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Sample records for endotoxin-induced nitric oxide

  1. Aldose Reductase Mediates Endotoxin-Induced Production of Nitric oxide and Cytotoxicity in Murine Macrophages.

    PubMed Central

    Ramana, Kota V; Reddy, Aramati BM.; Tammali, Ravinder; Srivastava, Satish K.

    2007-01-01

    Aldose reductase (AR) is a ubiquitously expressed protein with pleiotrophic roles as an efficient catalyst for the reduction of toxic lipid aldehydes and mediator of hyperglycemia, cytokine and growth factor –induced redox sensitive signals that cause secondary diabetic complications. Although AR inhibition has been shown to be protective against oxidative stress signals, the role of AR in regulating nitric oxide (NO) synthesis and NO-mediated apoptosis has not been elucidated to date. We therefore investigated the role of AR in regulating lipopolysaccharide (LPS)-induced NO synthesis and apoptosis in RAW 264.7 macrophages. Inhibition or RNA interference ablation of AR suppressed LPS-stimulated production of NO and over-expression of iNOS mRNA. Inhibition or ablation of AR also prevented the LPS-induced apoptosis, cell cycle arrest, activation of caspase-3, p38-MAPK, JNK, NF-κB and AP1. In addition, AR inhibition prevented the LPS-induced down-regulation of Bcl-xl and up-regulation of Bax and Bak in macrophages. L-arginine increased and L-NAME decreased the severity of cell death caused by LPS and AR inhibitors prevented it. Furthermore, inhibition of AR prevents cell death caused by HNE and GS-HNE, but not GS-DHN. Our findings for the first time suggest that AR catalyzed lipid aldehyde-glutathione conjugates regulates the LPS-induced production of inflammatory marker NO and cytotoxicity in RAW 264.7 cells. Inhibition or ablation of AR activity may be potential therapeutic target in endotoximia and other inflammatory diseases. PMID:17382209

  2. Inhibition of endotoxin-induced nitric oxide synthase production in microglial cells by the presence of astroglial cells: a role for transforming growth factor beta.

    PubMed

    Vincent, V A; Tilders, F J; Van Dam, A M

    1997-03-01

    In mixed glial cell cultures from cerebral cortices of newborn rats, endotoxin induces inducible nitric oxide (iNOS), nitric oxide (NO), and interleukin-1 beta (IL-1 beta) production in microglial cells. Earlier we demonstrated that endotoxin induced iNOS but not IL-1 beta expression in microglial cells is inhibited by the presence of astroglial cells. In the present paper we describe studies on the mechanism by which astroglial cells exert selective suppressive action on iNOS expression by microglial cells. Expression of iNOS and IL-1 beta was studied by single or double label immunocytochemical techniques and cell identification was performed with GSA-I-B4-isolectin and an antibody against GFAP. Production of IL-1 beta and NO was determined by measurement of IL-1 beta and nitrite concentrations in cell lysates and the culture medium, respectively. TGF beta, a cytokine known to inhibit NO production by endotoxin challenged macrophages, was measured in culture medium of mixed glial cell cultures using a bioassay. Microglial, astroglial, and mixed glial cell cultures produced similar concentrations of TGF beta. The potential effect of TGF beta was studied by using immunoneutralizing antibodies against TGF beta 1 and TGF beta 2 on the induction of iNOS in microglial cells in the presence of astroglial cells. Incubation of the mixed glial cell culture with these TGF beta antibodies (3 micrograms/ml) markedly increased endotoxin-induced NO production and iNOS expression in microglial cells, whereas the production of IL-1 beta was not affected. The antibodies against TGF beta 1 and TGF beta 2 marginally increased NO production in pure microglial cell cultures, nonetheless in cultures of purified microglial cells recombinant TGF beta 1 and TGF beta 2 together with endotoxin inhibited NO production. We conclude that the presence of astroglial cells is essential for the inhibitory effect of TGF beta on NO production by microglial cells (possibly) by activation of TGF beta

  3. Endotoxin-induced nitric oxide production rescues airway growth and maturation in atrophic fetal rat lung explants

    SciTech Connect

    Rae, C.; Cherry, J.I.; Land, F.M.; Land, S.C. . E-mail: s.c.land@dundee.ac.uk

    2006-10-13

    Inflammation induces premature maturation of the fetal lung but the signals causing this effect remain unclear. We determined if nitric oxide (NO) synthesis, evoked by Escherichia coli lipopolysaccharide (LPS, 2 {mu}g ml{sup -1}), participated in this process. Fetal rat lung airway surface complexity rose 2.5-fold over 96 h in response to LPS and was associated with increased iNOS protein expression and activity. iNOS inhibition by N6-(1-iminoethyl)-L-lysine-2HCl (L-NIL) abolished this and induced airway atrophy similar to untreated explants. Surfactant protein-C (SP-C) expression was also induced by LPS and abolished by L-NIL. As TGF{beta} suppresses iNOS activity, we determined if feedback regulation modulated NO-dependent maturation. LPS induced TGF{beta}1 release and SMAD4 nuclear translocation 96 h after treatment. Treatment of explants with a blocking antibody against TGF{beta}1 sustained NO production and airway morphogenesis whereas recombinant TGF{beta}1 antagonized these effects. Feedback regulation of NO synthesis by TGF{beta} may, thus, modulate airway branching and maturation of the fetal lung.

  4. Attenuation of endotoxin-induced multiple organ dysfunction by 1-amino-2-hydroxy-guanidine, a potent inhibitor of inducible nitric oxide synthase.

    PubMed Central

    Ruetten, H.; Southan, G. J.; Abate, A.; Thiemermann, C.

    1996-01-01

    1. We have investigated the effects of (i) several guanidines on the activity of the inducible isoform of nitric oxide (NO) synthase (iNOS) in murine cultured macrophages and rat aortic vascular smooth muscle cells (RASM); and (ii) 1-amino-2-hydroxy-guanidine, the most potent inhibitor of iNOS activity discovered, on haemodynamics, multiple organ (liver, renal, and pancreas) dysfunction and iNOS activity in rats with endotoxic shock. 2. The synthesized guanidine analogues caused concentration-dependent inhibitions of the increase in nitrite formation caused by lipopolysaccaride (LPS, 1 microgram ml-1) in J774.2 macrophages and RASM cells with the following rank order of potency: 1-amino-2-hydroxy-guanidine > 1-amino-2-methyl-guanidine > 1-amino-1-methyl-guanidine > 1-amino-1,2-dimethyl-guanidine. Interestingly, 1-amino-2-hydroxy-guanidine (IC50: J774.2, 68 microM; RASM, 114 microM) was more potent in inhibiting nitrite formation caused by LPS than NG-methyl-L-arginine, but less potent than aminoethyl-isothiourea. 3. In the anaesthetized rat, LPS caused a fall in mean arterial blood pressure (MAP) from 115 +/- 4 mmHg (time 0) to 98 +/- 5 mmHg at 2 h (P < 0.05, n = 10) and 69 +/- 5 mmHg at 6 h (P < 0.05, n = 10). The pressor effect of noradrenaline (NA, 1 mg kg-1, i.v.) was also significantly reduced at 1 to 6 h after LPS (vascular hyporeactivity). Treatment of LPS-rats with 1-amino-2-hydroxy-guanidine (10 mg kg-1, i.v. plus 10 mg kg-1 h-1 starting at 2 h after LPS) prevented the delayed hypotension and vascular hyporeactivity seen in LPS-rats. However, 1-amino-2-hydroxy-guanidine had no effect on either MAP or the pressor effect elicited by NA in rats infused with saline rather than LPS. 4. Endotoxaemia for 6 h caused a significant rise in the serum levels of aspartate or alanine aminotransferase (i.e. GOT or GPT) and bilirubin, and hence, liver dysfunction. Treatment of LPS-rats with 1-amino-2-hydroxy-guanidine significantly attenuated the liver dysfunction caused

  5. Oxidation of Plasma Cysteine/Cystine Redox State in Endotoxin-Induced Lung Injury

    PubMed Central

    Iyer, Smita S.; Jones, Dean P.; Brigham, Kenneth L.; Rojas, Mauricio

    2009-01-01

    Several lines of evidence indicate that perturbations in the extracellular thiol/disulfide redox environment correlate with the progression and severity of acute lung injury (ALI). Cysteine (Cys) and its disulfide Cystine (CySS) constitute the most abundant, low-molecular-weight thiol/disulfide redox couple in the plasma, and Cys homeostasis is adversely affected during the inflammatory response to infection and injury. While much emphasis has been placed on glutathione (GSH) and glutathione disulfide (GSSG), little is known about the regulation of the Cys/CySS couple in ALI. The purpose of the present study was to determine whether endotoxin administration causes a decrease in Cys and/or an oxidation of the plasma Cys/CySS redox state (Eh Cys/CySS), and to determine whether these changes were associated with changes in plasma Eh GSH/GSSG. Mice received endotoxin intraperitoneally, and GSH and Cys redox states were measured at time points known to correlate with the progression of endotoxin-induced lung injury. Eh in mV was calculated using Cys, CySS, GSH, and GSSG values by high-performance liquid chromatography and the Nernst equation. We observed distinct effects of endotoxin on the GSH and Cys redox systems during the acute phase; plasma Eh Cys/CySS was selectively oxidized early in response to endotoxin, while Eh GSH/GSSG remained unchanged. Unexpectedly, subsequent oxidation of Eh GSH/GSSG and Eh Cys/CySS occurred as a consequence of endotoxin-induced anorexia. Taken together, the results indicate that enhanced oxidation of Cys, altered transport of Cys and CySS, and decreased food intake each contribute to the oxidation of plasma Cys/CySS redox state in endotoxemia. PMID:18664641

  6. 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

  7. Nitric oxide inhibition strategies

    PubMed Central

    Wong, Vivian (Wai Chong); Lerner, Ethan

    2015-01-01

    Nitric oxide is involved in many physiologic processes. There are efforts, described elsewhere in this volume, to deliver nitric oxide to tissues as a therapy. Nitric oxide also contributes to pathophysiologic processes. Inhibiting nitric oxide or its production can thus also be of therapeutic benefit. This article addresses such inhibitory strategies. PMID:26634146

  8. Arginase Activity Mediates Retinal Inflammation in Endotoxin-Induced Uveitis

    PubMed Central

    Zhang, Wenbo; Baban, Babak; Rojas, Modesto; Tofigh, Sohrab; Virmani, Suvika K.; Patel, Chintan; Behzadian, M. Ali; Romero, Maritza J.; Caldwell, Robert W.; Caldwell, Ruth B.

    2009-01-01

    Arginase has been reported to reduce nitric oxide bioavailability in cardiovascular disease. However, its specific role in retinopathy has not been studied. In this study, we assessed the role of arginase in a mouse model of endotoxin-induced uveitis induced by lipopolysaccharide (LPS) treatment. Measurement of arginase expression and activity in the retina revealed a significant increase in arginase activity that was associated with increases in both mRNA and protein levels of arginase (Arg)1 but not Arg2. Immunofluorescence and flow cytometry confirmed this increase in Arg1, which was localized to glia and microglia. Arg1 expression and activity were also increased in cultured Muller cells and microglia treated with LPS. To test whether arginase has a role in the development of retinal inflammation, experiments were performed in mice deficient in one copy of the Arg1 gene and both copies of the Arg2 gene or in mice treated with a selective arginase inhibitor. These studies showed that LPS-induced increases in inflammatory protein production, leukostasis, retinal damage, signs of anterior uveitis, and uncoupling of nitric oxide synthase were blocked by either knockdown or inhibition of arginase. Furthermore, the LPS-induced increase in Arg1 expression was abrogated by blocking NADPH oxidase. In conclusion, these studies suggest that LPS-induced retinal inflammation in endotoxin-induced uveitis is mediated by NADPH oxidase-dependent increases in arginase activity. PMID:19590038

  9. Chlorogenic acid ameliorates endotoxin-induced liver injury by promoting mitochondrial oxidative phosphorylation.

    PubMed

    Zhou, Yan; Ruan, Zheng; Zhou, Lili; Shu, Xugang; Sun, Xiaohong; Mi, Shumei; Yang, Yuhui; Yin, Yulong

    2016-01-22

    Acute or chronic hepatic injury is a common pathology worldwide. Mitochondrial dysfunction and the depletion of adenosine triphosphate (ATP) play important roles in liver injury. Chlorogenic acids (CGA) are some of the most abundant phenolic acids in human diet. This study was designed to test the hypothesis that CGA may protect against chronic lipopolysaccharide (LPS)-induced liver injury by modulating mitochondrial energy generation. CGA decreased the activities of serum alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase. The contents of ATP and adenosine monophosphate (AMP), as well as the ratio of AMP/ATP, were increased after CGA supplementation. The activities of enzymes that are involved in glycolysis were reduced, while those of enzymes involved in oxidative phosphorylation were increased. Moreover, phosphorylated AMP-activated protein kinase (AMPK), and mRNA levels of AMPK-α, peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α), nuclear respiratory factor 1, and mitochondrial DNA transcription factor A were increased after CGA supplementation. Collectively, these findings suggest that the hepatoprotective effect of CGA might be associated with enhanced ATP production, the stimulation of mitochondrial oxidative phosphorylation and the inhibition of glycolysis. PMID:26740181

  10. Biomarkers of oxidative stress study VI. Endogenous plasma antioxidants fail as useful biomarkers of endotoxin-induced oxidative stress.

    PubMed

    Kadiiska, Maria B; Peddada, Shyamal; Herbert, Ronald A; Basu, Samar; Hensley, Kenneth; Jones, Dean P; Hatch, Gary E; Mason, Ronald P

    2015-04-01

    This is the newest report in a series of publications aiming to identify a blood-based antioxidant biomarker that could serve as an in vivo indicator of oxidative stress. The goal of the study was to test whether acutely exposing Göttingen mini pigs to the endotoxin lipopolysaccharide (LPS) results in a loss of antioxidants from plasma. We set as a criterion that a significant effect should be measured in plasma and seen at both doses and at more than one time point. Animals were injected with two doses of LPS at 2.5 and 5 µg/kg iv. Control plasma was collected from each animal before the LPS injection. After the LPS injection, plasma samples were collected at 2, 16, 48, and 72 h. Compared with the controls at the same time point, statistically significant losses were not found for either dose at multiple time points in any of the following potential markers: ascorbic acid, tocopherols (α, δ, γ), ratios of GSH/GSSG and cysteine/cystine, mixed disulfides, and total antioxidant capacity. However, uric acid, total GSH, and total Cys were significantly increased, probably because LPS had a harmful effect on the liver. The leakage of substances from damaged cells into the plasma may have increased plasma antioxidant concentrations, making changes difficult to interpret. Although this study used a mini-pig animal model of LPS-induced oxidative stress, it confirmed our previous findings in different rat models that measurement of antioxidants in plasma is not useful for the assessment of oxidative damage in vivo. PMID:25614459

  11. Differential anti-inflammatory and anti-oxidative effects of dexamethasone and N-acetylcysteine in endotoxin-induced lung inflammation

    PubMed Central

    Rocksén, D; Lilliehöök, B; Larsson, R; Johansson, T; Bucht, A

    2000-01-01

    Inhalation of bacterial endotoxin induces an acute inflammation in the lower respiratory tract. In this study, the anti-inflammatory effects of the anti-oxidant N-acetylcysteine (NAC) and the glucocorticoid dexamethasone were investigated in mice exposed to aerosolized endotoxin (lipopolysaccharide (LPS)). Powerful reduction of neutrophils in bronchoalveolar lavage fluid (BALF) was obtained by a single i.p. injection of dexamethasone (10 mg/kg), whereas treatment with NAC only resulted in reduction of neutrophils when administered at a high dose (500 mg/kg). Measurement of cytokine and chemokine expression in lung tissue revealed a significant decrease of tumour necrosis factor-alpha, IL-1α, IL-1β, IL-6, IL-12p40, and MIP-1α mRNA when mice where treated with dexamethasone but not when treated with NAC. Analysis of oxidative burst demonstrated a remarkable reduction of oxygen radicals in BALF neutrophils after treatment with dexamethasone, whereas the effect of NAC was not significantly different from that in untreated animals. In conclusion, dexamethasone exerted both anti-inflammatory and anti-oxidative effects in acute airway inflammation, probably by blocking early events in the inflammatory cascade. In contrast, treatment with NAC resulted in a weak reduction of the inflammatory response but no inhibition of proinflammatory cytokines or reduction of oxidative burst in neutrophils. These results demonstrate dramatic differences in efficiency and also indicate that the two drugs have different actions. Combined treatment with NAC and dexamethasone revealed an additive action but no synergy was observed. PMID:11091282

  12. Idh1 protects murine hepatocytes from endotoxin-induced oxidative stress by regulating the intracellular NADP(+)/NADPH ratio.

    PubMed

    Itsumi, M; Inoue, S; Elia, A J; Murakami, K; Sasaki, M; Lind, E F; Brenner, D; Harris, I S; Chio, I I C; Afzal, S; Cairns, R A; Cescon, D W; Elford, A R; Ye, J; Lang, P A; Li, W Y; Wakeham, A; Duncan, G S; Haight, J; You-Ten, A; Snow, B; Yamamoto, K; Ohashi, P S; Mak, T W

    2015-11-01

    Isocitrate dehydrogenase-1 (Idh1) is an important metabolic enzyme that produces NADPH by converting isocitrate to α-ketoglutarate. Idh1 is known to reduce reactive oxygen species (ROS) induced in cells by treatment with lipopolysaccharide (LPS) in vitro. Here, we used Idh1-deficient knockout (Idh1 KO) mice to investigate the role of Idh1 in antioxidant defense in vivo. Idh1 KO mice showed heightened susceptibility to death induced by LPS and exhibited increased serum levels of inflammatory cytokines such as tumor necrosis factor-α and interleukin-6. The serum of LPS-injected Idh1 KO mice also contained elevated levels of AST, a marker of inflammatory liver damage. Furthermore, after LPS injection, livers of Idh1 KO mice showed histological evidence of elevated oxidative DNA damage compared with livers of wild-type (WT) mice. Idh1 KO livers showed a faster and more pronounced oxidative stress than WT livers. In line with that, Idh1 KO hepatocytes showed higher ROS levels and an increase in the NADP(+)/NADPH ratio when compared with hepatocytes isolated from WT mice. These results suggest that Idh1 has a physiological function in protecting cells from oxidative stress by regulating the intracellular NADP(+)/NADPH ratio. Our findings suggest that stimulation of Idh1 activity may be an effective therapeutic strategy for reducing oxidative stress during inflammatory responses, including the early stages of septic shock.

  13. Nitric oxide suppression reversibly attenuates mitochondrial dysfunction and cholestasis in endotoxemic rat liver.

    PubMed

    Shiomi, M; Wakabayashi, Y; Sano, T; Shinoda, Y; Nimura, Y; Ishimura, Y; Suematsu, M

    1998-01-01

    This study aimed to examine whether nitric oxide (NO) plays a causal role in endotoxin-induced dysfunction of biliary transport. Rats were treated with intraperitoneal injection of endotoxin (O111B4, 4 mg/kg). At 2 hours, the liver was excised and perfused ex vivo with taurocholate (TC)-containing Krebs-Ringer solution under monitoring bile output and NO2 in the perfusate and tissue cyclic guanosine monophosphate (cGMP) levels as indices of NO production. The endotoxin treatment evoked a marked decrease in the bile acid-dependent bile formation concurrent with the increasing NO2 output, cGMP elevation, and a reduction of hepatic adenosine triphosphate (ATP) contents and oxygen consumption. Perfusion with 1 mmol/L aminoguanidine (AG), an inhibitor of inducible NO synthase, but not with L-nitroarginine methyl ester, an inhibitor of the constitutive form of the enzyme, significantly reversed the endotoxin-induced increment of the bile formation in concert with the recovery of oxygen consumption and ATP levels. Laser confocal microfluorography of the liver lobules using rhodamine 123 (Rh), a fluoroprobe sensitive to mitochondrial membrane potential, revealed that endotoxin elicited a significant mitochondrial dysfunction panlobularly. The AG administration reversed the endotoxin-induced decrease in mitochondrial membrane potential. Collectively, up-regulation of NO by inducible NO synthase accounts for a mechanism through which endotoxin impairs the bile formation, and its suppression serves as a therapeutic strategy for improvement of hepatobiliary function. PMID:9425925

  14. 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.

  15. Therapeutic anti-inflammatory effects of luteolin on endotoxin-induced uveitis in Lewis rats

    PubMed Central

    KANAI, Kazutaka; NAGATA, Sho; HATTA, Takuya; SUGIURA, Yuichi; SATO, Kazuaki; YAMASHITA, Yohei; KIMURA, Yuya; ITOH, Naoyuki

    2016-01-01

    The present study aimed to investigate the therapeutic efficacy of post-inflammatory treatment with luteolin on endotoxin-induced uveitis (EIU) in rats. Intraperitoneal injection of 10 mg/kg luteolin or 1 mg/kg prednisolone (Pred) at 4 hr post-lipopolysaccharide (LPS) injection (200 µg) was associated at 24 hr post-LPS injection with decreased clinical severity scores, number of inflammatory cells, protein levels and levels of tumor necrosis factor (TNF)-α, nitric oxide (NO) and prostaglandin (PG) E2 in the aqueous humor (AqH) and degrees of histological ocular tissue injury. The anti-inflammatory potency of luteolin was comparable to that of Pred. Luteolin exhibited robust efficacy in the treatment of EIU in rats, indicating its potential clinical utility in treating uveitis. PMID:27170432

  16. 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

  17. Biotransformation of nitric oxide

    SciTech Connect

    Yoshida, K.; Kasama, K.

    1987-08-01

    Previous investigations into the health effects of nitrogen oxides (NO/sub x/) have mostly been conducted with special reference to nitrogen dioxide (NO/sub 2/) and its direct effects on the respiratory system, while the study of nitric oxide (NO) has been disregarded. The authors carried out a study on NO by exposing rats and mice to /sup 15/NO or administering /sup 15/N-nitrite and /sup 15/N-nitrate to these animals by IP injection in order to elucidate the metabolic fate of NO. The results of their study and previous findings led them to assume that the major metabolic path of inhaled NO is as follows: inhaled NO reacts with hemoglobin, forming nitrosyl-hemoglobin (NOHb), and from NOHb, nitrate (NO/sub 2//sup -/ and nitrate (NO/sub 3//sup -/) are generated. Major quantities of NO/sub 3//sup -/ are discharged into the urine and a certain amount is discharged into the oral cavity through the salivary glands and transformed to NO/sub 2//sup -/. Part of this NO/sub 2//sup -/ is converted to N/sub 2/ gas in the stomach. Nitrate in the intestine is partly reduced to ammonia (NH/sub 3/) through NO/sub 2//sup -/, reabsorbed into the body, and converted to urea. Most of the metabolites of inhaled NO are excreted rapidly from the body within 48 hr.

  18. 49 CFR 173.337 - Nitric oxide.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 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. Luteolin attenuates endotoxin-induced uveitis in Lewis rats

    PubMed Central

    KANAI, Kazutaka; HATTA, Takuya; NAGATA, Sho; SUGIURA, Yuichi; SATO, Kazuaki; YAMASHITA, Yohei; KIMURA, Yuya; ITOH, Naoyuki

    2016-01-01

    The aim of the present study was to investigate the efficacy of luteolin on endotoxin-induced uveitis (EIU) in rats. EIU was induced in Lewis rats by subcutaneous injections of lipopolysaccharide (LPS). One hr before the LPS injection, 0.1, 1 or 10 mg/kg luteolin or 1 mg/kg prednisolone was intraperitoneally injected. We investigated its effect upon clinical scores, cellular infiltration and protein leakage, as well as on the level of tumor necrosis factor (TNF)-α, nitric oxide (NO) and prostaglandin (PG) E2 in the aqueous humor (AqH). Histologic examination and immunohistochemical analysis in the iris-ciliary body (ICB) were performed to determine the expressions of cyclooxygenase (COX)-2 and inducible NO synthase (iNOS), and then the activated nuclear factor (NF)-κB p65, I kappa B (IκB)-α degradation, phosphorylated (p)-IκB kinase (IKK) α/β and activator protein (AP)-1 c-Jun. Luteolin suppressed, in a dose-dependent manner, the clinical scores, number of inflammatory cells, the protein concentration, and the TNF-α, NO and PGE2 levels in the AqH and improved the histiologic status of the ocular tissue. Luteolin suppressed the expression of iNOS and COX-2 and the activated NF-κB p65, IκB-α degradation, p-IKKα/β and AP-1 p-c-Jun in the ICB. The anti-inflammatory potency of 10 mg/kg luteolin was as strong as that observed with 1 mg/kg prednisolone. These results demonstrate that luteolin attenuates ocular inflammation by inhibiting expression and release of inflammatory markers, along with the inhibition of the activated NF-κB pathway and at least partly AP-1 activity in the ICB. PMID:27098110

  20. Nitric oxide as an antioxidant

    SciTech Connect

    Kanner, J.; Harel, S.; Granit, R. )

    1991-08-15

    Benzoate monohydroxy compounds, and in particular salicylate, were produced during interaction of ferrous complexes with hydrogen peroxide (Fenton reaction) in a N2 environment. These reactions were inhibited when Fe complexes were flushed, prior to the addition in the model system, by nitric oxide. Methionine oxidation to ethylene by Fenton reagents was also inhibited by nitric oxide. Myoglobin in several forms such as metmyoglobin, oxymyoglobin, and nitric oxide-myoglobin were interacted with an equimolar concentration of hydrogen peroxide. Spectra changes in the visible region and the changes in membrane (microsomes) lipid peroxidation by the accumulation of thiobarbituric acid-reactive substances (TBA-RS) were determined. The results showed that metmyoglobin and oxymyoglobin were activated by H2O2 to ferryl myoglobin, which initiates membrane lipid peroxidation; but not nitric oxide-myoglobin, which, during interaction with H2O2, did not form ferryl but metmyoglobin which only poorly affected lipid peroxidation. It is assumed that nitric oxide, liganded to ferrous complexes, acts to prevent the prooxidative reaction of these complexes with H2O2.

  1. [Nitric oxide and nitric oxide synthase related to male reproduction].

    PubMed

    Ji, Jiajia; Zhao, Yanfang; Chen, Guoyuan

    2007-09-01

    Nitric oxide (NO) may be a kind of signal molecule which may have multiplicate physiological function such as secondary messenger, neurotransmitter and effect molecule. NO may play a crucial role in organism. The production of NO can not get away from nitric oxide synthase (NOS) which may distribute in almost all kind of organs of male reproductive system. NO and NOS may have the function of bifunctional regulation for reproduction. In this paper, the regulatory function of NO and NOS on male reproductive system were reviewed.

  2. Selective endothelin-A receptor blockade attenuates endotoxin-induced pulmonary hypertension and pulmonary vascular dysfunction

    PubMed Central

    2014-01-01

    Abstract Endothelin-1 is a potent mediator of sepsis-induced pulmonary hypertension (PH). The pulmonary vascular effects of selective blockade of endothelin receptor subtype A (ETAR) during endotoxemia remain unknown. We hypothesized that selective ETAR antagonism attenuates endotoxin-induced PH and improves pulmonary artery (PA) vasoreactivity. Adult male Sprague-Dawley rats (250–450 g) received lipopolysaccharide (LPS; Salmonella typhimurium; 20 mg/kg intraperitoneally) or vehicle 6 hours before hemodynamic assessment and tissue harvest. The selective ETAR antagonist sitaxsentan (10 or 20 mg/kg) or vehicle was injected intravenously 3 hours after receipt of LPS. Right ventricular systolic pressure, mean arterial pressure (MAP), cardiac output (CO), oxygenation (P/F ratio), and serum bicarbonate were measured. Bronchoalveolar lavage (BAL) cell differential and lung wet-to-dry ratios were obtained. Endothelium-dependent and endothelium-independent vasorelaxations were determined in isolated PA rings. PA interleukin (IL)-1β, IL-6, tumor necrosis factor α (TNF-α), and inducible nitric oxide synthase (iNOS) messenger RNA (mRNA) were measured. LPS caused PH, decreased MAP, CO, and serum bicarbonate, and increased PA IL-1β, IL-6, TNF-α, and iNOS mRNA. Sitaxsentan attenuated sepsis-induced PH and increased MAP. The P/F ratio, CO, serum bicarbonate, and BAL neutrophilia were not affected by sitaxsentan. In isolated PA rings, while not affecting phenylephrine-induced vasocontraction or endothelium-dependent relaxation, sitaxsentan dose-dependently attenuated LPS-induced alterations in endothelium-independent relaxation. PA cytokine mRNA levels were not significantly attenuated by ETAR blockade. We conclude that ETAR blockade attenuates endotoxin-induced alterations in systemic and PA pressures without negatively affecting oxygenation. This protective effect appears to be mediated not by attenuation of sepsis-induced cardiac dysfunction, acidosis, or alveolar

  3. Expression Profile of Cationic Amino Acid Transporters in Rats with Endotoxin-Induced Uveitis

    PubMed Central

    Chang, Shu-Wen; Lee, Yi-An; Kao, Tzu-Yun

    2016-01-01

    Purpose. The transcellular arginine transportation via cationic amino acid transporter (CAT) is the rate-limiting step in nitric oxide (NO) synthesis, which is crucial in intraocular inflammation. In this study, CAT isoforms and inducible nitric oxide synthase (iNOS) expression was investigated in endotoxin-induced uveitis (EIU). Methods. EIU was induced in Lewis rats by lipopolysaccharide (LPS) injection. In the treatment group, the rats were injected intraperitoneally with the proteasome inhibitor bortezomib before EIU induction. After 24 hours, leukocyte quantification, NO measurement of the aqueous humor, and histopathological examination were evaluated. The expression of CAT isoforms and iNOS was determined by reverse transcription-polymerase chain reaction, western blotting, and immunofluorescence staining. Nuclear factor-kappa B (NF-κB) binding activity was evaluated by electrophoretic mobility shift assay. The mouse macrophage cell line RAW 264.7 was used to validate the in vivo findings. Results. LPS significantly stimulated iNOS, CAT-2A, and CAT-2B mRNA and protein expression but did not affect CAT-1 in EIU rats and RAW 264.7 cells. Bortezomib attenuated inflammation and inhibited iNOS, CAT-2A, and CAT-2B expression through NF-κB inhibition. Conclusions. CAT-2 and iNOS, but not CAT-1, are specifically involved in EIU. NF-κB is essential in the induction of CAT-2 and iNOS in EIU. PMID:27413255

  4. An electrogenic nitric oxide reductase.

    PubMed

    Al-Attar, Sinan; de Vries, Simon

    2015-07-22

    Nitric oxide reductases (Nors) are members of the heme-copper oxidase superfamily that reduce nitric oxide (NO) to nitrous oxide (N₂O). In contrast to the proton-pumping cytochrome oxidases, Nors studied so far have neither been implicated in proton pumping nor have they been experimentally established as electrogenic. The copper-A-dependent Nor from Bacillus azotoformans uses cytochrome c₅₅₁ as electron donor but lacks menaquinol activity, in contrast to our earlier report (Suharti et al., 2001). Employing reduced phenazine ethosulfate (PESH) as electron donor, the main NO reduction pathway catalyzed by Cu(A)Nor reconstituted in liposomes involves transmembrane cycling of the PES radical. We show that Cu(A)Nor reconstituted in liposomes generates a proton electrochemical gradient across the membrane similar in magnitude to cytochrome aa₃, highlighting that bacilli using Cu(A)Nor can exploit NO reduction for increased cellular ATP production compared to organisms using cNor. PMID:26149211

  5. [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. PMID:18399354

  6. 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.

  7. 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.

  8. Citalopram reduces endotoxin-induced fatigue.

    PubMed

    Hannestad, Jonas; DellaGioia, Nicole; Ortiz, Nyrma; Pittman, Brian; Bhagwagar, Zubin

    2011-02-01

    Increased levels of inflammatory cytokines such as tumor necrosis factor (TNF) and interleukin-6 (IL-6) may play a role in depression. Mild depressive-like symptoms can be induced in humans through activation of the innate immune system with endotoxin. Whether preventive treatment with antidepressants can reduce endotoxin-induced symptoms has never been tested. In a double-blind, randomized, placebo-controlled, cross-over study, we administered intravenous low-dose endotoxin (0.8 ng/kg) or placebo to 11 healthy subjects who had received oral pre-treatment with citalopram (10 mg twice a day) or placebo for 5 days. The Montgomery-Åsberg Depression Rating Scale, the State and Trait Anxiety Inventory, and a visual analog scale were used to measure depressive and anxiety symptoms and social anhedonia. Serum levels of TNF and IL-6 were measured with immunoassays. Compared to placebo, endotoxin administration increased serum levels of TNF and IL-6, and caused mild depressive-like symptoms, in particular lassitude and social anhedonia. While citalopram pre-treatment had no effect on the innate immune response to endotoxin, it reduced the endotoxin-induced MADRS total score by 50%, with a moderate effect size (Cohen's d=0.5). Most of the MADRS total score was due to the lassitude item, and citalopram pre-treatment specifically reduced endotoxin-induced lassitude with a large effect size (Cohen's d=0.9). These results suggest that subchronic pre-treatment with the serotonin-reuptake inhibitor citalopram blunts mood symptoms induced by acute immune system activation with endotoxin without inhibiting the peripheral immune response.

  9. Nitric oxide and nitric oxide synthase in Huntington's disease.

    PubMed

    Deckel, A W

    2001-04-15

    Nitric oxide (NO) is a biologically active inorganic molecule produced when the semiessential amino acid l-arginine is converted to l-citrulline and NO via the enzyme nitric oxide synthase (NOS). NO is known to be involved in the regulation of many physiological processes, such as control of blood flow, platelet adhesion, endocrine function, neurotransmission, neuromodulation, and inflammation, to name only a few. During neuropathological conditions, the production of NO can be either protective or toxic, dependent on the stage of the disease, the isoforms of NOS involved, and the initial pathological event. This paper reviews the properties of NO and NOS and the pathophysiology of Huntington's disease (HD). It discusses ways in which NO and NOS may interact with the protein product of HD and reviews data implicating NOS in the neuropathology of HD. This is followed by a synthesis of current information regarding how NO/NOS may contribute to HD-related pathology and identification of areas for potential future research. PMID:11288139

  10. Nitric oxide and nitric oxide synthase in Huntington's disease.

    PubMed

    Deckel, A W

    2001-04-15

    Nitric oxide (NO) is a biologically active inorganic molecule produced when the semiessential amino acid l-arginine is converted to l-citrulline and NO via the enzyme nitric oxide synthase (NOS). NO is known to be involved in the regulation of many physiological processes, such as control of blood flow, platelet adhesion, endocrine function, neurotransmission, neuromodulation, and inflammation, to name only a few. During neuropathological conditions, the production of NO can be either protective or toxic, dependent on the stage of the disease, the isoforms of NOS involved, and the initial pathological event. This paper reviews the properties of NO and NOS and the pathophysiology of Huntington's disease (HD). It discusses ways in which NO and NOS may interact with the protein product of HD and reviews data implicating NOS in the neuropathology of HD. This is followed by a synthesis of current information regarding how NO/NOS may contribute to HD-related pathology and identification of areas for potential future research.

  11. Chemoprevention with phytochemicals targeting inducible nitric oxide synthase.

    PubMed

    Murakami, Akira

    2009-01-01

    A regulated low level of nitric oxide (NO) production in the body is essential for maintaining homeostasis (neuroprotection, vasorelaxation, etc.), though certain pathophysiological conditions associated with inflammation involve de novo synthesis of inducible NO synthase (iNOS) in immune cells, including macrophages. A large body of evidence indicates that many inflammatory diseases, such as colitis and gastritis, as well as many types of cancer, occur through sustained and elevated activation of this particular enzyme. The biochemical process of iNOS protein expression is tightly regulated and complex, in which the endotoxin lipopolysaccharide selectively binds to toll-like receptor 4 and thereby activates its adaptor protein MyD88, which in turn targets downstream proteins such as IRAK and TRAF6. This leads to functional activation of key protein kinases, including IkB kinases and mitogen-activated protein kinases (MAPKs), such as p38 MAPK, JNK1/2, and ERK1/2, all of which are involved in activating key transcription factors, including nuclear factor-kappaB and activator protein-1. In addition, the production of proinflammatory cytokines such as interferon-gamma and interleukin-12 potentiates iNOS induction in autocrine fashions. Meanwhile, an LPS-stimulated p38 MAPK pathway plays a pivotal role in the stabilization of iNOS mRNA, which has the AU-rich element in its 3'-untranslated region, for rapid NO production. Thus, suppression and/or inhibition of the above-mentioned signaling molecules may have a great potential for the prevention and treatment of inflammation-associated carcinogenesis. In fact, there have been numerous reports of phytochemicals found capable of targeting NO production by unique mechanisms, including polyphenols, terpenoids, and others. This review article briefly highlights the molecular mechanisms underlying endotoxin-induced iNOS expression in macrophages, and also focuses on promising natural agents that may be useful for anti

  12. [Does nitric oxide stress exist?].

    PubMed

    Torreilles, J; Guérin, M C

    1995-01-01

    Ten years ago, the term "oxidative stress" (sigma -O2) was created to define oxidative damage inflicted to the organism. This definition brings together processes involving reactive oxygen species production and action such as free radical production during univalent reduction of oxygen within mitochondria, activation of NADPH-dependent oxidase system on the membrane surface of neutrophils, flavoprotein-catalyzed redox cycling of xenobiotics and exposure to chemical and physical agents in the environment. Since the discovery of the nitric oxide biosynthetic pathway, the deleterious effects of uncontrolled nitric oxide generation are generally classified as oxidative stress. Indeed, products of the reaction of NO and superoxide lead to oxidants such as peroxinitrite, nitrogen dioxide and hydroxyl radical, which are involved in mechanisms of cell-mediated immune reactions and defence of the intracellular environment against microbiol invasion. However NO can also regulate many biological reactions and signal transduction pathways that lead to a variety of physiological responses such as blood pressure, neurotransmission, platelet aggregation, endothelin generation or smooth muscle cell proliferation. Then the uncontrolled NO production can lead to a variety of physiological and pathophysiological responses similar to a Nitric Oxide Stress: activation of guanylate cyclase and production of cGMP: overstimulation of the inducible L-arginine to L-citrulline and NO pathway by bactericidal endotoxins and cytokines has been shown to promote undesired increases in vasodilatation, which may account for hypotension in septic shock and cytokine therapy. stimulation of auto-ADP-ribosylation and modification of SH-groups of glyceraldehyde-3-phosphate dehydrogenase in a cGMP-independent mechanism: by this way, NO in excess can strongly inhibits this important glycolytic enzyme and reduce the cellular energy production. inhibition of ribonucleotide reductase: extensive inhibition

  13. 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.

  14. Vascular oxidative stress, nitric oxide and atherosclerosis.

    PubMed

    Li, Huige; Horke, Sven; Förstermann, Ulrich

    2014-11-01

    In the vascular wall, reactive oxygen species (ROS) are produced by several enzyme systems including NADPH oxidase, xanthine oxidase, uncoupled endothelial nitric oxide synthase (eNOS) and the mitochondrial electron transport chain. On the other hand, the vasculature is protected by antioxidant enzyme systems, including superoxide dismutases, catalase, glutathione peroxidases and paraoxonases, which detoxify ROS. Cardiovascular risk factors such as hypercholesterolemia, hypertension, and diabetes mellitus enhance ROS generation, resulting in oxidative stress. This leads to oxidative modification of lipoproteins and phospholipids, mechanisms that contribute to atherogenesis. In addition, oxidation of tetrahydrobiopterin may cause eNOS uncoupling and thus potentiation of oxidative stress and reduction of eNOS-derived NO, which is a protective principle in the vasculature. This review summarizes the latest advances in the role of ROS-producing enzymes, antioxidative enzymes as well as NO synthases in the initiation and development of atherosclerosis.

  15. Role of TFEB Mediated Autophagy, Oxidative Stress, Inflammation, and Cell Death in Endotoxin Induced Myocardial Toxicity of Young and Aged Mice

    PubMed Central

    Li, Fang; Lang, Fangfang; Zhang, Huilin; Xu, Liangdong; Wang, Yidan; Hao, Enkui

    2016-01-01

    Elderly patients are susceptible to sepsis. LPS induced myocardial injury is a widely used animal model to assess sepsis induced cardiac dysfunction. The age dependent mechanisms behind sepsis susceptibility were not studied. We analyzed age associated changes to cardiac function, cell death, inflammation, oxidative stress, and autophagy in LPS induced myocardial injury. Both young and aged C57BL/6 mice were used for LPS administration. The results demonstrated that LPS induced more cardiac injury (creatine kinase, lactate dehydrogenase, troponin I, and cardiac myosin-light chains 1), cardiac dysfunction (left ventricular inner dimension, LVID, and ejection fraction (EF)), cell death, inflammation, and oxidative stress in aged mice compared to young mice. However, a significant age dependent decline in autophagy was observed. Translocation of Transcription Factor EB (TFEB) to nucleus and formation of LC3-II were significantly reduced in LPS administered aged mice compared to young ones. In addition to that, downstream effector of TFEB, LAMP-1, was induced in response to LPS challenge in young mice. The present study newly demonstrates that TFEB mediated autophagy is crucial for protection against LPS induced myocardial injury particularly in aging senescent heart. Targeting this autophagy-oxidative stress-inflammation-cell death axis may provide a novel therapeutic strategy for cardioprotection in the elderly. PMID:27200146

  16. Nitric oxide releasing acetaminophen (nitroacetaminophen).

    PubMed

    Moore, P K; Marshall, M

    2003-05-01

    The nitric oxide releasing derivative of acetaminophen (nitroacetaminophen) exhibits potent anti-inflammatory and anti-nociceptive activity in a variety of animal models. On a mol for mol basis nitroacetaminophen is some 3-20 times more potent than acetaminophen. Nitroacetaminophen exhibits little or no hepatotoxicity following administration in rat or mouse and indeed protects against the hepatotoxic activity of acetaminophen. Nitroacetaminophen does not affect blood pressure or heart rate of anaesthetised rats but has similar potency to acetaminophen as an anti-pyretic agent. The enhanced anti-inflammatory and anti-nociceptive activity of nitroacetaminophen and the reduced hepatotoxicity in these animal models is likely to be secondary to the slow release of nitric oxide from the molecule. As yet the precise molecular mechanism(s) underlying these actions of nitroacetaminophen are not clear. Evidence for inhibition of cytokine-directed formation of pro-inflammatory molecule production (e.g. COX-2, iNOS) by an effect on the NF-kappaB transduction system and/or nitrosylation (and thence inhibition) of caspase enzyme activity has been reported. Data described in this review indicate that the profile of pharmacological activity of nitroacetaminophen and acetaminophen are markedly different. The possibility that nitroacetaminophen could be an attractive alternative to acetaminophen in the clinic is discussed. PMID:12846444

  17. Nitric oxide fumigation for postharvest pest control

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 ...

  18. Nitric oxide synthases in pregnant rat uterus.

    PubMed

    Farina, M; Ribeiro, M L; Franchi, A

    2001-03-01

    The conversion of [14C]arginine into [14C]citrulline as an indicator of nitric oxide synthesis was studied in uteri isolated from rats on different days of gestation, after labour and during dioestrus. Nitric oxide synthesis was present in uterine tissues isolated at each stage of gestation and also in tissues collected during dioestrus and after labour. Expression of neuronal nitric oxide synthase was not detectable at any of the stages studied. Endothelial nitric oxide synthase was present at all the stages studied, but there was a significant increase on day 13 of gestation and a decrease thereafter, with the lowest expression recorded on the day after labour. Inducible nitric oxide synthase expression in rat uteri increased substantially during pregnancy, with the highest expression on day 13 of gestation; expression decreased at term and after labour. The changes in expression of inducible nitric oxide synthase were coincident with the changes in nitric oxide synthase activity in uteri treated with aminoguanidine. Thus, these findings indicate that an increase in expression of inducible nitric oxide synthase in the uterus may be important for maintenance of uterine quiescence during pregnancy and its decrease near the time of labour could have an effect on the start of uterine contractility. PMID:11226066

  19. 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.

  20. Preventive and therapeutic anti-inflammatory effects of systemic and topical thalidomide on endotoxin-induced uveitis in rats.

    PubMed

    Rodrigues, Gustavo Büchele; Passos, Giselle Fazzioni; Di Giunta, Gabriella; Figueiredo, Cláudia Pinto; Rodrigues, Eduardo Büchele; Grumman, Astor; Medeiros, Rodrigo; Calixto, João B

    2007-03-01

    The present study examined the outcomes of systemic or topical treatment with thalidomide, a compound that possesses anti-inflammatory, immunomodulatory and anti-angiogenic properties, in rats subjected to endotoxin-induced uveitis (EIU). The effects of thalidomide were evaluated on endotoxin-induced leucocyte and protein infiltration and also on the production of interleukin (IL)-1beta and tumour necrosis factor (TNF)-alpha in rat aqueous humour (AqH). Moreover, the actions of thalidomide were assessed on the cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) protein expression in retinal tissue. EIU was produced by a hindpaw injection of lipopolysaccharide (LPS), in male Wistar rats. Thalidomide (5, 25 and 50 mg/kg) was administered orally 1 h before LPS injection. In another set of experiments, to evaluate the therapeutic efficacy, 5% thalidomide was applied topically to both eyes at 6, 12 and 18 h after LPS administration. The oral pre-treatment with thalidomide decreased, in a dose-dependent manner, the number of inflammatory cells, the protein concentration, and the levels of IL-1beta and TNF-alpha in the AqH. Similar results were found in the AqH of rats that received a topical application of thalidomide. Furthermore, oral (50 mg/kg) and local (5%) thalidomide treatment also reduced expression of the pro-inflammatory proteins COX-2 and iNOS in the posterior segment of the eye. Thalidomide exhibited marked preventive and curative ocular effects in EIU in rats, a property that might be associated with its ability to inhibit the production of inflammatory cytokines and the expression of COX-2 and iNOS. This assembly of data provides additional molecular and functional insights into beneficial effects of thalidomide as an agent for the management of ocular inflammation.

  1. Nitric oxide in liver diseases.

    PubMed

    Iwakiri, Yasuko; Kim, Moon Young

    2015-08-01

    Nitric oxide (NO) and its derivatives play important roles in the physiology and pathophysiology of the liver. Despite its diverse and complicated roles, certain patterns of the effect of NO on the pathogenesis and progression of liver diseases are observed. In general, NO derived from endothelial NO synthase (eNOS) in liver sinusoidal endothelial cells (LSECs) is protective against disease development, while inducible NOS (iNOS)-derived NO contributes to pathological processes. This review addresses the roles of NO in the development of various liver diseases with a focus on recently published articles. We present here two recent advances in understanding NO-mediated signaling - nitrated fatty acids (NO2-FAs) and S-guanylation - and conclude with suggestions for future directions in NO-related studies on the liver. PMID:26027855

  2. NITRIC OXIDE IN LIVER DISEASES

    PubMed Central

    Iwakiri, Yasuko; Kim, Moon Young

    2015-01-01

    Nitric oxide (NO) and its derivatives play important roles in the physiology and pathophysiology of the liver. Despite its diverse and complicated roles, certain patterns of the effect of NO on the pathogenesis and progression of liver diseases are observed. In general, NO derived from endothelial NO synthase (eNOS) in liver sinusoidal endothelial cells (LSECs) is protective against disease development, while inducible NOS (iNOS)-derived NO contributes to pathological processes. This review addresses the roles of NO in the development of various liver diseases with a focus on recently published articles. We present here two recent advances in understanding NO-mediated signaling, nitrated fatty acids and S-guanylation, and conclude with suggestions on future directions of NO-related studies on the liver. PMID:26027855

  3. Exhaled nitric oxide in sarcoidosis

    PubMed Central

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

    2005-01-01

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

  4. 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

  5. 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

  6. [Progesterone and nitric oxide systems].

    PubMed

    Wieser, F; Gruber, D M; Tschugguel, W; Huber, J C

    1997-01-01

    Sexual steroids play an established role in the mechanisms concerning reproduction, ovulation, menstruation and onset of labour. However, sexual steroids are also involved in extragenital mechanisms, which were described for both oestrogen, and progesterone. Progesterone and its mechanisms of signal transduction still remain to be fully understood. However, there is evidence, that nitric oxide (NO) seems to be an important mediator in these mechanisms. NO, the molecule, which was described to exist in acid rain, was elected the molecule of the year 1992 from the American Academy of Science. NO is a short-lived molecule, which is involved in many reactions as an modulating transmitter due to its high diffusibility and its polarity. NO regulates the immune response of mononuclear cells, contractility of smooth muscle cells and neuronal transmission of non-adrenergic and non-cholinergic nerves. Additionally it was found, that NO may be important in the regulation of menstruation, the maintenance of uterine quiescence as well as the initiation of labour and the maturation of the uterine cervix.

  7. Nitric Oxide Homeostasis in Neurodegenerative Diseases.

    PubMed

    Hannibal, Luciana

    2016-01-01

    The role of nitric oxide in the pathogenesis and progression of neurodegenerative illnesses such as Parkinson's and Alzheimer's diseases has become prominent over the years. Increased activity of the enzymes that produce reactive oxygen species, decreased activity of antioxidant enzymes and imbalances in glutathione pools mediate and mark the neurodegenerative process. Much of the oxidative damage of proteins is brought about by the overproduction of nitric oxide by nitric oxide synthases (NOS) and its subsequent reactivity with reactive oxygen species. Proteomic methods have advanced the field tremendously, by facilitating the quantitative assessment of differential expression patterns and oxidative modifications of proteins and alongside, mapping their non-canonical functions. As a signaling molecule involved in multiple biochemical pathways, the level of nitric oxide is subject to tight regulation. All three NOS isoforms display aberrant patterns of expression in Alzheimer's disease, altering intracellular signaling and routing oxidative stress in directions that are uncompounded. This review discusses the prime factors that control nitric oxide biosynthesis, reactivity footprints and ensuing effects in the development of neurodegenerative diseases.

  8. Median eminence nitric oxide signaling.

    PubMed

    Prevot, V; Bouret, S; Stefano, G B; Beauvillain, J

    2000-11-01

    It is becoming increasingly clear that nitric oxide (NO), an active free radical formed during the conversion of arginine to citrulline by the enzyme NO synthase (NOS), is a critical neurotransmitter and biological mediator of the neuroendocrine axis. Current evidence suggests that NO modulates the activity of both the hypothalamic-pituitary-gonadal axis and the hypothalamic-pituitary-adrenal axis. Supporting this hypothesis is the finding that the highest expression of neuronal NOS in the brain is found within the hypothalamus in areas where the cell bodies of the neurons from the different neuroendocrine systems are located. In this regard, the influence of neuronal NO on the regulation of the neuroendocrine neural cell body activity has been well-documented whereas little is known about NO signaling that directly modulates neurohormonal release into the pituitary portal vessels from the neuroendocrine terminals within the median eminence, the common termination field of the adenohypophysiotropic systems. Studies in rat suggest that NO is an important factor controlling both gonadotropin-releasing hormone (GnRH) and corticotropin-releasing hormone (CRH) release at the median eminence. The recent use of amperometric NO detection from median eminence fragments coupled to the use of selective NOS inhibitors demonstrated that a major source of NO at the median eminence might be endothelial in origin rather than neuronal. The present article reviews the recent progress in identifying the origin and the role of the NO produced at the median eminence in the control of neurohormonal release. We also discuss the potential implications of the putative involvement of the median eminence endothelial cells in a neurovascular regulatory process for hypothalamic neurohormonal signaling.

  9. Nitro-oleic acid protects against endotoxin-induced endotoxemia and multiorgan injury in mice

    PubMed Central

    Wang, Haiping; Liu, Haiying; Jia, Zhunjun; Olsen, Curtis; Litwin, Sheldon

    2010-01-01

    Nitroalkene derivatives of nitro-oleic acid (OA-NO2 ) are endogenous lipid products with potent anti-inflammatory properties in vitro. The present study was undertaken to evaluate the in vivo anti-inflammatory effect of OA-NO2 in mice given LPS. Two days before LPS administration, C57BL/6J mice were chronically infused with vehicle (LPS vehicle) or OA-NO2 (LPS OA-NO2) at 200 μg·kg−1·day−1 via osmotic minipumps; LPS was administered via a single intraperitoneal (ip) injection (10 mg/kg in saline). A third group received an ip injection of saline without LPS or OA-NO2 and served as controls. At 18 h of LPS administration, LPS vehicle mice displayed multiorgan dysfunction as evidenced by elevated plasma urea and creatinine (kidney), aspartate aminotransferase (AST) and alanine aminotransferase (ALT; liver), and lactate dehydrogenase (LDH) and reduced ejection fraction (heart). In contrast, the severity of multiorgan dysfunction was less in LPS OA-NO2 animals. The levels of circulating TNF-α and renal TNF-α mRNA expression, together with renal mRNA expression of monocyte chemoattractant protein-1, ICAM-1, and VCAM-1, and with renal mRNA and protein expression of inducible nitric oxide synthase and cyclooxygenase 2, and renal cGMP and PGE2 contents, were greater in LPS vehicle vs. control mice, but were attenuated in LPS OA-NO2 animals. Similar patterns of changes in the expression of inflammatory mediators were observed in the liver. Together, pretreatment with OA-NO2 ameliorated the inflammatory response and multiorgan injury in endotoxin-induced endotoxemia in mice. PMID:20032118

  10. 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.

  11. 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

  12. 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 ...

  13. 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.

  14. 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.

  15. 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.

  16. Ginseng, sex behavior, and nitric oxide.

    PubMed

    Murphy, Laura L; Lee, Tony Jer-Fu

    2002-05-01

    In Asia, ginseng is commonly included in herbals used for the treatment of sexual dysfunction. Recent studies in laboratory animals have shown that both Asian and American forms of ginseng enhance libido and copulatory performance. These effects of ginseng may not be due to changes in hormone secretion, but to direct effects of ginseng, or its ginsenoside components, on the central nervous system and gonadal tissues. Indeed, there is good evidence that ginsenosides can facilitate penile erection by directly inducing the vasodilatation and relaxation of penile corpus cavernosum. Moreover, the effects of ginseng on the corpus cavernosum appear to be mediated by the release and/or modification of release of nitric oxide from endothelial cells and perivascular nerves. Treatment with American ginseng also affects the central nervous system and has been shown to significantly alter the activity of hypothalamic catecholamines involved in the facilitation of copulatory behavior and hormone secretion. Recent findings that ginseng treatment decreased prolactin secretion also suggested a direct nitric oxide-mediated effect of ginseng at the level of the anterior pituitary. Thus, animal studies lend growing support for the use of ginseng in the treatment of sexual dysfunction and provide increasing evidence for a role of nitric oxide in the mechanism of ginsenoside action. PMID:12076988

  17. Nitric oxide and the control of reproduction.

    PubMed

    Dixit, V D; Parvizi, N

    2001-01-31

    The free radical gas, nitric oxide is now known to be an important biological messenger in animals. Signal transmission by a gas that is produced by one cell, penetrates through membranes and regulates the function of another cell, represents new principles for signalling in biological systems. Nitric oxide is synthesised from L-arginine by enzyme nitric oxide synthase, which exists in multiple isoforms in a wide range of mammalian cells. Studies conducted in recent years point at a strong influence of NO in a wide range of reproductive functions. It is implicated in the control of gonadotrophin secretion at both hypothalamic and hypophyseal levels, LH surge mechanism, sexual behaviour, estradiol synthesis, follicle survival and ovulation. While considerable work lies ahead in unravelling the role of NO at the peripheral, cellular and molecular level in the domestic animal reproduction, findings presented in this review provide a general overview of growing appreciation of NO as a vital molecule controlling hypothalamic-pituitary-gonadal (HPG) axis.

  18. Biological nitric oxide signalling: chemistry and terminology

    PubMed Central

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

    2013-01-01

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

  19. 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.

  20. Processes regulating nitric oxide emissions from soils.

    PubMed

    Pilegaard, Kim

    2013-07-01

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

  1. Processes regulating nitric oxide emissions from soils.

    PubMed

    Pilegaard, Kim

    2013-07-01

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

  2. 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

  3. Nitric oxide regulates vascular adaptive mitochondrial dynamics.

    PubMed

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

    2013-06-15

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

  4. Allosteric inhibitors of inducible nitric oxide synthase dimerization discovered via combinatorial chemistry

    PubMed Central

    McMillan, Kirk; Adler, Marc; Auld, Douglas S.; Baldwin, John J.; Blasko, Eric; Browne, Leslie J.; Chelsky, Daniel; Davey, David; Dolle, Ronald E.; Eagen, Keith A.; Erickson, Shawn; Feldman, Richard I.; Glaser, Charles B.; Mallari, Cornell; Morrissey, Michael M.; Ohlmeyer, Michael H. J.; Pan, Gonghua; Parkinson, John F.; Phillips, Gary B.; Polokoff, Mark A.; Sigal, Nolan H.; Vergona, Ronald; Whitlow, Marc; Young, Tish A.; Devlin, James J.

    2000-01-01

    Potent and selective inhibitors of inducible nitric oxide synthase (iNOS) (EC 1.14.13.39) were identified in an encoded combinatorial chemical library that blocked human iNOS dimerization, and thereby NO production. In a cell-based iNOS assay (A-172 astrocytoma cells) the inhibitors had low-nanomolar IC50 values and thus were >1,000-fold more potent than the substrate-based direct iNOS inhibitors 1400W and N-methyl-l-arginine. Biochemical studies confirmed that inhibitors caused accumulation of iNOS monomers in mouse macrophage RAW 264.7 cells. High affinity (Kd ≈ 3 nM) of inhibitors for isolated iNOS monomers was confirmed by using a radioligand binding assay. Inhibitors were >1,000-fold selective for iNOS versus endothelial NOS dimerization in a cell-based assay. The crystal structure of inhibitor bound to the monomeric iNOS oxygenase domain revealed inhibitor–heme coordination and substantial perturbation of the substrate binding site and the dimerization interface, indicating that this small molecule acts by allosterically disrupting protein–protein interactions at the dimer interface. These results provide a mechanism-based approach to highly selective iNOS inhibition. Inhibitors were active in vivo, with ED50 values of <2 mg/kg in a rat model of endotoxin-induced systemic iNOS induction. Thus, this class of dimerization inhibitors has broad therapeutic potential in iNOS-mediated pathologies. PMID:10677491

  5. 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.

  6. 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

  7. Nitric oxide synthesis in locust olfactory interneurones

    PubMed

    Elphick; Rayne; Riveros-Moreno; Moncada; Shea

    1995-01-01

    The brain of the locust Schistocerca gregaria contains a nitric oxide synthase (NOS) that has similar properties to mammalian neuronal NOS. It catalyses the production of equimolar quantities of nitric oxide (NO) and citrulline from l-arginine in a Ca2+/calmodulin- and NADPH-dependent manner and is inhibited by the Nomega-nitro and Nomega-monomethyl analogues of l-arginine. In Western blots, an antiserum to the 160 kDa rat cerebellar NOS subunit recognises a locust brain protein with a molecular mass of approximately 135 kDa. NOS is located in several parts of the locust brain, including the mushroom bodies, but it is particularly abundant in the olfactory processing centres, the antennal lobes. Here it is present in two groups of local interneurones (a pair and a cluster of about 50) that project into the neuropile of the antennal lobes. The processes of these neurones terminate in numerous glomerulus-like structures where the synapses between primary olfactory receptor neurones and central interneurones are formed. NOS-containing local interneurones have also been identified in the mammalian olfactory bulb, suggesting that NO performs analogous functions in locust and mammalian olfactory systems. As yet, nothing is known about the role of NO in olfaction, but it seems likely that it is involved in the processing of chemosensory input to the brain. The locust antennal lobe may be an ideal 'simple' system in which this aspect of NO function can be examined.

  8. 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. PMID:26499181

  9. Supercritical extract of Seabuckthorn Leaves (SCE200ET) inhibited endotoxemia by reducing inflammatory cytokines and nitric oxide synthase 2 expression.

    PubMed

    Jayashankar, Bindhya; Mishra, K P; Ganju, L; Singh, S B

    2014-05-01

    Endotoxins from infectious organisms lead to sepsis, a systemic inflammatory response, and a major cause of death. Numerous studies have shown the potential role of plants and plant-derived compounds in the suppression of LPS induced endotoxemia in vivo. In the present study, we have identified a plant namely Seabuckthorn (Hippophae rhamnoides L.) as a potent agent for the treatment of endotoxemia. The objective of the study was to investigate the influence of Supercritical Extract of Seabuckthorn Leaves (SCE200ET) and its active component Isorhamnetin (IR) on the LPS induced endotoxemia in Balb/c mice by measuring the level of nitric oxide (NO), TNF-α and IL-6. Expression of COX-2 and iNOS was measured to understand the involvement of various pathways in the mechanism of action of SCE200ET and IR. The results indicated that SCE200ET and IR inhibited LPS induced NO production by peritoneal macrophages. Cytokines mediated effector functions were influenced by the reduction of IL-6 and TNF-α production and CD40 expression was also markedly diminished in the extract or IR treated groups. In addition, the anti-inflammatory properties were further characterized by decreased expression of COX-2 and iNOS proteins. Fractionation and phytochemical analysis of the extract by RP-HPLC led to identification of isorhamnetin, as bioactive component. Thus, SCE200ET extract and its active component Isorhamnetin could be potential therapeutic agents for the treatment of endotoxin induced sepsis.

  10. 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.

  11. 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…

  12. 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....

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

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

  15. 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 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....

  16. 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 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....

  17. 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 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....

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

  19. 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 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....

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

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

  2. Nitric oxide and septic shock. From bench to bedside.

    PubMed Central

    Kuhl, S J; Rosen, H

    1998-01-01

    Refractory hypotension with end-organ hypoperfusion is an ominous feature of inflammatory shock. In the past fifteen years, nitric oxide (a diffusible, short-lived product of arginine metabolism) has been found to be an important regulatory molecule in several areas of metabolism, including vascular tone control. Vascular endothelial cells constitutively produce low levels of nitric oxide that regulate blood pressure by mediating adjacent smooth-muscle relaxation. In an inflammatory shock state, cytokines, like interleukin-1 and tumor necrosis factor-alpha, induce a separate, high-output form of the enzyme that synthesizes nitric oxide in both endothelial and smooth-muscle cells. The ensuing high rates of nitric oxide formation result in extensive smooth-muscle relaxation, pressor refractory vasodilation, and--ultimately--shock. The concept of the pathogenesis of inflammatory shock explains many limitations of current therapies and may foster the development of new interventions to mitigate the effects of nitric oxide overproduction in this syndrome. PMID:9549416

  3. 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

  4. 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.

  5. Nitric oxide and the cardiovascular system.

    PubMed

    Bohlen, Harold Glenn

    2015-04-01

    Nitric oxide (NO) generated by endothelial cells to relax vascular smooth muscle is one of the most intensely studied molecules in the past 25 years. Much of what is known about NO regulation of NO is based on blockade of its generation and analysis of changes in vascular regulation. This approach has been useful to demonstrate the importance of NO in large scale forms of regulation but provides less information on the nuances of NO regulation. However, there is a growing body of studies on multiple types of in vivo measurement of NO in normal and pathological conditions. This discussion will focus on in vivo studies and how they are reshaping the understanding of NO's role in vascular resistance regulation and the pathologies of hypertension and diabetes mellitus. The role of microelectrode measurements in the measurement of [NO] will be considered because much of the controversy about what NO does and at what concentration depends upon the measurement methodology. For those studies where the technology has been tested and found to be well founded, the concept evolving is that the stresses imposed on the vasculature in the form of flow-mediated stimulation, chemicals within the tissue, and oxygen tension can cause rapid and large changes in the NO concentration to affect vascular regulation. All these functions are compromised in both animal and human forms of hypertension and diabetes mellitus due to altered regulation of endothelial cells and formation of oxidants that both damage endothelial cells and change the regulation of endothelial nitric oxide synthase. PMID:25880514

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  7. 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

  8. Nitric Oxide Release Part II. Therapeutic Applications

    PubMed Central

    Carpenter, Alexis W.; Schoenfisch, Mark H.

    2012-01-01

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

  9. 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

  10. Nitric oxide and plant iron homeostasis.

    PubMed

    Buet, Agustina; Simontacchi, Marcela

    2015-03-01

    Like all living organisms, plants demand iron (Fe) for important biochemical and metabolic processes. Internal imbalances, as a consequence of insufficient or excess Fe in the environment, lead to growth restriction and affect crop yield. Knowledge of signals and factors affecting each step in Fe uptake from the soil and distribution (long-distance transport, remobilization from old to young leaves, and storage in seeds) is necessary to improve our understanding of plant mineral nutrition. In this context, the role of nitric oxide (NO) is discussed as a key player in maintaining Fe homeostasis through its cross talk with hormones, ferritin, and frataxin and the ability to form nitrosyl-iron complexes. PMID:25612116

  11. 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

  12. Nitric oxide-releasing porous silicon nanoparticles.

    PubMed

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

    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.

  13. 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.

  14. Nitric Oxide Synthase in Spontaneously Hypertensive Rats.

    PubMed

    Wu, Ch.Ch.; Yen, M.-H.

    1997-01-01

    Since its discovery by Furchgott and Zawadzki in 1980 [18], endothelium-derived relaxing factor (EDRF) has been shown to play a central role in the cardiovascular system [10]. The endothelial product is chemically equivalent to nitric oxide (NO) [23, 40] or a biochemical congener thereof [48]. Fifteen years ago, this small, simple and highly toxic molecule was known as a lengthy list of environmental pollutants found in unsavory haunts such as smoke and smog, and even as destroyer of ozone, suspected carcinogen, and precursor of acid rain. In addition, NO seems an unlikely biological jack of all trades for most of the body's functions are regulated by extraordinarily large and complex proteins and compounds. But over the past decade, diverse lines of evidence have converged to show that this sometime poison is a fundamental player in the everyday business of the human body.

  15. Superoxide reactivates nitric oxide-inhibited catalase.

    PubMed

    Kim, Y S; Han, S

    2000-12-01

    Catalase binds nitric oxide (NO) to generate ferricatalase-NO, an inhibited form of the enzyme. Superoxide (O2-) is also an inactivator of the enzyme. We found, however, that O2- efficiently converted the inhibited ferricatalase-NO to the active ferricatalase without producing detectable intermediates. The reaction slowed down when O2- was disproportionated to H2O2 and O2 by superoxide dismutase, but H2O2 could displace the heme-bound NO slowly to regenerate ferricatalase. Reactivation was observed even under simultaneous generation of NO and O2-, suggesting that ferricatalase-NO reacts with O2- fast enough to compete with the rapid reaction of O2- and NO. Formation of peroxynitrite by the simultaneous generation of NO and O2- was only partially inhibited by ferricatalase, presumably due to slow binding of NO to catalase in comparison with the reaction of NO and O2-. PMID:11209763

  16. 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

  17. Nitric Oxide and Respiratory Helminthic Diseases

    PubMed Central

    Muro, Antonio; Pérez-Arellano, José-Luís

    2010-01-01

    Nitric oxide (NO) is a very simple molecule that displays very important functions both in helminths (mainly those involved in respiratory pathology) and in mammalian hosts. In this paper we review four issues related to interaction of NO and lung helminthic diseases. Firstly, we evaluated data available on the NO synthesis and release by helminths and their biological role. Next, we summarized the effect of antigens obtained from different phases of the biological cycle on NO production by host mammalian cells (mainly from human sources). Thirdly, we revised the evaluation of NO on the biological activities and/or the viability of respiratory helminths. Lastly, the deleterious consequences of increased production of NO during helminthic human infection are detailed. PMID:20169170

  18. Nitric oxide: a synchronizing chemical messenger.

    PubMed

    Anbar, M

    1995-06-14

    Nitric oxide (NO) has been recognized as a ubiquitous chemical messenger in a large number of different biological systems. Its chemical properties make it less specific and less controllable than practically any other neurotransmitter or hormone. In view of this, its extensive biological role as a chemical messenger seems surprising. It is suggested that the biological function of NO evolved early in the anaerobic stage of evolution. In view of its low molecular weight, limited interaction with water, and its electrical neutrality, which allow it to diffuse rapidly through the cytoplasm and biomembranes, it is suggested that the need for NO has been retained by and maintained in eukaryote cells because of its ability to affect many biochemical functions simultaneously, acting primarily as an intracellular synchronizing chemical messenger.

  19. 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

  20. Nitric oxide in liver fibrosis: The role of inducible nitric oxide synthase.

    PubMed

    Iwakiri, Yasuko

    2015-12-01

    The inducible form of nitric oxide synthase (iNOS) is expressed in hepatic cells in pathological conditions. Its induction is involved in the development of liver fibrosis, and thus iNOS could be a therapeutic target for liver fibrosis. This review summarizes the role of iNOS in liver fibrosis, focusing on 1) iNOS biology, 2) iNOS-expressing liver cells, 3) iNOS-related therapeutic strategies, and 4) future directions.

  1. Nitric oxide in liver fibrosis: The role of inducible nitric oxide synthase

    PubMed Central

    2015-01-01

    The inducible form of nitric oxide synthase (iNOS) is expressed in hepatic cells in pathological conditions. Its induction is involved in the development of liver fibrosis, and thus iNOS could be a therapeutic target for liver fibrosis. This review summarizes the role of iNOS in liver fibrosis, focusing on 1) iNOS biology, 2) iNOS-expressing liver cells, 3) iNOS-related therapeutic strategies, and 4) future directions. PMID:26770919

  2. Nitric oxide regulation of monkey myometrial contractility

    PubMed Central

    Kuenzli, Karri A; Buxton, Iain L O; Bradley, Michael E

    1998-01-01

    We evaluated the effect of the nitric oxide (NO) donor CysNO (S-nitroso-L-cysteine) and endogenous NO upon spontaneous contractility in non-pregnant cynomolgus monkeys. We also assessed the role of intracellular guanosine 3′,5′-cyclic monophosphate ([cyclic GMP]i) as a second messenger for NO in monkey uterine smooth muscle.CysNO reduced spontaneous contractility by 84% (P<0.05) at maximal concentrations, and significantly elevated [cyclic GMP]i (P<0.05). However, increases in [cyclic GMP]i were not required for CysNO-induced relaxations; CysNO inhibited contractile activity despite the complete inhibition of guanylyl cyclase by methylene blue or LY83,583.Analogues of cyclic GMP had no significant effect upon spontaneous contractile activity. L-arginine produced a 62% reduction in spontaneous activity (P<0.05) while D-arginine had no effect. The competitive nitric oxide synthase (NOS) inhibitor Nω-nitro-L-arginine (L-NOARG) not only blocked L-arginine-induced relaxations, but also significantly increased spontaneous contractile activity when added alone (P<0.05); the inactive D-enantiomer of NOARG had no such effect.While both endogenous NO and the NO donor CysNO relax monkey myometrium, this effect is not causally related to CysNO-induced elevations in [cyclic GMP]i. The failure of cyclic GMP analogues to alter monkey uterine smooth muscle tension also argues against a role for [cyclic GMP]i in the regulation of uterine contractility. Not only do these findings argue for the existence of a functionally-relevant NOS in the monkey uterus, but increases in contractile activity seen in the presence of NOS inhibitors suggest a role for NO in the moment-to-moment regulation of contractile activity in this organ. PMID:9630344

  3. 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

  4. The Oxyhemoglobin Reaction of Nitric Oxide

    NASA Astrophysics Data System (ADS)

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

    1999-08-01

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

  5. 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.

  6. 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.

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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.

  13. Budesonide inhalation ameliorates endotoxin-induced lung injury in rabbits

    PubMed Central

    Gao, Wei

    2015-01-01

    Acute respiratory distress syndrome (ARDS) is a serious clinical problem that has a 30–50% mortality rate. Budesonide has been used to reduce lung injury. This study aims to investigate the effects of nebulized budesonide on endotoxin-induced ARDS in a rabbit model. Twenty-four rabbits were randomized into three groups. Rabbits in the control and budesonide groups were injected with endotoxin. Thereafter, budesonide or saline was instilled, ventilated for four hours, and recovered spontaneous respiratory. Peak pressure, compliance, and PaO2/FiO2 were monitored for 4 h. After seven days, PaO2/FiO2 ratios were measured. Wet-to-dry weight ratios, total protein, neutrophil elastase, white blood cells, and percentage of neutrophils in BALF were evaluated. TNF-α, IL-1β, IL-8, and IL-10 in BALF were detected. Lung histopathologic injury and seven-day survival rate of the three groups were recorded. Peak pressure was downregulated, but compliance and PaO2/FiO2 were upregulated by budesonide. PaO2/FiO2 ratios significantly increased due to budesonide. Wet-to-dry weight ratios, total protein, neutrophil elastase, white blood cells and percentage of neutrophils in BALF decreased in the budesonide group. TNF-α, IL-1β, and IL-8 levels decreased in BALF, while IL-10 levels increased in the budesonide group. Lung injuries were reduced and survival rate was upregulated by budesonide. Budesonide effectively ameliorated respiratory function, attenuated endotoxin-induced lung injury, and improved the seven-day survival rate. PMID:25956681

  14. Nitric oxide and cancer: a review

    PubMed Central

    2013-01-01

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

  15. 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.

  16. Nitric oxide and oral cancer: a review.

    PubMed

    Korde Choudhari, Sheetal; Sridharan, Gokul; Gadbail, Amol; Poornima, V

    2012-06-01

    Nitric oxide (NO), a short-lived, endogenously produced gas, plays key role in various physiological as well as pathological processes. NO-inducing cell signaling events within the cell producing it and the diffusibility of it in other cells have led to the discovery of various physiological functions of NO including vasodilation, respiration, cell migration, immune response and apoptosis. On the other hand, excessive and unregulated NO synthesis has been implicated in many pathophysiological conditions including cancer. Research on NO, during the past few years is one of the growing areas in cancer biology. The high incidence of oral cancer and precancer has been linked with habits of tobacco chewing and smoking and NO has been said as the "messenger of death" in tobacco related diseases. NO seems to play a part in various stages of carcinogenesis from initiation to progression. However, there is considerable controversy and confusion in understanding its role in cancer biology. It is said to have both, tumoricidal as well as tumor promoting effects and these depend on its timing, location and concentration. Further, NO has also been shown to have antitumor, chemopreventive and therapeutic abilities. Here is an overview in which efforts are made to understand the role of this molecule in oral carcinogenesis. PMID:22356896

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

    PubMed

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

    2016-09-01

    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. Vascular nitric oxide: formation and function

    PubMed Central

    Jin, Richard C; Loscalzo, Joseph

    2010-01-01

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

  19. Nitric oxide releasing material adsorbs more fibrinogen.

    PubMed

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

    2013-11-01

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

  20. 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

  1. Nitric oxide modulates sensitivity to ABA.

    PubMed

    Lozano-Juste, Jorge; León, José

    2010-03-01

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

  2. Nitric oxide production in critically ill patients.

    PubMed Central

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

    1996-01-01

    OBJECTIVE: To measure serum nitrite and nitrate levels in critically ill children as indicators of endogenous nitric oxide (NO) production. HYPOTHESIS: Endogenous NO production is increased in children with conditions characterised by immune stimulation. DESIGN: Prospective descriptive study in a multidisciplinary paediatric intensive care unit. PATIENTS: 137 consecutive critically ill children with a variety of clinical conditions. INTERVENTIONS: Using a rapid microtitre plate technique, daily serum nitrite and nitrate levels were measured from serum samples that remained in the clinical laboratory after daily routine phlebotomy. Clinical and laboratory information was also gathered daily for each patient. RESULTS: The maximum serum nitrite plus nitrate levels (microM) reached by children with infection (41.8 (SD 18.1)), sepsis syndrome (85.1 (39.9)), shock without sepsis (36.4 (19.1)), transplantation alone (61.0 (43.4)), transplantation with sepsis (200.7 (150.5)), or rejection (161.7 (70.4)), were higher than in controls (18.1 (9.3)). In the absence of exogenous NO donors, levels greater than 80 microM were reached only in children with the sepsis syndrome, organ transplantation, or acute rejection. CONCLUSIONS: Increased endogenous NO production occurs in children with clinical conditions associated with immune stimulation. Further investigation is warranted to determine the value of this simple and rapid test as a clinically useful diagnostic tool and therapeutic monitor in the evaluation of children at risk for the sepsis syndrome or acute allograft rejection. PMID:8758122

  3. 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

  4. 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.

  5. Hypotension and reduced nitric oxide-elicited vasorelaxation in transgenic mice overexpressing endothelial nitric oxide synthase.

    PubMed Central

    Ohashi, Y; Kawashima, S; Hirata, K i; Yamashita, T; Ishida, T; Inoue, N; Sakoda, T; Kurihara, H; Yazaki, Y; Yokoyama, M

    1998-01-01

    Nitric oxide (NO), constitutively produced by endothelial nitric oxide synthase (eNOS), plays a major role in the regulation of blood pressure and vascular tone. We generated transgenic mice overexpressing bovine eNOS in the vascular wall using murine preproendothelin-1 promoter. In transgenic lineages with three to eight transgene copies, bovine eNOS-specific mRNA, protein expression in the particulate fractions, and calcium-dependent NOS activity were confirmed by RNase protection assay, immunoblotting, and L-arginine/citrulline conversion. Immunohistochemical studies revealed that eNOS protein was predominantly localized in the endothelial cells of aorta, heart, and lung. Blood pressure was significantly lower in eNOS-overexpressing mice than in control littermates. In the transgenic aorta, basal NO release (estimated by Nomega-nitro-L-arginine-induced facilitation of the contraction by prostaglandin F2alpha) and basal cGMP levels (measured by enzyme immunoassay) were significantly increased. In contrast, relaxations of transgenic aorta in response to acetylcholine and sodium nitroprusside were significantly attenuated, and the reduced vascular reactivity was associated with reduced response of cGMP elevation to these agents as compared with control aortas. Thus, our novel mouse model of chronic eNOS overexpression demonstrates that, in addition to the essential role of eNOS in blood pressure regulation, tonic NO release by eNOS in the endothelium induces the reduced vascular reactivity to NO-mediated vasodilators, providing several insights into the pathogenesis of nitrate tolerance. PMID:9854041

  6. 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

  7. Role of nitric oxide in parasitic infections.

    PubMed Central

    James, S L

    1995-01-01

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

  8. 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...

  9. Potential role of 8-oxoguanine DNA glycosylase 1 as a STAT1 coactivator in endotoxin-induced inflammatory response.

    PubMed

    Kim, Hong Sook; Kim, Byung-Hak; Jung, Joo Eun; Lee, Chang Seok; Lee, Hyun Gyu; Lee, Jung Weon; Lee, Kun Ho; You, Ho Jin; Chung, Myung-Hee; Ye, Sang-Kyu

    2016-04-01

    Human 8-oxoguanine DNA glycosylase 1 (OGG1) is the major DNA repair enzyme that plays a key role in excision of oxidative damaged DNA bases such as 8-oxoguainine (8-oxoG). Recent studies suggest another function of OGG1, namely that it may be involved in the endotoxin- or oxidative stress-induced inflammatory response. In this study, we investigated the role of OGG1 in the inflammatory response. OGG1 expression is increased in the organs of endotoxin-induced or myelin oligodendrocyte glycoprotein (MOG)-immunized mice and immune cells, resulting in induction of the expression of pro-inflammatory mediators at the transcriptional levels. Biochemical studies showed that signal transducer and activator of transcription 1 (STAT1) plays a key role in endotoxin-induced OGG1 expression and inflammatory response. STAT1 regulates the transcriptional activity of OGG1 through recruiting and binding to the gamma-interferon activation site (GAS) motif of the OGG1 promoter region, and chromatin remodeling by acetylation and dimethylation of lysine-14 and -4 residues of histone H3. In addition, OGG1 acts as a STAT1 coactivator and has transcriptional activity in the presence of endotoxin. The data presented here identifies a novel mechanism, and may provide new therapeutic strategies for the treatment of endotoxin-mediated inflammatory diseases. PMID:26496208

  10. Racial Differences in Nitric Oxide-Dependent Vasorelaxation

    PubMed Central

    Mata-Greenwood, Eugenia; Chen, Dong-Bao

    2008-01-01

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

  11. Nitric oxide in the bovine oviduct: influence on contractile activity and nitric oxide synthase isoforms localization.

    PubMed

    Yilmaz, O; Całka, J; Bukowski, R; Zalecki, M; Wasowicz, K; Jaroszewski, J J; Markiewicz, W; Bulbul, A; Ucar, M

    2012-04-15

    The oviducts of 64 Holstein cows in luteal (early I, early II and late) and follicular phases were evaluated to determine the protein expression and mRNA transcription of different nitric oxide synthase isoforms (eNOS, iNOS, nNOS) as well as the effect of nitric oxide (NO) on spontaneous contractility in vitro. The expression patterns of nitric oxide synthase (NOS) isoforms in isthmus and ampulla (n = 6 for each phase) were determined by immunohistochemistry, reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot analysis. In the contractility studies, longitudinal and circular isolated strips of isthmus and ampulla (n = 10 for each phase) of oviducts located ipsilateral to the luteal structure or preovulatory follicle were treated as follows: a) L-arginine, an endogenous NO donor (10(-8) to 10(-3)m), b) N(ω)-nitro-L-arginine methyl ester (L-NAME), a NOS inhibitor (10(-5)m) and L-arginine (10(-3)m), c) methylene blue (MB), an inhibitor of soluble guanylate (10(-5)m) and L-arginine (10(-3)m) and d) sodium nitroprusside (SNP), an exogenous NO donor (10(-8) to 10(-4)m). Immunohistochemical evaluation revealed that endothelial NOS (eNOS) expression detected in epithelial layer of isthmus and ampulla was strong in early I luteal phase, moderate in follicular phase and weak in other phases. Neuronal NOS (nNOS) immunoreactivity was strong in isthmus and moderate in ampulla, and staining of nerve fibers was observed mostly in early I luteal and follicular phases. All eNOS, nNOS and inducible NOS (iNOS) isoforms were detected by RT-PCR. eNOS and iNOS proteins were evident, whereas nNOS was undetectable by Western blot analysis in the tissue examined. L-arginine applied alone or after L-NAME did not alter or increase the contractile tension of the strips in most tissues examined. However, L-arginine applied after MB increased contractile tension in the strips of ampulla and longitudinal isthmus from early I luteal phase and circular isthmus from

  12. Nitric Oxide in Astrocyte-Neuron Signaling

    SciTech Connect

    Nianzhen Li

    2002-06-27

    Astrocytes, a subtype of glial cell, have recently been shown to exhibit Ca{sup 2+} elevations in response to neurotransmitters. A Ca{sup 2+} elevation can propagate to adjacent astrocytes as a Ca{sup 2+} wave, which allows an astrocyte to communicate with its neighbors. Additionally, glutamate can be released from astrocytes via a Ca{sup 2+}-dependent mechanism, thus modulating neuronal activity and synaptic transmission. In this dissertation, the author investigated the roles of another endogenous signal, nitric oxide (NO), in astrocyte-neuron signaling. First the author tested if NO is generated during astrocytic Ca{sup 2+} signaling by imaging NO in purified murine cortical astrocyte cultures. Physiological concentrations of a natural messenger, ATP, caused a Ca{sup 2+}-dependent NO production. To test the roles of NO in astrocytic Ca{sup 2+} signaling, the author applied NO to astrocyte cultures via addition of a NO donor, S-nitrosol-N-acetylpenicillamine (SNAP). NO induced an influx of external Ca{sup 2+}, possibly through store-operated Ca{sup 2+} channels. The NO-induced Ca{sup 2+} signaling is cGMP-independent since 8-Br-cGMP, an agonistic analog of cGMP, did not induce a detectable Ca{sup 2+} change. The consequence of this NO-induced Ca{sup 2+} influx was assessed by simultaneously monitoring of cytosolic and internal store Ca{sup 2+} using fluorescent Ca{sup 2+} indicators x-rhod-1 and mag-fluo-4. Blockage of NO signaling with the NO scavenger PTIO significantly reduced the refilling percentage of internal stores following ATP-induced Ca{sup 2+} release, suggesting that NO modulates internal store refilling. Furthermore, locally photo-release of NO to a single astrocyte led to a Ca{sup 2+} elevation in the stimulated astrocyte and a subsequent Ca{sup 2+} wave to neighbors. Finally, the author tested the role of NO inglutamate-mediated astrocyte-neuron signaling by recording the astrocyte-evoked glutamate-dependent neuronal slow inward current (SIC

  13. Nitric oxide and exercise in the horse.

    PubMed Central

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

    1996-01-01

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

  14. Nitric Oxide Catalysis of Diazene E/Z Isomerization.

    PubMed

    Bohle, D Scott; Rosadiuk, Kristopher A

    2015-08-01

    Nitric oxide is an efficient catalyst for the cis-trans (E/Z) isomerization of diazenes. We compare the effect of room temperature solutions bearing low concentrations of nitric oxide, nitrogen dioxide, or oxygen on the rate of cis-trans isomerization, CTI, of the alkene bond in stilbene and on the azo double bond in azobenzene, as well as in four azo derivatives as measured by UV-vis spectroscopy. These rate enhancements can be as large as 3 orders of magnitude for azobenzene in solution. A mechanism is proposed where catalysis is promoted by the interaction of the nitric oxide with the diazene nitrogen lone pairs. Density functional theory, B3LYP/6-311++g** suggests that the binding of NO to the diazene should be weak and reversible but that its NO adduct has an E/Z isomerization barrier of 7.5 kcal/mol.

  15. Thyroid disorders and nitric oxide in cardiovascular adaptation to hypovolemia.

    PubMed

    Ogonowski, Natalia; Piro, Giselle; Pessah, Déborah; Arreche, Noelia; Puchulu, Bernardita; Balaszczuk, Ana M; Fellet, Andrea L

    2016-08-01

    This study aimed to investigate whether nitric oxide participates in the cardiovascular function and haemodynamic adaptation to acute haemorrhage in animals with thyroid disorders. Sprague-Dawley rats aged 2months old treated with T3 (hyper, 20μg/100g body weight) or 0.02% methimazole (hypo, w/v) during 28days were pre-treated with N(G) nitro-l-arginine methyl ester (L-NAME) and submitted to 20% blood loss. Heart function was evaluated by echocardiography. Measurements of arterial blood pressure, heart rate, nitric oxide synthase activity and protein levels were performed. We found that hypo decreased fractional shortening and ejection fraction and increased left ventricle internal diameter. Hyper decreased ventricle diameter and no changes in cardiac contractility. Haemorrhage elicited a hypotension of similar magnitude within 10min. Then, this parameter was stabilized at about 30-40min and maintained until finalized, 120min. L-NAME rats showed that the immediate hypotension would be independent of nitric oxide. Nitric oxide synthase inhibition blunted the changes of heart rate induced by blood loss. Hyper and hypo had lower atrial enzyme activity associated with a decreased enzyme isoform in hypo. In ventricle, hyper and hypo had a higher enzyme activity, which was not correlated with changes in protein levels. Haemorrhage induced an increased heart nitric oxide production. We concluded that thyroid disorders were associated with hypertrophic remodelling which impacted differently on cardiac function and its adaptation to a hypovolemia. Hypovolemia triggered a nitric oxide synthase activation modulating the heart function to maintain haemodynamic homeostasis. This involvement depends on a specific enzyme isoform, cardiac chamber and thyroid state.

  16. Nitric oxide and biopterin in depression and stress.

    PubMed

    van Amsterdam, J G; Opperhuizen, A

    1999-01-18

    Depression has been hypothesized to be related to the reduced biosynthesis of neurotransmitters such as serotonin, noradrenalin and dopamine. Much past research has also been devoted to dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in depression. The present article reviews the evidence linking tetrahydrobiopterin, a co-factor in the biosynthesis of neurotransmitters, and nitric oxide, an apparent neuroendocrine modulator of the HPA axis, to the immune system and to neuronal control within affective disorder and stress. On the basis of this review, it is suggested that future psychoneuroimmunological research should more fully explore the possible role of tetrahydrobiopterin and nitric oxide in depressive disorders. PMID:10195314

  17. The energy-conserving nitric-oxide-reductase system in Paracoccus denitrificans. Distinction from the nitrite reductase that catalyses synthesis of nitric oxide and evidence from trapping experiments for nitric oxide as a free intermediate during denitrification.

    PubMed

    Carr, G J; Page, M D; Ferguson, S J

    1989-02-15

    1. A Clark-type electrode that responds to nitric oxide has been used to show that cytoplasmic membrane vesicles of Paracoccus denitrificans have a nitric-oxide reductase activity. Nitrous oxide is the reaction product. NADH, succinate or isoascorbate plus 2,3,5,6-tetramethyl-1,4-phenylene diamine can act as reductants. The NADH-dependent activity is resistant to freezing of the vesicles and thus the NADH:nitric-oxide oxidoreductase activity of stored frozen vesicles provides a method for calibrating the electrode by titration of dissolved nitric oxide with NADH. The periplasmic nitrite reductase and nitrous-oxide reductase enzymes are absent from the vesicles which indicates that nitric-oxide reductase is a discrete enzyme associated with the denitrification process. This conclusion was supported by the finding that nitric-oxide reductase activity was absent from both membranes prepared from aerobically grown P. denitrificans and bovine heart submitochondrial particles. 2. The NADH: nitric-oxide oxidoreductase activity was inhibited by concentrations of antimycin or myxothiazol that were just sufficient to inhibit the cytochrome bc1 complex of the ubiquinol--cytochrome-c oxidoreductase. The activity was deduced to be proton translocating by the observations of: (a) up to 3.5-fold stimulation upon addition of an uncoupler; and (b) ATP synthesis with a P:2e ratio of 0.75. 3. Nitrite reductase of cytochrome cd1 type was highly purified from P. denitrificans in a new, high-yield, rapid two- or three-step procedure. This enzyme catalysed stoichiometric synthesis of nitric oxide. This observation, taken together with the finding that the maximum rate of NADH:nitric-oxide oxidoreductase activity catalysed by the vesicles was comparable with that of NADH:nitrate-oxidoreductase, is consistent with a role for nitric-oxide reductase in the physiological conversion of nitrate or nitrite to dinitrogen gas. 4. Intact cells of P. denitrificans also reduced nitric oxide in an

  18. Negative regulation of inducible nitric-oxide synthase expression mediated through transforming growth factor-beta-dependent modulation of transcription factor TCF11.

    PubMed

    Berg, David T; Gupta, Akanksha; Richardson, Mark A; O'Brien, Lee A; Calnek, David; Grinnell, Brian W

    2007-12-21

    Inducible nitric-oxide synthase (iNOS) plays a central role in the regulation of vascular function and response to injury. A central mediator controlling iNOS expression is transforming growth factor-beta (TGF-beta), which represses its expression through a mechanism that is poorly understood. We have identified a binding site in the iNOS promoter that interacts with the nuclear heterodimer TCF11/MafG using chromatin immunoprecipitation and mutation analyses. We demonstrate that binding at this site acts to repress the induction of iNOS gene expression by cytokines. We show that this repressor is induced by TGF-beta1 and by Smad6-short, which enhances TGF-beta signaling. In contrast, the up-regulation of TCF11/MafG binding could be suppressed by overexpression of the TGF-beta inhibitor Smad7, and a small interfering RNA to TCF11 blocked the suppression of iNOS by TGF-beta. The binding of TCF11/MafG to the iNOS promoter could be enhanced by phorbol 12-myristate 13-acetate and suppressed by the protein kinase C inhibitor staurosporine. Moreover, the induction of TCF11/MafG binding by TGF-beta and Smad6-short could be blocked by staurosporine, and the effect of TGF-beta was blocked by the selective protein kinase C inhibitor calphostin C. Consistent with the in vitro data, we found suppression of TCF11 coincident with iNOS up-regulation in a rat model of endotoxemia, and we observed a highly significant negative correlation between TCF11 and nitric oxide production. Furthermore, treatment with activated protein C, a serine protease effective in septic shock, blocked the down-regulation of TCF11 and suppressed endotoxin-induced iNOS. Overall, our results demonstrate a novel mechanism by which iNOS expression is regulated in the context of inflammatory activation.

  19. Ocular Albumin Fluorophotometric Quantitation of Endotoxin-Induced Vascular Permeability

    PubMed Central

    Cousins, Scott W.; Rosenbaum, James T.; Guss, Robert B.; Egbert, Peter R.

    1982-01-01

    Bacterial endotoxin (lipopolysaccharide; LPS) is known to alter systemic vascular permeability, but this effect is difficult to monitor and quantitate in vivo. The ocular vessels of the rabbit are particularly sensitive to LPS. Using a slit lamp equipped with a fluorophotometer, we have adapted a method to quantitate endotoxin-induced ocular vascular permeability by measuring the accumulation of fluorescein isothiocyanate-conjugated albumin into the anterior chamber of the eye. After intravenous administration of Salmonella typhimurim LPS, the anterior chamber fluorescence and blood fluorescence were measured at intervals of 15 min and 1 h, respectively, over 4 h. In controls, maximal fluorescence in the anterior chamber was 3.1 ± 0.8% of blood fluorescence. Doses of LPS as low as 0.25 μg/kg produced an ocular/serum fluorescence ratio of 17.6 ± 4.9. A dose of 2.5 μg of LPS per kg tended to produce a higher ratio (68.0 ± 7.1) than a larger dose of 50 μg/kg (30.5 ± 16.6). Permeability changes began within 30 min after LPS, and the rate of dye accumulation varied over time, with maximal leakage usually occurring 90 min after LPS, but occasionally occurring much later. Repeated doses produced tolerance. By conjugating albumin to rhodamine and utilizing a second filter with the slit lamp to measure accumulation of this dye, we demonstrated the persistence of marked permeability during a period when intraocular fluorescein isothiocyanate and albumin levels were relatively constant. This methodology indicates that extremely low doses of LPS induce ocular permeability changes and that neither the time course nor the dose response of this effect is linear. Ocular fluorophotometry is a sensitive, noninvasive technique to study the dynamics and pharmacology of LPS-induced permeability changes. PMID:6806194

  20. Exogenous surfactant suppresses inflammation in experimental endotoxin-induced lung injury.

    PubMed

    Mittal, Neha; Sanyal, Sankar Nath

    2009-01-01

    Our objective was to evaluate the anti-inflammatory effects of exogenous surfactant and surfactant phospholipids on the lipopolysaccharide (LPS)-induced lung injury. Exogenous surfactant (porcine surfactant) and surfactant phospholipid (dipalmitoyl phospholipid DPPC, hexadecanol, tylaxopol) were instilled intratracheally with LPS in rats. Expression of surfactant apoproteins (SP-A) and the cyclooxygenase enzymes (COX-1 and -2) was studied by immunohistochemistry, and apoptosis was analyzed by in situ terminal dUTP nick end labeling TUNEL assay. The intracellular reactive oxygen species (ROS) was measured in the isolated macrophages by fluorescence measurement with dichlorofluorescein diacetate (DCFH-DA). LPS-induced oxidative burst and apoptosis at 72 hours were reduced by both porcine and synthetic surfactant. SP-A as well as COX-1 and -2 expressions were suppressed with synthetic surfactant treatment, whereas with porcine surfactant (P-SF) the SP-A expression was enhanced in response to LPS administration. These results indicate that exogenous surfactant inhibits LPS-induced inflammation. This anti-inflammatory activity may be an important outcome of surfactant therapy in endotoxin-induced respiratory distress.

  1. Dexmedetomidine inhibits vasoconstriction via activation of endothelial nitric oxide synthase

    PubMed Central

    Nong, Lidan; Ma, Jue; Zhang, Guangyan; Deng, Chunyu; Mao, Songsong; Li, Haifeng

    2016-01-01

    Despite the complex vascular effects of dexmedetomidine (DEX), its actions on human pulmonary resistance arteries remain unknown. The present study tested the hypothesis that DEX inhibits vascular tension in human pulmonary arteries through the endothelial nitric oxide synthase (eNOS) mediated production of nitric oxide (NO). Pulmonary artery segments were obtained from 62 patients who underwent lung resection. The direct effects of DEX on human pulmonary artery tension and changes in vascular tension were determined by isometric force measurements recorded on a myograph. Arterial contractions caused by increasing concentrations of serotonin with DEX in the presence or absence of L-NAME (endothelial nitric oxide synthase inhibitor), yohimbine (α2-adrenoceptor antagonist) and indomethacin (cyclooxygenase inhibitor) as antagonists were also measured. DEX had no effect on endothelium-intact pulmonary arteries, whereas at concentrations of 10–8~10–6 mol/L, it elicited contractions in endothelium-denuded pulmonary arteries. DEX (0.3, 1, or 3×10–9 mmol/L) inhibited serotonin-induced contraction in arteries with intact endothelium in a dose-dependent manner. L-NAME and yohimbine abolished DEX-induced inhibition, whereas indomethacin had no effect. No inhibitory effect was observed in endothelium-denuded pulmonary arteries. DEX-induced inhibition of vasoconstriction in human pulmonary arteries is mediated by NO production induced by the activation of endothelial α2-adrenoceptor and nitric oxide synthase.

  2. Apple fruit responses following exposure to nitric oxide

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  4. Arginine, citrulline and nitric oxide metabolism in sepsis

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  5. Cross sections for electron collisions with nitric oxide

    NASA Astrophysics Data System (ADS)

    Itikawa, Yukikazu

    2016-09-01

    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.

  6. 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.

  7. Dexmedetomidine inhibits vasoconstriction via activation of endothelial nitric oxide synthase

    PubMed Central

    Nong, Lidan; Ma, Jue; Zhang, Guangyan; Deng, Chunyu; Mao, Songsong; Li, Haifeng

    2016-01-01

    Despite the complex vascular effects of dexmedetomidine (DEX), its actions on human pulmonary resistance arteries remain unknown. The present study tested the hypothesis that DEX inhibits vascular tension in human pulmonary arteries through the endothelial nitric oxide synthase (eNOS) mediated production of nitric oxide (NO). Pulmonary artery segments were obtained from 62 patients who underwent lung resection. The direct effects of DEX on human pulmonary artery tension and changes in vascular tension were determined by isometric force measurements recorded on a myograph. Arterial contractions caused by increasing concentrations of serotonin with DEX in the presence or absence of L-NAME (endothelial nitric oxide synthase inhibitor), yohimbine (α2-adrenoceptor antagonist) and indomethacin (cyclooxygenase inhibitor) as antagonists were also measured. DEX had no effect on endothelium-intact pulmonary arteries, whereas at concentrations of 10–8~10–6 mol/L, it elicited contractions in endothelium-denuded pulmonary arteries. DEX (0.3, 1, or 3×10–9 mmol/L) inhibited serotonin-induced contraction in arteries with intact endothelium in a dose-dependent manner. L-NAME and yohimbine abolished DEX-induced inhibition, whereas indomethacin had no effect. No inhibitory effect was observed in endothelium-denuded pulmonary arteries. DEX-induced inhibition of vasoconstriction in human pulmonary arteries is mediated by NO production induced by the activation of endothelial α2-adrenoceptor and nitric oxide synthase. PMID:27610030

  8. Dexmedetomidine inhibits vasoconstriction via activation of endothelial nitric oxide synthase.

    PubMed

    Nong, Lidan; Ma, Jue; Zhang, Guangyan; Deng, Chunyu; Mao, Songsong; Li, Haifeng; Cui, Jianxiu

    2016-09-01

    Despite the complex vascular effects of dexmedetomidine (DEX), its actions on human pulmonary resistance arteries remain unknown. The present study tested the hypothesis that DEX inhibits vascular tension in human pulmonary arteries through the endothelial nitric oxide synthase (eNOS) mediated production of nitric oxide (NO). Pulmonary artery segments were obtained from 62 patients who underwent lung resection. The direct effects of DEX on human pulmonary artery tension and changes in vascular tension were determined by isometric force measurements recorded on a myograph. Arterial contractions caused by increasing concentrations of serotonin with DEX in the presence or absence of L-NAME (endothelial nitric oxide synthase inhibitor), yohimbine (α2-adrenoceptor antagonist) and indomethacin (cyclooxygenase inhibitor) as antagonists were also measured. DEX had no effect on endothelium-intact pulmonary arteries, whereas at concentrations of 10(-8)~10(-6) mol/L, it elicited contractions in endothelium-denuded pulmonary arteries. DEX (0.3, 1, or 3×10(-9) mmol/L) inhibited serotonin-induced contraction in arteries with intact endothelium in a dose-dependent manner. L-NAME and yohimbine abolished DEX-induced inhibition, whereas indomethacin had no effect. No inhibitory effect was observed in endothelium-denuded pulmonary arteries. DEX-induced inhibition of vasoconstriction in human pulmonary arteries is mediated by NO production induced by the activation of endothelial α2-adrenoceptor and nitric oxide synthase. PMID:27610030

  9. Nitric oxide and the autonomic regulation of cardiac excitability. The G.L. Brown Prize Lecture.

    PubMed

    Paterson, D

    2001-01-01

    Cardiac sympathetic imbalance and arrhythmia; Nitric oxide-cGMP pathway and the cholinergic modulation of cardiac excitability; Nitric oxide-cGMP pathway and the sympathetic modulation of cardiac excitability; Functional significance of nitric oxide in the autonomic regulation of cardiac excitability; Summary; References. Experimental Physiology (2001) 86.1, 1-12.

  10. 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.

  11. Nitric oxide and the autonomic regulation of cardiac excitability. The G.L. Brown Prize Lecture.

    PubMed

    Paterson, D

    2001-01-01

    Cardiac sympathetic imbalance and arrhythmia; Nitric oxide-cGMP pathway and the cholinergic modulation of cardiac excitability; Nitric oxide-cGMP pathway and the sympathetic modulation of cardiac excitability; Functional significance of nitric oxide in the autonomic regulation of cardiac excitability; Summary; References. Experimental Physiology (2001) 86.1, 1-12. PMID:11429613

  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. PMID:20874688

  13. Nitric oxide production and inducible nitric oxide synthase expression in inflammatory arthritides.

    PubMed Central

    Sakurai, H; Kohsaka, H; Liu, M F; Higashiyama, H; Hirata, Y; Kanno, K; Saito, I; Miyasaka, N

    1995-01-01

    In this study, we have identified the source of nitric oxide (NO) produced in the human inflammatory joints by analyzing expression of inducible NO synthase. In ex vivo organ cultures, both inflammatory synovium and cartilage from patients with rheumatoid arthritis produced NO. The NO production was suppressed by NG-monomethyl-L-arginine, an inhibitor of NO synthase. The amount of NO produced by the synovium correlated with the proportion of CD14+ cells in the corresponding tissue (r = 0.8, P < 0.05). Immunohistochemical analysis as well as in situ hybridization showed that inducible NO synthase was predominantly expressed in synovial lining cells, endothelial cells, chondrocytes, and to a lesser extent, in infiltrating mononuclear cells and synovial fibroblasts. The synovial lining cells and the infiltrating cells expressing inducible NO synthase were identified where CD14+ cells were located. Together with morphological features, this suggests that they are type A synoviocytes. NO production from freshly isolated synoviocytes and chondrocytes was up-regulated by in vitro stimulation with a combination of IL-TNF-beta, TNF-alpha, and LPS. In summary, the present results suggest that NO is produced primarily by CD14+ synoviocytes, chondrocytes, and endothelial cells in inflammatory joints of arthritides. NO production can be upregulated by cytokines present in inflamed joints. The increased NO production may thus contribute to the pathological features in inflammatory arthritides. Images PMID:7593623

  14. 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.

  15. 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

  16. Endotoxin-induced endothelial fibrosis is dependent on expression of transforming growth factors β1 and β2.

    PubMed

    Echeverría, César; Montorfano, Ignacio; Tapia, Pablo; Riedel, Claudia; Cabello-Verrugio, Claudio; Simon, Felipe

    2014-09-01

    During endotoxemia-induced inflammatory disease, bacterial endotoxins circulate in the bloodstream and interact with endothelial cells (ECs), inducing dysfunction of the ECs. We previously reported that endotoxins induce the conversion of ECs into activated fibroblasts. Through endotoxin-induced endothelial fibrosis, ECs change their morphology and their protein expression pattern, thereby suppressing endothelial markers and upregulating fibrotic proteins. The most commonly used fibrotic inducers are transforming growth factor β1 (TGF-β1) and TGF-β2. However, whether TGF-β1 and TGF-β2 participate in endotoxin-induced endothelial fibrosis remains unknown. We have shown that the endotoxin-induced endothelial fibrosis process is dependent on the TGF-β receptor, ALK5, and the activation of Smad3, a protein that is activated by ALK5 activation, thus suggesting that endotoxin elicits TGF-β production to mediate endotoxin-induced endothelial fibrosis. Therefore, we investigated the dependence of endotoxin-induced endothelial fibrosis on the expression of TGF-β1 and TGF-β2. Endotoxin-treated ECs induced the expression and secretion of TGF-β1 and TGF-β2. TGF-β1 and TGF-β2 downregulation inhibited the endotoxin-induced changes in the endothelial marker VE-cadherin and in the fibrotic proteins α-SMA and fibronectin. Thus, endotoxin induces the production of TGF-β1 and TGF-β2 as a mechanism to promote endotoxin-induced endothelial fibrosis. To the best of our knowledge, this is the first report showing that endotoxin induces endothelial fibrosis via TGF-β secretion, which represents an emerging source of vascular dysfunction. These findings contribute to understanding the molecular mechanism of endotoxin-induced endothelial fibrosis, which could be useful in the treatment of inflammatory diseases.

  17. Endotoxin-Induced Endothelial Fibrosis Is Dependent on Expression of Transforming Growth Factors β1 and β2

    PubMed Central

    Echeverría, César; Montorfano, Ignacio; Tapia, Pablo; Riedel, Claudia; Cabello-Verrugio, Claudio

    2014-01-01

    During endotoxemia-induced inflammatory disease, bacterial endotoxins circulate in the bloodstream and interact with endothelial cells (ECs), inducing dysfunction of the ECs. We previously reported that endotoxins induce the conversion of ECs into activated fibroblasts. Through endotoxin-induced endothelial fibrosis, ECs change their morphology and their protein expression pattern, thereby suppressing endothelial markers and upregulating fibrotic proteins. The most commonly used fibrotic inducers are transforming growth factor β1 (TGF-β1) and TGF-β2. However, whether TGF-β1 and TGF-β2 participate in endotoxin-induced endothelial fibrosis remains unknown. We have shown that the endotoxin-induced endothelial fibrosis process is dependent on the TGF-β receptor, ALK5, and the activation of Smad3, a protein that is activated by ALK5 activation, thus suggesting that endotoxin elicits TGF-β production to mediate endotoxin-induced endothelial fibrosis. Therefore, we investigated the dependence of endotoxin-induced endothelial fibrosis on the expression of TGF-β1 and TGF-β2. Endotoxin-treated ECs induced the expression and secretion of TGF-β1 and TGF-β2. TGF-β1 and TGF-β2 downregulation inhibited the endotoxin-induced changes in the endothelial marker VE-cadherin and in the fibrotic proteins α-SMA and fibronectin. Thus, endotoxin induces the production of TGF-β1 and TGF-β2 as a mechanism to promote endotoxin-induced endothelial fibrosis. To the best of our knowledge, this is the first report showing that endotoxin induces endothelial fibrosis via TGF-β secretion, which represents an emerging source of vascular dysfunction. These findings contribute to understanding the molecular mechanism of endotoxin-induced endothelial fibrosis, which could be useful in the treatment of inflammatory diseases. PMID:24935972

  18. 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

  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. Roscovitine ameliorates endotoxin-induced uveitis through neutrophil apoptosis

    PubMed Central

    Jiang, Zhao-Xin; Qiu, Suo; Lou, Bing-Sheng; Yang, Yao; Wang, Wen-Cong; Lin, Xiao-Feng

    2016-01-01

    Neutrophils have been recognized as critical response cells during the pathogenesis of endotoxin-induced uveitis (EIU). Apoptosis of neutrophils induced by roscovitine has previously been demonstrated to ameliorate inflammation in several in vivo models. The present study aimed to assess whether roscovitine ameliorates EIU. EIU was induced in female C57BL/6 mice by a single intravitreal injection of lipopolysaccharide (LPS; 250 ng). The mice were divided into three groups as follows: LPS alone, LPS plus vehicle, LPS plus roscovitine (50 mg/kg). The mice were euthanized 12, 24, 48 and 72 h after LPS-induced uveitis. Accumulation of inflammatory cells in the vitreous body was confirmed by immunohistochemistry, and quantified following hematoxylin and eosin staining. Terminal deoxynucleotidyl transferase dUTP nick-end labeling was performed to detect of apoptotic cells. The mRNA levels of inflammatory cytokines were analyzed by reverse transcription-quantitative polymerase chain reaction and the changes in protein levels were analyzed by western blotting. Inflammatory cells accumulated in the vitreous near the optic nerve head and the quantity peaked at 24 h after LPS injection. Immunohistochemistry revealed that the majority of the inflammatory cells were neutrophils. The number of infiltrating cells was similar in the LPS and LPS plus vehicle groups, while there were significantly less in the roscovitine group at 24 h. Apoptosis of neutrophils was observed between 12 and 48 h after roscovitine injection, while no apoptosis was observed in the other groups. The mRNA expression levels of GMCSF, CINC-1 and ICAM-1 peaked at 12 h after LPS injection, and decreased to normal levels at 72 h. This trend in mRNA expression was similar in the LPS and LPS plus vehicle groups; however, the expression levels decreased more quickly in the roscovitine group at 24 and 48 h. Following roscovitine administration, upregulated cleaved caspase 3 expression levels and downregulated Mcl-1

  1. 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.

  2. 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

  3. Interleukin-12 gene-expression of macrophages is regulated by nitric oxide.

    PubMed

    Rothe, H; Hartmann, B; Geerlings, P; Kolb, H

    1996-07-01

    Interleukin-12 is a heterodimeric cytokine, mainly produced by macrophages. In our present study we demonstrate that interleukin-12 expression is regulated by nitric oxide. Incubation of the macrophage cell line IC 21 with interferon-gamma gave rise to both interleukin-12 p40 mRNA and nitric oxide production. The concurrent addition of the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine inhibited nitrite production and in parallel completely suppressed interleukin-12 p40 mRNA formation. This indicated that endogenous nitric oxide synthase activity was required for IL-12 p40 gene expression. Exposure of the cells towards the nitric oxide generating compounds nitroprusside or S-nitroso-N-acetyl-penicillamine induced interleukin-12 p40 mRNA. Maximal mRNA levels were induced with nitric oxide donors at 1 microM concentration. We conclude that nitric oxide may exert an autoregulatory and paracrine control of interleukin-12 gene expression. PMID:8694804

  4. Exogenous nitric oxide donors and inhibitors of its formation (the chemical aspects)

    NASA Astrophysics Data System (ADS)

    Granik, Vladimir G.; Ryabova, Svetlana Yu; Grigoriev, Nikita B.

    1997-08-01

    The published data on the biological role of nitric oxide formed in vivo by enzymatic oxidation of L-arginine are generalised. Special attention is given to exogenous nitric oxide donors, which can release NO in vitro and in vivo in oxidation, reduction, or hydrolytic cleavage. Also considered are the data on the chemical nature of inhibitors of NO-synthase responsible for nitric oxide formation from L-arginine. The bibliography includes 161 references.

  5. Refractory Oxide Coatings on Titanium for Nitric Acid Applications

    NASA Astrophysics Data System (ADS)

    Ravi Shankar, A.; Kamachi Mudali, U.

    2014-07-01

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

  6. ENDOTHELIAL NITRIC OXIDE (NO) AND ITS PATHOPHYSIOLOGIC REGULATION

    PubMed Central

    Chatterjee, A.; Catravas, J.D.

    2008-01-01

    Nitric oxide (NO) is a gaseous lipophilic free radical generated by three distinct isoforms of nitric oxide synthases (NOS), type 1 or neuronal (nNOS), type 2 or inducible (iNOS) and type 3 or endothelial NOS (eNOS). Expression of eNOS is altered in many types of cardiovascular disease, such as atherosclerosis, diabetes and hypertension. The ubiquitous chaperone heat shock protein 90 (hsp90) associates with NOS and is important for its proper folding and function. Current studies point toward a therapeutic potential by modulating hsp90-NOS association in various vascular diseases. Here we review the transcriptional regulation of endothelial NOS and factors affecting eNOS activity and function, as well as the important vascular pathologies associated with altered NOS function, focusing on the regulatory role of hsp90 and other factors in NO-associated pathogenesis of these diseases. PMID:18692595

  7. Nitric oxide mediates caerulein-induced suppression of locomotor activity.

    PubMed

    Volke, V; Soosaar, A; Kõks, S; Bourin, M; Männistö, P T; Vasar, E

    1996-08-01

    Caerulein, a non-selective agonist of cholecystokinin (CCK) receptors, is shown to suppress locomotor activity in rodents via stimulation of CCK(A) receptors. In the present study we examined the possible involvement of nitric oxide (NO) in caerulein-induced hypolocomotion in rats. Caerulein (10 microg/kg) markedly decreased the horizontal and vertical components of locomotor activity in rats measured in dark motility boxes. Pretreatment with a nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME), at 5 mg/kg i.p., abolished the inhibiting action of caerulein on the horizontal activity, but did not affect the reduced frequency of rearing. The other doses of L-NAME (1, 10 and 20 mg/kg) were ineffective against caerulein. As L-NAME at this dose range does not stimulate locomotor activity, it is likely that NO is involved in the motor suppressant effect of systemically administered caerulein.

  8. 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

  9. Effect of fuel/air nonuniformity on nitric oxide emissions

    NASA Technical Reports Server (NTRS)

    Lyons, V. J.

    1979-01-01

    A flame tube combustor holding jet A fuel was used in experiments performed at a pressure of .3 Mpa and a reference velocity of 25 meters/second for three inlet air temperatures of 600, 700, and 800 K. The gas sample measurements were taken at locations 18 cm and 48 cm downstream of the perforated plate flameholder. Nonuniform fuel/air profiles were produced using a fuel injector by separately fueling the inner five fuel tubes and the outer ring of twelve fuel tubes. Six fuel/air profiles were produced for nominal overall equivalence ratios of .5 and .6. An example of three of three of these profiles and their resultant nitric oxide NOx emissions are presented. The uniform fuel/air profile cases produced uniform and relatively low profile levels. When the profiles were either center-peaked or edge-peaked, the overall mass-weighted nitric oxide levels increased.

  10. Nitric oxide: a regulator of eukaryotic initiation factor 2 kinases.

    PubMed

    Tong, Lingying; Heim, Rachel A; Wu, Shiyong

    2011-06-15

    Generation of nitric oxide (NO(•)) can upstream induce and downstream mediate the kinases that phosphorylate the α subunit of eukaryotic initiation factor 2 (eIF2α), which plays a critical role in regulating gene expression. There are four known eIF2α kinases (EIF2AKs), and NO(•) affects each one uniquely. Whereas NO(•) directly activates EIF2AK1 (HRI), it indirectly activates EIF2AK3 (PERK). EIF2AK4 (GCN2) is activated by depletion of l-arginine, which is used by nitric oxide synthase (NOS) during the production of NO(•). Finally EIF2AK2 (PKR), which can mediate inducible NOS expression and therefore NO(•) production, can also be activated by NO(•). The production of NO(•) and activation of EIF2AKs coordinately regulate physiological and pathological events such as innate immune response and cell apoptosis. PMID:21463677

  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. Tutorial Review: Electrochemical Nitric Oxide Sensors for Physiological Measurements

    PubMed Central

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

    2013-01-01

    Summary The important biological roles of nitric oxide (NO) have prompted the development of analytical techniques capable of sensitive and selective detection of NO. Electrochemical sensing, more than any other NO-detection method, embodies the parameters necessary for quantifying NO in challenging physiological environments such as blood and the brain. Herein, we provide a broad overview of the field of electrochemical NO sensors, including design, fabrication, and analytical performance characteristics. Both electrochemical sensors and biological applications are detailed. PMID:20502795

  13. Hemoglobin-based red blood cell substitutes and nitric oxide.

    PubMed

    Yu, Binglan; Bloch, Kenneth D; Zapol, Warren M

    2009-04-01

    Hemoglobin-based oxygen carriers (HBOCs) have been studied for decades as red blood cell substitutes. Profound vasoconstrictor effects have limited the clinical utility of HBOCs and are attributable to avid scavenging of nitric oxide (NO). Inhaling NO can charge the body's stores of NO metabolites without producing hypotension and can prevent systemic hypertension induced when HBOCs are subsequently infused. Concurrent breathing of low NO doses can prevent pulmonary vasoconstriction after HBOC infusion without augmenting plasma methemoglobinemia.

  14. Microwave torch as a plasmachemical generator of nitric oxides

    SciTech Connect

    Gritsinin, S. I.; Knyazev, V. Yu.; Kossyi, I. A.; Popov, N. A.

    2006-06-15

    The possibility of using a microwave coaxial plasmatron (a microwave torch) as an efficient plasmachemical generator of nitric oxides in an air jet has been studied experimentally. A plasmachemical model of the generator is developed. Results of calculations by this model do not contradict experimental results. A conclusion about the mechanisms governing NO{sub x} production in a plasma torch is drawn by comparing the experimental and calculated results.

  15. Atorvastatin reduces endotoxin-induced microvascular inflammation via NOSII.

    PubMed

    McGown, Caroline C; Brookes, Zoë L S; Hellewell, Paul G; Ross, Jonathan J; Brown, Nicola J

    2015-05-01

    In a lipopolysaccharide (LPS)-induced rat model of sepsis (endotoxaemia), we previously demonstrated that pravastatin reduced microvascular inflammation via increased endothelial nitric oxide synthase III (NOSIII). This study aimed to determine whether atorvastatin, the most commonly used statin for lowering cholesterol, exerted beneficial pleiotropic effects via a similar mechanism. The mesenteric microcirculation of anaesthetised male Wistar rats (308 ± 63 g, n = 54) was prepared for fluorescent intravital microscopy. Over 4 h, animals received intravenous (i.v.) administration of either saline, LPS (150 μg kg(-1) h(-1)) or LPS + atorvastatin (200 μg kg(-1) s.c., 18 and 3 h before LPS), with/without the non-specific NOS inhibitor L-NG-Nitroarginine Methyl Ester (L-NAME) (10 μg kg(-1) h(-1)) or NOSII-specific inhibitor 1400 W (20 μg kg(-1) min(-1)). LPS decreased mean arterial blood pressure (MAP) (4 h, control 113 ± 20 mmHg; LPS 70 ± 23 mmHg), being reversed by atorvastatin (105 ± 3 mmHg) (p < 0.05). LPS also increased macromolecular leak measured after 100 mg kg(-1) of i.v FITC-BSA (arbitrary grey level adjacent to venules), which again was attenuated by atorvastatin (control 1.9 ± 4.0; LPS 12.0 ± 2.4; LPS + atorvastatin 4.5 ± 2.2) (p < 0.05). Furthermore, immunohistochemistry identified that atorvastatin decreased LPS-induced upregulation of endothelial cell NOSII expression, but NOSIII was unchanged in all groups. Atorvastatin improved MAP and reduced microvascular inflammation during endotoxaemia, associated with a reduction of pro-inflammatory NOSII. This differs from previous studies, whereby pravastatin increased expression of NOSIII. Thus preoperative statins have beneficial anti-inflammatory effects during endotoxaemia, but careful consideration must be given to the specific statin being used. PMID:25678054

  16. An Anti-Interleukin-2 Receptor Drug Attenuates T- Helper 1 Lymphocytes-Mediated Inflammation in an Acute Model of Endotoxin-Induced Uveitis

    PubMed Central

    Navea, Amparo; Almansa, Inmaculada; Muriach, María; Bosch-Morell, Francisco

    2014-01-01

    The aim of the present study was to evaluate the anti-inflammatory efficacy of Daclizumab, an anti-interleukin-2 receptor drug, in an experimental uveitis model upon a subcutaneous injection of lipopolysaccharide into Lewis rats, a valuable model for ocular acute inflammatory processes. The integrity of the blood-aqueous barrier was assessed 24 h after endotoxin-induced uveitis by evaluating two parameters: cell count and protein concentration in aqueous humors. The histopathology of all the ocular structures (cornea, lens, sclera, choroid, retina, uvea, and anterior and posterior chambers) was also considered. Enzyme-linked immunosorbent assays of the aqueous humor samples were performed to quantify the levels of the different chemokine and cytokine proteins. Similarly, a biochemical analysis of oxidative stress-related markers was also assessed. The inflammation observed in the anterior chamber of the eyes when Daclizumab was administered with endotoxin was largely prevented since the aqueous humor protein concentration substantially lowered concomitantly with a significant reduction in the uveal and vitreous histopathological grading. Th1 lymphocytes-related cytokines, such as Interleukin-2 and Interferon-γ, also significantly reduced with related anti-oxidant systems recovery. Daclizumab treatment in endotoxin-induced uveitis reduced Th1 lymphocytes-related cytokines, such as Interleukin-2 and Interferon gamma, by about 60–70% and presented a preventive role in endotoxin-induced oxidative stress. This antioxidant protective effect of Daclizumab may be related to several of the observed Daclizumab effects in our study, including IL-6 cytokine regulatory properties and a substantial concomitant drop in INFγ. Concurrently, Daclizumab treatment triggered a significant reduction in both the uveal histopathological grading and protein concentration in aqueous humors, but not in cellular infiltration. PMID:24595020

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

    PubMed

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

    2013-11-30

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

  18. 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.

  19. 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.

  20. Nitric oxide mediates interleukin-1-induced cellular cytotoxicity in the rat ovary. A potential role for nitric oxide in the ovulatory process.

    PubMed Central

    Ellman, C; Corbett, J A; Misko, T P; McDaniel, M; Beckerman, K P

    1993-01-01

    Treatment of primary cultures of rat ovarian dispersates with IL-1 beta results in morphologic and cytotoxic changes, thought to reflect tissue remodeling events associated with ovulation. We examined the role that the free radical nitric oxide plays in this process and report that IL-1 beta induces expression of the inducible isoform of nitric oxide synthase in ovarian cells as demonstrated by immunoprecipitation. We show that IL-1 beta treatment results in the formation of nitric oxide (as measured by accumulation of nitrite and cGMP) in both a time- and concentration-dependent manner that is prevented by aminoguanidine, a selective inhibitor of the inducible isoform of nitric oxide synthase. Aminoguanidine also inhibits IL-1-induced ovarian cellular cytotoxicity. These results suggest that nitric oxide is an important mediator of cell death and may act as a physiologically significant mediator of tissue remodeling events that occur in vivo during the ovulatory process. Images PMID:7504698

  1. Deferoxamine reduces tissue damage during endotoxin-induced mastitis in dairy cows.

    PubMed

    Lauzon, K; Zhao, X; Lacasse, P

    2006-10-01

    The protective effects of 3 antioxidants on polymorphonuclear neutrophil-induced damage to mammary cells were evaluated in vivo using an endotoxin-induced mastitis model. Fifteen healthy, midlactation cows with no history of clinical Escherichia coli mastitis were randomly assigned to 1 of the 3 treatment groups corresponding to each modulator to be evaluated, that is, deferoxamine, catechin, and glutathione ethyl ester. Each cow had 1 quarter infused with saline and 1 quarter infused with the selected modulator; a third quarter was infused with lipopolysaccharides (LPS), whereas the fourth quarter received a combination of LPS and the modulator. Infusion of LPS caused acute mastitis as determined by visual observations and by large increases in milk somatic cell count, BSA, and proteolytic activity. These parameters were not affected by antioxidant administration. The extent of cell damage was evaluated by measuring milk levels of lactate dehydrogenase and N-acetyl-beta-D-glucosaminidase activity. Levels of these parameters were several times higher after LPS administration. Intramammary infusions of catechin or glutathione ethyl ester did not exert any protective effect, whereas infusion of deferoxamine, a chelator of iron, decreased milk lactate dehydrogenase and NA-Gase activity, suggesting a protective effect against neutrophil-induced damage. The protective effect of deferoxamine was also evidenced by a lower milk level of haptoglobin. The proteolytic activity of mastitic milk was not influenced by the presence of deferoxamine. Overall, our results suggest that local infusion of deferoxamine may be an effective tool to protect mammary tissue against neutrophil-induced oxidative stress during bovine mastitis. PMID:16960060

  2. 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.

  3. 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.

  4. 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.

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

    PubMed Central

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

    1997-01-01

    The use of inhaled nitric oxide as a selective pulmonary vasodilator has expanded to include patients with congenital heart disease and pulmonary hypertension. The therapeutic and diagnostic roles of inhaled nitric oxide offer additional alternatives and benefits to these patients with pulmonary hypertension, particularly in the postoperative setting. This article reviews the background, mechanism of action, toxicities, and current clinical applications of inhaled nitric oxide in the child with congenital heart disease and pulmonary hypertension. PMID:9456484

  6. 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

  7. Nitric Oxide Suppresses β-Cell Apoptosis by Inhibiting the DNA Damage Response.

    PubMed

    Oleson, Bryndon J; Broniowska, Katarzyna A; Naatz, Aaron; Hogg, Neil; Tarakanova, Vera L; Corbett, John A

    2016-08-01

    Nitric oxide, produced in pancreatic β cells in response to proinflammatory cytokines, plays a dual role in the regulation of β-cell fate. While nitric oxide induces cellular damage and impairs β-cell function, it also promotes β-cell survival through activation of protective pathways that promote β-cell recovery. In this study, we identify a novel mechanism in which nitric oxide prevents β-cell apoptosis by attenuating the DNA damage response (DDR). Nitric oxide suppresses activation of the DDR (as measured by γH2AX formation and the phosphorylation of KAP1 and p53) in response to multiple genotoxic agents, including camptothecin, H2O2, and nitric oxide itself, despite the presence of DNA damage. While camptothecin and H2O2 both induce DDR activation, nitric oxide suppresses only camptothecin-induced apoptosis and not H2O2-induced necrosis. The ability of nitric oxide to suppress the DDR appears to be selective for pancreatic β cells, as nitric oxide fails to inhibit DDR signaling in macrophages, hepatocytes, and fibroblasts, three additional cell types examined. While originally described as the damaging agent responsible for cytokine-induced β-cell death, these studies identify a novel role for nitric oxide as a protective molecule that promotes β-cell survival by suppressing DDR signaling and attenuating DNA damage-induced apoptosis. PMID:27185882

  8. Nitric oxide is involved in heat-induced HSP70 accumulation.

    PubMed

    Malyshev IYu; Manukhina, E B; Mikoyan, V D; Kubrina, L N; Vanin, A F

    1995-08-21

    Heat shock potentiated the nitric oxide production (EPR assay) in the liver, kidney, heart, spleen, intestine, and brain. The heat shock-induced sharp transient increase in the rate of nitric oxide production preceded the accumulation of heat shock proteins (HSP70) (Western blot analysis) as measured in the heart and liver. In all organs the nitric oxide formation was completely blocked by the NO-synthase inhibitor N omega-nitro-L-arginine (L-NNA). L-NNA also markedly attenuated the heat shock-induced accumulation of HSP70. The results suggests that nitric oxide is involved in the heat shock-induced activation of HSP70 synthesis. PMID:7544743

  9. 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.

  10. Obesity, insulin resistance, and skeletal muscle nitric oxide synthase

    PubMed Central

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

    2012-01-01

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

  11. 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?

  12. Pterins inhibit nitric oxide synthase activity in rat alveolar macrophages.

    PubMed Central

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

    1992-01-01

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

  13. Nitric oxide and cell death in liver cancer cells.

    PubMed

    Muntané, Jordi; De la Rosa, Angel J; Marín, Luís M; Padillo, Francisco J

    2013-05-01

    Nitric oxide (NO) is a lipophillic, highly diffusible, and short-lived physiological messenger which regulates a variety of physiopathological responses. NO may exert its cellular action through cGMP-dependent and cGMP-independent pathways which includes different postranslational modifications. The effect of NO in cancer depends on the activity and localization of NOS isoforms, concentration and duration of NO exposure, cellular sensitivity, and hypoxia/re-oxygenation process. NO regulates critical factors such as the hypoxia inducible factor-1 (HIF-1) and p53 generally leading to growth arrest, apoptosis or adaptation. NO sensitizes hepatoma cells to chemotherapeutic compounds probably through increased p53 and cell death receptor expressions.

  14. [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. PMID:23544386

  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. Nitric oxide, a protective molecule in the cardiovascular system.

    PubMed

    Lei, Jing; Vodovotz, Yoram; Tzeng, Edith; Billiar, Timothy R

    2013-11-30

    Nitric oxide (NO) is an intra- and inter-signaling molecule that regulates vessel dilatation, neuronal transmission, cardiac contraction, immunomodulation, and stem cell differentiation and proliferation. NO plays an important protective role in the cardiovascular system. NO inhibits smooth muscle cells proliferation and migration; enhances proliferation and migration of endothelial cell and inhibits apoptosis; suppresses platelet aggregation; and prevents platelet, leukocyte and monocyte adhesion to endothelium. NO exerts an inhibitory effect on the development of intimal hyperplasia in mechanically or immunologically injured vessel. New therapeutic approaches aimed at enhancing NO bioavailability or assisting delivery of NO locally may help patients with cardiovascular disease.

  17. Biochemistry of nitric oxide and its redox-activated forms.

    PubMed

    Stamler, J S; Singel, D J; Loscalzo, J

    1992-12-18

    Nitric oxide (NO.), a potentially toxic molecule, has been implicated in a wide range of biological functions. Details of its biochemistry, however, remain poorly understood. The broader chemistry of nitrogen monoxide (NO) involves a redox array of species with distinctive properties and reactivities: NO+ (nitrosonium), NO., and NO- (nitroxyl anion). The integration of this chemistry with current perspectives of NO biology illuminates many aspects of NO biochemistry, including the enzymatic mechanism of synthesis, the mode of transport and targeting in biological systems, the means by which its toxicity is mitigated, and the function-regulating interaction with target proteins.

  18. Direct Reaction of Amides with Nitric Oxide To Form Diazeniumdiolates

    PubMed Central

    2015-01-01

    We report the apparently unprecedented direct reaction of nitric oxide (NO) with amides to generate ions of structure R(C=O)NH–N(O)=NO–, with examples including R = Me (1a) or 3-pyridyl (1b). The sodium salts of both released NO in pH 7.4 buffer, with 37 °C half-lives of 1–3 min. As NO-releasing drug candidates, diazeniumdiolated amides would have the advantage of generating only 1 equiv of base on hydrolyzing exhaustively to NO, in contrast to their amine counterparts, which generate 2 equiv of base. PMID:25210948

  19. Effect of exogenous nitric oxide in experimental trichinellosis.

    PubMed

    Hadaś, Edward; Derda, Monika; Wandurska-Nowak, Elzbieta

    2002-01-01

    Nitric oxide (NO) is a free radical that has been given much attention over the past few years. It has been nicknamed a "killer" and "mediator" due to its toxic and signaling properties. Apart from its regular physiological function, NO indirectly participates in infectious diseases. Our investigations showed that NO administered as a drug may involve higher histopathological changes in infected animals and can involve higher infection. This report seems to be the first presentation of the participation of NO reactive nitrogen intermediates in the morphological transformation of muscle cells in trichinellosis.

  20. 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

  1. 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

  2. Role of inducible nitric oxide synthase-derived nitric oxide in lipopolysaccharide plus interferon-gamma-induced pulmonary inflammation.

    PubMed

    Zeidler, Patti C; Millecchia, Lyndell M; Castranova, Vincent

    2004-02-15

    Exposure of mice to lipopolysaccharide (LPS) plus interferon-gamma (IFN-gamma) increases nitric oxide (NO) production, which is proposed to play a role in the resulting pulmonary damage and inflammation. To determine the role of inducible nitric oxide synthase (iNOS)-induced NO in this lung reaction, the responses of inducible nitric oxide synthase knockout (iNOS KO) versus C57BL/6J wild-type (WT) mice to aspirated LPS + IFN-gamma were compared. Male mice (8-10 weeks) were exposed to LPS (1.2 mg/kg) + IFN-gamma (5000 U/mouse) or saline. At 24 or 72 h postexposure, lungs were lavaged with saline and the acellular fluid from the first bronchoalveolar lavage (BAL) was analyzed for total antioxidant capacity (TAC), lactate dehydrogenase (LDH) activity, albumin, tumor necrosis factor-alpha (TNF-alpha), and macrophage inflammatory protein-2 (MIP-2). The cellular fraction of the total BAL was used to determine alveolar macrophage (AM) and polymorphonuclear leukocyte (PMN) counts, and AM zymosan-stimulated chemiluminescence (AM-CL). Pulmonary responses 24 h postexposure to LPS + IFN-gamma were characterized by significantly decreased TAC, increased BAL AMs and PMNs, LDH, albumin, TNF-alpha, and MIP-2, and enhanced AM-CL to the same extent in both WT and iNOS KO mice. Responses 72 h postexposure were similar; however, significant differences were found between WT and iNOS KO mice. iNOS KO mice demonstrated a greater decline in total antioxidant capacity, greater BAL PMNs, LDH, albumin, TNF-alpha, and MIP-2, and an enhanced AM-CL compared to the WT. These data suggest that the role of iNOS-derived NO in the pulmonary response to LPS + IFN-gamma is anti-inflammatory, and this becomes evident over time. PMID:14962504

  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. Endothelial Caveolar Subcellular Domain Regulation of Endothelial Nitric Oxide Synthase

    PubMed Central

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

    2015-01-01

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

  5. A nitric oxide synthase inhibitor impairs memory storage in mice.

    PubMed

    Baratti, C M; Kopf, S R

    1996-05-01

    Posttraining administration of the L-enantiomer of the competitive inhibitor of nitric oxide synthase, NG-nitro-L-arginine methyl ester (L-NAME, 3-100 mg/kg, ip), impaired 48-h retention of a one-trial step-through inhibitory shock-avoidance task in male Swiss mice. The effects were dose-dependent and were not observed when the D-enantiomer (D-NAME, 3-100 mg/kg, ip) was injected instead of L-NAME. Retention latencies of mice that had not received a footshock during training were not affected by L-NAME. The memory impairment produced by L-NAME was time-dependent, suggesting an action on memory storage. The effects of L-NAME on memory were overcome by the injection of L-(but not D-)arginine (300 mg/kg, ip) along with the inhibitor. Considered together, these findings suggest that the L-arginine/nitric oxide pathway may be involved in memory storage of an inhibitory avoidance response in mice. PMID:8616582

  6. Compartmentalized nitric oxide signaling in the resistance vasculature.

    PubMed

    Mutchler, Stephanie M; Straub, Adam C

    2015-09-15

    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.

  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. 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.

  9. 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

  10. 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

  11. 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

  12. Implications of glial nitric oxide in neurodegenerative diseases.

    PubMed

    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

  13. Kinetics of the reaction of nitric oxide with hydrogen

    NASA Technical Reports Server (NTRS)

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

    1975-01-01

    The reaction of nitric oxide with hydrogen has been studied in the temperature range 2400-4500 K using a shock-tube technique. 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 decomposition of nitric oxide behind the shock was found to be modeled well by a fifteen-reaction system. A principal result of the study was the determination of the rate constant k1 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 k1 were obtained for each test through comparisons of measured and numerically predicted NO profiles. The data are fit closely by the expression k1 = 1.34 times 10 to the fourteenth power exp(-49 200/RT) cu cm/mole-sec. These data appear to be the first available for this rate constant.

  14. 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

  15. 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. PMID:21294419

  16. Shear-Induced Nitric Oxide Production by Endothelial Cells.

    PubMed

    Sriram, Krishna; Laughlin, Justin G; Rangamani, Padmini; Tartakovsky, Daniel M

    2016-07-12

    We present a biochemical model of the wall shear stress-induced activation of endothelial nitric oxide synthase (eNOS) in an endothelial cell. The model includes three key mechanotransducers: mechanosensing ion channels, integrins, and G protein-coupled receptors. The reaction cascade consists of two interconnected parts. The first is rapid activation of calcium, which results in formation of calcium-calmodulin complexes, followed by recruitment of eNOS from caveolae. The second is phosphorylation of eNOS by protein kinases PKC and AKT. The model also includes a negative feedback loop due to inhibition of calcium influx into the cell by cyclic guanosine monophosphate (cGMP). In this feedback, increased nitric oxide (NO) levels cause an increase in cGMP levels, so that cGMP inhibition of calcium influx can limit NO production. The model was used to predict the dynamics of NO production by an endothelial cell subjected to a step increase of wall shear stress from zero to a finite physiologically relevant value. Among several experimentally observed features, the model predicts a highly nonlinear, biphasic transient behavior of eNOS activation and NO production: a rapid initial activation due to the very rapid influx of calcium into the cytosol (occurring within 1-5 min) is followed by a sustained period of activation due to protein kinases. PMID:27410748

  17. Nitric oxide and peroxynitrite production in ocular inflammation.

    PubMed Central

    Allen, J B; Keng, T; Privalle, C

    1998-01-01

    Recent studies have implicated nitric oxide and peroxynitrite in the pathogenesis of many diseases, such as septic shock, arthritis, lung disease, and atherosclerosis. Nitric oxide (.NO) exerts many diverse effects on vascular tone, affecting neurotransmission and cellular cytotoxicity/communication. Our laboratory and others have documented a proinflammatory role for .NO in ocular inflammation. Uveitis, which is an inflammation of the highly vascular uveal tract in the eye, is a debilitating condition that can lead to visual impairment and blindness. It is characterized by acute, recurrent, or persistent inflammation with disruption of the blood-aqueous barrier and is accompanied by protein leakage and leukocyte infiltration into the aqueous humor and anterior chamber. Systemic injection of endotoxin into mice and rats, or intraocular injection of endotoxin into mice, rats, and rabbits induces acute uveitis, which clinically and histologically resembles acute anterior uveitis in humans. These models facilitate the study of pathogenic mechanisms that contribute to ocular inflammation. In addition to .NO, superoxide anion radicals (O2.-), and peroxynitrite (ONOO-), the products of the reaction between .NO and O2.-, are also implicated in uveitis. The role of peroxynitrite in ocular inflammation is still largely unknown. Characterization of the roles of these important uveitic mediators in the ocular inflammatory response will provide information critical to the understanding of the pathogenesis of intraocular inflammation so that more effective therapeutic intervention(s) can be developed. PMID:9788889

  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. Shear-Induced Nitric Oxide Production by Endothelial Cells

    NASA Astrophysics Data System (ADS)

    Sriram, Krishna; Laughlin, Justin G.; Rangamani, Padmini; Tartakovsky, Daniel M.

    2016-07-01

    We present a biochemical model of the wall shear stress (WSS)-induced activation of endothelial nitric oxide synthase (eNOS) in an endothelial cell (EC). The model includes three key mechanotransducers: mechanosensing ion channels, integrins and G-protein-coupled receptors. The reaction cascade consists of two interconnected parts. The first is rapid activation of calcium, which results in formation of calcium-calmodulin complexes, followed by recruitment of eNOS from caveolae. The second is phosphoryaltion of eNOS by protein kinases PKC and AKT. The model also includes a negative feedback loop due to inhibition of calcium influx into the cell by cyclic guanosine monophosphate (cGMP). In this feedback, increased nitric oxide (NO) levels cause an increase in cGMP levels, so that cGMP inhibition of calcium influx can limit NO production. The model was used to predict the dynamics of NO production by an EC subjected to a step increase of WSS from zero to a finite physiologically relevant value. Among several experimentally observed features, the model predicts a highly nonlinear, biphasic transient behavior of eNOS activation and NO production: a rapid initial activation due to the very rapid influx of calcium into the cytosol (occurring within 1 to 5 minutes) is followed by a sustained period of activation due to protein kinases.

  20. Inducible Nitric Oxide Synthase Expression in Human Colorectal Cancer

    PubMed Central

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

    2003-01-01

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

  1. Endostatin induces acute endothelial nitric oxide and prostacyclin release

    SciTech Connect

    Li Chunying; Harris, M. Brennan; Venema, Virginia J.; Venema, Richard C. . E-mail: rvenema@mcg.edu

    2005-04-15

    Chronic exposure to endostatin (ES) blocks endothelial cell (EC) proliferation, and migration and induces EC apoptosis thereby inhibiting angiogenesis. Nitric oxide (NO) and prostacyclin (PGI{sub 2}), in contrast, play important roles in promoting angiogenesis. In this study, we examined the acute effects of ES on endothelial NO and PGI{sub 2} production. Unexpectedly, a cGMP reporter cell assay showed that ES-induced acute endothelial NO release in cultured bovine aortic endothelial cells (BAECs). Enzyme immunoassay showed that ES also induced an acute increase in PGI{sub 2} production in BAECs. These results were confirmed by ex vivo vascular ring studies that showed vascular relaxation in response to ES. Immunoblot analysis showed that ES stimulated acute phosphorylation of endothelial nitric oxide synthase (eNOS) at Ser116, Ser617, Ser635, and Ser1179, and dephosphorylation at Thr497 in BAECs, events associated with eNOS activation. Short-term exposure of EC to ES, therefore, unlike long-term exposure which is anti-angiogenic, may be pro-angiogenic.

  2. A nitric oxide synthase inhibitor impairs memory storage in mice.

    PubMed

    Baratti, C M; Kopf, S R

    1996-05-01

    Posttraining administration of the L-enantiomer of the competitive inhibitor of nitric oxide synthase, NG-nitro-L-arginine methyl ester (L-NAME, 3-100 mg/kg, ip), impaired 48-h retention of a one-trial step-through inhibitory shock-avoidance task in male Swiss mice. The effects were dose-dependent and were not observed when the D-enantiomer (D-NAME, 3-100 mg/kg, ip) was injected instead of L-NAME. Retention latencies of mice that had not received a footshock during training were not affected by L-NAME. The memory impairment produced by L-NAME was time-dependent, suggesting an action on memory storage. The effects of L-NAME on memory were overcome by the injection of L-(but not D-)arginine (300 mg/kg, ip) along with the inhibitor. Considered together, these findings suggest that the L-arginine/nitric oxide pathway may be involved in memory storage of an inhibitory avoidance response in mice.

  3. 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

  4. Nitric oxide rapidly scavenges tyrosine and tryptophan radicals.

    PubMed Central

    Eiserich, J P; Butler, J; van der Vliet, A; Cross, C E; Halliwell, B

    1995-01-01

    By utilizing a pulse-radiolytic technique, we demonstrate for the first time that the rate constant for the reaction of nitric oxide (.NO) with biologically relevant tyrosine and tryptophan radicals (Tyr. and Trp. respectively) in amino acids, peptides and proteins is of the order of (1-2) x 10(9) M-1.s-1. We also show that .NO effectively interferes with electron-transfer processes between tryptophan and tyrosine residues in proteins subjected to pulse radiolysis. The near diffusion-controlled rates of these reactions, coupled with the increasingly recognized role of protein radicals in enzyme catalysis and oxidative damage, suggest that Tyr. and Trp. are likely and important targets for .NO generated in vivo. PMID:7575405

  5. Estimation of nitric oxide as an inflammatory marker in periodontitis

    PubMed Central

    Menaka, K. B.; Ramesh, Amitha; Thomas, Biju; Kumari, N. Suchetha

    2009-01-01

    Nitric oxide (NO) is not only important in host defense and homeostasis but it is also regarded as harmful and has been implicated in the pathogenesis of a wide variety of inflammatory and autoimmune diseases. The presence of NO in periodontal disease may reflect the participation of an additional mediator of bone resorption responsible for disease progression. The aim of this study was to assess the level of NO in serum in chronic periodontitis, and correlate these levels with the severity of periodontal disease. Sixty subjects participated in the study and were divided into two groups. NO levels were assayed by measuring the accumulation of stable oxidative metabolite, nitrite with Griess reaction. Results showed subjects with periodontitis had significantly high nitrite in serum than healthy subjects. NO production is increased in periodontal disease, this will enable us to understand its role in disease progression and selective inhibition of NO may be of therapeutic utility in limiting the progression of periodontitis. PMID:20407654

  6. In-vitro susceptibility of hydatid cysts of Echinococcus granulosus to nitric oxide and the effect of the laminated layer on nitric oxide production.

    PubMed

    Steers, N J; Rogan, M T; Heath, S

    2001-08-01

    Murine hydatid cysts of Echinococcus granulosus were incubated in vitro in the presence of nitric oxide produced from S-nitroso-N-acetylpenicillamine (SNAP) or interferon-gamma activated peritoneal macrophages. In both situations, evidence of cyst damage and death was observed by microscopy in over 77% of cysts after 3 days, indicating that intact hydatid cysts could be susceptible to a Th1 driven macrophage attack. A crude extract of the laminated layer from cysts was found to be able to reduce the production of nitric oxide from activated macrophages in vitro and in vivo and this may have been due to phagocytosis of laminated layer fragments by the macrophages. The results indicate that, although cysts may be susceptible to the effects of nitric oxide, the laminated layer may be involved in downregulating nitric oxide production.

  7. Interaction of caveolin-1, nitric oxide, and nitric oxide synthases in hypoxic human SK-N-MC neuroblastoma cells.

    PubMed

    Shen, Jiangang; Lee, Waisin; Li, Yue; Lau, Chi Fai; Ng, Kwong Man; Fung, Man Lung; Liu, Ke Jian

    2008-10-01

    Neuroblastoma cells are capable of hypoxic adaptation, but the mechanisms involved are not fully understood. We hypothesized that caveolin-1 (cav-1), a plasma membrane signal molecule, might play a role in protecting neuroblastoma cells from oxidative injury by modulating nitric oxide (NO) production. We investigated the alterations of cav-1, cav-2, nitric oxide synthases (NOS), and NO levels in human SK-N-MC neuroblastoma cells exposed to hypoxia with 2% [O2]. The major discoveries include: (i) cav-1 but not cav-2 was up-regulated in the cells exposed to 15 h of hypoxia; (ii) NO donor 1-[N, N-di-(2-aminoethyl) amino] diazen-1-ium-1, 2-diolate up-regulated the expression of cav-1, whereas the non-selective NOS inhibitor N(G)-nitro-L-arginine methyl ester and inducible NOS (iNOS) inhibitor 1400W each abolished the increase in cav-1 expression in the hypoxic SK-N-MC cells. These results suggest that iNOS-induced NO production contributes to the up-regulation of cav-1 in the hypoxic SK-N-MC cells. Furthermore, we studied the roles played by cav-1 in regulating NO, NOS, and apoptotic cell death in the SK-N-MC cells subjected to 15 h of hypoxic treatment. Both cav-1 transfection and cav-1 scaffolding domain peptide abolished the induction of iNOS, reduced the production of NO, and reduced the rates of apoptotic cell death in the hypoxic SK-N-MC cells. These results suggest that increased expression of cav-1 in response to hypoxic stimulation could prevent oxidative injury induced by reactive oxygen species. The interactions of cav-1, NO, and NOS could be an important signal pathway in protecting the neuroblastoma cells from oxidative injury, contributing to the hypoxic tolerance of neuroblastoma cells. PMID:18717816

  8. Nitric oxide and its congeners in mitochondria: implications for apoptosis.

    PubMed Central

    Richter, C

    1998-01-01

    Apoptosis is an evolutionarily conserved form of physiologic cell death important for tissue development and homeostasis. The causes and execution mechanisms of apoptosis are not completely understood. Nitric oxide (NO) and its congeners, oxidative stress, Ca2+, proteases, nucleases, and mitochondria are considered mediators of apoptosis. Recent findings strongly suggest that mitochondria contain a factor or factors that upon release from the destabilized organelles, induce apoptosis. We have found that oxidative stress-induced release of Ca2+ from mitochondria followed by Ca2+ reuptake (Ca2+ cycling) causes destabilization of mitochondria and apoptosis. The protein product of the protooncogene bcl-2 protects mitochondria and thereby prevents apoptosis. We have also found that NO and its congeners can induce Ca2+ release from mitochondria. Thus, nitrogen monoxide (.NO) binds to cytochrome oxidase, blocks respiration, and thereby causes mitochondrial deenergization and Ca2+ release. Peroxynitrite (ONOO-), on the other hand, causes Ca2+ release from mitochondria by stimulating a specific Ca2+ release pathway. This pathway requires oxidized nicotinamide adenine dinucleotide (NAD+) hydrolysis to adenosine diphosphate ribose and nicotinamide. NAD+ hydrolysis is only possible when some vicinal thiols are cross-linked. ONOO- is able to oxidize them. Our findings suggest that NO and its congeners can induce apoptosis by destabilizing mitochondria via deenergization and/or by inducing a specific Ca2+ release followed by Ca2+ cycling. PMID:9788886

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

    PubMed Central

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

    2004-01-01

    Background Platelet-activating factor and nitric oxide may be involved in the initiation of human labour as inflammatory mediators. The aim of this study was to test whether platelet-activating factor and lipopolysaccharide were able to induce nitric oxide synthase expression and stimulate the production of nitric oxide in human fetal membrane explants in culture. Methods Fetal membranes were collected from Caesarean sections at term. RNA was extracted from membranes and subjected to a qualitative RT-PCR to assess the baseline expression of iNOS. Discs of fetal membranes were cultured for 24 hours in the presence of platelet-activating factor at a dose range of 0.1 nanomolar – 1 micomolar or 1 microgram/ml lipopolysaccharide. Nitric oxide production was measured via nitrite ions in the culture medium and mRNA for iNOS was detected by RT-PCR. Results Culturing the membrane discs in medium containing serum induced nitric oxide synthase expression and platelet-activating factor significantly stimulated the production of nitric oxide under these conditions. When cultured without serum inducible nitric oxide synthase expression was induced by lipopolysaccharide, but not by platelet-activating factor. Conclusion Platelet-activating factor may have a role in the initiation of labour, at term or preterm, via the increased local production of nitric oxide as an inflammatory mediator. In this model of intrauterine infection, lipopolysaccharide was found to induce iNOS expression by fetal membranes, and this mechanism could be involved in preterm labour. PMID:15191613

  10. 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

  11. 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.

  12. Nitric-oxide supplementation for treatment of long-term complications in argininosuccinic aciduria

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Argininosuccinate lyase (ASL) is required for the synthesis and channeling of L-arginine to nitric oxide synthase (NOS) for nitric oxide (NO) production. Congenital ASL deficiency causes argininosuccinic aciduria (ASA), the second most common urea cycle disorder, and leads to deficiency of both urea...

  13. 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. PMID:22022485

  14. 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

  15. Mitochondrial nitric oxide synthase participates in septic shock myocardial depression by nitric oxide overproduction and mitochondrial permeability transition pore opening.

    PubMed

    Xu, Ce; Yi, Chenju; Wang, Huiping; Bruce, Iain C; Xia, Qiang

    2012-01-01

    The aim of this study was to determine whether mitochondrial nitric oxide (NO) synthase (NOS) is involved in septic shock myocardial depression. The cecal ligation and puncture (CLP) method was used to induce septic shock. There was a significant depression of hemodynamic parameters recorded in the septic shock stage. After using nonselective NOS inhibitor N-nitro-L-arginine methyl ester (L-NAME), inducible NOS inhibitor aminoguanidine (AMG), and neuronal NOS inhibitor 7-nitroindazole (7-NI), depression of the parameters was partly attenuated. Nitric oxide production in isolated cardiac mitochondria increased obviously in the CLP-septic shock stage, L-NAME and 7-NI both decreased NO production significantly. Nitrite/nitrate (NOx) production in the septic shock stage was much greater than those in the corresponding sham groups, and NOx production in the cytosol by inducible NOS was greater. Treatment with AMG suppressed NOx production in the cytosol by iNOS, whereas treatment with 7-NI decreased NOx production in the mitochondria. Mitochondrial NOS expression increased significantly in the septic shock stage, and its overexpression was attenuated using 7-NI. There was no significant decrease in the mitochondrial permeability transition pore measurement in the CLP-septic shock group, whereas a significant decrease was observed in those treated with L-NAME or 7-NI. These results indicate that overexpression of mitochondrial NOS is involved in myocardial depression. PMID:21993446

  16. Direct measurements of nitric oxide release in relation to expression of endothelial nitric oxide synthase in isolated porcine mitral valves.

    PubMed

    Moesgaard, S G; Olsen, L H; Aasted, B; Viuff, B M; Pedersen, L G; Pedersen, H D; Harrison, A P

    2007-04-01

    The aim of this study was to measure the direct release of nitric oxide (NO) from the porcine mitral valve using a NO microelectrode. Furthermore, the expression and localization of endothelial nitric oxide synthase (eNOS) in the mitral valve was studied using immunohistochemistry, Western blotting and RT-PCR. Results show that bradykinin increases NO release from mitral valves (DeltaBradykinin: 33.71 +/- 10.41 nm NO, P < 0.001, n = 10), whereas N-nitro-l-arginine methyl esther (l-NAME) decreases NO release when compared with basal level (Deltal-NAME: 82.69 +/- 15.66 nm NO, P < 0.005, n = 4). Both protein and mRNA expression of eNOS in mitral valves and in isolated valvular endothelial cells suggest that the NO release is mainly associated with the mitral valve endothelium. It is concluded that direct NO release from porcine mitral valves coincides with eNOS expression. This study documents useful techniques for investigations into the role of local NO release in mitral valve diseases.

  17. Effect of L-arginine-nitric oxide system on chemical-induced diabetes mellitus.

    PubMed

    Mohan, I K; Das, U N

    1998-11-01

    Several in vitro studies have suggested that nitric oxide may be the mediator of cytokine-induced beta-cell destruction. On the other hand, in vivo studies have given conflicting results: some studies suggesting that nitric oxide synthase inhibitors do not suppress streptozotocin-induced diabetes in mice, while others revealed that nitric oxide synthase inhibitors can reduce the incidence of insulin-dependent diabetes mellitus in rats. The results of the present study indicate that alloxan-induced diabetes in the male Wistar rats can be abrogated to a large extent by prior and simultaneous administration of the precursor of nitric oxide, L-arginine, where as NG-monomethy-L-arginine (L-NMMA), a specific inhibitor of nitric oxide synthase, can completely block the beneficial action of L-arginine. Sodium nitroprusside, a nitric oxide donor, also showed significant inhibitory effect on the severity of diabetes induced by alloxan. Alloxan treatment reduced nitric oxide generation, whereas L-arginine and sodium nitroprusside, when given along with alloxan, enhanced nitric oxide production to control values. Induction of diabetes by alloxan in the experimental animals was associated with a marked elevation in plasma lactate, ketone body, and lipid peroxide levels with a simultaneous fall in plasma insulin and nitric oxide levels. Alloxan-induced diabetes also induced a fall in the levels of anti-oxidant enzymes such as superoxide dismutase, glutathione reductase, and total glutathione, and antioxidants: vitamin E and ceruloplasmin, and an increase in glutathione peroxidase and glutathione-S-transferase. All these biochemical abnormalities and antioxidant levels have improved to near normal levels in animals treated with insulin, L-arginine, and sodium nitroprusside. From the results of the present study, it is apparent that L-arginine and nitric oxide can prevent alloxan-induced beta-cell damage, and the development of diabetes, and restore the antioxidant status to near

  18. 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. PMID:26677898

  19. 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.

  20. Dietary flavonoids and nitrate: effects on nitric oxide and vascular function.

    PubMed

    Bondonno, Catherine P; Croft, Kevin D; Ward, Natalie; Considine, Michael J; Hodgson, Jonathan M

    2015-04-01

    Emerging evidence highlights dietary flavonoids and nitrate as candidates that may explain at least part of the cardioprotective effect of a fruit and vegetable diet. Nitric oxide plays a pivotal role in cardiovascular health. Components of a fruit and vegetable diet that are cardioprotective, in part through effects on nitric oxide status, could substantially reduce the cardiovascular risk profile of the general population with increased intake of such a diet. Epidemiological evidence suggests that dietary flavonoids and nitrate have a cardioprotective effect. Clinical trials with flavonoid- and nitrate-rich foods have shown benefits on measures of vascular health. While the molecular mechanisms by which flavonoids and nitrate are cardioprotective are not completely understood, recent evidence suggests both nonspecific and specific effects through nitric oxide pathways. This review presents an overview of nitric oxide and its key role in cardiovascular health and discusses the possible vascular benefits of flavonoids and nitrate, individually and in combination, through effects on nitric oxide status.

  1. Expression of inducible nitric oxide synthase in experimental viral myocarditis.

    PubMed

    Glück, B; Merkle, I; Dornberger, G; Stelzner, A

    2000-05-01

    Nitric oxide (NO) is an important bioactive molecule with regulatory, cytotoxic or cytoprotective properties. In virus-induced myocarditis, NO mediates host defense mechanisms against the infection or causes cardiac dysfunctions. NO is synthesized from L-arginine by the enzyme nitric oxide synthase (NOS). The expression of the inducible form of the nitric oxide synthase (iNOS) is regulated by cytokines, involved in the complex myocardial immune response to enterovirus infections. The present study was undertaken to characterize the role of iNOS and NO in the murine model of viral myocarditis induced by coxsackievirus B3 (CVB3). In response to CVB3 infection we investigated the time course of iNOS induction in correlation with cytokine mRNA expression (TNF-alpha, IL-1 alpha, IFN-gamma, TGF-beta) in the heart of NMRI mice by RT-PCR. Positive PCR signals for viral RNA were found in the acute and chronic stage of disease by seminested PCR, indicating the persistence of viral genome. We found distinct expression of iNOS at all time points (1, 2, 3, 4, 7, 14, 28, 56, 98 days post infection [p.i.]). Higher iNOS mRNA levels were identified between days 4 until 28 p.i. in comparison to day 56 and 98 p.i. using densitometric values. The mRNA of the inflammatory cytokines TNF-alpha, IL-1 alpha, IFN-gamma appeared at days 1, 4, and 7 p.i., peaked at day 7 p.i. and persisted until day 98 p.i. Similar like the iNOS mRNA pattern was the expression profile of TGF-beta. Using in situ hybridization and immunohistochemistry iNOS was localized in infiltrates, vascular endothelial cells, smooth muscle cells, myocytes and throughout the interstitial spaces between myocardial fibers in the heart sections of NMRI mice. Increased levels of NO were measured as total nitrate/nitrite concentration in the sera of mice from day 7 until day 28 p.i.

  2. 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.

  3. 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. PMID:21645628

  4. 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.

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

    PubMed Central

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

    2014-01-01

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

  6. mRNA expressions of inducible nitric oxide synthase, endothelial nitric oxide synthase, and neuronal nitric oxide synthase genes in meningitis patients.

    PubMed

    Oztuzcu, Serdar; Igci, Yusuf Ziya; Arslan, Ahmet; Sivasli, Ercan; Ozkara, Esma; Igci, Mehri; Demiryürek, Seniz; Cengiz, Beyhan; Gogebakan, Bulent; Namiduru, Mustafa; Coskun, Mehmet Yavuz; Cakmak, Ecir Ali

    2011-03-01

    Meningitis is an inflammation of the protective membranes covering the brain and spinal cord caused by bacteria, fungi, or viruses with various clinical symptoms. Although meningitis is not so prevalent, it remains the most serious contagious disease. The aim of our study was to investigate the effect of gene expressions of nitric oxide synthases (NOS) on meningitis patients. Using samples taken from 61 meningitis patients, inducible NOS, endothelial NOS (eNOS), and neuronal NOS mRNA levels were assessed in both blood and cerebrospinal fluid (CSF). A control group was constructed of 64 healthy persons. The gene expression analysis was made using real-time polymerase chain reaction method. There was no neuronal NOS expression in either group, whereas inducible NOS expression was detected in 40 blood samples and 12 CSF samples from meningitis patients. However, there were no marked differences between groups (p=0.5104). eNOS expression was detected in all blood and CSF samples, which was markedly higher in patients (p=0.0367). Because the increase in eNOS expression increases NO production, eNOS expression in meningitis patients is of great importance. This increase of eNOS in meningitis patients compared with healthy subjects may lead to novel treatments for reducing the severity of the disease.

  7. Endotoxin induces fibrosis in vascular endothelial cells through a mechanism dependent on transient receptor protein melastatin 7 activity.

    PubMed

    Echeverría, Cesar; Montorfano, Ignacio; Hermosilla, Tamara; Armisén, Ricardo; Velásquez, Luis A; Cabello-Verrugio, Claudio; Varela, Diego; Simon, Felipe

    2014-01-01

    The pathogenesis of systemic inflammatory diseases, including endotoxemia-derived sepsis syndrome, is characterized by endothelial dysfunction. It has been demonstrated that the endotoxin lipopolysaccharide (LPS) induces the conversion of endothelial cells (ECs) into activated fibroblasts through endothelial-to-mesenchymal transition mechanism. Fibrogenesis is highly dependent on intracellular Ca2+ concentration increases through the participation of calcium channels. However, the specific molecular identity of the calcium channel that mediates the Ca2+ influx during endotoxin-induced endothelial fibrosis is still unknown. Transient receptor potential melastatin 7 (TRPM7) is a calcium channel that is expressed in many cell types, including ECs. TRPM7 is involved in a number of crucial processes such as the conversion of fibroblasts into activated fibroblasts, or myofibroblasts, being responsible for the development of several characteristics of them. However, the role of the TRPM7 ion channel in endotoxin-induced endothelial fibrosis is unknown. Thus, our aim was to study whether the TRPM7 calcium channel participates in endotoxin-induced endothelial fibrosis. Using primary cultures of ECs, we demonstrated that TRPM7 is a crucial protein involved in endotoxin-induced endothelial fibrosis. Suppression of TRPM7 expression protected ECs from the fibrogenic process stimulated by endotoxin. Downregulation of TRPM7 prevented the endotoxin-induced endothelial markers decrease and fibrotic genes increase in ECs. In addition, TRPM7 downregulation abolished the endotoxin-induced increase in ECM proteins in ECs. Furthermore, we showed that intracellular Ca2+ levels were greatly increased upon LPS challenge in a mechanism dependent on TRPM7 expression. These results demonstrate that TRPM7 is a key protein involved in the mechanism underlying endotoxin-induced endothelial fibrosis.

  8. Endotoxin Induces Fibrosis in Vascular Endothelial Cells through a Mechanism Dependent on Transient Receptor Protein Melastatin 7 Activity

    PubMed Central

    Echeverría, Cesar; Montorfano, Ignacio; Hermosilla, Tamara; Armisén, Ricardo; Velásquez, Luis A.; Cabello-Verrugio, Claudio; Varela, Diego; Simon, Felipe

    2014-01-01

    The pathogenesis of systemic inflammatory diseases, including endotoxemia-derived sepsis syndrome, is characterized by endothelial dysfunction. It has been demonstrated that the endotoxin lipopolysaccharide (LPS) induces the conversion of endothelial cells (ECs) into activated fibroblasts through endothelial­to­mesenchymal transition mechanism. Fibrogenesis is highly dependent on intracellular Ca2+ concentration increases through the participation of calcium channels. However, the specific molecular identity of the calcium channel that mediates the Ca2+ influx during endotoxin-induced endothelial fibrosis is still unknown. Transient receptor potential melastatin 7 (TRPM7) is a calcium channel that is expressed in many cell types, including ECs. TRPM7 is involved in a number of crucial processes such as the conversion of fibroblasts into activated fibroblasts, or myofibroblasts, being responsible for the development of several characteristics of them. However, the role of the TRPM7 ion channel in endotoxin-induced endothelial fibrosis is unknown. Thus, our aim was to study whether the TRPM7 calcium channel participates in endotoxin-induced endothelial fibrosis. Using primary cultures of ECs, we demonstrated that TRPM7 is a crucial protein involved in endotoxin-induced endothelial fibrosis. Suppression of TRPM7 expression protected ECs from the fibrogenic process stimulated by endotoxin. Downregulation of TRPM7 prevented the endotoxin-induced endothelial markers decrease and fibrotic genes increase in ECs. In addition, TRPM7 downregulation abolished the endotoxin-induced increase in ECM proteins in ECs. Furthermore, we showed that intracellular Ca2+ levels were greatly increased upon LPS challenge in a mechanism dependent on TRPM7 expression. These results demonstrate that TRPM7 is a key protein involved in the mechanism underlying endotoxin-induced endothelial fibrosis. PMID:24710004

  9. Endotoxin induces fibrosis in vascular endothelial cells through a mechanism dependent on transient receptor protein melastatin 7 activity.

    PubMed

    Echeverría, Cesar; Montorfano, Ignacio; Hermosilla, Tamara; Armisén, Ricardo; Velásquez, Luis A; Cabello-Verrugio, Claudio; Varela, Diego; Simon, Felipe

    2014-01-01

    The pathogenesis of systemic inflammatory diseases, including endotoxemia-derived sepsis syndrome, is characterized by endothelial dysfunction. It has been demonstrated that the endotoxin lipopolysaccharide (LPS) induces the conversion of endothelial cells (ECs) into activated fibroblasts through endothelial-to-mesenchymal transition mechanism. Fibrogenesis is highly dependent on intracellular Ca2+ concentration increases through the participation of calcium channels. However, the specific molecular identity of the calcium channel that mediates the Ca2+ influx during endotoxin-induced endothelial fibrosis is still unknown. Transient receptor potential melastatin 7 (TRPM7) is a calcium channel that is expressed in many cell types, including ECs. TRPM7 is involved in a number of crucial processes such as the conversion of fibroblasts into activated fibroblasts, or myofibroblasts, being responsible for the development of several characteristics of them. However, the role of the TRPM7 ion channel in endotoxin-induced endothelial fibrosis is unknown. Thus, our aim was to study whether the TRPM7 calcium channel participates in endotoxin-induced endothelial fibrosis. Using primary cultures of ECs, we demonstrated that TRPM7 is a crucial protein involved in endotoxin-induced endothelial fibrosis. Suppression of TRPM7 expression protected ECs from the fibrogenic process stimulated by endotoxin. Downregulation of TRPM7 prevented the endotoxin-induced endothelial markers decrease and fibrotic genes increase in ECs. In addition, TRPM7 downregulation abolished the endotoxin-induced increase in ECM proteins in ECs. Furthermore, we showed that intracellular Ca2+ levels were greatly increased upon LPS challenge in a mechanism dependent on TRPM7 expression. These results demonstrate that TRPM7 is a key protein involved in the mechanism underlying endotoxin-induced endothelial fibrosis. PMID:24710004

  10. Salivary Nitric Oxide, a Biomarker for Stress and Anxiety?

    PubMed Central

    Al-Smadi, Ahmed Mohammad; Ashour, Ala Fawzi; Al-Awaida, Wajdy

    2016-01-01

    Objective To investigate if salivary nitrate correlates to the daily psychological stress and anxiety in a group of human subjects. Methods The convenient sample recruitment method was employed; data from seventy three subjects were analyzed. The Perceived Stress Scale (PSS) and Hamilton Anxiety Rating Scale (HAM-A) inventories were used to determine stress and anxiety scores respectively. Salivary nitric oxide was measured through nitrate (NOx) levels using the Griess reaction method. Results Although stress and anxiety were correlated. No significant correlation exists between salivary nitrate and daily psychological stress and anxiety in the study's participants. Conclusion While all previous studies focused NOx levels in acute stress models. This is the first study to investigate the correlation between salivary nitrates and daily psychological stress and anxiety. Although stress and anxiety were correlated, there is no correlation between salivary nitrates and daily psychological stress and anxiety. Further studies are required to investigate this correlation using other biological samples such as plasma. PMID:27247597

  11. 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

  12. 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

  13. Apoplastic Synthesis of Nitric Oxide by Plant Tissues

    PubMed Central

    Bethke, Paul C.; Badger, Murray R.; Jones, Russell L.

    2004-01-01

    Nitric oxide (NO) is an important signaling molecule in animals and plants. In mammals, NO is produced from Arg by the enzyme NO synthase. In plants, NO synthesis from Arg using an NO synthase–type enzyme and from nitrite using nitrate reductase has been demonstrated previously. The data presented in this report strongly support the hypothesis that plant tissues also synthesize NO via the nonenzymatic reduction of apoplastic nitrite. As measured by mass spectrometry or an NO-reactive fluorescent probe, Hordeum vulgare (barley) aleurone layers produce NO rapidly when nitrite is added to the medium in which they are incubated. NO production requires an acid apoplast and is accompanied by a loss of nitrite from the medium. Phenolic compounds in the medium can increase the rate of NO production. The possible significance of apoplastic NO production for germinating grain and for plant roots is discussed. PMID:14742874

  14. 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

  15. A multifaceted molecule, nitric oxide in oral and periodontal diseases.

    PubMed

    Uğar-Cankal, Dilek; Ozmeric, Nurdan

    2006-04-01

    Nitric oxide (NO) is a molecule with multiple effects on different tissues. NO takes important roles in vasodilatation, bacterial challenge and cytokine stimulation, regulation of mineralized tissue function, neurotransmission, and platelet aggregation, etc. However, under pathological conditions, NO has damaging effects. NO is synthesized by NO synthases (NOS) and inducible isoform of NOS (iNOS) is closely related to the pathophysiological characteristics of inflammatory diseases such as periodontal diseases. The expression of iNOS has been investigated in salivary gland-related diseases, temporomandibular joint disorders and oral cancer as well. The beneficial and damaging effects of NO in diseases related with periodontal, dental and maxillofacial area are discussed in this review. The biological pathways involved with NO and NO inhibitors may be good drug targets to have a role in the future management of patients with diseases in orofacial region. PMID:16387291

  16. Visualisation of nitric oxide generated by activated murine macrophages.

    PubMed

    Leone, A M; Furst, V W; Foxwell, N A; Cellek, S; Moncada, S

    1996-04-01

    We have visualised the release and approximate diffusion profile of nitric oxide (NO) from activated murine macrophages using a high transmission microscope coupled to a high sensitivity photon counting camera. The images generated by NO were cell-associated and spread over an area of approximately 175 micrometers from the activated macrophage. The signals obtained were dependent on the presence of exogenous L-arginine in the medium and followed a time course similar to that previously described for the generation of NO by the inducible form of NO synthase. The light signal was attenuated by the inhibitor of NO synthase, N omega-nitro-L-arginine methyl ester. Studies using superoxide-deficient macrophages further confirmed that the signals detected were generated by NO rather than reactive oxygen intermediates. PMID:8660339

  17. 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.

  18. Transcriptomic Response to Nitric Oxide Treatment in Larix olgensis Henry.

    PubMed

    Hu, Xiaoqing; Yang, Jingli; Li, Chenghao

    2015-12-02

    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.

  19. 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.

  20. The reactions of copper proteins with nitric oxide.

    PubMed

    Torres, J; Wilson, M T

    1999-05-01

    Nitric oxide (NO) can act as a ligand for copper atoms and may also engage in redox chemistry with the metal once bound. Furthermore NO posses an unpaired electron which can couple with the unpaired electron on Cu2+. These properties have been exploited to probe the active sites of copper-containing enzymes and proteins. We review these studies. In addition to the use as a spectroscopic probe for the active site we draw attention to the rapid reactions of NO at the copper sites in Cytochrome c oxidase (CcO) and laccase. These reactions in CcO occur in the ms time range, at low NO concentrations and in the presence of oxygen and may therefore be of physiological relevance to the control of respiration. Finally we speculate on the wider role that NO may play in regulation of an important group of Type 2 copper containing enzymes. PMID:10320665

  1. 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

  2. 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

  3. Nitric oxide inhibitory constituents from the barks of Cinnamomum cassia.

    PubMed

    He, Shan; Zeng, Ke-Wu; Jiang, Yong; Tu, Peng-Fei

    2016-07-01

    Six new compounds including one γ-butyrolactone, cinncassin A (1), two tetrahydrofuran derivatives, cinncassins B and C (2, 3), two lignans, cinncassins D and E (4, 5), and one phenylpropanol glucoside, cinnacassoside D (6), together with 14 known lignans (7-20) were isolated from the barks of Cinnamomum cassia. The structures of 1-6 were elucidated by extensive 1D and 2D NMR spectroscopic data analysis as well as chemical methods, and the absolute configurations were established by experimental and calculated ECD data. The anti-inflammatory activities of the isolates were evaluated on nitric oxide (NO) production in lipopolysaccharide (LPS)-induced BV-2 microglial cells. Compounds 5, 7, 8, and 15 showed potent inhibition activities with IC50 values of 17.6, 17.7, 18.7, and 17.5μM, respectively. PMID:27223848

  4. Nitric oxide evoked p53-accumulation and apoptosis.

    PubMed

    Brüne, Bernhard; Schneiderhan, Nicole

    2003-04-01

    The tumor suppressor p53 accumulates under conditions of cellular stress and affects cell cycle progression and/or apoptosis. This has been exemplified for endogenously produced or exogenously supplied nitric oxide (NO) and thus accounts at least in part for cell destructive signaling qualities of this bioactive molecule and/or derived reactive nitrogen species. However, detailed mechanisms of toxicity and pathways of cell demise remain to be elucidated. Establishing that NO-treatment left the ubiquitination and the p53-Mdm2 interaction intact may point to an impaired nuclear-cytoplasmic shuttling to account for p53 stabilization. This was verified by heterokaryon analysis. We conclude that attenuated nuclear export contributes to stabilization and activation of p53 under the influence of NO.

  5. Hemoglobin, nitric oxide and molecular mechanisms of hypoxic vasodilation

    PubMed Central

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

    2009-01-01

    The protected transport of nitric oxide (NO) by hemoglobin (Hb) links the metabolic activity of working tissue to the regulation of its local blood supply through hypoxic vasodilation. This physiologic mechanism is allosterically coupled to the O2 saturation of Hb and involves the covalent binding of NO to a cysteine residue in the β-chain of Hb (Cys β93) to form S-nitrosohemoglobin (SNO-Hb). Subsequent S-transnitrosation, the transfer of NO groups to thiols on the RBC membrane and then in the plasma, preserves NO vasodilator activity for delivery to the vascular endothelium. This SNO-Hb paradigm provides insight into the respiratory cycle and a new therapeutic focus for diseases involving abnormal microcirculatory perfusion. In addition, the formation of S-nitrosothiols in other proteins may regulate an array of physiological functions. PMID:19781996

  6. Nitric Oxide Regulates Neurogenesis in the Hippocampus following Seizures.

    PubMed

    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.

  7. 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

  8. 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.

  9. Removal of nitric oxide from exhaust gas with cyanuric acid--

    SciTech Connect

    Siebers, D.L. . Combustion Research Faclity); Caton, J.A. . Dept. of Mechanical Engineering)

    1990-01-01

    Addition of gaseous isocyanic acid (HNCO) to the exhaust of combustion systems or chemical process is proposed as a method for reducing nitric oxide (NO) emissions. The HNCO selectively reduces NO in the exhaust through a multistep chemical reaction mechanism. This article presents an experimental investigation of the proposed NO reduction process using cyanuric acid as the source of HNCO. At elevated temperature cyanuric acid decomposes and forms HNCO. The effects of temperature, exhaust gas composition, cyanuric acid concentration (i.e., HNCO concentration), and surfaces were examined. The experiments were conducted in an electrically heated quartz flow reactor using either exhaust from a diesel engine or simulated exhaust gas. The results demonstrate that gas phase NO reduction approaching 100% can be obtained.

  10. Calmodulin-induced structural changes in endothelial nitric oxide synthase

    PubMed Central

    Persechini, Anthony; Tran, Quang-Kim; Black, D.J.; Gogol, Edward P.

    2013-01-01

    We have derived structures of intact calmodulin(CaM)-free and CaM-bound endothelial nitric oxide synthase (eNOS) by reconstruction from cryo-electron micrographs. The CaM-free reconstruction is well fitted by the oxygenase domain dimer, but the reductase domains are not visible, suggesting they are mobile and thus delocalized. Additional protein is visible in the CaM-bound reconstruction, concentrated in volumes near two basic patches on each oxygenase domain. One of these corresponds with a presumptive docking site for the reductase domain FMN-binding module. The other is proposed to correspond with a docking site for CaM. A model is suggested in which CaM binding and docking position the reductase domains near the oxygenase domains and promote docking of the FMN-binding modules required for electron transfer. PMID:23266515

  11. Natural Product Nitric Oxide Chemistry: New Activity of Old Medicines

    PubMed Central

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

    2012-01-01

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

  12. Strategies to increase nitric oxide signalling in cardiovascular disease.

    PubMed

    Lundberg, Jon O; Gladwin, Mark T; Weitzberg, Eddie

    2015-09-01

    Nitric oxide (NO) is a key signalling molecule in the cardiovascular, immune and central nervous systems, and crucial steps in the regulation of NO bioavailability in health and disease are well characterized. Although early approaches to therapeutically modulate NO bioavailability failed in clinical trials, an enhanced understanding of fundamental subcellular signalling has enabled a range of novel therapeutic approaches to be identified. These include the identification of: new pathways for enhancing NO synthase activity; ways to amplify the nitrate-nitrite-NO pathway; novel classes of NO-donating drugs; drugs that limit NO metabolism through effects on reactive oxygen species; and ways to modulate downstream phosphodiesterases and soluble guanylyl cyclases. In this Review, we discuss these latest developments, with a focus on cardiovascular disease.

  13. 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. PMID:26812915

  14. Role of nitric oxide in cellular iron metabolism.

    PubMed

    Kim, Sangwon; Ponka, Prem

    2003-03-01

    Iron regulatory proteins (IRP1 and IRP2) control the synthesis of transferrin receptors (TfR) and ferritin by binding to iron-responsive elements (IREs) which are located in the 3' untranslated region (UTR) and the 5' UTR of their respective mRNAs. Cellular iron levels affect binding of IRPs to IREs and consequently expression of TfR and ferritin. Moreover, NO*, a redox species of nitric oxide that interacts primarily with iron, can activate IRP1 RNA-binding activity resulting in an increase in TfR mRNA levels. We have shown that treatment of RAW 264.7 cells (a murine macrophage cell line) with NO+ (nitrosonium ion, which causes S-nitrosylation of thiol groups) resulted in a rapid decrease in RNA-binding of IRP2, followed by IRP2 degradation, and these changes were associated with a decrease in TfR mRNA levels. Moreover, we demonstrated that stimulation of RAW 264.7 cells with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) increased IRP1 binding activity, whereas RNA-binding of IRP2 decreased and was followed by a degradation of this protein. Furthermore, the decrease of IRP2 binding/protein levels was associated with a decrease in TfR mRNA levels in LPS/IFN-gamma-treated cells, and these changes were prevented by inhibitors of inducible nitric oxide synthase. These results suggest that NO+-mediated degradation of IRP2 plays a major role in iron metabolism during inflammation.

  15. Phosphorylated neuronal nitric oxide synthase in neuropathic pain in rats

    PubMed Central

    Zhou, Zhidong; Liang, Yingping; Deng, Fumou; Cheng, Yong; Sun, Jing; Guo, Lian; Xu, Guohai

    2015-01-01

    Neuropathic pain caused by nervous system damage or system dysfunction. The pathogenesis and the mechanism underlying neuropathic pain remains unclear. The only known neurobiological component involved in the neuropathic pain is nitric oxide (NO). NO is synthesized by nitric oxide synthase (nNOS) from L-arginine and oxygen. nNOS is involved in the inflammatory pain and neuropathic pain. In this study, we aimed to identify whether KN93 reduced the pain in the rats. Sixty adult male SD rat were randomly divided into 4 groups. Sham group and model group were not received treatment. Experimental group received intrathecal injection of KN93, and negative control group received DMSO injection 30 min before pain test. After last test of pain threshold, the rats were sacrificed and lumbar spinal tissues were sampled for analysis of the expression of pnNOS and pCaMK II by quantitative PCR and Western blotting. Pain threshold was increased in the rats received KN93 treatment (P<0.01), and the expression levels of pnNOS was increased (P<0.05) in experimental group and accompanied with decrease of CaMK II expression (P<0.05). By administration of KN93, the interaction of nNOS and the adaptor protein CAPON was reduced through inhibition of CaMK II by KN93. In conclusion, this study reveals that KN93 can reduce neuropathic pain via inhibiting the activity of CaMK II, and then increase the level of phosphorylated nNOS, to reduce the interaction with CAPON. PMID:26722464

  16. Nitric oxide alters metabolism in isolated alveolar type II cells.

    PubMed

    Miles, P R; Bowman, L; Huffman, L

    1996-07-01

    Alveolar type II cells may be exposed to nitric oxide (.NO) from external sources, and these cells can also generate .NO. Therefore we studied the effects of altering .NO levels on various type II cell metabolic processes. Incubation of cells with the .NO generator, S-nitroso-N-acetylpenicillamine (SNAP; 1 mM), leads to reductions of 60-70% in the synthesis of disaturated phosphatidylcholines (DSPC) and cell ATP levels. Cellular oxygen consumption, an indirect measure of cell ATP synthesis, is also reduced by SNAP. There is no direct effect of SNAP on lung mitochondrial ATP synthesis, suggesting that .NO does not directly inhibit this process. On the other hand, incubation of cells with NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase (NOS), the enzyme responsible for .NO synthesis, results in increases in DSPC synthesis, cell ATP content, and cellular oxygen consumption. The L-NAME effects are reversed by addition of L-arginine, the substrate for NOS. Production of .NO by type II cells is inhibited by L-NAME, a better inhibitor of constitutive NOS (cNOS) than inducible NOS (iNOS), and is reduced in the absence of external calcium. Aminoguanidine, a specific inhibitor of iNOS, has no effect on cell ATP content or on .NO production. These results indicate that alveolar type II cell lipid and energy metabolism can be affected by .NO and suggest that there may be cNOS activity in these cells. PMID:8760128

  17. Phosphorylated neuronal nitric oxide synthase in neuropathic pain in rats.

    PubMed

    Zhou, Zhidong; Liang, Yingping; Deng, Fumou; Cheng, Yong; Sun, Jing; Guo, Lian; Xu, Guohai

    2015-01-01

    Neuropathic pain caused by nervous system damage or system dysfunction. The pathogenesis and the mechanism underlying neuropathic pain remains unclear. The only known neurobiological component involved in the neuropathic pain is nitric oxide (NO). NO is synthesized by nitric oxide synthase (nNOS) from L-arginine and oxygen. nNOS is involved in the inflammatory pain and neuropathic pain. In this study, we aimed to identify whether KN93 reduced the pain in the rats. Sixty adult male SD rat were randomly divided into 4 groups. Sham group and model group were not received treatment. Experimental group received intrathecal injection of KN93, and negative control group received DMSO injection 30 min before pain test. After last test of pain threshold, the rats were sacrificed and lumbar spinal tissues were sampled for analysis of the expression of pnNOS and pCaMK II by quantitative PCR and Western blotting. Pain threshold was increased in the rats received KN93 treatment (P<0.01), and the expression levels of pnNOS was increased (P<0.05) in experimental group and accompanied with decrease of CaMK II expression (P<0.05). By administration of KN93, the interaction of nNOS and the adaptor protein CAPON was reduced through inhibition of CaMK II by KN93. In conclusion, this study reveals that KN93 can reduce neuropathic pain via inhibiting the activity of CaMK II, and then increase the level of phosphorylated nNOS, to reduce the interaction with CAPON.

  18. Estetrol Modulates Endothelial Nitric Oxide Synthesis in Human Endothelial Cells

    PubMed Central

    Montt-Guevara, Maria Magdalena; Giretti, Maria Silvia; Russo, Eleonora; Giannini, Andrea; Mannella, Paolo; Genazzani, Andrea Riccardo; Genazzani, Alessandro David; Simoncini, Tommaso

    2015-01-01

    Estetrol (E4) is a natural human estrogen that is present at high concentrations during pregnancy. E4 has been reported to act as an endogenous estrogen receptor modulator, exerting estrogenic actions on the endometrium or the central nervous system but presenting antagonistic effects on the breast. Due to these characteristics, E4 is currently being developed for a number of clinical applications, including contraception and menopausal hormone therapy. Endothelial nitric oxide (NO) is a key player for vascular function and disease during pregnancy and throughout aging in women. Endothelial NO is an established target of estrogens that enhance its formation in human endothelial cells. We here addressed the effects of E4 on the activity and expression of the endothelial nitric oxide synthase (eNOS) in cultured human umbilical vein endothelial cells (HUVEC). E4 stimulated the activation of eNOS and NO secretion in HUVEC. E4 was significantly less effective compared to E2, and a peculiar concentration-dependent effect was found, with higher amounts of E4 being less effective than lower concentrations. When E2 was combined with E4, an interesting pattern was noted. E4 antagonized NO synthesis induced by pregnancy-like E2 concentrations. However, E4 did not impede the modest induction of NO synthesis associated with postmenopausal-like E2 levels. These results support the hypothesis that E4 may be a regulator of NO synthesis in endothelial cells and raise questions on its peculiar signaling in this context. Our results may be useful to interpret the role of E4 during human pregnancy and possibly to help develop this interesting steroid for clinical use. PMID:26257704

  19. Estetrol Modulates Endothelial Nitric Oxide Synthesis in Human Endothelial Cells.

    PubMed

    Montt-Guevara, Maria Magdalena; Giretti, Maria Silvia; Russo, Eleonora; Giannini, Andrea; Mannella, Paolo; Genazzani, Andrea Riccardo; Genazzani, Alessandro David; Simoncini, Tommaso

    2015-01-01

    Estetrol (E4) is a natural human estrogen that is present at high concentrations during pregnancy. E4 has been reported to act as an endogenous estrogen receptor modulator, exerting estrogenic actions on the endometrium or the central nervous system but presenting antagonistic effects on the breast. Due to these characteristics, E4 is currently being developed for a number of clinical applications, including contraception and menopausal hormone therapy. Endothelial nitric oxide (NO) is a key player for vascular function and disease during pregnancy and throughout aging in women. Endothelial NO is an established target of estrogens that enhance its formation in human endothelial cells. We here addressed the effects of E4 on the activity and expression of the endothelial nitric oxide synthase (eNOS) in cultured human umbilical vein endothelial cells (HUVEC). E4 stimulated the activation of eNOS and NO secretion in HUVEC. E4 was significantly less effective compared to E2, and a peculiar concentration-dependent effect was found, with higher amounts of E4 being less effective than lower concentrations. When E2 was combined with E4, an interesting pattern was noted. E4 antagonized NO synthesis induced by pregnancy-like E2 concentrations. However, E4 did not impede the modest induction of NO synthesis associated with postmenopausal-like E2 levels. These results support the hypothesis that E4 may be a regulator of NO synthesis in endothelial cells and raise questions on its peculiar signaling in this context. Our results may be useful to interpret the role of E4 during human pregnancy and possibly to help develop this interesting steroid for clinical use. PMID:26257704

  20. 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.

  1. Endothelial nitric oxide: protector of a healthy mind.

    PubMed

    Katusic, Zvonimir S; Austin, Susan A

    2014-04-01

    Endothelial nitric oxide (NO) is generated by constitutively active endothelial nitric oxide synthase (eNOS), an essential enzyme responsible for cardiovascular homeostasis. Historically, endothelial NO was first recognized as a major vasodilator involved in control of vasomotor function and local blood flow. In this review, our attention is focused on the emerging role of endothelial NO in linking cerebrovascular function with cognition. We will discuss the recognized ability of endothelial NO to modulate processing of amyloid precursor protein (APP), influence functional status of microglia, and affect cognitive function. Existing evidence suggests that the loss of NO in cultured human cerebrovascular endothelium causes increased expression of APP and β-site APP-cleaving enzyme 1 (BACE1) thereby resulting in increased secretion of amyloid β peptides (Aβ1-40 and Aβ1-42). Furthermore, increased expression of APP and BACE1 as well as increased production of Aβ peptides was detected in the cerebral microvasculature and brain tissue of eNOS-deficient mice. Since Aβ peptides are considered major cytotoxic molecules responsible for the pathogenesis of Alzheimer's disease, these observations support the concept that a loss of endothelial NO might significantly contribute to the initiation and progression of cognitive decline. In addition, genetic inactivation of eNOS causes activation of microglia and promotes a pro-inflammatory phenotype in the brain. Behavioural analysis revealed that eNOS-deficient mice exhibit impaired cognitive performance thereby indicating that selective loss of endothelial NO has a detrimental effect on the function of neuronal cells. Together with findings from prior studies demonstrating the ability of endothelial NO to affect synaptic plasticity, mitochondrial biogenesis, and function of neuronal progenitor cells, it is becoming apparent that the role of endothelial NO in the control of central nervous system function is very complex. We

  2. 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.

  3. Superoxide reacts with nitric oxide to nitrate tyrosine at physiological pH via peroxynitrite.

    PubMed

    Reiter, C D; Teng, R J; Beckman, J S

    2000-10-20

    Tyrosine nitration is a widely used marker of peroxynitrite (ONOO(-)) produced from the reaction of nitric oxide with superoxide. Pfeiffer and Mayer (Pfeiffer, S., and Mayer, B. (1998) J. Biol. Chem. 273, 27280-27285) reported that superoxide produced from hypoxanthine plus xanthine oxidase in combination with nitric oxide produced from spermine NONOate did not nitrate tyrosine at neutral pH. They suggested that nitric oxide and superoxide at neutral pH form a less reactive intermediate distinct from preformed alkaline peroxynitrite that does not nitrate tyrosine. Using a stopped-flow spectrophotometer to rapidly mix potassium superoxide with nitric oxide at pH 7.4, we report that an intermediate spectrally and kinetically identical to preformed alkaline cis-peroxynitrite was formed in 100% yield. Furthermore, this intermediate nitrated tyrosine in the same yield and at the same rate as preformed peroxynitrite. Equivalent concentrations of nitric oxide under aerobic conditions in the absence of superoxide did not produce detectable concentrations of nitrotyrosine. Carbon dioxide increased the efficiency of nitration by nitric oxide plus superoxide to the same extent as peroxynitrite. In experiments using xanthine oxidase as a source of superoxide, tyrosine nitration was substantially inhibited by urate formed from hypoxanthine oxidation, which was sufficient to account for the lack of tyrosine nitration previously reported. We conclude that peroxynitrite formed from the reaction of nitric oxide with superoxide at physiological pH remains an important species responsible for tyrosine nitration in vivo. PMID:10906340

  4. Nitric Oxide and Peroxynitrite in Health and Disease

    PubMed Central

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

    2008-01-01

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

  5. Endotoxin-induced mortality in rats is reduced by nitrones

    SciTech Connect

    Hamburger, S.A.; McCay, P.B. )

    1989-12-01

    The goal of these investigations was to determine if nitrone spin-trapping agents can alter mortality associated with endotoxemia in the rat. Reactive free radicals attack nitrone spin-trapping agents forming relatively reactive, persistent free radical spin adducts. We administered 85 mM (10 ml/kg) of alpha-phenyl N-tert-butyl nitrone (PBN), alpha-4-pyridyl-N-oxide N-tert-butyl nitrone (4-POBN), 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), or vehicle (saline i.p.) 30 min before endotoxin (25 mg/kg i.p.) or vehicle to Sprague-Dawley (SD) or Holtzman virus-free (HVF) rats (n = 10-17/group). All vehicle-treated rats receiving endotoxin were dead by 1 day. At 7 days, 83% of PBN-treated SD, 42% of PBN- or POBN-treated HVF, and 25% of DMPO-treated HVF rats were alive. The difference in survival of PBN-treated animals between strains may reflect the higher susceptibility of HVF rats to endotoxin. The observed reduction in mortality may be related to the well-established capacity of spin-trapping agents to capture reactive free radicals that may be generated in target tissues in response to endotoxin, and that would otherwise react with cell components and produce tissue injury.

  6. Nitric oxide synthase and NADPH-diaphorase after acute hypobaric hypoxia in the rat caudate putamen.

    PubMed

    Encinas, Juan Manuel; Fernández, Ana Patricia; Salas, Eduardo; Castro-Blanco, Susana; Muñoz, Priscila; Rodrigo, José; Serrano, Julia

    2004-03-01

    Changes in the production system of nitric oxide (NO), a multifunctional biological messenger known to participate in blood-flow regulation, neuromodulation, and neuroprotection or neurotoxicity, were investigated in the caudate putamen of adult rats submitted to hypobaric hypoxia. Employing immunohistochemistry, Western blotting, enzymatic assay, and NADPH-diaphorase staining, we demonstrate that neuronal nitric oxide synthase (nNOS) expression and constitutive nitric oxide synthase (cNOS) activity were transiently activated by 7 h of exposure to a simulated altitude of 8325 m (27,000 ft). In addition, endothelial nitric oxide synthase (eNOS) immunoreactivity and blood vessel NADPH-diaphorase staining peaked immediately after the hypoxic stimulus, whereas inducible nitric oxide synthase (iNOS) expression and activity remained unaltered. Nitrotyrosine formation, a marker of protein nitration, was evaluated by immunohistochemistry and Western blotting, and was found to increase parallel to nitric oxide synthesis. We conclude that the nitric oxide system undergoes significant transient alterations in the caudate putamen of adult rats submitted to acute hypobaric hypoxia.

  7. Indium Tin Oxide Resistor-Based Nitric Oxide Microsensors

    NASA Technical Reports Server (NTRS)

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

    2012-01-01

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

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

    SciTech Connect

    M.V. D'yakov; A.I. Kozlov; E.S. Lukin

    2004-03-15

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

  9. Increasing nitric oxide content in Arabidopsis thaliana by expressing rat neuronal nitric oxide synthase resulted in enhanced stress tolerance.

    PubMed

    Shi, Hai-Tao; Li, Rong-Jun; Cai, Wei; Liu, Wen; Wang, Chao-Lun; Lu, Ying-Tang

    2012-02-01

    Nitric oxide (NO) plays essential roles in many physiological and developmental processes in plants, including biotic and abiotic stresses, which have adverse effects on agricultural production. However, due to the lack of findings regarding nitric oxide synthase (NOS), many difficulties arise in investigating the physiological roles of NO in vivo and thus its utilization for genetic engineering. Here, to explore the possibility of manipulating the endogenous NO level, rat neuronal NOS (nNOS) was expressed in Arabidopsis thaliana. The 35S::nNOS plants showed higher NOS activity and accumulation of NO using the fluorescent probe 3-amino, 4-aminomethyl-2', 7'-difluorescein, diacetate (DAF-FM DA) assay and the hemoglobin assay. Compared with the wild type, the 35S::nNOS plants displayed improved salt and drought tolerance, which was further confirmed by changes in physiological parameters including reduced water loss rate, reduced stomatal aperture, and altered proline and malondialdehyde content. Quantitative real-time PCR analyses revealed that the expression of several stress-regulated genes was up-regulated in the transgenic lines. Furthermore, the transgenic lines also showed enhanced disease resistance against Pseudomonas syringae pv. tomato (Pst) DC3000 by activating the expression of defense-related genes. In addition, we found that the 35S::nNOS lines flowered late by regulating the expression of CO, FLC and LFY genes. Together, these results demonstrated that it is a useful strategy to exploit the roles of plant NO in various processes by the expression of rat nNOS. The approach may also be useful for genetic engineering of crops with increased environmental adaptations. PMID:22186181

  10. The production of nitric oxide by marine ammonia-oxidizing archaea and inhibition of archaeal ammonia oxidation by a nitric oxide scavenger.

    PubMed

    Martens-Habbena, Willm; Qin, Wei; Horak, Rachel E A; Urakawa, Hidetoshi; Schauer, Andrew J; Moffett, James W; Armbrust, E Virginia; Ingalls, Anitra E; Devol, Allan H; Stahl, David A

    2015-07-01

    Nitrification is a critical process for the balance of reduced and oxidized nitrogen pools in nature, linking mineralization to the nitrogen loss processes of denitrification and anammox. Recent studies indicate a significant contribution of ammonia-oxidizing archaea (AOA) to nitrification. However, quantification of the relative contributions of AOA and ammonia-oxidizing bacteria (AOB) to in situ ammonia oxidation remains challenging. We show here the production of nitric oxide (NO) by Nitrosopumilus maritimus SCM1. Activity of SCM1 was always associated with the release of NO with quasi-steady state concentrations between 0.05 and 0.08 μM. NO production and metabolic activity were inhibited by the nitrogen free radical scavenger 2-phenyl-4,4,5,5,-tetramethylimidazoline-1-oxyl-3-oxide (PTIO). Comparison of marine and terrestrial AOB strains with SCM1 and the recently isolated marine AOA strain HCA1 demonstrated a differential sensitivity of AOB and AOA to PTIO and allylthiourea (ATU). Similar to the investigated AOA strains, bulk water column nitrification at coastal and open ocean sites with sub-micromolar ammonia/ammonium concentrations was inhibited by PTIO and insensitive to ATU. These experiments support predictions from kinetic, molecular and biogeochemical studies, indicating that marine nitrification at low ammonia/ammonium concentrations is largely driven by archaea and suggest an important role of NO in the archaeal metabolism.

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

    Gow, Andrew J.

    2006-01-01

    The chemical properties of nitric oxide (NO) have been studied for over 200 years. However, it is only within the last 20 years that the biological implications of this chemistry have been considered. The classical model of NO action within the vasculature centers on production in the endothelium, diffusion to the smooth muscle, and subsequent activation of guanylate cyclase via binding to its heme iron. In the context of this model, it is difficult to conceptualize extrapulmonary effects of inhaled NO. However, NO possesses complex redox chemistry and is capable of forming a range of nitrogen oxide species and is therefore capable of interacting with a variety of biomolecules. Of particular interest is its reaction with reduced cysteine to form an S-nitrosothiol (SNO). SNOs are formed throughout NO biology and are a post-translational modification that has been shown to regulate many proteins under physiologic conditions. Hemoglobin, which was considered to be solely a consumer of NO, can form SNO in a conformationally dependent manner, which allows for the transport of inhaled NO beyond the realm of the lung. Higher oxides of nitrogen are capable of modifying proteins via nitration of tyrosines, which has been shown to occur under pathologic conditions. By virtue of its redox reactivity, one can appreciate that inhaled NO has a variety of routes by which it can act and that these routes may lead to extrapulmonary effects. PMID:16565423

  13. A hypothesis about cellular signaling with nitric oxide in the earliest life forms in evolution.

    PubMed

    Murad, Ferid; Barber, Roger

    2009-11-01

    We propose that nitric oxide participated as an extracellular and intracellular messenger in the early evolution of life. From a toxic and noxious substance it evolved into an important material for cellular communication and regulation with unique chemistry and properties. The presence of some nitric oxide complexes in extraterrestrial samples may support evidence for life forms in the past or present. Although nitric oxide probably participated in the evolution and maintenance of life, if pollution continues at an ever-increasing rate, it could also end life on the planet as we know it today.

  14. The role of soda lime during administration of inhaled nitric oxide.

    PubMed

    Pickett, J A; Moors, A H; Latimer, R D; Mahmood, N; Ghosh, S; Oduro, A

    1994-06-01

    We have studied the ability of three commercially available preparations of soda lime to act as nitrogen dioxide scavengers during administration of inhaled nitric oxide. Soda lime, with a green to brown colour change (indicator = potassium permanganate), markedly reduced concentrations of nitrogen dioxide, but also markedly reduced inhaled concentrations of nitric oxide. The other varieties of soda lime, with colour changes from pink to white (indicator = kenazol yellow) or white to violet (indicator = ethyl violet), produced little effect on concentrations of nitrogen dioxide. None of the above soda limes can be recommended for use as a nitrogen dioxide scavenger during administration of inhaled nitric oxide.

  15. Diurnal and seasonal effects in E region low-latitude nitric oxide

    NASA Technical Reports Server (NTRS)

    Stewart, A. I.; Cravens, T. E.

    1978-01-01

    Measurements of nitric oxide in the lower E region made by the ultraviolet nitric oxide experiment on Atmosphere Explorer C during 1974 are used to demonstrate diurnal and seasonal effects at low latitudes. At the equator, NO increases by about a factor of 2 between sunrise and the early afternoon: this is followed by a small decline toward sunset. Seasonally, NO shows an asymmetry about the equator with more NO on the summer side than on the winter side; at equinox the asymmetry vanishes. These effects are in qualitative accord with the current theoretical understanding of thermospheric nitric oxide.

  16. Nitric oxide-releasing NSAIDs: a novel class of GI-sparing anti-inflammatory drugs.

    PubMed

    Wallace, J L; Pittman, Q J; Cirino, G

    1995-01-01

    The addition of a nitric oxide-releasing moiety to a number of common nonsteroidal anti-inflammatory drugs markedly reduces their toxicity in the gastrointestinal tract without interfering with their ability to inhibit prostaglandin synthesis. Moreover, the anti-inflammatory and anti-pyretic activities of the nitric-oxide releasing NSAID were comparable to the parent compound, while the anti-thrombotic activity in vivo was significantly enhanced. Nitric oxide-releasing NSAIDs may represent an alternative to existing anti-inflammatory, anti-pyretic and anti-thrombotic agents with greatly reduced toxicity in the gastrointestinal tract. PMID:7610982

  17. Nitric oxide formation from hydroxylamine by myoglobin and hydrogen peroxide.

    PubMed

    Taira, J; Misík, V; Riesz, P

    1997-10-20

    Hydroxylamine (HA), which is a natural product of mammalian cells, has been shown to possess vasodilatory properties in several model systems. In this study, HA and methyl-substituted hydroxylamines, N-methylhydroxylamine (NMHA) and N,N-dimethylhydroxylamine (NDMHA), have been tested for their ability to generate free diffusible nitric oxide (NO) in the presence of myoglobin (Mb) and hydrogen peroxide. A NO-specific conversion of 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO) to 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl (carboxy-PTI), measured by electron spin resonance (ESR) spectroscopy, along with nitrite and nitrate production, was observed for HA but not for NMHA and NDMHA. ESR measurements at 77 K showed the formation of the ferrous nitrosyl myoglobin, Mb-NO, in the reaction mixtures containing Mb, H2O2 and HA. Our data also demonstrate that Mb-NO is an end product of the reaction pathway involving Mb, H2O2 and HA, rather than a reaction intermediate in the formation of NO. In summary, our results demonstrate a possible pathway of NO formation from HA, however, the significance of this mechanism for bioactivation of HA in vivo is unknown at the present time.

  18. Endothelial cell expression of haemoglobin α regulates nitric oxide signalling.

    PubMed

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

    2012-11-15

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

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

    NASA Technical Reports Server (NTRS)

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

    1982-01-01

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

  20. Modeling toxic compounds from nitric oxide emission measurements

    NASA Astrophysics Data System (ADS)

    Vallero, Daniel A.; Peirce, Jeffrey; Cho, Ki Don

    Determining the amount and rate of degradation of toxic pollutants in soil and groundwater is difficult and often requires invasive techniques, such as deploying extensive monitoring well networks. Even with these networks, degradation rates across entire systems cannot readily be extrapolated from the samples. When organic compounds are degraded by microbes, especially nitrifying bacteria, oxides or nitrogen (NO x) are released to the atmosphere. Thus, the flux of nitric oxide (NO) from the soil to the lower troposphere can be used to predict the rate at which organic compounds are degraded. By characterizing and applying biogenic and anthropogenic processes in soils the rates of degradation of organic compounds. Toluene was selected as a representative of toxic aromatic compounds, since it is inherently toxic, it is a substituted benzene compound and is listed as a hazardous air pollutant under Section 12 of the Clean Air Act Amendments of 1990. Measured toluene concentrations in soil, microbial population growth and NO fluxes in chamber studies were used to develop and parameterize a numerical model based on carbon and nitrogen cycling. These measurements, in turn, were used as indicators of bioremediation of air toxic (i.e. toluene) concentrations. The model found that chemical concentration, soil microbial abundance, and NO production can be directly related to the experimental results (significant at P < 0.01) for all toluene concentrations tested. This indicates that the model may prove useful in monitoring and predicting the fate of toxic aromatic contaminants in a complex soil system. It may also be useful in predicting the release of ozone precursors, such as changes in reservoirs of hydrocarbons and oxides of nitrogen. As such, the model may be a tool for decision makers in ozone non-attainment areas.

  1. Production and Consumption of Nitric Oxide by Three Methanotrophic Bacteria

    PubMed Central

    Ren, Tie; Roy, Réal; Knowles, Roger

    2000-01-01

    We studied nitrogen oxide production and consumption by methanotrophs Methylobacter luteus (group I), Methylosinus trichosporium OB3b (group II), and an isolate from a hardwood swamp soil, here identified by 16S ribosomal DNA sequencing as Methylobacter sp. strain T20 (group I). All could consume nitric oxide (nitrogen monoxide, NO), and produce small amounts of nitrous oxide (N2O). Only Methylobacter strain T20 produced large amounts of NO (>250 parts per million by volume [ppmv] in the headspace) at specific activities of up to 2.0 × 10−17 mol of NO cell−1 day−1, mostly after a culture became O2 limited. Production of NO by strain T20 occurred mostly in nitrate-containing medium under anaerobic or nearly anaerobic conditions, was inhibited by chlorate, tungstate, and O2, and required CH4. Denitrification (methanol-supported N2O production from nitrate in the presence of acetylene) could not be detected and thus did not appear to be involved in the production of NO. Furthermore, cd1 and Cu nitrite reductases, NO reductase, and N2O reductase could not be detected by PCR amplification of the nirS, nirK, norB, and nosZ genes, respectively. M. luteus and M. trichosporium produced some NO in ammonium-containing medium under aerobic conditions, likely as a result of methanotrophic nitrification and chemical decomposition of nitrite. For Methylobacter strain T20, arginine did not stimulate NO production under aerobiosis, suggesting that NO synthase was not involved. We conclude that strain T20 causes assimilatory reduction of nitrate to nitrite, which then decomposes chemically to NO. The production of NO by methanotrophs such as Methylobacter strain T20 could be of ecological significance in habitats near aerobic-anaerobic interfaces where fluctuating O2 and nitrate availability occur. PMID:10966405

  2. Superoxide fluxes limit nitric oxide-induced signaling.

    PubMed

    Thomas, Douglas D; Ridnour, Lisa A; Espey, Michael Graham; Donzelli, Sonia; Ambs, Stefan; Hussain, S Perwez; Harris, Curtis C; DeGraff, William; Roberts, David D; Mitchell, James B; Wink, David A

    2006-09-01

    Independently, superoxide (O2-) and nitric oxide (NO) are biologically important signaling molecules. When co-generated, these radicals react rapidly to form powerful oxidizing and nitrating intermediates. Although this reaction was once thought to be solely cytotoxic, herein we demonstrate using MCF7, macrophage, and endothelial cells that when nanomolar levels of NO and O2- were produced concomitantly, the effective NO concentration was established by the relative fluxes of these two radicals. Differential regulation of sGC, pERK, HIF-1alpha, and p53 were used as biological dosimeters for NO concentration. Introduction of intracellular- or extracellular-generated O2- during NO generation resulted in a concomitant increase in oxidative intermediates with a decrease in steady-state NO concentrations and a proportional reduction in the levels of sGC, ERK, HIF-1alpha, and p53 regulation. NO responses were restored by addition of SOD. The intermediates formed from the reactions of NO with O2- were non-toxic, did not form 3-nitrotyrosine, nor did they elicit any signal transduction responses. H2O2 in bolus or generated from the dismutation of O2- by SOD, was cytotoxic at high concentrations and activated p53 independent of NO. This effect was completely inhibited by catalase, suppressed by NO, and exacerbated by intracellular catalase inhibition. We conclude that the reaction of O2- with NO is an important regulatory mechanism, which modulates signaling pathways by limiting steady-state levels of NO and preventing H2O2 formation from O2-.

  3. 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

  4. Two isofunctional nitric oxide reductases in Alcaligenes eutrophus H16.

    PubMed Central

    Cramm, R; Siddiqui, R A; Friedrich, B

    1997-01-01

    Two genes, norB and norZ, encoding two independent nitric oxide reductases have been identified in Alcaligenes eutrophus H16. norB and norZ predict polypeptides of 84.5 kDa with amino acid sequence identity of 90%. While norB resides on the megaplasmid pHG1, the norZ gene is located on a chromosomal DNA fragment. Amino acid sequence analysis suggests that norB and norZ encode integral membrane proteins composed of 14 membrane-spanning helices. The region encompassing helices 3 to 14 shows similarity to the NorB subunit of common bacterial nitric oxide reductases, including the positions of six strictly conserved histidine residues. Unlike the Nor enzymes characterized so far from denitrifying bacteria, NorB and NorZ of A. eutrophus contain an amino-terminal extension which may form two additional helices connected by a hydrophilic loop of 203 amino acids. The presence of a NorB/NorZ-like protein was predicted from the genome sequence of the cyanobacterium Synechocystis sp. strain PCC6803. While the common NorB of denitrifying bacteria is associated with a second cytochrome c subunit, encoded by the neighboring gene norC, the nor loci of A. eutrophus and Synechocystis lack adjacent norC homologs. The physiological roles of norB and norZ in A. eutrophus were investigated with mutants disrupted in the two genes. Mutants bearing single-site deletions in norB or norZ were affected neither in aerobic nor in anaerobic growth with nitrate or nitrite as the terminal electron acceptor. Inactivation of both norB and norZ was lethal to the cells under anaerobic growth conditions. Anaerobic growth was restored in the double mutant by introducing either norB or norZ on a broad-host-range plasmid. These results show that the norB and norZ gene products are isofunctional and instrumental in denitrification. PMID:9352929

  5. Association of expired nitric oxide with occupational particulate exposure.

    PubMed Central

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

    2003-01-01

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

  6. Modulation of adenovirus-mediated gene transfer by nitric oxide.

    PubMed

    Haddad, I Y; Sorscher, E J; Garver, R I; Hong, J; Tzeng, E; Matalon, S

    1997-05-01

    We assessed the role of .NO in recombinant adenovirus-mediated gene transfer both in vitro and in vivo. NIH3T3 fibroblasts, stably transfected with the human inducible nitric oxide synthase, but lacking tetrahydrobiopterin (NIH3T3/iNOS [inducibile nitric oxide synthase]), were infected with replication-deficient adenovirus (E1-deleted), containing either the luciferase or the Lac Z reporter genes (AdCMV-Luc and AdCMV-Lac Z; 1-10 plaque forming units [pfu]/cell). Incubation of infected cells with sepiapterin (50 microM), a precursor of tetrahydrobiopterin, progressively increased nitrate/nitrite levels in the medium and decreased both luciferase and beta-galactosidase protein expression to approximately 60% of their corresponding control values, 24 h later. NIH3T3/iNOS cells had normal ATP (adenosine 5'-triphosphate) levels and did not release LDH(lactic dehydrogenase) into the medium. Pretreatment of these cells with N(G)-monomethyl-L-arginine (L-NMMA; 1 mM), an inhibitor of iNOS, prevented the sepiapterin-mediated induction of .NO and restored gene transfer to baseline values. Incubation of NIH3T3/iNOS with 8-bromo-cGMP (400 microM) in the absence of sepiapterin, or exposure of AdCMV-Luc to large concentrations of .NO, did not alter the efficacy of gene transfer. .NO produced by NIH3T3/iNOS cells also suppressed beta-galactosidase expression in NIH3T3 cocultured cells stably transfected with beta-galactosidase gene, suggesting .NO inhibited gene expression at either the transriptional or posttranscriptional levels. To investigate the effects of inhaled .NO on gene transfer in vivo, CD1 mice received an intratracheal instillation of AdCMV-Luc (4 x 10(9) pfu in 80 microl of saline) and exposed to .NO (25 ppm in room air) for 72 h. At that time, no significant degree of lung inflammation was detected by histological examination. However, lung luciferase activity decreased by 53% as compared with air breathing controls (P < 0.05; n > or = 8). We concluded that

  7. The biogenic emission potential of nitric oxide from sandy soils

    NASA Astrophysics Data System (ADS)

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

    2009-04-01

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

  8. Nitric oxide and thiol redox regulation of Janus kinase activity

    PubMed Central

    Duhé, Roy J.; Evans, Gerald A.; Erwin, Rebecca A.; Kirken, Robert A.; Cox, George W.; Farrar, William L.

    1998-01-01

    The activation of Janus kinases (JAKs) is crucial for propagation of the proliferative response initiated by many cytokines. The proliferation of various cell lines, particularly those of hematopoietic origin, is also modulated by mediators of oxidative stress such as nitric oxide and thiol redox reagents. Herein we demonstrate that nitric oxide and other thiol oxidants can inhibit the autokinase activity of rat JAK2 in vitro, presumably through oxidation of crucial dithiols to disulfides within JAK2. The reduced form of JAK2 is the most active form, and the oxidized JAK2 form is inactive. Nitric oxide pretreatment of quiescent Ba/F3 cells also inhibits the interleukin 3-triggered in vivo activation of JAK2, a phenomenon that correlates with inhibited proliferation. Furthermore, we observed that the autokinase activity of JAK3 responds in a similar fashion to thiol redox reagents in vitro and to nitric oxide donors in vivo. We suggest that the thiol redox regulation of JAKs may partially explain the generally immunosuppressive effects of nitric oxide and of other thiol oxidants. PMID:9419340

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

    NASA Astrophysics Data System (ADS)

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

    2010-01-01

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

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

    PubMed Central

    Sanchez–Padilla, J.; Guzman, J.N.; Ilijic, E.; Kondapalli, J.; Galtieri, D.J.; Yang, B.; Schieber, S.; Oertel, W.; Wokosin, D.; Schumacker, P. T.; Surmeier, D. J.

    2014-01-01

    Summary Loss of noradrenergic locus coeruleus (LC) neurons is a prominent feature of aging–related neurodegenerative diseases, like Parkinson’s disease (PD). The basis of this vulnerability is not understood. To explore possible physiological determinants, LC neurons were studied using electrophysiological and optical approaches in ex vivo mouse brain slices. These studies revealed that autonomous activity in LC neurons was accompanied by oscillations in dendritic Ca2+ concentration attributable to opening of L–type Ca2+ channels. This oscillation elevated mitochondrial oxidant stress and was attenuated by inhibition of nitric oxide synthase. The relationship between activity and stress was malleable, as arousal and carbon dioxide, each increased the spike rate, but differentially affected mitochondrial oxidant stress. Oxidant stress also was increased in an animal model of PD. Thus, our results point to activity–dependent Ca2+ entry and a resulting mitochondrial oxidant stress as factors contributing to the vulnerability of LC neurons. PMID:24816140

  11. Contribution of complement-stimulated hepatic macrophages and neutrophils to endotoxin-induced liver injury in rats.

    PubMed

    Jaeschke, H; Farhood, A; Smith, C W

    1994-04-01

    The role of complement as potential activator for tissue macrophages and neutrophils was investigated in an experimental model of endotoxin-induced liver injury in male Fischer rats. Injection of Salmonella enteritidis endotoxin (1 mg/kg) into Corynebacterium parvum-pretreated animals (7 mg/kg; single dose 6 days before endotoxin) resulted in severe oxidant stress, as indicated by a 37-fold increase of plasma levels of glutathione disulfide (basal concentration, 0.36 +/- 14 mumol/L), accumulation of neutrophils in the liver (600 +/- 31 neutrophils/50 high-power fields) and liver injury (plasma ALT, 1184 +/- 185 U/l; necrosis; 19% +/- 3%) 10 hr after endotoxin. The oxidant stress induced by 1 mg/kg endotoxin in the C. parvum-treated animals was always significantly higher than that in control animals receiving the same dose of endotoxin. Inhibition of complement activation with the soluble complement receptor type 1 attenuated the oxidant stress and liver injury by 50% to 65% but had no effect on hepatic neutrophil accumulation or plasma tumor necrosis factor-alpha levels. Treatment with a monoclonal antibody directed against the alpha-chain of CD11b/CD18 adhesion proteins (clone 17), which was highly effective in attenuating ischemia-reperfusion injury in the liver by reducing the number of neutrophils and functionally inactivating these cells, neither protected against parenchymal cell injury nor affected hepatic neutrophil infiltration in the C. parvum model. We conclude that reactive oxygen derived from complement-stimulated macrophages is critical for the development of liver injury in the C. parvum/endotoxin model. PMID:8138272

  12. Nitric Oxide Plasma Sources for Bio-Decontamination and Plasma Therapy

    NASA Astrophysics Data System (ADS)

    Vasilets, Victor N.; Shekhter, Anatoly B.

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

  13. Advanced glycosylation products quench nitric oxide and mediate defective endothelium-dependent vasodilatation in experimental diabetes.

    PubMed Central

    Bucala, R; Tracey, K J; Cerami, A

    1991-01-01

    Nitric oxide (an endothelium-derived relaxing factor) induces smooth muscle relaxation and is an important mediator in the regulation of vascular tone. Advanced glycosylation end products, the glucose-derived moieties that form nonenzymatically and accumulate on long-lived tissue proteins, have been implicated in many of the complications of diabetes and normal aging. We demonstrate that advanced glycosylation products quench nitric oxide activity in vitro and in vivo. Acceleration of the advanced glycosylation process in vivo results in a time-dependent impairment in endothelium-dependent relaxation. Inhibition of advanced glycosylation with aminoguanidine prevents nitric oxide quenching, and ameliorates the vasodilatory impairment. These results implicate advanced glycosylation products as important modulators of nitric oxide activity and endothelium-dependent relaxation. PMID:1991829

  14. The effect of nitric oxide on the growth of marine phytoplankton

    NASA Astrophysics Data System (ADS)

    Zhengbin, Zhang; Cai, Lin; Chunying, Liu; Mingyi, Sun; Haibing, Ding

    2003-10-01

    The incubation experiments of Skeletonema costatum, Dicrateria zhanjiangensis nov. sp., and Platymonas subcordiformis, and those of Emiliania huxleyi were carried out in the Marine Physical Chemistry Laboratory in Ocean University of China and in the Marine Organic Geochemistry Laboratory in the University of Georgia respectively. Nitric oxide was added into the media when these marine microalgae were growing. We found the growth of these four microalgae were promoted or inhibited when nitric oxide of different concentrations was added one or two times each day during the cultivation process. The results are consistent with the influence of nitric oxide on the growth of high plants. The results show that nitric oxide may be a new factor of regulation and control for the phytoplankton growth in seawater.

  15. Centrally produced nitric oxide and the regulation of body fluid and blood pressure homeostases.

    PubMed

    Kadekaro, M; Summy-Long, J Y

    2000-01-01

    1. Nitric oxide (NO) tonically inhibits the basal release of vasopressin and oxytocin into plasma. 2. Nitric oxide inhibition on vasopressin secretion is removed, while that on oxytocin is enhanced, during water deprivation, hypovolaemia, moderate osmotic stimulation and angiotensin (Ang)II. This results in a preferential release of vasopressin over oxytocin that promotes conservation of water. 3. Nitric oxide facilitates drinking behaviour stimulated by water deprivation, osmotic stimulation, haemorrhage and AngII. Together with the hormonal response, NO produces a positive water balance during reductions in intracellular and intravascular volumes. 4. Nitric oxide produced within the central nervous system maintains resting arterial blood pressure partially by attenuating the pressor actions of AngII and prostaglandins. 5. Central production of NO is enhanced during osmotic stimulation to counterbalance the salt-induced pressor response. 6. Paradoxically, central production of NO is also enhanced during haemorrhage, presumably to maintain peripheral vasodilation and blood flow to vital organs.

  16. What is nitric oxide and why are so many people studying it?

    PubMed

    Gibaldi, M

    1993-06-01

    From social outcast to citizen of the year in less than a decade is the stuff of fiction. That is precisely what has happened, however, to a remarkably simple molecule, nitric oxide. Nitric oxide is still an environmental pollutant, suspected carcinogen, and precursor of acid rain, but biologists are looking past its dark side. They now see a molecule that is uniting neuroscience, physiology, and immunology. Its ubiquitous distribution in the body and its multifaceted roles are revising our understanding of how cells communicate and protect themselves. This report examines nitric oxide's role in physiology and pathophysiology and reviews novel therapeutic approaches which involve inhibition or induction of the activity of endogenous nitric oxide.

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

    SciTech Connect

    Bredt, D.S.; Snyder, S.H. )

    1989-11-01

    Nitric oxide, which mediates influences of numerous neurotransmitters and modulators on vascular smooth muscle and leukocytes, can be formed in the brain from arginine by an enzymatic activity that stoichiometrically generates citrulline. The authors show that glutamate and related amino acids, such as N-methyl-D-aspartate, markedly stimulate arginine-citrulline transformation in cerebellar slices stoichiometrically with enhancement of cGMP levels. N{sup {omega}}-monomethyl-L-arginine blocks the augmentation both of citrulline and cGMP with identical potencies. Arginine competitively reverses both effects of N{sup {omega}}-monomethyl-L-arginine with the same potencies. Hemoglobin, which complexes nitric oxide, prevents the stimulation by N-methyl-D-aspartate of cGMP levels, and superoxide dismutase, which elevates nitric oxide levels, increases cGMP formation. These data establish that nitric oxide mediates the stimulation by glutamate of cGMP formation.

  18. EXAMINING THE TEMPORAL VARIABILITY OF AMMONIA AND NITRIC OXIDE EMISSIONS FROM AGRICULTURAL PROCESSES

    EPA Science Inventory

    This paper examines the temporal variability of airborne emissions of ammonia from livestock operations and fertilizer application and nitric oxide from soils. In the United States, the livestock operations and fertilizer categories comprise the majority of the ammonia emissions...

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

    PubMed Central

    2012-01-01

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

  20. Nitric Oxide Mediates Glutamate-Linked Enhancement of cGMP Levels in the Cerebellum

    NASA Astrophysics Data System (ADS)

    Bredt, David S.; Snyder, Solomon H.

    1989-11-01

    Nitric oxide, which mediates influences of numerous neurotransmitters and modulators on vascular smooth muscle and leukocytes, can be formed in the brain from arginine by an enzymatic activity that stoichiometrically generates citrulline. We show that glutamate and related amino acids, such as N-methyl-D-aspartate, markedly stimulate arginine-citrulline transformation in cerebellar slices stoichiometrically with enhancement of cGMP levels. Nω-monomethyl-L-arginine blocks the augmentation both of citrulline and cGMP with identical potencies. Arginine competitively reverses both effects of Nω-monomethyl-L-arginine with the same potencies. Hemoglobin, which complexes nitric oxide, prevents the stimulation by N-methyl-D-aspartate of cGMP levels, and superoxide dismutase, which elevates nitric oxide levels, increases cGMP formation. These data establish that nitric oxide mediates the stimulation by glutamate of cGMP formation.

  1. Biological role of nitric oxide: history, modern state, and perspectives for research.

    PubMed

    Vanin, A F

    1998-07-01

    This paper is an introduction to this issue of review papers on the biological role of nitric oxide. The history, modern state, and promising directions for research in this field are briefly considered. PMID:9721326

  2. Nitric Oxide Measurement from Purified Enzymes and Estimation of Scavenging Activity by Gas Phase Chemiluminescence Method.

    PubMed

    Kumari, Aprajita; Gupta, Alok Kumar; Mishra, Sonal; Wany, Aakanksha; Gupta, Kapuganti Jagadis

    2016-01-01

    In plants, nitrate reductase (NR) is a key enzyme that produces nitric oxide (NO) using nitrite as a substrate. Lower plants such as algae are shown to have nitric oxide synthase enzyme and higher plants contain NOS activity but enzyme responsible for NO production in higher plants is subjected to debate. In plant nitric oxide research, it is very important to measure NO very precisely in order to determine its functional role. A significant amount of NO is being scavenged by various cell components. The net NO production depends in production minus scavenging. Here, we describe methods to measure NO from purified NR and inducible nitric oxide synthase from mouse (iNOS), we also describe a method of measure NO scavenging by tobacco cell suspensions and mitochondria from roots. PMID:27094408

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

    PubMed

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

    1994-04-28

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

  4. Nitric oxide releasing plasma polymer coating with bacteriostatic properties and no cytotoxic side effects.

    PubMed

    Michl, Thomas D; Coad, Bryan R; Doran, Michael; Osiecki, Michael; Kafshgari, Morteza Hasanzadeh; Voelcker, Nicolas H; Hüsler, Amanda; Vasilev, Krasimir; Griesser, Hans J

    2015-04-25

    We report a stable plasma polymer coating, using isopentyl nitrite as a volatile precursor, which releases nitric oxide at bacteriostatic concentrations when contacted with water, inhibiting bacterial growth without cytotoxic side effects to human mesenchymal stem/stromal cells.

  5. Vanillic acid prevents the deregulation of lipid metabolism, endothelin 1 and up regulation of endothelial nitric oxide synthase in nitric oxide deficient hypertensive rats.

    PubMed

    Kumar, Subramanian; Prahalathan, Pichavaram; Saravanakumar, Murugesan; Raja, Boobalan

    2014-11-15

    Hypertension is one of the main factors causing cardiovascular diseases. The present study was designed to evaluate the protective effect of vanillic acid against nitric oxide deficient rats. Hypertension was induced in adult male albino rats of Wistar strain, weighing 180-220g, by oral administration of N(ω)-nitro-l arginine methyl ester (l-NAME) 40mg/kg in drinking water for 4 weeks. Vanillic acid was administered orally at a dose of 50mg/kg b.w. Nitric oxide deficient rats showed increased levels of mean arterial pressure (MAP), heart rate (HR) and decreased heart nitric oxide metabolites (NOx). A significant increase in the levels of plasma cholesterol, low density lipoprotein-cholesterol (LDL-C), very low density lipoprotein-cholesterol (VLDL-C), triglycerides (TG), free fatty acids (FFA), phospholipids (PL), 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase in the plasma, liver and kidney and decreased level of high density lipoprotein-cholesterol (HDL-C) are observed, whereas there is a decrease in the activities of plasma lipoprotein lipase (LPL) and lecithin cholesterol acyl transferase (LCAT) in nitric oxide deficient rats. l-NAME rats also showed an increase in TC, TG, FFA and PL levels in the liver and kidney tissues. Vanillic acid treatment brought the above parameters towards near normal level. Moreover the down regulated endothelial nitric oxide synthase (eNOS) and up regulated expression of endothelin 1 (ET1) components was also attenuated by vanillic acid treatment. All the above outcomes were confirmed by the histopathological examination. These results suggest that vanillic acid has enough potential to attenuate hypertension, dyslipidemia and hepatic and renal damage in nitric oxide deficient rats. PMID:25239071

  6. Human very low density lipoproteins and chylomicrons can protect against endotoxin-induced death in mice.

    PubMed Central

    Harris, H W; Grunfeld, C; Feingold, K R; Rapp, J H

    1990-01-01

    Endotoxemia stimulates many physiologic responses including disturbances in lipid metabolism. We hypothesized that this lipemia may be part of a defensive mechanism by which the body combats the toxic effects of circulating endotoxin. We tested the effects of mixtures of endotoxin, lipoproteins, and lipoprotein-free plasma and determined the ability of varying concentrations of human very low density lipoproteins (VLDL) and chylomicrons, as well as low density lipoproteins (LDL) and high density lipoproteins (HDL), and of the synthetic lipid emulsion SOYACAL to prevent endotoxin-induced death in mice. This study demonstrates that the triglyceride-rich VLDL and chylomicrons, as well as cholesterol-rich LDL and HDL, and cholesterol-free SOYACAL can protect against endotoxin-induced death. Protection required small amounts of lipoprotein-free plasma, and depended on the incubation time and the concentration of lipoprotein lipid. Despite stringent techniques to prevent exogenous endotoxin contamination eight of ten duplicate VLDL preparations contained endotoxin (5,755 +/- 3,514 ng endotoxin/mg triglyceride, mean +/- SEM) making the isolation of endotoxin-free VLDL difficult. In contrast, simultaneous preparations of LDL and HDL were relatively free of endotoxin contamination (3 +/- 3 and 320 +/- 319 ng/mg total cholesterol, respectively), suggesting that the contamination of VLDL occurs in vivo and not during the isolation procedure. These observations suggest a possible role for increased triglyceride-rich lipoproteins in the host's defense against endotoxemia and infection. Images PMID:2394827

  7. Dynamics of Antagonistic Potency of Rhodobacter capsulatus PG Lipopolysaccharide against Endotoxin-Induced Effects.

    PubMed

    Kabanov, D S; Serov, D A; Zubova, S V; Grachev, S V; Prokhorenko, I R

    2016-03-01

    The dynamics of antagonistic potency of lipopolysaccharide (LPS) isolated from Rhodobacter capsulatus PG on the synthesis of proinflammatory (TNF-α, IL-1β, IL-8, IL-6, IFN-γ) and antiinflammatory (IL-10, IL-1Ra) cytokines induced by highly stimulatory endotoxins from Escherichia coli or Salmonella enterica have been studied. Using human whole blood, we have shown that R. capsulatus PG LPS inhibited most pronouncedly the endotoxin-induced synthesis of TNF-α, IL-1β, IL-8, and IL-6 during the first 6 h after endotoxin challenge. Similarly, the endotoxin-induced release of IFN-γ was abolished by R. capsulatus PG LPS as well (24 h). In contrast to the above-mentioned cytokines, the relatively weak antagonistic activity of R. capsulatus PG LPS against endotoxin-triggered production of IL-6 and IL-8 was revealed. Since R. capsulatus PG LPS displays more potent antagonistic activity against deleterious effects of S. enterica LPS than those of E. coli LPS in the cases of such cytokines as IL-1β (6 and 24 h), IL-6 and IL-8 (4 h), we conclude that the effectiveness of protective action of antagonist is mostly determined by the primary lipid A structure of the employed agonist.

  8. Aspirin, but Not Tirofiban Displays Protective Effects in Endotoxin Induced Lung Injury

    PubMed Central

    Gombert, Alexander; Jacobs, Michael J.; Drechsler, Maik; Döring, Yvonne; Soehnlein, Oliver; Grommes, Jochen

    2016-01-01

    Background Treatment of acute lung injury (ALI) remains an unsolved problem in intensive care medicine. Recruitment of neutrophils into the lungs, regarded as a key mechanism in progression of ALI, depends on signaling between neutrophils and platelets. Consequently we explored the effect of platelet-targeted aspirin and tirofiban treatment in endotoxin induced acute lung injury Methods C57Bl/6 mice were exposed to aerosolized LPS (500μg/ml) for 30min and treated with Aspirin (100μg/g bodyweight via intraperitoneal injection, 30 min before or 1 hour after LPS inhalation) or Tirofiban (0.5μg/ g bodyweight via tail vein injection 30 min before or 1 hour after LPS inhalation). The count of alveolar, interstitial, and intravascular neutrophils was assessed 4h later by flow cytometry. Lung permeability changes were assessed by FITC-dextran clearance and protein content in the BAL fluid. Results Aspirin both before and after LPS inhalation reduced neutrophil influx into the lung and lung permeability indicating the protective role of Aspirin in ALI. Tirofiban, however, did not alter neutrophil recruitment after LPS inhalation. Release of platelet-derived chemokines CCL5 and PF4 and neutrophil extracellular traps was reduced by Aspirin but not by Tirofiban. Conclusion Aspirin, but not Tirofiban reduces neutrophil recruitment and displays protective effects during endotoxin induced lung injury. PMID:27583400

  9. Reduced graphene oxide electrically contacted graphene sensor for highly sensitive nitric oxide detection.

    PubMed

    Li, Weiwei; Geng, Xiumei; Guo, Yufen; Rong, Jizan; Gong, Youpin; Wu, Liqiong; Zhang, Xuemin; Li, Peng; Xu, Jianbao; Cheng, Guosheng; Sun, Mengtao; Liu, Liwei

    2011-09-27

    We develop graphene-based devices fabricated by alternating current dielectrophoresis (ac-DEP) for highly sensitive nitric oxide (NO) gas detection. The novel device comprises the sensitive channels of palladium-decorated reduced graphene oxide (Pd-RGO) and the electrodes covered with chemical vapor deposition (CVD)-grown graphene. The highly sensitive, recoverable, and reliable detection of NO gas ranging from 2 to 420 ppb with response time of several hundred seconds has been achieved at room temperature. The facile and scalable route for high performance suggests a promising application of graphene devices toward the human exhaled NO and environmental pollutant detections. PMID:21834585

  10. Mercury Exposure and Endothelial Dysfunction: An Interplay Between Nitric Oxide and Oxidative Stress.

    PubMed

    Omanwar, Swati; Fahim, M

    2015-01-01

    Vascular endothelium plays a vital role in the organization and function of the blood vessel and maintains homeostasis of the circulatory system and normal arterial function. Functional disruption of the endothelium is recognized as the beginning event that triggers the development of consequent cardiovascular disease (CVD) including atherosclerosis and coronary heart disease. There is a growing data associating mercury exposure with endothelial dysfunction and higher risk of CVD. This review explores and evaluates the impact of mercury exposure on CVD and endothelial function, highlighting the interplay of nitric oxide and oxidative stress.

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

    NASA Technical Reports Server (NTRS)

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

    1988-01-01

    Recent measurements indicate significantly enhanced biogenic soil emissions of both nitric oxide (NO) and nitrous oxide (N2O) following surface burning. These enhanced fluxes persisted for at least six months following the burn. Simultaneous measurements indicate enhanced levels of exchangeable ammonium in the soil following the burn. Biomass burning is known to be an instantaneous source of NO and N2O resulting from high-temperature combustion. Now it is found that biomass burning also results in significantly enhanced biogenic emissions of these gases, which persist for months following the burn.

  12. Role of nitric oxide and mechanisms involved in cerebral injury after subarachnoid hemorrhage: is nitric oxide a possible answer to cerebral vasospasm?

    PubMed

    Crobeddu, Emanuela; Pilloni, Giulia; Tardivo, Valentina; Fontanella, Marco M; Panciani, Pier P; Spena, Giannantonio; Fornaro, Riccardo; Altieri, Roberto; Agnoletti, Alessandro; Ajello, Marco; Zenga, Francesco; Ducati, Alessandro; Garbossa, Diego

    2016-09-01

    Cerebral vasospasm represents the most critical event that could occur after subarachnoid hemorrhage (SAH). Therapy is only partially effective because cerebral arterial constriction is not fully understood yet. One of the most important biological messenger associated to SAH is nitric oxide (NO), that is considered local regulator of cerebral blood flow. Different nitric oxide synthase (NOS) forms play a role in different biological processes, one of which is to link neuronal activity to blood flow in cerebral cortex. We performed a reassessment of the literature to summarize the role of NO as the main inflammatory pathway activated after SAH to clarify its importance for treatment of vasospasm.

  13. Nitric oxide synthase inhibitors in post-myocardial infarction cardiogenic shock--an update.

    PubMed

    Kaluski, Edo; Hendler, Alberto; Blatt, Alex; Uriel, Nir

    2006-11-01

    Cardiogenic shock (CS) in acute myocardial infarction, after successful coronary angioplasty, still carries a case fatality rate of 50%. These patients succumb to a systemic metabolic storm, superimposed on extensive myocardial necrosis and stunning. Nitric oxide (NO) overproduction contributes to the pathophysiology of this morbid state. Current data regarding the physiologic effects of NO and nitric oxide synthase (NOS) inhibitors on the cardiovascular system are reviewed. Clinical trials assessing the safety and efficacy of NOS inhibitors in CS are summarized.

  14. Cloned and expressed nitric oxide synthase structurally resembles cytochrome P-450 reductase

    NASA Astrophysics Data System (ADS)

    Bredt, David S.; Hwang, Paul M.; Glatt, Charles E.; Lowenstein, Charles; Reed, Randall R.; Snyder, Solomon H.

    1991-06-01

    Nitric oxide is a messenger molecule, mediating the effect of endothelium-derived relaxing factor in blood vessels and the cytotoxic actions of macrophages, and playing a part in neuronal communication in the brain. Cloning of a complementary DNA for brain nitric oxide synthase reveals recognition sites for NADPH, FAD, flavin mononucleotide and calmodulin as well as phosphorylation sites, indicating that the synthase is regulated by many different factors. The only known mammalian enzyme with close homology is cytochrome P-450 reductase.

  15. Evaluation of Salivary Nitric Oxide Levels in Smokers, Tobacco Chewers and Patients with Oral Lichenoid Reactions

    PubMed Central

    Jose, Joy Idiculla; Sivapathasundharam, B.; Sabarinath, B.

    2016-01-01

    Introduction Nitric oxide (NO), a free radical, acts as a signalling molecule affecting numerous physiological and pathological processes. Role of nitric oxide as a mediator in tobacco related habits and the resultant oral lichenoid reactions was assessed. Aim The aim of the study is to evaluate and compare the salivary nitric oxide levels in normal patients with that of smokers, tobacco chewers and patients with oral lichenoid reactions. Materials and Methods One hundred and twenty patients were enrolled in the study which included 30 healthy patients without any chronic inflammatory lesion and habit as controls (group I), 30 smokers without the habit of tobacco/betel nut chewing and any oral lesion (group II), 30 tobacco chewers without the habit of smoking and any oral lesion (group III) and 30 histologically confirmed cases of oral lichenoid reaction with the habit of tobacco usage (group IV). Saliva from these patients was collected and the nitrite concentration was assessed. Results Our results concluded that there was highly significant increase in the nitric oxide levels in smokers, tobacco chewers and patients with oral lichenoid reactions compared to that of controls. Also, there was a significant increase in nitric oxide levels in patients with smoking associated oral lichenoid reactions in comparison with smokers and in patients with lichenoid reactions associated with tobacco chewing in comparison with tobacco chewers. Conclusion Estimation of salivary nitric oxide levels is a simple, non-invasive procedure and could be analysed to suggest the role of nitric oxide in the pathogenesis of these lesions. The increased activity of the enzyme may indicate that nitric oxide has a pathophysiological role in these lesions. PMID:26894179

  16. Role of nitric oxide and lipid peroxidation in mechanisms of febrile convulsions in Wistar rat pups.

    PubMed

    Klyueva, Y A; Bashkatova, V G; Vitskova, G Y; Narkevich, V B; Mikoyan, V D; Vanin, A F; Chepurnov, S A; Chepurnova, N E

    2001-01-01

    Generation of nitric oxide and the content of lipid peroxidation products in the brain are increased in rat pups during febrile convulsions. NO-synthase inhibitor N-nitro-L-arginine in a dose of 250 mg/kg prevented hyperthermia-induced accumulation of nitric oxide, increased the latency febrile convulsions, and had no effect on the content of lipid peroxidation products. PMID:11329081

  17. The reaction of hydrogen peroxide with nitrogen dioxide and nitric oxide.

    NASA Technical Reports Server (NTRS)

    Gray, D.; Lissi, E.; Heicklen, J.

    1972-01-01

    The reactions were studied with the aid of a mass spectrometer. A pinhole bleed system provided continuous sampling of the gas mixture in the cell during the reaction. It was found that the homogeneous reactions of nitric oxide and nitrogen dioxide with hydrogen peroxide are too slow to be of any significance in the upper atmosphere. However, the heterogeneous reactions may be important in the conversion of nitric oxide to nitrogen dioxide in the case of polluted urban atmospheres.

  18. Measurement of nitric oxide in human exhaled breath

    SciTech Connect

    Gordon, S.M.; Spicer, C.W.; Ollison, W.M.

    1997-12-31

    This project was initiated to confirm the reliability of nitric oxide (NO) measurement in the breath matrix, using two different analytical techniques - ozone and luminol chemiluminescence - and to corroborate literature reports of elevated breath NO values. To measure peak oral and nasal NO levels, subjects performed slow vital capacity and breath holding maneuvers directly into the monitors through the mouth and the nose, respectively. Additional measurements were made using normal breathing techniques. Initial interferent tests indicate that measured NO signals are real and are not confounded by measurement artifacts. Similar results were obtained using the two independent analytical methods in dry or humid air. The NO signal was unaffected by maximum concentrations of potential breath interferents, such as sulfur compounds and alkenes. The measured breath NO concentrations were greater than typical room air levels and differed significantly with the breathing technique used. During these tests room air averaged 4-5 ppb NO. Peak oral NO levels were 4.3 {+-} 1.5 ppb during a slow vital capacity maneuver and 8.0 {+-} 5.0 ppb during a breath holding maneuver. By contrast, higher peak nasal NO levels were measured for both slow vital capacity (17.8 {+-} 7.8 ppb) and breath holding maneuvers (45.4 {+-} 29.5 ppb).

  19. Vascular system: role of nitric oxide in cardiovascular diseases.

    PubMed

    Bian, Ka; Doursout, Marie-Françoise; Murad, Ferid

    2008-04-01

    In contrast with the short research history of the enzymatic synthesis of nitric oxide (NO), the introduction of nitrate-containing compounds for medicinal purposes marked its 150th anniversary in 1997. Glyceryl trinitrate (nitroglycerin) is the first compound of this category. On October 12, 1998, the Nobel Assembly awarded the Nobel Prize in Medicine or Physiology to scientists Robert Furchgott, Louis Ignarro, and Ferid Murad for their discoveries concerning NO as a signaling molecule in the cardiovascular system. NO-mediated signaling is a recognized component in various physiologic processes (eg, smooth muscle relaxation, inhibition of platelet and leukocyte aggregation, attenuation of vascular smooth muscle cell proliferation, neurotransmission, and immune defense), to name only a few. NO has also been implicated in the pathology of many inflammatory diseases, including arthritis, myocarditis, colitis, and nephritis and a large number of pathologic conditions such as amyotrophic lateral sclerosis, cancer, diabetes, and neurodegenerative diseases. Some of these processes (eg, smooth muscle relaxation, platelet aggregation, and neurotransmission) require only a brief production of NO at low nanomolar concentrations and are dependent on the recruitment of cyclic guanosine monophosphate (cGMP)-dependent signaling. Other processes are associated with direct interaction of NO or reactive nitrogen species derived from it with target proteins and requires a more sustained production of NO at higher concentrations but do not involve the cGMP pathway.

  20. Nitric oxide and cyclic guanosine monophosphate signaling in the eye.

    PubMed

    Murad, Ferid

    2008-06-01

    This brief review describes the components and pathways utilized in nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) signaling. Since the discovery of the effects of NO and cGMP on smooth muscle relaxation about 30 years ago, the field has expanded in many directions such that many, but not all, biochemical and biological effects seem to be regulated by these unique signaling molecules. While many of the effects of NO are due to activation of soluble guanylyl cyclase (sGC) that can be considered the receptor for NO, cGMP, in turn, can activate a cGMP-dependent protein kinase (PKG) to phosphorylate an array of proteins. Some of the effects of cGMP can be independent of PKG and are due to effects on ion channels or cyclic nucleotide phosphodiesterases. Also, some of the effects of NO can be independent of sGC activation. The isoenzymes and macromolecules that participate in these signaling pathways can serve as molecular targets to identify compounds that increase or decrease their activation and thus serve as chemical leads for discovering novel drugs for a variety of diseases. Some examples are given. However, with about 90,000 publications in the field since our first reports in 1977, this brief review can only give the readers a sample of the excitement and opportunities we have found in this cell signaling system.

  1. Nasal nitric oxide in children with recurrent acute otitis media.

    PubMed

    Torretta, S; Marchisio, P; Capaccio, P; Pignataro, L

    2016-01-01

    Recently, reduced Nasal nitric oxide (nNO) nNO levels have been reported in children with adenoidal hypertrophy predisposing to chronic nasosinusal inflammation. Given the strict anatomic and physiopathologic link between the nasopharyngeal and middle ear compartments, and considering the high prevalence of otitis prone children among those affected with chronic adenoiditis, we designed a study aimed to test any possible difference in nNO levels between non-allergic children with and without recurrent acute otitis media (RAOM) associated with chronic adenoiditis. The study involved 54 children with RAOM (44.4% males; mean age= 7.5±3.5 years) and 51 children without RAOM (47.4% males; mean age= 7.0±3.8 years). nNO levels were significantly reduced in children with RAOM compared to children without RAOM (676.9±250.7 ppb vs 831.8±320.4 ppb, respectively; p= 0.02). Our results could be related to reduced NO production by the ciliated paranasal, nasopharyngeal and middle ear epithelium and the impaired sinusal ostial and Eustachian tube patency due to chronic inflammation, and seem to confirm the involvement of NO pathway in recurrent upper airway infections related to impaired ciliated respiratory mucosa.

  2. Nitric oxide selectively tunes inhibitory synapses to modulate vertebrate locomotion.

    PubMed

    McLean, David L; Sillar, Keith T

    2002-05-15

    We have explored the possible modulation by nitric oxide (NO) of inhibitory synaptic transmission mediated by either glycine or GABA during episodes of rhythmic fictive swimming in postembryonic Xenopus laevis tadpoles. Extracellular ventral-root recordings suggest a stage-dependent increase in the reliability and extent of the NO donor S-nitroso-n-acetylpenicillamine (SNAP; 0.1-1 mm) to inhibit swimming by reducing the frequency and shortening the duration of swim episodes. These effects of SNAP on the swimming rhythm at both developmental stages are corroborated by intracellular recordings from presumed motor neurons with sharp microelectrodes, which also suggest that NO inhibits swimming by facilitating both glycinergic and GABAergic inhibition. However, we found no evidence for NO modulation of the excitatory drive for swimming. In addition to presynaptic effects on inhibitory transmitter release, a pronounced postsynaptic membrane depolarization ( approximately 5-10 mV) and conductance decrease ( approximately 10-20%) are associated with bath application of SNAP. Hence, NO exerts inhibitory effects on swimming through multiple but selective actions on both the electrical properties of spinal neurons and on particular synaptic interconnections. The presynaptic and postsynaptic effects of NO act in concert to tune inhibitory synapses.

  3. Nitric oxide and its role in ischaemic brain injury.

    PubMed

    Keynes, Robert G; Garthwaite, John

    2004-03-01

    The role of the neural messenger nitric oxide (NO) in cerebral ischaemia has been investigated extensively in the past decade. NO may play either a protective or destructive role in ischaemia and the literature is plagued with contradictory findings. Working with NO presents many unique difficulties and here we review the potential artifacts that may have contributed to discrepancies and cause future problems for the unwary investigator. Recent evidence challenges the idea that NO from neurones builds up to levels (micromolar) sufficient to directly elicit cell death during the post-ischaemic period. Concomitantly, the case is strengthened for a role of NO in delayed death mediated post-ischaemia by the inducible NO synthase. Mechanistically it seems unlikely that NO is released in high enough quantities to inhibit respiration in vivo; the formation of reactive nitrogen species, such as peroxynitrite, represents the more likely pathway to cell death. The protective and restorative properties of NO have become of increasing interest. NO from endothelial cells may, via stimulating cGMP production, protect the ischaemic brain by acutely augmenting blood flow, and by helping to form new blood vessels in the longer term (angiogenesis). Elevated cGMP production may also stop cells dying by inhibiting apoptosis and help repair damage by stimulating neurogenesis. In addition NO may act as a direct antioxidant and participate in the triggering of protective gene expression programmes that underlie cerebral ischaemic preconditioning. Better understanding of the molecular mechanisms by which NO is protective may ultimately identify new potential therapeutic targets.

  4. 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.

  5. Nitric oxide removal by wastewater bacteria in a biotrickling filter.

    PubMed

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

    2014-03-01

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

  6. Nitric oxide induces caspase activity in boar spermatozoa.

    PubMed

    Moran, J M; Madejón, L; Ortega Ferrusola, C; Peña, F J

    2008-07-01

    Nitric oxide (NO) is a highly reactive free radical that plays a key role in intra- and intercellular signaling. Production of radical oxygen species and an apoptotic-like phenomenon have recently been implicated in cryodamage during sperm cryopreservation. The objective of the present study was to evaluate the effect of sodium nitroprusside (SNP), an NO donor, on boar sperm viability. Semen samples were pooled from four boars that were routinely used for artificial insemination. Flow cytometry was used to compare semen incubated with SNP to control semen. Specifically, NO production was measured using the NO indicator dye diaminofluorescein diacetate, and caspase activity was determined using the permeable pan-caspase inhibitor Z-VAD linked to FITC. SNP induced a significant increase in the percentage of sperm cells showing caspase activity, from 9.3% in control samples to 76.2% in SNP-incubated samples (P<0.01). This study suggests that NO is a major free radical involved in boar sperm damage. PMID:18433854

  7. [Nitric Oxide in Modulation of Crystallogenic Propeties of Biological Fluid].

    PubMed

    Martusevich, A K; Kovaleva, L K; Davyduk, A V

    2016-01-01

    The aim of this work was a comparative analysis of the influence of different NO forms on dehydration structurization of human blood serum. Blood specimens from 15 healthy people were treated by NO-containing gas flow (800 and 80 ppm) generated with the "Plazon" unit, experimental NO-generator (20, 50, 75 and 100 ppm) and by water solution of thiol-containing dinitrosyl iron complexes (3 mM/L). The influence of blood sodium on blood serum crystallization in original and NO-treated blood specimens was estimated. It was found, that the effect of NO on crystallogenic properties of blood serum depends directly on its concentration and form (free or bound), as well as on the presence of reactive oxygen species in gas flow. The most pronounced stimulating effect was observed for the bound form of NO--dinitrosyl iron complexes with glutathione ligands. Low NO concentrations modulated crystallogenic properties of blood serum and the most optimal stimulating action was demonstrated in gas flow containing 20 ppm nitric oxide. In contrast, high NO concentration (800 ppm) inhibited the crystallogenic activity of biological fluid with multiply increasing of structural elements destruction leading to the formation of an additional belt in marginal zone of dehydrated specimens.

  8. Response to nitric oxide in term and preterm infants.

    PubMed

    Laubscher, B; Greenough, A; Kavvadia, V; Devane, S P

    1997-08-01

    The response to three levels (10 ppm, 20 ppm and 40 ppm) of nitric oxide (NO) was assessed in 30 infants, median gestational age 30 (range 24-42) weeks. All the infants required an inspired oxygen concentration of more than 0.5, despite receiving surfactant where appropriate. All but one infant had a positive response to NO (median reduction in the oxygenation index (OI) was 33%, range -9%-90%), but only 20 infants showed a greater than 20% reduction in the OI. There was no obvious relationship of the optimum NO level (i.e. that associated with the maximum reduction in OI) and either diagnosis (congenital diaphragmatic hernia, meconium aspiration syndrome, respiratory distress syndrome, pulmonary interstitial emphysema (PIE), hydrops and sepsis) or maturity, except that five of six infants with PIE responded best to 40 ppm, as did eight of nine infants less than 28 weeks gestational age. We conclude NO dosage should be individualized and NO levels up to 40 ppm should be considered in very immature infants.

  9. A Novel Protocol for Detection of Nitric Oxide in Plants.

    PubMed

    Jain, Prachi; David, Anisha; Bhatla, Satish C

    2016-01-01

    Detection of nitric oxide (NO) in plant cells is mostly undertaken using diaminofluorescein (DAF) dyes. Serious drawbacks and limitations have been identified in methods using DAF as a probe for NO detection. The present work reporting an alternative fluorescent probe for NO detection is thus proposed for varied applications in plant systems for physiological investigations. This method involves a simple, two-step synthesis, characterization, and application of MNIP-Cu {Copper derivative of [4-methoxy-2-(1H-napthol[2,3-d]imidazol-2-yl)phenol]} for specific and rapid binding with NO, leading to its detection in plant cells by epifluorescence microscopy and confocal laser scanning microscopy (CLSM). Using sunflower (Helianthus annuus L.) whole seedlings, hypocotyl segments, stigmas from capitulum, protoplasts, and isolated oil bodies, present investigations demonstrate the versatile nature of MNIP-Cu in applications for NO localization studies. MNIP-Cu can detect NO in vivo without any time lag (ex. 330-385 nm; em. 420-500 nm). It exhibits fluorescence both under anoxic and oxygen-rich conditions. This probe is specific to NO, which enhances its fluorescence due to MNIP-Cu complexing with NO and treatment with PTIO leads to quenching of fluorescence. It is relatively nontoxic when used at a concentration of up to 50 μM. PMID:27094412

  10. Partitioned Exhaled Nitric Oxide to Non-Invasively Assess Asthma

    PubMed Central

    Puckett, James L.; George, Steven C.

    2008-01-01

    Asthma is a chronic inflammatory disease of the lungs, characterized by airway hyperresponsiveness. Chronic repetitive bouts of acute inflammation lead to airway wall remodeling and possibly the sequelae of fixed airflow obstruction. Nitric oxide (NO) is a reactive molecule synthesized by NO synthases (NOS). NOS are expressed by cells within the airway wall and functionally, two NOS isoforms exist: constitutive and inducible. In asthma, the inducible isoform is over expressed, leading to increased production of NO, which diffuses into the airway lumen, where it can be detected in the exhaled breath. The exhaled NO signal can be partitioned into airway and alveolar components by measuring exhaled NO at multiple flows and applying mathematical models of pulmonary NO dynamics. The airway NO flux and alveolar NO concentration can be elevated in adults and children with asthma and have been correlated with markers of airway inflammation and airflow obstruction in cross-sectional studies. Longitudinal studies which specifically address the clinical potential of partitioning exhaled NO for diagnosis, managing therapy, and predicting exacerbation are needed. PMID:18718562

  11. Effect of Electrode Configuration on Nitric Oxide Gas Sensor Behavior.

    PubMed

    Cui, Ling; Murray, Erica P

    2015-01-01

    The influence of electrode configuration on the impedancemetric response of nitric oxide (NO) gas sensors was investigated for solid electrochemical cells [Au/yttria-stabilized zirconia (YSZ)/Au)]. Fabrication of the sensors was carried out at 1050 °C in order to establish a porous YSZ electrolyte that enabled gas diffusion. Two electrode configurations were studied where Au wire electrodes were either embedded within or wrapped around the YSZ electrolyte. The electrical response of the sensors was collected via impedance spectroscopy under various operating conditions where gas concentrations ranged from 0 to 100 ppm NO and 1%-18% O₂ at temperatures varying from 600 to 700 °C. Gas diffusion appeared to be a rate-limiting mechanism in sensors where the electrode configuration resulted in longer diffusion pathways. The temperature dependence of the NO sensors studied was independent of the electrode configuration. Analysis of the impedance data, along with equivalent circuit modeling indicated the electrode configuration of the sensor effected gas and ionic transport pathways, capacitance behavior, and NO sensitivity. PMID:26404312

  12. GAPDH regulates cellular heme insertion into inducible nitric oxide synthase

    PubMed Central

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

    2010-01-01

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

  13. A motif for reversible nitric oxide interactions in metalloenzymes.

    PubMed

    Zhang, Shiyu; Melzer, Marie M; Sen, S Nermin; Çelebi-Ölçüm, Nihan; Warren, Timothy H

    2016-07-01

    Nitric oxide (NO) participates in numerous biological processes, such as signalling in the respiratory system and vasodilation in the cardiovascular system. Many metal-mediated processes involve direct reaction of NO to form a metal-nitrosyl (M-NO), as occurs at the Fe(2+) centres of soluble guanylate cyclase or cytochrome c oxidase. However, some copper electron-transfer proteins that bear a type 1 Cu site (His2Cu-Cys) reversibly bind NO by an unknown motif. Here, we use model complexes of type 1 Cu sites based on tris(pyrazolyl)borate copper thiolates [Cu(II)]-SR to unravel the factors involved in NO reactivity. Addition of NO provides the fully characterized S-nitrosothiol adduct [Cu(I)](κ(1)-N(O)SR), which reversibly loses NO on purging with an inert gas. Computational analysis outlines a low-barrier pathway for the capture and release of NO. These findings suggest a new motif for reversible binding of NO at bioinorganic metal centres that can interconvert NO and RSNO molecular signals at copper sites. PMID:27325092

  14. Nitric oxide transport and storage in the cardiovascular system.

    PubMed

    Muller, Bernard; Kleschyov, Andrei L; Alencar, Jacicarlos L; Vanin, Anatoly; Stoclet, Jean-Claude

    2002-05-01

    Despite short halflife in biological fluids, nitric oxide (NO) can produce remote or long lasting effect in the cardiovascular system. Long distance transport or local storage of NO might explain these effects. In blood, recent findings suggest that in addition to being a major consumption pathway, interaction of NO with hemoglobin may permit O(2)-governed transport of NO (as S-nitrosohemoglobin) to tissues in which NO may be released together with O(2), via transnitrosation of a transport protein. In blood vessels, two different putative NO stores have been characterized. The first is the photosensitive store, formed from endothelium-derived NO. The mechanism of NO release from this store in the body (in absence of light) and its physiological relevance are unknown. The second store is generated in conditions of high tissue NO levels, as a consequence of the inducible NO synthase activity or in various stress conditions. This NO store involves formation of protein-bound dinitrosyl iron complexes or S-nitrosated proteins, or both. Low molecular weight thiols can displace NO from these stores and probably transfer it to target membrane protein(s) such as K(+) channels, via transnitrosation reactions. These stores may be involved in defence mechanisms against inflammation or stress. Thus, NO transport and storage mechanisms may be implicated in a variety of NO effects. The mechanisms of their formation and of NO release and their physiologic and pathophysiologic relevance deserve further investigations.

  15. Disruption of Fas Receptor Signaling by Nitric Oxide in Eosinophils

    PubMed Central

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

    1998-01-01

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

  16. Starved Escherichia coli preserve reducing power under nitric oxide stress.

    PubMed

    Gowers, Glen-Oliver F; Robinson, Jonathan L; Brynildsen, Mark P

    2016-07-15

    Nitric oxide (NO) detoxification enzymes, such as NO dioxygenase (NOD) and NO reductase (NOR), are important to the virulence of numerous bacteria. Pathogens use these defense systems to ward off immune-generated NO, and they do so in environments that contain additional stressors, such as reactive oxygen species, nutrient deprivation, and acid stress. NOD and NOR both use reducing equivalents to metabolically deactivate NO, which suggests that nutrient deprivation could negatively impact their functionality. To explore the relationship between NO detoxification and nutrient deprivation, we examined the ability of Escherichia coli to detoxify NO under different levels of carbon source availability in aerobic cultures. We observed failure of NO detoxification under both carbon source limitation and starvation, and those failures could have arisen from inabilities to synthesize Hmp (NOD of E. coli) and/or supply it with sufficient NADH (preferred electron donor). We found that when limited quantities of carbon source were provided, NO detoxification failed due to insufficient NADH, whereas starvation prevented Hmp synthesis, which enabled cells to maintain their NADH levels. This maintenance of NADH levels under starvation was confirmed to be dependent on the absence of Hmp. Intriguingly, these data show that under NO stress, carbon-starved E. coli are better positioned with regard to reducing power to cope with other stresses than cells that had consumed an exhaustible amount of carbon. PMID:27207837

  17. REGULATION OF NITRIC OXIDE PRODUCTION IN HEALTH AND DISEASE

    PubMed Central

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

    2010-01-01

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

  18. Structure-based design of bacterial nitric oxide synthase inhibitors.

    PubMed

    Holden, Jeffrey K; Kang, Soosung; Hollingsworth, Scott A; Li, Huiying; Lim, Nathan; Chen, Steven; Huang, He; Xue, Fengtian; Tang, Wei; Silverman, Richard B; Poulos, Thomas L

    2015-01-22

    Inhibition of bacterial nitric oxide synthase (bNOS) has the potential to improve the efficacy of antimicrobials used to treat infections by Gram-positive pathogens Staphylococcus aureus and Bacillus anthracis. However, inhibitor specificity toward bNOS over the mammalian NOS (mNOS) isoforms remains a challenge because of the near identical NOS active sites. One key structural difference between the NOS isoforms is the amino acid composition of the pterin cofactor binding site that is adjacent to the NOS active site. Previously, we demonstrated that a NOS inhibitor targeting both the active and pterin sites was potent and functioned as an antimicrobial ( Holden , , Proc. Natl. Acad. Sci. U.S.A. 2013 , 110 , 18127 ). Here we present additional crystal structures, binding analyses, and bacterial killing studies of inhibitors that target both the active and pterin sites of a bNOS and function as antimicrobials. Together, these data provide a framework for continued development of bNOS inhibitors, as each molecule represents an excellent chemical scaffold for the design of isoform selective bNOS inhibitors.

  19. Protein kinase D activity controls endothelial nitric oxide synthesis.

    PubMed

    Aicart-Ramos, Clara; Sánchez-Ruiloba, Lucía; Gómez-Parrizas, Mónica; Zaragoza, Carlos; Iglesias, Teresa; Rodríguez-Crespo, Ignacio

    2014-08-01

    Vascular endothelial growth factor (VEGF) regulates key functions of the endothelium, such as angiogenesis or vessel repair in processes involving endothelial nitric oxide synthase (eNOS) activation. One of the effector kinases that become activated in endothelial cells upon VEGF treatment is protein kinase D (PKD). Here, we show that PKD phosphorylates eNOS, leading to its activation and a concomitant increase in NO synthesis. Using mass spectrometry, we show that the purified active kinase specifically phosphorylates recombinant eNOS on Ser1179. Treatment of endothelial cells with VEGF or phorbol 12,13-dibutyrate (PDBu) activates PKD and increases eNOS Ser1179 phosphorylation. In addition, pharmacological inhibition of PKD and gene silencing of both PKD1 and PKD2 abrogate VEGF signaling, resulting in a clear diminished migration of endothelial cells in a wound healing assay. Finally, inhibition of PKD in mice results in an almost complete disappearance of the VEGF-induced vasodilatation, as monitored through determination of the diameter of the carotid artery. Hence, our data indicate that PKD is a new regulatory kinase of eNOS in endothelial cells whose activity orchestrates mammalian vascular tone. PMID:24928905

  20. Effect of Electrode Configuration on Nitric Oxide Gas Sensor Behavior

    PubMed Central

    Cui, Ling; Murray, Erica P.

    2015-01-01

    The influence of electrode configuration on the impedancemetric response of nitric oxide (NO) gas sensors was investigated for solid electrochemical cells [Au/yttria-stabilized zirconia (YSZ)/Au)]. Fabrication of the sensors was carried out at 1050 °C in order to establish a porous YSZ electrolyte that enabled gas diffusion. Two electrode configurations were studied where Au wire electrodes were either embedded within or wrapped around the YSZ electrolyte. The electrical response of the sensors was collected via impedance spectroscopy under various operating conditions where gas concentrations ranged from 0 to 100 ppm NO and 1%–18% O2 at temperatures varying from 600 to 700 °C. Gas diffusion appeared to be a rate-limiting mechanism in sensors where the electrode configuration resulted in longer diffusion pathways. The temperature dependence of the NO sensors studied was independent of the electrode configuration. Analysis of the impedance data, along with equivalent circuit modeling indicated the electrode configuration of the sensor effected gas and ionic transport pathways, capacitance behavior, and NO sensitivity. PMID:26404312

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

    PubMed Central

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

    2009-01-01

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

  2. Combination of complex adsorption and anammox for nitric oxide removal.

    PubMed

    Wang, Xiaojing; Xu, Xiaochen; Liu, Sitong; Zhang, Yun; Zhao, Chuanqi; Yang, Fenglin

    2016-07-15

    High-efficiency Fe(II)EDTA (approximately 80%) was selected to remove nitric oxide (NO) in a complex adsorption process; subsequently, this Fe(II)EDTA was combined with the anammox process to eliminate the NO in flue gas. The Fe(II)EDTA-NO solution negatively affected the conventional nitrite-dependent anammox bacteria when the solution concentration exceeded 0.5mM. Fe(II)EDTA-NO-cultivated anammox bacteria removed the ammonium coupled to complex NO reduction (≤3.5mM). The batch test results demonstrated that NH4(+) was eliminated through Fe(II)EDTA-NO reduction via anammox. The removal of complex NO and NH4(+) exhibited high relativity relevance, and the Fe(II)EDTA-NO/NH4(+) molar ratio was approximately 0.97. The complex NO-dependent process generates lesser nitrate than that generated by conventional anammox. Moreover, Candidatus Kuenenia stuttgartiensitiensis became the dominant anammox bacterial community when the biomass is cultivated using the inoculated bacteria, and the proportion of the former increased to 90% from the initial 38% for ribosomal intergenic spacer analysis and library construction. PMID:27037471

  3. The message of nitric oxide in cadmium challenged plants.

    PubMed

    Arasimowicz-Jelonek, Magdalena; Floryszak-Wieczorek, Jolanta; Gwóźdź, Edward A

    2011-11-01

    During the last decade it has been found that cadmium (Cd), one of the most toxic elements occurring in polluted environments, interferes with nitric oxide (NO), a multifunctional signaling molecule in living organisms. The formation of NO has been demonstrated in vivo in various plant tissues exposed to Cd stress, but unfortunately, the time and intensity of NO generation, relatively frequently shows conflicting data. What is more, there is still limited information regarding the functional role of endogenously produced NO in plants challenged with heavy metals. The first pharmacological approaches revealed that exogenously applied NO can alleviate cadmium toxicity in plants, promoting the direct scavenging of reactive oxygen species (ROS) or activating antioxidant enzymes. However, recent reports have indicated that NO even contributes to Cd toxicity by promoting Cd uptake and participates in metal-induced reduction of root growth. In view of this heterogeneous knowledge, much more puzzling if we consider results first obtained using exogenous NO sources, this review is focused mainly on the implication of endogenous NO in plant response to Cd exposure. Furthermore, a basic draft for NO mode of action during cadmium stress is proposed.

  4. Role of nitric oxide in subventricular zone neurogenesis.

    PubMed

    Matarredona, Esperanza R; Murillo-Carretero, Maribel; Moreno-López, Bernardo; Estrada, Carmen

    2005-09-01

    A possible role of nitric oxide (NO) in adult neurogenesis has been suggested based on anatomical findings showing that subventricular zone (SVZ) neuroblasts are located close to NO-producing cells, and on the known antiproliferative actions of NO in many cell types. Experiments have been performed in rodents with systemic and intracerebroventricular administrations of the NO synthase (NOS) inhibitor L-NAME. NOS inhibition leads to significant increases in the number of proliferating cells in the SVZ and olfactory bulb (OB). NO exerts its cytostatic action preferentially on the cell population expressing nestin but not betaIII-tubulin, which may correspond to the type C cells described in the SVZ. The negative effect of NO on SVZ cell proliferation has also been confirmed in SVZ primary cultures. An inhibition of the tyrosine kinase activity of the epidermal growth factor receptor (EGFR) is described as one of the molecular mechanisms responsible for the antiproliferative effect of NO in SVZ cells. Biochemical data supporting this conclusion has been obtained using the neuroblastoma cell line NB69, which endogenously expresses the EGFR. In these cells, the antimitotic action of NO occurs upon inhibition of the EGFR tyrosine phosphorylation, probably by a direct S-nitrosylation of the receptor. The latest published reports on NO and neurogenesis indicate that NO physiologically participates in the control of adult neurogenesis by modulating the proliferation and fate of the SVZ progenitor cells. These effects might be partially due to a direct inhibition of the EGFR by S-nitrosylation.

  5. Role of nitric oxide in cardiovascular adaptation to intermittent hypoxia.

    PubMed

    Manukhina, Eugenia B; Downey, H Fred; Mallet, Robert T

    2006-04-01

    Hypoxia is one of the most frequently encountered stresses in health and disease. The duration, frequency, and severity of hypoxic episodes are critical factors determining whether hypoxia is beneficial or harmful. Adaptation to intermittent hypoxia has been demonstrated to confer cardiovascular protection against more severe and sustained hypoxia, and, moreover, to protect against other stresses, including ischemia. Thus, the direct and cross protective effects of adaptation to intermittent hypoxia have been used for treatment and prevention of a variety of diseases and to increase efficiency of exercise training. Evidence is mounting that nitric oxide (NO) plays a central role in these adaptive mechanisms. NO-dependent protective mechanisms activated by intermittent hypoxia include stimulation of NO synthesis as well as restriction of NO overproduction. In addition, alternative, nonenzymic sources of NO and negative feedback of NO synthesis are important factors in optimizing NO concentrations. The adaptive enhancement of NO synthesis and/or availability activates or increases expression of other protective factors, including heat shock proteins, antioxidants and prostaglandins, making the protection more robust and sustained. Understanding the role of NO in mechanisms of adaptation to hypoxia will support development of therapies to prevent and treat hypoxic or ischemic damage to organs and cells and to increase adaptive capabilities of the organism. PMID:16565431

  6. Kinetic-dependent Killing of Oral Pathogens with Nitric Oxide

    PubMed Central

    Backlund, C.J.; Worley, B.V.; Sergesketter, A.R.

    2015-01-01

    Nitric oxide (NO)–releasing silica nanoparticles were synthesized via the co-condensation of tetramethyl orthosilicate with aminosilanes and subsequent conversion of secondary amines to N-diazeniumdiolate NO donors. A series of ~150 nm NO-releasing particles with different NO totals and release kinetics (i.e., half-lives) were achieved by altering both the identity and mol% composition of the aminosilane precursors. Independent of identical 2 h NO-release totals, enhanced antibacterial action was observed against the periodontopathogens Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis with extended NO-release kinetics at pH 7.4. Negligible bactericidal effect was observed against cariogenic Streptococcus mutans at pH 7.4, even when using NO-releasing silica particles with greater NO-release totals. However, antibacterial activity was observed against S. mutans at lower pH (6.4). This result was attributed to more rapid proton-initiated decomposition of the N-diazeniumdiolate NO donors and greater NO-release payloads. The data suggest a differential sensitivity to NO between cariogenic and periodontopathogenic bacteria with implications for the future development of NO-releasing oral care therapeutics. PMID:26078424

  7. Origin and Impact of Nitric Oxide in Pseudomonas aeruginosa Biofilms

    PubMed Central

    2015-01-01

    The formation of the organized bacterial community called biofilm is a crucial event in bacterial physiology. Given that biofilms are often refractory to antibiotics and disinfectants to which planktonic bacteria are susceptible, their formation is also an industrially and medically relevant issue. Pseudomonas aeruginosa, a well-known human pathogen causing acute and chronic infections, is considered a model organism to study biofilms. A large number of environmental cues control biofilm dynamics in bacterial cells. In particular, the dispersal of individual cells from the biofilm requires metabolic and morphological reprogramming in which the second messenger bis-(3′-5′)-cyclic dimeric GMP (c-di-GMP) plays a central role. The diatomic gas nitric oxide (NO), a well-known signaling molecule in both prokaryotes and eukaryotes, is able to induce the dispersal of P. aeruginosa and other bacterial biofilms by lowering c-di-GMP levels. In this review, we summarize the current knowledge on the molecular mechanisms connecting NO sensing to the activation of c-di-GMP-specific phosphodiesterases in P. aeruginosa, ultimately leading to c-di-GMP decrease and biofilm dispersal. PMID:26260455

  8. Nitric oxide synthase deficiency and the pathophysiology of muscular dystrophy

    PubMed Central

    Tidball, James G; Wehling-Henricks, Michelle

    2014-01-01

    The secondary loss of neuronal nitric oxide synthase (nNOS) that occurs in dystrophic muscle is the basis of numerous, complex and interacting features of the dystrophic pathology that affect not only muscle itself, but also influence the interaction of muscle with other tissues. Many mechanisms through which nNOS deficiency contributes to misregulation of muscle development, blood flow, fatigue, inflammation and fibrosis in dystrophic muscle have been identified, suggesting that normalization in NO production could greatly attenuate diverse aspects of the pathology of muscular dystrophy through multiple regulatory pathways. However, the relative importance of the loss of nNOS from the sarcolemma versus the importance of loss of total nNOS from dystrophic muscle remains unknown. Although most current evidence indicates that nNOS localization at the sarcolemma is not required to achieve NO-mediated reductions of pathology in muscular dystrophy, the question remains open concerning whether membrane localization would provide a more efficient rescue from features of the dystrophic phenotype. PMID:25194047

  9. Electrospun nitric oxide releasing bandage with enhanced wound healing.

    PubMed

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

    2015-02-01

    Research has shown that nitric oxide (NO) enhances wound healing. The incorporation of NO into polymers for medical materials and surgical devices has potential benefits for many wound healing applications. In this work, acrylonitrile (AN)-based terpolymers were electrospun to form non-woven sheets of bandage or wound dressing type materials. NO is bound to the polymer backbone via the formation of a diazeniumdiolate group. In a 14 day NO release study, the dressings released 79 μmol NO g(-1) polymer. The NO-loaded dressings were tested for NO release in vivo, which demonstrate upregulation of NO-inducible genes with dressing application compared to empty dressings. Studies were also conducted to evaluate healing progression in wounds with dressing application performed weekly and daily. In two separate studies, excisional wounds were created on the dorsa of 10 mice. Dressings with NO loaded on the fibers or empty controls were applied to the wounds and measurements of the wound area were taken at each dressing change. The data show significantly enhanced healing progression in the wounds with weekly NO application, which is more dramatic with daily application. Further, the application of daily NO bandages results in improved wound vascularity. These data demonstrate the potential for this novel NO-releasing dressing as a valid wound healing therapy. PMID:25463501

  10. Sodium nitrite: the "cure" for nitric oxide insufficiency.

    PubMed

    Parthasarathy, Deepa K; Bryan, Nathan S

    2012-11-01

    This process of "curing" food is a long practice that dates back thousands of years long before refrigeration or food safety regulations. Today food safety and mass manufacturing are dependent upon safe and effective means to cure and preserve foods including meats. Nitrite remains the most effective curing agent to prevent food spoilage and bacterial contamination. Despite decades of rigorous research on its safety and efficacy as a curing agent, it is still regarded by many as a toxic undesirable food additive. However, research within the biomedical science community has revealed enormous therapeutic benefits of nitrite that is currently being developed as novel therapies for conditions associated with nitric oxide (NO) insufficiency. Much of the same biochemistry that has been understood for decades in the meat industry has been rediscovered in human physiology. This review will highlight the fundamental biochemistry of nitrite in human physiology and highlight the risk benefit evaluation surrounding nitrite in food and meat products. Foods or diets enriched with nitrite can have profound positive health benefits.

  11. Inhibition of implant-associated infections via nitric oxide release.

    PubMed

    Nablo, Brian J; Prichard, Heather L; Butler, Renita D; Klitzman, Bruce; Schoenfisch, Mark H

    2005-12-01

    The in vivo antibacterial activity of nitric oxide (NO)-releasing xerogel coatings was evaluated against an aggressive subcutaneous Staphylococcus aureus infection in a rat model. The NO-releasing implants were created by coating a medical-grade silicone elastomer with a sol-gel-derived (xerogel) film capable of storing NO. Four of the bare or xerogel-coated silicone materials were subcutaneously implanted into male rats. Ten rats were administered 10 microl of a 10(8) cfuml(-1)S. aureus colony directly into the subcutaneous pocket with the implant prior to wound closure. Infection was quantitatively and qualitatively evaluated after 8d of implantation with microbiological and histological methods, respectively. A 82% reduction in the number of infected implants was achieved with the NO-releasing coating. Histology revealed that the capsule formation around infected bare silicone rubber controls was immunoactive and that a biofilm may have formed. Capsule formation in response to NO-releasing implants had greater vascularity in comparison with uninoculated or untreated controls. These results suggest that NO-releasing coatings may dramatically reduce the incidence of biomaterial-associated infection.

  12. Nitric Oxide (NO) Measurements in Stomatal Guard Cells.

    PubMed

    Agurla, Srinivas; Gayatri, Gunja; Raghavendra, Agepati S

    2016-01-01

    The quantitative measurement of nitric oxide (NO) in plant cells acquired great importance, in view of the multifaceted function and involvement of NO as a signal in various plant processes. Monitoring of NO in guard cells is quite simple because of the large size of guard cells and ease of observing the detached epidermis under microscope. Stomatal guard cells therefore provide an excellent model system to study the components of signal transduction. The levels and functions of NO in relation to stomatal closure can be monitored, with the help of an inverted fluorescence or confocal microscope. We can measure the NO in guard cells by using flouroprobes like 4,5-diamino fluorescein diacetate (DAF-2DA). This fluorescent dye, DAF-2DA, is cell permeable and after entry into the cell, the diacetate group is removed by the cellular esterases. The resulting DAF-2 form is membrane impermeable and reacts with NO to generate the highly fluorescent triazole (DAF-2T), with excitation and emission wavelengths of 488 and 530 nm, respectively. If time-course measurements are needed, the epidermis can be adhered to a cover-glass or glass slide and left in a small petri dishes. Fluorescence can then be monitored at required time intervals; with a precaution that excitation is done minimally, only when a fluorescent image is acquired. The present method description is for the epidermis of Arabidopsis thaliana and Pisum sativum and should work with most of the other dicotyledonous plants.

  13. Molecular dynamics simulation of nitric oxide in myoglobin

    USGS Publications Warehouse

    Lee, Myung Won; Meuwly, Markus

    2012-01-01

    The infrared (IR) spectroscopy and ligand migration of photodissociated nitric oxide (NO) in and around the active sites in myoglobin (Mb) are investigated. A distributed multipolar model for open-shell systems is developed and used, which allows one to realistically describe the charge distribution around the diatomic probe molecule. The IR spectra were computed from the trajectories for two conformational substates at various temperatures. The lines are narrow (width of 3–7 cm–1 at 20–100 K), in agreement with the experimental observations where they have widths of 4–5 cm–1 at 4 K. It is found that within one conformational substate (B or C) the splitting of the spectrum can be correctly described compared with recent experiments. Similar to photodissociated CO in Mb, additional substates exist for NO in Mb, which are separated by barriers below 1 kcal/mol. Contrary to full quantum mechanical calculations, however, the force field and mixed QM/MM simulations do not correctly describe the relative shifts between the B- and C-states relative to gas-phase NO. Free energy simulations establish that NO preferably localizes in the distal site and the barrier for migration to the neighboring Xe4 pocket is ΔGB→C = 1.7–2.0 kcal/mol. The reverse barrier is ΔGB←C = 0.7 kcal/mol, which agrees well with the experimental value of 0.7 kcal/mol, estimated from kinetic data.

  14. Nitric oxide: platelet protectant properties during cardiopulmonary bypass/ECMO.

    PubMed

    Jacobson, Julie

    2002-06-01

    Postoperative bleeding is a major complication in patients who have been placed on extracorporeal circulatory support for various cardiac procedures (1). The increase in hemorrhage is well documented and is associated with various factors, which include, high-dose systemic heparinization, thrombocytopenia, and impaired platelet function. Platelets activate when exposed to the large foreign surface of the extracorpeal circuit, with the largest area being the oxygenator. Despite adequate heparinization, platelet levels continue to decrease. This aggregation phenomenon has also been extensively studied, and it cannot be attributed to the use of aminocarproic acid, aprotinin, propofol, or amicar (2). Other factors found to be unrelated include, the brand or type of oxygenator, the use of heparin coatings (3), activated clotting time (ACT) levels while on bypass, the operative procedure, preoperative medications, or the types of anesthetic agents used (2). Therefore, it may be beneficial to add nitric oxide to the sweep gas to decrease platelet loss, platelet damage, postoperative bleeding, and lessening the need for post-operative blood transfusions.

  15. Nitric Oxide-Releasing Chitosan Oligosaccharides as Antibacterial Agents

    PubMed Central

    Lu, Yuan; Slomberg, Danielle L.; Schoenfisch, Mark H.

    2014-01-01

    Secondary amine-functionalized chitosan oligosaccharides of different molecular weights (i.e., ~2500, 5000, 10000) were synthesized by grafting 2-methyl aziridine from the primary amines on chitosan oligosaccharides, followed by reaction with nitric oxide (NO) gas under basic conditions to yield N-diazeniumdiolate NO donors. The total NO storage, maximum NO flux, and half-life of the resulting NO-releasing chitosan oligosaccharides were controlled by the molar ratio of 2-methyl aziridine to primary amines (e.g., 1:1, 2:1) and the functional group surrounding the N-diazeniumdiolates (e.g., polyethylene glycol (PEG) chains), respectively. The secondary amine-modified chitosan oligosaccharides greatly increased the NO payload over existing biodegradable macromolecular NO donors. In addition, the water-solubility of the chitosan oligosaccharides enabled their penetration across the extracellular polysaccharides matrix of Pseudomonas aeruginosa biofilms and association with embedded bacteria. The effectiveness of these chitosan oligosaccharides at biofilm eradication was shown to depend on both the molecular weight and ionic characteristics. Low molecular weight and cationic chitosan oligosaccharides exhibited rapid association with bacteria throughout the entire biofilm, leading to enhanced biofilm killing. At concentrations resulting in 5-log killing of bacteria in Pseudomonas aeruginosa biofilms, the NO-releasing and control chitosan oligosaccharides elicited no significant cytotoxicity to mouse fibroblast L929 cells in vitro. PMID:24268196

  16. Structure-Based Design of Bacterial Nitric Oxide Synthase Inhibitors

    PubMed Central

    2015-01-01

    Inhibition of bacterial nitric oxide synthase (bNOS) has the potential to improve the efficacy of antimicrobials used to treat infections by Gram-positive pathogens Staphylococcus aureus and Bacillus anthracis. However, inhibitor specificity toward bNOS over the mammalian NOS (mNOS) isoforms remains a challenge because of the near identical NOS active sites. One key structural difference between the NOS isoforms is the amino acid composition of the pterin cofactor binding site that is adjacent to the NOS active site. Previously, we demonstrated that a NOS inhibitor targeting both the active and pterin sites was potent and functioned as an antimicrobial (Holden, , Proc. Natl. Acad. Sci. U.S.A.2013, 110, 1812724145412). Here we present additional crystal structures, binding analyses, and bacterial killing studies of inhibitors that target both the active and pterin sites of a bNOS and function as antimicrobials. Together, these data provide a framework for continued development of bNOS inhibitors, as each molecule represents an excellent chemical scaffold for the design of isoform selective bNOS inhibitors. PMID:25522110

  17. Nitric oxide diffusion rate is reduced in the aortic wall.

    PubMed

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

    2008-03-01

    Endogenous nitric oxide (NO) plays important physiological roles in the body. As a small diatomic molecule, NO has been assumed to freely diffuse in tissues with a diffusion rate similar to that in water. However, this assumption has not been tested experimentally. In this study, a modified Clark-type NO electrode attached with a customized aorta holder was used to directly measure the flux of NO diffusion across the aortic wall at 37 degrees C. Experiments were carefully designed for accurate measurements of the apparent NO diffusion coefficient D and the partition coefficient alpha in the aortic wall. A mathematical model was presented for analyzing experimental data. It was determined that alpha = 1.15 +/- 0.11 and D = 848 +/- 45 mum(2)/s (n = 12). The NO diffusion coefficient in the aortic wall is nearly fourfold smaller than the reported diffusion coefficient in solution at 37 degrees C, indicating that NO diffusion in the vascular wall is no longer free, but markedly dependent on the environment in the tissue where these NO molecules are. These results imply that the NO diffusion rate in the vascular wall may be upregulated and downregulated by certain physiological and/or pathophysiological processes affecting the composition of tissues.

  18. [Nitric Oxide in Modulation of Crystallogenic Propeties of Biological Fluid].

    PubMed

    Martusevich, A K; Kovaleva, L K; Davyduk, A V

    2016-01-01

    The aim of this work was a comparative analysis of the influence of different NO forms on dehydration structurization of human blood serum. Blood specimens from 15 healthy people were treated by NO-containing gas flow (800 and 80 ppm) generated with the "Plazon" unit, experimental NO-generator (20, 50, 75 and 100 ppm) and by water solution of thiol-containing dinitrosyl iron complexes (3 mM/L). The influence of blood sodium on blood serum crystallization in original and NO-treated blood specimens was estimated. It was found, that the effect of NO on crystallogenic properties of blood serum depends directly on its concentration and form (free or bound), as well as on the presence of reactive oxygen species in gas flow. The most pronounced stimulating effect was observed for the bound form of NO--dinitrosyl iron complexes with glutathione ligands. Low NO concentrations modulated crystallogenic properties of blood serum and the most optimal stimulating action was demonstrated in gas flow containing 20 ppm nitric oxide. In contrast, high NO concentration (800 ppm) inhibited the crystallogenic activity of biological fluid with multiply increasing of structural elements destruction leading to the formation of an additional belt in marginal zone of dehydrated specimens. PMID:27192838

  19. Nitric oxide: a multitasked signaling gas in plants.

    PubMed

    Domingos, Patricia; Prado, Ana Margarida; Wong, Aloysius; Gehring, Christoph; Feijo, Jose A

    2015-04-01

    Nitric oxide (NO) is a gaseous reactive oxygen species (ROS) that has evolved as a signaling hormone in many physiological processes in animals. In plants it has been demonstrated to be a crucial regulator of development, acting as a signaling molecule present at each step of the plant life cycle. NO has also been implicated as a signal in biotic and abiotic responses of plants to the environment. Remarkably, despite this plethora of effects and functional relationships, the fundamental knowledge of NO production, sensing, and transduction in plants remains largely unknown or inadequately characterized. In this review we cover the current understanding of NO production, perception, and action in different physiological scenarios. We especially address the issues of enzymatic and chemical generation of NO in plants, NO sensing and downstream signaling, namely the putative cGMP and Ca(2+) pathways, ion-channel activity modulation, gene expression regulation, and the interface with other ROS, which can have a profound effect on both NO accumulation and function. We also focus on the importance of NO in cell-cell communication during developmental processes and sexual reproduction, namely in pollen tube guidance and embryo sac fertilization, pathogen defense, and responses to abiotic stress.

  20. Characterization of a Fluorescent Probe for Imaging Nitric Oxide

    PubMed Central

    Ghebremariam, Yohannes T; Huang, Ngan F; Kambhampati, Swetha; Volz, Katharina S; Joshi, Gururaj G; Anslyn, Eric V; Cooke, John P

    2014-01-01

    Background Nitric Oxide (NO), a potent vasodilator and anti-atherogenic molecule, is synthesized in various cell types including vascular endothelial cells (ECs). The biological importance of NO enforces the need to develop and characterize specific and sensitive probes. To date, several fluorophores, chromophores and colorimetric techniques have been developed to detect NO or its metabolites (NO2 and NO3) in biological fluids, viable cells or cell lysates. Methods Recently, a novel probe (NO550) has been developed and reported to detect NO in solution and in primary astrocytes and neuronal cells with a fluorescence signal arising from a non-fluorescent background. Results Here, we report further characterization of this probe by optimizing conditions for the detection and imaging of NO products in primary vascular endothelial cells, fibroblasts, embryonic stem cell (ESC)- and induced pluripotent stem cell (iPSC)- derived endothelial cells (ESC-ECs. and iPSC-ECs respectively) in the absence and presence of pharmacological agents that modulate NO levels. In addition, we studied the stability of this probe in cells over time and evaluated its compartmentalization in reference to organelle-labeling dyes. Finally, we synthesized an inherently fluorescent diazo ring compound (AZO550) that is expected to form when the non-fluorescent NO550 reacts with cellular NO and compared its cellular distribution with that of NO550. Conclusion NO550 is a promising agent for imaging NO at baseline and in response to pharmacological agents that modulate its levels. PMID:24335468

  1. Biosynthesis of nitric oxide activates iron regulatory factor in macrophages.

    PubMed

    Drapier, J C; Hirling, H; Wietzerbin, J; Kaldy, P; Kühn, L C

    1993-09-01

    Biosynthesis of nitric oxide (NO) from L-arginine modulates activity of iron-dependent enzymes, including mitochondrial acontiase, an [Fe-S] protein. We examined the effect of NO on the activity of iron regulatory factor (IRF), a cytoplasmic protein which modulates both ferritin mRNA translation and transferrin receptor mRNA stability by binding to specific mRNA sequences called iron responsive elements (IREs). Murine macrophages were activated with interferon-gamma and lipopolysaccharide to induce NO synthase activity and cultured in the presence or absence of NG-substituted analogues of L-arginine which served as selective inhibitors of NO synthesis. Measurement of the nitrite concentration in the culture medium was taken as an index of NO production. Mitochondria-free cytosols were then prepared and aconitase activity as well as IRE binding activity and induction of IRE binding activity were correlated and depended on NO synthesis after IFN-gamma and/or LPS stimulation. Authentic NO gas as well as the NO-generating compound 3-morpholinosydnonimine (SIN-1) also conversely modulated aconitase and IRE binding activities of purified recombinant IRF. These results provide evidence that endogenously produced NO may modulate the post-transcriptional regulation of genes involved in iron homeostasis and support the hypothesis that the [Fe-S] cluster of IRF mediates iron-dependent regulation. PMID:7504626

  2. Nitric oxide cycle in mammals and the cyclicity principle.

    PubMed

    Reutov, V P

    2002-03-01

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

  3. REGULATION OF OBESITY AND INSULIN RESISTANCE BY NITRIC OXIDE

    PubMed Central

    Sansbury, Brian E.; Hill, Bradford G.

    2014-01-01

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

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

    PubMed

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

    2011-08-01

    Nitric oxide (NO) is a potent regulator of keratinocyte growth and differentiation that has been implicated in the pathogenesis of psoriasis (Ps). The NOS3 -786 T/C (SNP id rs2070744; http://www.ensembl.org ), intron 4 variable number tandem repeat (VNTR), and Glu298Asp (SNP id rs1799983) polymorphisms, have been associated with differences in NO plasma concentrations and with the risk of hypertension (HT) and ischemic cardiac disease. The aim of this study was to determine whether the above-mentioned NOS3 variants contributed to the risk of Ps, and were associated with the risk for HT and CAD in these patients. A total of 368 patients with chronic plaque Ps and 400 healthy controls were genotyped for the NOS3 -786 T/C, intron 4 VNTR, and Glu298Asp polymorphisms. Carriers of the -786 C allele were significantly more frequent among the patients (p < 0.001). Carriers of the 4-repeats allele (45 + 44 genotypes) were also more frequent a (p < 0.001). No significant difference was found for the Glu298Asp polymorphism. None of the NOS3 variants was associated with Ht and CAD in our population. In conclusion, NOS3 gene polymorphism would be risk factors for developing Ps. PMID:21293869

  5. Altered L-arginine/nitric oxide synthase/nitric oxide pathway in the vascular adventitia of rats with sepsis.

    PubMed

    Jia, Yue Xia; Pan, Chun Shui; Yang, Jing Hui; Liu, Xiu Hua; Yuan, Wen Jun; Zhao, Jing; Tang, Chao Shu; Qi, Yong Fen

    2006-12-01

    1. In recent studies, the vascular adventitia has been established as an important source of inducible nitric oxide synthase (iNOS) and subsequent nitric oxide (NO) production, even more powerful than the media in response to certain inflammatory factors, such as lipopolysaccharide (LPS). The adventitia has an independent L-arginine (L-Arg)/NOS/NO pathway and is involved in the regulation of vascular function. In the present study, we explored the changes in and the pathophysiological significance of the L-Arg/NOS/NO pathway in the adventitia of rats with sepsis. 2. Sepsis was induced by caecal ligation and puncture in order to observe changes in L-Arg transport, NOS gene expression and activity and NO generation in the vascular adventitia to determine the mechanism of activation of the L-Arg/NOS/NO pathway. 3. Severe sepsis resulted in severe disturbance of haemodynamic features, with decreased mean arterial blood pressure, brachycardia and inhibited cardiac function (decreased left ventricular +/-dP/dt(max)). Left ventricular end-diastolic pressure was elevated threefold (P < 0.01) under anaesthesia. Rats with sepsis showed severe glucopenia and lacticaemia. Plasma levels of the inflammatory factors macrophage chemoattractant protein-1 and interleukin-8 were increased five- and 29-fold, respectively (P < 0.01). 4. In the adventitia of the thoracic and abdominal aortas, the L-Arg/NO pathway was similarly characterized: the uptake of [(3)H]-L-Arg was Na(+) independent, with the peak occurring at approximately 40 min incubation. Total NOS activity was largely calcium independent (> 90%). The V(max) of L-Arg transport in the sepsis group was increased by 83.5% (P < 0.01), but the K(m) value was not significantly different compared with controls. 5. The mRNA levels of cationic amino acid transporter (CAT)-1 and CAT-2B in the sepsis group were increased by 86 and 62%, respectively (both P < 0.01). Inducible NOS activity was increased 2.8-fold compared with controls (P

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

    PubMed

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

    2014-01-01

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

  7. Ethanol Metabolism and Effects: Nitric Oxide and its Interaction

    PubMed Central

    Deng, Xin-sheng; Deitrich, Richard A.

    2008-01-01

    Ethanol (EtOH) in alcoholic beverages is consumed by a large number of individuals and its elimination is primarily by oxidation. The role of nitric oxide (NO) in ethanol’s effects is important since NO is one of the most prominent biological factors in mammals. NO is constantly formed endogenously from L-arginine. Dose and length of EtOH exposure, and cell type are the main factors affecting EtOH effects on NO production. Either acute or chronic EtOH ingestion affects inducible NO synthase (iNOS) activity. However it seems that EtOH suppresses induced-NO production by inhibition of iNOS in different cells. On the other hand, it is clear that acute low doses of EtOH increase both the release of NO and endothelial NOS (eNOS) expression, and augment endothelium-mediated vasodilatation, whereas higher doses impair endothelial functions. EtOH selectively affects neuronal NOS (nNOS) activity in different brain cells, which may relate to various behavioral interactions. Therefore, there is an excellent chance for EtOH and NO to react with each other. Effects of EtOH on NO production and NOS activity may be important to ethanol modification of cell or organ function. Nitrosated compounds (alkyl nitrites) are often found as the interaction products, which might be one of the minor pathways of EtOH metabolism. NO also inhibits EtOH metabolizing enzymes. Furthermore, NO is involved in EtOH induced liver damage and has a role in fetal development during ethanol exposure in pregnancy. The mechanisms underlying these effects are only partially understood. Hence, the current discussion of the interaction of ethanol and NO is presented. PMID:18690862

  8. Absorption of nitrogen dioxide and nitric oxide by soda lime.

    PubMed

    Ishibe, T; Sato, T; Hayashi, T; Kato, N; Hata, T

    1995-09-01

    Inhaled nitric oxide (NO) is used for the treatment of pulmonary hypertension as a selective pulmonary vasodilator. However, NO is oxidized rapidly to the more toxic nitrogen dioxide (NO2). Elimination of NO2 from inspired gas is essential for safe clinical use NO. We therefore investigated the efficacy of soda lime in absorbing NO2 from NO2-containing gases. Commercially available soda limes (Soda sorb and Wako lime-A), were exposed to the following six gas mixtures containing NO and NO2 in a hypoxic carrier gas for 20 min: No. 1: NO 40 ppm; No. 2: NO 35 ppm and NO2 5 ppm; No. 3: NO 30 ppm and NO2 10 ppm; No. 4: NO 20 ppm and NO2 20 ppm; No. 5: NO 10 ppm and NO2 30 ppm; and No. 6: NO2 40 ppm. Both types of soda lime completely absorbed the NO2 in all samples when it was present (Nos 2-6). NO concentration in these gas mixtures was reduced by an amount equal to the NO2 absorbed by soda lime. NO was absorbed minimally when NO2 was not present in the mixture. Nitrite was detected from the Wako lime-A granules exposed to the test gas by the chemical analysis. These findings suggest that soda lime completely absorbs NO2 by chemical neutralization, but NO is absorbed as simultaneously absorbed NO2 only where NO and NO2 coexist. Therefore, we conclude that soda lime is useful for NO2 absorption during NO inhalation therapy but NO monitoring from a point distal to the soda lime is required for precise control of inspired NO concentration.

  9. Rational Design of a Structural and Functional Nitric Oxide Reductase

    SciTech Connect

    Yeung, N.; Lin, Y; Gao, Y; Zhao, X; Russell, B; Lei, L; Miner, L; Robinson, H; Lu, Y

    2009-01-01

    Protein design provides a rigorous test of our knowledge about proteins and allows the creation of novel enzymes for biotechnological applications. Whereas progress has been made in designing proteins that mimic native proteins structurally, it is more difficult to design functional proteins. In comparison to recent successes in designing non-metalloproteins, it is even more challenging to rationally design metalloproteins that reproduce both the structure and function of native metalloenzymes. This is because protein metal-binding sites are much more varied than non-metal-containing sites, in terms of different metal ion oxidation states, preferred geometry and metal ion ligand donor sets. Because of their variability, it has been difficult to predict metal-binding site properties in silico, as many of the parameters, such as force fields, are ill-defined. Therefore, the successful design of a structural and functional metalloprotein would greatly advance the field of protein design and our understanding of enzymes. Here we report a successful, rational design of a structural and functional model of a metalloprotein, nitric oxide reductase (NOR), by introducing three histidines and one glutamate, predicted as ligands in the active site of NOR, into the distal pocket of myoglobin. A crystal structure of the designed protein confirms that the minimized computer model contains a haem/non-haem FeB centre that is remarkably similar to that in the crystal structure. This designed protein also exhibits NO reduction activity, and so models both the structure and function of NOR, offering insight that the active site glutamate is required for both iron binding and activity. These results show that structural and functional metalloproteins can be rationally designed in silico.

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

    PubMed Central

    2013-01-01

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

  11. Investigation on oxidative stress of nitric oxide synthase interacting protein from Clonorchis sinensis.

    PubMed

    Bian, Meng; Xu, Qingxia; Xu, Yanquan; Li, Shan; Wang, Xiaoyun; Sheng, Jiahe; Wu, Zhongdao; Huang, Yan; Yu, Xinbing

    2016-01-01

    Numerous evidences indicate that excretory-secretory products (ESPs) from liver flukes trigger the generation of free radicals that are associated with the initial pathophysiological responses in host cells. In this study, we first constructed a Clonorchis sinensis (C. sinensis, Cs)-infected BALB/c mouse model and examined relative results respectively at 3, 5, 7, and 9 weeks postinfection (p.i.). Quantitative reverse transcription (RT)-PCR indicated that the transcriptional level of both endothelial nitric oxide synthase (eNOS) and superoxide dismutase (SOD) gradually decreased with lastingness of infection, while the transcriptional level of inducible NOS (iNOS) significantly increased. The level of malondialdehyde (MDA) in sera of infected mouse significantly increased versus the healthy control group. These results showed that the liver of C. sinensis-infected mouse was in a state with elevated levels of oxidation stress. Previously, C. sinensis NOS interacting protein coding gene (named CsNOSIP) has been isolated and recombinant CsNOSIP (rCsNOSIP) has been expressed in Escherichia coli, which has been confirmed to be a component present in CsESPs and confirmed to play important roles in immune regulation of the host. In the present paper, we investigated the effects of rCsNOSIP on the lipopolysaccharide (LPS)-induced activated RAW264.7, a murine macrophage cell line. We found that endotoxin-free rCsNOSIP significantly promoted the levels of nitric oxide (NO) and reactive oxygen species (ROS) after pretreated with rCsNOSIP, while the level of SOD decreased. Furthermore, rCsNOSIP could also increase the level of lipid peroxidation MDA. Taken together, these results suggested that CsNOSIP was a key molecule which was involved in the production of nitric oxide (NO) and its reactive intermediates, and played an important role in oxidative stress during C. sinensis infection. PMID:26391171

  12. Investigation on oxidative stress of nitric oxide synthase interacting protein from Clonorchis sinensis.

    PubMed

    Bian, Meng; Xu, Qingxia; Xu, Yanquan; Li, Shan; Wang, Xiaoyun; Sheng, Jiahe; Wu, Zhongdao; Huang, Yan; Yu, Xinbing

    2016-01-01

    Numerous evidences indicate that excretory-secretory products (ESPs) from liver flukes trigger the generation of free radicals that are associated with the initial pathophysiological responses in host cells. In this study, we first constructed a Clonorchis sinensis (C. sinensis, Cs)-infected BALB/c mouse model and examined relative results respectively at 3, 5, 7, and 9 weeks postinfection (p.i.). Quantitative reverse transcription (RT)-PCR indicated that the transcriptional level of both endothelial nitric oxide synthase (eNOS) and superoxide dismutase (SOD) gradually decreased with lastingness of infection, while the transcriptional level of inducible NOS (iNOS) significantly increased. The level of malondialdehyde (MDA) in sera of infected mouse significantly increased versus the healthy control group. These results showed that the liver of C. sinensis-infected mouse was in a state with elevated levels of oxidation stress. Previously, C. sinensis NOS interacting protein coding gene (named CsNOSIP) has been isolated and recombinant CsNOSIP (rCsNOSIP) has been expressed in Escherichia coli, which has been confirmed to be a component present in CsESPs and confirmed to play important roles in immune regulation of the host. In the present paper, we investigated the effects of rCsNOSIP on the lipopolysaccharide (LPS)-induced activated RAW264.7, a murine macrophage cell line. We found that endotoxin-free rCsNOSIP significantly promoted the levels of nitric oxide (NO) and reactive oxygen species (ROS) after pretreated with rCsNOSIP, while the level of SOD decreased. Furthermore, rCsNOSIP could also increase the level of lipid peroxidation MDA. Taken together, these results suggested that CsNOSIP was a key molecule which was involved in the production of nitric oxide (NO) and its reactive intermediates, and played an important role in oxidative stress during C. sinensis infection.

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

    NASA Technical Reports Server (NTRS)

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

    1986-01-01

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

  14. NO to cancer: The complex and multifaceted role of nitric oxide and the epigenetic nitric oxide donor, RRx-001.

    PubMed

    Scicinski, Jan; Oronsky, Bryan; Ning, Shoucheng; Knox, Susan; Peehl, Donna; Kim, Michelle M; Langecker, Peter; Fanger, Gary

    2015-12-01

    The endogenous mediator of vasodilation, nitric oxide (NO), has been shown to be a potent radiosensitizer. However, the underlying mode of action for its role as a radiosensitizer - while not entirely understood - is believed to arise from increased tumor blood flow, effects on cellular respiration, on cell signaling, and on the production of reactive oxygen and nitrogen species (RONS), that can act as radiosensitizers in their own right. NO activity is surprisingly long-lived and more potent in comparison to oxygen. Reports of the effects of NO with radiation have often been contradictory leading to confusion about the true radiosensitizing nature of NO. Whether increasing or decreasing tumor blood flow, acting as radiosensitizer or radioprotector, the effects of NO have been controversial. Key to understanding the role of NO as a radiosensitizer is to recognize the importance of biological context. With a very short half-life and potent activity, the local effects of NO need to be carefully considered and understood when using NO as a radiosensitizer. The systemic effects of NO donors can cause extensive side effects, and also affect the local tumor microenvironment, both directly and indirectly. To minimize systemic effects and maximize effects on tumors, agents that deliver NO on demand selectively to tumors using hypoxia as a trigger may be of greater interest as radiosensitizers. Herein we discuss the multiple effects of NO and focus on the clinical molecule RRx-001, a hypoxia-activated NO donor currently being investigated as a radiosensitizer in the clinic.

  15. Inhaled Nitric Oxide Increases Urinary Nitric Oxide Metabolites and Cyclic Guanosine Monophosphate in Premature Infants: Relationship to Pulmonary Outcome

    PubMed Central

    Ballard, Philip L.; Keller, Roberta L.; Black, Dennis M.; Durand, David J.; Merrill, Jeffrey D.; Eichenwald, Eric C.; Truog, William E.; Mammel, Mark C.; Steinhorn, Robin; Ryan, Rita M.; Courtney, Sherry E.; Horneman, Hart; Ballard, Roberta A.

    2016-01-01

    Objective Inhaled nitric oxide (iNO) has been tested to prevent bronchopulmonary dysplasia (BPD) in premature infants, however, the role of cyclic guanosine monophosphate (cGMP) is not known. We hypothesized that levels of NO metabolites (NOx) and cGMP in urine, as a noninvasive source for biospecimen collection, would reflect the dose of iNO and relate to pulmonary outcome. Study Design Studies were performed on 125 infants who required mechanical ventilation at 7 to 14 days and received 24 days of iNO at 20–2 ppm. A control group of 19 infants did not receive iNO. Results In NO-treated infants there was a dose-dependent increase of both NOx and cGMP per creatinine (maximal 3.1- and 2-fold, respectively, at 10–20 ppm iNO) compared with off iNO. NOx and cGMP concentrations at both 2 ppm and off iNO were inversely related to severity of lung disease during the 1st month, and the NOx levels were lower in infants who died or developed BPD at term. NOx was higher in Caucasian compared with other infants at all iNO doses. Conclusion Urinary NOx and cGMP are biomarkers of endogenous NO production and lung uptake of iNO, and some levels reflect the severity of lung disease. These results support a role of the NO–cGMP pathway in lung development. PMID:24968129

  16. NO to cancer: The complex and multifaceted role of nitric oxide and the epigenetic nitric oxide donor, RRx-001☆

    PubMed Central

    Scicinski, Jan; Oronsky, Bryan; Ning, Shoucheng; Knox, Susan; Peehl, Donna; Kim, Michelle M.; Langecker, Peter; Fanger, Gary

    2015-01-01

    The endogenous mediator of vasodilation, nitric oxide (NO), has been shown to be a potent radiosensitizer. However, the underlying mode of action for its role as a radiosensitizer – while not entirely understood – is believed to arise from increased tumor blood flow, effects on cellular respiration, on cell signaling, and on the production of reactive oxygen and nitrogen species (RONS), that can act as radiosensitizers in their own right. NO activity is surprisingly long-lived and more potent in comparison to oxygen. Reports of the effects of NO with radiation have often been contradictory leading to confusion about the true radiosensitizing nature of NO. Whether increasing or decreasing tumor blood flow, acting as radiosensitizer or radioprotector, the effects of NO have been controversial. Key to understanding the role of NO as a radiosensitizer is to recognize the importance of biological context. With a very short half-life and potent activity, the local effects of NO need to be carefully considered and understood when using NO as a radiosensitizer. The systemic effects of NO donors can cause extensive side effects, and also affect the local tumor microenvironment, both directly and indirectly. To minimize systemic effects and maximize effects on tumors, agents that deliver NO on demand selectively to tumors using hypoxia as a trigger may be of greater interest as radiosensitizers. Herein we discuss the multiple effects of NO and focus on the clinical molecule RRx-001, a hypoxia-activated NO donor currently being investigated as a radiosensitizer in the clinic. PMID:26164533

  17. NO to cancer: The complex and multifaceted role of nitric oxide and the epigenetic nitric oxide donor, RRx-001.

    PubMed

    Scicinski, Jan; Oronsky, Bryan; Ning, Shoucheng; Knox, Susan; Peehl, Donna; Kim, Michelle M; Langecker, Peter; Fanger, Gary

    2015-12-01

    The endogenous mediator of vasodilation, nitric oxide (NO), has been shown to be a potent radiosensitizer. However, the underlying mode of action for its role as a radiosensitizer - while not entirely understood - is believed to arise from increased tumor blood flow, effects on cellular respiration, on cell signaling, and on the production of reactive oxygen and nitrogen species (RONS), that can act as radiosensitizers in their own right. NO activity is surprisingly long-lived and more potent in comparison to oxygen. Reports of the effects of NO with radiation have often been contradictory leading to confusion about the true radiosensitizing nature of NO. Whether increasing or decreasing tumor blood flow, acting as radiosensitizer or radioprotector, the effects of NO have been controversial. Key to understanding the role of NO as a radiosensitizer is to recognize the importance of biological context. With a very short half-life and potent activity, the local effects of NO need to be carefully considered and understood when using NO as a radiosensitizer. The systemic effects of NO donors can cause extensive side effects, and also affect the local tumor microenvironment, both directly and indirectly. To minimize systemic effects and maximize effects on tumors, agents that deliver NO on demand selectively to tumors using hypoxia as a trigger may be of greater interest as radiosensitizers. Herein we discuss the multiple effects of NO and focus on the clinical molecule RRx-001, a hypoxia-activated NO donor currently being investigated as a radiosensitizer in the clinic. PMID:26164533

  18. Relation between Endothelial Nitric Oxide Synthase Genotypes and Oxidative Stress Markers in Larynx Cancer.

    PubMed

    Yanar, K; Çakatay, U; Aydın, S; Verim, A; Atukeren, P; Özkan, N E; Karatoprak, K; Cebe, T; Turan, S; Ozkök, E; Korkmaz, G; Cacına, C; Küçükhüseyin, O; Yaylım, İ

    2016-01-01

    Nitric oxide synthase (eNOS/NOS3) is responsible for the endothelial synthesis of nitric oxide (NO(•)). G894T polymorphism leads to the amino acid substitution from Glu298Asp that causes lower NOS3 activity and basal NO(•) production in NOS3 894T (298Asp) allele carriers compared with the GG homozygotes. NO(•) acts as an antioxidant protecting against Fenton's reaction which generates highly reactive hydroxyl radicals. Allelic variation of NOS3 may influence an individual's risk of laryngeal cancer (LC). In the current study we have examined the possible relationship between NOS3 G894T genotypes and various systemic oxidative damage markers such as protein carbonyl, advanced oxidation protein products, Cu, Zn-superoxide dismutase, thiol group fractions, and lipid hydroperoxides in LC patients. Genotyping was carried out by PCR-RFLP. In LC patients with TT genotype, Cu, Zn-superoxide dismutase activities and nonprotein thiol levels were significantly higher than the controls. In patients with GT and GG genotype, high levels of lipid hydroperoxides showed statistical significance when compared to controls. Our results indicate a potential relationship among G894T polymorphism of NOS3, and impaired redox homeostasis. Further studies are required to determine the role of NOS3 gene polymorphism and impaired plasma redox homeostasis. PMID:26682008

  19. Effect of Nitric Oxide on the Antifungal Activity of Oxidative Stress and Azoles Against Candida albicans.

    PubMed

    Li, De-Dong; Yang, Chang-Chun; Liu, Ping; Wang, Yan; Sun, Yan

    2016-06-01

    Nitric oxide (NO) is a small molecule with a wide range of biological activities in mammalian and bacteria. However, the role of NO in fungi, especially Candida albicans, is not clear. In this study, we confirmed the generation of endogenous NO in C. albicans, and found that the production of endogenous NO in C. albicans was associated with nitric oxide synthase pathway. Our results further indicated that the production of endogenous NO in C. albicans was reduced under oxidative stress such as menadione or H2O2 treatment. Meanwhile, exogenous NO donor, sodium nitroprusside (SNP), synergized with H2O2 against C. albicans. Interestingly, SNP could inhibit the antifungal effect of azoles against C. albicans in vitro, suggesting that NO might be involved in the resistance of C. albicans to antifungals. Collectively, this study demonstrated the production of endogenous NO in C. albicans, and indicated that NO may play an important role in the response of C. albicans to oxidative stress and azoles. PMID:27570314

  20. Mamao Pomace Extract Alleviates Hypertension and Oxidative Stress in Nitric Oxide Deficient Rats

    PubMed Central

    Kukongviriyapan, Upa; Kukongviriyapan, Veerapol; Pannangpetch, Patchareewan; Donpunha, Wanida; Sripui, Jintana; Sae-Eaw, Amporn; Boonla, Orachorn

    2015-01-01

    Reactive oxygen species (ROS)-induced oxidative stress plays a major role in pathogenesis of hypertension. Antidesma thwaitesianum (local name: Mamao) is a tropical plant distributed in the tropical/subtropical areas of the world, including Thailand. Mamao pomace (MP), a by-product generated from Mamao fruits, contains large amounts of antioxidant polyphenolic compounds. The aim of this study was to investigate the antihypertensive and antioxidative effects of MP using hypertensive rats. For this purpose, male Sprague-Dawley rats were given Nω-nitro-l-arginine methyl ester (l-NAME), an inhibitor of endothelial nitric oxide synthase (eNOS), in drinking water (50 mg/kg) for three weeks. MP extract was orally administered daily at doses of 100 and 300 mg/kg. l-NAME administration induced marked increase in blood pressure, peripheral vascular resistance, and oxidative stress. MP treatment significantly prevented the increase in blood pressure, hindlimb blood flow and hindlimb vascular resistance of l-NAME treated hypertensive rats (p < 0.05). The antihypertensive effect of MP treatment was associated with suppression of superoxide production from carotid strips and also with an increase in eNOS protein expression and nitric oxide bioavailability. The present results provide evidence for the antihypertensive effect of MP and suggest that MP might be useful as a dietary supplement against hypertension. PMID:26225998

  1. Relation between Endothelial Nitric Oxide Synthase Genotypes and Oxidative Stress Markers in Larynx Cancer

    PubMed Central

    Yanar, K.; Çakatay, U.; Aydın, S.; Verim, A.; Atukeren, P.; Özkan, N. E.; Karatoprak, K.; Cebe, T.; Turan, S.; Ozkök, E.; Korkmaz, G.; Cacına, C.; Küçükhüseyin, O.; Yaylım, İ.

    2016-01-01

    Nitric oxide synthase (eNOS/NOS3) is responsible for the endothelial synthesis of nitric oxide (NO•). G894T polymorphism leads to the amino acid substitution from Glu298Asp that causes lower NOS3 activity and basal NO• production in NOS3 894T (298Asp) allele carriers compared with the GG homozygotes. NO• acts as an antioxidant protecting against Fenton's reaction which generates highly reactive hydroxyl radicals. Allelic variation of NOS3 may influence an individual's risk of laryngeal cancer (LC). In the current study we have examined the possible relationship between NOS3 G894T genotypes and various systemic oxidative damage markers such as protein carbonyl, advanced oxidation protein products, Cu, Zn-superoxide dismutase, thiol group fractions, and lipid hydroperoxides in LC patients. Genotyping was carried out by PCR-RFLP. In LC patients with TT genotype, Cu, Zn-superoxide dismutase activities and nonprotein thiol levels were significantly higher than the controls. In patients with GT and GG genotype, high levels of lipid hydroperoxides showed statistical significance when compared to controls. Our results indicate a potential relationship among G894T polymorphism of NOS3, and impaired redox homeostasis. Further studies are required to determine the role of NOS3 gene polymorphism and impaired plasma redox homeostasis. PMID:26682008

  2. Heat stress stimulates nitric oxide production in Symbiodinium microadriaticum: a possible linkage between nitric oxide and the coral bleaching phenomenon.

    PubMed

    Bouchard, Josée Nina; Yamasaki, Hideo

    2008-04-01

    Nitric oxide (NO) is a gas displaying multiple physiological functions in plants, animals and bacteria. The enzymes nitrate reductase and NO synthase have been suggested to be involved in the production of NO in plants and algae, but the implication of those enzymes in NO production under physiological conditions remains obscure. Symbiodinium microadriaticum, commonly referred to as zooxanthellae, is a marine microalga commonly found in symbiotic association with a cnidarian host including reef-building corals. Here we demonstrate NO production in zooxanthellae upon supplementation of either sodium nitrite or L-arginine as a substrate. The nitrite-dependent NO production was detected electrochemically and confirmed by the application of 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO), a specific NO scavenger. Cells stained with the diaminofluorescein, DAF-2 DA, an NO fluorescent probe, showed an increase in fluorescence intensity upon supplementation of both sodium nitrite and L-arginine. Microscopic observations of DAF-stained cells verified that NO was produced inside the cells. NO production in S. microadriaticum was found to increase upon exposure of cells to an acute heat stress which also caused a decline in the photosynthetic efficiency of PSII (F(v)/F(m)). This study provides substantial evidence to confirm that zooxanthellae can synthesize NO even when they are not in a symbiotic association with a coral host. The increase in NO production at high temperatures suggests that heat stress stimulates the microalgal NO production in a temperature-dependent manner. The implications of these findings are discussed in the light of the coral bleaching phenomenon which is associated with elevated sea surface temperature due to global warming.

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

    NASA Astrophysics Data System (ADS)

    Barker, Susan Lynn Ritenour

    1999-11-01

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

  4. Solubilization and Resolution of the Membrane-Bound Nitrite Reductase from Paracoccus Halodenitrificans into Nitrite and Nitric Oxide Reductases

    NASA Technical Reports Server (NTRS)

    Grant, Michael A.; Cronin, Sonja E.; Hochstein, Lawrence I.

    1984-01-01

    Membranes prepared from Paracoccus halodenitrificans reduced nitrite or nitric oxide to nitrous oxide. Extraction of these membranes with the detergent CHAPSO [3-(3-Chlolamidoporopyldimethylammonio)-1-(2- hydroxy-1-propanesulfonate)], followed by ammonium sulfate fractionation of the solubilized proteins, resulted in the separation of nitrite and nitric oxide reductase activities. The fraction containing nitrite reductase activity spectrally resembled a cd-type cytochrome. Several cytochromes were detected in the nitric oxide reductase fraction. Which, if any, of these cytochromes is associated with the reduction of nitric oxide is not clear at this time.

  5. The co-immobilization of P450-type nitric oxide reductase and glucose dehydrogenase for the continuous reduction of nitric oxide via cofactor recycling.

    PubMed

    Garny, Seike; Beeton-Kempen, Natasha; Gerber, Isak; Verschoor, Jan; Jordaan, Justin

    2016-04-01

    The co-immobilization of enzymes on target surfaces facilitates the development of self-contained, multi-enzyme biocatalytic platforms. This generally entails the co-immobilization of an enzyme with catalytic value in combination with another enzyme that performs a complementary function, such as the recycling of a critical cofactor. In this study, we co-immobilized two enzymes from different biological sources for the continuous reduction of nitric oxide, using epoxide- and carboxyl-functionalized hyper-porous microspheres. Successful co-immobilization of a fungal nitric oxide reductase (a member of the cytochrome P450 enzyme family) and a bacterial glucose dehydrogenase was obtained with the carboxyl-functionalized microspheres, with enzyme activity maintenance of 158% for nitric oxide reductase and 104% for glucose dehydrogenase. The optimal stoichiometric ratio of these two enzymes was subsequently determined to enable the two independent chemical reactions to be catalyzed concomitantly, allowing for near-synchronous cofactor conversion rates. This dual-enzyme system provides a novel research tool with potential for in vitro investigations of nitric oxide, and further demonstrates the successful immobilization of a P450 enzyme with potential application towards the immobilization of other cytochrome P450 enzymes.

  6. Oleic acid-dependent modulation of Nitric oxide associated 1 protein levels regulates nitric oxide-mediated defense signaling in Arabidopsis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The conserved cellular metabolites nitric oxide (NO) and oleic acid (18:1) are well-known regulators of disease physiologies in diverse organism. We show that NO production in plants is regulated via 18:1. Reduction in 18:1 levels, via a genetic mutation in the 18:1-synthesizing gene SUPPRESSOR OF S...

  7. Effect of Zen Meditation on serum nitric oxide activity and lipid peroxidation.

    PubMed

    Kim, Do-Hoon; Moon, Yoo-Sun; Kim, Hee-Sung; Jung, Jun-Sub; Park, Hyung-Moo; Suh, Hong-Won; Kim, Yung-Hi; Song, Dong-Keun

    2005-02-01

    This study was designed to investigate the effect of Zen Meditation on serum nitric oxide activity (NO) and oxidative stress (lipid peroxidation). The experimental group included 20 subjects who had practiced the Zen Meditation program in Meditation Center located in Seoul, South Korea. The control group included 20 subjects who did not practice any formal stress management technique and were age and sex matched with experimental group. To provide an assessment of nitric oxide production, the serum level of nitrate/nitrite was determined using the Griess reagent. Malondialdehyde (MDA) concentration was measured as a convenient index of lipid peroxidation by thiobarbituric acid (TBA) method. Meditation group showed a significant higher level of serum nitrate+nitrite concentration and a significant reduced level of serum malondialdehyde (MDA) than control group. A comprehensive randomized controlled trial should be performed to prove the causal relationship between meditation and level of nitric oxide or oxidative stress in reducing cardiovascular risk factors.

  8. Energy landscapes and catalysis in nitric-oxide synthase.

    PubMed

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

    2014-04-25

    Nitric oxide (NO) plays diverse roles in mammalian physiology. It is involved in blood pressure regulation, neurotransmission, and immune response, and is generated through complex electron transfer reactions catalyzed by NO synthases (NOS). In neuronal NOS (nNOS), protein domain dynamics and calmodulin binding are implicated in regulating electron flow from NADPH, through the FAD and FMN cofactors, to the heme oxygenase domain, the site of NO generation. Simple models based on crystal structures of nNOS reductase have invoked a role for large scale motions of the FMN-binding domain in shuttling electrons from the FAD-binding domain to the heme oxygenase domain. However, molecular level insight of the dynamic structural transitions in NOS enzymes during enzyme catalysis is lacking. We use pulsed electron-electron double resonance spectroscopy to derive inter-domain distance relationships in multiple conformational states of nNOS. These distance relationships are correlated with enzymatic activity through variable pressure kinetic studies of electron transfer and turnover. The binding of NADPH and calmodulin are shown to influence interdomain distance relationships as well as reaction chemistry. An important effect of calmodulin binding is to suppress adventitious electron transfer from nNOS to molecular oxygen and thereby preventing accumulation of reactive oxygen species. A complex landscape of conformations is required for nNOS catalysis beyond the simple models derived from static crystal structures of nNOS reductase. Detailed understanding of this landscape advances our understanding of nNOS catalysis/electron transfer, and could provide new opportunities for the discovery of small molecule inhibitors that bind at dynamic protein interfaces of this multidimensional energy landscape.

  9. The Endothelium-Dependent Nitric Oxide-cGMP Pathway.

    PubMed

    Mónica, F Z; Bian, K; Murad, F

    2016-01-01

    Nitric oxide (NO)-cyclic 3'-5' guanosine monophosphate (cGMP) signaling plays a critical role on smooth muscle tone, platelet activity, cardiac contractility, renal function and fluid balance, and cell growth. Studies of the 1990s established endothelium dysfunction as one of the major causes of cardiovascular diseases. Therapeutic strategies that benefit NO bioavailability have been applied in clinical medicine extensively. Basic and clinical studies of cGMP regulation through activation of soluble guanylyl cyclase (sGC) or inhibition of cyclic nucleotide phosphodiesterase type 5 (PDE5) have resulted in effective therapies for pulmonary hypertension, erectile dysfunction, and more recently benign prostatic hyperplasia. This section reviews (1) how endothelial dysfunction and NO deficiency lead to cardiovascular diseases, (2) how soluble cGMP regulation leads to beneficial effects on disorders of the circulation system, and (3) the epigenetic regulation of NO-sGC pathway components in the cardiovascular system. In conclusion, the discovery of the NO-cGMP pathway revolutionized the comprehension of pathophysiological mechanisms involved in cardiovascular and other diseases. However, considering the expression "from bench to bedside" the therapeutic alternatives targeting NO-cGMP did not immediately follow the marked biochemical and pathophysiological revolution. Some therapeutic options have been effective and released on the market for pulmonary hypertension and erectile dysfunction such as inhaled NO, PDE5 inhibitors, and recently sGC stimulators. The therapeutic armamentarium for many other disorders is expected in the near future. There are currently numerous active basic and clinical research programs in universities and industries attempting to develop novel therapies for many diseases and medical applications.

  10. Altered Nitric Oxide System in Cardiovascular and Renal Diseases

    PubMed Central

    Bae, Eun Hui; Ma, Seong Kwon; Kim, Soo Wan

    2016-01-01

    Nitric oxide (NO) is synthesized by a family of NO synthases (NOS), including neuronal, inducible, and endothelial NOS (n/i/eNOS). NO-mediated effects can be beneficial or harmful depending on the specific risk factors affecting the disease. In hypertension, the vascular relaxation response to acetylcholine is blunted, and that to direct NO donors is maintained. A reduction in the activity of eNOS is mainly responsible for the elevation of blood pressure, and an abnormal expression of iNOS is likely to be related to the progression of vascular dysfunction. While eNOS/nNOS-derived NO is protective against the development of atherosclerosis, iNOS-derived NO may be proatherogenic. eNOS-derived NO may prevent the progression of myocardial infarction. Myocardial ischemia/reperfusion injury is significantly enhanced in eNOS-deficient animals. An important component of heart failure is the loss of coronary vascular eNOS activity. A pressure-overload may cause severer left ventricular hypertrophy and dysfunction in eNOS null mice than in wild-type mice. iNOS-derived NO has detrimental effects on the myocardium. NO plays an important role in regulating the angiogenesis and slowing the interstitial fibrosis of the obstructed kidney. In unilateral ureteral obstruction, the expression of eNOS was decreased in the affected kidney. In triply n/i/eNOS null mice, nephrogenic diabetes insipidus developed along with reduced aquaporin-2 abundance. In chronic kidney disease model of subtotal-nephrectomized rats, treatment with NOS inhibitors decreased systemic NO production and induced left ventricular systolic dysfunction (renocardiac syndrome). PMID:27231671

  11. Xiaokening stimulates endothelial nitric oxide release in diabetic rats

    PubMed Central

    Liu, Hong; Liu, Lei; Wei, Qunli; Cui, Jie; Yan, Changdong; Wang, Xin; Wu, Yongping

    2015-01-01

    INTRODUCTION Diabetes mellitus induces microangiopathic changes that lead to endothelial dysfunction. This study investigated the effect of Xiaokening, a type of Chinese compound medicine, on the mesenteric arteriolar endothelial cell function of diabetic rats and its underlying mechanism. METHODS Diabetes mellitus was induced in rat models via intraperitoneal injection of 60 mg/kg streptozotocin and observed over three weeks. Mesenteric arterioles, which were isolated in a cannulated and pressurised state, were incubated with intravascular injections of 1, 3 or 5 g/L Xiaokening for 24, 48 or 72 hours. The effects of Xiaokening on the release of nitric oxide (NO) on the mesenteric arterioles were detected under shear stress of 1, 10 and 20 dyn/cm2. Biochemical methods were used to determine the activities of superoxide dismutase (SOD) and xanthine oxidase (XO). The expressions of endothelial NO synthase (eNOS), SOD and XO in the mesenteric arterioles were assessed using Western blot. RESULTS Compared to normal rat arterioles, less NO was released in the mesenteric arterioles of diabetic rats. Xiaokening was found to have a concentration- and time-dependent effect on NO release; when the shear stress was increased, there was a gradual increase in the release of NO. Compared to normal arterioles, the expression of eNOS in the mesenteric arterioles of diabetic rats was lower. Incubation with Xiaokening increased SOD activity and expression, and decreased XO activity and expression in the mesenteric arterioles of the diabetic rats. CONCLUSION Xiaokening was able to significantly increase NO release and improve the endothelial function of mesenteric arterioles through antioxidative mechanisms. PMID:26243977

  12. Nitric oxide, antioxidants and prooxidants in plant defence responses

    PubMed Central

    Groß, Felicitas; Durner, Jörg; Gaupels, Frank

    2013-01-01

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

  13. DISSECTING STRUCTURAL AND ELECTRONIC EFFECTS IN INDUCIBLE NITRIC OXIDE SYNTHASE

    PubMed Central

    Hannibal, Luciana; Page, Richard C.; Haque, Mohammad Mahfuzul; Bolisetty, Karthik; Yu, Zhihao; Misra, Saurav; Stuehr, Dennis J.

    2015-01-01

    Nitric oxide synthases (NOS) are haem-thiolate enzymes that catalyse the conversion of L-Arginine (LArg) into NO and citrulline. Inducible NOS (iNOS) is responsible for delivery of NO in response to stressors during inflammation. The catalytic performance of iNOS is proposed to rely mainly on the haem midpoint potential and the ability of the substrate L-Arg to provide an H-bond for oxygen activation (O-O scission). We present a comparative study of native iNOS versus iNOS-mesohaem, and investigate the formation of a low-spin ferric haem-aquo or -hydroxo species (P) in iNOS mutant W188H substituted with mesohaem. iNOS-mesohaem and W188H-mesohaem were stable and dimeric, and presented substrate-binding affinities comparable to their native counterparts. Single turnover reactions catalysed by iNOSoxy with LArg (first reaction step) or N-hydroxyarginine (second reaction step) showed that mesohaem substitution triggered faster rates of FeIIO2 conversion and altered other key kinetic parameters. We elucidated the first crystal structure of a NOS substituted with mesohaem and found essentially identical features compared to the structure of iNOS carrying native haem. This facilitated the dissection of structural and electronic effects. Mesohaem substitution substantially reduced the build-up of species P in W188H iNOS during catalysis, thus increasing its proficiency toward NO synthesis. The marked structural similarities of iNOSoxy containing native haem or mesohaem indicate that the kinetic behaviour observed in mesohaem-substituted iNOS is most heavily influenced by electronic effects rather than structural alterations. PMID:25608846

  14. Dissecting structural and electronic effects in inducible nitric oxide synthase.

    PubMed

    Hannibal, Luciana; Page, Richard C; Haque, Mohammad Mahfuzul; Bolisetty, Karthik; Yu, Zhihao; Misra, Saurav; Stuehr, Dennis J

    2015-04-01

    Nitric oxide synthases (NOSs) are haem-thiolate enzymes that catalyse the conversion of L-arginine (L-Arg) into NO and citrulline. Inducible NOS (iNOS) is responsible for delivery of NO in response to stressors during inflammation. The catalytic performance of iNOS is proposed to rely mainly on the haem midpoint potential and the ability of the substrate L-Arg to provide a hydrogen bond for oxygen activation (O-O scission). We present a study of native iNOS compared with iNOS-mesohaem, and investigate the formation of a low-spin ferric haem-aquo or -hydroxo species (P) in iNOS mutant W188H substituted with mesohaem. iNOS-mesohaem and W188H-mesohaem were stable and dimeric, and presented substrate-binding affinities comparable to those of their native counterparts. Single turnover reactions catalysed by iNOSoxy with L-Arg (first reaction step) or N-hydroxy-L-arginine (second reaction step) showed that mesohaem substitution triggered higher rates of Fe(II)O₂ conversion and altered other key kinetic parameters. We elucidated the first crystal structure of a NOS substituted with mesohaem and found essentially identical features compared with the structure of iNOS carrying native haem. This facilitated the dissection of structural and electronic effects. Mesohaem substitution substantially reduced the build-up of species P in W188H iNOS during catalysis, thus increasing its proficiency towards NO synthesis. The marked structural similarities of iNOSoxy containing native haem or mesohaem indicate that the kinetic behaviour observed in mesohaem-substituted iNOS is most heavily influenced by electronic effects rather than structural alterations.

  15. Inducible nitric oxide synthase haplotype associated with migraine and aura.

    PubMed

    de O S Mansur, Thiago; Gonçalves, Flavia M; Martins-Oliveira, Alisson; Speciali, Jose G; Dach, Fabiola; Lacchini, Riccardo; Tanus-Santos, Jose E

    2012-05-01

    Migraine is a complex neurological disorder with a clear neurogenic inflammatory component apparently including enhanced nitric oxide (NO) formation. Excessive NO amounts possibly contributing to migraine are derived from increased expression and activity of inducible NO synthase (iNOS). We tested the hypothesis that two functional, clinically relevant iNOS genetic polymorphisms (C(-1026)A-rs2779249 and G2087A-rs2297518) are associated with migraine with or without aura. We studied 142 healthy women without migraine (control group) and 200 women with migraine divided into two groups: 148 with migraine without aura (MWA) and 52 with aura (MA). Genotypes were determined by real-time polymerase chain reaction using the Taqman(®) allele discrimination assays. The PHASE 2.1 software was used to estimate the haplotypes. The A allele for the G2087A polymorphism was more commonly found in the MA group than in the MWA group (28 vs. 18%; P < 0.05). No other significant differences in the alleles or genotypes distributions were found (P > 0.05). The haplotype combining both A alleles for the two polymorphisms was more commonly found in the MA group than in the control group or in the MWA group (19 vs. 10 or 8%; P = 0.0245 or 0.0027, respectively). Our findings indicate that the G2087A and the C(-1026)A polymorphism in the iNOS gene affect the susceptibility to migraine with aura when their effects are combined within haplotypes, whereas the G2087A affects the susceptibility to aura in migraine patients. These finding may have therapeutic implications when examining the effects of selective iNOS inhibitors.

  16. Nitric oxide synthase-3 promotes embryonic development of atrioventricular valves.

    PubMed

    Liu, Yin; Lu, Xiangru; Xiang, Fu-Li; Lu, Man; Feng, Qingping

    2013-01-01

    Nitric oxide synthase-3 (NOS3) has recently been shown to promote endothelial-to-mesenchymal transition (EndMT) in the developing atrioventricular (AV) canal. The present study was aimed to investigate the role of NOS3 in embryonic development of AV valves. We hypothesized that NOS3 promotes embryonic development of AV valves via EndMT. To test this hypothesis, morphological and functional analysis of AV valves were performed in wild-type (WT) and NOS3(-/-) mice at postnatal day 0. Our data show that the overall size and length of mitral and tricuspid valves were decreased in NOS3(-/-) compared with WT mice. Echocardiographic assessment showed significant regurgitation of mitral and tricuspid valves during systole in NOS3(-/-) mice. These phenotypes were all rescued by cardiac specific NOS3 overexpression. To assess EndMT, immunostaining of Snail1 was performed in the embryonic heart. Both total mesenchymal and Snail1(+) cells in the AV cushion were decreased in NOS3(-/-) compared with WT mice at E10.5 and E12.5, which was completely restored by cardiac specific NOS3 overexpression. In cultured embryonic hearts, NOS3 promoted transforming growth factor (TGFβ), bone morphogenetic protein (BMP2) and Snail1expression through cGMP. Furthermore, mesenchymal cell formation and migration from cultured AV cushion explants were decreased in the NOS3(-/-) compared with WT mice. We conclude that NOS3 promotes AV valve formation during embryonic heart development and deficiency in NOS3 results in AV valve insufficiency.

  17. Nitric oxide inhibits the degradation of IRP2.

    PubMed

    Wang, Jian; Chen, Guohua; Pantopoulos, Kostas

    2005-02-01

    Iron-regulatory protein 2 (IRP2), a posttranscriptional regulator of iron metabolism, undergoes proteasomal degradation in iron-replete cells, while it is stabilized in iron deficiency or hypoxia. IRP2 also responds to nitric oxide (NO), as shown in various cell types exposed to pharmacological NO donors and in gamma interferon/lipopolysaccharide-stimulated macrophages. However, the diverse experimental systems have yielded conflicting results on whether NO activates or inhibits IRP2. We show here that a treatment of mouse B6 fibroblasts or human H1299 lung cancer cells with the NO-releasing drug S-nitroso-N-acetyl-penicillamine (SNAP) activates IRP2 expression. Moreover, the exposure of H1299 cells to SNAP leads to stabilization of hemagglutinin (HA)-tagged IRP2, with kinetics analogous to those elicited by the iron chelator desferrioxamine. Similar results were obtained with IRP2(Delta)(73), a mutant lacking a conserved, IRP2-specific proline- and cysteine-rich domain. Importantly, SNAP fails to stabilize HA-tagged p53, suggesting that under the above experimental conditions, NO does not impair the capacity of the proteasome for protein degradation. Finally, by employing a coculture system of B6 and H1299 cells expressing NO synthase II or IRP2-HA cDNAs, respectively, we demonstrate that NO generated in B6 cells stabilizes IRP2-HA in target H1299 cells by passive diffusion. Thus, biologically synthesized NO promotes IRP2 stabilization without compromising the overall proteasomal activity. These results are consistent with the idea that NO may negatively affect the labile iron pool and thereby trigger responses to iron deficiency.

  18. Significant blood resistance to nitric oxide transfer in the lung.

    PubMed

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

    2010-05-01

    Lung diffusing capacity for nitric oxide (DLNO) is used to measure alveolar membrane conductance (DMNO), but disagreement remains as to whether DMNO=DLNO, and whether blood conductance (thetaNO)=infinity. Our previous in vitro and in vivo studies suggested that thetaNO

  19. Interplay between connexin40 and nitric oxide signaling during hypertension.

    PubMed

    Le Gal, Loïc; Alonso, Florian; Mazzolai, Lucia; Meda, Paolo; Haefliger, Jacques-Antoine

    2015-04-01

    Connexins (Cxs) and endothelial nitric oxide synthase (eNOS) contribute to the adaptation of endothelial and smooth muscle cells to hemodynamic changes. To decipher the in vivo interplay between these proteins, we studied Cx40-null mice, a model of renin-dependent hypertension which displays an altered endothelium-dependent relaxation of the aorta because of reduced eNOS levels. These mice, which were either untreated or subjected to the 1-kidney, 1-clip (1K1C) procedure, a model of volume-dependent hypertension, were compared with control mice submitted to either the 1K1C or the 2-kidney, 1-clip (2K1C) procedure, a model of renin-dependent hypertension. All operated mice became hypertensive and featured hypertrophy and altered Cx expression of the aorta. The combination of volume- and renin-dependent hypertension in Cx40-/- 1K1C mice raised blood pressure and cardiac weight index. Under these conditions, all aortas showed increased levels of Cx40 in endothelial cells and of both Cx37 and Cx45 in smooth muscle cells. In the wild-type 1K1C mice, the interactions between Cx40 and Cx37 with eNOS were enhanced, resulting in increased NO release. The Cx40-eNOS interaction could not be observed in mice lacking Cx40, which also featured decreased levels of eNOS. In these animals, the volume overload caused by the 1K1C procedure resulted in increased phosphorylation of eNOS and in a higher NO release. The findings provide evidence that Cx40 and Cx37 play an in vivo role in the regulation of eNOS.

  20. Nitric Oxide Directly Promotes Vascular Endothelial Insulin Transport

    PubMed Central

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

    2013-01-01

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

  1. Increased angiogenesis in portal hypertensive rats: role of nitric oxide.

    PubMed

    Sumanovski, L T; Battegay, E; Stumm, M; van der Kooij, M; Sieber, C C

    1999-04-01

    Systemic and especially splanchnic arterial vasodilation accompany chronic portal hypertension. Different soluble mediators causing this vasodilation have been proposed, the strongest evidence being for nitric oxide (NO). No data exist if structural vascular changes may partly account for this vasodilatory state. Here, we developed a new in vivo quantitative angiogenesis assay in the abdominal cavity and determined if: 1) portal hypertensive rats show increased angiogenesis; and 2) angiogenesis is altered by inhibiting NO formation. Portal hypertension was induced by partial portal vein ligation (PVL). Sham-operated rats served as controls (CON). During the index operation (day 0), a teflon ring filled with collagen I (Vitrogen 100) was sutured in the mesenteric cavity. After 16 days, rings were explanted, embedded in paraffin, and ingrown vessels counted using a morphometry system. The role of NO was tested by adding an antagonist of NO formation (Nomega-nitro-L-arginine [NNA], 3.3 mg/kg/d) into the drinking water. The mean number of ingrown vessels per implant was significantly higher in PVL rats compared with CON rats, i.e., 1,453 +/- 187 versus 888 +/- 116, respectively (P <.05; N = 5 per group). NNA significantly (P <.01) inhibited angiogenesis in PVL (202 +/- 124; N = 5) and in CON (174 +/- 25; N = 6) rats, respectively. In contrast, the beta-adrenergic blocker, propranolol, did not prevent angiogenesis either in PVL or CON rats in a separate set of experiments (data not shown). The conclusions drawn from this study are that: 1) rats with portal hypertension show increased angiogenesis; and 2) inhibition of NO formation significantly prevents angiogenesis in both PVL and CON rats. Therefore, splanchnic vasodilation in chronic portal hypertension may also be a result of structural changes.

  2. The use of nitric oxide donors in pharmacological studies.

    PubMed

    Feelisch, M

    1998-07-01

    A growing appreciation of the involvement of nitric oxide (NO) in numerous bioregulatory pathways has not only opened up new therapeutic avenues for organic nitrates and other NO donors but also led to an increased use of such compounds in pharmacological studies. By definition, all NO donors produce NO-related activity when applied to biological systems and are thus principally suited to either mimic an endogenous NO-related response or substitute for an endogenous NO deficiency. However, the pathways leading to enzymatic and/or non-enzymatic formation of NO differ greatly among individual compound classes, as do their chemical reactivities and kinetics of NO release. Moreover, since the reaction of NO with oxygen is a function of its concentration, the same absolute amounts of NO generated over different periods of time may lead to substantially different rates of NOx formation and, consequently, to varying extents of side reactions, such as nitration and/or nitrosation of biomolecules. Matters are further complicated by compound-specific formation of by-products, which may arise during decomposition or metabolism, sometimes in amounts far exceeding those of NO. The term "NO donor" implies that the compound releases the active mediator, NO. Ultimately, this may be true for many different chemical classes of compound, since the principal NO-related species generated may be converted to NO, if not directly released as such. However, in a biological system, the redox form of nitrogen monoxide (NO+, NO. or NO-) that is actually released makes a substantial difference to the NO donor's reactivity towards other biomolecules, the profile of by-products, and the bioresponse. Such considerations are likely to account for much of the discrepancy in experimental results obtained using the same cell or tissue preparation but different NO mimetics. Thus, compound selection is not a trivial issue and the investigator should be aware of the key properties and differences

  3. Nitric oxide inhibitory substances from the rhizomes of Dioscorea membranacea.

    PubMed

    Tewtrakul, Supinya; Itharat, Arunporn

    2007-02-12

    Thai medicinal plants locally known as Hua-Khao-Yen were examined for their inhibitory activities against lipopolysaccharide (LPS) induced nitric oxide (NO) production in RAW 264.7 cell lines. Among the plant species studied, an ethanolic extract of Dioscorea membranacea exhibited the most potent inhibitory activity, with an IC(50) value of 23.6 microg/ml. From this extract, eight compounds [two naphthofuranoxepins (1, 2), one phenanthraquinone (3), three steroids (4-6) and two steroidal saponins (7, 8)] were isolated and further investigated for their inhibitory properties of NO production. It was found that diosgenin-3-O-alpha-L-rhamnosyl (1-->2)-beta-D-glucopyranoside (7) possessed the highest activity (IC(50)=3.5 microM), followed by dioscoreanone (3, IC(50)=9.8 microM) and dioscorealide B (2, IC(50)=24.9 microM). Regarding structural requirements of diosgenin derivatives for NO production inhibitory activity, compound 7 which has a rhamnoglucosyl moiety at C-3 exhibited much higher activity than compounds that have either a diglucosyl substitution (8) or its aglycone (9); whereas, hydroxyl substitution at position 8 of naphthofuranoxepin derivatives conferred higher activity than the methoxyl group. It is concluded that diosgenin-3-O-alpha-L-rhamnosyl (1-->2)-beta-D-glucopyranoside (7), dioscoreanone (3) and dioscorealide B (2) are active principles for NO inhibitory activity of Dioscorea membranacea. Compounds 1-3 were also tested for the inhibitory effect on LPS-induced TNF-alpha release in RAW 264.7 cells. The result revealed that 3 possessed potent activity against TNF-alpha release with an IC(50) value of 17.6 microM, whereas, 1 and 2 exhibited mild activity. The present study may support the use of Dioscorea membranacea by Thai traditional doctors for treatment of the inflammatory diseases. PMID:16979312

  4. Nitric oxide regulates retinal vascular tone in humans.

    PubMed

    Dorner, Guido T; Garhofer, Gerhard; Kiss, Barbara; Polska, Elzbieta; Polak, Kaija; Riva, Charles E; Schmetterer, Leopold

    2003-08-01

    The purpose of the present study was to investigate the contribution of basal nitric oxide (NO) on retinal vascular tone in humans. In addition, we set out to elucidate the role of NO in flicker-induced retinal vasodilation in humans. Twelve healthy young subjects were studied in a three-way crossover design. Subjects received an intravenous infusion of either placebo or NG-monomethyl-L-arginine (L-NMMA; 3 or 6 mg/kg over 5 min), an inhibitor of NO synthase. Thereafter, diffuse luminance flicker was consecutively performed for 16, 32, and 64 s at a frequency of 8 Hz. The effect of L-NMMA on retinal arterial and venous diameter was assessed under resting conditions and during the hyperemic flicker response. Retinal vessel diameter was measured with a Zeiss retinal vessel analyzer. L-NMMA significantly reduced arterial diameter (3 mg/kg: -2%; 6 mg/kg: -4%, P < 0.001) and venous diameter (3 mg/kg: -5%; 6 mg/kg: -8%, P < 0.001). After placebo infusion, flicker induced a significant increase in retinal vessel diameter (P < 0.001). At a flicker duration of 64 s, arterial diameter increased by 4% and venous diameter increased by 3%. L-NMMA did not abolish these hyperemic responses but blunted venous vasodilation (P = 0.017) and arterial vasodilation (P = 0.02) in response to flicker stimulation. Our data indicate that NO contributes to basal retinal vascular tone in humans. In addition, NO appears to play a role in flicker-induced vasodilation of the human retinal vasculature.

  5. Cough and exhaled nitric oxide levels: what happens with exercise?

    PubMed

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

    2013-01-01

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

  6. Nitric oxide and phytohormone interactions: current status and perspectives

    PubMed Central

    Freschi, Luciano

    2013-01-01

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

  7. Nitric Oxide Regulates Neutrophil Migration through Microparticle Formation

    PubMed Central

    Nolan, Sarah; Dixon, Rachel; Norman, Keith; Hellewell, Paul; Ridger, Victoria

    2008-01-01

    The role of nitric oxide (NO) in regulating neutrophil migration has been investigated. Human neutrophil migration to interleukin (IL)-8 (1 nmol/L) was measured after a 1-hour incubation using a 96-well chemotaxis plate assay. The NO synthase inhibitor NG-nitro-l-arginine methyl ester (L-NAME) significantly (P < 0.001) enhanced IL-8-induced migration by up to 45%. Anti-CD18 significantly (P < 0.001) inhibited both IL-8-induced and L-NAME enhanced migration. Antibodies to L-selectin or PSGL-1 had no effect on IL-8-induced migration but prevented the increased migration to IL-8 induced by L-NAME. L-NAME induced generation of neutrophil-derived microparticles that was significantly (P < 0.01) greater than untreated neutrophils or D-NAME. This microparticle formation was dependent on calpain activity and superoxide production. Only microparticles from L-NAME and not untreated or D-NAME-treated neutrophils induced a significant (P < 0.01) increase in IL-8-induced migration and transendothelial migration. Pretreatment of microparticles with antibodies to L-selectin (DREG-200) or PSGL-1 (PL-1) significantly (P < 0.001) inhibited this effect. The ability of L-NAME-induced microparticles to enhance migration was found to be dependent on the number of microparticles produced and not an increase in microparticle surface L-selectin or PSGL-1 expression. These data show that NO can modulate neutrophil migration by regulating microparticle formation. PMID:18079439

  8. Sympathetic activation and nitric oxide function in early hypertension

    PubMed Central

    Okamoto, Luis E.; Diedrich, André; Choi, Leena; Robertson, David; Farley, Ginnie; Paranjape, Sachin; Biaggioni, Italo

    2012-01-01

    The purpose of this study was to determine if tonic restrain of blood pressure by nitric oxide (NO) is impaired early in the development of hypertension. Impaired NO function is thought to contribute to hypertension, but it is not clear if this is explained by direct effects of NO on vascular tone or indirect modulation of sympathetic activity. We determined the blood pressure effect of NO synthase inhibition with Nω-monomethyl-l-arginine (l-NMMA) during autonomic blockade with trimethaphan to eliminate baroreflex buffering and NO modulation of autonomic tone. In this setting, impaired NO modulation of vascular tone would be reflected as a blunted pressor response to l-NMMA. We enrolled a total of 66 subjects (39 ± 1.3 yr old, 30 females), 20 normotensives, 20 prehypertensives (blood pressure between 120/80 and 140/90 mmHg), 17 hypertensives, and 9 smokers (included as “positive” controls of impaired NO function). Trimethaphan normalized blood pressure in hypertensives, suggesting increased sympathetic tone contributing to hypertension. In contrast, l-NMMA produced similar increases in systolic blood pressure in normal, prehypertensive, and hypertensive subjects (31 ± 2, 32 ± 2, and 30 ± 3 mmHg, respectively), whereas the response of smokers was blunted (16 ± 5 mmHg, P = 0.012). Our results suggest that sympathetic activity plays a role in hypertension. NO tonically restrains blood pressure by ∼30 mmHg, but we found no evidence of impaired modulation by NO of vascular tone contributing to the early development of hypertension. If NO deficiency contributes to hypertension, it is likely to be through its modulation of the autonomic nervous system, which was excluded in this study. PMID:22287587

  9. Energy Landscapes and Catalysis in Nitric-oxide Synthase*

    PubMed Central

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

    2014-01-01

    Nitric oxide (NO) plays diverse roles in mammalian physiology. It is involved in blood pressure regulation, neurotransmission, and immune response, and is generated through complex electron transfer reactions catalyzed by NO synthases (NOS). In neuronal NOS (nNOS), protein domain dynamics and calmodulin binding are implicated in regulating electron flow from NADPH, through the FAD and FMN cofactors, to the heme oxygenase domain, the site of NO generation. Simple models based on crystal structures of nNOS reductase have invoked a role for large scale motions of the FMN-binding domain in shuttling electrons from the FAD-binding domain to the heme oxygenase domain. However, molecular level insight of the dynamic structural transitions in NOS enzymes during enzyme catalysis is lacking. We use pulsed electron-electron double resonance spectroscopy to derive inter-domain distance relationships in multiple conformational states of nNOS. These distance relationships are correlated with enzymatic activity through variable pressure kinetic studies of electron transfer and turnover. The binding of NADPH and calmodulin are shown to influence interdomain distance relationships as well as reaction chemistry. An important effect of calmodulin binding is to suppress adventitious electron transfer from nNOS to molecular oxygen and thereby preventing accumulation of reactive oxygen species. A complex landscape of conformations is required for nNOS catalysis beyond the simple models derived from static crystal structures of nNOS reductase. Detailed understanding of this landscape advances our understanding of nNOS catalysis/electron transfer, and could provide new opportunities for the discovery of small molecule inhibitors that bind at dynamic protein interfaces of this multidimensional energy landscape. PMID:24610812

  10. Nitric oxide produced during murine listeriosis is protective.

    PubMed Central

    Boockvar, K S; Granger, D L; Poston, R M; Maybodi, M; Washington, M K; Hibbs, J B; Kurlander, R L

    1994-01-01

    Nitric oxide (NO) has been shown to be important for intracellular microbiostasis in vitro. To determine the role of NO in immune function in vivo, groups of C57BL/6 mice were given a sublethal intravenous inoculum of Listeria monocytogenes EGD, and their urine was monitored daily for nitrate, the mammalian end product of NO metabolism. Urinary nitrate levels peaked at 5 to 10 times the basal level on days 5 to 6, when spleen and liver Listeria counts declined most steeply, and decreased thereafter, when spleens and livers were nearly sterile. Peritoneal macrophages explanted from Listeria-infected mice produced nitrite spontaneously, whereas macrophages from uninfected mice did not. The inducible NO synthase mRNA was detectable in the spleens of infected mice on days 1 to 4 of infection. When Listeria-infected mice were treated orally throughout the infection with NG-monomethyl-L-arginine (NMMA), a specific NO synthase inhibitor they showed no detectable rise in urinary nitrate excretion. Mean Listeria counts in the livers and spleens NMMA-treated mice were 1 to 3 orders of magnitude greater than counts in control mice on days 4 through 8 of infection. Compared with control mice, NMMA-treated mice also showed worse clinical signs of infection, namely, weight loss, hypothermia, decreased food and water intake, and decreased urine output. Histologically NMMA-treated mice had many more inflammatory foci in their livers and spleens than control mice. The histologic observation that mononuclear cells are present at sites of infection suggests that inhibiting NO production did not block the flux of macrophages into infected viscera. As controls for possible drug toxicity, a group of uninfected mice given NMMA orally showed no detrimental effects on weight, temperature, and food and water intake. These experiments demonstrate that inhibition of NO production in Listeria-infected mice results in an exacerbated infection and thus that NO synthesis is important for immune

  11. Effects of nitric oxide and nitrogen dioxide on bacterial growth.

    PubMed Central

    Mancinelli, R L; McKay, C P

    1983-01-01

    The effects of low concentrations of nitric oxide (NO) and nitrogen dioxide (NO2) on actively dividing cultures of Staphylococcus aureus, Micrococcus luteus, Micrococcus roseus, Serratia marcescens, Bacillus subtilis, Bacillus circulans, Bacillus megaterium, and Bacillus cereus were studied. Fresh cultures of each organism were incubated for 24 h at 25 degrees C on both nutrient agar and mineral salts glucose agar plates under atmospheres containing various low concentrations of NO in air (0 to 1.9 ppm [0 to 2.0 micrograms/g of air]), NO2 in air (0 to 5.5 ppm [0 to 8.8 micrograms/g of air]), or NO and NO2 in air. Bacteria grown under air only were used as controls. After incubation, the colonies that developed on the plates were counted. None of the bacteria tested was affected by NO or NO2 at the indicated concentrations while growing on nutrient agar. Serratia marcescens, B. circulans, B. subtilis, B. megaterium, and B. cereus grown on mineral salts glucose agar were not significantly affected by NO or NO2. Low concentrations (0 to 1.9 ppm) of NO were bacteriostatic to log-phase cultures of M. roseus, M. luteus, and Staphylococcus aureus grown on mineral salts glucose agar. Bacteriostatic activity over a 24-h interval was maximal at an initial NO concentration of 1 ppm. Appreciable amounts of NO2 were produced in 24 h at initial NO concentrations greater than 1 ppm. These results suggest that NO2 may reduce the bacteriostatic activity of NO. Low concentrations (0 to 5.5 ppm) of NO2 in air did not affect any of the bacteria tested. At these low concentrations, NO affected bacterial growth, although NO2, NO2-, and NO3- did not. In addition, it was determined that the bacteriostatic activity observed in this study was not due to an increase in the acidity of the medium. PMID:6351744

  12. Possible role of adrenomedullin and nitric oxide in major depression.

    PubMed

    Akpinar, Abdullah; Yaman, Gozde Bacik; Demirdas, Arif; Onal, Suleyman

    2013-10-01

    Adrenomedullin (ADM) and nitric oxide (NO) have been implicated in the pathogenesis of certain psychiatric disorders such as schizophrenia and bipolar disorder. ADM induces vasorelaxation by activating adenylate cyclase and stimulating the release of NO. These two molecules are known to influence cerebral activity. In this study, we aimed to examine the serum levels of ADM and NO in patients with major depression (MD). We enrolled 50 patients with MD and 50 healthy control subjects. The diagnosis of MD was established on the basis of a structured clinical interview using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). The severity of depressive symptoms was evaluated using Hamilton's 17-item Depression Rating Scale. The mean serum levels of ADM and NO in patients with MD were significantly higher than those in healthy subjects (p=0.001, for both). The severity of psychomotor retardation in patients with MD was significantly correlated with the ADM (r=0.37, p=0.007) and NO levels (r=0.29, p=0.038). The patients with obvious psychomotor retardation had significantly higher levels of ADM and NO than did the patients with no psychomotor retardation (p=0.025, p=0.030). A significantly positive correlation was found between ADM and NO levels in patients with MD (r=0.79, p=0.001). Serum levels of ADM and NO levels were not correlated with the severity or duration of depression or depressive symptoms (except psychomotor retardation). In conclusion, our study indicates that serum levels of ADM and NO are elevated in patients with MD and that increased serum levels of ADM and NO may be associated with psychomotor retardation. The ADM-NO system may serve as a new target in the treatment of patients with MD and psychomotor retardation. PMID:23867466

  13. Gas-phase disproportionation of nitric oxide at elevated pressures.

    PubMed

    Tsukahara, Hirokazu; Ishida, Takanobu; Todoroki, Yukiko; Hiraoka, Masahiro; Mayumi, Mitsufumi

    2003-02-01

    T.P. Melia's chemical kinetics study of the disproportionation of nitric oxide (NO), 3NO --> NO2 + N2O, (Melia, T.P. (1965) J. Inorg. Nucl. Chem., 27, 95-98), which is the most quoted quantitative investigation presently available, revealed a rather strong dependence of the effective rate constant, Kk' of Melia's third-order rate law, -d[NO]/dt = Kk'[NO]3, on the initial pressure of NO. In order to estimate extent of accumulation of NO2 and N2O as a function of time by integration of the rate law, we have evaluated the dependence of the effective rate constant as a function of pressure and thus as a function of time on the basis of the non-ideality of NO gas. Although our approach is crude in that the non-idealities of NO2 and N2O and other NOx products and a probable deviation of the gas mixture from the Dalton's law have not been considered, it provides a means for approximately estimating the rate of accumulation of NO2 and N2O based on Melia's data. According to these calculations, the extent of the disproportionation is generally negligible at low initial pressures, e.g. 5 atm or less, while at 200 atm, the mole fractions of NO2 and N2O can become as high as 12-13% only after 10 days. These values are alarmingly high for handling pressured NO- in N2-mixture in either research or clinical settings. This information must be borne in mind when compressed NO in commercial cylinders is employed in high precision experiments. Disproportionation of NO under pressure also deserves attention in inhalation of low doses of NO in the treatment of diseases characterized by pulmonary hypertension and hypoxemia.

  14. Release and Elementary Mechanisms of Nitric Oxide in Hair Cells

    PubMed Central

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

    2010-01-01

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

  15. Role for Nitric Oxide in Hookworm-Associated Immune Suppression▿

    PubMed Central

    Dondji, Blaise; Bungiro, Richard D.; Harrison, Lisa M.; Vermeire, Jon J.; Bifulco, Carlo; McMahon-Pratt, Diane; Cappello, Michael

    2008-01-01

    Hookworm infection is a major cause of anemia and malnutrition in resource-poor countries. Human and animal studies suggest that infection with these intestinal nematodes is associated with impaired cellular immunity, characterized by reduced lymphocyte proliferation in response to both parasite and heterologous antigens. We report here data from studies aimed at defining mechanisms through which hookworms modulate the host cellular immune response. Splenocytes and mesenteric lymph node (MLN) cells from hamsters infected with Ancylostoma ceylanicum showed minimal proliferation in response to mitogen at days 20 and 30 postinfection (p.i.), with partial recovery noted at day 70 p.i. The proliferative capacity of enriched splenocyte T-cell preparations from infected animals following stimulation with hookworm antigens was partially restored in the presence of antigen-presenting cells from uninfected hamsters. Analysis by fluorescence-activated cell sorting revealed that hookworm infection is associated with reduced percentages of both CD4+ and surface immunoglobulin G-positive lymphocytes in the spleen and MLN cells. Splenocytes from infected hamsters also secreted more nitric oxide (NO) in culture than did those from naïve animals. Inhibition of NO secretion was associated with partial restoration of the proliferative capacity of splenocytes from infected animals in response to concanavalin A, suggesting a role for NO in mediating this effect. Together, these data demonstrate that hookworm infection is associated with impaired function of antigen-presenting cells and depletion of important lymphocyte subpopulations and also suggests a role for NO in parasite-induced immunosuppression. PMID:18347036

  16. Triazine herbicides inhibit relaxin signaling and disrupt nitric oxide homeostasis.

    PubMed

    Park, Si Eun; Lim, Sa Rang; Choi, Hyung-Kyoon; Bae, Jeehyeon

    2016-09-15

    Triazines are herbicides that are widely used worldwide, and we previously observed that the maternal exposure of mice to simazine (50 or 500μg/kg) resulted in smaller ovaries and uteri of their female offspring. Here, we investigated the underlying mechanism that may account for the reproductive dysfunction induced by simazine. We found that following maternal exposure, simazine is transmitted to the offspring, as evidenced by its presence in the offspring ovaries. Analyses of the simazine-exposed offspring revealed that the expression of the relaxin hormone receptor, relaxin-family peptide receptor 1 (RXFP1), prominently decreased in their ovaries and uteri. In addition, downstream target genes of the relaxin pathway including nitric oxide (NO) synthase 2 (Nos2), Nos3, matrix metallopeptidase 9 (Mmp9), and vascular endothelial growth factor (Vegf) were downregulated in their ovaries. Moreover, AKT and extracellular signal-regulated kinases (ERK) levels and their phosphorylated active forms decreased in simazine-exposed ovaries. In vitro exposure of the human ovarian granulosa cells (KGN) and uterine endometrium cells (Hec-1A) to very low concentrations (0.001 to 1nM) of triazines including atrazine, terbuthylazine, and propazine repressed NO production with a concurrent reduction in RXFP1, NOS2, and NOS3. The inhibitory action of triazines on NO release was dependent on RXFP1, phosphoinositol 3-kinase (PI3K)/AKT, and ERK. Radioligand-binding assay also confirmed that triazines competitively inhibited the binding of relaxin to its receptor. Therefore, the present study suggests that triazine herbicides act as endocrine disrupters by interfering with relaxin hormone signaling. Thus, further evaluation of their impact on human health is imperative. PMID:27431321

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

    PubMed

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

    2009-07-01

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

  18. Identification of gene variants related to the nitric oxide pathway in patients with acute coronary syndrome.

    PubMed

    Umman, B; Cakmakoglu, B; Cincin, Z B; Kocaaga, M; Emet, S; Tamer, S; Gokkusu, C

    2015-12-10

    Dysfunction of vascular endothelium is known to have an essential role in the atherosclerotic process by releasing mediators including nitric oxide (NO). Nitric oxide maintains endothelial balance by controlling cellular processes of vascular smooth muscle cells. Evidence suggests that variations in the NO pathway could include atherosclerotic events. The objective of this study was to determine the possible effects of genes on the nitric oxide pathway in the development of acute coronary syndrome (ACS). The blood samples of 100 patients with ACS and 100 controls were collected at Istanbul University, Department of Cardiology. DNA samples were genotyped by using Illumina Cyto-SNP-12 BeadChip. The additive model and Correlation/Trend Test were selected for association analysis. Afterwards, a Q-Q graphic was drawn to compare expected and obtained values. A Manhattan plot was produced to display p-values that were generated by -log10(P) function for each SNP. The p-values under 1×10(-4) were selected as statistically significant SNPs while p-values under 5×10(-2) were considered as suspicious biomarker candidates. Nitric oxide pathway analysis was then used to find the single nucleotide polymorphisms (SNPs) related to ACS. As a result, death-associated protein kinase 3 (DAPK) (rs10426955) was found to be most statistically significant SNP. The most suspicious biomarker candidates associated with the nitric oxide pathway analysis were vascular endothelial growth factor A (VEGFA), methionine sulfoxide reductase A (MSRA), nitric oxide synthase 1 (NOS1), and GTP cyclohydrolase I (GCH-1). Further studies with large sample groups are necessary to clarify the exact role of nitric oxide in the development of disease.

  19. Identification of gene variants related to the nitric oxide pathway in patients with acute coronary syndrome.

    PubMed

    Umman, B; Cakmakoglu, B; Cincin, Z B; Kocaaga, M; Emet, S; Tamer, S; Gokkusu, C

    2015-12-10

    Dysfunction of vascular endothelium is known to have an essential role in the atherosclerotic process by releasing mediators including nitric oxide (NO). Nitric oxide maintains endothelial balance by controlling cellular processes of vascular smooth muscle cells. Evidence suggests that variations in the NO pathway could include atherosclerotic events. The objective of this study was to determine the possible effects of genes on the nitric oxide pathway in the development of acute coronary syndrome (ACS). The blood samples of 100 patients with ACS and 100 controls were collected at Istanbul University, Department of Cardiology. DNA samples were genotyped by using Illumina Cyto-SNP-12 BeadChip. The additive model and Correlation/Trend Test were selected for association analysis. Afterwards, a Q-Q graphic was drawn to compare expected and obtained values. A Manhattan plot was produced to display p-values that were generated by -log10(P) function for each SNP. The p-values under 1×10(-4) were selected as statistically significant SNPs while p-values under 5×10(-2) were considered as suspicious biomarker candidates. Nitric oxide pathway analysis was then used to find the single nucleotide polymorphisms (SNPs) related to ACS. As a result, death-associated protein kinase 3 (DAPK) (rs10426955) was found to be most statistically significant SNP. The most suspicious biomarker candidates associated with the nitric oxide pathway analysis were vascular endothelial growth factor A (VEGFA), methionine sulfoxide reductase A (MSRA), nitric oxide synthase 1 (NOS1), and GTP cyclohydrolase I (GCH-1). Further studies with large sample groups are necessary to clarify the exact role of nitric oxide in the development of disease. PMID:26232608

  20. Lipopolysaccharide-induced murine embryonic resorption involves nitric oxide-mediated inhibition of the NAD+-dependent 15-hydroxyprostaglandin dehydrogenase.

    PubMed

    Aisemberg, Julieta; Bariani, María V; Vercelli, Claudia A; Wolfson, Manuel L; Franchi, Ana M

    2012-10-01

    The initial inactivation of prostaglandins (PGs) is mediated by 15-hydroxyprostaglandin dehydrogenase (15-PGDH). PGs are potent mediators of several biological processes, including inflammation and reproduction. In uterus, PGs play a key role in infection-induced pregnancy loss, in which concentration of this mediator increased. This process is accompanied with the induction of nitric oxide synthase expression and a marked increase in uterine levels of nitric oxide. There is no information concerning nitric oxide contribution to potential changes in PG catabolism, but experimental evidence suggests that nitric oxide modulates PG pathways. The specific objectives of the study were to evaluate the protein expression of HPGD (15-PGDH) and to characterize the nitric oxide-dependent regulation of this enzyme in a model of lipopolysaccharide (LPS)-induced embryonic resorption. Results show that LPS decreased HPGD protein expression and augmented PGE synthase activity; therefore, PGE₂ levels increased in uterus in this inflammatory condition. Just as LPS, the treatment with a nitric oxide donor diminished HPGD protein expression in uterine tissue. In contrast, the inhibition of nitric oxide synthesis both in control and in LPS-treated mice increased 15-PGDH levels. Also, we have found that this enzyme and PGE₂ levels are not modulated by peroxynitrite, an oxidant agent derived from nitric oxide. This study suggests that LPS and nitric oxide promote a decrease in the ability of the uterus for PG catabolism during bacterially triggered pregnancy loss in mice. PMID:22843771

  1. Nitric oxide interactions with cobalamins: biochemical and functional consequences.

    PubMed

    Brouwer, M; Chamulitrat, W; Ferruzzi, G; Sauls, D L; Weinberg, J B

    1996-09-01

    Nitric oxide (NO) is a paramagnetic gas that has been implicated in a wide range of biologic functions. The common pathway to evoke the functional response frequently involves the formation of an iron-nitrosyl complex in a target (heme) protein. In this study, we report on the interactions between NO and cobalt-containing vitamin B12 derivatives. Absorption spectroscopy showed that of the four Co(III) derivatives (cyanocobalamin [CN-Cbl], aquocobalamin [H2O-Cbl], adenosylcobalamin [Ado-Cbl], and methylcobalamin [MeCbl]), only the H2O-Cbl combined with NO. In addition, electron paramagnetic resonance spectroscopy of H2O-Cbl preparations showed the presence of a small amount of Cob-(II)alamin that was capable of combining with NO. The Co(III)-NO complex was very stable, but could transfer its NO moiety to hemoglobin (Hb). The transfer was accompanied by a reduction of the Co(III) to Co(II), indicating that NO+ (nitrosonium) was the leaving group. In accordance with this, the NO did not combine with the Hb Fe(II)-heme, but most likely with the Hb cysteine-thiolate. Similarly, the Co(III)-NO complex was capable of transferring its NO to glutathione. Ado-Cbl and Me-Cbl were susceptible to photolysis, but CN-Cbl and H2O-Cbl were not. The homolytic cleavage of the Co(III)-Ado or Co(III)-Me bond resulted in the reduction of the metal. When photolysis was performed in the presence of NO, formation of NO-Co(II) was observed. Co(II)-nitrosyl oxidized slowly to form Co(III)-nitrosyl. The capability of aquocobalamin to combine with NO had functional consequences. We found that nitrosylcobalamin had diminished ability to serve as a cofactor for the enzyme methionine synthase, and that aquocobalamin could quench NO-mediated inhibition of cell proliferation. Our in vitro studies therefore suggest that interactions between NO and cobalamins may have important consequences in vivo. PMID:8781445

  2. Particulate Oxidative Burden as a Predictor of Exhaled Nitric Oxide in Children with Asthma

    PubMed Central

    Maikawa, Caitlin L.; Weichenthal, Scott; Wheeler, Amanda J.; Dobbin, Nina A.; Smargiassi, Audrey; Evans, Greg; Liu, Ling; Goldberg, Mark S.; Pollitt, Krystal J. Godri

    2016-01-01

    Background: Epidemiological studies have provided strong evidence that fine particulate matter (PM2.5; aerodynamic diameter ≤ 2.5 μm) can exacerbate asthmatic symptoms in children. Pro-oxidant components of PM2.5 are capable of directly generating reactive oxygen species. Oxidative burden is used to describe the capacity of PM2.5 to generate reactive oxygen species in the lung. Objective: In this study we investigated the association between airway inflammation in asthmatic children and oxidative burden of PM2.5 personal exposure. Methods: Daily PM2.5 personal exposure samples (n = 249) of 62 asthmatic school-aged children in Montreal were collected over 10 consecutive days. The oxidative burden of PM2.5 samples was determined in vitro as the depletion of low-molecular-weight antioxidants (ascorbate and glutathione) from a synthetic model of the fluid lining the respiratory tract. Airway inflammation was measured daily as fractional exhaled nitric oxide (FeNO). Results: A positive association was identified between FeNO and glutathione-related oxidative burden exposure in the previous 24 hr (6.0% increase per interquartile range change in glutathione). Glutathione-related oxidative burden was further found to be positively associated with FeNO over 1-day lag and 2-day lag periods. Results further demonstrate that corticosteroid use may reduce the FeNO response to elevated glutathione-related oxidative burden exposure (no use, 15.8%; irregular use, 3.8%), whereas mold (22.1%), dust (10.6%), or fur (13.1%) allergies may increase FeNO in children with versus children without these allergies (11.5%). No association was found between PM2.5 mass or ascorbate-related oxidative burden and FeNO levels. Conclusions: Exposure to PM2.5 with elevated glutathione-related oxidative burden was associated with increased FeNO. Citation: Maikawa CL, Weichenthal S, Wheeler AJ, Dobbin NA, Smargiassi A, Evans G, Liu L, Goldberg MS, Godri Pollitt KJ. 2016. Particulate oxidative burden

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

    SciTech Connect

    Elespuru, R.K.; Mark, T.W.

    1995-11-01

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

  4. Anticancer efficacy of a nitric oxide-modified derivative of bifendate against multidrug-resistant cancer cells.

    PubMed

    Ren, Zhiguang; Gu, Xiaoke; Lu, Bin; Chen, Yaqiong; Chen, Guojiang; Feng, Jiannan; Lin, Jizhen; Zhang, Yihua; Peng, Hui

    2016-06-01

    The development of multidrug resistance (MDR) not only actively transports a wide range of cytotoxic drugs across drug transporters but is also a complex interaction between a number of important cellular signalling pathways. Nitric oxide donors appear to be a new class of anticancer therapeutics for satisfying all the above conditions. Previously, we reported furoxan-based nitric oxide-releasing compounds that exhibited selective antitumour activity in vitro and in vivo. Herein, we demonstrate that bifendate (DDB)-nitric oxide, a synthetic furoxan-based nitric oxide-releasing derivative of bifendate, effectively inhibits the both sensitive and MDR tumour cell viability at a comparatively low concentration. Interestingly, the potency of DDB-nitric oxide is the independent of inhibition of the functions and expressions of three major ABC transporters. The mechanism of DDB-nitric oxide appears to be in two modes of actions by inducing mitochondrial tyrosine nitration and apoptosis, as well as by down-regulating HIF-1α expression and protein kinase B (AKT), extracellular signal-regulated kinases (ERK), nuclear factor κB (NF-κB) activation in MDR cells. Moreover, the addition of a typical nitric oxide scavenger significantly attenuated all the effects of DDB-nitric oxide, indicating that the cytotoxicity of DDB-nitric oxide is as a result of higher levels of nitric oxide release in MDR cancer cells. Given that acquired MDR to nitric oxide donors is reportedly difficult to achieve and genetically unstable, compound like DDB-nitric oxide may be a new type of therapeutic agent for the treatment of MDR tumours.

  5. Fucoidan extracted from Fucus evanescens prevents endotoxin-induced damage in a mouse model of endotoxemia.

    PubMed

    Kuznetsova, Tatyana A; Besednova, Natalya N; Somova, Larisa M; Plekhova, Natalya G

    2014-01-31

    An important problem of treating patients with endotoxemia is to find drugs to reduce the negative effects of endotoxin on the organism. We tested fucoidan (sulfated polysaccharide) from the brown alga Fucus evanescens as a potential drug in a mouse model of endotoxemia inducted by lipopolysaccharide (LPS). The survival time of mice injected with LPS increased under fucoidan treatment compared with the group of mice injected with LPS only. The preventive administration of fucoidan to mice with endotoxemia resulted in inhibition of increased levels of proinflammatory cytokines (TNFα and IL-6), as well as decreasing of the processes of hypercoagulability. The parenteral or per os administration of fucoidan resulted in decreasing the degree of microcirculatory disorders and secondary dystrophic-destructive changes in parenchymal organs of mice with endotoxemia. Taken together, these results demonstrate that fucoidan prevents endotoxin-induced damage in a mouse model of endotoxemia and increases the mice's resistance to LPS.

  6. Proliferation of macrophages due to the inhibition of inducible nitric oxide synthesis by oxidized low-density lipoproteins

    PubMed Central

    Brunner, Monika; Gruber, Miriam; Schmid, Diethart; Baran, Halina; Moeslinger, Thomas

    2015-01-01

    Oxidized low-density lipoprotein (ox-LDL) is assumed to be a major causal agent in hypercholesteraemia-induced atherosclerosis. Because the proliferation of lipid-loaden macrophages within atherosclerotic lesions has been described, we investigated the dependence of macrophage proliferation on the inhibition of inducible nitric oxide synthase (iNOS) by hypochlorite oxidized LDL. Ox-LDL induces a dose dependent inhibition of inducible nitric oxide synthesis in lipopolysaccharide-interferon stimulated mouse macrophages (J774.A1) with concomitant macrophage proliferation as assayed by cell counting, tritiated-thymidine incorporation and measurement of cell protein. Native LDL did not influence macrophage proliferation and inducible nitric oxide synthesis. iNOS protein and mRNA was reduced by HOCl-oxidized LDL (0-40 µg/ml) as revealed by immunoblotting and competitive semiquantitative PCR. Macrophage proliferation was increased by the addition of the iNOS inhibitor L-NAME. The addition of ox-LDL to L-NAME containing incubations induced no further statistically significant increase in cell number. Nitric oxide donors decreased ox-LDL induced macrophage proliferation and nitric oxide scavengers restored macrophage proliferation to the initial values achieved by ox-LDL. The decrease of cytosolic DNA fragments in stimulated macrophages incubated with ox-LDL demonstrates that the proliferative actions of ox-LDL are associated with a decrease of NO-induced apoptosis. Our data show that inhibition of iNOS dependent nitric oxide production caused by hypochlorite oxidized LDL enhances macrophage proliferation. This might be a key event in the pathogenesis of atherosclerotic lesions. PMID:26600745

  7. Aerobic Oxidation of an Osmium(III) N-Hydroxyguanidine Complex To Give Nitric Oxide.

    PubMed

    Xiang, Jing; Wang, Qian; Yiu, Shek-Man; Man, Wai-Lun; Kwong, Hoi-Ki; Lau, Tai-Chu

    2016-05-16

    The aerobic oxidation of the N-hydroxyguanidinum moiety of N-hydroxyarginine to NO is a key step in the biosynthesis of NO by the enzyme nitric oxide synthase (NOS). So far, there is no chemical system that can efficiently carry out similar aerobic oxidation to give NO. We report here the synthesis and X-ray crystal structure of an osmium(III) N-hydroxyguanidine complex, mer-[Os(III){NH═C(NH2)(NHOH)}(L)(CN)3](-) (OsGOH, HL = 2-(2-hydroxyphenyl)benzoxazole), which to the best of our knowledge is the first example of a transition metal N-hydroxyguanidine complex. More significantly, this complex readily undergoes aerobic oxidation at ambient conditions to generate NO. The oxidation is pH-dependent; at pH 6.8, fac-[Os(NO)(L)(CN)3](-) is formed in which the NO produced is bound to the osmium center. On the other hand, at pH 12, aerobic oxidation of OsGOH results in the formation of the ureato complex [Os(III)(NHCONH2)(L)(CN)3](2-) and free NO. Mechanisms for this aerobic oxidation at different pH values are proposed. PMID:27135258

  8. [Effect of xuebijing oral effervescent tablet on endotoxin induced fever and disseminated intravascular coagulation rabbit model].

    PubMed

    Guo, Shan-Shan; Gao, Ying-Jie; Tian, Xue-Chuan; Jin, Ya-Hong; Liu, Fang-Zhou; Cui, Xiao-Lan

    2013-08-01

    In order to discover the mechanism of Xuebijing oral effervescent tablet (XBJOET) to treat infectious diseases, the effect of XBJOET on endotoxin induced rabbit fever and disseminated intravascular coagulation (DIC) was investigated. Auricle microcirculation in rabbit was detected by laser speckle blood perfusion imager system; coagulation function was measured by coagulation analyzer, fibrinolytic system was quantified by Elisa assay and micro thrombosis in tissues was observed with HE staining under light microscope. The results demonstrated that the body temperature of rabbit decreased significantly at 1-3 h after administration with 4.8, 2.4 and 1.2 g x kg(-1) XBJOET to endotoxin induced DIC rabbit model, the auricle microcirculation blood flow in model group (54.45 +/- 14.53) PU was lower than that in control group (77.18 +/- 12.32) PU. The auricle microcirculation blood flow increased markedly and there was significant difference between model group and 1.2 g x kg(-1) XBJOET group. There was significant difference between model group and control group in the content of PAI1 and FIB. The PAI1 levels in model and control groups were (30.48 +/- 2.46) ng x mL(-1) and (20.93 +/- 3.25) ng x mL(-1), respectively. The FIB levels in model and control group were (3.34 +/- 1.09) g x L(-1) and (4.84 +/- 1.10) g x L(-1), respectively. The content of PAI1 in rabbit plasma decreased notably, there were significant differences between model group and 4.8, 2.4 g x kg(-1) XBJOET groups. On the contrary the content of FIB increased. XBJOET possessed pharmacological activities of curing infectious fever and DIC, the mechanism of which is related to amelioration of microcirculation disturbance, inhibition of fibrinolytic system activation and coagulation and micro thrombosis elimination.

  9. Danaparoid sodium inhibits systemic inflammation and prevents endotoxin-induced acute lung injury in rats

    PubMed Central

    Hagiwara, Satoshi; Iwasaka, Hideo; Hidaka, Seigo; Hishiyama, Sohei; Noguchi, Takayuki

    2008-01-01

    Introduction Systemic inflammatory mediators, including high mobility group box 1 (HMGB1), play an important role in the development of sepsis. Anticoagulants, such as danaparoid sodium (DA), may be able to inhibit sepsis-induced inflammation, but the mechanism of action is not well understood. We hypothesised that DA would act as an inhibitor of systemic inflammation and prevent endotoxin-induced acute lung injury in a rat model. Methods We used male Wistar rats. Animals in the intervention arm received a bolus of 50 U/kg of DA or saline injected into the tail vein after lipopolysaccharide (LPS) administration. We measured cytokine (tumour necrosis factor (TNF)α, interleukin (IL)-6 and IL-10) and HMGB1 levels in serum and lung tissue at regular intervals for 12 h following LPS injection. The mouse macrophage cell line RAW 264.7 was assessed following stimulation with LPS alone or concurrently with DA with identification of HMGB1 and other cytokines in the supernatant. Results Survival was significantly higher and lung histopathology significantly improved among the DA (50 U/kg) animals compared to the control rats. The serum and lung HMGB1 levels were lower over time among DA-treated animals. In the in vitro study, administration of DA was associated with decreased production of HMGB1. In the cell signalling studies, DA administration inhibited the phosphorylation of IκB. Conclusion DA decreases cytokine and HMGB1 levels during LPS-induced inflammation. As a result, DA ameliorated lung pathology and reduces mortality in endotoxin-induced systemic inflammation in a rat model. This effect may be mediated through the inhibition of cytokines and HMGB1. PMID:18380908

  10. Anti-inflammatory and protective properties of daphnetin in endotoxin-induced lung injury.

    PubMed

    Yu, Wen-wen; Lu, Zhe; Zhang, Hang; Kang, Yan-hua; Mao, Yun; Wang, Huan-huan; Ge, Wei-hong; Shi, Li-yun

    2014-12-24

    Uncontrolled inflammatory responses cause tissue injury and severe immunopathology. Pharmacological interference of intracellular pro-inflammatory signaling may confer a therapeutic benefit under these conditions. Daphnetin, a natural coumarin derivative, has been used to treat inflammatory diseases including bronchitis. However, the protective effect of daphnetin in inflammatory airway disorders has yet to be determined, and the molecular basis for its anti-inflammatory properties is unknown. This paper shows that daphnetin treatment conferred substantial protection from endotoxin-induced acute lung injury (ALI), in parallel with reductions in the production of inflammatory mediators, symptoms of airway response, and infiltration of inflammatory cells. Further studies indicate that activation of macrophage and human alveolar epithelial cells in response to lipopolysaccharide (LPS) was remarkably suppressed by daphnetin, which was related to the down-regulation of NF-κB-dependent signaling events. Importantly, this study demonstrates that TNF-α-induced protein 3 (TNFAIP3), also known as A20, was significantly induced by daphnetin, which appeared to be largely responsible for the down-regulation of NF-κB activity through modulation of nondegradative TRAF6 ubiquitination. Accordingly, the deletion of TNFAIP3 in primary macrophages reversed daphnetin-elicited inhibition of immune response, and the beneficial effect of daphnetin in the pathogenesis of ALI was, partially at least, abrogated by TNFAIP3 knockdown. These findings demonstrate the anti-inflammatory and protective functions of daphnetin in endotoxin-induced lung inflammation and injury and also reveal the key mechanism underlying its action in vitro as well as in vivo.

  11. Inhaled nitric oxide decreases pulmonary endothelial nitric oxide synthase expression and activity in normal newborn rat lungs

    PubMed Central

    Hua-Huy, Thông; Duong-Quy, Sy; Pham, Hoa; Pansiot, Julien; Mercier, Jean-Christophe; Baud, Olivier

    2016-01-01

    Inhaled nitric oxide (iNO) is commonly used in the treatment of very ill pre-term newborns. Previous studies showed that exogenous NO could affect endothelial NO synthase (eNOS) activity and expression in vascular endothelial cell cultures or adult rat models, but this has never been fully described in newborn rat lungs. We therefore aimed to assess the effects of iNO on eNOS expression and activity in newborn rats. Rat pups, post-natal day (P) 0 to P7, and their dams were placed in a chamber containing NO at 5 ppm (iNO-5 ppm group) or 20 ppm (iNO-20 ppm group), or in room air (control group). Rat pups were sacrificed at P7 and P14 for evaluation of lung eNOS expression and activity. At P7, eNOS protein expression in total lung lysates, in bronchial and arterial sections, was significantly decreased in the iNO-20 ppm versus control group. At P14, eNOS expression was comparable among all three groups. The amounts of eNOS mRNA significantly differed at P7 between the iNO-20 ppm and control groups. NOS activity decreased in the iNO-20 ppm group at P7 and returned to normal levels at P14. There was an imbalance between superoxide dismutase and NOS activities in the iNO-20 ppm group at P7. Inhalation of NO at 20 ppm early after birth decreases eNOS gene transcription, protein expression and enzyme activity. This decrease might account for the rebound phenomenon observed in patients treated with iNO.

  12. Nitric oxide-mediated hyporeactivity to noradrenaline precedes the induction of nitric oxide synthase in endotoxin shock.

    PubMed Central

    Szabó, C.; Mitchell, J. A.; Thiemermann, C.; Vane, J. R.

    1993-01-01

    1. The role of an enhanced formation of nitric oxide (NO) and the relative importance of the constitutive and inducible NO synthase (NOS) for the development of immediate (within 60 min) and delayed (at 180 min) vascular hyporeactivity to noradrenaline was investigated in a model of circulatory shock induced by endotoxin (lipopolysaccharide; LPS) in the rat. 2. Male Wistar rats were anaesthetized and instrumented for the measurement of mean arterial blood pressure (MAP) and heart rate. In addition, the calcium-dependent and calcium-independent NOS activity was measured ex vivo by the conversion of [3H]-arginine to [3H]-citrulline in homogenates from several organs obtained from vehicle- and LPS-treated rats. 3. E. coli LPS (10 mg kg-1, i.v. bolus) caused a rapid (within 5 min) and sustained fall in MAP. At 30 and 60 min after LPS, pressor responses to noradrenaline (0.3, 1 or 3 micrograms kg-1, i.v.) were significantly reduced. The pressor responses were restored by NG-nitro-L-arginine methyl ester (L-NAME, 1 mg kg-1, i.v. at 60 min), a potent inhibitor of NO synthesis. In contrast, L-NAME did not potentiate the noradrenaline-induced pressor responses in control animals. 4. Dexamethasone (3 mg kg-1, i.v., 60 min prior to LPS), a potent inhibitor of the induction of NOS, did not alter initial MAP or pressor responses to noradrenaline in control rats, but significantly attenuated the LPS-induced fall in MAP at 15 to 60 min after LPS. Dexamethasone did not influence the development of the LPS-induced immediate (within 60 min) hyporeactivity to noradrenaline.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7682137

  13. Traumatic Brain Injury Disrupts Cerebrovascular Tone Through Endothelial Inducible Nitric Oxide Synthase Expression and Nitric Oxide Gain of Function

    PubMed Central

    Villalba, Nuria; Sonkusare, Swapnil K.; Longden, Thomas A.; Tran, Tram L.; Sackheim, Adrian M.; Nelson, Mark T.; Wellman, George C.; Freeman, Kalev

    2014-01-01

    Background Traumatic brain injury (TBI) has been reported to increase the concentration of nitric oxide (NO) in the brain and can lead to loss of cerebrovascular tone; however, the sources, amounts, and consequences of excess NO on the cerebral vasculature are unknown. Our objective was to elucidate the mechanism of decreased cerebral artery tone after TBI. Methods and Results Cerebral arteries were isolated from rats 24 hours after moderate fluid‐percussion TBI. Pressure‐induced increases in vasoconstriction (myogenic tone) and smooth muscle Ca2+ were severely blunted in cerebral arteries after TBI. However, myogenic tone and smooth muscle Ca2+ were restored by inhibition of NO synthesis or endothelium removal, suggesting that TBI increased endothelial NO levels. Live native cell NO, indexed by 4,5‐diaminofluorescein (DAF‐2 DA) fluorescence, was increased in endothelium and smooth muscle of cerebral arteries after TBI. Clamped concentrations of 20 to 30 nmol/L NO were required to simulate the loss of myogenic tone and increased (DAF‐2T) fluorescence observed following TBI. In comparison, basal NO in control arteries was estimated as 0.4 nmol/L. Consistent with TBI causing enhanced NO‐mediated vasodilation, inhibitors of guanylyl cyclase, protein kinase G, and large‐conductance Ca2+‐activated potassium (BK) channel restored function of arteries from animals with TBI. Expression of the inducible isoform of NO synthase was upregulated in cerebral arteries isolated from animals with TBI, and the inducible isoform of NO synthase inhibitor 1400W restored myogenic responses following TBI. Conclusions The mechanism of profound cerebral artery vasodilation after TBI is a gain of function in vascular NO production by 60‐fold over controls, resulting from upregulation of the inducible isoform of NO synthase in the endothelium. PMID:25527626

  14. Endothelial nitric oxide synthase gene haplotypes and circulating nitric oxide levels significantly associate with risk of essential hypertension.

    PubMed

    Nejatizadeh, Azim; Kumar, Rahul; Stobdan, Tsering; Goyal, A K; Sikdar, Sunandan; Gupta, Mohit; Javed, Saleem; Pasha, M A Qadar

    2008-06-01

    Nitric oxide (NO), a potent vasodilator, plays a pivotal role in blood pressure regulation. Endothelial NO synthase gene (NOS3) polymorphisms influence NO levels. Here, we investigated the role of the -922A/G, -786T/C, 4b/4a, and 894G/T polymorphisms of the NOS3 and NO(x) levels in 800 consecutive unrelated subjects comprising 455 patients of essential hypertension and 345 controls. The polymorphisms were investigated independently and as haplotypes. Plasma NO(x) levels (nitrate and nitrite) were estimated by the Griess method. Genotype frequencies for the -786T/C, 4b/4a, and 894G/T polymorphisms differed significantly (P<0.001) between patients and controls and were associated with an increased risk of hypertension (OR=2.0, OR=3.8, OR=1.6, respectively). The 4-locus haplotypes ATaG (H1), ATaT (H2), and GCaG (H3) were significantly associated with essential hypertension and served as susceptible haplotypes (P

  15. Intracellular Conversion of Environmental Nitrate and Nitrite to Nitric Oxide with Resulting Developmental Toxicity to the Crustacean Daphnia magna

    PubMed Central

    Hannas, Bethany R.; Das, Parikshit C.; Li, Hong; LeBlanc, Gerald A.

    2010-01-01

    Background Nitrate and nitrite (jointly referred to herein as NOx) are ubiquitous environmental contaminants to which aquatic organisms are at particularly high risk of exposure. We tested the hypothesis that NOx undergo intracellular conversion to the potent signaling molecule nitric oxide resulting in the disruption of endocrine-regulated processes. Methodology/Principal Findings These experiments were performed with insect cells (Drosophila S2) and whole organisms Daphnia magna. We first evaluated the ability of cells to convert nitrate (NO3−) and nitrite (NO2−) to nitric oxide using amperometric real-time nitric oxide detection. Both NO3− and NO2− were converted to nitric oxide in a substrate concentration-dependent manner. Further, nitric oxide trapping and fluorescent visualization studies revealed that perinatal daphnids readily convert NO2− to nitric oxide. Next, daphnids were continuously exposed to concentrations of the nitric oxide-donor sodium nitroprusside (positive control) and to concentrations of NO3− and NO2−. All three compounds interfered with normal embryo development and reduced daphnid fecundity. Developmental abnormalities were characteristic of those elicited by compounds that interfere with ecdysteroid signaling. However, no compelling evidence was generated to indicate that nitric oxide reduced ecdysteroid titers. Conclusions/Significance Results demonstrate that nitrite elicits developmental and reproductive toxicity at environmentally relevant concentrations due likely to its intracellular conversion to nitric oxide. PMID:20805993

  16. Analysis of Nitric Oxide-Dependent Antimicrobial Actions in Macrophages and Mice

    PubMed Central

    Vazquez-Torres, Andrés; Stevanin, Tania; Jones-Carson, Jessica; Castor, Margaret; Read, Robert C.; Fang, Ferric C.

    2009-01-01

    Nitric oxide (NO•) is a critical component of mammalian host defense that is produced in macrophages and other cells comprising the innate immune system. Isolated mammalian macrophages have been utilized to measure the kinetics of NO production and to demonstrate NO-related antimicrobial actions. Some microorganisms possess enzymes to detoxify nitrogen oxides, and mutant strains lacking these enzymes can be used to demonstrate the importance of these mechanisms for intracellular bacterialsurvival. This chapter describes techniques with which to analyze the antimicrobial actions of nitric oxide in murine and human macrophages and in laboratory mice. PMID:18433645

  17. Nitric oxide and beyond: new insights and therapies for pulmonary hypertension

    PubMed Central

    Steinhorn, RH

    2009-01-01

    Persistent pulmonary hypertension of the newborn (PPHN) contributes significantly to the morbidity and mortality associated with meconium aspiration syndrome. This review article discusses new insights into the vascular abnormalities that are associated with PPHN, including the recent recognition of the importance of oxidant stress in its pathogenesis. Recent data are presented showing that treatment with high oxygen concentrations may increase production of oxygen free radicals. The rationale for the use of inhaled nitric oxide, and strategies for enhancing nitric oxide signaling are discussed. Finally, the rationale for new treatment approaches is reviewed, including inhibition of cyclic guanosine monophosphate-specific phosphodiesterases and scavengers of reactive oxygen species. PMID:19057613

  18. Remote sensing of nitric oxide emissions from planes, trains and automobiles

    NASA Astrophysics Data System (ADS)

    Popp, Peter John

    Remote sensing has been proven as an effective method for measuring in-use mobile source emissions. This document describes the development of a remote sensor for mobile source nitric oxide, based on an instrument previously developed at the University of Denver for measuring carbon monoxide and hydrocarbon emissions. The new remote sensor makes use of a high-speed ultraviolet spectrometer to quantify nitric oxide by absorption spectroscopy at 226 nm in the ultraviolet region. The high-speed spectrometer is coupled to an existing FEAT remote sensor, for the simultaneous measurement of CO, CO2 and hydrocarbons by non-dispersive infrared absorption spectroscopy. The utility of the instrument was demonstrated in the measurement of nitric oxide emissions from automobiles, commercial aircraft, and railroad locomotives. The remote sensor was used to measure nitric oxide emissions from motor vehicles in Chicago in 1997 and 1998, as part of a five-year study to characterize motor vehicle emissions and deterioration in that city. Emissions data were collected for over 19,000 vehicles in 1997 and almost 23,000 vehicles in 1998. All of these records contained valid measurements for carbon monoxide and hydrocarbons, in addition to nitric oxide. In September of 1997, a study was conducted with the cooperation of British Airways and the British Airports Authority to demonstrate the capability of the remote sensor in measuring nitric oxide emissions from in-use commercial aircraft. In two days of sampling at London Heathrow Airport, a total of 122 measurements were made of 90 different aircraft, ranging in size from Gulfstream executive jets to Boeing 747-400s. The measured nitric oxide emission indices were not inconsistent with commercial aircraft emission indices published by the International Civil Aviation Organization. The utility of the remote sensor in measuring nitric oxide emissions from railroad locomotives was demonstrated in January of 1999, in a study conducted with

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

    NASA Technical Reports Server (NTRS)

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

    2000-01-01

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

  20. Reduction in nitrogen dioxide concentration by soda lime preparations during simulated nitric oxide inhalation.

    PubMed

    Weimann, J; Hagenah, J U; Motsch, J

    1997-11-01

    Nitrogen dioxide is formed during delivery of inhaled nitric oxide for the treatment of patients with pulmonary hypertension. Soda lime has been shown to absorb nitrogen dioxide. We tested three different commercially available soda lime preparations (Sodasorb, Drägersorb 800 and Sofnolime) for their efficacy in absorbing nitrogen dioxide and nitric oxide during simulated nitric oxide inhalation. All soda lime preparation absorbed nitrogen dioxide (15%, 24% and 34%, respectively). To test if this difference could be attributed to the potassium hydroxide (KOH) content of the different preparations, two other preparations with a higher (3.0% and 7.3% w/w, respectively) KOH content were tested and we found an increase in nitrogen dioxide removal up to 47% and 46%, respectively. We conclude that soda lime absorbed nitrogen dioxide during nitric oxide inhalation. This effect seemed to be moderate under simulated clinical conditions, but increased using soda lime with a higher KOH content. Nevertheless, we recommend continuous monitoring of inspired nitrogen dioxide concentration during clinical inhalation of nitric oxide.

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

    NASA Technical Reports Server (NTRS)

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

    2001-01-01

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

  2. Caffeinated nitric oxide-releasing lozenge improves cycling time trial performance.

    PubMed

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

    2015-02-01

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

  3. Caffeinated nitric oxide-releasing lozenge improves cycling time trial performance.

    PubMed

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

    2015-02-01

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

  4. Nitric oxide-releasing polymeric nanoparticles against Trypanosoma cruzi

    NASA Astrophysics Data System (ADS)

    Seabra, A. B.; Kitice, N. A.; Pelegrino, M. T.; Lancheros, C. A. C.; Yamauchi, L. M.; Pinge-Filho, P.; Yamada-Ogatta, S. F.

    2015-05-01

    Chagas disease, also known as American trypanosomiasis, is a potentially life-threatening illness caused by the protozoan parasite, Trypanosoma cruzi (T. cruzi), and the disease remains a major health problem in many Latin American countries. Several papers report that the killing of the parasite is dependent on the production of nitric oxide (NO). The endogenous free radical NO is an important cellular signalling molecule that plays a key role in the defense against pathogens, including T. cruzi. As T. cruzi is able to compromise host macrophages decreasing endogenous NO production, the administration of exogenous NO donors represents an interesting strategy to combat Chagas disease. Thus, the aims of this study were to prepare and evaluate the antimicrobial activity of NO-releasing polymeric nanoparticles against T. cruzi. Biocompatible polymeric nanoparticles composed of chitosan/sodium tripolyphosphate(TPP) were prepared and used to encapsulate mercaptosuccinic acid (MSA), which is a thiol-containing molecule. Nitrosation of free thiols (SH) groups of MSA were performed by the addition of equimolar amount of sodium nitrite (NaNO2), leading to the formation of S-nitroso-MSA-containing nanoparticles. These polymeric nanoparticles act as spontaneous NO donors, with free NO release. The results show the formation of nanoparticles with average hydrodynamic diameter ranging from 270 to 500 nm, average of polydispersity index of 0.35, and encapsulation efficiency in the range of 99%. The NO release kinetics from the S-nitroso-MSA-containing nanoparticles showed sustained and controlled NO release over several hours. The microbicidal activity of S-nitroso-MSA-containing nanoparticles was evaluated by incubating NO-releasing nanoparticles (200 - 600 μg/mL) with replicative and non-infective epimastigote, and non-replicative and infective trypomastigote forms of T. cruzi. In addition, a significant decrease in the percentage of macrophage-infected (with amastigotes) and

  5. Significant blood resistance to nitric oxide transfer in the lung

    PubMed Central

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

    2010-01-01

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

  6. A neurovascular transmission model for acupuncture-induced nitric oxide.

    PubMed

    Hsiao, Sheng-Hsiung; Tsai, Li-Jen

    2008-09-01

    Acupuncture is the practice of inserting needles into the body to reduce pain or induce anesthesia. More broadly, acupuncture is a family of procedures involving the stimulation of anatomical locations on or in the skin by a variety of techniques. Employing acupuncture to treat human disease or maintain bodily condition has been practiced for thousands of years. However, the mechanism(s) of action of acupuncture at the various meridians are poorly understood. Most studies have indicated that acupuncture is able to increase blood flow. The acupuncture points have high electrical conductance and a relationship of the acupuncture points and meridians with the connective tissue planes and the perivascular space has also been suggested. Several studies employing the human and animal models have shown that acupuncture enhances the generation of nitric oxide (NO) and increases local circulation. Specifically, electroacupuncture (EA) seems to prevent the reduction in NO production from endothelial NO synthetase (eNOS) and neuronal NO synthase (nNOS) that is associated with hypertension and this process involves a stomach-meridian organ but not a non-stomach-meridian organ such as the liver. How can we explain the phenomena of EA and meridian effect? Here, we proposed a neurovascular transmission model for acupuncture induced NO. In this proposed model, the acupuncture stimulus is able to influence connective tissue via mechanical force transfer to the extracellular matrix (ECM). Through the ECM, the mechanotransduction stimulus can be translated or travel from the acupuncture points, which involve local tissue and cells. Cells in the local tissue that have received mechanotransduction induce different types of NO production that can induce changes in blood flow and local circulation. The local mechanical stress produced is coupled to a cyclic strain of the blood vessels and this could then change the frequency of resonance. According to the resonance theory, an oscillatory

  7. Inhaled nitric oxide in cardiac surgery: Evidence or tradition?

    PubMed

    Benedetto, Maria; Romano, Rosalba; Baca, Georgiana; Sarridou, Despoina; Fischer, Andreas; Simon, Andre; Marczin, Nandor

    2015-09-15

    Inhaled nitric oxide (iNO) therapy as a selective pulmonary vasodilator in cardiac surgery has been one of the most significant pharmacological advances in managing pulmonary hemodynamics and life threatening right ventricular dysfunction and failure. However, this remarkable story has experienced a roller-coaster ride with high hopes and nearly universal demonstration of physiological benefits but disappointing translation of these benefits to harder clinical outcomes. Most of our understanding on the iNO field in cardiac surgery stems from small observational or single centre randomised trials and even the very few multicentre trials fail to ascertain strong evidence base. As a consequence, there are only weak clinical practice guidelines on the field and only European expert opinion for the use of iNO in routine and more specialised cardiac surgery such as heart and lung transplantation and left ventricular assist device (LVAD) insertion. In this review the authors from a specialised cardiac centre in the UK with a very high volume of iNO usage provide detailed information on the early observations leading to the European expert recommendations and reflect on the nature and background of these recommendations. We also provide a summary of the progress in each of the cardiac subspecialties for the last decade and initial survey data on the views of senior anaesthetic and intensive care colleagues on these recommendations. We conclude that the combination of high price tag associated with iNO therapy and lack of substantial clinical evidence is not sustainable on the current field and we are risking loosing this promising therapy from our daily practice. Overcoming the status quo will not be easy as there is not much room for controlled trials in heart transplantation or in the current atmosphere of LVAD implantation. However, we call for international cooperation to conduct definite studies to determine the place of iNO therapy in lung transplantation and high

  8. Modeling nitric oxide emissions from biosolid amended soils

    NASA Astrophysics Data System (ADS)

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

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

  9. Inhaled nitric oxide in cardiac surgery: Evidence or tradition?

    PubMed

    Benedetto, Maria; Romano, Rosalba; Baca, Georgiana; Sarridou, Despoina; Fischer, Andreas; Simon, Andre; Marczin, Nandor

    2015-09-15

    Inhaled nitric oxide (iNO) therapy as a selective pulmonary vasodilator in cardiac surgery has been one of the most significant pharmacological advances in managing pulmonary hemodynamics and life threatening right ventricular dysfunction and failure. However, this remarkable story has experienced a roller-coaster ride with high hopes and nearly universal demonstration of physiological benefits but disappointing translation of these benefits to harder clinical outcomes. Most of our understanding on the iNO field in cardiac surgery stems from small observational or single centre randomised trials and even the very few multicentre trials fail to ascertain strong evidence base. As a consequence, there are only weak clinical practice guidelines on the field and only European expert opinion for the use of iNO in routine and more specialised cardiac surgery such as heart and lung transplantation and left ventricular assist device (LVAD) insertion. In this review the authors from a specialised cardiac centre in the UK with a very high volume of iNO usage provide detailed information on the early observations leading to the European expert recommendations and reflect on the nature and background of these recommendations. We also provide a summary of the progress in each of the cardiac subspecialties for the last decade and initial survey data on the views of senior anaesthetic and intensive care colleagues on these recommendations. We conclude that the combination of high price tag associated with iNO therapy and lack of substantial clinical evidence is not sustainable on the current field and we are risking loosing this promising therapy from our daily practice. Overcoming the status quo will not be easy as there is not much room for controlled trials in heart transplantation or in the current atmosphere of LVAD implantation. However, we call for international cooperation to conduct definite studies to determine the place of iNO therapy in lung transplantation and high

  10. Functional Inducible Nitric Oxide Synthase Gene Variants Associate With Hypertension

    PubMed Central

    Nikkari, Seppo T.; Määttä, Kirsi M.; Kunnas, Tarja A.

    2015-01-01

    Abstract Increased inducible nitric oxide synthase (iNOS) activity and expression has been associated with hypertension, but less is known whether the 2 known functional polymorphic sites in the iNOS gene (g.–1026 C/A (rs2779249), g.2087 G/A (rs2297518)) affect susceptibility to hypertension. The objective of this study was to investigate the association between the genetic variants of iNOS and diagnosed hypertension in a Finnish cohort. This study included 320 hypertensive cases and 439 healthy controls. All participants were 50-year-old men and women and the data were collected from the Tampere adult population cardiovascular risk study (TAMRISK). DNA was extracted from buccal swabs and iNOS single nucleotide polymorphisms (SNPs) were analyzed using KASP genotyping PCR. Data analysis was done by logistic regression. At the age of 50 years, the SNP rs2779249 (C/A) associated significantly with hypertension (P = 0.009); specifically, subjects carrying the A-allele had higher risk of hypertension compared to those carrying the CC genotype (OR = 1.47; CI = 1.08–2.01; P = 0.015). In addition, a 15-year follow-up period (35, 40, and 45 years) of the same individuals showed that carriers of the A-allele had more often hypertension in all of the studied age-groups. The highest risk for developing hypertension was obtained among 35-year-old subjects (odds ratio [OR] 3.83; confidence interval [CI] = 1.20–12.27; P = 0.024). Those carrying variant A had also significantly higher readings of both systolic (P = 0.047) and diastolic (P = 0.048) blood pressure during the follow-up. No significant associations between rs2297518 (G/A) variants alone and hypertension were found. However, haplotype analysis of rs2779249 and rs2297518 revealed that individuals having haplotype H3 which combines both A alleles (CA–GA, 19.7% of individuals) was more commonly found in the hypertensive group than in the normotensive group (OR = 2.01; CI = 1

  11. Febrigenic signaling to the brain does not involve nitric oxide

    PubMed Central

    Steiner, Alexandre A; Rudaya, Alla Y; Ivanov, Andrei I; Romanovsky, Andrej A

    2004-01-01

    The involvement of peripheral nitric oxide (NO) in febrigenic signaling to the brain has been proposed because peripherally administered NO synthase (NOS) inhibitors attenuate lipopolysaccharide (LPS)-induced fever in rodents. However, how the unstable molecule of NO can reach the brain to trigger fever is unclear. It is also unclear whether NOS inhibitors attenuate fever by blocking febrigenic signaling or, alternatively, by suppressing thermogenesis in brown fat. Male Wistar rats were chronically implanted with jugular catheters; their colonic and tail skin temperatures (Tc and Tsk) were monitored. Study 1 was designed to determine whether the relatively stable, physiologically relevant forms of NO, that is, S-nitrosoalbumin (SNA) and S-nitrosoglutathione (SNG), are pyrogenic and whether they enhance LPS fever. At a neutral ambient temperature (Ta) of 31°C, afebrile or LPS (1 μg kg−1, i.v.)-treated rats were infused i.v. with SNA (0.34 or 4.1 μmol kg−1; the controls received NaNO2 and albumin) or SNG (10 or 60 μmol kg−1; the controls received glutathione). Tc of SNA- or SNG-treated rats never exceeded that of the controls. In Study 2, we tested whether the known fever-attenuating effect of the NOS inhibitor Nω-nitro-L-arginine methyl ester (L-NAME) at a subneutral Ta (when fever is brought about by thermogenesis) also occurs at a neutral Ta (when fever is brought about by skin vasoconstriction). At a subneutral Ta of 24°C, L-NAME (2.5 mg kg−1, i.v.) attenuated LPS (10 μg kg−1, i.v.) fever, presumably by inhibiting thermogenesis. At 31°C, L-NAME enhanced LPS fever by augmenting skin vasoconstriction (Tsk fall). In summary, both SNA and SNG had no pyrogenic effect of their own and failed to enhance LPS fever; peripheral L-NAME attenuated only fever brought about by increased thermogenesis. It is concluded that NO is uninvolved in febrigenic signaling to the brain. PMID:15006900

  12. Modeling of the Nitric Oxide Transport in the Human Lungs

    PubMed Central

    Karamaoun, Cyril; Van Muylem, Alain; Haut, Benoît

    2016-01-01

    In the human lungs, nitric oxide (NO) acts as a bronchodilatator, by relaxing the bronchial smooth muscles and is closely linked to the inflammatory status of the lungs, owing to its antimicrobial activity. Furthermore, the molar fraction of NO in the exhaled air has been shown to be higher for asthmatic patients than for healthy patients. Multiple models have been developed in order to characterize the NO dynamics in the lungs, owing to their complex structure. Indeed, direct measurements in the lungs are difficult and, therefore, these models are valuable tools to interpret experimental data. In this work, a new model of the NO transport in the human lungs is proposed. It belongs to the family of the morphological models and is based on the morphometric model of Weibel (1963). When compared to models published previously, its main new features are the layered representation of the wall of the airways and the possibility to simulate the influence of bronchoconstriction (BC) and of the presence of mucus on the NO transport in lungs. The model is based on a geometrical description of the lungs, at rest and during a respiratory cycle, coupled with transport equations, written in the layers composing an airway wall and in the lumen of the airways. First, it is checked that the model is able to reproduce experimental information available in the literature. Second, the model is used to discuss some features of the NO transport in healthy and unhealthy lungs. The simulation results are analyzed, especially when BC has occurred in the lungs. For instance, it is shown that BC can have a significant influence on the NO transport in the tissues composing an airway wall. It is also shown that the relation between BC and the molar fraction of NO in the exhaled air is complex. Indeed, BC might lead to an increase or to a decrease of this molar fraction, depending on the extent of the BC and on the possible presence of mucus. This should be confirmed experimentally and might

  13. Inhibition of nitric oxide synthase does not impair spatial learning.

    PubMed

    Bannerman, D M; Chapman, P F; Kelly, P A; Butcher, S P; Morris, R G

    1994-12-01

    Nitric oxide (NO), a putative intercellular messenger in the CNS, may be involved in certain forms of synaptic plasticity and learning. This article reports a series of experiments investigating the effects of N omega-nitro-L-arginine methyl ester (L-NAME) upon various forms of learning and memory in the watermaze. L-NAME (75 mg/kg, i.p., sufficient to bring about > 90% inhibition of NO synthesis in brain) produced an apparent impairment in spatial learning when given to naive rats during acquisition (3 d, six training trials per day). This impairment was dose related, stereoselective, and attenuated by coadministration of L-arginine. A second study showed that L-NAME did not affect the retention of a previously learned spatial task. In addition, in a visual discrimination task, the rate at which criterion levels of performance were reached was unaffected by L-NAME. Thus, inhibition of NO synthase may cause a selective impairment of spatial learning without effect upon retention. However, analysis of the early training trials of the visual discrimination task revealed significantly elevated escape latencies in the L-NAME-treated rats, suggesting that inhibition of NO synthase may have more general effects. As normal rats learn the spatial task very rapidly, the possibility arises that the apparent deficit in learning is due to a disruption of some process other than learning per se. A further series of experiments investigated this possibility. L-NAME was found not to impair the learning of a new platform position in the same spatial environment. Surprisingly, L-NAME also had no effect on spatial learning in a second watermaze located in a novel spatial environment by rats well practiced with all aspects of watermaze training. Finally, L-NAME had no effect on spatial learning in naive rats trained with just one trial per day. Thus, systemic injection of an NO synthase inhibitor impairs behavioral performance in two tasks during their initial acquisition, but the

  14. Nitric oxide dependent vasodilation in young spontaneously hypertensive rats.

    PubMed

    Radaelli, A; Mircoli, L; Mori, I; Mancia, G; Ferrari, A U

    1998-10-01

    Conflicting evidence exists on the possible impairment of tonic nitric oxide (NO) mediated vasodilation as a causative factor in the genesis of human as well as experimental hypertension. We evaluated the tonic NO-dependent vasodilation from the pressor response to NO synthesis inhibition by NG-monomethyl-L-arginine (L-NMMA) in 9 conscious, chronically instrumented spontaneously hypertensive rats (SHR) at 12 weeks of age, ie, during the early established hypertensive stage. Nine age-matched Wistar-Kyoto rats (WKY) were used as controls. The pressor responses to L-NMMA (100 mg . kg-1 IV bolus plus 1.5 mg . kg-1 . min-1 infusion for 60 minutes) as well as to non NO-dependent pressor stimuli, namely, vasopressin (2, 4, and 8 ng . kg-1) and phenylephrine (0.5, 1, and 2 microg . kg-1) given as IV boluses, were assessed both under control conditions and during suppression of autonomic reflexes by hexamethonium (30 mg . kg-1 IV bolus+1.5 mg . kg-1 . min-1 infusion). Rather than being reduced, the pressor responses to L-NMMA were 39% and 71% larger in the control and areflexic conditions, respectively, than those observed in WKY (both P<0.01). A similar pattern was observed for the pressor responses to vasopressin (+37% and +68% in the control and areflexic conditions, respectively; both P<0.01) and phenylephrine, (+20% and +52%; both P<0.05). Additional groups of 6-week-old prehypertensive SHR (n=11) and age-matched WKY (n=11) were subjected to an identical protocol: in these animals, the pressor responses to L-NMMA were similar in each strain, as were the pressor responses to vasopressin and phenylephrine in both control and areflexic conditions. In conclusion, our observations indicate that during the developmental phase of hypertension in the SHR model, namely, during the prehypertensive as well as the early established hypertensive stage, NO-dependent vasodilation is preserved (if not enhanced) so that a putative impairment of this function provides no significant

  15. Nitric oxide and coronary vascular endothelium adaptations in hypertension.

    PubMed

    Levy, Andrew S; Chung, Justin C S; Kroetsch, Jeffrey T; Rush, James W E

    2009-01-01

    This review highlights a number of nitric oxide (NO)-related mechanisms that contribute to coronary vascular function and that are likely affected by hypertension and thus become important clinically as potential considerations in prevention, diagnosis, and treatment of coronary complications of hypertension. Coronary vascular resistance is elevated in hypertension in part due to impaired endothelium-dependent function of coronary arteries. Several lines of evidence suggest that other NO synthase isoforms and dilators other than NO may compensate for impairments in endothelial NO synthase (eNOS) to protect coronary artery function, and that NO-dependent function of coronary blood vessels depends on the position of the vessel in the vascular tree. Adaptations in NOS isoforms in the coronary circulation to hypertension are not well described so the compensatory relationship between these and eNOS in hypertensive vessels is not clear. It is important to understand potential functional consequences of these adaptations as they will impact the efficacy of treatments designed to control hypertension and coronary vascular disease. Polymorphisms of the eNOS gene result in significant associations with incidence of hypertension, although mechanistic details linking the polymorphisms with alterations in coronary vasomotor responses and adaptations to hypertension are not established. This understanding should be developed in order to better predict those individuals at the highest risk for coronary vascular complications of hypertension. Greater endothelium-dependent dilation observed in female coronary arteries is likely related to endothelial Ca(2+) control and eNOS expression and activity. In hypertension models, the coronary vasculature has not been studied extensively to establish mechanisms for sex differences in NO-dependent function. Genomic and nongenomic effects of estrogen on eNOS and direct and indirect antioxidant activities of estrogen are discussed as

  16. 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

  17. Control of nitric oxide, nitrous oxide, and ammonia emissions using microwave plasmas

    PubMed

    Wojtowicz; Miknis; Grimes; Smith; Serio

    2000-05-29

    The subject of this paper is mitigation of the undesirable side-effects of selective non-catalytic reduction (SNCR) and selective catalytic reduction (SCR): ammonia slip, residual NO(x), and N(2)O emissions. The use of microwave-plasma discharge within the flue gas was explored as a potential pollution-control method. The key issues addressed were: (1) N(2)O, NH(3), and NO removal efficiencies; and (2) sustaining a stable plasma at atmospheric, or close to atmospheric, pressure. In non-oxidizing atmospheres, removal efficiencies were always close to 100% for all species. In the presence of oxygen, however, appreciable amounts of nitric oxide and ammonia were formed. Methods leading to preventing these undesirable effects were examined. In a number of runs, stable plasma operation was attained at pressures close to atmospheric.

  18. Oxidative stress, nitric oxide production, and renal sodium handling in leptin-induced hypertension.

    PubMed

    Beltowski, Jerzy; Wójcicka, Grazyna; Marciniak, Andrzej; Jamroz, Anna

    2004-04-30

    Chronic hyperleptinemia induces arterial hypertension in experimental animals and may contribute to the development of hypertension in obese humans; however, the mechanism of hypertensive effect of leptin is not completely elucidated. We investigated the effect of leptin on whole-body oxidative stress, nitric oxide production, and renal sodium handling. The study was performed on male Wistar rats divided into 3 groups: 1) control, fed standard chow ad libitum, 2) leptin-treated group, receiving leptin injections (0.25 mg/kg twice daily s.c. for 7 days), 3) pair-fed group, in which food intake was adjusted to the leptin group. Leptin caused 30.5% increase in systolic blood pressure. Plasma concentration and urinary excretion of 8-isoprostanes in animals receiving leptin was 46.4% and 49.2% higher, respectively. The level of lipid peroxidation products, malonyldialdehyde + 4-hydroxyalkenals, increased by 52.5% in the renal cortex and by 48.4% in the renal medulla following leptin treatment, whereas aconitase activity decreased in these regions of the kidney by 45.3% and 39.2%, respectively. Urinary excretion of nitric oxide metabolites (NOx) was 55.0% lower, and fractional excretion of NOx was 55.8% lower in the leptin-treated group. Urinary excretion of cGMP decreased in leptin-treated rats by 26.3%. Following leptin treatment, absolute and fractional sodium excretion decreased by 35.0% and 41.2%, respectively. These results indicate that hyperleptinemia induces systemic and intrarenal oxidative stress, decreases the amount of bioactive NO possibly due to its degradation by reactive oxygen species, and causes renal sodium retention by stimulating tubular sodium reabsorption. NO deficiency and abnormal renal Na+ handling may contribute to leptin-induced hypertension.

  19. Inhibition of lipopolysaccharide-inducible nitric oxide synthase and IL-1beta through suppression of NF-kappaB activation by 3-(1'-1'-dimethyl-allyl)-6-hydroxy-7-methoxy-coumarin isolated from Ruta graveolens L.

    PubMed

    Raghav, Sunil Kumar; Gupta, Bhawna; Shrivastava, Anju; Das, Hasi Rani

    2007-03-29

    The Ruta graveolens L. plant is used in traditional medicine to treat a large number of diseases. The methanol (50%) extract of the whole plant was observed to inhibit the expression of inducible nitric oxide synthase (iNOS) and the cycloxygenase-2 (COX-2) gene in lipopolysaccharide (LPS)-induced macrophage cells (J774A.1, [Raghav, S.K., Gupta, B., Agrawal, C., Goswami, K., Das, H.R., 2006b. Anti-inflammatory effect of Ruta graveolens L. in murine macrophage cells. J. Ethnopharmacol. 104, 234-239]). The effect of whole plant extract on the expression of other pro-inflammatory genes such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-12, interferon-gamma (IFN-gamma) and the activation of nuclear factor-kB (NF-kappaB) were investigated in LPS stimulated macrophage cells. An active compound was isolated from this methanol extract by further solvent fractionation and reverse phase high performance liquid chromatography (RP-HPLC). The purified compound was identified as 3-(1'-1'-dimethyl-allyl)-6-hydroxy-7-methoxy-coumarin having IUPAC nomenclature of 6-hydroxy-7-methoxy-3-(2-methyl but-3-en-2yl)-2H-chromen-2-one by ESI-MS, MALDI, FT-IR and NMR. Effect of this purified compound was assessed on iNOS, COX-2 and various pro-inflammatory cytokine genes and was observed to inhibit both the protein and mRNA expression of iNOS and IL-1beta in LPS challenged macrophages. Electrophoretic mobility shift assay (EMSA) and Western blot analyses indicated that the plant extract and the isolated active compound blocked the LPS-induced activation of NF-kappaB through the prevention of inhibitor-kB (IkB) degradation. The purified compound also showed the anti-oxidant activity. The active compound at a dose of 40 mg/kg body weight was observed to inhibit the iNOS and IL-1beta gene expression significantly in endotoxin-induced inflammatory model of BALB/c mice. The low level of nitric oxide production was also observed in the sera of compound treated mice

  20. Proton and electron pathways in the bacterial nitric oxide reductase.

    PubMed

    Hendriks, Janneke H M; Jasaitis, Audrius; Saraste, Matti; Verkhovsky, Michael I

    2002-02-19

    Electron- and proton-transfer reactions in bacterial nitric oxide reductase (NOR) have been investigated by optical spectroscopy and electrometry. In liposomes, NOR does not show any generation of an electric potential during steady-state turnover. This electroneutrality implies that protons are taken up from the same side of the membrane as electrons during catalysis. Intramolecular electron redistribution after photolysis of the partially reduced CO-bound enzyme shows that the electron transfer in NOR has the same pathway as in the heme-copper oxidases. The electron is transferred from the acceptor site, heme c, via a low-spin heme b to the binuclear active site (heme b3/FeB). The electron-transfer rate between hemes c and b is (3 +/- 2) x 10(4) s(-1). The rate of electron transfer between hemes b and b3 is too fast to be resolved (>10(6) s(-1)). Only electron transfer between heme c and heme b is coupled to the generation of an electric potential. This implies that the topology of redox centers in NOR is comparable to that in the heme-copper cytochrome oxidases. The optical and electrometric measurements allow identification of the intermediate states formed during turnover of the fully reduced enzyme, as well as the associated proton and electron movement linked to the NO reduction. The first phase (k = 5 x 10(5) s(-1)) is electrically silent, and characterized by the disappearance of absorbance at 433 nm and the appearance of a broad peak at 410 nm. We assign this phase to the formation of a ferrous NO adduct of heme b3. NO binding is followed by a charge separation phase (k = 2.2 x 10(5) s(-1)). We suggest that the formation of this intermediate that is not linked to significant optical changes involves movement of charged side chains near the active site. The next step creates a negative potential with a rate constant of approximately 3 x 10(4) s(-1) and a weak optical signature. This is followed by an electrically silent phase with a rate constant of 5 x 10

  1. [Nitric oxide (NO)--Nobel prize in medicine and physiology for 1998].

    PubMed

    Derentowicz, P; Markiewicz, K; Wawrzyniak, M; Czerwińska-Kartowicz, I; Buława, E; Siwińska-Gołebiowska, H

    2000-01-01

    On October 12, 1998. The Nobel Assembly announced the award of the Nobel Prize in Medicine and Physiology to pharmacologists Robert Furchgott, Louis Ignarro, and Ferid Murad. The Nobel Committee decided to award the prize for their discoveries concerning--nitric oxide as a signalling molecule in the cardiovascular system. Nitric oxide (NO) has a key importance for vascular tonus, acts as a signal molecule in the nervous system and plays an important function in the immunological system. Nitric oxide is a multifunction molecule which controls the blood pressure, modulates gastrointestinal motility. It is produced in abnormal level intensifies septic shock and destruction of nervous tissue. NO is important in different branches of medicine. For instance NO gas has been used to reduced high blood pressure in the lung of infants. Several unknown NO applications in medicine are waiting for discovery.

  2. Nitric oxide synthase in cat brain: cofactors--enzyme-substrate interaction.

    PubMed

    Côté, J F; Roberge, A G

    1996-01-01

    Nitric oxide, derived from L-arginine by the enzyme nitric oxide synthase, is an activator of the soluble guanylate cyclase and a cellular messenger. This work demonstrates that, in cat brain, the neuronal constitutive nitric oxide synthase activity is a) NADPH/calcium dependent, b) independent upon exogenous calmodulin in crude brain supernatant, c) significantly enhanced by exogenous FAD and tetrahydrobiopterin (Vmax: 118 instead of 59.4 pmol of citrulline formed .mg of prot.-1 min-1, d) inhibited by calcium chelators and calmodulin antagonist, and e) present in several neuroanatomical structures. Moreover, the Km value for L-arginine was of 11 microM instead of 41 microM in the presence of FAD and tetrahydrobiopterin in the incubation mixture, thus demonstrating that these cofactors are able to stabilize the enzyme-substrate interactions.

  3. Satellite ultraviolet measurements of nitric oxide fluorescence with a diffusive transport model.

    NASA Technical Reports Server (NTRS)

    Rusch, D. W.

    1973-01-01

    Twilight measurements of fluorescence in the (1, 0) gamma band of nitric oxide were made from June 1967 to January 1969 by an ultraviolet scanning spectrometer on board the polar orbiting satellite Ogo 4. Nitric oxide vertical column emission rates were measured between solar zenith angles of 93 and 98 deg. Seasonal and latitudinal variations were found to be less than a factor of 1.3, the scatter and uncertainty in the data prohibiting more precise determinations from being made. Time independent chemical diffusion models for the vertical distribution of nitric oxide agree well with profiles measured from sounding rockets. The column emission rates calculated from the theoretical models are larger than the satellite measurements by a factor of 3.

  4. Progesterone modulates the LPS-induced nitric oxide production by a progesterone-receptor independent mechanism.

    PubMed

    Wolfson, Manuel Luis; Schander, Julieta Aylen; Bariani, María Victoria; Correa, Fernando; Franchi, Ana María

    2015-12-15

    Genital tract infections caused by Gram-negative bacteria induce miscarriage and are one of the most common complications of human pregnancy. LPS administration to 7-day pregnant mice induces embryo resorption after 24h, with nitric oxide playing a fundamental role in this process. We have previously shown that progesterone exerts protective effects on the embryo by modulating the inflammatory reaction triggered by LPS. Here we sought to investigate whether the in vivo administration of progesterone modulated the LPS-induced nitric oxide production from peripheral blood mononuclear cells from pregnant and non-pregnant mice. We found that progesterone downregulated LPS-induced nitric oxide production by a progesterone receptor-independent mechanism. Moreover, our results suggest a possible participation of glucocorticoid receptors in at least some of the anti-inflammatory effects of progesterone.

  5. Nitric oxide production by chicken macrophages activated by Acemannan, a complex carbohydrate extracted from Aloe vera.

    PubMed

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

    1995-03-01

    Cultures of normal chicken spleen cells and HD11 line cells produce nitric oxide (NO) in response to Acemannan, a complex carbohydrate derived from the Aloe vera plant. Neither cell type produced detectable amounts of NO in response to similar concentrations of yeast mannan, another complex carbohydrate. Nitric oxide production was dose dependent and inhibitable by the nitric oxide synthase inhibitor NG-methyl-L-arginine. In addition, the production of NO was inhibited by preincubation of ACM with concanavalin A in a dose-dependent manner. These results suggest that ACM-induced NO synthesis may be mediated through macrophage mannose receptors, and macrophage activation may be accountable for some of the immunomodulatory effects of ACM in chickens.

  6. Disruption and eradication of P. aeruginosa biofilms using nitric oxide-releasing chitosan oligosaccharides

    PubMed Central

    Reighard, Katelyn P.; Hill, David B.; Dixon, Graham A.; Worley, Brittany; Schoenfisch, Mark H.

    2015-01-01

    Biofilm disruption and eradication were investigated as a function of nitric oxide- (NO) releasing chitosan oligosaccharide dose with results compared to control (ie non-NO-releasing) chitosan oligosaccharides and tobramycin. Quantification of biofilm expansion/contraction and multiple-particle tracking microrheology were used to assess the structural integrity of the biofilm before and after antibacterial treatment. While tobramycin had no effect on the physical properties of the biofilm, NO-releasing chitosan oligosaccharides exhibited dose-dependent behavior with biofilm degradation. Control chitosan oligosaccharides increased biofilm elasticity, indicating that the scaffold may mitigate the biofilm disrupting power of nitric oxide somewhat. The results from this study indicate that nitric oxide-releasing chitosan oligosaccharides act as dual-action therapeutics capable of eradicating and physically disrupting P. aeruginosa biofilms. PMID:26610146

  7. Suppression of inducible nitric oxide synthase pathway by 7-deacetylgedunin, a limonoid from Xylocarpus sp.

    PubMed

    Sarigaputi, Chanin; Sangpech, Nuanpan; Palaga, Tanapat; Pudhom, Khanitha

    2015-03-01

    In this study, limonoids isolated from Xylocarpus plants were tested for their in vitro anti-inflammatory effects. The results demonstrated that only 7-deacetylgedunin (1), a gedunin-type limonoid, significantly inhibited lipopolysaccharide- and interferon-γ-stimulated production of nitric oxide in murine macrophage RAW 264.7 cells. The suppression of nitric oxide production by 1 was correlated with the downregulation of mRNA and protein expression of inducible nitric oxide synthase. Mechanistic studies revealed that the transcriptional activity of nuclear factor-κB, IκBα degradation, and the activation of mitogen-activated protein kinases, stimulated with lipopolysaccharide and interferon-γ, were suppressed by 1. PMID:25714725

  8. Negative Inotropic Effects of Cytokines on the Heart Mediated by Nitric Oxide

    NASA Astrophysics Data System (ADS)

    Finkel, Mitchell S.; Oddis, Carmine V.; Jacob, Timothy D.; Watkins, Simon C.; Hattler, Brack G.; Simmons, Richard L.

    1992-07-01

    The direct effects of pro-inflammatory cytokines on the contractility of mammalian heart were studied. Tumor necrosis factor α, interleukin-6, and interleukin-2 inhibited contractility of isolated hamster papillary muscles in a concentration-dependent, reversible manner. The nitric oxide synthase inhibitor N^G-monomethyl-L-arginine (L-NMMA) blocked these negative inotropic effects. L-Arginine reversed the inhibition by L-NMMA. Removal of the endocardial endothelium did not alter these responses. These findings demonstrate that the direct negative inotropic effect of cytokines is mediated through a myocardial nitric oxide synthase. The regulation of pro-inflammatory cytokines and myocardial nitric oxide synthase may provide new therapeutic strategies for the treatment of cardiac disease.

  9. BIOCHEMISTRY OF MOBILE ZINC AND NITRIC OXIDE REVEALED BY FLUORESCENT SENSORS

    PubMed Central

    Pluth, Michael D.; Tomat, Elisa; Lippard, Stephen J.

    2010-01-01

    Biologically mobile zinc and nitric oxide (NO) are two prominent examples of inorganic compounds involved in numerous signaling pathways in living systems. In the past decade, a synergy of regulation, signaling, and translocation of these two species has emerged in several areas of human physiology, providing additional incentive for developing adequate detection systems for Zn(II) ions and NO in biological specimens. Fluorescent probes for both of these bioinorganic analytes provide excellent tools for their detection, with high spatial and temporal resolution. We review the most widely used fluorescent sensors for biological zinc and nitric oxide, together with promising new developments and unmet needs of contemporary Zn(II) and NO biological imaging. The interplay between zinc and nitric oxide in the nervous, cardiovascular, and immune systems is highlighted to illustrate the contributions of selective fluorescent probes to the study of these two important bioinorganic analytes. PMID:21675918

  10. Evaluation of nitrogen dioxide scavengers during delivery of inhaled nitric oxide.

    PubMed

    Lindberg, L; Rydgren, G

    1998-09-01

    We have analysed the ability of three nitrogen dioxide absorbing materials (soda lime, noXon and zeolite) to act as nitrogen dioxide scavengers during delivery of inhaled nitric oxide. Different mixtures of gas were produced in a ventilator (Servo Ventilator 300) and passed through an inspiratory tube. Concentrations of nitrogen dioxide and nitric oxide were measured in the distal part of the tube, with and without the gas having passed through a canister containing the different filter materials. Our findings indicated that nitrogen dioxide was absorbed effectively by all filter materials but that there was re-formation of nitrogen dioxide from nitric oxide and oxygen in or immediately after the canister. This initial production of nitrogen dioxide was very rapid and could not be prevented by the use of scavengers. Thus soda lime and zeolite had no practical effect as scavengers in this delivery system, and the effect of noXon was very slight.

  11. Endothelial nitric oxide synthase mediates the nitric oxide component of reflex cutaneous vasodilatation during dynamic exercise in humans.

    PubMed

    McNamara, Tanner C; Keen, Jeremy T; Simmons, Grant H; Alexander, Lacy M; Wong, Brett J

    2014-12-01

    Recent data suggests neuronal nitric oxide synthase (nNOS) mediates the NO component of reflex cutaneous vasodilatation with passive heat stress. We tested the hypothesis that nNOS inhibition would attenuate reflex cutaneous vasodilatation during sustained dynamic exercise in young healthy humans. All subjects first performed an incremental V̇O2, peak test to exhaustion on a custom-built supine cycle ergometer. On a separate day, subjects were instrumented with four intradermal microdialysis fibres on the forearm and each randomly assigned as: (1) lactated Ringer's (control); (2) 20 mm Nω-nitro-l-arginine methyl ester hydrochloride (non-selective NOS inhibitor); (3) 5 mm N-propyl-l-arginine (nNOS inhibitor); and (4) 10 mm N(5)-(1-iminoethyl)-l-ornithine dihydrochloride [endothelial NOS (eNOS) inhibitor]. Following microdialysis placement, subjects performed supine cycling with the experimental arm at heart level at 60% V̇O2, peak for a period sufficient to raise core temperature 0.8°C. At the end of cycling, all microdialysis sites were locally heated to 43°C and sodium nitroprusside was perfused to elicit maximal vasodilatation. Mean arterial pressure, skin blood flow via laser-Doppler flowmetry and core temperature via ingestible telemetric pill were measured continuously; cutaneous vascular conductance (CVC) was calculated as laser-Doppler flowmetry/mean arterial pressure and normalized to maximum. There was no significant difference between control (58 ± 2%CVCmax) and nNOS-inhibited (56 ± 3%CVCmax) sites in response to exercise-induced hyperthermia. The increase in CVC at eNOS-inhibited (41 ± 3%CVCmax) and non-selective NOS-inhibited (40 ± 4%CVCmax) sites were significantly attenuated compared to control and nNOS-inhibited (P < 0.001 all conditions) but there was no difference between eNOS-inhibited and non-selective NOS-inhibited sites. These data suggest eNOS, not nNOS, mediate NO synthesis during reflex cutaneous vasodilatation with

  12. Endothelial nitric oxide synthase mediates the nitric oxide component of reflex cutaneous vasodilatation during dynamic exercise in humans.

    PubMed

    McNamara, Tanner C; Keen, Jeremy T; Simmons, Grant H; Alexander, Lacy M; Wong, Brett J

    2014-12-01

    Recent data suggests neuronal nitric oxide synthase (nNOS) mediates the NO component of reflex cutaneous vasodilatation with passive heat stress. We tested the hypothesis that nNOS inhibition would attenuate reflex cutaneous vasodilatation during sustained dynamic exercise in young healthy humans. All subjects first performed an incremental V̇O2, peak test to exhaustion on a custom-built supine cycle ergometer. On a separate day, subjects were instrumented with four intradermal microdialysis fibres on the forearm and each randomly assigned as: (1) lactated Ringer's (control); (2) 20 mm Nω-nitro-l-arginine methyl ester hydrochloride (non-selective NOS inhibitor); (3) 5 mm N-propyl-l-arginine (nNOS inhibitor); and (4) 10 mm N(5)-(1-iminoethyl)-l-ornithine dihydrochloride [endothelial NOS (eNOS) inhibitor]. Following microdialysis placement, subjects performed supine cycling with the experimental arm at heart level at 60% V̇O2, peak for a period sufficient to raise core temperature 0.8°C. At the end of cycling, all microdialysis sites were locally heated to 43°C and sodium nitroprusside was perfused to elicit maximal vasodilatation. Mean arterial pressure, skin blood flow via laser-Doppler flowmetry and core temperature via ingestible telemetric pill were measured continuously; cutaneous vascular conductance (CVC) was calculated as laser-Doppler flowmetry/mean arterial pressure and normalized to maximum. There was no significant difference between control (58 ± 2%CVCmax) and nNOS-inhibited (56 ± 3%CVCmax) sites in response to exercise-induced hyperthermia. The increase in CVC at eNOS-inhibited (41 ± 3%CVCmax) and non-selective NOS-inhibited (40 ± 4%CVCmax) sites were significantly attenuated compared to control and nNOS-inhibited (P < 0.001 all conditions) but there was no difference between eNOS-inhibited and non-selective NOS-inhibited sites. These data suggest eNOS, not nNOS, mediate NO synthesis during reflex cutaneous vasodilatation with

  13. Iron(II) porphyrins induced conversion of nitrite into nitric oxide: A computational study.

    PubMed

    Zhang, Ting Ting; Liu, Yong Dong; Zhong, Ru Gang

    2015-09-01

    Nitrite reduction to nitric oxide by heme proteins was reported as a protective mechanism to hypoxic injury in mammalian physiology. In this study, the pathways of nitrite reduction to nitric oxide mediated by iron(II) porphyrin (P) complexes, which were generally recognized as models for heme proteins, were investigated by using density functional theory (DFT). In view of two type isomers of combination of nitrite and Fe(II)(P), N-nitro- and O-nitrito-Fe(II)-porphyrin complexes, and two binding sites of proton to the different O atoms of nitrite moiety, four main pathways for the conversion of nitrite into nitric oxide mediated by iron(II) porphyrins were proposed. The results indicate that the pathway of N-bound Fe(II)(P)(NO2) isomer into Fe(III)(P)(NO) and water is similar to that of O-bound isomer into nitric oxide and Fe(III)(P)(OH) in both thermodynamical and dynamical aspects. Based on the initial computational studies of five-coordinate nitrite complexes, the conversion of nitrite into NO mediated by Fe(II)(P)(L) complexes with 14 kinds of proximal ligands was also investigated. Generally, the same conclusion that the pathways of N-bound isomers are similar to those of O-bound isomer was obtained for iron(II) porphyrin with ligands. Different effects of ligands on the reduction reactions were also found. It is notable that the negative proximal ligands can improve reactive abilities of N-nitro-iron(II) porphyrins in the conversion of nitrite into nitric oxide compared to neutral ligands. The findings will be helpful to expand our understanding of the mechanism of nitrite reduction to nitric oxide by iron(II) porphyrins.

  14. Effects of Smokeless Tobacco “Maras Powder” Use on Nitric Oxide and Cardiovascular Risk Parameters

    PubMed Central

    Guven, Aytekin; Tolun, Fatma

    2012-01-01

    Background: Smokeless tobacco use is common in various parts of the world. In Turkey a type of smokeless tobacco called “Maras powder” is widely used in southeastern region. Smoking is known to have an adverse effect on nitric oxide and cardiovascular risk factors. The aim of this study was to evaluate whether there is difference between the effects of Maras powder and cigarette smoking on the cardiovascular risk factors and nitric oxide levels. Methods: In the study, participants were 48 Maras powder users, 50 cigarette smokers and 45 nontobacco user subjects. Blood samples were collected and hematological parameters and lipid parameters were measured. Plasma Nitric oxide level was also detected by using the Griess method. Results: Plasma total cholesterol, LDL-cholesterol, triglyceride levels were significantly higher in Maras powder and cigarette smokers group than in the nontobacco user group (p<0.001). Plasma HDL-cholesterol levels were significantly lower in Maras powder and cigarette smokers group than in the nontobacco user group (p<0.001). Plasma Nitric oxide levels were found significantly lower in Maras powder and cigarette smokers group compared to the nontobacco user group (4.9±0.9 µmol/l, 4.8±1 µmol/l, 9.4±3.4 µmol/l, respectively, p<0.001) whereas there was no significant difference between the Maras powder and cigarette smokers group. In multivariate logistic regression model, cigarette smoking (Odds ratio=17.832, p<0.001), Maras powder usage (Odds ratio=12.311, p=0.002) and mean platelet volume (Odds ratio=1.425, p=0.030) remained independently associated with lower Nitric oxide levels. Conclusion: We conclude that Maras powder has similar adverse effects on nitric oxide level and cardiovascular risk parameters and thereby it appears to be harmful as cigarette smoking. PMID:23136542

  15. Iron(II) porphyrins induced conversion of nitrite into nitric oxide: A computational study.

    PubMed

    Zhang, Ting Ting; Liu, Yong Dong; Zhong, Ru Gang

    2015-09-01

    Nitrite reduction to nitric oxide by heme proteins was reported as a protective mechanism to hypoxic injury in mammalian physiology. In this study, the pathways of nitrite reduction to nitric oxide mediated by iron(II) porphyrin (P) complexes, which were generally recognized as models for heme proteins, were investigated by using density functional theory (DFT). In view of two type isomers of combination of nitrite and Fe(II)(P), N-nitro- and O-nitrito-Fe(II)-porphyrin complexes, and two binding sites of proton to the different O atoms of nitrite moiety, four main pathways for the conversion of nitrite into nitric oxide mediated by iron(II) porphyrins were proposed. The results indicate that the pathway of N-bound Fe(II)(P)(NO2) isomer into Fe(III)(P)(NO) and water is similar to that of O-bound isomer into nitric oxide and Fe(III)(P)(OH) in both thermodynamical and dynamical aspects. Based on the initial computational studies of five-coordinate nitrite complexes, the conversion of nitrite into NO mediated by Fe(II)(P)(L) complexes with 14 kinds of proximal ligands was also investigated. Generally, the same conclusion that the pathways of N-bound isomers are similar to those of O-bound isomer was obtained for iron(II) porphyrin with ligands. Different effects of ligands on the reduction reactions were also found. It is notable that the negative proximal ligands can improve reactive abilities of N-nitro-iron(II) porphyrins in the conversion of nitrite into nitric oxide compared to neutral ligands. The findings will be helpful to expand our understanding of the mechanism of nitrite reduction to nitric oxide by iron(II) porphyrins. PMID:26112152

  16. Experimental and analytical study of nitric oxide formation during combustion of propane in a jet-stirred combustor

    NASA Technical Reports Server (NTRS)

    Wakelyn, N. T.; Jachimowski, C. J.; Wilson, C. H.

    1978-01-01

    A jet-stirred combustor, constructed of castable zirconia and with an Inconel injector, was used to study nitric oxide formation in propane-air combustion with residence times in the range from 3.2 to 3.3 msec and equivalence ratios varying from 0.7 to 1.4. Measurements were made of combustor operating temperature and of nitric oxide concentration. Maximum nitric oxide concentrations of the order of 55 ppm were found in the range of equivalence ratio from 1.0 to 1.1. A finite-rate chemical kinetic mechanism for propane combustion and nitric oxide formation was assembled by coupling an existing propane oxidation mechanism with the Zeldovich reactions and reactions of molecular nitrogen with hydrocarbon fragments. Analytical studies using this mechanism in a computer simulation of the experimental conditions revealed