Neurally intact control animals; 1 week after anesthesia and sham celiotomy, and either 1 week or 8 weeks after isogeneic, orthotopic small bowel transplantation. Full-thickness jejunal circular muscle strips were evaluated under isometric conditions for spontaneous contractile activity, response to electrical field stimulation, and effects of exogenous nitric oxide and nitric oxide antagonists. Spontaneous activity did not differ among groups. Electrical field stimulation inhibited activity similarly in all groups. Exogenous nitric oxide, NG-monomethyl L-arginine monoacetate salt (a nitric oxide synthase inhibitor), and methylene blue (cGMP antagonist) had no effect on spontaneous activity. Neither nitric oxide antagonist altered the inhibitory response to neural excitation by electrical field stimulation in any group. Nitric oxide, a known inhibitory neurotransmitter in other gut smooth muscle, has no apparent role in rat jejunal circular muscle before or after small bowel transplantation.

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

    SciTech Connect

    Stadler, J.; Curran, R.D.; Ochoa, J.B.; Harbrecht, B.G.; Hoffman, R.A.; Simmons, R.L.; Billiar, T.R. )

    1991-02-01

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

  1. Naked eye detection of nitric oxide release from nitrosothiols aided by gold nanoparticles.

    PubMed

    Priya, S; Kaviyarasan, T; Berchmans, Sheela

    2012-04-07

    In this work we have demonstrated that nitric oxide can be monitored spectrophotometrically using cyclodextrin encapsulated ferrocene. The detection course showed the colour change from yellow to blue which can be detected with the naked eye. Also we describe the catalytic effect of gold nanoparticles in enhancing nitric oxide release from S-nitrosothiols.

  2. Nitric oxide mediates the stress response induced by diatom aldehydes in the sea urchin Paracentrotus lividus.

    PubMed

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

    2011-01-01

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

  3. Effect of soy isoflavone supplementation on nitric oxide metabolism and blood pressure in menopausal women

    USDA-ARS?s Scientific Manuscript database

    Isoflavones, having chemical structures similar to estrogens, are believed to stimulate nitric oxide production and thus lower blood pressure. The efficacy of soy isoflavone supplementation to stimulate nitric oxide production and lower blood pressure in menopausal women with high normal blood press...

  4. Polarographic detection of nitric oxide released from cardiovascular compounds in aqueous solutions.

    PubMed

    Pataricza, J; Penke, B; Balogh, G E; Papp, J G

    1998-03-01

    In order to detect the concentration of nitric oxide, known to be one of the biologically active principles of certain cardiovascular compounds, a highly selective polarographic/amperometric device was used. The nitric oxide-releasing properties of sodium nitroprusside, nitroglycerine, nicorandil, and the molsidomine metabolite, 3-morpholinosydnonimine, were compared in the following cell-free experimental solutions in vitro: in Krebs-Henseleit solution with and without a sulfhydryl donor, L-cysteine, in an acidic, reducing medium, and in Krebs-Henseleit solution with superoxide dismutase enzyme. Sodium nitroprusside released similar concentrations of nitric oxide in Krebs-Henseleit solution and in the acidic, reducing medium. L-Cysteine inhibited the release of nitric oxide at physiological pH. In the presence of nitroglycerine, nitric oxide signals were detected in the acidic, reducing environment and in L-cysteine-rich Krebs-Henseleit solution but not in the absence of the sulfhydryl donor. Amperometric signals could not be detected after adding nicorandil in all the experimental conditions used. 3-Morpholinosydnonimine released nitric oxide only in the presence of the superoxide dismutase enzyme. Our results suggest that the polarographic electrode is able to detect the release of nitric oxide from sodium nitroprusside, nitroglycerine, and 3-morpholinosydnonimine in the absence of biological material. The present observations support the importance of the chemical environment during the detection of nitric oxide from donor compounds in the common in vitro bathing systems.

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

    PubMed Central

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

    2011-01-01

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

  6. Neuro-immune-endocrine mechanisms during septic shock: role for nitric oxide in vasopressin and oxytocin release.

    PubMed

    Carnio, E C; Moreto, V; Giusti-Paiva, A; Antunes-Rodrigues, J

    2006-06-01

    Septic shock is a major cause of death following trauma and a persistent problem in surgical patients. It is a challenge to the critical care medicine specialist and carries an unacceptably high mortality rate, despite adequate antibiotic and vasopressor therapy. The prevalent hypothesis regarding its mechanism is that the syndrome is caused by an excessive defensive and inflammatory response. During the acute phase some signalling mechanisms are activated, particularly hormone release, which function to restore the host homeostasis that has been disturbed by the infection. Since the neuroendocrine and immune systems are functionally related, so the exposure to antigens induces a synchronized response, which allows the organism to successfully endure immunology changes. An important characteristic of this communication includes the appearance of proteins released into the circulation by activated immune cells. These proteins, called cytokines can enter the circulation and reach neuroendocrine organs, where they act either themselves or through the release of intermediates such as prostaglandin, catecholamines and nitric oxide. The synthesis of nitric oxide may be induced in brain as a consequence of infection and may alter the function of the hypothalamic-pituitary axis. In this review we discuss the physiologic roles of the nitric oxide in central nervous system controlling the regulation of vasopressin and oxytocin during the pathophysiology of sepsis.

  7. The Arabidopsis Prohibitin Gene PHB3 Functions in Nitric Oxide-Mediated Responses and in Hydrogen Peroxide-Induced Nitric Oxide Accumulation.

    PubMed

    Wang, Yong; Ries, Amber; Wu, Kati; Yang, Albert; Crawford, Nigel M

    2010-01-01

    To discover genes involved in nitric oxide (NO) metabolism, a genetic screen was employed to identify mutants defective in NO accumulation after treatment with the physiological inducer hydrogen peroxide. In wild-type Arabidopsis thaliana plants, NO levels increase eightfold in roots after H(2)O(2) treatment for 30 min. A mutant defective in H(2)O(2)-induced NO accumulation was identified, and the corresponding mutation was mapped to the prohibitin gene PHB3, converting the highly conserved Gly-37 to an Asp in the protein's SPFH domain. This point mutant and a T-DNA insertion mutant were examined for other NO-related phenotypes. Both mutants were defective in abscisic acid-induced NO accumulation and stomatal closure and in auxin-induced lateral root formation. Both mutants were less sensitive to salt stress, showing no increase in NO accumulation and less inhibition of primary root growth in response to NaCl treatment. In addition, light-induced NO accumulation was dramatically reduced in cotyledons. We found no evidence for impaired H(2)O(2) metabolism or signaling in the mutants as H(2)O(2) levels and H(2)O(2)-induced gene expression were unaffected by the mutations. These findings identify a component of the NO homeostasis system in plants and expand the function of prohibitin genes to include regulation of NO accumulation and NO-mediated responses.

  8. Traditional Chinese medicine's intervention in endothelial nitric oxide synthase activation and nitric oxide synthesis in cardiovascular system.

    PubMed

    Zhu, Jin-Qiang; Song, Wan-Shan; Hu, Zhen; Ye, Qiao-Feng; Liang, Yu-Bin; Kang, Li-Yuan

    2015-02-10

    Cardiovascular disease (CVD) is one of the most dangerous diseases which has become a major cause of human death. Many researches evidenced that nitric oxide (NO)/endothelial nitric oxide synthase (eNOS) system plays a significant role in the occurrence and development of CVD. NO, an important signaling molecule, closely associated with the regulation of vasodilatation, blood rheology, blood clotting and other physiological and pathological processes. The synthesis of NO in the endothelial cells primarily depends on the eNOS activity, thus the exploration of the mechanisms and effects of the eNOS activation on NO production is of great significance. Recently, studies on the effects of traditional Chinese medicine (TCM) and its extracts on eNOS activation and NO synthesis have gradually attracted more and more attentions. In this paper, we reviewed the mechanisms of NO synthesis and eNOS activation in the vascular endothelial cells (VECs) and intervention of TCM, so as to provide reference and train of thought to the intensive study of NO/eNOS system and the research and development of new drug for the treatment of CVD.

  9. Use of inhaled nitric oxide in the new born period: results from the European Inhaled Nitric Oxide Registry.

    PubMed

    Dewhurst, Chris; Ibrahim, Hafis; Göthberg, Sylvia; Jónsson, Baldvin; Subhedar, Nimish

    2010-06-01

    The aim of this study was to present data relating to the use of inhaled nitric oxide (iNO) in newborn infants included in the European Inhaled Nitric Oxide Registry. Demographic, clinical and therapeutic data from seven European centres are reported. Univariate analyses were performed to identify factors associated with acute response to iNO and survival without extra corporeal membrane oxygenation (ECMO). A total of 112 newborn infants received iNO, with 40% being less than 34 weeks gestational age. The commonest indication for iNO was secondary pulmonary hypertension. Acute response to iNO was more common in infants with a higher oxygenation index (median OI 32.7 vs 22.6, p = 0.040), although acute response did not predict survival without ECMO. Infants who survived without ECMO had a lower OI prior to therapy (median OI 24 vs 43, p = 0.009), were commenced on a higher starting dose (median dose 20 ppm vs 10 ppm p = 0.013) and received a lower maintenance dose (median dose 10 vs 17 ppm, p = 0.027) than those who died or received ECMO. Collating and reporting data about iNO therapy in neonates across a number of European centres using a web-based system is feasible. These data may be used to monitor the clinical use of iNO, identify adverse effects, generate research hypotheses and promote high standards in the clinical use of iNO.

  10. Monophosphoryl lipid A stimulated up-regulation of nitric oxide synthase and nitric oxide release by human monocytes in vitro.

    PubMed

    Saha, D C; Astiz, M E; Lin, R Y; Rackow, E C; Eales, L J

    1997-10-01

    Monophosphoryl lipid A (MPL) is a derivative of lipopolysaccharide (LPS) with reduced toxicity which has been shown to modulate various immune functions in monocytes. We examined whether human monocytes can be stimulated to produce nitric oxide (NO) and its catalytic enzyme nitric oxide synthase (NOS). Monocytes were stimulated with LPS or MPL and both NOS and NO (as nitrite) production were measured. MPL at high doses (> 100 micrograms/ml) stimulated monocytes to release NO that was significantly greater than both the control and LPS-treated monocytes (p < 0.05). NO release by control cells and the LPS treated cells was not significantly different. Both arginase and N-monomethyl arginine (NMLA) inhibited the MPL stimulated release of NO (p < 0.01). MPL significantly increased inducible NOS (iNOS) expression as measured by both fluorescent microscopy and flow cytometry (p < 0.05). Similarly, both soluble NOS (sNOS) and particulate NOS (pNOS) activity were significantly up-regulated by MPL (p < 0.05). Significant correlations were found between pNOS expression and sNOS release (r = 0.72, p < 0.0001) and between 12 h NO release and sNOS production (r = 0.44, p < 0.005). These experiments confirm that human monocytes can be stimulated with MPL to produce NO in vitro and suggest that up-regulation of pNOS does not preclude NO release.

  11. Study of nitric oxide catalytic oxidation on manganese oxides-loaded activated carbon at low temperature

    NASA Astrophysics Data System (ADS)

    You, Fu-Tian; Yu, Guang-Wei; Wang, Yin; Xing, Zhen-Jiao; Liu, Xue-Jiao; Li, Jie

    2017-08-01

    Nitric oxide (NO) is an air pollutant that is difficult to remove at low concentration and low temperature. Manganese oxides (MnOx)-loaded activated carbon (MLAC) was prepared by a co-precipitation method and studied as a new catalyst for NO oxidation at low temperature. Characterization of MLAC included X-ray diffraction (XRD), scanning electron microscopy (SEM), N2 adsorption/desorption and X-ray photoelectron spectroscopy (XPS). Activity tests demonstrated the influence of the amount of MnOx and the test conditions on the reaction. MLAC with 7.5 wt.% MnOx (MLAC003) exhibits the highest NO conversion (38.7%) at 1000 ppm NO, 20 vol.% O2, room temperature and GHSV ca. 16000 h-1. The NO conversion of MLAC003 was elevated by 26% compared with that of activated carbon. The results of the MLAC003 activity test under different test conditions demonstrated that NO conversion is also influenced by inlet NO concentration, inlet O2 concentration, reaction temperature and GHSV. The NO adsorption-desorption process in micropores of activated carbon is fundamental to NO oxidation, which can be controlled by pore structure and reaction temperature. The activity elevation caused by MnOx loading is assumed to be related to Mn4+/Mn3+ ratio. Finally, a mechanism of NO catalytic oxidation on MLAC based on NO adsorption-desorption and MnOx lattice O transfer is proposed.

  12. Nitrones: not only extraordinary spin traps, but also good nitric oxide sources in vivo.

    PubMed

    Croitoru, Mircea Dumitru; Petkes, Hermina Iulia; Fülöp, Ibolya; Cotârlan, Remus; Şerban, Oana Elena; Dogaru, Titica Maria; Gâz Florea, Şerban Andrei; Tőkés, Béla; Majdik, Cornelia

    2015-12-01

    Free radicals are involved in the development of reperfusion injuries. Using a spin trap, the intensity of such lesions can be reduced. Nitrones (effective in vivo spin traps) were tried in this work as in vivo nitric oxide donors. Nitrite and nitrate concentration values (rabbit blood) were used as biomarkers of nitric oxide production. Most nitrones did not increase plasma concentrations of nitrite and nitrate; on the contrary, reduced plasma concentrations of these indicators were noted. However, glyoxal isopropyldinitrone, in a dose of 50 mg kg-1, was highly effective in increasing nitric oxide production. At the same time, nitrones do not react with hepatic homogenates, proving that the release of nitric oxide takes place in the tissues and is not related to hepatic metabolism. Before using nitrones in vivo, they were tested in vitro for the ability to release nitric oxide following a reaction with the hydroxyl radical.

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

    PubMed

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

    2015-03-01

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

  14. Redox interactions of nitric oxide with dopamine and its derivatives.

    PubMed

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

    2005-03-15

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

  15. Nitrones are able to release nitric oxide in aqueous environment under hydroxyl free radical attack.

    PubMed

    Croitoru, Mircea Dumitru; Ibolya, Fülöp; Pop, Maria Cristiana; Dergez, Timea; Mitroi, Brânduşa; Dogaru, Maria Titica; Tokés, Béla

    2011-10-30

    Importance of a nitric oxide donor that can act as a spin trap might bring some new therapeutic possibilities regarding the treatment of ischemic diseases by reducing the intensity of free radical produced reperfusion lesions. These substances might be also used as a new type of photo protectors since they can absorb UV radiation, capture free radicals formed by interaction of UV radiation with tissue constituents, and tanning of the skin will be permitted due to nitric oxide release. The purpose of this work was to measure the ability of nitrones to release nitric oxide and how different factors (temperature, nitrone concentration, and free radicals) influence the releasing ability. Mostly, indirect determination of nitric oxide was carried out, by measuring nitrite and nitrate amounts (as decomposition products of nitric oxide), all nitrones proved to release significant amounts of nitric oxide. Nitrite measurements were made based on an HPLC-VIS method that uses pre-column derivatization of nitrite by forming an azo dye (limit of quantification: 5ng/ml). No good correlation was found between the amount of nitric oxide and temperature for most studied nitrones but between the formation of nitric oxide and nitrone concentration an asymptotic correlation was found. Fenton reagent also yielded formation of nitric oxide from nitrones and formed amounts were not different from those recorded for UV irradiation. Most of the nitrones effectively released about 0.5% of the maximum amount of nitric oxide that is chemically possible and estimated concentrations of 0.1μM were present in the solutions during decomposition.

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2014-01-01

    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. 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. 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). 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.

  18. Oxidative stress modulates the nitric oxide defense promoted by Escherichia coli flavorubredoxin.

    PubMed

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

    2012-07-01

    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.

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

    PubMed Central

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

    2012-01-01

    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

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

    PubMed

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

    2000-09-15

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

  1. NITRIC OXIDE, MITOCHONDRIAL HYPERPOLARIZATION AND T-CELL ACTIVATION

    PubMed Central

    Nagy, Gyorgy; Koncz, Agnes; Fernandez, David; Perl, Andras

    2007-01-01

    T lymphocyte activation is associated with nitric oxide (NO) production that plays an essential role in multiple T cell functions. NO acts as a messenger, activating soluble guanyl cyclase and participating in the transduction signaling pathways involving cyclic GMP. NO modulates mitochondrial events that are involved in apoptosis and regulates mitochondrial membrane potential and mitochondrial biogenesis in many cell types, including lymphocytes. Mitochondrial hyperpolarization (MHP), an early and reversible event during both T lymphocyte activation and apoptosis, is regulated by NO. Here, we discuss recent evidence that NO-induced MHP represents a molecular switch in multiple T cell signaling pathways. Overproduction of NO in systemic lupus erythematosus (SLE) induces mitochondrial biogenesis and alters Ca2+ signaling. Thus, while NO plays a physiological role in lymphocyte cell signaling, its overproduction may disturb normal T cell function, contributing to the pathogenesis of autoimmunity. PMID:17462531

  2. Nitric oxide regulates synaptic transmission between spiny projection neurons.

    PubMed

    Sagi, Yotam; Heiman, Myriam; Peterson, Jayms D; Musatov, Sergei; Scarduzio, Mariangela; Logan, Stephen M; Kaplitt, Michael G; Surmeier, Dalton J; Heintz, Nathaniel; Greengard, Paul

    2014-12-09

    Recurrent axon collaterals are a major means of communication between spiny projection neurons (SPNs) in the striatum and profoundly affect the function of the basal ganglia. However, little is known about the molecular and cellular mechanisms that underlie this communication. We show that intrastriatal nitric oxide (NO) signaling elevates the expression of the vesicular GABA transporter (VGAT) within recurrent collaterals of SPNs. Down-regulation of striatal NO signaling resulted in an attenuation of GABAergic signaling in SPN local collaterals, down-regulation of VGAT expression in local processes of SPNs, and impaired motor behavior. PKG1 and cAMP response element-binding protein are involved in the signal transduction that transcriptionally regulates VGAT by NO. These data suggest that transcriptional control of the vesicular GABA transporter by NO regulates GABA transmission and action selection.

  3. Upstream and downstream signals of nitric oxide in pathogen defence.

    PubMed

    Gaupels, Frank; Kuruthukulangarakoola, Gitto Thomas; Durner, Jörg

    2011-12-01

    Nitric oxide (NO) is now recognised as a crucial player in plant defence against pathogens. Considerable progress has been made in defining upstream and downstream signals of NO. Recently, MAP kinases, cyclic nucleotide phosphates, calcium and phosphatidic acid were demonstrated to be involved in pathogen-induced NO-production. However, the search for inducers of NO synthesis is difficult because of the still ambiguous enzymatic source of NO. Accumulation of NO triggers signal transduction by other second messengers. Here we depict NON-EXPRESSOR OF PATHOGENESIS-RELATED 1 and glyceraldehyde-3-phosphate dehydrogenase as central redox switches translating NO redox signalling into cellular responses. Although the exact position of NO in defence signal networks is unresolved at last some NO-related signal cascades are emerging.

  4. Antibacterial Efficacy of Exogenous Nitric Oxide on Periodontal Pathogens

    PubMed Central

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

    2014-01-01

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

  5. Transcriptomic Response to Nitric Oxide Treatment in Larix olgensis Henry

    PubMed Central

    Hu, Xiaoqing; Yang, Jingli; Li, Chenghao

    2015-01-01

    Larix olgensis Henry is an important coniferous species found in plantation forests in northeastern China, but it is vulnerable to pathogens. Nitric oxide (NO) is an important molecule involved in plant resistance to pathogens. To study the regulatory role of NO at the transcriptional level, we characterized the transcriptomic response of L. olgensis seedlings to sodium nitroprusside (SNP, NO donor) using Illumina sequencing and de novo transcriptome assembly. A significant number of putative metabolic pathways and functions associated with the unique sequences were identified. Genes related to plant pathogen infection (FLS2, WRKY33, MAPKKK, and PR1) were upregulated with SNP treatment. This report describes the potential contribution of NO to disease resistance in L. olgensis as induced by biotic stress. Our results provide a substantial contribution to the genomic and transcriptomic resources for L. olgensis, as well as expanding our understanding of the involvement of NO in defense responses at the transcriptional level. PMID:26633380

  6. Nitric oxide in the middle to upper thermosphere

    NASA Technical Reports Server (NTRS)

    Siskind, David E.; Rusch, David W.

    1992-01-01

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

  7. Solar cycle variation of thermospheric nitric oxide at solstice

    NASA Technical Reports Server (NTRS)

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

    1990-01-01

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

  8. Nitric oxide production in striatum and pallidum of cirrhotic rats.

    PubMed

    Montes, Sergio; Pérez-Severiano, Francisca; Vergara, Paula; Segovia, José; Ríos, Camilo; Muriel, Pablo

    2006-01-01

    Ammonium and manganese are neurotoxic agents related to brain metabolic disturbances observed after prolonged liver damage. The aim of this study was to assess the production of nitric oxide (NO) in the brain of cirrhotic rats exposed to manganese. We induced cirrhosis by bile duct ligation for 4 weeks in rats. From brain, striatum and globus pallidus were dissected out, and NO synthase activity and the content of nitrites plus nitrates (NOx) were determined. In pallidum we found a diminished constitutive NO synthase activity from cirrhotic rats, independently of manganese exposure. This result was confirmed by low levels of NOx in the same brain area (P<0.05, two-way ANOVA). This finding was not related to protein expression of NO synthase since no differences were observed in immunoblot signals between cirrhotic and sham-operated animals. Results from present study suggest that the production of NO is reduced in basal ganglia during cirrhosis.

  9. Solar cycle variation of thermospheric nitric oxide at solstice

    NASA Technical Reports Server (NTRS)

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

    1990-01-01

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

  10. Inhaled nitric oxide induces cerebrovascular effects in anesthetized pigs.

    PubMed

    Kuebler, W M; Kisch-Wedel, H; Kemming, G I; Meisner, F; Bruhn, S; Koehler, C; Flondor, M; Messmer, K; Zwissler, B

    2003-09-11

    Although inhaled nitric oxide (NO(i)) is considered to act selectively on pulmonary vessels, EEG abnormalities and even occasional neurotoxic effects of NO(i) have been proposed. Here, we investigated cerebrovascular effects of increasing concentrations of 5, 10 and 50 ppm NO(i) in seven anesthetized pigs. Cerebral hemodynamics were assessed non-invasively by use of near-infared spectroscopy and indicator dilution techniques. NO(i) increased cerebral blood volume significantly and reversibly. This effect was not attributable to changes of macrohemodynamic parameters or arterial blood gases. Simultaneously, cerebral transit time increased while cerebral blood flow remained unchanged. These data demonstrate a vasodilatory action of NO(i) in the cerebral vasculature, which may occur preferentially in the venous compartment.

  11. Therapeutic effects of nitric oxide-aspirin hybrid drugs.

    PubMed

    Turnbull, Catriona M; Rossi, Adriano G; Megson, Ian L

    2006-12-01

    This review examines the therapeutic potential and mechanisms of action of drugs known as nitric oxide (NO)-aspirins. Drugs of this class have an NO-releasing moiety joined by ester linkage to the aspirin molecule. NO-aspirins have the capability to release NO in addition to retaining the cyclooxygenase-inhibitory action of aspirin. The protective nature of NO led to the development of NO-aspirins in the hope that they might avoid the gastric side effects associated with aspirin. However, it has become apparent that the drug-derived NO instills potential for a wide range of added beneficial effects over the parent compound. In this review, the authors focus on the analgesic, anti-inflammatory, cardiovascular and chemopreventative actions of compounds of this emerging drug class.

  12. Role of nitric oxide in genotoxicity: implication for carcinogenesis.

    PubMed

    Felley-Bosco, E

    1998-03-01

    Reactive oxygen species can initiate carcinogenesis by virtue of their capacity to react with DNA and cause mutations. Recently, it has been suggested that nitric oxide (NO) and its derivatives produced in inflamed tissues could contribute to the carcinogenesis process. Genotoxicity of NO follows its reaction with oxygen and superoxide. It can be due either to direct DNA damage or indirect DNA damage. Direct damage includes DNA base deamination, peroxynitrite-induced adducts formation and single strand breaks in the DNA. Indirect damage is due to the interaction of NO reactive species with other molecules such as amines, thiols and lipids. The efficiency of one pathway or another might depend on the cellular antioxidant status or the presence of free metals.

  13. Nitric Oxide Regulates Neurogenesis in the Hippocampus following Seizures

    PubMed Central

    Carreira, Bruno P.; Santos, Daniela F.; Santos, Ana I.; Carvalho, Caetana M.; Araújo, Inês M.

    2015-01-01

    Hippocampal neurogenesis is changed by brain injury. When neuroinflammation accompanies injury, activation of resident microglial cells promotes the release of inflammatory cytokines and reactive oxygen/nitrogen species like nitric oxide (NO). In these conditions, NO promotes proliferation of neural stem cells (NSC) in the hippocampus. However, little is known about the role of NO in the survival and differentiation of newborn cells in the injured dentate gyrus. Here we investigated the role of NO following seizures in the regulation of proliferation, migration, differentiation, and survival of NSC in the hippocampus using the kainic acid (KA) induced seizure mouse model. We show that NO increased the proliferation of NSC and the number of neuroblasts following seizures but was detrimental to the survival of newborn neurons. NO was also required for the maintenance of long-term neuroinflammation. Taken together, our data show that NO positively contributes to the initial stages of neurogenesis following seizures but compromises survival of newborn neurons. PMID:26587180

  14. Pharmacologic strategies in neonatal pulmonary hypertension other than nitric oxide.

    PubMed

    Lakshminrusimha, Satyan; Mathew, Bobby; Leach, Corinne L

    2016-04-01

    Inhaled nitric oxide (iNO) is approved for use in persistent pulmonary hypertension of the newborn (PPHN) but does not lead to sustained improvement in oxygenation in one-third of patients with PPHN. Inhaled NO is less effective in the management of PPHN secondary to congenital diaphragmatic hernia (CDH), extreme prematurity, and bronchopulmonary dysplasia (BPD). Intravenous pulmonary vasodilators such as prostacyclin, alprostadil, sildenafil, and milrinone have been successfully used in PPHN resistant to iNO. Oral pulmonary vasodilators such as endothelin receptor antagonist bosentan and phosphodiesterase-5 inhibitors such as sildenafil and tadalafil are used both during acute and chronic phases of PPHN. In the absence of infection, glucocorticoids may also be effective in PPHN. Many of these pharmacologic agents are not approved for use in PPHN and our knowledge is based on case reports and small trials. Large multicenter randomized controlled trials with long-term follow-up are required to evaluate alternate pharmacologic strategies in PPHN.

  15. Nitric oxide deficiency and endothelial dysfunction in pulmonary arterial hypertension.

    PubMed

    Klinger, James R; Abman, Steven H; Gladwin, Mark T

    2013-09-15

    Nitric oxide (NO) signaling plays a major role in modulating vascular tone and remodeling in the pulmonary circulation, but its role in the pathogenesis of pulmonary vascular diseases is still not completely understood. Numerous abnormalities of NO synthesis and signaling have been identified in animal models of pulmonary vascular disease and in humans with pulmonary hypertension. Many of these abnormalities have become targets of new therapies for the treatment of pulmonary hypertension. However, it is unclear to what extent alterations in NO signaling contribute to pulmonary hypertensive responses or merely reflect abnormalities induced by the underlying disease. This perspective examines the current understanding of altered NO signaling in pulmonary hypertensive diseases and discusses how these alterations may contribute to the pathogenesis of pulmonary hypertension. The efficacy and limitations of presently available therapies for pulmonary hypertension that target NO signaling are reviewed along with an update on investigational therapies that use this pathway to reverse pulmonary hypertensive changes.

  16. Nitric oxide: promoter or suppressor of programmed cell death?

    PubMed

    Wang, Yiqin; Chen, Chen; Loake, Gary J; Chu, Chengcai

    2010-02-01

    Nitric oxide (NO) is a short-lived gaseous free radical that predominantly functions as a messenger and effector molecule. It affects a variety of physiological processes, including programmed cell death (PCD) through cyclic guanosine monophosphate (cGMP)-dependent and - independent pathways. In this field, dominant discoveries are the diverse apoptosis networks in mammalian cells, which involve signals primarily via death receptors (extrinsic pathway) or the mitochondria (intrinsic pathway) that recruit caspases as effector molecules. In plants, PCD shares some similarities with animal cells, but NO is involved in PCD induction via interacting with pathways of phytohormones. NO has both promoting and suppressing effects on cell death, depending on a variety of factors, such as cell type, cellular redox status, and the flux and dose of local NO. In this article, we focus on how NO regulates the apoptotic signal cascade through protein S-nitrosylation and review the recent progress on mechanisms of PCD in both mammalian and plant cells.

  17. The biphasic nature of nitric oxide responses in tumor biology.

    PubMed

    Ridnour, Lisa A; Thomas, Douglas D; Donzelli, Sonia; Espey, Michael G; Roberts, David D; Wink, David A; Isenberg, Jeffrey S

    2006-01-01

    The dual or biphasic responses of cancer to nitric oxide (NO) arise from its concentration dependent ability to regulate tumor growth, migration, invasion, survival, angiogenesis, and metastasis. The outcome of these various NO-dependent processes is dictated by several factors including NO flux, the chemical redox environment, and the duration of NO exposure. Further, it was recently discovered that an NO-induced redox flux in vascular endothelial cells hypersensitizes these cells to the antiangiogenic effects of thrombospondin-1. This suggests a novel treatment paradigm for targeting tumor-driven angiogenesis that combines redox modulation with mimetic derivatives of thrombospondin-1. This article discusses the biphasic nature of NO in cancer biology and the implications of NO-driven redox flux for modulation of tumor-stimulated angiogenesis, growth, and metastasis.

  18. Regulation of Injury-Induced Neurogenesis by Nitric Oxide

    PubMed Central

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

    2012-01-01

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

  19. Insulin affects sperm capacity in pig through nitric oxide.

    PubMed

    Aquila, Saveria; Giordano, Francesca; Guido, Carmela; Rago, Vittoria; Carpino, Amalia

    2013-11-01

    Insulin (Ins) has recently been demonstrated to have the ability to induce the capacitation process in pig spermatozoa. In various mammalian species, capacitation has been linked to the nitric oxide (NO) signalling; therefore, this study investigated NO production in Ins-treated pig spermatozoa by fluorescence-activated cell sorting. For the same samples, sperm capacitation was evaluated by chlortetracycline staining, protein tyrosine phosphorylation pattern and acrosomal status. A significant increase of the intrasperm NO level and the activation of three capacitation indices were detected in response to Ins treatment. Conversely, sperm preincubation with an NO synthase inhibitor (N-nitro-L-arginine methyl ester) or with the anti-Ins receptor β (IRβ) antibody reversed all of the Ins-related effects. These results suggest that Ins has the capacity to enhance intracellular NO concentrations in pig spermatozoa and indicate a possible NO implication upon Ins promotion of capacitation.

  20. Influence of nitric oxide in the improvement of muscle power

    PubMed Central

    Bernardo, Daniela Navarro D'Almeida; Bryk, Flávio Fernandes; Fucs, Patrícia Maria de Moraes Barros

    2015-01-01

    ABSTRACT OBJECTIVE To evaluate whether nitric oxide (NO) supplementa-tion is directly related to increased muscle power in response to strength exercise training METHODS The study included 36 individuals who underwent training for eight weeks (three times per week) with weights, who were randomly divided into two groups, both receiving the same training protocol, but one group used 3g of arginine, as a precursor of NO, and the other received placebo RESULTS There was no significant difference between groups, only a significant difference for both groups between moments: before and after the training protocol CONCLUSION Oral administration of arginine asso-ciated with a training program did not increase the muscular power of individuals. Level of Evidence I, Study Type: Highquality randomized trial with statistically significant diffe-rence or no statistically significant difference but narrow confidence intervals. PMID:27057140

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

    PubMed

    Pitsikas, Nikolaos

    2015-05-15

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

  2. Kinetic characteristics of nitric oxide synthase from rat brain.

    PubMed Central

    Knowles, R G; Palacios, M; Palmer, R M; Moncada, S

    1990-01-01

    The relationship between the rate of synthesis of nitric oxide (NO) and guanylate cyclase stimulation was used to characterize the kinetics of the NO synthase from rat forebrain and of some inhibitors of this enzyme. The NO synthase had an absolute requirement for L-arginine and NADPH and did not require any other cofactors. The enzyme had a Vmax. of 42 pmol of NO formed.min-1.mg of protein-1 and a Km for L-arginine of 8.4 microM. Three analogues of L-arginine, namely NG-monomethyl-L-arginine, NG-nitro-L-arginine and NG-iminoethyl-L-ornithine inhibited the brain NO synthase. All three compounds were competitive inhibitors of the enzyme with Ki values of 0.7, 0.4 and 1.2 microM respectively. PMID:1695842

  3. Working with nitric oxide and hydrogen sulfide in biological systems

    PubMed Central

    Yuan, Shuai; Kevil, Christopher G.

    2014-01-01

    Nitric oxide (NO) and hydrogen sulfide (H2S) are gasotransmitter molecules important in numerous physiological and pathological processes. Although these molecules were first known as environmental toxicants, it is now evident that that they are intricately involved in diverse cellular functions with impact on numerous physiological and pathogenic processes. NO and H2S share some common characteristics but also have unique chemical properties that suggest potential complementary interactions between the two in affecting cellular biochemistry and metabolism. Central among these is the interactions between NO, H2S, and thiols that constitute new ways to regulate protein function, signaling, and cellular responses. In this review, we discuss fundamental biochemical principals, molecular functions, measurement methods, and the pathophysiological relevance of NO and H2S. PMID:25550314

  4. Reaction between nitric oxide and ozone in solid nitrogen

    NASA Technical Reports Server (NTRS)

    Lucas, D.; Pimentel, G. C.

    1979-01-01

    Nitrogen dioxide, NO2, is produced when nitric oxide, NO, and ozone, O3, are suspended in a nitrogen matrix at 11-20 K. The NO2 is formed with first-order kinetics, a 12 K rate constant of (1.4 + or - 0.2) x 0.00001/sec, and an apparent activation energy of 106 + or - 10 cal/mol. Isotopic labeling, variation of concentrations, and cold shield experiments show that the growth of NO2 is due to reaction between ozone molecules and NO monomers, and that the reaction is neither infrared-induced nor does it seem to be a heavy atom tunneling process. Reaction is attributed to nearest-neighbor NO.O3 pairs probably held in a specific orientational relationship that affects the kinetic behavior. When the temperature is raised, more such reactive pairs are generated, presumably by local diffusion. Possible mechanisms are discussed.

  5. Kinetics of the reaction of nitric oxide with hydrogen

    NASA Technical Reports Server (NTRS)

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

    1974-01-01

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

  6. Nitric oxide counters ethylene effects on ripening fruits

    PubMed Central

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

    2012-01-01

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

  7. Fabrication of nitric oxide-releasing polyurethane glucose sensor membranes

    PubMed Central

    Koh, Ahyeon; Riccio, Daniel A.; Sun, Bin; Carpenter, Alexis W.; Nichols, Scott P.; Schoenfisch, Mark H.

    2011-01-01

    Despite clear evidence that polymeric nitric oxide (NO) release coatings reduce the foreign body response (FBR) and may thus improve the analytical performance of in vivo continuous glucose monitoring devices when used as sensor membranes, the compatibility of the NO release chemistry with that required for enzymatic glucose sensing remains unclear. Herein, we describe the fabrication and characterization of NO-releasing polyurethane sensor membranes using NO donor-modified silica vehicles embedded within the polymer. In addition to demonstrating tunable NO release as a function of the NO donor silica scaffold and polymer compositions and concentrations, we describe the impact of the NO release vehicle and its release kinetics on glucose sensor performance. PMID:21795038

  8. Nitric oxide counters ethylene effects on ripening fruits.

    PubMed

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

    2012-04-01

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

  9. Nitric oxide radical scavenging active components from Phyllanthus emblica L.

    PubMed

    Kumaran, A; Karunakaran, R Joel

    2006-03-01

    An activity-directed fractionation and purification process was used to identify the nitric oxide (NO) scavenging components of Phyllanthus emblica. Dried fruit rind of P. emblica was extracted with methanol and then separated into hexane, ethyl acetate, and water fractions. Among these only the ethyl acetate phase showed strong NO scavenging activity in vitro, when compared with water and hexane phases. The ethyl acetate fraction was then subjected to separation and purification using Sephadex LH-20 chromatography. Five compounds showing strong NO scavenging activity were identified by spectral methods (1H NMR, 13C NMR, and MS) and by comparison with literature values to be Gallic acid, Methyl gallate, Corilagin, Furosin, and Geraniin. In addition, HPLC identification and quantification of isolated compounds were also performed. Gallic acid was found to be a major compound in the ethyl acetate extract and Geraniin showed highest NO scavenging activity among the isolated compounds.

  10. Nitric oxide inhibits viral replication in murine myocarditis.

    PubMed Central

    Lowenstein, C J; Hill, S L; Lafond-Walker, A; Wu, J; Allen, G; Landavere, M; Rose, N R; Herskowitz, A

    1996-01-01

    Nitric oxide (NO) is a radical molecule that not only serves as a vasodilator and neurotransmitter but also acts as a cytotoxic effector molecule of the immune system. The inducible enzyme making NO, inducible NO synthase (iNOS), is transcriptionally activated by IFN-gamma and TNF-alpha, cytokines which are produced during viral infection. We show that iNOS is induced in mice infected with the Coxsackie B3 virus. Macrophages expressing iNOS are identified in the hearts and spleens of infected animals with an antibody raised against iNOS. Infected mice have increased titers of virus and a higher mortality when fed NOS inhibitors. Thus, viral infection induces iNOS in vivo, and NO inhibits viral replication. NO is a novel, nonspecific immune defense against viruses in vivo. PMID:8621766

  11. Nitric oxide and the enigma of cardiac hypertrophy.

    PubMed

    Kempf, Tibor; Wollert, Kai C

    2004-06-01

    In pathological conditions associated with persistent increases in hemodynamic workload (old myocardial infarction, high blood pressure, valvular heart disease), a number of signalling pathways are activated in the heart, all of which promote hypertrophic growth of the heart, characterised at the cellular level by increases in individual cardiac myocyte size. Some of these pathways are required for a successful adaptation to cardiac injury. Other pathways are maladaptive, however, as they lead to progressive contractile dysfunction and heart failure. The free radical gas nitric oxide and natriuretic peptides, both of which are produced in the heart, have emerged as endogenous inhibitors of maladaptive hypertrophy signalling. Overall, it appears that cardiac hypertrophy is controlled by an interplay of pro- and antihypertrophic signalling networks. This delicate balance can tip towards adaptation or heart failure. In the future, patients living with cardiac disease may benefit from therapeutic strategies targeting maladaptive hypertrophy signalling pathways. Copyright 2004 Wiley Periodicals, Inc.

  12. Electrochemistry of xanthine oxidase and its interaction with nitric oxide.

    PubMed

    Zhou, Hui; Xu, Yi; Chen, Ting; Suzuki, Iwao; Li, Genxi

    2006-02-01

    With the help of nanocrystalline TiO2, the direct electrochemistry of xanthine oxidase (XOD) was achieved and two pairs of redox waves were observed. The interaction between XOD and nitric oxide (NO) was also investigated. The experimental results reveal that NO can be reduced at a XOD-nano TiO2 film modified electrode. When the NO concentration was low, the reduced product, HNO, would inactivate the protein. However, when the NO concentration was high, HNO would continue to react with NO to form N2O2- and N3O3-, which would not inhibit XOD, and thus the amount of active protein did not decrease any further.

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

    Foster, Joshua D; Dunford, Catherine; Sillar, Keith T; Miles, Gareth B

    2014-02-01

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

  15. Elevation in Exhaled Nitric Oxide Predicts for Radiation Pneumonitis

    SciTech Connect

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

    2012-02-01

    Purpose: Radiation pneumonitis is a major toxicity after thoracic radiotherapy (RT), with no method available to accurately predict the individual risk. This was a prospective study to evaluate exhaled nitric oxide as a predictive biomarker for radiation pneumonitis in esophageal cancer patients. Patients and Methods: A total of 34 patients prescribed neoadjuvant chemoradiotherapy for esophageal cancer were enrolled in the present trial. Each patient underwent respiratory surveys and exhaled nitric oxide (NO) measurements before, at the end of, and 1 to 2 months after completing RT. Pneumonitis toxicity was scored using the Common Terminology Criteria for Adverse Events, version 4.0. The demographics, dosimetric factors, and exhaled NO levels were evaluated for correlation with symptomatic patients (scores {>=}2). Results: Of the 34 patients, 28 were evaluable. All had received 50.4 Gy RT with concurrent chemotherapy. The pneumonitis toxicity score was Grade 3 for 1, Grade 2 for 3, Grade 1 for 7, and Grade 0 for 17. The dosimetric factors were not predictive of symptoms. The mean exhaled NO level measured before, at completion, and at restaging was 17.3 {+-} 8.5 (range, 5.5-36.7), 16.0 {+-} 14.2 (range, 5.8-67.7), and 14.7 {+-} 6.2 (range, 5.5-28.0) parts per billion, respectively. The ratio of exhaled NO at the end of RT vs. before treatment was 3.4 (range, 1.7-6.7) for the symptomatic and 0.8 (range, 0.3-1.3) for the asymptomatic (p = .0017) patients. The elevation in exhaled NO preceded the peak symptoms by 33 days (range, 21-50). The interval to peak symptoms was inversely related to the exhaled NO elevation. Conclusions: Elevations in exhaled NO at the end of RT was found to predict for radiation pneumonitis symptoms.

  16. Impaired nitric oxide-mediated vasodilation in transgenic sickle mouse.

    PubMed

    Kaul, D K; Liu, X D; Fabry, M E; Nagel, R L

    2000-06-01

    Transgenic sickle mice expressing human beta(S)- and beta(S-Antilles)-globins show intravascular sickling, red blood cell adhesion, and attenuated arteriolar constriction in response to oxygen. We hypothesize that these abnormalities and the likely endothelial damage, also reported in sickle cell anemia, alter nitric oxide (NO)-mediated microvascular responses and hemodynamics in this mouse model. Transgenic mice showed a lower mean arterial pressure (MAP) compared with control groups (90 +/- 7 vs. 113 +/- 8 mmHg, P < 0.00001), accompanied by increased endothelial nitric oxide synthase (eNOS) expression. N(G)-nitro-L-arginine methyl ester (L-NAME), a nonselective inhibitor of NOS, caused an approximately 30% increase in MAP and approximately 40% decrease in the diameters of cremaster muscle arterioles (branching orders: A2 and A3) in both control and transgenic mice, confirming NOS activity; these changes were reversible after L-arginine administration. Aminoguanidine, an inhibitor of inducible NOS, had no effect. Transgenic mice showed a decreased (P < 0.02-0.01) arteriolar dilation in response to NO-mediated vasodilators, i.e., ACh and sodium nitroprusside (SNP). Indomethacin did not alter the responses to ACh and SNP. Forskolin, a cAMP-activating agent, caused a comparable dilation of A2 and A3 vessels ( approximately 44 and 70%) in both groups of mice. Thus in transgenic mice, an increased eNOS/NO activity results in lower blood pressure and diminished arteriolar responses to NO-mediated vasodilators. Although the increased NOS/NO activity may compensate for flow abnormalities, it may also cause pathophysiological alterations in vascular tone.

  17. Nitric oxide production and blood pressure reduction during haemodialysis.

    PubMed

    Chang, Chiz-Tzung; Chien, Ming-Hui; Yang, Kai-Liang; Yu, Chien-Chih; Hsu, Jing-Fang; Wang, I-Kuan; Lim, Paik-Seong; Huang, Chiu-Ching

    2014-09-01

    A decrease of systolic blood pressure in excess of 20 mmHg during haemodialysis treatment (IDD) is common for haemodialysis patients. Intradialytic hypotension (IDH) is symptomatic IDD by definition. Overproduction of nitric oxide (NO) is a possible cause of IDD. Dialysate nitrate and nitrite amount can be used as an indicator of intradialysis NO production. Our aim was to find the predictor of NO production in IDD patients. Partial dialysate samples were collected during the whole haemodialysis session and total dialysate nitrate and nitrite amount was measured to assess the association of intradialysis NO production with blood pressure change. There were 31 IDD patients and 71 patients who did not develop IDD (NIDD) included in the study. Among the IDD patients, 13 were IDH patients with a mean systolic blood pressure lower than that of the other 18 symptomless IDD patients (96.6 ± 3.4 mmHg vs 125.0 ± 3.8 mmHg, P<0.001). The median value of NO production was higher in the IDD than in the NIDD patients (447.7 μg vs 238.8 μg, P<0.001). The NO production correlated linearly with blood pressure reduction (R=0.487, P<0.001). The multivariate analysis showed that NO production was positively associated with predialysis systolic blood pressure. Nitric oxide production during haemodialysis was higher in IDD than in NIDD patients. IDH often occurred when systolic blood pressure was reduced to below 100 mmHg. The amount of NO produced during haemodialysis, which may be associated with predialysis systolic blood pressure, can be used to predict intradialysis blood pressure decrease. © 2014 Asian Pacific Society of Nephrology.

  18. Nitric oxide is negatively correlated to pain during acute inflammation

    PubMed Central

    2010-01-01

    Background The role that nitric oxide (NO) plays in modulating pain in the periphery is unclear. We show here, the results of two independent clinical studies (microdialysis and gene expression studies) and a pilot dose finding study (glyceryl trinitrate study), to study the role of NO in the early phase of acute inflammatory pain following oral surgery. The effect of ketorolac on NO production and nitric oxide synthase (NOS) gene expression was also studied. Results Microdialysis samples showed significantly higher levels of NO at the first 100 min compared to the last 80 minutes in the placebo treated group. In the ketorolac group, on the other hand, NO levels gradually decreased over the first 60 min but were similar to placebo over the later 100-180 min, with no significant change in NO level over time. The levels of NO were negatively correlated to pain intensity scores. Local infusion of the NO donor glyceryl trinitrate at the site of surgery, showed a small analgesic effect that did not reach statistical significance in the sample size used. While the gene expression of iNOS and eNOS were not up-regulated, 3 hours after surgery, nNOS was downregulated in both treatment groups and eNOS gene expression was significantly lower in the ketorolac group compared to the placebo group. Further, there was a positive correlation between the change in gene expression of nNOS and eNOS in the placebo goup but not in the ketorolac group. Conclusion We suggest that at this early stage of inflammatory pain in man, NO is analgesic in the periphery. Further, ketorolac down-regulates eNOS gene expression. PMID:20843331

  19. Oxalomalate affects the inducible nitric oxide synthase expression and activity.

    PubMed

    Irace, Carlo; Esposito, Giuseppe; Maffettone, Carmen; Rossi, Antonietta; Festa, Michela; Iuvone, Teresa; Santamaria, Rita; Sautebin, Lidia; Carnuccio, Rosa; Colonna, Alfredo

    2007-03-13

    Inducible nitric oxide synthase (iNOS) is an homodimeric enzyme which produces large amounts of nitric oxide (NO) in response to inflammatory stimuli. Several factors affect the synthesis and catalytic activity of iNOS. Particularly, dimerization of NOS monomers is promoted by heme, whereas an intracellular depletion of heme and/or L-arginine considerably decreases NOS resistance to proteolysis. In this study, we found that oxalomalate (OMA, oxalomalic acid, alpha-hydroxy-beta-oxalosuccinic acid), an inhibitor of both aconitase and NADP-dependent isocitrate dehydrogenase, inhibited nitrite production and iNOS protein expression in lipopolysaccharide (LPS)-activated J774 macrophages, without affecting iNOS mRNA content. Furthermore, injection of OMA precursors to LPS-stimulated rats also decreased nitrite production and iNOS expression in isolated peritoneal macrophages. Interestingly, alpha-ketoglutarate or succinyl-CoA administration reversed OMA effect on NO production, thus correlating NO biosynthesis with the anabolic capacity of Krebs cycle. When protein synthesis was blocked by cycloheximide in LPS-activated J774 cells treated with OMA, iNOS protein levels, evaluated by Western blot analysis and (35)S-metabolic labelling, were decreased, suggesting that OMA reduces iNOS biosynthesis and induces an increase in the degradation rate of iNOS protein. Moreover, we showed that OMA inhibits the activity of the iNOS from lung of LPS-treated rats by enzymatic assay. Our results, demonstrating that OMA acts regulating synthesis, catalytic activity and degradation of iNOS, suggest that this compound might have a potential role in reducing the NO overproduction occurring in some pathological conditions.

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  2. Nitric Oxide And Hypoxia Response In Pluripotent Stem Cells.

    PubMed

    Infantes, Estefanía Caballano; Prados, Ana Belén Hitos; Contreras, Irene Díaz; Cahuana, Gladys M; Hmadcha, Abdelkrim; Bermudo, Franz Martín; Soria, Bernat; Huamán, Juan R Tejedo; Bergua, Francisco J Bedoya

    2015-08-01

    The expansion of pluripotent cells (ESCs and iPSCs) under conditions that maintain their pluripotency is necessary to implement a cell therapy program. Previously, we have described that low nitric oxide (NO) donor diethylenetriamine/nitric oxide adduct (DETA-NO) added to the culture medium, promote the expansion of these cell types. The molecular mechanisms are not yet known. We present evidences that ESC and iPSCs in normoxia in presence of low NO triggers a similar response to hypoxia, thus maintaining the pluripotency. We have studied the stability of HIF-1α (Hypoxia Inducible Factor) in presence of low NO. Because of the close relationship between hypoxia, metabolism, mitochondrial function and pluripotency we have analyzed by q RT-PCR the expression of genes involved in the glucose metabolism such as: HK2, LDHA and PDK1; besides other HIF-1α target gene. We further analyzed the expression of genes involved in mitochondrial biogenesis such as PGC1α, TFAM and NRF1 and we have observed that low NO maintains the same pattern of expression that in hypoxia. The study of the mitochondrial membrane potential using Mito-Tracker dye showed that NO decrease the mitochondrial function. We will analyze other metabolic parameters, to determinate if low NO regulates mitochondrial function and mimics Hypoxia Response. The knowledge of the role of NO in the Hypoxia Response and the mechanism that helps to maintain self-renewal in pluripotent cells in normoxia, can help to the design of culture media where NO could be optimal for stem cell expansion in the performance of future cell therapies.

  3. Nitric oxide (NO) stimulates steroidogenesis and folliculogenesis in fish.

    PubMed

    Singh, Vinay Kumar; Lal, Bechan

    2017-02-01

    The present study was undertaken to understand the physiological significance of the existence of nitric oxide synthase (NOS)/nitric oxide (NO) system in fish ovary. For this, two doses of NO donor, sodium nitroprusside (SNP, 25 µg and 50 µg) and NOS inhibitor, N-nitro-l-arginine methyl ester (l-NAME, 50 µg and 100 µg)/100 g body weight were administered during the two reproductive phases of reproductive cycle of the Clarias batrachus During the late-quiescence phase, high dose of l-NAME decreased the NO, testosterone, 17β-estradiol, vitellogenin contents in serum and ovary and activities of 5-ene-3β-hydroxysteroid dehydrogenases (3β-HSD) and 17β-hydroxysteroid dehydrogenases (17β-HSD) in ovary, whereas higher dose of SNP increased these parameters. l-NAME also reduced oocytes-I but increased perinucleolar oocytes in the ovary, whereas SNP treatment increased the number of advanced oocytes (oocytes-I and II) than the perinucleolar oocytes when compared with control ovary. During the mid-recrudescence phase, both doses of SNP increased NO, testosterone, 17β-estradiol and vitellogenin in serum and ovary; however, l-NAME treatment lowered their levels. The activities of ovarian 3β-HSD and 17β-HSD were also stimulated by SNP, but l-NAME suppressed their activities compared to the control. The SNP-treated ovaries were dominated by oocyte-II and III stages, whereas l-NAME-treated ovary revealed more perinucleolar oocytes and oocytes-I and practically no advanced oocytes. Expression of endothelial NOS (eNOS), inducible NOS (iNOS) and neuronal NOS (nNOS) was augmented by the SNP and declined by l-NAME treatments as compared to the control. This study, thus, provides distinct evidence of NO-stimulated steroidogenesis, vitellogenesis and folliculogenesis in fish.

  4. Exhaled Nitric Oxide in Systemic Sclerosis Lung Disease

    PubMed Central

    Kozij, Natalie K.; Silkoff, Philip E.; Thenganatt, John; Chakravorty, Shobha

    2017-01-01

    Background. Exhaled nitric oxide (eNO) is a potential biomarker to distinguish systemic sclerosis (SSc) associated pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD). We evaluated the discriminative validity, feasibility, methods of eNO measurement, and magnitude of differences across lung diseases, disease-subsets (SSc, systemic lupus erythematosus), and healthy-controls. Methods. Consecutive subjects in the UHN Pulmonary Hypertension Programme were recruited. Exhaled nitric oxide was measured at 50 mL/s intervals using chemiluminescent detection. Alveolar and conducting airway NO were partitioned using a two-compartment model of axial diffusion (CMAD) and the trumpet model of axial diffusion (TMAD). Results. Sixty subjects were evaluated. Using the CMAD model, control subjects had lower median (IQR) alveolar NO than all PAH subjects (2.0 (1.5, 2.5) versus 3.14 ppb (2.3, 4.0), p = 0.008). SSc-ILD had significantly lower median conducting airway NO compared to controls (1009.5 versus 1342.1 ml⁎ppb/s, p = 0.04). SSc-PAH had increased median (IQR) alveolar NO compared to controls (3.3 (3.0, 5.7) versus 2.0 ppb (1.5, 2.5), p = 0.01). SSc-PAH conducting airway NO inversely correlated with DLCO (r −0.88 (95% CI −0.99, −0.26)). Conclusion. We have demonstrated feasibility, identified that CMAD modeling is preferred in SSc, and reported the magnitude of differences across cases and controls. Our data supports discriminative validity of eNO in SSc lung disease. PMID:28293128

  5. Nitric oxide synthases and cyclophosphamide-induced cystitis in rats.

    PubMed

    Alfieri, A B; Malave, A; Cubeddu, L X

    2001-03-01

    The role of inducible (iNOS) and neuronal nitric oxide (nNOS) synthases and of tachykinin NK1 receptors on the pathogenesis of cyclophosphamide (CYP)-induced cystitis was investigated, in rats. CYP-induced cystitis was characterized by large increases in bladder-protein plasma extravasation (PPE), increases in the urinary excretion of nitric oxide (NO) metabolites and histological evidences of urothelial damage, edema, extensive white blood cell infiltrates and vascular congestion of the bladder. The specific iNOS inhibitor, S-methylthiourea (MITU), produced marked inhibition (>90%) of CYP-induced increases in PPE associated with amelioration of tissue inflammatory changes. Treatment with 7-nitroindazole (7-NI; 20, 40 and 80 mg/kg), a selective nNOS inhibitor, did not significantly reduce CYP-induced increases in PPE and failed to produce histological improvement. In addition, treatment with MITU, but not with 7-NI, inhibited the increases in the urinary excretion of NO metabolites induced by CYP treatment. WIN 51,708 (17-beta-hydroxy-17-alpha-ethynyl-androstano[3,2-b]pyrimido[1,2-a]benzimidazole; WIN), a selective NK1-receptor antagonist, reduced the increases in EPP and ameliorated the inflammatory changes in the bladder induced by CYP. However, the maximal degree of protection achieved with WIN was significantly less than that produced by MITU. Combined treatment with the iNOS inhibitor and the NK1 antagonist produced no greater effect than that produced by the iNOS inhibitor alone. Our results suggest that NO plays a fundamental role in the production of the cystitis associated with CYP treatment. The iNOS, and not nNOS, seems responsible for the inflammatory changes. Part of the increases in NO may due to activation of NK1 receptors by neuropeptides such as substance P possibly released from primary afferent fibers.

  6. Nitric oxide production during Eimeria tenella infections in chickens.

    PubMed

    Allen, P C

    1997-06-01

    The objective of this study was to gather evidence for production of nitric oxide (NO) during a primary infection with the protozoan parasite Eimeria tenella, which carries out its life cycle in the ceca of chickens. Relationships of plasma levels of NO2(-)+NO3-, stable metabolites of NO, with parasite dose and with time after infection were examined, as well as effects of administration of aminoguanidine, an inhibitor of induced nitric oxide synthase (iNOS). Inoculation with 5 x 10(4) and 1 x 10(6) but not 1 x 10(3) oocysts per chick caused significant (P < or = 0.05) increases in micromolar concentrations of plasma NO3(-)+NO3- when measured at 7 d postinoculation (PI). In chickens inoculated with 5 x 10(4) oocysts, significant (P < or = 0.05) increases in plasma NO2(-)+NO3- were seen at 5 and 7 but not 3 d PI. Daily intraperitoneal administration of 1.25 mg per chick aminoguanidine during the period of infection did not lower the increases in plasma NO2(-)+NO3- seen at 5 and 7 d PI, and did not affect the degree of colonization of the cecal tissue by the parasite. However, administration of aminoguanidine did alter the gross appearance of the ceca, which were less swollen and filled with blood at 5 and 7 d PI as compared with ceca from untreated chickens. Hemorrhage is a major pathological manifestation of E. tenella infections, associated with the disruption of the cecal mucosa by the developing parasite. The results of this experiment are consistent with the hypothesis that an aminoguanidine-inhibitable NO synthase, perhaps in the vascular endothelium of the cecal blood vessels, may contribute to hemorrhage by causing vasodilation.

  7. Nitric Oxide and Major Depressive Disorder: Pathophysiology and Treatment Implications.

    PubMed

    Kudlow, P; Cha, D S; Carvalho, A F; McIntyre, R S

    2016-01-01

    Major depressive disorder (MDD) is a multi-factorial and heterogeneous disease. Robust evidence suggests that inflammation is involved in the pathogenesis of MDD for a subpopulation of individuals. However, it remains unclear what traits and/or states precede the onset of inflammation in this subpopulation of individuals with MDD. Several recent studies have implicated nitric oxide (NO) as a critical regulator of neuroinflammation, thus suggesting a possible role in the pathophysiology of MDD. The aim of this review is to evaluate the evidentiary base supporting the hypothesis that the increased hazard for developing MDD in certain subpopulations may be mediated, in part, by inflammogenic trait and/or state variations in NO signaling pathways. We conducted a non-systematic literature search for English language studies via PubMed and Google Scholar, from 1985 to October 2014. Replicated evidence suggests that NO has contrasting effects in the central nervous system (CNS). Low concentrations of NO are neuroprotective and mediate physiological signaling whereas higher concentrations mediate neuroinflammatory actions and are neurotoxic. Certain polymorphisms in the neuronal nitric oxide synthase gene (NOS1) are associated MDD. Furthermore, state variations (e.g. decreased levels of essential co-factor, 5,6,7,8-tetrahydrobiopterin [BH4], enhanced microglial cell activity) in the NO signaling pathway are associated with an increased risk of developing MDD. Increased concentrations of NO enhance the production of reactive nitrogen species (RNS) and reactive oxygen species (ROS), which are associated with an increase in pro-inflammatory cytokines. Taken together, evidences suggest that abnormalities in NO signaling may constitute a trait-marker related to MDD pathophysiology, which could be explored for novel therapeutic targets.

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

    NASA Technical Reports Server (NTRS)

    Jachimowski, C. J.

    1975-01-01

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

  9. Expression and activity of inducible nitric oxide synthase and endothelial nitric oxide synthase correlate with ethanol-induced liver injury

    PubMed Central

    Yuan, Guang-Jin; Zhou, Xiao-Rong; Gong, Zuo-Jiong; Zhang, Pin; Sun, Xiao-Mei; Zheng, Shi-Hua

    2006-01-01

    AIM: To study the expression and activity of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) in rats with ethanol-induced liver injury and their relation with liver damage, activation of nuclear factor-κB (NF-κB) and tumor necrosis factor-α (TNF-α) expression in the liver. METHODS: Female Sprague-Dawley rats were given fish oil (0.5 mL) along with ethanol or isocaloric dextrose daily via gastrogavage for 4 or 6 wk. Liver injury was assessed using serum alanine aminotransferase (ALT) activity and pathological analysis. Liver malondialdehyde (MDA), nitric oxide contents, iNOS and eNOS activity were determined. NF-κB p65,iNOS, eNOS and TNF-α protein or mRNA expression in the liver were detected by immunohistochemistry or reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: Chronic ethanol gavage for 4 wk caused steatosis, inflammation and necrosis in the liver, and elevated serum ALT activity. Prolonged ethanol administration (6 wk) enhanced the liver damage. These responses were accompanied with increased lipid peroxidation, NO contents, iNOS activity and reduced eNOS activity. NF-κB p65, iNOS and TNF-α protein or mRNA expression were markedly induced after chronic ethanol gavage, whereas eNOS mRNA expression remained unchanged. The enhanced iNOS activity and expression were positively correlated with the liver damage, especially the necro-inflammation, activation of NF-κB, and TNF-α mRNA expression. CONCLUSION: iNOS expression and activity are induced in the liver after chronic ethanol exposure in rats, which are correlated with the liver damage, especially the necro-inflammation, activation of NF-κB and TNF-α expression. eNOS activity is reduced, but its mRNA expression is not affected. PMID:16688828

  10. Expression of nitric oxide-containing structures in the rat carotid body.

    PubMed

    Atanasova, Dimitrinka Y; Dimitrov, Nikolay D; Lazarov, Nikolai E

    2016-10-01

    The carotid body (CB) is a major peripheral arterial chemoreceptor organ that evokes compensatory reflex responses so as to maintain gas homeostasis. It is dually innervated by sensory fibers from petrosal ganglion (PG) neurons, and autonomic fibers from postganglionic sympathetic neurons of the superior cervical ganglion (SCG) and parasympathetic vasomotor fibers of intrinsic ganglion cells in the CB. The presence of nitric oxide (NO), a putative gaseous neurotransmitter substance in a number of neuronal and non-neuronal structures, was examined in the CB, PG and SCG of the rat using nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry, nitric oxide synthase (NOS) immunohistochemistry and retrograde tracing. One week after injecting the retrograde tracer Fast Blue (FB) in the CB, we found that a subset of perikarya in the caudal portions of the PG and SCG were FB-labeled. Histochemistry and immunohistochemistry revealed that the majority of large- and medium-sized PG and SCG cells were NADPH-d positive and displayed a strong NOS immunostaining. We also observed that many varicose nerve fibers penetrating the CB and enveloping the glomus cells and blood vessels were NADPH-d reactive and expressed the constitutive isoforms of NOS, nNOS and eNOS. In addition, some autonomic microganglion cells embedded within, or located at the periphery of the CB, and not glomus or sustentacular cells were nNOS-immunopositive while CB microvasculature expressed eNOS. The present results suggest that NO is a transmitter in the autonomic nerve endings supplying the CB and is involved in efferent chemoreceptor inhibition by a dual mechanism.

  11. Chlorine Gas Exposure Causes Systemic Endothelial Dysfunction by Inhibiting Endothelial Nitric Oxide Synthase–Dependent Signaling

    PubMed Central

    Honavar, Jaideep; Samal, Andrey A.; Bradley, Kelley M.; Brandon, Angela; Balanay, Joann; Squadrito, Giuseppe L.; MohanKumar, Krishnan; Maheshwari, Akhil; Postlethwait, Edward M.; Matalon, Sadis; Patel, Rakesh P.

    2011-01-01

    Chlorine gas (Cl2) exposure during accidents or in the military setting results primarily in injury to the lungs. However, the potential for Cl2 exposure to promote injury to the systemic vasculature leading to compromised vascular function has not been studied. We hypothesized that Cl2 promotes extrapulmonary endothelial dysfunction characterized by a loss of endothelial nitric oxide synthase (eNOS)-derived signaling. Male Sprague Dawley rats were exposed to Cl2 for 30 minutes, and eNOS-dependent vasodilation of aorta as a function of Cl2 dose (0–400 ppm) and time after exposure (0–48 h) were determined. Exposure to Cl2 (250–400 ppm) significantly inhibited eNOS-dependent vasodilation (stimulated by acetycholine) at 24 to 48 hours after exposure without affecting constriction responses to phenylephrine or vasodilation responses to an NO donor, suggesting decreased NO formation. Consistent with this hypothesis, eNOS protein expression was significantly decreased (∼ 60%) in aorta isolated from Cl2–exposed versus air-exposed rats. Moreover, inducible nitric oxide synthase (iNOS) mRNA was up-regulated in circulating leukocytes and aorta isolated 24 hours after Cl2 exposure, suggesting stimulation of inflammation in the systemic vasculature. Despite decreased eNOS expression and activity, no changes in mean arterial blood pressure were observed. However, injection of 1400W, a selective inhibitor of iNOS, increased mean arterial blood pressure only in Cl2–exposed animals, suggesting that iNOS-derived NO compensates for decreased eNOS-derived NO. These results highlight the potential for Cl2 exposure to promote postexposure systemic endothelial dysfunction via disruption of vascular NO homeostasis mechanisms. PMID:21131444

  12. Beneficial effects of L-arginine–nitric oxide-producing pathway in rats treated with alloxan

    PubMed Central

    Vasilijević, Ana; Buzadžić, Biljana; Korać, Aleksandra; Petrović, Vesna; Janković, Aleksandra; Korać, Bato

    2007-01-01

    In an attempt to elucidate molecular mechanisms and factors involved in β cell regeneration, we evaluated a possible role of the l-arginine–nitric oxide (NO)-producing pathway in alloxan-induced diabetes mellitus. Diabetes was induced in male Mill Hill rats with a single alloxan dose (120 mg kg−1). Both non-diabetic and diabetic groups were additionally separated into three subgroups: (i) receiving l-arginine · HCl (2.25%), (ii) receiving l-NAME · HCl (0.01%) for 12 days as drinking liquids, and (iii) control. Treatment of diabetic animals started after diabetes induction (glucose level ≥ 12 mmol l−1). We found that disturbed glucose homeostasis, i.e. blood insulin and glucose levels in diabetic rats was restored after l-arginine treatment. Immunohistochemical findings revealed that l-arginine had a favourable effect on β cell neogenesis, i.e. it increased the area of insulin-immunopositive cells. Moreover, confocal microscopy showed colocalization of insulin and pancreas duodenum homeobox-1 (PDX-1) in both endocrin