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Sample records for chronic nitric oxide

  1. Nitric oxide and chronic colitis

    Directory of Open Access Journals (Sweden)

    Matthew B Grisham

    1996-01-01

    Full Text Available Nitric oxide (NO is thought to play an important role in modulating the inflammatory response by virtue of its ability to affect bloodflow, leukocyte function and cell viability. The objective of this study was to assess the role that NO may play in mediating the mucosal injury and inflammation in a model of chronic granulomatous colitis using two pharmacologically different inhibitors of nitric oxide synthase (NOS. Chronic granulomatous colitis with liver and spleen inflammation was induced in female Lewis rats via the subserosal (intramural injection of peptidoglycan/polysaccharide (PG/PS derived from group A streptococci. Chronic NOS inhibition by oral administration of NG-nitro-L-arginine methyl ester (L-NAME (15 µmol/kg/day or amino-guanidine (AG (15 µmol/ kg/day was found to attenuate the PG/PS-induced increases in macroscopic colonic inflammation scores and colonic myeloperoxidase activity. Only AG -- not L-NAME – attenuated the PG/PS-induced increases in colon dry weight. Both L-NAME and AG significantly attenuated the PG/PS-induced increases in spleen weight whereas neither was effective at significantly attenuating the PG/PS-induced increases in liver weight. Although both L-NAME and AG inhibited NO production in vivo, as measured by decreases in plasma nitrite and nitrate levels, only AG produced significantly lower values (38±3 versus 83±8 µM, respectively, P<0.05. Finally, L-NAME, but not AG, administration significantly increased mean arterial pressure from 83 mmHg in colitic animals to 105 mmHg in the PG/PS+ L-NAME-treated animals (P<0.05. It is concluded that NO may play an important role in mediating some of the pathophysiology associated with this model of chronic granulomatous colitis.

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

    Science.gov (United States)

    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 (Pdepression.

  3. Exhaled nitric oxide in stable chronic obstructive pulmonary disease

    International Nuclear Information System (INIS)

    The objective of the study was to test the hypothesis that fraction of exhaled nitric oxide (FENO) is elevated in nonsmoking subjects with stable chronic obstructive pulmonary disease (COPD) and compare it with the results in patients with asthma and a control population. Pulmonology Clinic at a University Hospital. Twenty five control subjects, 25 steroid naive asthmatics and 14 COPD patients were studied. All the patients were nonsmokers and stable at the time of the study. All subjects completed a questionnaire and underwent spirometry. Exhaled nitric oxide was measured online by chemiluminescence, using single-breath technique. All the study subjects were males. Subjects with stable COPD had significantly higher values of FENO than controls (56.54+ - 28.01 vs 22.00 + -6.69; P =0.0001) but lower than the subjects with asthma (56.54+ - 28.01 vs 84.78+ - 39.32 P 0.0285). The FENO values in COPD subjects were inversely related to the FEV 1 /FVC ratio. There was a significant overlap between the FENO values in COPD and the control subjects. There is a significant elevation in FENO in patients with stable COPD, but the elevation is less than in asthmatic subjects. Its value in clinical practice may be limited by the significant overlap with control subjects. (author)

  4. Exhaled nitric oxide in stable chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Beg Mohammed

    2009-01-01

    Full Text Available Study Objective : The objective of the study was to test the hypothesis that fraction of exhaled nitric oxide (FENO is elevated in nonsmoking subjects with stable chronic obstructive pulmonary disease (COPD and compare it with the results in patients with asthma and a control population. Design : Cross-sectional study. Materials and Methods : Pulmonology Clinic at a University Hospital. Twenty five control subjects, 25 steroid naοve asthmatics and 14 COPD patients were studied. All the patients were nonsmokers and stable at the time of the study. All subjects completed a questionnaire and underwent spirometry. Exhaled nitric oxide was measured online by chemiluminescence, using single-breath technique. Results : All the study subjects were males. Subjects with stable COPD had significantly higher values of FENO than controls (56.54±28.01 vs 22.00±6.69; P =0.0001 but lower than the subjects with asthma (56.54±28.01 vs 84.78±39.32 P = 0.0285.The FENO values in COPD subjects were inversely related to the FEV 1 /FVC ratio. There was a significant overlap between the FENO values in COPD and the control subjects. Conclusion : There is a significant elevation in FENO in patients with stable COPD, but the elevation is less than in asthmatic subjects. Its value in clinical practice may be limited by the significant overlap with control subjects.

  5. HYPOTHALAMIC BLOOD-FLOW REMAINS UNALTERED FOLLOWING CHRONIC NITRIC-OXIDE SYNTHASE BLOCKADE IN RATS

    NARCIS (Netherlands)

    BENYO, Z; SZABO, C; STUIVER, BT; BOHUS, B; SANDOR, P

    1995-01-01

    The effect of the chronic oral application of N-G-nitro-L-arginine methyl eater (L-NAME), a potent inhibitor of nitric oxide (NO) production, was studied on hypothalamic blood flow (HBF) and hypothalamic nitric oxide synthase (NOS) activity in rats. L-NAME was dissolved in the drinking water, in a c

  6. Nitric Oxide Resistance Reduces Arteriovenous Fistula Maturation in Chronic Kidney Disease in Rats

    DEFF Research Database (Denmark)

    Geenen, Irma L; Kolk, Felix F; Molin, Daniel G;

    2016-01-01

    BACKGROUND: Autologous arteriovenous (AV) fistulas are the first choice for vascular access but have a high risk of non-maturation due to insufficient vessel adaptation, a process dependent on nitric oxide (NO)-signaling. Chronic kidney disease (CKD) is associated with oxidative stress that can...

  7. Exhaled nitric oxide levels in exacerbations of asthma, chronic obstructive pulmonary disease and pneumonia

    International Nuclear Information System (INIS)

    Nitric oxide is known to be present in the exhaled air of normal subjects and at higher concentrations in asthmatics. The aim of this study was to measure exhaled nitric oxide levels in patients admitted to hospital with acute exacerbations of asthma, or chronic obstructive pulmonary disease, or with pneumonia. Within 24 hours of admission exhaled nitric oxide levels were measured by a chemiluminescent analyzer in 11 patients with acute sever asthma, 19 patients with acute exacerbation of chronic obstructive pulmonary disease, and in 12 patients with pneumonia. In asthmatics measurements were made on 3 occasions, at day 1, 4, and 28 and were related to changes in peak expiratory flow rate. On admission median exhaled nitric oxide levels (range) were significantly higher in asthmatics 22 (9.3-74) parts per billion in comparison to patients with chronic obstructive pulmonary disease 10.3 (2.7-34) parts per billion; p<0.01, pneumonia 7 (4-17) parts per billion; p<0.001, and normal subjects 8.7 (5-13.3) parts per billion; p<0.001. Following treatment the asthmatics had a significant reduction in their exhaled nitric oxide levels from 22 (9.3-74) parts per billion on day 1 to 9.7 (5.7-18.3) parts per billion on day 28; p=0.005. Peak expiratory flow rate measurements increased from 200 (120-280) l/min on day 1 to 280 (150-475) l/min on day 4; p<0.05 and to 390 (150-530) l/min on day 28; p<0.01. A strong negative correlation existed between peak expiratory flow rate measurements and exhaled nitric oxide levels in asthmatics on day 28 (r=-0.70; p=0.017). Acute exacerbations of asthma are associated with increased levels of exhaled nitric oxide in contrast to exacerbations of chronic obstructive pulmonary disease and acute pneumonia. Exhaled nitric oxide may be a useful indirect marker of asthmatic airway inflammation. The differing time course of response of nitric oxide to peak flow measures suggests that these two measures are reflecting differing airway events. (author)

  8. Chronic nitric oxide synthase inhibition exacerbates renal dysfunction in cirrhotic rats

    DEFF Research Database (Denmark)

    Graebe, Martin; Brond, Lone; Christensen, Sten;

    2004-01-01

    The present study investigated sodium balance and renal tubular function in cirrhotic rats with chronic blockade of the nitric oxide (NO) system. Rats were treated with the nonselective NO synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME) starting on the day of common bile duct ligatio...

  9. Endothelial Nitric Oxide Synthase Single Nucleotide Polymorphism and Left Ventricular Function in Early Chronic Kidney Disease

    OpenAIRE

    Sourabh Chand; Colin D Chue; Edwards, Nicola C.; James Hodson; Simmonds, Matthew J.; Alexander Hamilton; Gough, Stephen C L; Lorraine Harper; Steeds, Rick P.; Townend, Jonathan N.; Ferro, Charles J.; Richard Borrows

    2015-01-01

    Chronic kidney disease (CKD) is associated with accelerated cardiovascular disease and heart failure. Endothelial nitric oxide synthase (eNOS) Glu298Asp single nucleotide polymorphism (SNP) genotype has been associated with a worse phenotype amongst patients with established heart failure and in patients with progression of their renal disease. The association of a cardiac functional difference in non-dialysis CKD patients with no known previous heart failure, and eNOS gene variant is investi...

  10. Endothelial nitric oxide synthase gene intron4 VNTR polymorphism in patients with chronic kidney disease.

    Science.gov (United States)

    Elshamaa, Manal F; Sabry, Samar; Badr, Ahmed; El-Ahmady, Mostafa; Elghoroury, Eman A; Thabet, Eman H; Kandil, Dina; Kamel, Solaf

    2011-09-01

    Nitric oxide production is reduced in renal disease, partially due to decreased endothelial nitric oxide production. Evidence indicates that nitric oxide deficiency contributes to cardiovascular events and progression of kidney damage. A polymorphism in intron 4 of the endothelial constitutive nitric oxide synthase (ecNOS) gene is a candidate gene in cardiovascular and renal diseases. We investigated a potential involvement of this polymorphism in chronic renal failure. A case-control study involved 78 children with chronic kidney disease (CKD) and 30 healthy controls. All participants were genotyped for the ecNOS4 polymorphism by the polymerase chain reaction (PCR). Dialyzed (maintenance hemodialysis) and conservative treatment children had significantly higher frequency of the aa genotype and ecNOS4a allele (Pnitric oxide level was found to be lower in carriers of the ecNOS 4a allele than in noncarriers (100.29±27.32 vs. 152.73±60.39 μmol/l, P=0.04). Interestingly, 85.95% of the ecNOS 4a allele ESRD patients were found hypertensive in comparison to the 60.67% patients of non noncarriers (bb genotype) (P=0.04). Also, 35.90% of the ecNOS 4a allele ESRD patients were found to have cardiovascular disease in comparison to the 5.13% patients of noncarriers (bb genotype) (P=0.01). On multiple linear regression analysis, a allele was independently associated with hypertension (P=0.03). There was a significantly higher frequency of the ecNOS4a allele carriers among CKD children, both on MHD and conservative treatment than in controls. This suggests that the ecNOS gene polymorphism may be associated with an increased risk of chronic renal failure. PMID:21519233

  11. Nitric oxide supersensitivity

    DEFF Research Database (Denmark)

    Olesen, J; Iversen, Helle Klingenberg; Thomsen, L L

    1993-01-01

    Nitroglycerin, which may be regarded as a prodrug for nitric oxide, induces a mild to moderate headache in healthy subjects. In order to study whether migraine patients are more sensitive to nitric oxide than non-migrainous subjects, four different doses of intravenous nitroglycerin were given...... previously shown a similar supersensitivity to histamine which in human cerebral arteries activates endothelial H1 receptors and causes endothelial production of nitric oxide. Migraine patients are thus supersensitive to exogenous nitric oxide from nitroglycerin as well as to endothelially produced nitric...... oxide. It is suggested that nitric oxide may be partially or completely responsible for migraine pain....

  12. Influence of chronic stress and terahertz radiation at nitric oxide frequency on functional activity of thyroid gland

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    Tsymbal А.А.

    2010-12-01

    Full Text Available In the chronic stress conditions oppression of functional activity of thyroid gland is revealed. Influence of terahertz radiation at the nitric oxide frequency of 150,176-150,664 GHz on functional activity of thyroid gland in the conditions of chronic experimental stress was studied. It was shown that during 15 minutes of influence of terahertz waves at nitric oxide frequency partial restoration of studied indicators of activity of thyroid gland was observed in stressed animals. At 30 minute mode of influence of specified waves a complete recovery of broken indicators of functional condition of thyroid gland was determined

  13. Nitric Oxide Resistance Reduces Arteriovenous Fistula Maturation in Chronic Kidney Disease in Rats.

    Directory of Open Access Journals (Sweden)

    Irma L Geenen

    Full Text Available Autologous arteriovenous (AV fistulas are the first choice for vascular access but have a high risk of non-maturation due to insufficient vessel adaptation, a process dependent on nitric oxide (NO-signaling. Chronic kidney disease (CKD is associated with oxidative stress that can disturb NO-signaling. Here, we evaluated the influence of CKD on AV fistula maturation and NO-signaling.CKD was established in rats by a 5/6th nephrectomy and after 6 weeks, an AV fistula was created between the carotid artery and jugular vein, which was followed up at 3 weeks with ultrasound and flow assessments. Vessel wall histology was assessed afterwards and vasoreactivity of carotid arteries was studied in a wire myograph. The soluble guanylate cyclase (sGC activator BAY 60-2770 was administered daily to CKD animals for 3 weeks to enhance fistula maturation.CKD animals showed lower flow rates, smaller fistula diameters and increased oxidative stress levels in the vessel wall. Endothelium-dependent relaxation was comparable but vasorelaxation after sodium nitroprusside was diminished in CKD vessels, indicating NO resistance of the NO-receptor sGC. This was confirmed by stimulation with BAY 60-2770 resulting in increased vasorelaxation in CKD vessels. Oral administration of BAY 60-2770 to CKD animals induced larger fistula diameters, however; flow was not significantly different from vehicle-treated CKD animals.CKD induces oxidative stress resulting in NO resistance that can hamper AV fistula maturation. sGC activators like BAY 60-2770 could offer therapeutic potential to increase AV fistula maturation.

  14. Review article: the potential role of nitric oxide in chronic inflammatory bowel disorders

    DEFF Research Database (Denmark)

    Perner, Anders; Rask-Madsen, J

    1999-01-01

    impairment have all been proposed as playing important roles in the pathogenesis of this spectrum of diseases. A variety of proinflammatory mediators, including tumour necrosis factor alpha, interleukin-1beta, interferon gamma, leukotriene B4 and platelet activating factor, promote the adherence...... of phagocytes to the venular endothelium and extravasation of these cells into the colonic mucosa. In addition to large amounts of nitric oxide (NO), injurious peroxynitrite may be formed in the epithelium by the inducible nitric oxide synthase (iNOS), which is considered to elicit cytotoxicity...

  15. Inducible nitric oxide synthase is involved in the modulation of depressive behaviors induced by unpredictable chronic mild stress

    OpenAIRE

    Peng Yun-Li; Liu Yu-Ning; Liu Lei; Wang Xia; Jiang Chun-Lei; Wang Yun-Xia

    2012-01-01

    Abstract Background Experiences and inflammatory mediators are fundamental in the provocation of major depressive disorders (MDDs). We investigated the roles and mechanisms of inducible nitric oxide synthase (iNOS) in stress-induced depression. Methods We used a depressive-like state mouse model induced by unpredictable chronic mild stress (UCMS). Depressive-like behaviors were evaluated after 4 weeks of UCMS, in the presence and absence of the iNOS inhibitor N-(3-(aminomethyl)benzyl)acetamid...

  16. Concentration of nitric oxide (NO in spinal fluid of chronic spinal disease.

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    Yumite Y

    2001-08-01

    Full Text Available We studied total nitric oxide (nitrite + nitrate (NO levels in cerebrospinal fluid (CSF of chronic spinal diseases in nonsmokers (133 patients: 76 men and 57 women; mean age, 63 years; range, 15-92 years by the Griess method to clarify the role of NO in different spinal diseases. The extent of compression in terms of numbers of disc level at the compressed spinal nerve and neurological evaluation were also assessed according to the Japanese Orthopaedic Association scores. The spinal diseases included cervical myelopathy and radiculopathy (cervical disease group, ossification of yellow ligament (thoracic disease group, and lumbar disc herniation, lumbar canal stenosis and lumbar spondylolisthesis (lumbar disease group. NO levels in the spinal disease groups (4.98+/-2.28 micromol/l: mean +/- SD were significantly higher than that in the control group (2.53+/-0.94 micromol/l. An inverse correlation was detected between the elevated levels of NO and the grade of clinical symptoms in the cervical disorders. The number of disc level at the compressed spinal nerve was positively correlated with elevated NO levels in CSF in the cervical and lumbar disorder groups. These results indicate that nerve compression may elevate NO levels in CSF, and that NO concentration in the CSF might be a useful marker of damage to nervous system in spinal disorders.

  17. Comparison of the Salivary and the Serum Nitric Oxide Levels in Chronic and Aggressive Periodontitis: A Biochemical Study

    Science.gov (United States)

    Sundar, N. Mani; Krishnan, V; Krishnaraj, S; Hemalatha, V.T.; Alam, Md Nazish

    2013-01-01

    Background and Objectives: Nitric oxide (NO) is a ubiquitous intercellular messenger molecule with important cardiovascular, neurological, and immune functions. In addition, it has been postulated that the pharmacological inhibition of NO or its actions may be therapeutically valuable in the disease management. The levels of nitric oxide may provide clues about the severity and the state of the underlying disease process. It could be an inflammatory biomarker that may enable clinicians to direct the environmentally based prevention or treatment programmes and to establish whether NO plays a role in the pathogenesis of periodontitis or not. Hence, the aim of the present study was to evaluate the salivary and the serum levels of NO in generalized chronic and aggressive periodontitis. The Study Design: Unstimulated whole saliva and serum samples were collected from a total of 60 subjects who were in the age group of 18-45 years, who participated in this study. They were divided into three equal groups with 20 subjects in each group; group A (healthy controls), group B (chronic periodontitis) and group C (aggressive periodontitis). The clinical parameters were assessed, based on the oral hygiene index simplified (OHI-S), the gingival index (GI), the probing pocket depth and the clinical attachment loss (CAL). A biochemical analysis was performed to evaluate and compare the salivary and the serum nitric oxide levels of the above groups. Statistical Analysis and Results: The statistical comparisons were done under the Griess Reaction. There were statistically significant salivary and serum levels of NO in the groups of periodontitis (group B and C) as compared to those in the healthy controls (group A). A significant positive correlation was found between the values of the salivary and the serum NO levels in chronic and aggressive periodontitis. Conclusion: Nitric oxide is a potent modulator of the inflammatory disease processes and under pathological conditions, NO has

  18. Inducible nitric oxide synthase and inflammation.

    Science.gov (United States)

    Salvemini, D; Marino, M H

    1998-01-01

    Nitric oxide (NO), derived from L-arginine (L-Arg) by the enzyme nitric oxide synthase (NOS), is involved in acute and chronic inflammatory events. In view of the complexity associated with the inflammatory response, the dissection of possible mechanisms by which NO modulates this response will be profitable in designing novel and more efficacious NOS inhibitors. In this review we describe the consequences associated with the induction of inducible nitric oxide synthase (iNOS) and its therapeutic implications. PMID:15991919

  19. Endothelial nitric oxide synthase single nucleotide polymorphism and left ventricular function in early chronic kidney disease.

    Directory of Open Access Journals (Sweden)

    Sourabh Chand

    Full Text Available Chronic kidney disease (CKD is associated with accelerated cardiovascular disease and heart failure. Endothelial nitric oxide synthase (eNOS Glu298Asp single nucleotide polymorphism (SNP genotype has been associated with a worse phenotype amongst patients with established heart failure and in patients with progression of their renal disease. The association of a cardiac functional difference in non-dialysis CKD patients with no known previous heart failure, and eNOS gene variant is investigated.140 non-dialysis CKD patients, who had cardiac magnetic resonance (CMR imaging and tissue doppler echocardiography as part of two clinical trials, were genotyped for eNOS Glu298Asp SNP retrospectively.The median estimated glomerular filtration rate (eGFR was 50 mls/min and left ventricular ejection fraction (LVEF was 74% with no overt diastolic dysfunction in this cohort. There were significant differences in LVEF across eNOS genotypes with GG genotype being associated with a worse LVEF compared to other genotypes (LVEF: GG 71%, TG 76%, TT 73%, p = 0.006. After multivariate analysis, (adjusting for age, eGFR, baseline mean arterial pressure, contemporary CMR heart rate, total cholesterol, high sensitive C-reactive protein, body mass index and gender GG genotype was associated with a worse LVEF, and increased LV end-diastolic and systolic index (p = 0.004, 0.049 and 0.009 respectively.eNOS Glu298Asp rs1799983 polymorphism in CKD patients is associated with relevant sub-clinical cardiac remodelling as detected by CMR. This gene variant may therefore represent an important genetic biomarker, and possibly highlight pathways for intervention, in these patients who are at particular risk of worsening cardiac disease as their renal dysfunction progresses.

  20. Nitric oxide availability in deeply hypoxic crucian carp: acute and chronic changes and utilization of ambient nitrite reservoirs.

    Science.gov (United States)

    Hansen, Marie N; Gerber, Lucie; Jensen, Frank B

    2016-03-15

    Recent research suggest that anoxia-tolerant fish transfer extracellular nitrite into the tissues, where it is used for nitric oxide (NO) generation, iron-nitrosylation, and S-nitrosation of proteins, as part of the cytoprotective response toward prolonged hypoxia and subsequent reoxygenation. We hypothesized that crucian carp take up ambient nitrite and use it as a source of cellular NO availability during hypoxia. Fish were exposed for 1 day to normoxia (Po2 > 140 mmHg) and deep hypoxia (1 nitric oxide synthase-2 gene variant. The data support that ambient nitrite is taken up across the gills to be distributed via the blood to the tissues, particularly the heart, where it assists in cytoprotection and other functions. Cardiac nitrite was not elevated in acutely exposed fish, revealing that the response requires time. NO metabolite levels were higher during acute than chronic exposures, possibly caused by increased swimming activity and stress in acutely exposed fish.

  1. Chronic treatment with nitric oxide-releasing aspirin reduces plasma low-density lipoprotein oxidation and oxidative stress, arterial oxidation-specific epitopes, and atherogenesis in hypercholesterolemic mice

    Science.gov (United States)

    Napoli, Claudio; Ackah, Eric; de Nigris, Filomena; Del Soldato, Piero; D'Armiento, Francesco P.; Crimi, Ettore; Condorelli, Mario; Sessa, William C.

    2002-01-01

    The effects of chronic treatment with nitric oxide-containing aspirin (NO-aspirin, NCX-4016) in comparison with regular aspirin or placebo on the development of a chronic disease such as atherosclerosis were investigated in hypercholesterolemic low-density lipoprotein (LDL)-receptor-deficient mice. Male mice were assigned randomly to receive in a volume of 10 ml/kg either placebo (n = 10), 30 mg/kg/day NO-aspirin (n = 10), or 18 mg/kg/day of regular aspirin (n = 10). After 12 weeks of treatment, the computer-assisted imaging analysis revealed that NO-aspirin reduced the aortic cumulative lesion area by 39.8 ± 12.3% compared with that of the placebo (P < 0.001). Regular aspirin did not reduce significantly aortic lesions (−5.1 ± 2.3%) compared with the placebo [P = 0.867, not significant (NS)]. Furthermore, NO-aspirin reduced significantly plasma LDL oxidation compared with aspirin and placebo, as shown by the significant reduction of malondialdehyde content (P < 0.001) as well as by the prolongation of lag-time (P < 0.01). Similarly, systemic oxidative stress, measured by plasma isoprostanes, was significantly reduced by treatment with NCX-4016 (P < 0.05). More importantly, mice treated with NO-aspirin revealed by immunohistochemical analysis of aortic serial sections a significant decrease in the intimal presence of oxidation-specific epitopes of oxLDL (E06 monoclonal antibody, P < 0.01), and macrophages–derived foam cells (F4/80 monoclonal antibody, P < 0.05), compared with placebo or aspirin. These data indicate that enhanced NO release by chronic treatment with the NO-containing aspirin has antiatherosclerotic and antioxidant effects in the arterial wall of hypercholesterolemic mice. PMID:12209007

  2. Sustained pulmonary hypertension and right ventricular hypertrophy after chronic hypoxia in mice with congenital deficiency of nitric oxide synthase 3.

    OpenAIRE

    Steudel, W.; Scherrer-Crosbie, M; Bloch, K D; Weimann, J.; Huang, P L; Jones, R. C.; Picard, M H; Zapol, W M

    1998-01-01

    Chronic hypoxia induces pulmonary hypertension and right ventricular (RV) hypertrophy. Nitric oxide (NO) has been proposed to modulate the pulmonary vascular response to hypoxia. We investigated the effects of congenital deficiency of endothelial NO synthase (NOS3) on the pulmonary vascular responses to breathing 11% oxygen for 3-6 wk. After 3 wk of hypoxia, RV systolic pressure was greater in NOS3-deficient than in wild-type mice (35+/-2 vs 28+/-1 mmHg, x+/-SE, P < 0.001). Pulmonary artery p...

  3. Nitric Oxide Bioavailability and Adiponectin Production in Chronic Systolic Heart Failure: Relation to Severity of Cardiac Dysfunction

    Science.gov (United States)

    Tang, W.H. Wilson; Shrestha, Kevin; Tong, Wilson; Wang, Zeneng; Troughton, Richard W.; Borowski, Allen G.; Klein, Allan L.; Hazen, Stanley L.

    2013-01-01

    Adiponectin is an anti-inflammatory, anti-atherogenic adipokine elevated in heart failure (HF) that may protect against endothelial dysfunction by influencing underlying nitric oxide bioavailablity. In this study, we examine the relationship between plasma adiponectin levels and measures of nitric oxide bioavailability and myocardial performance in patients with chronic systolic HF. In 139 ambulatory patients with stable, chronic systolic HF (left ventricular [LV] ejection fraction ≤40%, New York Heart Association [NYHA] class I to IV), we measured plasma levels of adiponectin, asymmetric dimethylarginine (ADMA) and global arginine bioavailability (GABR), and performed comprehensive echocardiography with assessment of cardiac structure and performance. Adverse events (all-cause mortality or cardiac transplantation) were prospectively tracked for a median of 39 months. Plasma adiponectin levels directly correlated with plasma ADMA levels (Spearman’s r=0.41, p<0.001) and NT-proBNP levels (r=0.55, p<0.001), inversely correlated with GABR (r= −0.39, p<0.001), and were not associated with hsCRP (p=0.81) or MPO (p=0.07). Interestingly, increased plasma adiponectin levels remained positively correlated with plasma ADMA levels only in patients with elevated NT-proBNP levels (r= 0.33, p=0.009). Higher plasma adiponectin levels were associated with worse LV diastolic dysfunction (rank sums p=0.002), RV systolic dysfunction (rank sums p=0.002), and RV diastolic dysfunction (rank sums p=0.011), but not after adjustment for plasma ADMA and NT-proBNP levels. Plasma adiponectin levels predicted increased risk of adverse clinical events (HR [95% CI]: 1.45 [1.02–2.07], p=0.038) but not after adjustment for plasma ADMA and NT-proBNP levels, or echocardiographic indices of diastolic or RV systolic dysfunction. In patients with chronic systolic HF, adiponectin production is more closely linked with nitric oxide bioavailability than inflammation, and appears to be more robust

  4. Chronic Running Exercise Alleviates Early Progression of Nephropathy with Upregulation of Nitric Oxide Synthases and Suppression of Glycation in Zucker Diabetic Rats

    OpenAIRE

    Daisuke Ito; Pengyu Cao; Takaaki Kakihana; Emiko Sato; Chihiro Suda; Yoshikazu Muroya; Yoshiko Ogawa; Gaizun Hu; Tadashi Ishii; Osamu Ito; Masahiro Kohzuki; Hideyasu Kiyomoto

    2015-01-01

    Exercise training is known to exert multiple beneficial effects including renal protection in type 2 diabetes mellitus and obesity. However, the mechanisms regulating these actions remain unclear. The present study evaluated the effects of chronic running exercise on the early stage of diabetic nephropathy, focusing on nitric oxide synthase (NOS), oxidative stress and glycation in the kidneys of Zucker diabetic fatty (ZDF) rats. Male ZDF rats (6 weeks old) underwent forced treadmill exercise ...

  5. Reduction of blood nitric oxide levels is associated with clinical improvement of the chronic pelvic pain related to endometriosis

    Directory of Open Access Journals (Sweden)

    M.G. Rocha

    2015-04-01

    Full Text Available The objective of this prospective study was to determine the plasma levels of nitric oxide (NO in women with chronic pelvic pain secondary to endometriosis (n=24 and abdominal myofascial pain syndrome (n=16. NO levels were measured in plasma collected before and 1 month after treatment. Pretreatment NO levels (μM were lower in healthy volunteers (47.0±12.7 than in women with myofascial pain (64.2±5.0, P=0.01 or endometriosis (99.5±12.9, P<0.0001. After treatment, plasma NO levels were reduced only in the endometriosis group (99.5±12.9 vs 61.6±5.9, P=0.002. A correlation between reduction of pain intensity and reduction of NO level was observed in the endometriosis group [correlation = 0.67 (95%CI = 0.35 to 0.85, P<0.0001]. Reduction of NO levels was associated with an increase of pain threshold in this group [correlation = -0.53 (-0.78 to -0.14, P<0.0001]. NO levels appeared elevated in women with chronic pelvic pain diagnosed as secondary to endometriosis, and were directly associated with reduction in pain intensity and increase in pain threshold after treatment. Further studies are needed to investigate the role of NO in the pathophysiology of pain in women with endometriosis and its eventual association with central sensitization.

  6. The Effects of Sub-Chronic Treatment with Pioglitazone on the Septic Mice Mortality in the Model of Cecal Ligation and Puncture: Involvement of Nitric Oxide Pathway

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    Hamed Shafaroodi

    2015-10-01

    Full Text Available Sepsis is a systemic inflammatory response syndrome caused by an infection and remains as a major challenge in health care. Many studies have reported that pioglitazone may display anti-inflammatory effects. This study was designed to evaluate the effect of subchronic treatment with pioglitazone on high-grade septic mice survival and nitrergic system involvement. Diffused sepsis was induced by cecal ligation and puncture (CLP surgery in male NMRI mice (20-30 g. Pioglitazone (5,10 and 20 mg/kg was administered by gavage daily for 5 days prior to surgery. Nitric oxide involvement was assessed by sub-chronic administration of a non-selective nitric oxide synthase inhibitor, L-NAME and a selective inducible nitric oxide synthase inhibitor, aminoguanidine. TNF-α  and IL-1β plasma levels were measured by ELISA. Pioglitazone (10 and 20 mg/kg significantly improved survival rate in septic mice. The chronic intraperitoneally co-administration of L-NAME (0.5 mg/kg, daily or aminoguanidine (1 mg/kg, daily with a daily dose of pioglitazone, 5 mg/kg, significantly increased the survival rate. This survival improving effect was accompanied by a significant reduction in pro-inflammatory cytokines TNF-α and IL-1β plasma levels. In conclusion, sub-chronic pioglitazone treatment can improve survival in mouse sepsis model by CLP. Inhibition of nitric oxide release, probably through inducible nitric oxide synthase at least in part is responsible for this effect. Suppression of TNF-α and IL-1β could be another mechanism in pioglitazone-induced survival improving effect in septic mice.

  7. Demystified … Nitric oxide

    Science.gov (United States)

    Stuart-Smith, K

    2002-01-01

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

  8. Cellular mechanisms for the treatment of chronic heart failure: the nitric oxide- and adenosine-dependent pathways.

    Science.gov (United States)

    Minamino, Tetsuo; Kitakaze, Masafumi

    2002-05-01

    Accumulated evidence suggests that several drugs proven to improve survival in patients with chronic heart failure (CHF) enhance endogenous nitric oxide (NO)- and/or adenosine-dependent pathways. Indeed, we and others have demonstrated that: i) antagonists of either renin-angiotensin-aldosterone or beta-adrenergic systems enhance NO-dependent pathways; ii) although carvedilol and amlodipine belong to different drug classes, both of them can increase cardiac adenosine levels; iii) increased adenosine levels by dipyridamole are associated with the improvement of CHF. Interestingly, both NO and adenosine have multifactorial beneficial actions in cardiovascular systems. First of all, both of them induce vasodilation and decrease myocardial hypercontractility, which may contribute to a reduction in the severity of myocardial ischaemia. Both adenosine and NO are also involved in cardioprotection attributable to acute and late phases of ischaemic preconditioning, respectively. Secondly, they can modulate the neurohormonal systems that contribute to the progression of CHF. Thus, we propose that enhancement of endogenous NO and/or adenosine as potential therapeutic targets in a new strategy for the treatment for CHF. PMID:15989539

  9. Chronic deficit in nitric oxide elicits oxidative stress and augments T-type calcium-channel contribution to vascular tone of rodent arteries and arterioles

    DEFF Research Database (Denmark)

    Howitt, Lauren; Kuo, Ivana Y; Ellis, Anthie;

    2013-01-01

    AIMS: As cardiovascular disease is characterized by reduced nitric oxide bioavailability, our aim was to determine the impact of this change on the mechanism underlying vascular tone of pressurized arteries in vitro and in vivo. METHODS AND RESULTS: We used pressurized cerebral and mesenteric......, by regulating the bioavailability of reactive oxygen species produced by NADPH oxidase. Our data provide evidence for a novel causal link between nitric oxide deficit, oxidative stress, and T-type calcium channel function....

  10. 49 CFR 173.337 - Nitric oxide.

    Science.gov (United States)

    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...

  11. Review article: the potential role of nitric oxide in chronic inflammatory bowel disorders

    DEFF Research Database (Denmark)

    Perner, Anders; Rask-Madsen, J

    1999-01-01

    The aetiology of the chronic inflammatory bowel diseases-ulcerative colitis and Crohn's disease-as well as 'microscopic colitis'-both collagenous (COC) and lymphocytic colitis (LC)-remains unknown. Autoimmune mechanisms, cytokine polymorphism, commensal bacteria, infectious agents and vascular...... by the generation of superoxide with reduced L-arginine availability. In active ulcerative colitis, and to a lesser extent in Crohn's disease, a greatly increased production of NO has been demonstrated by indirect and direct measurements. Surprisingly, even higher rates of production have been observed in COC...

  12. Expression of Nitric Oxide Synthase Isoenzyme in Lung Tissue of Smokers with and without Chronic Obstructive Pulmonary Disease

    Directory of Open Access Journals (Sweden)

    Wen-Ting Jiang

    2015-01-01

    Full Text Available Background: It has been demonstrated that only 10%-20% cigarette smokers finally suffer chronic obstructive pulmonary disease (COPD. The underlying mechanism of development remains uncertain so far. Nitric oxide (NO has been found to be closely associated with the pathogenesis of COPD, the alteration of NO synthase (NOS expression need to be revealed. The study aimed to investigate the alterations of NOS isoforms expressions between smokers with and without COPD, which might be helpful for identifying the susceptibility of smokers developing into COPD. Methods: Peripheral lung tissues were obtained from 10 nonsmoker control subjects, 15 non-COPD smokers, and 15 smokers with COPD. Neuronal NOS (nNOS, inducible NOS (iNOS, and endothelial NOS (eNOS mRNA and protein levels were measured in each sample by using real-time polymerase chain reaction and Western blotting. Results: INOS mRNA was significantly increased in patients with COPD compared with nonsmokers and smokers with normal lung function (P < 0.001, P = 0.001, respectively. iNOS protein was also higher in COPD patients than nonsmokers and smokers with normal lung function (P < 0.01 and P = 0.01, respectively. However, expressions of nNOS and eNOS did not differ among nonsmokers, smokers with and without COPD. Furthermore, there was a negative correlation between iNOS protein level and lung function parameters forced expiratory volume in 1 s (FEV 1 (% predicted (r = −0.549, P = 0.001 and FEV 1 /forced vital capacity (%, r = −0.535, P = 0.001. Conclusions: The expression of iNOS significantly increased in smokers with COPD compared with that in nonsmokers or smokers without COPD. The results suggest that iNOS might be involved in the pathogenesis of COPD, and may be a potential marker to identify the smokers who have more liability to suffer COPD.

  13. Exhaled hydrogen sulfide in patients with chronic obstructive pulmonary disease and its correlation with exhaled nitric oxide

    Institute of Scientific and Technical Information of China (English)

    SUN Yun; WANG Xin-mao; CHEN Ya-hong; ZHU Rui-xia; LIAO Cheng-cheng

    2013-01-01

    Background Exhaled nitric oxide (NO) is a noninvasive biomarker of airway inflammation in pulmonary diseases.Hydrogen sulfide (H2S),as the third member of the gasotransmitter family,is involved in the pathophysiological process in lung diseases.H2S also exists in exhaled breath and can be sampled non-invasively.The study investigated the level of exhaled H2S in patients with chronic obstructive pulmonary disease (COPD) and its correlation with exhaled NO.Methods Levels of exhaled NO and H2S,lung function,and cell differential counts in induced sputum were studied in 19patients with acute exacerbation of COPD (AECOPD),19 patients with stable COPD and seven healthy smoke controls.Results Exhaled H2S levels were similar in patients with AECOPD (10.0 parts per billion (ppb),8.0-13.0 ppb),stable COPD (10.0 ppb,9.0-12.0 ppb),and healthy controls (9.0 ppb,8.0-16.0 ppb) (P >0.05).Exhaled NO levels were similar in patients with AECOPD (155.0 ppb,129.0-190.0 ppb),stable COPD (154.0 ppb,133.0-175.0 ppb) and healthy controls (165.0 ppb,112.0-188.0 ppb) (P >0.05).Exhaled H2S levels correlated positively with exhaled NO in all healthy controls and patients with COPD (r=0.467,P <0.01).No significant correlation was found between the exhaled H2S level and percentage of predicted FEV1 (P >0.05) and proportion of different cell types in induced sputum (P >0.05).Conclusions There is a correlation between exhaled H2S and exhaled NO.The role of exhaled H2S in airway inflammation in COPD still needs further investigation.

  14. Sleep active cortical neurons expressing neuronal nitric oxide synthase are active after both acute sleep deprivation and chronic sleep restriction.

    Science.gov (United States)

    Zielinski, M R; Kim, Y; Karpova, S A; Winston, S; McCarley, R W; Strecker, R E; Gerashchenko, D

    2013-09-01

    Non-rapid eye movement (NREM) sleep electroencephalographic (EEG) delta power (~0.5-4 Hz), also known as slow wave activity (SWA), is typically enhanced after acute sleep deprivation (SD) but not after chronic sleep restriction (CSR). Recently, sleep-active cortical neurons expressing neuronal nitric oxide synthase (nNOS) were identified and associated with enhanced SWA after short acute bouts of SD (i.e., 6h). However, the relationship between cortical nNOS neuronal activity and SWA during CSR is unknown. We compared the activity of cortical neurons expressing nNOS (via c-Fos and nNOS immuno-reactivity, respectively) and sleep in rats in three conditions: (1) after 18-h of acute SD; (2) after five consecutive days of sleep restriction (SR) (18-h SD per day with 6h ad libitum sleep opportunity per day); (3) and time-of-day matched ad libitum sleep controls. Cortical nNOS neuronal activity was enhanced during sleep after both 18-h SD and 5 days of SR treatments compared to control treatments. SWA and NREM sleep delta energy (the product of NREM sleep duration and SWA) were positively correlated with enhanced cortical nNOS neuronal activity after 18-h SD but not 5days of SR. That neurons expressing nNOS were active after longer amounts of acute SD (18h vs. 6h reported in the literature) and were correlated with SWA further suggest that these cells might regulate SWA. However, since these neurons were active after CSR when SWA was not enhanced, these findings suggest that mechanisms downstream of their activation are altered during CSR. PMID:23685166

  15. Nitric Oxide Synthases and Atrial Fibrillation

    OpenAIRE

    CynthiaAnnCarnes; ArunSridhar; SandorGyorke

    2012-01-01

    Oxidative stress has been implicated in the pathogenesis of atrial fibrillation. There are multiple systems in the myocardium which contribute to redox homeostasis, and loss of homeostasis can result in oxidative stress. Potential sources of oxidants include nitric oxide synthases, which normally produce nitric oxide in the heart. Two nitric oxide synthase isoforms (1 and 3) are normally expressed in the heart. During pathologies such as heart failure, there is induction of nitric oxide syn...

  16. Inducible nitric oxide synthase is involved in the modulation of depressive behaviors induced by unpredictable chronic mild stress

    Directory of Open Access Journals (Sweden)

    Peng Yun-Li

    2012-07-01

    Full Text Available Abstract Background Experiences and inflammatory mediators are fundamental in the provocation of major depressive disorders (MDDs. We investigated the roles and mechanisms of inducible nitric oxide synthase (iNOS in stress-induced depression. Methods We used a depressive-like state mouse model induced by unpredictable chronic mild stress (UCMS. Depressive-like behaviors were evaluated after 4 weeks of UCMS, in the presence and absence of the iNOS inhibitor N-(3-(aminomethylbenzylacetamidine (1400 W compared with the control group. Immunohistochemistry was used to check the loss of Nissl bodies in cerebral cortex neurons. The levels of iNOS mRNA expression in the cortex and nitrites in the plasma were measured with real-time reverse transcription PCR (RT-PCR and Griess reagent respectively. Results Results showed that the 4-week UCMS significantly induced depressive-like behaviors, including decreased sucrose preference in a sucrose preference test, increased duration of immobility in a forced swim test, and decreased hole-searching time in a locomotor activity test. Meanwhile, in the locomotor activity test, UCMS had no effect on normal locomotor activities, such as resting time, active time and total travel distance. Furthermore, the levels of iNOS mRNA expression in the cortex and nitrites in the plasma of UCMS-exposed mice were significantly increased compared with that of the control group. Neurons of cerebral cortex in UCMS-exposed mice were shrunken with dark staining, together with loss of Nissl bodies. The above-mentioned stress-related depressive-like behaviors, increase of iNOS mRNA expression in the cortex and nitrites in the plasma, and neuron damage, could be abrogated remarkably by pretreating the mice with an iNOS inhibitor (1400 W. Moreover, neurons with abundant Nissl bodies were significantly increased in the 1400 W + UCMS group. Conclusions These results support the notion that stress-related NO (derived from iNOS may

  17. Effect of Angiotensin II on Blood Flow in Acute and Chronically Inflamed Knee Joints of Rabbits: The Role of Nitric Oxide

    Directory of Open Access Journals (Sweden)

    Hamid Najafipour

    2009-03-01

    Full Text Available Background: Angiotensin converting enzyme (ACE upregulationin stromal cells of joints affected by rheumatoid arthritismay lead to higher tissue angiotensin II that is a vasoconstrictorand mitogen factor. To date, the role of angiotensin II onregulating blood flow in inflamed joints has not been studied.Methods: Acute and chronic joint inflammation was inducedin rabbits by intra-articular injection of carrageenan and antigen-induced arthritis method, respectively. The ACE level ofsynovial fluid and the response of joint blood flow to angiotensinII, angiotensin II receptor antagonist, and the role ofnitric oxide (NO in modulation of the effects of angiotensin IIon joint blood vessels were examined.Results: The synovial fluid level of ACE was significantly increasedduring the process of inflammation and angiotensin IIincreased joint vascular resistance dose-dependently in both acuteand chronically inflamed joints. The angiotensin 1 receptor antagonistlosartan completely blocked the vasoconstrictor effect ofangiotensin II on joint blood vessels and induced vasodilatation.Nitric oxide synthase inhibitor N-omega -nitro L- argininemethyl ester (L-NAME increased joint vascular resistance andaugmented vascular response of inflamed joints to angiotensin II.Conclusion: Angiotensin II receptors in joint blood vesselsare angiotensin -1 subtype, and inflammation significantlyincreases the activity of synovial fluid ACE. Nitric oxide playsa significant role on regulating joint blood flow and in modulationof angiotensin 1 receptor-mediated vasoconstriction ofinflamed joint blood vessels.

  18. Low level and sub-chronic exposure to methylmercury induces hypertension in rats: nitric oxide depletion and oxidative damage as possible mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Grotto, Denise; Barcelos, Gustavo R.M.; Barbosa, Fernando [Universidade de Sao Paulo, Departamento de Analises Clinicas, Toxicologicas e Bromatologicas, Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, Ribeirao Preto, SP (Brazil); Castro, Michele M. de [Universidade de Sao Paulo, Departamento de Farmacologia, Faculdade de Medicina de Ribeirao Preto, Ribeirao Preto, SP (Brazil); Garcia, Solange C. [Universidade Federal de Santa Maria, Departamento de Analises Clinicas e Toxicologicas, Santa Maria, Rio Grande do Sul (Brazil)

    2009-07-15

    Increased risk of hypertension after methylmercury (MeHg) exposure has been suggested. However, the underlying mechanisms are not well explored. In this paper, we have analyzed whether sub-chronic exposure to MeHg increases systolic blood pressure even at very low levels. In addition, we analyzed if the methylmercury-induced hypertension is associated with a decreased plasmatic nitric oxide levels and with a dysregulation of the activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), as well as the levels of MDA and glutathione. For this study, Wistar rats were treated with methylmercury chloride (100 {mu}g/kg per day) or vehicle. Total treatment time was 100 days. Malondialdehyde (MDA) and circulating NOx levels and superoxide dismutase (SOD) and catalase (CAT) activities were determined in plasma, whereas glutathione levels were determined in erythrocytes. Our results show that long-term treatment at a low level of MeHg affected systolic blood pressure, increasing and reducing the levels of plasmatic MDA and NOx, respectively. However, the activity of SOD did not decrease in the MeHg exposed group when compared to the control. We found a negative correlation between plasmatic nitrite/nitrate (NOx) levels and systolic blood pressure (r=-0.67; P=0.001), and a positive correlation between MDA and systolic blood pressure (r=0.61; P=0.03), thus suggesting increased inhibition of NO formation with the increase of hypertension. In conclusion, long-term exposure to a low dose of MeHg increases the systolic pressure and is associated, at least in part, with increased production of ROS as judged by increased production of malondialdehyde and depressed NO availability. (orig.)

  19. [Value of Fractional Exhaled Nitric Oxide after Using a Beta-2 Bronchodilator in the Differential Diagnosis of Bronchial Asthma and Chronic Obstructive Pulmonary Disease].

    Science.gov (United States)

    Ura, Midori; Tanaka, Hitomi; Takahashi, Kaori; Yamazaki, Haruna; Fujimoto, Keisaku

    2016-02-01

    It has been established that an increase in fractional exhaled nitric oxide (FeNO) is one of the indicators of bronchial asthma (BA) in clinical settings. However, the differential diagnosis of BA and chronic obstructive pulmonary disease (COPD) is difficult due to pathological similarities. Therefore, to determine if FeNO may be utilized in the differential diagnosis of BA and COPD, we compared FeNO values before and after inhalation of a short-acting beta-2 agonist (SABA). There were 3 groups of subjects recruited to this study: (1) 23 normal healthy controls, (2) 36 patients with BA, and (3) 13 patients with COPD. We measured FeNO, forced vital capacity, forced expiratory volume in 1 second (FEV1), and FEV1%, calculated using spirometry. Then, after the subjects inhaled the SABA, we measured these data after 10 and 30 minutes. Here we found that after inhalation of a SABA, 8 cases in the BA group who showed reversibility of airway obstruction demonstrated significantly increased FeNO values compared to the BA patients with non-reversible airway obstruction, those with COPD, and healthy subjects. This finding may be because the obstructed pulmonary peripheral airway was expanded by inhaling a SABA, and nitric oxide, which had been produced in the peripheral airway, was then exhaled. These results suggest the possibility that FeNO may be utilized in the differential diagnosis of BA and COPD. PMID:27311275

  20. Effects of chronic prenatal ethanol exposure on locomotor activity, and hippocampal weight, neurons, and nitric oxide synthase activity of the young postnatal guinea pig.

    Science.gov (United States)

    Gibson, M A; Butters, N S; Reynolds, J N; Brien, J F

    2000-01-01

    Decreased nitric oxide synthase (NOS)-catalyzed formation of NO from L-arginine may be involved in ethanol teratogenesis involving the hippocampus. This hypothesis was tested by determining the effects of chronic prenatal ethanol exposure on locomotor activity and on hippocampal weight, number of CA1 and CA3 pyramidal cells and dentate gyrus granule cells, and NOS activity of the postnatal guinea pig. Timed, pregnant guinea pigs received one of the following chronic oral regimens throughout gestation: 4 g ethanol/kg maternal body weight/day, isocaloric-sucrose/pair-feeding, or water. At postnatal day (PD) 10, spontaneous locomotor activity was measured. At PD 12, histological analysis was performed on the hippocampal formation, in which hippocampal CA1 and CA3 pyramidal cells and dentate gyrus granule cells were counted; body, brain, and hippocampal weights were measured; and hippocampal NOS enzymatic activity was determined using a radiometric assay. Chronic prenatal ethanol exposure produced hyperactivity, decreased the brain and hippocampal weights with no change in body weight, decreased the number of hippocampal CA1 pyramidal cells by 25-30%, and had no effect on hippocampal NOS activity compared with the two control groups. These data, together with our previous findings in the fetal guinea pig, demonstrate that chronic prenatal ethanol exposure decreases hippocampal NOS activity in near-term fetal life that temporally precedes the selective loss of hippocampal CA1 pyramidal cells in postnatal life. PMID:10758347

  1. Effect of chronic prenatal ethanol exposure on nitric oxide synthase I and III proteins in the hippocampus of the near-term fetal guinea pig.

    Science.gov (United States)

    Kimura, K A; Chiu, J; Reynolds, J N; Brien, J F

    1999-01-01

    Chronic prenatal ethanol exposure suppresses nitric oxide synthase (NOS) enzymatic activity, in the hippocampus of the near-term fetal guinea pig at gestational day (GD) 62. The objective of this study was to determine if this decrease in NOS activity is the result of decreased NOS I and NOS III protein expression. Pregnant guinea pigs received oral administration of 4 g ethanol/kg maternal body weight/day (n = 8), isocaloric-sucrose/pair feeding (n = 8), or water (n = 8) from GD 2 to GD 61. The NOS I and NOS III protein expression and localization in the hippocampus were determined using Western blot analysis and immunohistochemistry, respectively. The chronic ethanol regimen produced fetal body, brain, and hippocampal growth restriction compared with the isocaloric-sucrose/pair fed and water groups but did not affect the expression or localization of NOS I and NOS III proteins in the hippocampus. The decrease in NOS enzymatic activity induced by chronic prenatal ethanol exposure may be the result of posttranslational modification of NOS I and/or NOS III protein in the hippocampus of the near-term fetal guinea pig. PMID:10386828

  2. Resveratrol and Endothelial Nitric Oxide

    Directory of Open Access Journals (Sweden)

    Ning Xia

    2014-10-01

    Full Text Available Nitric oxide (NO derived from the endothelial NO synthase (eNOS has antihypertensive, antithrombotic, anti-atherosclerotic and antiobesogenic properties. Resveratrol is a polyphenol phytoalexin with multiple cardiovascular and metabolic effects. Part of the beneficial effects of resveratrol are mediated by eNOS. Resveratrol stimulates NO production from eNOS by a number of mechanisms, including upregulation of eNOS expression, stimulation of eNOS enzymatic activity and reversal of eNOS uncoupling. In addition, by reducing oxidative stress, resveratrol prevents oxidative NO inactivation by superoxide thereby enhancing NO bioavailability. Molecular pathways underlying these effects of resveratrol involve SIRT1, AMPK, Nrf2 and estrogen receptors.

  3. Study of Atmospheric Nitric Oxide

    Science.gov (United States)

    Dalgarno, A.

    1998-01-01

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

  4. Attenuation by creatine of myocardial metabolic stress in Brattleboro rats caused by chronic inhibition of nitric oxide synthase.

    Science.gov (United States)

    Constantin-Teodosiu, D; Greenhaff, P L; Gardiner, S M; Randall, M D; March, J E; Bennett, T

    1995-12-01

    1. The present experiment was undertaken to investigate: (a) the effect of nitric oxide synthase (NOS) inhibition, mediated by oral supplementation of the NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), on measures of myocardial energy metabolism and function: (b) the effect of oral creatine supplementation on these variables, in the absence and presence of L-NAME. 2. In one series of experiments, 4 weeks oral administration of L-NAME (0.05 mg ml-1 day-1 in the drinking water) to Brattleboro rats caused significant reductions in myocardial ATP, creatine, and total creatine concentrations and an accumulation of tissue lactate when compared with control animals. Administration of creatine (0.63 mg ml-1 day-1 in the drinking water) for 4 weeks elevated myocardial creatine and total creatine concentrations and reduced lactate accumulation, but did not significantly affect ATP or phosphocreatine (PCr). Concurrent treatment with creatine and L-NAME prevented the reduction in creatine and total creatine concentrations, and significantly attenuated the accumulation of lactate and the reduction in ATP seen with L-NAME alone. 3. In a second series of experiments, 4 weeks treatment with L-NAME and creatine plus L-NAME increased mean arterial blood pressure in conscious Brattleboro rats. Hearts isolated from these animals showed decreased coronary flow and left ventricular developed pressure (LVDP), and total mechanical performance. Treatment with creatine alone had no measurable effect on either mean arterial blood pressure or coronary flow in isolated hearts. However, there was an increase in LVDP, but not in total mechanical performance, because there was a bradycardia. 4. These results indicate that creatine supplementation can attenuate the metabolic stress associated with L-NAME administration and that this effect occurs as a consequence of the action of creatine on myocardial energy metabolism.

  5. Novel effects of nitric oxide

    Science.gov (United States)

    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.

  6. THE STUDIES OF SERUM CVB-SPECIFIC IgM ANTIBODY AND NITRIC OXIDE AMONG THE PATIENTS WITH LATENT AND CHRONIC KESHAN DISEASE

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective To investigate the serum coxsackie virus B(CVB) infection and nitric oxide (NO)level of the patients suffer from latent or chronic Keshan disease and their characteristics in the etiopathology of Keshan disease. Methods Sera were isolated from 30 patients with latent or chronic Keshan disease in Huangling county.Shaanxi Province, and the CVB-specific IgM antibody and NO were tested. Control groups were health subjects in Huangling county or Xi'an city, Shaanxi Province. Results The percentage of CVB-specific IgM positive in patients in Huangling county was significantly higher than that of both control groups in Huangling county and Xi'an city (P<0. 05). The serum level of NO in patients was significantly higher than that of the control group in Huangling county (P<0.05) ,however,compared with control group in Xi'an city, there was no difference (P>0.05). In CVB-specific IgM positive patients,the serum level of NO was significantly higher than that of CVB-specific IgM negative group(P<0.05).Conclusion CVB infection and serum NO level might be related to the etiopathology and the development of Keshan disease.

  7. Nitric oxide treatment for fulminant pulmonary hypertension.

    OpenAIRE

    Allman, K G; Young, J D; Stevens, J E; Archer, L N

    1993-01-01

    A 3 year old child with known pulmonary haemosiderosis suffered acute circulatory collapse secondary to raised pulmonary vascular resistance. Nitric oxide inhalation produced a profound improvement in circulatory parameters and gaseous exchange. Nitric oxide may have a therapeutic role in acute pulmonary hypertensive crisis.

  8. Inducible nitric oxide synthase in renal transplantation

    NARCIS (Netherlands)

    Joles, JA; Vos, IH; Grone, HJ; Rabelink, TJ

    2002-01-01

    The importance of the endothelial isoform of nitric oxide synthase (eNOS) has been well established. Endothelium-derived nitric oxide has been shown to be essential for vascular homeostasis and modulation of eNOS has thus become a target in prevention of cardiovascular disease. The role of the induc

  9. Nitric oxide fumigation for postharvest pest control

    Science.gov (United States)

    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 ...

  10. Nitric oxide-releasing porous silicon nanoparticles

    Science.gov (United States)

    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.

  11. Study of T-lymphocyte subsets, nitric oxide, hexosamine and Helicobacter pylori infection in patients with chronic gastric diseases

    Institute of Scientific and Technical Information of China (English)

    Hui Zhang; Shu Lin Jiang; Xi Xian Yao

    2000-01-01

    Chronic gastritis ( CG ) and peptic ulcer ( PU ) are frequently-occurring diseases. It is now well recognized that Helicobacter pylori (Hp) is a major factor that leads to CG and PU[1-8] In order to study the relationship among T lymphocyte subsets, NO, Hexosamine and Hp infection in patients with chronic gastric diseases, the levelsof blood T lymphocyte subsets, plasma NO and hexosamine in gastric mucosa were measured respectively in 30 patients with CG and 32 patients of PU + CG.

  12. L-Arginine/nitric oxide pathway in chronic tension-type headache: relation with serotonin content and secretion and glutamate content.

    Science.gov (United States)

    Sarchielli, Paola; Alberti, Andrea; Floridi, Ardesio; Gallai, Virgilio

    2002-06-15

    Previous research of our group demonstrated an increase in L-arginine/nitric oxide (NO) pathway activity in patients with chronic daily headache (CDH) with a previous history of migraine, which was associated with a reduced platelet serotonin content and increased Ca(2+) levels. In the present work, we assessed the variations in L-arginine/NO pathway activity and platelet cyclic guanosine 3',5'-monophosphate (cGMP) levels in 25 patients affected by chronic tension-type headache (CTTH) (8 M, 17 F; age range: 34-54 years). The NO production, shown spectrophotometrically by stoichiometric transformation of oxyhemoglobin to methemoglobin due to NO synthase (NOS) activity, and inter platelet cGMP concentration, assessed with a RIA method, were determined in parallel to variations of aggregation response to 0.3 microg/ml collagen. The intracellular platelet calcium concentrations were also determined using fluorescence polarisation spectrometry. Platelet serotonin content and collagen-induced secretion as well as glutamate content were also determined with high-performance liquid chromatography (HPLC). The above parameters were compared with those of an age-matched control group. A reduction in aggregation platelet response was found. The reduction in platelet aggregation was coupled with an increased NO and cGMP production (pmyofascial cranial structures contributing to central sensitization. The increase in NOS activity seems to be associated with a hyposerotonergic status, particularly in patients with analgesic abuse, and this can contribute to central sensitization in CTTH patients. The increase in platelet glutamate content in the same patients suggests the implication of the above excitatory amino acid in spinal and supraspinal structures involved in head pain induction and maintenance.

  13. 21 CFR 868.2380 - Nitric oxide analyzer.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Nitric oxide analyzer. 868.2380 Section 868.2380...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2380 Nitric oxide analyzer. (a) Identification. The nitric oxide analyzer is a device intended to measure the concentration of nitric oxide...

  14. 21 CFR 862.3080 - Breath nitric oxide test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Breath nitric oxide test system. 862.3080 Section... Systems § 862.3080 Breath nitric oxide test system. (a) Identification. A breath nitric oxide test system is a device intended to measure fractional nitric oxide in human breath. Measurement of changes...

  15. Nitric Oxide: Role in Human Biology

    OpenAIRE

    Nikhil Omer; Ankur Rohilla; Seema Rohilla; Ashok Kushnoor

    2012-01-01

    Nitric oxide (NO), a free radical, possesses various modulatory effects on biological systems. NO is synthesized from L-arginine by converting it to L-citrulline via nitric oxide synthase (NOS) enzymes. Moreover, various precursors of NO have been reported that include arginine, citruline, arginine alphaketoglutarate (A-AKG) and arginineketoisocaproate (A-KIC). NO possess various direct and indirect effects that broadly affect various tissues and organ systems inside the body. The present rev...

  16. Nitric oxide synthase in the pineal gland

    OpenAIRE

    Lopez-Figueroa, M.O.; Moller, M.

    1996-01-01

    The recent discovery of nitric oxide (NO) as a biological messenger molecule with unique characteristics has opened a new field in pineal research. This free radical gas is synthesized by the enzyme nitric oxide synthase (NOS) from L-arginine. The activation of adrenoreceptors in the membrane of the pinealocytes mediates the increase in NO through a mechanism that involves G proteins. In the pinealocyte, NO stimulates guanylyl cyclase resulting in an increased ...

  17. Oxygen, nitric oxide and articular cartilage

    OpenAIRE

    Fermor, B.; Christensen, S. E.; I Youn; J M Cernanec; C M Davies; Weinberg, J. B.

    2007-01-01

    Molecular oxygen is required for the production of nitric oxide (NO), a pro-inflammatory mediator that is associated with osteoarthritis and rheumatoid arthritis. To date there has been little consideration of the role of oxygen tension in the regulation of nitric oxide production associated with arthritis. Oxygen tension may be particularly relevant to articular cartilage since it is avascular and therefore exists at a reduced oxygen tension. The superficial zone exists at approximately 6% O...

  18. Processes regulating nitric oxide emissions from soils

    DEFF Research Database (Denmark)

    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...

  19. Chronic Running Exercise Alleviates Early Progression of Nephropathy with Upregulation of Nitric Oxide Synthases and Suppression of Glycation in Zucker Diabetic Rats.

    Directory of Open Access Journals (Sweden)

    Daisuke Ito

    Full Text Available Exercise training is known to exert multiple beneficial effects including renal protection in type 2 diabetes mellitus and obesity. However, the mechanisms regulating these actions remain unclear. The present study evaluated the effects of chronic running exercise on the early stage of diabetic nephropathy, focusing on nitric oxide synthase (NOS, oxidative stress and glycation in the kidneys of Zucker diabetic fatty (ZDF rats. Male ZDF rats (6 weeks old underwent forced treadmill exercise for 8 weeks (Ex-ZDF. Sedentary ZDF (Sed-ZDF and Zucker lean (Sed-ZL rats served as controls. Exercise attenuated hyperglycemia (plasma glucose; 242 ± 43 mg/dL in Sed-ZDF and 115 ± 5 mg/dL in Ex-ZDF with increased insulin secretion (plasma insulin; 2.3 ± 0.7 and 5.3 ± 0.9 ng/mL, reduced albumin excretion (urine albumin; 492 ± 70 and 176 ± 11 mg/g creatinine and normalized creatinine clearance (9.7 ± 1.4 and 4.5 ± 0.8 mL/min per body weight in ZDF rats. Endothelial (e and neuronal (n NOS expression in kidneys of Sed-ZDF rats were lower compared with Sed-ZL rats (p<0.01, while both eNOS and nNOS expression were upregulated by exercise (p<0.01. Furthermore, exercise decreased NADPH oxidase activity, p47phox expression (p<0.01 and α-oxoaldehydes (the precursors for advanced glycation end products (p<0.01 in the kidneys of ZDF rats. Additionally, morphometric evidence indicated renal damage was reduced in response to exercise. These data suggest that upregulation of NOS expression, suppression of NADPH oxidase and α-oxoaldehydes in the kidneys may, at least in part, contribute to the renal protective effects of exercise in the early progression of diabetic nephropathy in ZDF rats. Moreover, this study supports the theory that chronic aerobic exercise could be recommended as an effective non-pharmacological therapy for renoprotection in the early stages of type 2 diabetes mellitus and obesity.

  20. Nitric Oxide Homeostasis in Neurodegenerative Diseases.

    Science.gov (United States)

    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.

  1. The effect of chronic antipsychotic drug on hypothalamic expression of neural nitric oxide synthase and dopamine D2 receptor in the male rat.

    Directory of Open Access Journals (Sweden)

    Xiang Rong Zhang

    Full Text Available Antipsychotic-induced sexual dysfunction is a common and serious clinical side effect. It has been demonstrated that both neuronal nitric oxide (nNOS and dopamine D2 receptor (DRD2 in the medial preoptic area (MPOA and the paraventricular nucleus (PVN of the hypothalamus have important roles in the regulation of sexual behaviour. We investigated the influences of 21 days' antipsychotic drug administration on expression of nNOS and DRD2 in the rat hypothalamus. Haloperidol (0.5 mg/kg/day i.p. significantly decreased nNOS integrated optical density in a sub-nucleus of the MPOA, medial preoptic nucleus (MPN, and decreased the nNOS integrated optical density and cell density in another sub-nucleus of the MPOA, anterodorsal preoptic nucleus (ADP. Risperidone (0.25 mg/kg inhibited the nNOS integrated optical density in the ADP. nNOS mRNA and protein in the MPOA but not the PVN was also significantly decreased by haloperidol. Haloperidol and risperidone increased DRD2 mRNA and protein expression in both the MPOA and the PVN. Quetiapine (20 mg/kg/day i.p. did not influence the expression of nNOS and DRD2 in either the MPOA or the PVN. These findings indicate that hypothalamic nNOS and DRD2 are affected to different extents by chronic administration of risperidone and haloperidol, but are unaffected by quetiapine. These central effects might play a role in sexual dysfunction induced by certain antipsychotic drugs.

  2. Inducible nitric oxide synthase is responsible for nitric oxide release from murine pituicytes

    DEFF Research Database (Denmark)

    Kjeldsen, T H; Rivier, C; Lee, S;

    2003-01-01

    This study investigated whether pituicytes were able to produce and release nitric oxide (NO), and which type of nitric oxide synthase (NOS) would be responsible for this phenomenon. Lipopolysaccharide (LPS) 1 micro g/ml was used as inflammatory mediator. Because pituicytes are known to secrete...

  3. Autotrophic Biofilters for Oxidation of Nitric Oxide

    Institute of Scientific and Technical Information of China (English)

    陈建孟; 陈浚; LanceHershman; 王家德; DanielP.Y.Chang

    2004-01-01

    Carbon foam—a kind of new engineering material as packing material was adopted in three biofilters with different pore dimensions and adapted autotrophic nitrite nitrobacteria to investigate the purification of nitric oxide (NO) in a gas stream. The biofilm was developed on the surface of carbon foams using nitrite as its only nitric source. The moisture in the filter was maintained by ultrasonic aerosol equipment which can minimize the thickness of the liquid film. The liquid phase nitrification test was conducted to determine the variability and the potential of performance among the three carbon foam biofilters. The investigation showed that during the NO2-—N inlet concentration of 200 g·L-1·min-1 to 800 g·L-1·min-1, the 24PPC (pores per centimeter) carbon foam biofilter had the greatest potential, achieving the NO2-—N removal efficiency of 94% to 98%. The 8PPC and 18PPC carbon foam biofilters achieved the NO2-—N removal efficiency of 15% to 21% and of 30% to 40%, respectively. The potential for this system to remove NO from a gas stream was shown on the basis of a steady removal efficiency of 41% to 50% which was attained for the 24PPC carbon foam biofilter at specified NO inlet concentration of 66.97 mg·m-3 to 267.86mg·m-3 and an empty-bed residence time of 3.5 min.

  4. Neural mechanisms in nitric-oxide-deficient hypertension

    Science.gov (United States)

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

    1999-01-01

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

  5. The associations between severity of early postoperative pain, chronic postsurgical pain and plasma concentration of stable nitric oxide products after breast surgery.

    LENUS (Irish Health Repository)

    Iohom, Gabriella

    2012-02-03

    In this study, we compared the effects of two analgesic regimens on perioperative nitric oxide index (NOx) and the likelihood of subsequent development of chronic postsurgical pain (CPSP) after breast surgery and sought to determine the association among early postoperative pain, NOx, and the likelihood of subsequent development of CPSP. Twenty-nine consecutive ASA I or II patients undergoing breast surgery with axillary clearance were randomly allocated to one of two groups. Patients in group S (n = 15) received a standard intraoperative and postoperative analgesic regimen (morphine sulfate, diclofenac, dextropropoxyphene hydrochloride + acetaminophen prn). Patients in group N (n = 14) received a continuous paravertebral block (for 48 h) and acetaminophen and parecoxib (followed by celecoxib up to 5 days). Visual analog scale pain scores at rest and on arm movement were recorded regularly until the fifth postoperative day. A telephone interview was conducted 10 wk postoperatively. The McGill Pain Questionnaire was used to characterize pain. NOx was estimated preoperatively, at the end of surgery, 30 min and 2, 4, 12, 24, 48 h postoperatively. Twelve (80%) patients in group S and no patient in group N developed CPSP (P = 0.009). Compared with patients with a pain rating index > or =1 (n = 18) 10 wk postoperatively, patients with a pain rating index = 0 (n = 11) had lesser visual analog scale pain scores on movement at each postoperative time point from 30 min until 96 h postoperatively (P < 0.005) and at rest 30 min (0.6 +\\/- 1.5 versus 30.2 +\\/- 26.8; P = 0.004), 4 h (2.3 +\\/- 7.5 versus 19.0 +\\/- 25.8; P = 0.013), 8 h (4.4 +\\/- 10.2 versus 21.4 +\\/- 27.0; P = 0.03) and 12 h (0.7 +\\/- 1.2 versus 15.4 +\\/- 27.0; P = 0.035) postoperatively. NOx values were greater in group N compared with group S 48 h postoperatively (40.6 +\\/- 20.1 versus 26.4 +\\/- 13.5; P = 0.04).

  6. 5/6th nephrectomy in combination with high salt diet and nitric oxide synthase inhibition to induce chronic kidney disease in the Lewis rat.

    Science.gov (United States)

    van Koppen, Arianne; Verhaar, Marianne C; Bongartz, Lennart G; Joles, Jaap A

    2013-07-03

    Chronic kidney disease (CKD) is a global problem. Slowing CKD progression is a major health priority. Since CKD is characterized by complex derangements of homeostasis, integrative animal models are necessary to study development and progression of CKD. To study development of CKD and novel therapeutic interventions in CKD, we use the 5/6th nephrectomy ablation model, a well known experimental model of progressive renal disease, resembling several aspects of human CKD. The gross reduction in renal mass causes progressive glomerular and tubulo-interstitial injury, loss of remnant nephrons and development of systemic and glomerular hypertension. It is also associated with progressive intrarenal capillary loss, inflammation and glomerulosclerosis. Risk factors for CKD invariably impact on endothelial function. To mimic this, we combine removal of 5/6th of renal mass with nitric oxide (NO) depletion and a high salt diet. After arrival and acclimatization, animals receive a NO synthase inhibitor (NG-nitro-L-Arginine) (L-NNA) supplemented to drinking water (20 mg/L) for a period of 4 weeks, followed by right sided uninephrectomy. One week later, a subtotal nephrectomy (SNX) is performed on the left side. After SNX, animals are allowed to recover for two days followed by LNNA in drinking water (20 mg/L) for a further period of 4 weeks. A high salt diet (6%), supplemented in ground chow (see time line Figure 1), is continued throughout the experiment. Progression of renal failure is followed over time by measuring plasma urea, systolic blood pressure and proteinuria. By six weeks after SNX, renal failure has developed. Renal function is measured using 'gold standard' inulin and para-amino hippuric acid (PAH) clearance technology. This model of CKD is characterized by a reduction in glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), hypertension (systolic blood pressure>150 mmHg), proteinuria (> 50 mg/24 hr) and mild uremia (>10 mM). Histological

  7. Tapentadol and nitric oxide synthase systems.

    Science.gov (United States)

    Bujalska-Zadrożny, Magdalena; Wolińska, Renata; Gąsińska, Emilia; Nagraba, Łukasz

    2015-04-01

    Tapentadol, a new analgesic drug with a dual mechanism of action (μ-opioid receptor agonism and norepinephrine reuptake inhibition), is indicated for the treatment of moderate to severe acute and chronic pain. In this paper, the possible additional involvement of the nitric oxide synthase (NOS) system in the antinociceptive activity of tapentadol was investigated using an unspecific inhibitor of NOS, L-NOArg, a relatively specific inhibitor of neuronal NOS, 7-NI, a relatively selective inhibitor of inducible NOS, L-NIL, and a potent inhibitor of endothelial NOS, L-NIO. Tapentadol (1-10 mg/kg, intraperitoneal) increased the threshold for mechanical (Randall-Selitto test) and thermal (tail-flick test) nociceptive stimuli in a dose-dependent manner. All four NOS inhibitors, administered intraperitoneally in the dose range 0.1-10 mg/kg, potentiated the analgesic action of tapentadol at a low dose of 2 mg/kg in both models of pain. We conclude that NOS systems participate in tapentadol analgesia. PMID:25485639

  8. Nitric oxide formation from nitrite in zebrafish

    DEFF Research Database (Denmark)

    Jensen, Frank Bo

    2007-01-01

    Nitrite is a potential nitric oxide (NO) donor and may have important biological functions at low concentrations. The present study tests the hypothesis that nitrite accumulation across the gills in fish will cause a massive NO production from nitrite. Zebrafish were exposed to three different...

  9. Targeting nitric oxide in the gastrointestinal tract

    NARCIS (Netherlands)

    Dijkstra, Gerard; van Goor, Harry; Jansen, Peter L M; Moshage, Han; van Goor, Harm

    2004-01-01

    This review discusses the contributions of the three nitric oxide (NO) synthase (NOS) isozymes neuronal NOS (nNOS), endothelial NOS (eNOS) and inducible NOS (iNOS) to the function and diseases of the gastrointestinal tract. Small (nanomolar) quantities of NO produced by calcium-dependent nNOS play a

  10. Nitric Oxide Synthase Inhibitors as Antidepressants

    DEFF Research Database (Denmark)

    Wegener, Gregers; Volke, Vallo

    2010-01-01

    been suggested to play major roles in the pathophysiology of mood and stress-related disorders. However, a few clinical and several pre-clinical studies, strongly suggest involvement of the nitric oxide (NO) signaling pathway in these disorders. Moreover, several of the conventional neurotransmitters...

  11. Nitric oxide synthase inhibition and cerebrovascular regulation

    DEFF Research Database (Denmark)

    Iadecola, C; Pelligrino, D A; Moskowitz, M A;

    1994-01-01

    There is increasing evidence that nitric oxide (NO) is an important molecular messenger involved in a wide variety of biological processes. Recent data suggest that NO is also involved in the regulation of the cerebral circulation. Thus, NO participants in the maintenance of resting cerebrovascular...

  12. Nitric oxide methods in seed biology

    Science.gov (United States)

    Nitric oxide (NO) is a gaseous, free radical that is involved in many aspects of plant growth, development, and responses to the environment. Compelling evidence points to a central role for NO in the loss of seed dormancy. NO is highly reactive, toxic at high concentrations, and unstable. Methods f...

  13. Circulating nitric oxide products do not solely reflect nitric oxide release in cirrhosis and portal hypertension

    DEFF Research Database (Denmark)

    Afzelius, P.; Bazeghi, N.; Bie, P.;

    2011-01-01

    Background: Patients with cirrhosis often develop a systemic vasodilatation and a hyperdynamic circulation with activation of vasoconstrictor systems such as the renin-angiotensin-aldosterone system (RAAS), and vasopressin. Increased nitric oxide (NO) synthesis has been implicated...

  14. Circulating nitric oxide products do not solely reflect nitric oxide release in cirrhosis and portal hypertension

    DEFF Research Database (Denmark)

    Afzelius, Pia; Bazeghi, Nassim; Bie, Peter;

    2011-01-01

    Patients with cirrhosis often develop a systemic vasodilatation and a hyperdynamic circulation with activation of vasoconstrictor systems such as the renin-angiotensin-aldosterone system (RAAS), and vasopressin. Increased nitric oxide (NO) synthesis has been implicated in the development...

  15. 21 CFR 868.5165 - Nitric oxide administration apparatus.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Nitric oxide administration apparatus. 868.5165... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5165 Nitric oxide administration apparatus. (a) Identification. The nitric oxide administration apparatus is a device used to add...

  16. Increased nitric oxide release and expression of endothelial and inducible nitric oxide synthases in mildly changed porcine mitral valve leaflets

    DEFF Research Database (Denmark)

    Moesgaard, Sophia Gry; Olsen, Lisbeth Høier; Viuff, Birgitte;

    2007-01-01

    Background and aim of the study: Little is known of the local role of nitric oxide (NO) in heart valves in relation to heart valve diseases. The study aim was to examine NO release and the expression of both endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (i...

  17. Modulatory role of nitric oxide in cardiac performance

    Directory of Open Access Journals (Sweden)

    Smiljić Sonja

    2014-01-01

    Full Text Available Nitric oxide is produced by almost all cardiac cells, endothelial cells, cardiomyocytes and nerve fibers. It is synthesized by an enzyme, a nitric oxide synthase, which occurs in endothelial, neural and inducible form. The distribution of nitric oxide synthase in the heart is characterized by a pronounced non-uniformity. Nitric oxide exerts its effects in physiological and pathophysiological conditions. The physiological effects of low concentrations of nitric oxide, which is released in the normal conditions under the influence of constituent enzymes, occur via cyclic guanosine monophosphate. The synthesized nitric oxide exhibits its effect in the cells where it is produced, in an autocrine manner, or by diffusing into the neighboring cells, in a paracrine manner. Nitric oxide acts by regulating the coronary vessel tonus, affecting the contractility of cardiomyocytes, generating an inotropic effect in a dose-dependent manner and controlling the cellular respiration. Other effects of nitric oxide in the cardiovascular system include the hyperpolarization of the smooth muscle cells in blood vessels, the inhibition of the monocyte adhesion, the inhibition of platelet migration, adhesion and aggregation and the proliferation of smooth muscle cells and fibroblasts. The anti-atherosclerotic effects of nitric oxide are based on these effects. Nitric oxide is a weak free radical in gaseous state, and the cytotoxic and/or the cytoprotective effects of the higher concentrations of nitric oxide are related to the chemical structure of nitric oxide as a free radical. The excessive production of nitric oxide by the activation of inducible nitric oxide synthase can lead to major irregularities in the function of cardiomyocytes and cardiac insufficiency. Understanding the nitric oxide molecular mechanisms of signaling pathways in the heart can provide a new strategic approach to prevention and treatment of cardiovascular diseases.

  18. CHANGES OF NITRIC OXIDE AND PROTECTIVE EFFECTS OF NITRIC OXIDE INHIBITORS IN NEWBORN RATS WITH SEPSIS

    Institute of Scientific and Technical Information of China (English)

    史源; 李华强; 潘捷; 沈际皋

    1995-01-01

    In a newborn rat model of sepsis, the changes of nitric oxide and the protective effects of methylene blue or/and dexaraethason were investigated. The results revealed that plasma nitric oxide levels were ele-cted at 6 h and peaked at 12 h after bacterial challenge. The treatment with methylene or/and dexam-etbasone was found to Munt hypoglycenua and hyperlacdcemla, to reduce the occurrence rate of loss ot re-sponse to pain, and to prolong the survival time. Moreover, therapy by dexamethasone was shown to de-crease the 24 h mortality. The results suggested that nitric coide play an important role during the course of fatal P. aeruginosa sepsis, hut it is clear that the clinical value of nitric oxide and its inhibitors need to be further studied.

  19. Role of Polymorphisms of Inducible Nitric Oxide Synthase and Endothelial Nitric Oxide Synthase in Idiopathic Environmental Intolerances

    OpenAIRE

    Chiara De Luca; Agnese Gugliandolo; Carlo Calabrò; Monica Currò; Riccardo Ientile; Desanka Raskovic; Ludmila Korkina; Daniela Caccamo

    2015-01-01

    Oxidative stress and inflammation play a pathogenetic role in idiopathic environmental intolerances (IEI), namely, multiple chemical sensitivity (MCS), fibromyalgia (FM), and chronic fatigue syndrome (CFS). Given the reported association of nitric oxide synthase (NOS) gene polymorphisms with inflammatory disorders, we aimed to investigate the distribution of NOS2A −2.5 kb (CCTTT) n as well as Ser608Leu and NOS3 −786T>C variants and their correlation with nitrite/nitrate levels, in a study coh...

  20. Nitric oxide production by polymorphonuclear leukocytes in infected cystic fibrosis sputum consumes oxygen

    DEFF Research Database (Denmark)

    Kolpen, Mette; Bjarnsholt, Thomas; Moser, Claus Ernst;

    2014-01-01

    )) due to production of superoxide (O(2)(-)). In this study, we show that the PMNs also consume O(2) for production of nitric oxide (NO) by the nitric oxide synthases (NOS) in the infected endobronchial mucus. Fresh expectorated sputum samples (n = 28) from chronically infected CF patients (n = 22) were...... analysed by quantifying and visualizing the NO production. NO production was detected by optode measurements combined with fluorescence microscopy, flow cytometry and spectrophotometry. Inhibition of nitric oxide synthases (NOS) with N(G) -monomethyl-L-arginine (L-NMMA) resulted in reduced O(2) consumption...

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

    Science.gov (United States)

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

    2006-05-01

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

  2. Endothelial nitric oxide synthase in the microcirculation.

    Science.gov (United States)

    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.

  3. Reactive Nitrogen Species and Nitric Oxide

    OpenAIRE

    D. Procházková; Wilhelmová, N. (Naděžda); Pavlík, M. (Milan)

    2015-01-01

    Free radical nitric oxide (NO) is a biological messenger with diverse functions in plant physiology, including in stress physiology. Together with NO, related molecules called reactive nitrogen species (RNS), e.g. peroxynitrite or S-nitrosothiols, are associated with plant metabolism under both physiological and stress conditions. These molecules are able to react with wide spectrum of biomolecules, and they may act as a transporters and reservoirs for NO in a broad range of plant cell signal...

  4. Radiation, nitric oxide and cellular death

    International Nuclear Information System (INIS)

    The mechanisms of radiation induced cellular death constitute an objective of research ever since the first biological effects of radiation were first observed. The explosion of information produced in the last 20 years calls for a careful analysis due to the apparent contradictory data related to the cellular system studied and the range of doses used. This review focuses on the role of the active oxygen species, in particular the nitric oxides, in its relevance as potential mediator of radiation induced cellular death

  5. Nitric oxide and mitochondria in metabolic syndrome

    OpenAIRE

    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...

  6. Oxygen, nitric oxide and articular cartilage

    Directory of Open Access Journals (Sweden)

    B Fermor

    2007-04-01

    Full Text Available Molecular oxygen is required for the production of nitric oxide (NO, a pro-inflammatory mediator that is associated with osteoarthritis and rheumatoid arthritis. To date there has been little consideration of the role of oxygen tension in the regulation of nitric oxide production associated with arthritis. Oxygen tension may be particularly relevant to articular cartilage since it is avascular and therefore exists at a reduced oxygen tension. The superficial zone exists at approximately 6% O2, while the deep zone exists at less than 1% O2. Furthermore, oxygen tension can alter matrix synthesis, and the material properties of articular cartilage in vitro.The increase in nitric oxide associated with arthritis can be caused by pro-inflammatory cytokines and mechanical stress. Oxygen tension significantly alters endogenous NO production in articular cartilage, as well as the stimulation of NO in response to both mechanical loading and pro-inflammatory cytokines. Mechanical loading and pro-inflammatory cytokines also increase the production of prostaglandin E2 (PGE2. There is a complex interaction between NO and PGE2, and oxygen tension can alter this interaction. These findings suggest that the relatively low levels of oxygen within the joint may have significant influences on the metabolic activity, and inflammatory response of cartilage as compared to ambient levels. A better understanding of the role of oxygen in the production of inflammatory mediators in response to mechanical loading, or pro-inflammatory cytokines, may aid in the development of strategies for therapeutic intervention in arthritis.

  7. Nitric oxide turnover in permeable river sediment

    DEFF Research Database (Denmark)

    Schreiber, Frank; Stief, Peter; Kuypers, Marcel M M;

    2014-01-01

    We measured nitric oxide (NO) microprofiles in relation to oxygen (O2) and all major dissolved N-species (ammonium, nitrate, nitrite, and nitrous oxide [N2O]) in a permeable, freshwater sediment (River Weser, Germany). NO reaches peak concentrations of 0.13 μmol L-1 in the oxic zone and is consumed...... in the oxic-anoxic transition zone. Apparently, NO is produced by ammonia oxidizers under oxic conditions and consumed by denitrification under microoxic conditions. Experimental percolation of sediment cores with aerated surface water resulted in an initial rate of NO production that was 12 times higher than...... the net NO production rate in steady state. This initial NO production rate is in the same range as the net ammonia oxidation rate, indicating that NO is transiently the main product of ammonia oxidizers. Stable isotope labeling experiments with the 15N-labeled chemical NO donor S...

  8. Effects of Standardised Fermented Papaya Gel on Clinical Symptoms, Inflammatory Cytokines, and Nitric Oxide Metabolites in Patients with Chronic Periodontitis: An Open Randomised Clinical Study.

    Science.gov (United States)

    Kharaeva, Zaira F; Zhanimova, Lyana R; Mustafaev, Magomet Sh; De Luca, Chiara; Mayer, Wolfgang; Chung Sheun Thai, Jeffrey; Tiew Siok Tuan, Rebecca; Korkina, Liudmila G

    2016-01-01

    The clinical efficacy of topical administration of standardised fermented papaya gel (SFPG), known to have antioxidant and anti-inflammatory properties, versus conventional therapy was evaluated in a group of 84 patients with moderate-to-severe periodontitis, randomly assigned to control group (n = 45) undergoing traditional pharmacologic/surgical protocols or to experimental group (n = 39), additionally treated with intragingival pocket SFPG (7 g) applications (15 min daily for 10 days). Patients undergoing SFPG treatment showed significant (P < 0.05), durable improvement of three major clinical indices of disease severity: reduced bleeding (day 7), plaque and gingival conditions (day 14), and consistent gingival pocket depth reduction (day 45). Proinflammatory nitric oxide metabolites reached normal values in plasma (day 14) and gingival crevicular fluid (GCF) at day 45 with SFPG applications compared to controls that did not reach normalisation. Levels of highly increased proinflammatory (IL-1B, IL-6) and suppressed anti-inflammatory (IL-10) cytokines normalised in the SFPG group by days 14 (plasma) and 45 (GCF), but never in the control group. Although not acting directly as antibiotic, SFPG acted in synergy with human granulocytes blocking adaptive catalase induction in S. aureus in response to granulocyte-derived oxidative stress, thus enhancing intracellular bacterial killing. PMID:26977121

  9. Effects of Standardised Fermented Papaya Gel on Clinical Symptoms, Inflammatory Cytokines, and Nitric Oxide Metabolites in Patients with Chronic Periodontitis: An Open Randomised Clinical Study

    Directory of Open Access Journals (Sweden)

    Zaira F. Kharaeva

    2016-01-01

    Full Text Available The clinical efficacy of topical administration of standardised fermented papaya gel (SFPG, known to have antioxidant and anti-inflammatory properties, versus conventional therapy was evaluated in a group of 84 patients with moderate-to-severe periodontitis, randomly assigned to control group (n=45 undergoing traditional pharmacologic/surgical protocols or to experimental group (n=39, additionally treated with intragingival pocket SFPG (7 g applications (15 min daily for 10 days. Patients undergoing SFPG treatment showed significant (P<0.05, durable improvement of three major clinical indices of disease severity: reduced bleeding (day 7, plaque and gingival conditions (day 14, and consistent gingival pocket depth reduction (day 45. Proinflammatory nitric oxide metabolites reached normal values in plasma (day 14 and gingival crevicular fluid (GCF at day 45 with SFPG applications compared to controls that did not reach normalisation. Levels of highly increased proinflammatory (IL-1B, IL-6 and suppressed anti-inflammatory (IL-10 cytokines normalised in the SFPG group by days 14 (plasma and 45 (GCF, but never in the control group. Although not acting directly as antibiotic, SFPG acted in synergy with human granulocytes blocking adaptive catalase induction in S. aureus in response to granulocyte-derived oxidative stress, thus enhancing intracellular bacterial killing.

  10. [Nitric oxide and the kidneys].

    Science.gov (United States)

    Dzúrik, R; Spustová, V

    2001-02-01

    Nitrogen oxide (NO) is one of the crucial modulators of the vascular tonus. Apart from its effect on the cardiovascular system it exerts an effect also on other types of cells and ensures their functions.Specially comprehensive is its synthesis and action in the kidneys: NO is formed in the endothelial cells due to the activity of constitutional endothelial synthase (eNOS), in mesangial cells of inductive synthase (iNOS), in smooth muscle cells (vsmNOS), in tubular cells neuronal NOS (nNOS) and iNOS and in the macula densa nNOS. By modulation of the v.afferens it influences the blood flow through the glomeruli and filtration pressure in the glomeruli. It participates in the tubuloglomerular feedback: the cells of the macula densa produce NO via nNOS, the genetic transcription and translation of which as well as the kationic translation system ensure the transport of the L-arginine precursor and regulate very sensitively NO formation. The latter diffuses via the extraglomerular mesangium into the iuxtaglomerular apparatus where renin is forned.NO reduces proteinuria and renal proliferation. During renal insufficiency NO production is inhibited and in diabetes NO production is increased. Diabetic hyperfiltration and hypertrophy are ascribed to produced NO. Experimental studies contributed substantially to the knowledge of renal effects of NO. At present intensive clinical research has been started which, no doubt, will influence medical practice. PMID:15635855

  11. Expression and activity of inducible nitric oxide synthase and endothelial nitric oxide synthase correlate with ethanol-induced liver injury

    Institute of Scientific and Technical Information of China (English)

    Guang-Jin Yuan; Xiao-Rong Zhou; Zuo-Jiong Gong; Pin Zhang; Xiao-Mei Sun; Shi-Hua Zheng

    2006-01-01

    AIM: To study the expression and activity of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) in rats with ethanol-induced liver injury and their relation with liver damage, activation of nuclear factor-KB (NF-кB) and tumor necrosis factor-α (TNF-α)expression in the liver.METHODS: Female Sprague-Dawley rats were given fish oil (0.5 mL) along with ethanol or isocaloric dextrose daily via gastrogavage for 4 or 6 wk. Liver injury was assessed using serum alanine aminotransferase (ALT)activity and pathological analysis. Liver malondialdehyde (MDA), nitric oxide contents, iNOS and eNOS activity were determined. NF-KB p65, iNOS, eNOS and TNF-αprotein or mRNA expression in the liver were detected by immunohistochemistry or reverse transcriptase-polymerase chain reaction (RT-PCR).RESULTS: Chronic ethanol gavage for 4 wk caused steatosis, inflammation and necrosis in the liver, and elevated serum ALT activity. Prolonged ethanol administration (6 wk) enhanced the liver damage. These responses were accompanied with increased lipid peroxidation, NO contents, iNOS activity and reduced eNOS activity. NF-кB p65, iNOS and TNF-α protein or mRNA expression were markedly induced after chronic ethanol gavage, whereas eNOS mRNA expression remained unchanged. The enhanced iNOS activity and expression were positively correlated with the liver damage, especially the necro-inflammation, activation of NF-кB, and TNF-α mRNA expression.CONCLUSION: iNOS expression and activity are induced in the liver after chronic ethanol exposure in rats, which are correlated with the liver damage, especially the necro-inflammation, activation of NF-KB and TNF-αexpression. eNOS activity is reduced, but its mRNA expression is not affected.

  12. Expression of inducible nitric oxide synthase and effects of L-arginine on colonic nitric oxide production and fluid transport in patients with "minimal colitis"

    DEFF Research Database (Denmark)

    Perner, Anders; Andresen, Lars; Normark, Michel;

    2005-01-01

    Some patients with idiopathic, chronic diarrhoea have minimal, non-specific colonic inflammation. As nitric oxide (NO) acts as a secretagogue in the colon, we studied the expression of inducible NO synthase (iNOS) in mucosal biopsies and the effects of NOS stimulation on colonic transfer of fluid...

  13. Nitric oxide in the psychobiology of mental disorders

    OpenAIRE

    Essizoglu, Altan; Yıldırım, Ejder Akgün

    2009-01-01

    Nitric oxide is in a gaseous form and is widespread in the human body. It functions by acting as a secondary messenger in the modulatory activities of neuronal functions of the central nervous system.Nitric oxide is the first identified neurotransmitter of the nontraditional neurotransmitter family.Studies conducted on experimental animals demonstrate that nitric oxide has a neuromodulatory efficacy on the secretions of other neurotransmitters and that it has an effect on learning and memory ...

  14. A nitric oxide donor (nitroglycerin) triggers genuine migraine attacks

    DEFF Research Database (Denmark)

    Thomsen, L L; Kruuse, C; Iversen, Helle Klingenberg;

    1994-01-01

    Supersensitivity to induction of headache and arterial dilatation by a donor of nitric oxide (nitroglycerin) has recently been demonstrated in migraine sufferers. The aims of the present study were to examine whether the nitric oxide donor nitroglycerin may induce a typical migraine attack.......03). The time pattern of headache and estimated middle cerebral artery dilatation corresponded well. The study therefore demonstrates that activation of the nitric oxide cGMP pathway may cause typical migraine attacks....

  15. Nitric oxide in the psychobiology of mental disorders

    OpenAIRE

    Altan Eşsizoğlu; Ejder Akgün Yıldırım

    2009-01-01

    Nitric oxide is in a gaseous form and is widespread in the human body. It functions by acting as a secondary messenger in the modulatory activities of neuronal functions of the central nervous system. Nitric oxide is the first identified neurotransmitter of the nontraditional neurotransmitter family.Studies conducted on experimental animals demonstrate that nitric oxide has a neuromodulatory efficacy on the secretions of other neurotransmitters and that it has an effect on learning and memory...

  16. Inducible nitric-oxide synthase attenuates vasopressin-dependent Ca2+ signaling in rat hepatocytes.

    Science.gov (United States)

    Patel, Sandip; Gaspers, Lawrence D; Boucherie, Sylviane; Memin, Elisabeth; Stellato, Kerri Anne; Guillon, Gilles; Combettes, Laurent; Thomas, Andrew P

    2002-09-13

    Increases in both Ca(2+) and nitric oxide levels are vital for a variety of cellular processes; however, the interaction between these two crucial messengers is not fully understood. Here, we demonstrate that expression of inducible nitric-oxide synthase in hepatocytes, in response to inflammatory mediators, dramatically attenuates Ca(2+) signaling by the inositol 1,4,5-trisphosphate-forming hormone, vasopressin. The inhibitory effects of induction were reversed by nitric oxide inhibitors and mimicked by prolonged cyclic GMP elevation. Induction was without effect on Ca(2+) signals in response to AlF(4)(-) or inositol 1,4,5-trisphosphate, indicating that phospholipase C activation and release of Ca(2+) from inositol 1,4,5-trisphosphate-sensitive Ca(2+) stores were not targets for nitric oxide inhibition. Vasopressin receptor levels, however, were dramatically reduced in induced cultures. Our data provide a possible mechanism for hepatocyte dysfunction during chronic inflammation. PMID:12097323

  17. Processes regulating nitric oxide emissions from soils.

    Science.gov (United States)

    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

  18. Oxidation of DOPAC by nitric oxide: effect of superoxide dismutase

    OpenAIRE

    Laranjinha, João; Cadenas, Enrique

    2002-01-01

    This study aimed to characterize the redox interaction between 3,4-dihydroxyphenylacetic acid (DOPAC) and nitric oxide (·NO), and to assess the reductive and oxidative decay pathways of the DOPAC semiquinone originating from this interaction. The reaction between DOPAC and ·NO led to the formation of the DOPAC semiquinone radical, detected by electron paramagnetic resonance (EPR) and stabilized by Mg2+, and the nitrosyl anion detected as nitrosylmyoglobin. The EPR signal corresponding to the ...

  19. The role of nitric oxide in cancer

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Nitric oxide (NO) is a pleiotropic regulator, critical to numerous biological processes, including va-sodilatation, neurotransmission and macrophage-mediated immunity. The family of nitric oxide synthases(NOS) comprises inducible NOS (iNOS), endothelial NOS (eNOS), and neuronal NOS (nNOS). Interest-ingly, various studies have shown that all three isoforms can be involved in promoting or inhibiting theetiology of cancer. NOS activity has been detected in tumour cells of various histogenetic origins and hasbeen associated with tumour grade, proliferation rate and expression of important signaling componentsassociated with cancer development such as the oestrogen receptor. It appears that high levels of NOSexpression (for example, generated by activated macrophages) may be cytostatic or cytotoxic for tumorcells, whereas low level activity can have the opposite effect and promote tumour growth. Paradoxicallytherefore, NO (and related reactive nitrogen species) may have both genotoxic and angiogenic properties.Increased NO-generation in a cell may select mutant p53 cells and contribute to tumour angiogenesis byupregulating VEGF. In addition, NO may modulate tumour DNA repair mechanisms by upregulating p53,poly(ADP-ribose) polymerase (PARP) and the DNA-dependent protein kinase (DNA-PK). An understand-ing at the molecular level of the role of NO in cancer will have profound therapeutic implications for thediagnosis and treatment of disease.

  20. Melatonin and its precursors scavenge nitric oxide

    Energy Technology Data Exchange (ETDEWEB)

    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.

  1. Hypoxia tolerance, nitric oxide, and nitrite

    DEFF Research Database (Denmark)

    Fago, Angela; Jensen, Frank Bo

    2015-01-01

    Among vertebrates able to tolerate periods of oxygen deprivation, the painted and red-eared slider turtles (Chrysemys picta and Trachemys scripta) and the crucian carp (Carassius carassius) are the most extreme and can survive even months of total lack of oxygen during winter. The key to hypoxia ...... of NO and nitrite signaling in the adaptive response to hypoxia in vertebrate animals....... survival resides in concerted physiological responses, including strong metabolic depression, protection against oxidative damage and – in air breathing animals - redistribution of blood flow. Each of these responses is known to be tightly regulated by nitric oxide (NO) and during hypoxia by its metabolite...... nitrite. The aim of this review is to highlight recent work illustrating the widespread roles of NO and nitrite in the tolerance to extreme oxygen deprivation, in particular in the red-eared slider turtle and crucian carp, but also in diving marine mammals. The emerging picture underscores the importance...

  2. 正常人、牙龈炎和牙周炎患者龈沟液内一氧化氮含量的检测%Detection of the Level of Nitric Oxide in Gingival Crevicular Fluid in Healthy Individuals, Gingivitis and Chronic Periodontitis Patients.

    Institute of Scientific and Technical Information of China (English)

    龚斌; 徐静舒; 戚慧; 雷雅燕

    2011-01-01

    Objective: To observe the level of nitric oxide in gingival crevicular fluid (GCF) in normal group and periodontitis group, and to study the possible role of NO in the periodontal disease. Methods: The GCF samples were collected in 20 periodontally healthy individuals, 22 gingivitis and 32 chronic periodontitis patients. The level of nitric oxide in gingival crevicular fluid was measured by immunofluorescence. Results: The nitric oxide in GCF was a significant difference in chronic periodontitis group and gingivitis group than that in control group(P<0.01). The nitric oxide in GCF was significantly different in chronic periodontitis group compared to that in gingivitis group (P<0.01). Conclusion: Nitric oxide exists in GCF of patients with chronic periodontitis and gingivitis and periodontally healthy individuals. Nitric oxide plays an important role in the development of chronic periodontal disease. The level of nitric oxide in GCF has close relation with degree of inflammation.%目的:检测正常人和牙周病患者龈沟液中NO含量,探讨NO在牙周病发病过程中的作用.方法:选择牙周健康组20例,牙龈炎组22例,慢性牙周炎组32例,分别采集龈沟液标本,免疫荧光法检测龈沟液内NO的含量.结果:慢性牙周炎患者和牙龈炎患者龈沟液内NO含量与牙周健康组相比均有高度显著性差异(P<0.01),慢性牙周炎患者龈沟液内N0含量与牙龈炎组相比有高度显著性差异(P<0.01).结论:牙周健康者、牙龈炎患者、慢性牙周炎患者龈沟液中能检测出N0的存在,NO参与了慢性牙周炎的发展过程,龈沟液内NO含量与慢性牙周炎炎症程度密切相关.

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

    Directory of Open Access Journals (Sweden)

    Menaka K

    2009-01-01

    Full Text Available 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.

  4. Sensory neuropeptides and nitric oxide in nasal vascular regulation

    OpenAIRE

    Rinder, Johan

    1996-01-01

    Sensory neuropeptides and nitric oxide in nasal vascular regulation By Johan Rinder, M.D. Division of Pharmacology, Department of Physiology and Pharmacology, Karolinska Institute, S- 171 77 Stockholm, Sweden and Department of Oto-Rhino-Laryngology, Karolinska Hospital, S-17176 Stockholm, SwedenThe role of sensory neuropeptides and nitric oxide in vascular regulation was investigated in the pig nasal mucosa...

  5. Nitric oxide: Orchestrator of endothelium-dependent responses

    DEFF Research Database (Denmark)

    Félétou, Michel; Köhler, Ralf; Vanhoutte, Paul M

    2012-01-01

    Abstract The present review first summarizes the complex chain of events, in endothelial and vascular smooth muscle cells, that leads to endothelium-dependent relaxations (vasodilatations) due to the generation of nitric oxide (NO) by endothelial nitric oxide synthase (eNOS) and how therapeutic...

  6. Catalytic abatement of nitrous oxide from nitric and production

    NARCIS (Netherlands)

    Oonk, J.

    1998-01-01

    Nitric acid production is identified as a main source of nitrous oxide. Options for emission reduction however are not available. TNO and Hydro Agri studied the technological and economic feasibility of catalytic decomposition of nitrous oxide in nitric acid tail-gases. Although in literature promis

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

    Energy Technology Data Exchange (ETDEWEB)

    Karraker, D.G.

    2001-07-17

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

  8. Nitric oxide modulators: an emerging class of medicinal agents.

    Science.gov (United States)

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

    2012-11-01

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

  9. Nitric oxide scavengers as a therapeutic approach to nitric oxide mediated disease.

    Science.gov (United States)

    Fricker, S P

    1999-08-01

    The essential role of nitric oxide (NO) in normal physiology and its involvement in the pathophysiology of a variety of diseases render the compound an attractive therapeutic target. NO donor drugs are used in the treatment of hypotension and angina where abnormalities in the L-arginine-nitric oxide pathway have been implicated. Overproduction of NO has been associated with a number of disease states including septic shock, inflammatory diseases, diabetes, ischaemia-reperfusion injury, adult respiratory distress syndrome, neurodegenerative diseases and allograft rejection. NO is produced by a group of enzymes, the nitric oxide synthases. Selective inhibition of the inducible isoform is one approach to the treatment of diseases where there is an overproduction of NO; an alternative approach is to scavenge or remove excess NO. A number of NO scavenger molecules have demonstrated pharmacological activity in disease models, particularly models of septic shock. These include organic molecules such as PTIO (2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide), haemoglobin derivatives such as the pyridoxalated haemoglobin polyoxyethylene conjugate (PHP), low molecular weight iron compounds of diethylenetriaminepentaacetic acid and diethyldithiocarbamate and ruthenium polyaminocarboxylate complexes. The data suggest a potential role for NO scavengers in the treatment of NO mediated disease. PMID:15992146

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

    DEFF Research Database (Denmark)

    Moesgaard, Sophia Gry; Olsen, Lisbeth Høier; Aasted, Bent;

    2007-01-01

    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...

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    Rosekeila Simões Nomelini

    2008-01-01

    Full Text Available Tumor sections from nonneoplastic (n=15, benign (n=28, and malignant ovarian tumors (n=20 were obtained from 63 women. Immunohistochemistry of the tumor sections demonstrated that inducible nitric oxide synthase (iNOS expression was increased in ovarian cancer samples compared to nonneoplastic or benign tumor samples. Using the Griess method, nitric oxide (NO metabolite levels were also found to be elevated in malignant tumor samples compared to benign tumor samples (P80 μM were more frequent than NO levels <80 μM, and iNOS expression in well-differentiated carcinomas was greater than in moderately/poorly differentiated carcinomas (P<.05. These data suggest an important role for NO in ovarian carcinogenesis.

  13. Nitric oxide flow tagging in unseeded air.

    Science.gov (United States)

    Dam, N; Klein-Douwel, R J; Sijtsema, N M; Meulen, J J

    2001-01-01

    A scheme for molecular tagging velocimetry is presented that can be used in air flows without any kind of seeding. The method is based on the local and instantaneous creation of nitric oxide (NO) molecules from N(2) and O(2) in the waist region of a focused ArF excimer laser beam. This NO distribution is advected by the flow and can be visualized any time later by laser-induced fluorescence in the gamma bands. The creation of NO is confirmed by use of an excitation spectrum. Two examples of the application of the new scheme for air-flow velocimetry are given in which single laser pulses are used for creation and visualization of NO. PMID:18033499

  14. Nitric oxide releasing-dendrimers: an overview

    Directory of Open Access Journals (Sweden)

    Antonio Carlos Roveda Júnior

    2013-01-01

    Full Text Available Platforms able to storage, release or scavenge NO in a controlled and specific manner is interesting for biological applications. Among the possible matrices for these purposes, dendrimers are excellent candidates for that. These molecules have been used as drug delivery systems and exhibit interesting properties, like the possibility to perform chemical modifications on dendrimers surface, the capacity of storage high concentrations of compounds of interest in the same molecule and the ability to improve the solubility and the biocompatibility of the compounds bonded to it. This review emphasizes the recent progress in the development and in the biological applications of different NO-releasing dendrimers and the nitric oxide release pathways in these compounds.

  15. Nitric oxide and mitochondria in metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Larisa eLitvinova

    2015-02-01

    Full Text Available 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.

  16. The nitric oxide synthase of mouse spermatozoa.

    Science.gov (United States)

    Herrero, M B; Goin, J C; Boquet, M; Canteros, M G; Franchi, A M; Perez Martinez, S; Polak, J M; Viggiano, J M; Gimeno, M A

    1997-07-01

    Nitric oxide synthase (NOS) was evidenced in mature mouse spermatozoa by means of biochemical techniques and Western blot. During 120 min of incubation, 10(7) spermatozoa synthesized 7 +/- 2 pmol of L-[14C]citrulline. Besides, L-citrulline formation depended on the incubation time and on the concentration of L-arginine present in the incubation medium. Different concentrations of N(G)-nitro-L-arginine methyl ester (L-NAME) but not aminoguanidine, inhibited L-[14C]citrulline formation. Western-blot analysis of solubilized sperm proteins revealed a unique band of M(r)=140 kDa with the neural, endothelial and inducible NOS antisera tested. These results provide evidence that mature mouse sperm contains a NOS isoform and that spermatozoa have the potential ability to synthesize NO, suggesting a role for endogenous NO on mammalian sperm function.

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

    OpenAIRE

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

    2006-01-01

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

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

    Science.gov (United States)

    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.

  19. Nitric oxide, stomatal closure, and abiotic stress.

    Science.gov (United States)

    Neill, Steven; Barros, Raimundo; Bright, Jo; Desikan, Radhika; Hancock, John; Harrison, Judith; Morris, Peter; Ribeiro, Dimas; Wilson, Ian

    2008-01-01

    Various data indicate that nitric oxide (NO) is an endogenous signal in plants that mediates responses to several stimuli. Experimental evidence in support of such signalling roles for NO has been obtained via the application of NO, usually in the form of NO donors, via the measurement of endogenous NO, and through the manipulation of endogenous NO content by chemical and genetic means. Stomatal closure, initiated by abscisic acid (ABA), is effected through a complex symphony of intracellular signalling in which NO appears to be one component. Exogenous NO induces stomatal closure, ABA triggers NO generation, removal of NO by scavengers inhibits stomatal closure in response to ABA, and ABA-induced stomatal closure is reduced in mutants that are impaired in NO generation. The data indicate that ABA-induced guard cell NO generation requires both nitric oxide synthase-like activity and, in Arabidopsis, the NIA1 isoform of nitrate reductase (NR). NO stimulates mitogen-activated protein kinase (MAPK) activity and cGMP production. Both these NO-stimulated events are required for ABA-induced stomatal closure. ABA also stimulates the generation of H2O2 in guard cells, and pharmacological and genetic data demonstrate that NO accumulation in these cells is dependent on such production. Recent data have extended this model to maize mesophyll cells where the induction of antioxidant defences by water stress and ABA required the generation of H2O2 and NO and the activation of a MAPK. Published data suggest that drought and salinity induce NO generation which activates cellular processes that afford some protection against the oxidative stress associated with these conditions. Exogenous NO can also protect cells against oxidative stress. Thus, the data suggest an emerging model of stress responses in which ABA has several ameliorative functions. These include the rapid induction of stomatal closure to reduce transpirational water loss and the activation of antioxidant defences

  20. Exhaled nitric oxide in diagnosis and management of respiratory diseases

    Directory of Open Access Journals (Sweden)

    Abba Abdullah

    2009-01-01

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

  1. Exhaled nitric oxide measure using multiple flows in clinically relevant subgroups of COPD

    DEFF Research Database (Denmark)

    Roberts, Nassim Bazeghi; Gerds, Thomas A; Budtz-Jørgensen, Esben;

    2011-01-01

    Although there is widespread interest in fractional exhaled nitric oxide (FeNO) as a non-invasive, time and cost effective biomarker for assessing airway inflammation in chronic obstructive pulmonary disease (COPD), its usefulness is still controversial. We examined the FeNO levels in clinically ...

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

    Science.gov (United States)

    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.

  3. Nitric oxide in the psychobiology of mental disorders

    Directory of Open Access Journals (Sweden)

    Altan Eşsizoğlu

    2009-03-01

    Full Text Available Nitric oxide is in a gaseous form and is widespread in the human body. It functions by acting as a secondary messenger in the modulatory activities of neuronal functions of the central nervous system. Nitric oxide is the first identified neurotransmitter of the nontraditional neurotransmitter family.Studies conducted on experimental animals demonstrate that nitric oxide has a neuromodulatory efficacy on the secretions of other neurotransmitters and that it has an effect on learning and memory functions, and on various neuronal mechanisms. Many studies have been conducted to investigate the location of nitric oxide in the central nervous system, its effect on anxiety and depression, its relationship with other neurotransmitters, and also about its role on neurotoxicity. There are clinical studies concerning the level of nitrate, a product of nitric oxide metabolism, and also experimental studies concerning its rewarding effect of alcohol and substance use, in patients with depression and schizophrenia. However, limited studies have been conducted to investigate its relationship with stress, which is an important factor in the etiology of psychiatric disorders. These studies demonstrate that nitric oxide is closely related with stress physiology.Nitric oxide is a neuromodulator, which is frequently being mentioned about nowadays in psychiatry. Clinical and experimental studies play an important role in the psychobiology of psychiatric disorders.

  4. Effect of Skin Sensitizers on Inducible Nitric Oxide Synthase Expression and Nitric Oxide Production in Skin Dendritic Cells: Role of Different Immunosuppressive Drugs

    OpenAIRE

    Cruz, M. T.; Neves, B. M.; Gonçalo, M; Figueiredo, A; C. B. Duarte; Lopes, M C

    2007-01-01

    Nitric oxide (NO) is involved in the pathogenesis of acute and chronic inflammatory conditions, namely in allergic contact dermatitis (ACD). However, the mechanism by which NO acts in ACD remains elusive. The present study focuses on the effects of different contact sensitizers (2,4-dinitrofluorbenzene, 1,4-phenylenediamine, nickel sulfate), the inactive analogue of DNFB, 2,4-dichloronitrobenzene, and two irritants (sodium dodecyl sulphate and benzalkonium chloride) on the expression of the i...

  5. Activation of macrophage nuclear factor-κB and induction of inducible nitric oxide synthase by LPS

    OpenAIRE

    Yan Zhong-Qun; Li Ying-Hua; Brauner Annelie; Tullus Kjell

    2002-01-01

    Abstract Background Chronic lung disease (CLD) of prematurity is a major problem of neonatal care. Bacterial infection and inflammatory response have been thought to play an important role in the development of CLD and steroids have been given, with some benefit, to neonates with this disease. In the present study, we assessed the ability of lipopolysaccharide (LPS) to stimulate rat alveolar macrophages to produce nitric oxide (NO), express inducible nitric oxide synthase (iNOS) and activate ...

  6. Beneficial Effects of Concomitant Neuronal and Inducible Nitric Oxide Synthase Inhibition in Ovine Burn and Inhalation Injury

    OpenAIRE

    Lange, Matthias; Hamahata, Atsumori; Enkhbaatar, Perenlei; Cox, Robert A.; Nakano, Yoshimitsu; Westphal, Martin; Traber, Lillian D.; Herndon, David N.; Traber, Daniel L.

    2011-01-01

    Different isoforms of nitric oxide synthase are critically involved in the development of pulmonary failure secondary to acute lung injury. Here we tested the hypothesis that simultaneous blockade of inducible and neuronal nitric oxide synthase effectively prevents the pulmonary lesions in an ovine model of acute respiratory distress syndrome (ARDS) induced by combined burn and smoke inhalation injury. Chronically instrumented sheep were allocated to a sham-injured group (n = 6), an injured a...

  7. The Effect of Nitric Oxide Donor in Diabetic Wound Healing

    Directory of Open Access Journals (Sweden)

    N Dashti

    2003-10-01

    Full Text Available Diabetes is characterized by a nitric oxide deficiency at the wound site. Diabetes is a factor that influences all stages of wound healing. In animals with acute experimental diabetes induced by streptozotocin (STZ, the early inflammatory responses after wounding is impaired, fibroblast and endothelial cell proliferation is reduced as well as accumulation of reparative collagen and gain in wound breaking strenght. This study investigated whether exogenous nitric oxide supplimentation with nitric oxide donor DETA NONOate could reverse impaired healing in diabetes. The results suggest nitric oxide donor DETA NONOate can reverse impaired healing associated with diabetes (P<0.001 and urinary nitrate (NO-3 output may reflect the extent of repair in this wound model (P<0.001.

  8. Adhesion Development and the Expression of Endothelial Nitric Oxide Synthase

    Directory of Open Access Journals (Sweden)

    David M. Svinarich

    2001-01-01

    Full Text Available Objective: This study was conducted to determine whether nitric oxide (NO, a potent vasodilator and inhibitor of thrombus formation, is involved in the formation and maintenance of adhesions.

  9. Nitric oxide damages neuronal mitochondria and induces apoptosis in neurons

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The cytotoxic effect of nitric oxide on primarily cultured rat cerebellar granule cells was studied,and the mechanisms were discussed.The results showed that nitric oxide donor S-nitroso-N-acetyl-penicillamine (SNAP; 500 μmol/L) could induce apoptosis in immature cultures of cerebellar granule cells.Flow cytometry and HPLC analyses revealed that after treatment with SNAP,the mitochondrial transmembrane potential and the cellular ATP content decreased significantly.Nitric oxide scavenger hemoglobin could effectively prevent the neuronal mitochondria from dysfunction and attenuate apoptosis.The results suggested that nitric oxide activated the apoptotic program by inhibiting the activity of mitochondrial respiratory chain and thus decreasing the cellular ATP content.

  10. Measurements of fractional exhaled nitric oxide in pediatric asthma

    OpenAIRE

    Youn-Soo Hahn

    2013-01-01

    Exhaled nitric oxide (NO) has been extensively investigated as a noninvasive marker of airway inflammation in asthma. The increased NO expression induced by inflammatory mediators in airways can be monitored easily in exhaled air from asthmatic children. Based on the relationship between the increased NO expression and eosinophilic airway inflammation, fractional exhaled nitric oxide (FeNO) measurements become an important adjunct for the evaluation of asthma. In addition, the availability of...

  11. The Effect of Nitric Oxide Donor in Diabetic Wound Healing

    OpenAIRE

    N Dashti; Ansari, M.; M. Shabani; S Vardasti; Mirsalehian, A.; MH Noori Mughehi; Hatmi ZN

    2003-01-01

    Diabetes is characterized by a nitric oxide deficiency at the wound site. Diabetes is a factor that influences all stages of wound healing. In animals with acute experimental diabetes induced by streptozotocin (STZ), the early inflammatory responses after wounding is impaired, fibroblast and endothelial cell proliferation is reduced as well as accumulation of reparative collagen and gain in wound breaking strenght. This study investigated whether exogenous nitric oxide supplimentation with ni...

  12. Nitric oxide and carbon monoxide diffusing capacity of the lung

    OpenAIRE

    Lee, I.

    2006-01-01

    The single breath diffusion capacity of the lung for carbon monoxide (DLCO) is measure for gas uptake by the lung, and consists of a membrane and a vascular component. Nitric oxide (NO) binds 400 times faster to hemoglobin than carbon monoxide, thus the uptake of NO by the blood is very large. Therefore the diffusion capacity of the lung for nitric oxide (DLNO) should reflect the alveolocapillary membrane diffusing capacity only, and should not be influenced by the vascular component. In this...

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

    Science.gov (United States)

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

    2002-01-01

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

  14. Hemoglobin: A Nitric-Oxide Dioxygenase

    Directory of Open Access Journals (Sweden)

    Paul R. Gardner

    2012-01-01

    Full Text Available 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.

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

    Science.gov (United States)

    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.

  16. [Inhalation of nitric oxide - dependence: case report

    Science.gov (United States)

    Carvalho, W B; Matsumoto, T; Horita, S M; Almeida, N M; Martins, F R

    2000-01-01

    OBJECTIVE: Describe the hemodynamic response with rebound of pulmonary hypertension after withdrawal of inhaled nitric oxide (NO) in a pediatric patient with acute respiratory distress syndrome (ARDS). METHODS: Case report of a child with ARDS and pulmonary hypertension evaluated through ecocardiografic with dopller, receiving inhaled NO for a period of 21 days. RESULTS: There was a decrease of the pulmonary artery pressure (PAP) from 52 mmHg to 44 mmHg after the initial titulation of NO inhalation dose. After the withdrawal of inhaled NO an elevation of PAP was observed (55 mmHg). It was necessary to reinstall the inhaled NO to obtain a more appropriate value (34 mmHg). A new attempt of interruption of the inhaled NO after prolonged inhalation (20 days) resulted in a new clinic worsening and increase of PAP, with the indication to reinstall the inhaled NO. In the 24th day of permanence in the intensive care unit the patient died due to multiple organ dysfunction. CONCLUSIONS: The possibility of pulmonary hypertension rebound after withdrawal of inhaled NO is a complication that may have important clinical implications for patients who need a prolonged treatment with NO. This case report emphasizes these implications. PMID:14647690

  17. Nitric oxide negatively regulates mammalian adult neurogenesis

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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. PMID:25976309

  19. Nitric oxide and cardiovascular risk factors

    Directory of Open Access Journals (Sweden)

    Livio Dai Cas

    2007-06-01

    Full Text Available The endothelium is a dynamic organ with many properties that takes part in the regulation of the principal mechanisms of vascular physiology. Its principal functions include the control of blood-tissue exchange and permeability, the vascular tonus, and the modulation of inflammatory or coagulatory mechanisms. Many vasoactive molecules, produced by the endothelium, are involved in the control of these functions. The most important is nitric oxide (NO, a gaseous molecule electrically neutral with an odd number of electrons that gives the molecule chemically reactive radical properties. Already known in the twentieth century, NO, sometimes considered as a dangerous molecule, recently valued as an important endogenous vasodilator factor. Recently, it was discovered that it is involved in several physiological mechanisms of endothelial protection (Tab. I. In 1992, Science elected it as “molecule of the year”; 6 yrs later three American researchers (Louis Ignarro, Robert Furchgott and Fried Murad obtained a Nobel Prize for Medicine and Physiology “for their discoveries about NO as signal in the cardiovascular system”.

  20. NITRIC OXIDE SYNTHESIS IN MYOCARDIUM FOLLOWING BURN INJURY IN RATS

    Institute of Scientific and Technical Information of China (English)

    王卫东; 陈宗荣; 李蓉; 楼淑芳

    1998-01-01

    The nitric oxide and cyclic GMP production in myocardium early after burn injury in tats were investigated. Nitric oxide synthase activity was measured in cytosols from the left ventricular wall of burned rats.Cytosols from the control group animals were shown to contain mainly Ca2+ dependent nitric oxide synthase (cNOS) with small amount of Ca2+ independent nitric oxide synthase (iNOS). Following burn injury,there was a marked increase in iNOS activity with a peak at 8h post-butyl, however, myocardial cNOS activity was found to decline obviously. Parallel to iNOS induction there was a significant increase in myocardial nitric oxide and cyelic GMP production. All these chenges were alleviated by treatment of the rats with dexamethasone. Since increases in cyclic GMP levels in the heart were associated with reduced myocardial contractility, it is possible that enhanced production of nitric oxide by a Ca2+ independent NO synthase accounts, at least in part, for the depression of myocardial contractility seen in burn animals and patients.

  1. Interleukin 1 beta induces diabetes and fever in normal rats by nitric oxide via induction of different nitric oxide synthases

    DEFF Research Database (Denmark)

    Reimers, J I; Bjerre, U; Mandrup-Poulsen, T;

    1994-01-01

    , hyperglycaemia, hypoinsulinemia, and hyperglucagonemia, and partially prevented lymphopenia and neutrophilia, but had no effect on IL-1 beta-induced anorexia and changes in plasma corticosterone. Preferential inhibition of the inducible form of nitric oxide synthase using two daily injections of 5 mg......, glucagon, corticosterone and leukocyte- and differential-counts in normal rats injected once daily for 5 days with interleukin 1 beta (IL-1 beta) (0.8 microgram/rat = 4.0 micrograms/kg). Inhibition of both the constitutive and the inducible forms of nitric oxide synthase prevented IL-1 beta-induced fever....../rat of aminoguanidine prevented IL-1 beta-induced hyperglycaemia and hypoinsulinaemia, and slightly reduced the pyrogenicity of IL-1 on 3 out of 5 days. Higher doses of aminoguanidine (100 mg/rat) prevented lymphopenia and neutrophilia. We conclude that nitric oxide produced by the inducible form of nitric oxide...

  2. 益肺活血颗粒对缺氧培养大鼠肺动脉平滑肌细胞NO,iNOS的影响%Effect of Yifei Huoxue Granule on Nitric Oxide and Inducible Nitric Oxide Synthesis in Rat Pulmonary Artery Smooth Muscle Cells Cultured in Chronic Hypoxia Condition in vitro

    Institute of Scientific and Technical Information of China (English)

    张凌云; 欧敏; 黄友章; 乔媛媛; 张达矜

    2011-01-01

    Objective:To investigate the effect of Yifei Huoxue granule< YFHXG) on the nitric oxide(NO) leveland inducible nitric oxide synthesis( iNOS) activation of rat pulmonary artery smooth muscle cells( PASMCs) upon exposure to chronic hypoxic conditions. Method: Tissue block anchorage was useed to the primary culture of rat PASMCs, PASMCs were randomly divided into normoxia group, hypoxia group, hypoxia + YFHXG group(7. 5, 1.5, 0. 15 g· L-1). NO level was measured by nitrate reductase method, mRNA abundance of iNOS was detected by RT-PCR, the expression of iNOS were examined by immunohistochemistry. Result: Compared with PASMCs in normoxia group, hypoxia caused NO levels to increase, the transcription and translation of iNOS improved a lot in hypoxia group ( P < 0. 05 ) ; But compared with hypoxia alone group, YFHXG group had a significantly effect in increasing NO level and iNOS activity which was based on hypoxia induced( P <0. 05 ). Conclusion:YFHXG can directly promote NO level and iNOS activation of PASMCs on hypoxic conditions through enhancing the transcriptionand translation of iNOS, thus inhibiting the proliferation of PASMCs and mediating vasodilation, it may play a crucial role in the protecting of hypoxic pulmonary arterial hypertension.%目的:观察益肺活血颗粒对缺氧条件下大鼠肺动脉平滑肌细胞(PASMCs)一氧化氮(NO)产生及诱导型一氧化氮合酶(iNOS)活性的影响.方法:采用组织块贴壁法培养大鼠PASMCs,取对数生长期PASMCs随机分为常氧组,缺氧组,缺氧+益肺活血颗粒组(7 5,1.5,0 15 g·L-1).利用硝酸还原酶法测定各组PASMCsNO的产生,RT-PCR测定iNOS mRNA的水平,免疫组化法测定胞内iNOS蛋白的表达量.结果:与单纯常氧组相比,缺氧组PASMCs iNOS转录和翻译增强,NO生成显著升高(P<0 05);且与单纯缺氧组相比,益肺活血颗粒组随着药物浓度的增加,可进一步提高PASMCs iNOS的活性和NO的生成(P<0 05).结论:益肺活血颗粒

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

    Science.gov (United States)

    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.

  4. Concentrations of Nitric Oxide in Rat Brain Tissues after Diffuse Brain Injury and Neuroprotection by the Selective Inducible Nitric Oxide Synthase Inhibitor Aminoguanidine

    Institute of Scientific and Technical Information of China (English)

    Yi-bao Wang; Shao-wu Ou; Guang-yu Li; Yun-hui Liu

    2005-01-01

    @@ To investigate the effects of nitric oxide (NO) and the selective inducible nitric oxide synthase (iNOS) inhibitor aminoguanidine (AG) on trauma, we explored the concentrations of nitric oxide in rat brain tissues at different time stamps after diffuse brain injury (DBI) with or without AG treatment.

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

    Science.gov (United States)

    Ahmed, Marwa A; Kurkar, Adel

    2014-04-01

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

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

    Science.gov (United States)

    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

  7. [Pathophysiological and therapeutic implications of nitric oxide in hepatology].

    Science.gov (United States)

    Battista, S; Bar, F; Pollet, C; Mengozzi, G; Molino, G

    2002-12-01

    The L-arginine/nitric oxide (NO) pathway has been recognized as a main regulator of several cell functions. Accordingly, there is an increasing number of pathophysiological conditions in which a precise knowledge of NO status could prove helpful in understanding the mechanisms involved in disease development, prevention and treatment. These include several hepatic disorders, such as liver cirrhosis and associated hyperdynamic circulation with portal hypertension, ischaemia-reperfusion injury occurring during liver transplantation, and chronic cholestatic conditions. Overall, NO seems to exert a dual role in the pathobiology of liver diseases: one mostly beneficial, due to its vasoactive effects; and one mostly negative, due to its local toxic effects. Protective actions are primarily mediated via vasodilation, antithrombosis, inhibition of neutrophil adhesion and inhibition of apoptosis. Deleterious effects are dependent upon the formation of highly reactive substances during oxidative stress. In this review aspects related to NO implications in the homeostasis of liver functions as well as in the pathogenesis of some relevant hepatic clinical syndromes will be discussed in view of possible therapeutic options. PMID:16491056

  8. Nitric Oxide in Astrocyte-Neuron Signaling

    Energy Technology Data Exchange (ETDEWEB)

    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

  9. Chronic estrogen treatment in female transgenic (mRen2)27 hypertensive rats augments endothelium-derived nitric oxide release.

    Science.gov (United States)

    Li, P; Ferrario, C M; Ganten, D; Brosnihan, K B

    1997-06-01

    Postmenopausal estrogen replacement therapy is associated with a reduction in cardiovascular events in women, but the mechanisms for this protection are unclear, especially in hypertensive subjects. In this study we investigated the effects of 17beta-estradiol (E2) treatment on blood pressure and endothelial function of transgenic [(mRen2)27] hypertensive and normotensive rats. Thirty female transgenic negative [Tg(-)] and hypertensive positive [Tg(+)] rats were ovariectomized and received either E2 (1.5 mg/rat, subcutaneously, for 3 weeks) or placebo. Chronic 17beta-estradiol treatment lowered mean blood pressure in both Tg hypertensive (159 +/- 4 v 145 +/- 4 mm Hg, P calcium ionophore (A23187)-induced endothelium-dependent relaxation was less potent in Tg(+) as compared to Tg(-) rats and was enhanced by E2 treatment only in Tg(+) animals. There were no differences in the vasodilator responses elicited by sodium nitroprusside. Removal of endothelium and blockade of NO production abolished the endothelium-dependent vasodilation. The selective NO synthase inhibitor, N(G)-monomethyl-L-arginine (LMMNA), was used to evaluate indirectly the basal contribution of NO in vascular rings. The response to LMMNA was attenuated in untreated Tg(+) as compared to Tg(-) rats. E2 treatment augmented the contraction response to NOS inhibition in both Tg(+) and Tg(-) rats, resulting in a response in Tg(+) rats that was no different from Tg(-) rats. These results indicate that untreated, surgically ovariectomized hypertensive rats show deficiencies in endothelial function, which can be improved by estrogen replacement.

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

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

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

  11. Hubungan Kadar Nitric Oxide Serum Pasien Psoriasis Vulgaris dengan Skor Psoriasis Area and Severity Index

    OpenAIRE

    Suhoyo, Wahyuni Widiyanti

    2015-01-01

    Background: Psoriasis is a common chronic skin disease mediated by cellular immune mechanisms and characterized by an intense neutrophile cell infiltrate and proliferative activation of epidermal keratinocytes. It is generally assumed that unbalanced immune responses contribute to the pathogenesis. One of the mediators responsible for the pathogenesis of psoriasis is Nitric oxide (NO). NO levels from psoriasis skin lesion had been known increased but only few studies that examined NO blood se...

  12. [Level of nitric oxide in the kidneys during apoptosis activation].

    Science.gov (United States)

    Komarievtseva, I O; Orlova, O A; Blahodarenko, Ie A

    2002-01-01

    The content of nitric oxide stable metabolites in a tissue of kidneys of rats in conditions of activation of apoptosis was investigated. Research was carried out in two models: acute renal failure and a hypertrophy of a unique kidney after a unilateral nephrectomy. Detection of apoptosis was carried out by definition of DNA fragmentation. Substantial increase of the nitric oxide stable metabolites contents is revealed at activation of apoptosis in both models. Change of a ratio of the contents of nitrite--anions in relation to the general contents of NO2- + NO3- is revealed, indicating the role of peroxide processes in effect of nitric oxide and its metabolites on the cell. PMID:14964872

  13. Pain modulation by nitric oxide in the spinal cord.

    Directory of Open Access Journals (Sweden)

    Marco Aurelio M Freire

    2009-09-01

    Full Text Available Nitric oxide (NO is a versatile messenger molecule first associated with endothelial relaxing effects. In the central nervous system (CNS, NO synthesis is primarily triggered by activation of N-methyl-D-aspartate (NMDA receptors and has a Janus face, with both beneficial and harmful properties, depending on concentration and the identity of its synthetic enzyme isoform. There are three isoforms of the NO synthesizing enzyme nitric oxide synthase (NOS: neuronal (nNOS, endothelial (eNOS, and inducible nitric oxide synthase (iNOS, each one involved with specific events in the brain. In CNS, nNOS is involved with modulation of synaptic transmission through long-term potentiation in several regions, including nociceptive circuits in the spinal cord. Here, we review the role played by NO on central pain sensitization.

  14. Parameters controlling nitric oxide emissions from gas turbine combustors

    Science.gov (United States)

    Heywood, J. B.; Mikus, T.

    1973-01-01

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

  15. Investigation of products of molybdenite oxidation by nitric acid

    International Nuclear Information System (INIS)

    Physicochemical study of products of oxidation by nitric acid of molybdenum concentrate containing 98% MoS2 is carried out. It is shown that appearing molybdenum oxide forms block oxidizer access to the surface of sulfide phase and hinder its complete oxidation. When complexing reagents (H2SO4, H3PO4, HCl) are introduced in the solution the bulk of oxidized molybdenum transfers into solution in the form of a stable complex, at that. The effect of internal diffusion decreases and a considerable increase of MoS2 oxidation rate and completeness is achieved

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

    Science.gov (United States)

    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.

  17. NO对慢性病贫血大鼠转铁蛋白受体表达的影响%Effect of Nitric Oxide on the Expressionof Transferrin Receptor in Rats with Anemia in Chronic Disease

    Institute of Scientific and Technical Information of China (English)

    王强; 廖清奎; 董巍

    2003-01-01

    目的探讨一氧化氮(NO)在慢性病贫血(ACD)发病中的作用及对骨髓血细胞转铁蛋白受体(TfR)的影响,为ACD的防治提供实验依据.方法用福氏完全佐剂建立传统的类风湿性关节炎大鼠动物模型,在此基础上通过反复注射福氏完全佐剂,建立ACD大鼠动物模型.利用此模型观察对照组、炎症组及炎症+一氧化氮合酶(NOS)抑制剂组的NO浓度的改变、贫血的程度及与TfR的关系.结果炎症组NO、NOS浓度显著高于对照组,贫血明显,TfR表达强度低于对照组,差异有显著性(P<0.01);用NOS抑制剂后,NO和NOS水平低于炎症组愿哂诙哉兆椋堆纳疲琓fR介于炎症组与对照组之间,差异有显著性(P<0.01).结论 NO参与了ACD 的发病及ACD时TfR的调节,为从NO对TfR影响角度进一步认识ACD的发病机制提供了实验依据;及早降低NO水平,有利于阻止贫血的发展,为ACD的治疗提供一条新途径.%Objective To study the influence of nitric oxide (NO) in rats with anemia in chronic disease (ACD) and the effect of NO on the expression of transferrin receptor (TfR) in bone marrows and to provide experimental evidence for the prevention and treatment of ACD. Methods The conventional animal model of rheumatoid arthritic (RA) was established by injection of Freund's complete adjuvant. On the basis of this model, we injected Freund's complete adjuvant repeatedly to establish the ACD model. The rats were randomly assigned into three groups (Group A: control group; Group B: inflammatory group; Group C: inflammatory+NO inhibitory agent group). The histopathological changes of the toe joints of the rats were observed and the contents of NO, Hb and nitric oxide synthetase (NOS), and the expression of TfR were measured in the three groups. Results In Group B, the contents of NO and NOS in the serum were higher than those in Group A; TfR expression in bone marrow cells was lower than that in Group A, and anemia was more severe than

  18. Inhibitors of nitric oxide synthase in inflammatory arthritis.

    Science.gov (United States)

    Boughton-Smith, N K; Tinker, A C

    1998-07-01

    There is considerable evidence that excessive nitric oxide (NO) synthesized from L-arginine by inducible nitric oxide synthase (iNOS) plays an important pathological role in inflammatory arthritis. Since NO synthesized by constitutive isoforms of NOS has a physiological role, a great deal of activity has been directed at identifying inhibitors of NOS that are selective for the induced isoform. The major chemical areas that have been described so far in the search for such selective iNOS inhibitors and the activity of some of these compounds in animal models of arthritis are reviewed. PMID:18465556

  19. Nitric oxide-related drug targets in headache

    DEFF Research Database (Denmark)

    Olesen, Jes

    2010-01-01

    SUMMARY: Nitric oxide (NO) is a very important molecule in the regulation of cerebral and extra cerebral cranial blood flow and arterial diameters. It is also involved in nociceptive processing. Glyceryl trinitrate (GTN), a pro-drug for NO, causes headache in normal volunteers and a so-called del......SUMMARY: Nitric oxide (NO) is a very important molecule in the regulation of cerebral and extra cerebral cranial blood flow and arterial diameters. It is also involved in nociceptive processing. Glyceryl trinitrate (GTN), a pro-drug for NO, causes headache in normal volunteers and a so...

  20. Sevoflurane and nitric oxide synthase expression in rat cochlea

    Institute of Scientific and Technical Information of China (English)

    Yuantao Li; Qingzhong Hou; Mingguang Wu; Xiaolei Huang; Jun Cao; Yin Gu; Xiaofei Qi; Yawen Li

    2010-01-01

    Sevoflurane exhibits anesthetic action by inhibiting the auditory cortex,brain stem nitric oxide synthase activity,and reducing nitric oxide(NO),thereby interfering with the hearing process.However,the influence of sevoflurane on peripheric receptor(cochlea)NO remains poorly understood.Results from the present study showed that sevoflurane downregulated cochlear inducible NO synthase,endothelial NO synthase and neuronal NO synthase expression in a dose dependent manner.This suggests that sevoflurane can decrease cochlear NO synthase expression in a dose dependent manner.

  1. Nitric oxide synthase expression and enzymatic activity in multiple sclerosis

    DEFF Research Database (Denmark)

    Broholm, H; Andersen, B; Wanscher, B;

    2004-01-01

    We used post-mortem magnetic resonance imaging (MRI) guidance to obtain paired biopsies from the brains of four patients with clinical definite multiple sclerosis (MS). Samples were analyzed for the immunoreactivity (IR) of the three nitric oxide (NO) synthase isoforms [inducible, neuronal...... and endothelial nitric oxide synthase (NOS)], and enzymatic NO synthase activity. MRI guided biopsies documented more active plaques than macroscopic examination, and histological examination revealed further lesions. Inducible NOS (iNOS) was the dominant IR isoform, while reactive astrocytes were the dominant i...

  2. DOES BRACHIAL ARTERY FMD PROVIDE A BIOASSAY FOR NITRIC OXIDE?

    OpenAIRE

    Wray, D. Walter; Witman, Melissa A. H.; Ives, Stephen J.; McDaniel, John; Trinity, Joel D.; Conklin, Jamie D.; Supiano, Mark A.; Richardson, Russell S.

    2013-01-01

    This study sought to better define the role of nitric oxide (NO) in brachial artery flow-mediated vasodilation (FMD) in young, healthy humans. Brachial artery blood velocity and diameter were determined (ultrasound Doppler) in eight volunteers (26 ± 1 yrs) before and after 5-min forearm circulatory occlusion with and without intra-arterial infusion of the endothelial nitric oxide synthase (eNOS) inhibitor L-NMMA (0.48 mg/dl/min). Control (CON) and L-NMMA trials were performed with the occlusi...

  3. Deciphering The Complex Biological Interactions Of Nitric Oxide In Cancer

    Directory of Open Access Journals (Sweden)

    S. Perwez Hussain

    2015-08-01

    Full Text Available NO• is a free radical and is involved in a number of critical physiological processes including vasodilation, neurotransmission, immune regulation and inflammation. There are convincing evidence suggesting a role of NO• in the development and progression of different cancer types. However, the role of NO• in tumorigenesis is highly complex and both pro- and anti-neoplastic functions have been reported, which largely depends on the amount of NO•, cell types, cellular microenvironment, its interaction with other reactive species and presence of metals. An interesting interaction occurs between NO• and p53 tumor suppressor, in which NO•-induced DNA damage causes the stabilization and accumulation of p53, which in turn, transrepresses inducible nitric oxide synthase (NOS2 in a negative feedback loop. In chronic inflammatory diseases, for example ulcerative colitis, NO• induces p53 stabilization and the initiation of DNA-damage response pathway, and also generation of p53 mutation and subsequent clonal selection of p53 mutant cells. Genetic deletion of NOS2 in p53-deficient mice can either suppress or enhance lymphomagenesis depending on the inflammatory microenvironment. These findings highlight the importance of understanding the complex biological interaction of NO• in the context of the molecular makeup of each individual cancer to design NO•-targeted treatment strategies.

  4. Inducible nitric oxide synthase is expressed in synovial fluid granulocytes

    Science.gov (United States)

    CEDERGREN, J; FORSLUND 2, T; SUNDQVIST 2, T; SKOGH 1, T

    2002-01-01

    The objective of the study was to evaluate the NO-producing potential of synovial fluid (SF) cells. SF from 15 patients with arthritis was compared with blood from the same individuals and with blood from 10 healthy controls. Cellular expression of inducible nitric oxide synthase (iNOS) was analysed by flow cytometry. High-performance liquid chromatography was used to measure l-arginine and l-citrulline. Nitrite and nitrate were measured colourimetrically utilizing the Griess’ reaction. Compared to whole blood granulocytes in patients with chronic arthritis, a prominent iNOS expression was observed in SF granulocytes (P < 0·001). A slight, but statistically significant, increase in iNOS expression was also recorded in lymphocytes and monocytes from SF. l-arginine was elevated in SF compared to serum (257 ± 78 versus 176 ± 65 µmol/l, P = 0·008), whereas a slight increase in l-citrulline (33 ± 11 versus 26 ± 9 µmol/l), did not reach statistical significance. Great variations but no significant differences were observed comparing serum and SF levels of nitrite and nitrate, respectively, although the sum of nitrite and nitrate tended to be elevated in SF (19·2 ± 20·7 versus 8·6 ± 6·5 µmol/l, P = 0·054). Synovial fluid leucocytes, in particular granulocytes, express iNOS and may thus contribute to intra-articular NO production in arthritis. PMID:12296866

  5. Asymmetric dimethylarginine, endothelial nitric oxide bioavailability and mortality in sepsis.

    Directory of Open Access Journals (Sweden)

    Joshua S Davis

    Full Text Available BACKGROUND: Plasma concentrations of asymmetric dimethylarginine (ADMA, an endogenous inhibitor of nitric oxide synthase, are raised in patients with chronic vascular disease, causing increased cardiovascular risk and endothelial dysfunction, but the role of ADMA in acute inflammatory states is less well defined. METHODS AND RESULTS: In a prospective longitudinal study in 67 patients with acute sepsis and 31 controls, digital microvascular reactivity was measured by peripheral arterial tonometry and blood was collected at baseline and 2-4 days later. Plasma ADMA and L-arginine concentrations were determined by high performance liquid chromatography. Baseline plasma L-arginine: ADMA ratio was significantly lower in sepsis patients (median [IQR] 63 [45-103] than in hospital controls (143 [123-166], p<0.0001 and correlated with microvascular reactivity (r = 0.34, R(2 = 0.12, p = 0.02. Baseline plasma ADMA was independently associated with 28-day mortality (Odds ratio [95% CI] for death in those in the highest quartile (≥ 0.66 µmol/L = 20.8 [2.2-195.0], p = 0.008, and was independently correlated with severity of organ failure. Increase in ADMA over time correlated with increase in organ failure and decrease in microvascular reactivity. CONCLUSIONS: Impaired endothelial and microvascular function due to decreased endothelial NO bioavailability is a potential mechanism linking increased plasma ADMA with organ failure and death in sepsis.

  6. 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.

    Science.gov (United States)

    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

  7. Elevated exhaled nitric oxide in high-risk neonates precedes transient early but not persistent wheeze

    DEFF Research Database (Denmark)

    Chawes, Bo L K; Buchvald, Frederik; Bischoff, Anne Louise;

    2010-01-01

    Elevated fractional exhaled nitric oxide (Fe(NO)) concentration has been suggested to predict early childhood wheeze and sensitization.......Elevated fractional exhaled nitric oxide (Fe(NO)) concentration has been suggested to predict early childhood wheeze and sensitization....

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

    OpenAIRE

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

    2013-01-01

    OBJECTIVE: Nitric oxide is produced by endothelial nitric oxide synthase, and its production can be influenced by polymorphisms of the endothelial nitric oxide synthase gene. Because candidate genes responsible for susceptibility to ankylosing spondylitis are mostly unknown and available data suggest that there may be problems related to the nitric oxide pathway, such as endothelial dysfunction and increased asymmetric dimethylarginine, this study aimed to assess the association of common end...

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

    Science.gov (United States)

    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.

  10. Effects of Nephritis No. 3 Recipe on Nitric Oxide, Nitric Oxide Synthase Secreted by Cultured Mesangial Cells in Rats and the Gene Expression of Inducible Nitric Oxide Synthase

    Institute of Scientific and Technical Information of China (English)

    陈志强; 黄怀鹏; 黄文政; 朱小棣; 林清棋

    2003-01-01

    Objective: To explore the effect of the Nephritis No. 3 (N-3) recipe on nitric oxide (NO),nitric oxide synthase (NOS) secreted by cultured mesangial cells (MC) and its gene expression of the inducible nitric oxide synthase (iNOS). Methods: The drug (nephritis No. 3)-containing serum was prepared with serum pharmacological technique, and then was applied to react on mesangial cells cultured in fetal calf serum (FCS) and cells cultured in FCS plus lipopolysaccharide. To observe the secretion of NO and NOS and the gene expression of iNOS by means of RT-PCR. Results: Under the two kinds of culture conditions, the content of NO and NOS in the groups with drug-containing serum were higher than those without drug-containing serum (P<0.05, P<0.01), and the expression of iNOS mRNA was up-regulated too. Conclusion: The N-3 could significantly promote the secretion of NO and NOS and the mRNA expression of iNOS in rats.

  11. Application of fractional exhaled nitric oxide and impulse oscillometry in patients with chronic cough%呼出气一氧化氮和脉冲振荡肺功能在慢性咳嗽中的应用

    Institute of Scientific and Technical Information of China (English)

    邱洁萍; 金晓燕; 沈海燕

    2012-01-01

    Objective To evaluate the diagnostic value of fraction exhaled nitric oxide (FeNO) and impulse oscillometry in patients with chronic cough.Methods Patients with chronic cough for at least eight weeks from February 2011 to September 2011 were enrolled.FeNO test and IOS test were performed in all of the patients.Bronchial challenge test and bronchodilator test were defined as golden standard for asthma diagnosis in patients.The diagnostic value of FeNO and IOS parameters were assessed,the optimal operating point of FeNO testing and IOS testing were determined by the means of the receiver operating characteristic (ROC) curve.Results A total of 102 patients were enrolled,in which 52 cases were diagnosed as asthma by clinical manifestation and positive result in bronchial challenge test or bronchodilator test,and the other 50 cases were non-asthma.The level of FeNO in asthma group was higher than non-asthma group,but FEV1 was lower than non asthma group.OF all subjects,FEV1 %pred was close linear correlated with FeNO and IOS parameters (except for R20 ) ( P < 0.05).The optimal diagnostic cut-off point was 30.5 ppb of FeNO or 16.46 Hz of Fres which was capable of differentiating asthma and non asthma.Conclusions FeNO test and IOS test have high sensitivity and specificity in the diagnosis of CVA,which contributes to the etiological diagnosis of chronic cough.%目的 评估呼出气一氧化氮(FeNO)检测和脉冲振荡肺功能技术(IOS)在慢性咳嗽临床诊断中的价值.方法 选取2011年2~9月因慢性咳嗽在我院就诊的患者102例,分别进行FeNO测定和IOS检测,以临床表现和支气管激发或舒张试验为支气管哮喘(简称哮喘)诊断的金标准,绘制ROC曲线,结合ROC曲线明确FeNO和IOS参数的诊断临界点,以评价FeNO和IOS参数对咳嗽变异性哮喘的诊断价值.结果 102名受试者中,诊断哮喘患者50例,非哮喘患者52例.哮喘组FEV1低于非哮喘组,FeNO高于非哮喘组.102例受试者中,FEV1

  12. Nitric Oxide Donor食品保健品作用机理综述%Nitric Oxide Donor Foods Mechanism Review

    Institute of Scientific and Technical Information of China (English)

    韩奇; 魏冰; 刘玉花; 朱伟丽; 刘震杰; 曹珍艳

    2016-01-01

    Nitric Oxide (NO) is an important signaling molecule for normal functioning of the body. which could improve the vascular endothelial cell nitric oxide (no) level to help speed up the blood circulation, and help the delivery of oxygen and nutrients to upper and lower extremity capillaries that fuel the skeletal muscle. NO can be generated endogenously from L-arginine (L-Arg) under Nitric Oxide Synthase (NOS) catalyzed process andentero-saliva Nitrate-Nitrite-NO process. And through the role of endothelial nitric oxide synthase endothelial nitric oxide synthase (eNOS) can improve vascular endothelial NO production and release, reach the vascular smooth muscle relaxation and vasodilation effect. Based on the recent research, this paper has written a review of the NO food health care products.%一氧化氮(Nitric Oxide,NO)是维持所有正常身体机能的重要信号分子,提高血管内皮细胞NO水平有助加速血液循环,并有助于将氧气和血液中的养分供给到身体四肢的中末端毛细血管,滋养骨骼肌。NO合成机理是通过一氧化氮合酶(Nitric Oxide Synthase,NOS)促进精氨酸(L-Arg)转化为NO,以及肠-唾液腺的硝酸盐-亚硝酸盐-NO途径产生NO。而通过血管内皮组织中一氧化氮合酶(Endothelial Nitric Oxide Synthase,eNOS)的作用,可以提高血管内皮组织中的NO的产生和释放,达到使血管平滑肌放松和扩张血管的效果。基于最近的研究,撰写了这篇NO食品保健品机理综述。

  13. Arginine, citrulline and nitric oxide metabolism in sepsis

    Science.gov (United States)

    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...

  14. Nitric oxide-induced signalling in rat lacrimal acinar cells

    DEFF Research Database (Denmark)

    Looms, Dagnia Karen; Tritsaris, K.; Dissing, S.

    2002-01-01

    The aim of the present study was to investigate the physiological role of nitric oxide (NO) in mediating secretory processes in rat lacrimal acinar cells. In addition, we wanted to determine whether the acinar cells possess endogenous nitric oxide synthase (NOS) activity by measuring NO productio...... not by itself causing fast transient increases in [Ca2+]i. In addition, we suggest that endogenously produced NO activated by ß-adrenergic receptor stimulation, plays an important role in signalling to the surrounding tissue.......The aim of the present study was to investigate the physiological role of nitric oxide (NO) in mediating secretory processes in rat lacrimal acinar cells. In addition, we wanted to determine whether the acinar cells possess endogenous nitric oxide synthase (NOS) activity by measuring NO production......-adrenergic stimulation and not by a rise in [Ca2+]i alone.   We show that in rat lacrimal acinar cells, NO and cGMP induce Ca2+ release from intracellular stores via G kinase activation. However, the changes in [Ca2+]i are relatively small, suggesting that this pathway plays a modulatory role in Ca2+ signalling, thus...

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

    Science.gov (United States)

    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

  16. Nitric oxide and almitrine: the definitive answer for hypoxemia.

    Science.gov (United States)

    Payen, D M; Muret, J

    1999-02-01

    Hypoxia-induced by acute lung injury results from abnormal ventilation/perfusion ratio distribution towards shunt or low ventilation/perfusion zones. Pharmacological modification of pulmonary blood flow distribution improving ventilation/perfusion ratio should correct hypoxia. The development of inhaled nitric oxide therapy had confirmed this concept, but with a relatively high proportion of 'non responders'. Then development of other drugs used alone or in association with nitric oxide may reinforce the benefit of nitric oxide. This has been tested with almitrine bismesylate, a lipophilic drug that reinforce hypoxic pulmonary vasoconstriction. Using inhaled nitric oxide in combination with almitrine, several studies in adult respiratory distress syndrome or acute lung injury patients have shown spectacular results in term of PaO2 and pulmonary shunt reduction. Moreover, the proportion of responders to this combination seems largely great than those observed for each drug alone. In conclusion, pulmonary blood flow manipulation improving ventilation/perfusion mismatching is one of the major strategies to correct severe hypoxia. PMID:17013295

  17. The levels of nitric oxide in megaloblastic anemia

    Directory of Open Access Journals (Sweden)

    Emin Kaya

    2009-12-01

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

  18. Generation of nitric oxide from nitrite by carbonic anhydrase

    DEFF Research Database (Denmark)

    Aamand, Rasmus; Dalsgaard, Thomas; Jensen, Frank B;

    2009-01-01

    bicarbonate and nitrite, we hypothesized that CA uses nitrite as a substrate to produce the potent vasodilator nitric oxide (NO) to increase local blood flow to metabolically active tissues. Here we show that CA readily reacts with nitrite to generate NO, particularly at low pH, and that the NO produced...

  19. Apple fruit responses following exposure to nitric oxide

    Science.gov (United States)

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

  20. Cross sections for electron collisions with nitric oxide

    Science.gov (United States)

    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.

  1. Can nitric oxide induce migraine in normal individuals?

    DEFF Research Database (Denmark)

    Olesen, Jes; Ashina, Messoud

    2015-01-01

    migraine expression. The question is whether any person may express a migraine attack given a sufficiently strong stimulus or provocation. Here, we reviewed and discussed the ability of nitric oxide to induce migraine-like attacks in normal individuals. CONCLUSION: Experimental data show that normal...

  2. Generation of nitric oxide from nitrite by carbonic anhydrase:

    DEFF Research Database (Denmark)

    Aamand, Rasmus; Dalsgaard, Thomas; Jensen, Frank Bo;

    2009-01-01

    bicarbonate and nitrite, we hypothesized that CA uses nitrite as a substrate to produce the potent vasodilator nitric oxide (NO) to increase local blood flow to metabolically active tissues. Here we show that CA readily reacts with nitrite to generate NO, particularly at low pH, and that the NO produced...

  3. Nitric oxide and reactive oxygen species in limb vascular function

    DEFF Research Database (Denmark)

    Gliemann, Lasse; Nyberg, Michael Permin; Hellsten, Ylva

    2014-01-01

    Abstract Nitric oxide (NO) is known to be one of the most important regulatory compounds within the cardiovascular system where it is central for functions such as regulation of blood pressure, blood flow and vascular growth. The bioavailability of NO is determined by a balance between, on one hand...

  4. Identification of free nitric oxide radicals in rat bone marrow

    DEFF Research Database (Denmark)

    Aleksinskaya, Marina A; van Faassen, Ernst E H; Nelissen, Jelly;

    2013-01-01

    Nitric oxide (NO) has been implicated in matrix metallopeptidase 9 (MMP9)-dependent mobilization of hematopoietic stem and progenitor cells from bone marrow (BM). However, direct measurement of NO in the BM remained elusive due to its low in situ concentration and short lifetime. Using NO spin...

  5. On EPR detection of nitric oxide in vivo

    NARCIS (Netherlands)

    van Faassen, E.E.H.

    2008-01-01

    Nitric oxide (NO ) is a peculiar radical: Ground state is not paramagnetic (g = 0 since orbital and spin magnetic moments cancel); low reactivity with other molecules except superoxide (O2 ); thermodynamically unstable; dimerizes to N2O2; difficult to detect in-vivo.

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

    Science.gov (United States)

    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...

  7. Nitric oxide and carbon monoxide diffusing capacity of the lung

    NARCIS (Netherlands)

    Lee, I. van der

    2006-01-01

    The single breath diffusion capacity of the lung for carbon monoxide (DLCO) is measure for gas uptake by the lung, and consists of a membrane and a vascular component. Nitric oxide (NO) binds 400 times faster to hemoglobin than carbon monoxide, thus the uptake of NO by the blood is very large. There

  8. NITRIC OXIDE INTERFERES WITH HYPOXIA SIGNALING DURING COLONIC INFLAMMATION

    Directory of Open Access Journals (Sweden)

    Cintia Rabelo e Paiva CARIA

    2014-12-01

    Full Text Available Context Intestinal inflammation can induce a local reduction in oxygen levels that triggers an adaptive response centered on the expression of hypoxia-inducible factors (HIFs. Nitric oxide, a well-described inflammatory mediator, may interfere with hypoxia signaling. Objectives We aimed to evaluate the role of nitric oxide in hypoxia signaling during colonic inflammation. Methods Colitis was induced by single (acute or repeated (reactivated colitis trinitrobenzenosulfonic acid administration in rats. In addition, one group of rats with reactivated colitis was also treated with Nw-Nitro-L-arginine methyl ester hydrochloride to block nitric oxide synthase. Colitis was assessed by macroscopic score and myeloperoxidase activity in the colon samples. Hypoxia was determined using the oxygen-dependent probe, pimonidazole. The expression of HIF-1α and HIF-induced factors (vascular endothelial growth factor - VEGF and apelin was assessed using Western blotting. Results The single or repeated administration of trinitrobenzenosulfonic acid to rats induced colitis which was characterized by a high macroscopic score and myeloperoxidase activity. Hypoxia was observed with both protocols. During acute colitis, HIF-1α expression was not increased, but VEGF and apelin were increased. HIF-1α expression was inhibited during reactivated colitis, and VEGF and apelin were not increased. Nw-Nitro-L-arginine methyl ester hydrochloride blockade during reactivated colitis restored HIF-1α, VEGF and apelin expression. Conclusions Nitric oxide could interfere with hypoxia signaling during reactivated colitis inflammation modifying the expression of proteins regulated by HIF-1α.

  9. Methodological aspects of exhaled nitric oxide measurements in infants.

    NARCIS (Netherlands)

    Gabriele, C.; Wiel, E.C. van der; Nieuwhof, E.M.; Moll, H.A.; Merkus, P.J.F.M.; Jongste, J.C. de

    2007-01-01

    Guidelines for the measurement of fractional exhaled nitric oxide (FE(NO)) recommend refraining from lung function tests (LFT) and certain foods and beverages before performing FE(NO) measurements, as they may lead to transiently altered FE(NO) levels. Little is known of such factors in infants. The

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

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

    International Nuclear Information System (INIS)

    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. (paper)

  13. NOSTRIN: A protein modulating nitric oxide release and subcellular distribution of endothelial nitric oxide synthase

    Science.gov (United States)

    Zimmermann, Kirstin; Opitz, Nils; Dedio, Jürgen; Renné, Christoph; Müller-Esterl, Werner; Oess, Stefanie

    2002-01-01

    Activity and localization of endothelial nitric oxide synthase (eNOS) is regulated in a remarkably complex fashion, yet the complex molecular machinery mastering stimulus-induced eNOS translocation and trafficking is poorly understood. In a search by the yeast two-hybrid system using the eNOS oxygenase domain as bait, we have identified a previously uncharacterized eNOS-interacting protein, dubbed NOSTRIN (for eNOS traffic inducer). NOSTRIN contains a single polypeptide chain of 506-aa residues of 58 kDa with an N-terminal cdc15 domain and a C-terminal SH3 domain. NOSTRIN mRNA is abundant in highly vascularized tissues such as placenta, kidney, lung, and heart, and NOSTRIN protein is expressed in vascular endothelial cells. Coimmunoprecipitation experiments demonstrated the eNOS–NOSTRIN interaction in vitro and in vivo, and NOSTRIN's SH3 domain was essential and sufficient for eNOS binding. NOSTRIN colocalized extensively with eNOS at the plasma membrane of confluent human umbilical venous endothelial cells and in punctate cytosolic structures of CHO-eNOS cells. NOSTRIN overexpression induced a profound redistribution of eNOS from the plasma membrane to vesicle-like structures matching the NOSTRIN pattern and at the same time led to a significant inhibition of NO release. We conclude that NOSTRIN contributes to the intricate protein network controlling activity, trafficking, and targeting of eNOS. PMID:12446846

  14. Discovery of nitric oxide in marine ecological system and the chemical characteristics of nitric oxide

    Institute of Scientific and Technical Information of China (English)

    ZHANG; Zhengbin; XING; Lei; WU; Zhenzhen; LIU; Chunying; LIN; Cai

    2006-01-01

    Nitric oxide was discovered in both the lab and the alga culture pond of Daya Bay (1-300 m3) before the growth of alga reached the maximum. The results included: (1) NO was detectd before the growth of alga reached the maximum in the case of red tide alga and food alga, and the concentration of NO decreased rapidly after the growth maximum; (2) the curve between NO concentration and time indicated that the concentration of NO in the daytime was more than that at night,and the maximal concentration of NO appeared in the midday (1-3 pm); (3) the growth of alga reached the maximum in the alga culture pond of Daya Bay in about 8- 10 d, and NO was discovered in 5-7 d; (4) the measured NO concentration was 10-9 mol/L, 10-9-10-8 mol/L, and 10-8 mol/L for Haeterosigma akashiwo, mixed alga in Daya Bay and Chaetoceros Curvisetus individually; (5) the relation of illumination with NO production was discussed.

  15. Coordinate Properties of Nitric Oxide in Hemoglobin Solution Containing a Minimal Amount of Nitric Oxide

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    Nitric oxide (NO) has a very important physiological function, and it is the unique small diffusible signaling molecule.When NO molecules bind to heme irons in α subunits in hemoglobin (Hb), they have two coordinate forms for Fe2+: one is 5-coordinate, and the other is 6-coordinate.However, there is only 6-coordinate for Fe2+ when NO molecules bind to heme irons in β subunits.When the amount of NO is at a minimal concentration, NO molecules mainly bind to α subunits.The results show that NO molecules do not transfer from heme irons of nitrosylhemoglobin (HbNO) to the thiol groups of Cysteine residues β93 (Cysβ93) to form s-nitrosohemoglobin (Hb-SNO) in the presence of minimal NO in hemoglobin solution.The presence of minimal NO in hemoglobin solution does not decrease the transportation of oxygen, but it does improve its transport ability.It is still under further research whether this mechanism is underlying in the therapy for the disease of cardiovascular system.

  16. Guidelines for the safe administration of inhaled nitric oxide.

    OpenAIRE

    Miller, O I; Celermajer, D S; Deanfield, J. E.; MacRae, D. J.

    1994-01-01

    Inhaled nitric oxide (NO) is a selective pulmonary vasodilator, potentially useful in the treatment of pulmonary hypertension and ventilation-perfusion mismatch. High doses of inhaled NO and its oxidative product nitrogen dioxide (NO2) may cause acute lung injury. Using a standard infant ventilator, ventilator circuit and test lung, an administration and monitoring strategy has been defined for inhaled NO and these observations validated in eight ventilated infants. In 90% oxygen, doses of in...

  17. Neuronal nitric oxide synthase is dislocated in type I fibers of myalgic muscle but can recover with physical exercise training

    DEFF Research Database (Denmark)

    Jensen, L; Andersen, L L; Schrøder, H D;

    2015-01-01

    Trapezius myalgia is the most common type of chronic neck pain. While physical exercise reduces pain and improves muscle function, the underlying mechanisms remain unclear. Nitric oxide (NO) signaling is important in modulating cellular function, and a dysfunctional neuronal NO synthase (nNOS) ma...

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

    Energy Technology Data Exchange (ETDEWEB)

    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. Effects of glucocorticoid dexamethasone on serum nitric oxide synthase activity and nitric oxide levels in a rat model of lung disease-induced brain injury

    Institute of Scientific and Technical Information of China (English)

    Huajun Li; Ligang Jiang; Meng Xia; Haiping Li; Fanhua Meng; Wei Li; Lifeng Liu; Zhaohui Wang

    2011-01-01

    In this study, we investigated the effects of dexamethasone, pertussis toxin (a Gi protein inhibitor), and actinomycin (a transcription inhibitor) on serum nitric oxide synthase activity and nitric oxide content in a rat model of lung disease-induced brain injury. High-dose dexamethasone (13 mg/kg) and dexamethasone + actinomycin reduced lung water content, increased serum nitric oxide synthase activity and nitric oxide content, diminished inflammatory cell infiltration in pulmonary alveolar interstitium, attenuated meningeal vascular hyperemia, reduced glial cell infiltration, and decreased cerebral edema. These results demonstrate that high-dose glucocorticoid treatment can reduce the severity of lung disease-induced brain injury by increasing nitric oxide synthase activity and nitric oxide levels.

  20. Whole body UVA irradiation lowers systemic blood pressure by release of nitric oxide from intracutaneous photolabile nitric oxide derivates

    NARCIS (Netherlands)

    Opländer, C.; Volkmar, C.M.; Paunel-Görgülü, A.; van Faassen, E.E.H.; Heiss, C.

    2009-01-01

    Rationale: Human skin contains photolabile nitric oxide derivates like nitrite and S-nitroso thiols, which after UVA irradiation, decompose and lead to the formation of vasoactive NO. Objective: Here, we investigated whether whole body UVA irradiation influences the blood pressure of healthy volunte

  1. Correlation of exhaled nitric oxide, nasal nitric oxide and atopic status: A cross-sectional study in bronchial asthma and allergic rhinitis

    OpenAIRE

    Nitesh Gupta; Nitin Goel; Raj Kumar

    2014-01-01

    Objective: Exhaled nitric oxide (FE NO ) and nasal nitric oxide (n NO) measurement is an area of ongoing research in the study of airway inflammation. The atopic status is known to influence the levels of FE NO and n NO. This study was undertaken to study the relationship between nitric oxide measurements in bronchial asthma and allergic rhinitis along with their correlation with atopic profile of Indian population. Materials and Methods: Ninety subjects were recruited for the study comprisin...

  2. Role of Polymorphisms of Inducible Nitric Oxide Synthase and Endothelial Nitric Oxide Synthase in Idiopathic Environmental Intolerances

    Directory of Open Access Journals (Sweden)

    Chiara De Luca

    2015-01-01

    Full Text Available Oxidative stress and inflammation play a pathogenetic role in idiopathic environmental intolerances (IEI, namely, multiple chemical sensitivity (MCS, fibromyalgia (FM, and chronic fatigue syndrome (CFS. Given the reported association of nitric oxide synthase (NOS gene polymorphisms with inflammatory disorders, we aimed to investigate the distribution of NOS2A −2.5 kb (CCTTTn as well as Ser608Leu and NOS3 −786T>C variants and their correlation with nitrite/nitrate levels, in a study cohort including 170 MCS, 108 suspected MCS (SMCS, 89 FM/CFS, and 196 healthy subjects. Patients and controls had similar distributions of NOS2A Ser608Leu and NOS3 −786T>C polymorphisms. Interestingly, the NOS3 −786TT genotype was associated with increased nitrite/nitrate levels only in IEI patients. We also found that the NOS2A −2.5 kb (CCTTT11 allele represents a genetic determinant for FM/CFS, and the (CCTTT16 allele discriminates MCS from SMCS patients. Instead, the (CCTTT8 allele reduces by three-, six-, and tenfold, respectively, the risk for MCS, SMCS, and FM/CFS. Moreover, a short number of (CCTTT repeats is associated with higher concentrations of nitrites/nitrates. Here, we first demonstrate that NOS3 −786T>C variant affects nitrite/nitrate levels in IEI patients and that screening for NOS2A −2.5 kb (CCTTTn polymorphism may be useful for differential diagnosis of various IEI.

  3. Oxidative desulfurization of askale coal by nitric acid solution

    Energy Technology Data Exchange (ETDEWEB)

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

    2007-07-01

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

  4. Nitric Oxide Generated from Isoniazid Activation by KatG: Source of Nitric Oxide and Activity against Mycobacterium tuberculosis

    OpenAIRE

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

    2004-01-01

    Isonicotinic acid hydrazide (INH) is a frontline antituberculosis agent. Once taken up by Mycobacterium tuberculosis, INH requires activation by the catalase-peroxidase KatG, converting INH from its prodrug form into a range of bactericidal reactive species. Here we used 15N-labeled INH together with electron paramagnetic resonance spin trapping techniques to demonstrate that nitric oxide (NȮ) is generated from oxidation at the hydrazide nitrogens during the activation of INH by M. tuberculos...

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

    Science.gov (United States)

    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.

  6. Combined atmospheric oxidant capacity and increased levels of exhaled nitric oxide

    Science.gov (United States)

    Yang, Changyuan; Li, Huichu; Chen, Renjie; Xu, Wenxi; Wang, Cuicui; Tse, Lap Ah; Zhao, Zhuohui; Kan, Haidong

    2016-07-01

    Nitrogen dioxide and ozone are two interrelated oxidative pollutants in the atmosphere. Few studies have evaluated the health effects of combined oxidant capacity (O x ). We investigated the short-term effects of O x on fractional exhaled nitric oxide (FeNO), a well-established biomarker for airway inflammation, in a group of chronic obstructive pulmonary disease patients. Real-time concentrations of O x were obtained by calculating directly the sum of nitrogen dioxide and ozone. Linear mixed-effect models were applied to explore the acute effects of O x on FeNO levels. Short-term exposure to Ox was significantly associated with elevated FeNO. This effect was strongest in the first 24 h after exposure, and was robust to the adjustment of PM2.5. A 10 μg m‑3 increase in 24 h average concentrations of O x was associated with 4.28% (95% confidence interval: 1.19%, 7.37%) increase in FeNO. The effect estimates were statistically significant only among males, elders, and those with body mass index ≥24 kg m‑2, a comorbidity, higher educational attainment, or moderate airflow limitation. This analysis demonstrated an independent effect of O x on respiratory inflammation, and suggested that a single metric O x might serve as a preferable indicator of atmospheric oxidative capacity in further air pollution epidemiological studies.

  7. Nitric Oxide Loaded Echogenic Liposomes for Nitric Oxide Delivery and Inhibition of Intimal Hyperplasia

    Science.gov (United States)

    Huang, Shao-Ling; Kee, Patrick H.; Kim, Hyunggun; Moody, Melanie R.; Chrzanowski, Stephen M.; MacDonald, Robert C.; McPherson, David D.

    2011-01-01

    Objective To develop a new bioactive gas delivery method using echogenic liposomes (ELIP) as the gas carrier. Background Nitric oxide (NO) is a bioactive gas with potent therapeutic effects. Bioavailability of NO by systemic delivery is low with potential systemic effects. Methods Liposomes containing phospholipids and cholesterol were prepared using a new freezing under pressure method. The encapsulation and release profile of NO from NO containing-ELIP (NO-ELIP) or a mixture of NO/Argon (NO/Ar-ELIP was studied. Uptake of NO from NO-ELIP by cultured vascular smooth muscle cells (VSMC) both in the absence and presence of hemoglobin was determined. The effect of NO-ELIP delivery to attenuate intimal hyperplasia in a balloon-injured artery was determined. Results Coencapsulation of NO with argon (Ar) enabled the adjustment the amount of encapsulated NO. A total of 10 µl of gas can be encapsulated into 1 mg liposomes. The release profile of NO from NO-ELIP demonstrated an initial rapid release followed by a slower release over 8 hours. Sixty-eight percent of cells remained viable when incubated with 80 µg/ml of NO/Ar-ELIP for 4 hours. NO delivery to VSMC using NO/Ar-ELIP was 7-fold higher than unencapsulated NO. NO/Ar-ELIP remained effective NO delivery to VSMC even in the presence of hemoglobin. Local NO-ELIP administration to balloon-injured carotid arteries attenuated the development of intimal hyperplasia and reduced arterial wall thickening by 41±9%. Conclusions Liposomes can protect and deliver a bioactive gas to target tissues with the potential for both visualization of gas delivery and controlled therapeutic gas release. PMID:19660697

  8. Nitric oxide promotes survival of cerebellar granule neurons cultured in vitro through the Akt pathway

    Institute of Scientific and Technical Information of China (English)

    Lin Wang; Mei Li; Lihua Zhou

    2011-01-01

    In this study, cerebellar granule neurons were used to examine the role of nitric oxide on cell survival. The N-methyl-D-aspartic acid receptor antagonist, MK-801, and the soluble guanylate cyclase antagonist, 1H-[1, 2, 4]oxadiazolo-[4, 3-a] quinoxalin-1-one, decreased cell viability, induced caspase-3, and decreased phosphorylated-Akt levels, suggesting that blockade of nitric oxide production promotes apoptosis of differentiating cerebellar granule neurons. After administration of sodium nitroprusside, an endogenous nitric oxide donor, cell viability recovered,caspase-3 expression was decreased, and phosphorylated-Akt levels increased. This study provides direct evidence that nitric oxide can sustain the survival of developing cerebellar granule neurons in vitro through the nitric oxide-Akt pathway. Moreover, endogenous nitric oxide exerts these effects in a cyclic guanosine monophosphate-dependent manner while exogenous nitric oxide does so in a cyclic guanosine monophosphate-independent manner.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  11. Refractory Oxide Coatings on Titanium for Nitric Acid Applications

    Science.gov (United States)

    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.

  12. Measurements of Fractional Exhaled Nitric Oxide in Pediatric Asthma

    Directory of Open Access Journals (Sweden)

    Youn-Soo Hahn

    2013-10-01

    Full Text Available Exhaled nitric oxide (NO has been extensively investigated as a noninvasive marker of airway inflammation in asthma. The increased NO expression induced by inflammatory mediators in airways can be monitored easily in exhaled air from asthmatic children. Based on the relationship between the increased NO expression and eosinophilic airway inflammation, fractional exhaled nitric oxide (FeNO measurements become an important adjunct for the evaluation of asthma. In addition, the availability of portable devices makes it possible to measure FeNO more easily and frequently in the routine pediatric practice. Despite various confounding factors affecting its levels, FeNO can be applicable in diagnosing asthma, monitoring treatment response, evaluating asthma control, and predicting asthma exacerbations. Thus, although pulmonary function tests are the standard tools for objective measurements of asthmatic control, FeNO can broaden the way of asthma monitoring and supplement standard clinical asthma care guidelines.

  13. Adrenoceptor-activated nitric oxide synthesis in salivary acinar cells

    DEFF Research Database (Denmark)

    Looms, Dagnia; Dissing, Steen; Tritsaris, Katerina;

    2000-01-01

    We investigated the cellular regulation of nitric oxide synthase (NOS) activity in isolated acinar cells from rat parotid and human labial salivary glands, using the newly developed fluorescent nitric oxide (NO) indicator, DAF-2. We found that sympathetic stimulation with norepinephrine (NE) caused...... a strong increase in NO synthesis that was not seen after parasympathetic stimulation with acetylcholine. In rat parotid acinar cells, we furthermore investigated to which extent the NOS activity was dependent on the intracellular free Ca2+ concentration ([Ca2+]i) by simultaneously measuring NO synthesis...... not cause significant NO synthesis. We furthermore found that activating adrenoceptors with NE causes synthesis of cGMP by activating a guanylyl cyclase, and that an enhanced [cGMP] evoked by use of caged cGMP causes Ca2+ release from internal stores. Thus, upon sympathetic stimulation, salivary gland acini...

  14. Measurement of arginine metabolites: regulators of nitric oxide metabolism.

    Science.gov (United States)

    Augustine, Molly S; Rogers, Lynette K

    2013-01-01

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

  15. INSULIN INDUCES NITRIC OXIDE PRODUCTION IN BOVINEAORTIC ENDOTHELIAL CELLS

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To examine the effects of insulin on cell proliferation, nitric oxide (NO) release and nitric oxide synthase (NOS) gene expression in bovine aortic endothelial cells ( BAEC ) . Methods The mi togenesis was assessed by MTT method; the products of NO in the culture media, by Griess reaction; and the levels of NOS mRNA in BAEC , by RT/PCR tech nique. Results BAEC were not responsive to the growth-promoting effects of insulin. Stimulation with insulin resulted a dose-dependent rise of NO in the culture supernatants 2h later, with a maximum at 12~24h and a decline at 24h. This rise was inhibited by an inhibitor of NOS (L-NAME). NOS mRNA increased slightly in BAEC without statistical significance. Conelu sion The study suggested that the insulin-induced NO release might be caused directly by NOS activation.

  16. Nitric oxide in female repro-ductive system

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    @@ Nitric oxide (NO), synthesized from L-arginine and oxygen by a family of enzymes known as nitric oxide synthase (NOS), is an effective and intercellular signal transduction molecule, and is ubiquitously present in vertebrates. To date, there are three distinct isoforms of NOS: neural NOS (nNOS), inducible NOS (iNOS), and endothelial NOS (eNOS). Among them, eNOS and nNOS, also called constitutive isoforms (cNOS), require calcium for activity, and are expressed constitutively in the physiological condition. The third isoforms, iNOS, whose activity is not dependent on calcium, are produced only in response to some stimulus, including cytokines and immune stimulating factors, etc.[1].

  17. Nitric oxide and coronary vascular endothelium adaptations in hypertension

    OpenAIRE

    Levy, Andrew S.; Justin CS Chung; Kroetsch, Jeffrey T; et al.,

    2009-01-01

    Andrew S Levy*, Justin CS Chung*, Jeffrey T Kroetsch*, James WE RushDepartment of Kinesiology, University of Waterloo, Waterloo, Ontario, Canada; *These authors contributed equally to this workAbstract: 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 compl...

  18. The clinical value of exhaled nitric oxide in asthma

    OpenAIRE

    Pisi, Roberta

    2012-01-01

    Bronchial asthma is an inflammatory disease and measurement of biomarkers in exhaled breath has recently become an attractive approach to non-invasively monitor airway inflammation. In bronchial asthma, increased fractional exhaled nitric oxide (FeNO) concentration in exhaled breath has been shown to reflect the extent of eosinophilic inflammation. Moreover, the increase of FeNO levels are suppressed by inhaled corticosteroids (ICS). Therefore, monitoring of FeNO is a useful marker of inf...

  19. Exhaled nitric oxide measurements: clinical application and interpretation

    OpenAIRE

    Taylor, D R; Pijnenburg, M W; Smith, A. D.

    2006-01-01

    The use of exhaled nitric oxide measurements (FEno) in clinical practice is now coming of age. There are a number of theoretical and practical factors which have brought this about. Firstly, FEno is a good surrogate marker for eosinophilic airway inflammation. High FEno levels may be used to distinguish eosinophilic from non‐eosinophilic pathologies. This information complements conventional pulmonary function testing in the assessment of patients with non‐specific respiratory symptoms. Secon...

  20. The effect of nitric oxide donors on human performance

    OpenAIRE

    Bescós García, Raúl

    2011-01-01

    [eng] Nitric oxide or nitrogen monoxide (NO) is a tiny free radical gas. The discovery of this intriguing molecule has revolutionized physiology and pharmacology research during the last 20 years. Currently, it is known that NO is endogenously synthesized by several molecules and tissues via two pathways: the synthase-dependent pathway and the synthase-independent pathway. In the first, the amino acid L-arginine is the main donnor of NO synthesis. In the second, inorganic nitrate is the main ...

  1. Protein kinase D activity controls endothelial nitric oxide synthesis

    OpenAIRE

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

    2014-01-01

    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 ...

  2. Nitric oxide-cyclic GMP signaling in stem cell differentiation

    OpenAIRE

    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 pat...

  3. EXOGENOUS NITRIC OXIDE PREVENTS CARDIOVASCULAR COLLAPSE DURING HEMORRHAGIC SHOCK

    OpenAIRE

    Nachuraju, Parimala; Friedman, Adam J.; Friedman, Joel M.; Cabrales, Pedro

    2011-01-01

    This study investigated the systemic and microvascular hemodynamic changes related to increased nitric oxide (NO) availability following significant hemorrhage, made available by administration of NO releasing nanoparticles (NO-nps). Hemodynamic responses to hemorrhagic shock were studied in the hamster window chamber. Acute hemorrhage was induced by arterial controlled bleeding of 50% of blood volume, and the resulting hemodynamic parameters were followed over 90 min. Exogenous NO was admini...

  4. A Dirofilaria immitis Polyprotein Up-Regulates Nitric Oxide Production

    Science.gov (United States)

    Tezuka, Hiroyuki; Imai, Shinjiro; Tsukidate, Setsuko; Fujita, Koichiro

    2002-01-01

    We investigated the effect of recombinant Dirofilaria immitis polyprotein (rDiAg) on nitric oxide (NO) production by peritoneal macrophages. rDiAg induced NO production by macrophages from wild-type and lipopolysaccharide-hyporesponsive C3H/HeJ, but not CD40−/−, mice. These results suggest that CD40 is involved in rDiAg-driven NO production by murine macrophages. PMID:12183583

  5. Nitric Oxide and eNOS Gene in Essential Hypertension

    OpenAIRE

    Kamna Srivastava; Nibhriti Das; Shubhangi Arora

    2009-01-01

    Background: Currently hypertension grips around 25% of the entire world population. More than 90% of the hypertensive patients suffer from essential hypertension. In Asian Indians hypertension is the predominant risk factor for Coronary Artery Disease among others. Nitric Oxide (NO) is synonymous with endothelial derived relaxation factor. Acting via cGMP (cyclic guanosine monophosphate) it causes smooth muscle relaxation, prevents platelet aggregation and acts as an anti-inflammatory agent. ...

  6. Nitric oxide produced by ultraviolet-irradiated keratinocytes stimulates melanogenesis.

    OpenAIRE

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

    1997-01-01

    Ultraviolet (UV) radiation is the main physiological stimulus for human skin pigmentation. Within the epidermal-melanin unit, melanocytes synthesize and transfer melanin to the surrounding keratinocytes. Keratinocytes produce paracrine factors that affect melanocyte proliferation, dendricity, and melanin synthesis. In this report, we show that normal human keratinocytes secrete nitric oxide (NO) in response to UVA and UVB radiation, and we demonstrate that the constitutive isoform of keratino...

  7. Protective role of nitric oxide in ocular toxoplasmosis.

    OpenAIRE

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

    1996-01-01

    AIMS: To evaluate the role of nitric oxide (NO) in ocular involvement during systemic toxoplasmosis. METHODS: C57B1/6 mice were infected with Toxoplasma gondii strain ME49. The synthesis of NO was inhibited by an intraperitoneal injection of aminoguanidine every 8 hours, starting on the day of infection. Control infected mice received phosphate buffered saline vehicle alone. After 14 days, the ocular lesions were evaluated by histopathological examination. The expression of NO synthase induce...

  8. A Cellular Model for Screening Neuronal Nitric Oxide Synthase Inhibitors

    OpenAIRE

    Fang, Jianguo; Silverman, Richard B.

    2009-01-01

    Nitric oxide synthase (NOS) inhibitors are potential drug candidates because it has been well demonstrated that excessive production of NO critically contributes to a range of diseases. Most inhibitors have been screened in vitro using recombinant enzymes, leading to the discovery of a variety of potent compounds. To make inhibition studies more physiologically relevant and bridge the gap between the in vitro assay and in vivo studies, we report here a cellular model for screening NOS inhibit...

  9. Nitric oxide inhibits cutaneous vasoconstriction to exogenous norepinephrine

    OpenAIRE

    Shibasaki, Manabu; David A Low; Davis, Scott L.; Crandall, Craig G.

    2008-01-01

    Previously, we found that nitric oxide (NO) inhibits cutaneous vasoconstrictor responsiveness evoked by whole body cooling, as well as an orthostatic stress in the heat-stressed human (Shibasaki M, Durand S, Davis SL, Cui J, Low DA, Keller DM, Crandall CG. J Physiol 585: 627–634, 2007). However, it remains unknown whether this response occurs via NO acting through presynaptic or postsynaptic mechanisms. The aim of this study was to test the hypothesis that NO is capable of impairing cutaneous...

  10. Modeling of nitric oxide emissions from temperate agricultural ecosystems.

    OpenAIRE

    Rolland, Marie-Noëlle; Gabrielle, Benoît; Laville, Patricia; Serça, Dominique; Cortinovis, Jérôme; Larmanou, Eric; Lehuger, Simon; Cellier, Pierre

    2006-01-01

    48 p. Arable soils are a significant source of nitric oxide (NO), most of which is derived from nitrogen fertilizers. Precise estimates of NO emissions from these soils are thus essential to devise strategies to mitigate the impact of agriculture on tropospheric ozone regulation. This paper presents the implementation of a soil NO emissions submodel within the environmentally-orientated soil crop model, CERES-EGC. The submodel simulates the NO production via nitrification pathway, as modul...

  11. Opposite actions of nitric oxide on cholinergic synapses: which pathways?

    OpenAIRE

    Mothet, J P; Fossier, P; Tauc, L; Baux, G

    1996-01-01

    Nitric oxide (NO) produced opposite effects on acetylcholine (ACh) release in identified neuroneuronal Aplysia synapses depending on the excitatory or the inhibitory nature of the synapse. Extracellular application of the NO donor, SIN-1, depressed the inhibitory postsynaptic currents (IPSCs) and enhanced the excitatory postsynaptic currents (EPSCs) evoked by presynaptic action potentials (1/60 Hz). Application of a membrane-permeant cGMP analog mimicked the effect of SIN-1 suggesting the par...

  12. Nitric oxide inhibition sustains vasopressin-induced vasoconstriction.

    OpenAIRE

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

    1995-01-01

    Hepatic parenchymal vasoconstriction increases cytotoxic drug uptake into hepatic metastases by increasing the tumour to liver blood flow ratio. Prolonged infusion of the vasoconstrictor vasopressin does not result in sustained vasoconstriction, and this may limit the benefit of vasopressin in infusional chemotherapy. We have assessed whether loss of vasopressin-induced vasoconstriction is mediated by nitric oxide. Hepatic and tumour blood flow were continuously monitored, in an animal hepati...

  13. Nitric oxide metabolites in cystic fibrosis lung disease

    OpenAIRE

    Grasemann, H; Ioannidis, I.; Tomkiewicz, R; de Groot, H.; Rubin, B; Ratjen, F

    1998-01-01

    Although the activity of nitric oxide (NO) synthases are increased in lung tissue of patients with cystic fibrosis, the concentrations of nasal and exhaled NO have recently been found to be decreased in cystic fibrosis. This could either be due to reduced NO formation or metabolism of NO within airway fluids. In this study, the stable NO metabolites, nitrate and nitrite, were determined in the saliva and sputum of 18 stable cystic fibrosis patients, 21 cystic fibrosis pat...

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

    OpenAIRE

    Luciano eFreschi

    2013-01-01

    Nitric oxide (NO) is currently considered a ubiquitous signal in plant systems, playing significant roles in a wide range of plant 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 degre...

  15. Interactions between nitric oxide and plant hormones in aluminum tolerance

    OpenAIRE

    He, Huyi; He, Longfei; Gu, Minghua

    2012-01-01

    Nitric oxide (NO) is involved, together with plant hormones, in the adaptation to Al stress in plants. However, the mechanism by which NO and plant hormones interplay to improve Al tolerance are still unclear. We have recently shown that patterns of plant hormones alteration differ between rye and wheat under Al stress. NO may enhance Al tolerance by regulating hormonal equilibrium in plants, as a regulator of plant hormones signaling. In this paper, some unsolved issues are discussed based o...

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

    OpenAIRE

    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...

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

    OpenAIRE

    Gammoh, Omar Salem; 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. Result...

  18. Application of a Nitric Oxide Sensor in Biomedicine

    Directory of Open Access Journals (Sweden)

    Carlota Saldanha

    2014-02-01

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

  19. Reversible suppression of nitric oxide system in essential hypertension

    OpenAIRE

    M Chandra; Maurya, D. R.; Kumar, S; Basara, H.; Ghatak, A.; Tekwani, B. L.; Kaur, G.; Misra, M. K.

    2003-01-01

    Despite enormous research in the field of hypertension, its pathophysiology still remains largely unresolved and appears to be multifactorial. In the present communication, we have analyzed the status of nitric oxide (NO) in the patients with essential hypertension and age matched controls. We have found that the levels of NO are lowered in essential hypertension. The normalization of blood pressure by administration of antihypertensive therapy causes rise in the NO level indicating that pert...

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

    OpenAIRE

    Niu, Hejingying; 牛何晶英.

    2013-01-01

    Nitric oxide (NO) is one of the most important air pollutants in atmosphere mainly emitted from combustion exhaust gas. In this research, a biotrickling filter was designed and operated to remove this pollutant from an air stream using bacteria extracted from the sewage sludge of a municipal sewage-treatment plant. The bacteria were cultured and enriched by either petri dish’s cultivation or liquid cultivation. The adsorption capacity of the ceramic material, which was used as the packing ma...

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

    OpenAIRE

    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 ...

  2. Nitric oxide availability in deeply hypoxic crucian carp

    DEFF Research Database (Denmark)

    Hansen, Marie Niemann; Gerber, Lucie; Jensen, Frank Bo

    2016-01-01

    Recent research suggest that anoxia-tolerant fish transfer extracellular nitrite into the tissues, where it is used for nitric oxide (NO) generation, iron-nitrosylation and S-nitrosation of proteins as part of the cytoprotective response towards prolonged oxygen lack and subsequent re-oxygenation......Recent research suggest that anoxia-tolerant fish transfer extracellular nitrite into the tissues, where it is used for nitric oxide (NO) generation, iron-nitrosylation and S-nitrosation of proteins as part of the cytoprotective response towards prolonged oxygen lack and subsequent re......(yl)ated compounds either increased or stayed constant, depending on O2 level and tissue type. Nitrite was notably increased in the heart during deep hypoxia, and the increase was amplified by elevated ambient [nitrite]. Raised nitrite also increased gill [nitrite] and decreased mRNA expression of an inducible...... nitric oxide synthase-2 gene variant. The data support that ambient nitrite is taken up across the gills to be distributed via the blood to tissues, particularly the heart, where it assists in cytoprotection and other functions. Cardiac nitrite was not elevated in acutely exposed fish, revealing...

  3. A Novel Amperometric Nitric Oxide Sensor Based on Polythionine /Nation Modified Glassy Carbon Electrode

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    A novel amperometric sensor for the determination of nitric oxide was developed by coating polythionine / nafion on a glassy carbon electrode. This sensor exhibited a great enhancement to the oxidation of nitric oxide. The oxidation peak currents were linear to the concentration of nitric oxide over the wide range from 3.6×10-7 to 6.8×10-5 mol. L-1, and the detection limit was 7.2×10-8 mol. L-1. Experimental results showed that this nitric oxide sensor possessed excellent selectivity and longer stability. NO releasing from rat kidney was monitored by this sensor.

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

    Science.gov (United States)

    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.

  5. Do endogenous opioids and nitric oxide participate in the anticonvulsant action of dipyrone?

    Directory of Open Access Journals (Sweden)

    G.M.L. Reis

    2003-09-01

    Full Text Available It was previously reported that systemic administration of dipyrone inhibited the tonic component of generalized tonic-clonic seizures in both the electroshock and the audiogenic seizure models. The aim of the present study was to investigate the mechanisms involved in the anticonvulsant action of dipyrone by assessing the role of nitric oxide and opioids in the electroshock (female 60- to 90-day-old Wistar rats, N = 5-11 and audiogenic seizure (female 60- to 90-day-old Wistar audiogenic rats, N = 5-11 models of epilepsy. Naloxone (5 mg/kg, sc significantly reversed the anticonvulsant effect of dipyrone in rats submitted to the induction of audiogenic seizures (ANOVA/Bonferroni's test, suggesting the involvement of opioid peptides in this action. In the electroshock model no reversal of the anticonvulsant effect of dipyrone by naloxone (5 mg/kg, sc was demonstrable. The acute (120 mg/kg, ip and chronic (25 mg/kg, ip, twice a day/4 days administration of L-NOARG did not reverse the anticonvulsant action of dipyrone in the audiogenic seizure model, suggesting that the nitric oxide pathway does not participate in such effect. Indomethacin (10, 20 and 30 mg/kg, ip used for comparison had no anticonvulsant effect in the audiogenic seizure model. In conclusion, opioid peptides but not nitric oxide seem to be involved in the anticonvulsant action of dipyrone in audiogenic seizures.

  6. Induction of insulin secretion in engineered liver cells by nitric oxide

    Directory of Open Access Journals (Sweden)

    Özcan Sabire

    2007-10-01

    Full Text Available Abstract Background Type 1 Diabetes Mellitus results from an autoimmune destruction of the pancreatic beta cells, which produce insulin. The lack of insulin leads to chronic hyperglycemia and secondary complications, such as cardiovascular disease. The currently approved clinical treatments for diabetes mellitus often fail to achieve sustained and optimal glycemic control. Therefore, there is a great interest in the development of surrogate beta cells as a treatment for type 1 diabetes. Normally, pancreatic beta cells produce and secrete insulin only in response to increased blood glucose levels. However in many cases, insulin secretion from non-beta cells engineered to produce insulin occurs in a glucose-independent manner. In the present study we engineered liver cells to produce and secrete insulin and insulin secretion can be stimulated via the nitric oxide pathway. Results Expression of either human insulin or the beta cell specific transcription factors PDX-1, NeuroD1 and MafA in the Hepa1-6 cell line or primary liver cells via adenoviral gene transfer, results in production and secretion of insulin. Although, the secretion of insulin is not significantly increased in response to high glucose, treatment of these engineered liver cells with L-arginine stimulates insulin secretion up to three-fold. This L-arginine-mediated insulin release is dependent on the production of nitric oxide. Conclusion Liver cells can be engineered to produce insulin and insulin secretion can be induced by treatment with L-arginine via the production of nitric oxide.

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

    Science.gov (United States)

    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.

  8. The role of nitrite in nitric oxide homeostasis

    DEFF Research Database (Denmark)

    Jensen, Frank Bo

    2009-01-01

    Nitrite is endogenously produced as an oxidative metabolite of nitric oxide, but it also functions as a NO donor that can be activated by a number of cellular proteins under hypoxic conditions. This article discusses the physiological role of nitrite and nitrite-derived NO in blood flow regulation...... mechanisms. Nitrite reduction to NO provides cytoprotection in tissues during ischemia-reperfusion events by inhibiting mitochondrial respiration and limiting reactive oxygen species. It is argued that the study of hypoxia-tolerant lower vertebrates and diving mammals may help evaluate mechanisms and a full...

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

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Wenzhen; Yang, Bingwu; Fu, Huiling; Ma, Long; Liu, Tingting; Chai, Rongfei; Zheng, Zhaodi [Shandong Provincial Key Laboratory of Animal Resistant Biology, School of Life Sciences, Shandong Normal University, Jinan 250014 (China); Zhang, Qunye, E-mail: wz.zhangqy@sdu.edu.cn [Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, Shandong (China); Li, Guorong, E-mail: grli@sdnu.edu.cn [Shandong Provincial Key Laboratory of Animal Resistant Biology, School of Life Sciences, Shandong Normal University, Jinan 250014 (China)

    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.

  10. Role of Nitric Oxide and Nitric Oxide Synthases in Ischemia-reperfusion Injury in Rat Organotypic Hippocampus Slice

    Institute of Scientific and Technical Information of China (English)

    MENG Xianfang; SHI Jing; LIU Xiaochun; ZHANG Jing; SUN Ning

    2005-01-01

    To investigate the effects of ischemia-reperfusion on the levels of nitric oxide and nitric oxide synthase isoforms (nNOS and iNOS), rat organotypic hippocampus slice were cultured in vitro and subjected to ischemia by oxygen glucose deprivation (OGD) for 30 min and then placed in the normal culture condition. The ischemia-reperfusion produced a time-dependent increase in nitrite levels in the culture medium. Reverse transcriptional-polymerase chain reaction showed augmented levels of mRNA for both nNOS and iNOS when compared with control at 12 h and remained increase at 36 h after OGD (P<0.05). The protein levels of both nitric oxide synthase isoforms increased significantly as determined by Western Blot. OGD also caused neurotoxicity in this model as revealed by the elevated lactate dehydrogenase (LDH) efflux into the incubation solution. The results suggest that organotypic hippocampus slice is a useful model in studying ischemia-reperfusion brain injury. NO and NOS may play a critical role in the ischemia-reperfusion brain damage in vitro.

  11. Role of neuronal nitric oxide synthase and inducible nitric oxide synthase in intestinal injury in neonatal rats

    Institute of Scientific and Technical Information of China (English)

    Hui LU; Bing Zhu; Xin-Dong Xue

    2006-01-01

    AIM: To investigate the dynamic change and role of neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) in neonatal rat with intestinal injury and to define whether necrotizing enterocolitis (NEC) is associated with the levels of nitric oxide synthase (NOS) in the mucosa of the affected intestine tissue.METHODS: Wistar rats less than 24 h in age received an intraperitoneal injection with 5 mg/kg lipopolysaccharide (LPS). Ileum tissues were collected at 1, 3, 6, 12 and 24 h following LPS challenge for histological evaluation of NEC and for measurements of nNOS and iNOS. The correlation between the degree of intestinal injury and levels of NOS was determined.RESULTS: The LPS-injected pups showed a significant increase in injury scores versus the control. The expression of nNOS protein and mRNA was diminished after LPS injection. There was a negative significant correlation between the nNOS protein and the grade of median intestinal injury within 24 h. The expression of iNOS protein and mRNA was significantly increased in the peak of intestinal injury.CONCLUSION: nNOS and iNOS play different roles in LPS-induced intestinal injury. Caution should be exerted concerning potential therapeutic uses of NOS inhibitors in NEC.

  12. The plasma level of nitric oxide and the expression of inducible nitric oxidesynthase in human hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Run Xuan Shao; Jiang Bin Wang; Jia He Guo

    2000-01-01

    AIM To study the relationship between nitric oxide (NO), nitric oxide synthase (NOS) and humanhepatocellular carcinoma (HCC).METHODS Plsama NO2-/NO3- was measured by Griess reaction in 122 patients with chronic hepatitis(CH) and compensated liver cirrhosis (LC), among which 62 patients were complicated with HCC(CH = 28, LC = 34), and the rest 60 patients were not (CH = 29, LC = 31). Thirty healthy persons served asnormal controls (NC). There were no prominent differences among the groups in sex, age and the ratio ofCH to LC. The expression of inducible nitric oxide synthase (iNOS) in HCC (n = 40), CH (n = 30) and LC(n = 30) samples obtained from liver biopsy or operation was compared with that in normal liver tissues byusing immunohistochemistry. Ten normal liver tissue samples obtained from liver operation served as normalcontrols. The samples were fixed in formalin and embeded in paraffin. Anti-iNOS antibody (Santacruzcompany) was served as antibody-Ⅰ in immunohistochemical assay of iNOS in tissue.RESULTS Plasma NO2-/NO3- level in normal was 11.5 μmol/L±4.2μmol/L. The plasma level ofNO2 /NO3- in CH (58.6±17.4 μmol/L) and LC (38.7±10.6μmol/L) accompanied with HCC wasnotably higher than in those patients without HCC (CH: 24.8±9.4 μmol/L; LC: 22.3±8.7μmol/L,t=2.901, 2.756, P<0.01). Plasma NO2-/NO3- level in HCC accompanied with CH was significantlyhigher than in those accompanied with LC ( t = 2.216, P<0.05). Positive rate of iNOS in HCC, CH and LCwas 95%, 93% and 57% respectively. iNOS was not expressed in normal liver tissues. The expression level ofiNOS in HCC (χ2=17.4, P<0.001) and CH (χ2=11.64, P<0.025) was much higher than in LC.CONCLUSION Plasma NO2 / NO3- level significantly increased in patients with HCC and theimmunohistochemical staining of iNOS was positive. This suggests that the liver secrets NO in the higherlevel may participate in the carcinogenesis and progression of HCC.

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

    Science.gov (United States)

    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.

  14. Asymmetric dimethylarginine, oxidative stress, and vascular nitric oxide synthase in essential hypertension

    DEFF Research Database (Denmark)

    Wang, Dan; Strandgaard, Svend; Iversen, Jens;

    2009-01-01

    We reported impaired endothelium-derived relaxation factor/nitric oxide (EDRF/NO) responses and constitutive nitric oxide synthase (cNOS) activity in subcutaneous vessels dissected from patients with essential hypertension (n = 9) compared with normal controls (n = 10). We now test the hypothesis...... and hypertensive subjects, the individual values for plasma levels of ADMA and HODE were both significantly (P blood pressure. In conclusion, elevated levels of ADMA and oxidative stress in a group of hypertensive...... patients could contribute to the associated microvascular endothelial dysfunction and elevated blood pressure....

  15. Dynamics of Nitric Oxide and Nitrous Oxide Emission during Nitrogen Conversion Processes

    NARCIS (Netherlands)

    Kampschreur, M.J.

    2010-01-01

    Nitric oxide (NO) and nitrous oxide (N2O) emissions can be a serious threat to the environment. Rising levels of N2O in the atmosphere contribute to global warming and destruction of the ozone layer. This thesis describes an investigation on the emission of NO and N2O during nitrogen conversion proc

  16. Oxidative aromatization of 3,5-disubstituted 2-isoxazolines by nitric oxide

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    3,5-Disubstituted 2-isoxazolines were oxidized to corresponding isoxazoles by nitric oxide in dichloromethane. The reaction more likely occurred via a one-electron transfer process.(C) 2007 Long Min Wu. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

  17. Nitric oxide modulates interleukin-2-induced proliferation in CTLL-2 cells

    OpenAIRE

    Padrón, J.; Glaría, L.; Martinez, O.; Torres, M.; Lopez, E.; Delgado, R.; Caveda, L.; Rojas, A.

    1996-01-01

    The role of the L-arginine–nitric oxide metabolic pathway was explored for interleukin-2-induced proliferation in the cytotoxic T lymphocyte clone CTLL-2. Specific inhibition of nitric oxide synthase significantly diminished, in a concentration-dependent manner, 3H-thymidine uptake of CTLL-2 cells in response to different concentrations of interleukin 2. Withdrawal of L-arginine from culture medium resulted as potent as the higher inhibition obtained when blocking nitric oxide synthase with L...

  18. Histochemical study of the nitric oxide synthase activity in experimental trichinellosis.

    Science.gov (United States)

    Hadaś, E; Gustowska, L; Boczoń, K; Janczewska, D

    1999-01-01

    Nitric oxide plays a critical role in a variety of biological activities. It has been nicknamed a "killer" and "mediator" due to its toxic and signalling properties. Apart from its regular physiological function, nitric oxide indirectly participates in infectious diseases. Our report seems to be the first presentation of the nitric oxide synthase participation in the host biochemical defence mechanisms and in morphological transformation of muscle cells in trichinellosis. PMID:16883715

  19. Inducible nitric-oxide synthase attenuates vasopressin-dependent Ca2+ signaling in rat hepatocytes

    OpenAIRE

    Patel, S.; Gaspers, L. D.; Boucherie, S.; Memin, E.; Stellato, K. A.; Guillon, G; Combettes, L; Thomas, A P

    2002-01-01

    Increases in both Ca2+ and nitric oxide levels are vital for a variety of cellular processes; however, the interaction between these two crucial messengers is not fully understood. Here, we demonstrate that expression of inducible nitric-oxide synthase in hepatocytes, in response to inflammatory mediators, dramatically attenuates Ca2+ signaling by the inositol 1,4,5-trisphosphate-forming hormone, vasopressin. The inhibitory effects of induction were reversed by nitric oxide inhibitors and mim...

  20. Immunohistochemical localization of endothelial nitric oxide synthase in endometrial tissue of women with unexplained infertility

    OpenAIRE

    Tohid Najafi; Marefat Ghaffari Novin; Jalil Pakravesh; Khadijeh Foghi; Fatemeh Fadayi; Gelareh Rahimi

    2012-01-01

    Background: Nitric oxide (NO) is a molecule that incorporates in many physiological processes of female reproductive system. Recent studies suggested the possible role of endothelial isoform of nitric oxide synthase (eNOS) enzyme in female infertility. Objective: The aim of this study is to evaluate the expression of endothelial nitric oxide synthase in endometrial tissue of women with unexplained infertility. Materials and Methods: In this case-control study a total of 18 endometrial tissues...

  1. Synthesis and antitumor activity of nitric oxide releasing derivatives of AT1 antagonist

    Institute of Scientific and Technical Information of China (English)

    Yan Chun Zhang; Jin Pei Zhou; Xiao Ming Wu; Wei Hong Pan

    2009-01-01

    A series of novel nitric oxide-donating derivatives (7a-e, 8a-e) were synthesized by coupling furoxan and nitric oxide with irbesartan analogue and their cytotoxicity against BEL7402 cells in vitro were evaluated by MTI" method. It was found that 8c exhibits the most cytotoxic activities with IC.so value of 12.5 umol/L. The hybrids of ATI antagonist and nitric oxide donor appear to have beneficial effects on antitumor.

  2. The Effect of Acute Fluoride Poisoning on Nitric Oxide and Methemoglobin Formation in the Guinea pig

    OpenAIRE

    ŞİRELİ, Meltem

    2004-01-01

    To study the effect of acute fluoride poisoning on nitric oxide and methemoglobin formation, 250 mg/kg bw sodium fluoride was applied alone and verapamil was applied together with fluoride. Blood nitric oxide (Griess reaction) and calcium levels; hemoglobin, methemoglobin and hematocrit values; and erythrocyte counts were determined and compared with those of the controls. After the fluoride application it was found that there was a relative relationship between the increase in nitric oxide a...

  3. The Expression of Inducible Nitric Oxide Synthase in Gingival Tissues of Chronic Periodontitis Patients%慢性牙周炎患者牙龈组织内诱导型一氧化氮合酶表达的研究

    Institute of Scientific and Technical Information of China (English)

    龚斌; 徐静舒; 李启艳; 张玉皓

    2012-01-01

    目的:研究牙周健康者和慢性牙周炎患者牙龈组织中诱导型一氧化氮合酶的表达强度,探讨一氧化氮在牙周病发病过程中的作用.方法:选择牙周健康组、慢性牙周炎活动期组,慢性牙周炎静止期组各20例,采取免疫组织化学的方法染色,光镜下观察牙龈组织内诱导型一氧化氮合酶的表达强度.结果:慢性牙周炎时牙龈组织中诱导型一氧化氮合酶主要在鳞状上皮和间质组织的细胞胞浆中阳性表达,正常组表达强度弱于慢性牙周炎静止期组和活动期组,慢性牙周炎静止期组表达强度弱于慢性牙周炎活动期组.结论:一氧化氮参与了慢性牙周炎的发生和发展过程,牙龈组织中诱导型一氧化氮合酶的表达强度与慢性牙周炎的炎症程度密切相关.%Objective: To evaluate the expression of inducible nitric oxide synthase (iNOS) in gingival tissues of periodontally healthy individuals and chronic periodontitis patients; and to study the possible role of Nitric Oxide (NO) in the initiation and progression of periodontal disease. Methods: Twenty patients with active chronic periodontitis, 20 patients with inactive chronic periodontitis, and 20 periodontally healthy subjects were recruited in this study. Immunohistochemistry was performed to evaluate iNOS expression in gingival tissues under the microscope. Results: The expression of iNOS was mainly observed in epithelial cells and inflammatory cells in connective tissue. The expression level in control group was lower than that in chronic periodontitis groups, which include active and inactive groups. Furthermore, the expression in inactive chronic periodontitis group was lower than that in active group. Conclusion: NO plays an important role in the initiation and progression of chronic periodontal disease. The iNOS expression in gingival tissue closely related with the degree of inflammation.

  4. Novel methods of measuring nitric oxide and nitrite concentrations using cobinamide and cobalamin

    OpenAIRE

    Duan, Kailin Catherine

    2012-01-01

    Nitric oxide (NO) is an important signaling molecule produced by isoforms of nitric oxide synthase in mammals. Methods of measuring NO must take into consideration the low concentrations (nanomolar to micromolar) at which it is found in the body. We developed a novel method of direct nitric oxide measurement by measuring the absorbance change of the binding of nitric oxide to cobinamide(II) (Cbi), a vitamin B12 analogue. The absorbance values of NO-Cbi change linearly at 366 nm and 469 nm as ...

  5. Nanomaterials-based electrochemical sensors for nitric oxide

    International Nuclear Information System (INIS)

    Electrochemical sensing has been demonstrated to represent an efficient way to quantify nitric oxide (NO) in challenging physiological environments. A sensing interface based on nanomaterials opens up new opportunities and broader prospects for electrochemical NO sensors. This review (with 141 refs.) gives a general view of recent advances in the development of electrochemical sensors based on nanomaterials. It is subdivided into sections on (i) carbon derived nanomaterials (such as carbon nanotubes, graphenes, fullerenes), (ii) metal nanoparticles (including gold, platinum and other metallic nanoparticles); (iii) semiconductor metal oxide nanomaterials (including the oxides of titanium, aluminum, iron, and ruthenium); and finally (iv) nanocomposites (such as those formed from carbon nanomaterials with nanoparticles of gold, platinum, NiO or TiO2). The various strategies are discussed, and the advances of using nanomaterials and the trends in NO sensor technology are outlooked in the final section. (author)

  6. Nitric oxide and thermogenesis--challenge in molecular cell physiology.

    Science.gov (United States)

    Otasevic, Vesna; Korac, Aleksandra; Buzadzic, Biljana; Stancic, Ana; Jankovic, Aleksandra; Korac, Bato

    2011-01-01

    Only recently we can link thermogenesis, mitochondria, nitric oxide, and redox regulation in biochemical terms. Currently, we are discussing these processes from the aspect of fundamental principles of molecular physiology. Thus, the present article highlights both cell physiology and the principles of the maintenance of energy homeostasis in organisms. Energy homeostasis means much more than simple combustion; adipose tissues at this point of evolution development are related to a broad spectrum of metabolic disturbances and all aspects of cellular remodeling (i.e. structural, metabolic and endocrine changes). Therefore, this paper addresses not only thermogenesis but also energy homeostasis, oxidative phosphorylation and ATP production, proliferation and differentiation of brown adipocytes, their life and death, mitochondriogenesis and angiogenesis. These processes will be united by molecular players of oxidation/reduction reactions, thus creating the principles based on the redox regulation. PMID:21622264

  7. Changes of nitric oxide synthase and cyclic guanosine monophosphate in form deprivation myopia in guinea pigs

    Institute of Scientific and Technical Information of China (English)

    WU Jie; LIU Qiong; YANG Xiao; YANG Hui; WANG Xin-mei; ZENG Jun-wen

    2007-01-01

    Background The form deprivation(FD)reduces spatial contrasts and induces myopia. Nitric oxide and cyclic guanosine monophosphate(cGMP)are involved in visual signal transmission.This study investigated changes in nitric oxide synthase(NOS)activity and cGMP concentration in ocular tissues in acute and chronic form deprivation myopia.Methods Guinea pigs had one eye covered by translucent glass for 7,14 or 21 days.Untreated litter mates were used as controls.NOS activity and cGMP concentrations in the retinal,choroidal and scleral tissues of FD eyes and controleyes were analyzed by radioimmunoassay after various durations of FD.The expression of NOS subtypes was identified by immunohistochemistry.Results Myopia was successfully induced in FD eyes after 14 days.Compared with control groups,the retinal NOS activity and cGMP concentrations in the FD eyes significantly increased after 14 and 21 days while the retinal NOS activity in the FD eyes was transiently suppressed by 7 days of FD.The NOS activity and cGMP concentrations of choroid and sclera in the FD eyes were higher than in the control groups at 21 days.The three isoenzymes of nitric oxide synthase were detected in the ocular tissues of guinea pigs.Conclusions The NOS activity and cGMP concentrations were upregulated after chronic FD and the retinal NOS activity was transiently suppressed at acute FD.The function of elevated NOS activity may be mediated by cGMP.

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

    Energy Technology Data Exchange (ETDEWEB)

    Grimes, Travis Shane [Idaho National Lab. (INL), Idaho Falls, ID (United States); Mincher, Bruce Jay [Idaho National Lab. (INL), Idaho Falls, ID (United States); Schmitt, Nicholas C [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    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.

  9. Nitric Oxide is Protective Against Mercury Induced Depression

    Directory of Open Access Journals (Sweden)

    Arezo Nahavandi

    2010-08-01

    Full Text Available A B S T R A C T Introduction: Mercury is the second most metal pollutant in the world and has the potential to induce many pathologic conditions, especially in nervous system, such as depression. Here we tried to find out if nitric oxide has any possible role in the pathophysiology of depression induced by this metal. Although the role of nitric oxide has been shown in mood control, here we use specific doses of nitric oxide inducer and/or inhibitors which had no effect on normal rats. Methods: 120 male wistar rats weighting 200-250 gram were divided into two main groups: control and methyl mercury(MM treated. Each main group was divided into four different sub-goups: Saline, L-Arginine, L-Name or 7-nitroindazole (7-NI respectively. The duration of taking MM or saline was daily for 15 days for both. After the 15th injection a forced swimming test was done. This test shows behavioral immobility (BI or latency of attempt to escape (LAE, as a depression indicator. Results: Our study showed that low dose L-arginine is protective against MM induced depression as it could turn behavioral immobility (BI to normal levels in groups taking MM plus L-Arginine, while in group taking just MM, BI was much longer showing the intensity of depression. L-Name and 7-NI did aggravated depression in MM groups but not control ones, on the other hand just in the case of 7-NI the result was significant. Discussion: Our results showed 1 MM could induce depression in rat 2 L-Arginine could improve depression to normal situation in MM group, while in control group has no effec 3 7-NI, a selective nNOS inhibitor can aggravate mental depression in intoxicated rats. These results showed the important role of nNOS in protection against MM induced depression.

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

    Science.gov (United States)

    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?

  11. Functional Inducible Nitric Oxide Synthase Gene Variants Associate With Hypertension

    OpenAIRE

    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 heal...

  12. Nitric Oxide Signaling in Plant Responses to Abiotic Stresses

    Institute of Scientific and Technical Information of China (English)

    Weihua Qiao; LiuMin Fan

    2008-01-01

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

  13. Nitric Oxide Manipulation: A Therapeutic Target for Peripheral Arterial Disease?

    Directory of Open Access Journals (Sweden)

    Gareth Williams

    2012-01-01

    Full Text Available Peripheral Arterial Disease (PAD is a cause of significant morbidity and mortality in the Western world. Risk factor modification and endovascular and surgical revascularisation are the main treatment options at present. However, a significant number of patients still require major amputation. There is evidence that nitric oxide (NO and its endogenous inhibitor asymmetric dimethylarginine (ADMA play significant roles in the pathophysiology of PAD. This paper reviews experimental work implicating the ADMA-DDAH-NO pathway in PAD, focussing on both the vascular dysfunction and effects within the ischaemic muscle, and examines the potential of manipulating this pathway as a novel adjunct therapy in PAD.

  14. H2S regulation of nitric oxide metabolism

    Science.gov (United States)

    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

  15. Nasal airway nitric oxide : Methodological aspects and influence of inflammation

    OpenAIRE

    Palm, Jörgen

    2004-01-01

    Nitric oxide (NO) is an endogenously formed free radical gas involved in numerous biological processes. In 1991 NO was discovered to be present in exhaled air of humans. Soon after, it was reported that the largest amounts of NO were found in the upper airways, and that the levels of NO were increased in the lower airways of patients with asthma. The high levels of NO in the nasal region are believed to be involved in functions as various as primary host defence, including k...

  16. Localization of nitric oxide synthase in human skeletal muscle

    DEFF Research Database (Denmark)

    Frandsen, Ulrik; Lopez-Figueroa, M.; Hellsten, Ylva

    1996-01-01

    cellular compartments and suggest that NO may have specific actions in relation to its site of production. The localization of type I NO synthase in the vicinity of mitochondria supports a specific action of NO on mitochondrial respiration, whereas the localization of type III NO synthase in vascular......The present study investigated the cellular localization of the neuronal type I and endothelial type III nitric oxide synthase in human skeletal muscle. Type I NO synthase immunoreactivity was found in the sarcolemma and the cytoplasm of all muscle fibres. Stronger immunoreactivity was expressed...

  17. Acute right heart syndrome: Rescue treatment with inhaled nitric oxide

    Directory of Open Access Journals (Sweden)

    Ashish Garg

    2014-01-01

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

  18. Arterial supersensitivity to nitric oxide (nitroglycerin) in migraine sufferers

    DEFF Research Database (Denmark)

    Thomsen, L L; Iversen, Helle Klingenberg; Brinck, T A;

    1993-01-01

    The sensitivity to nitroglycerin-induced dilatation of large intracranial arteries was studied in 17 patients with migraine without aura, 17 age and sex-matched healthy subjects and 9 patients with episodic tension-type headache. Nitroglycerin in the doses of 0.015, 0.03, 0.25 microgram/kg/min wa.......001). The response was more pronounced in migraine patients at the two higher doses (p nitric oxide (NO), these data support that NO supersensitivity may be an important molecular mechanism of migraine pain....

  19. Inaccuracies of nitric oxide measurement methods in biological media

    OpenAIRE

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

    2013-01-01

    Despite growing reports on the biological action of nitric oxide (NO) as a function of NO payload, the validity of such work is often questionable due to the manner in which NO is measured and/or the solution composition in which NO is quantified. To highlight the importance of measurement technique for a given sample type, NO produced from a small molecule NO donor (N-diazeniumdiolated l-proline, PROLI/NO) and a NO-releasing xerogel film were quantified in a number of physiological buffers a...

  20. Nitric oxide-oxygen radicals interactions in atherosclerosis.

    Science.gov (United States)

    Rubbo, H; Batthyany, C; Radi, R

    2000-01-01

    Atherosclerosis is one of the most common diseases and the principal cause of death in western civilization. The pathogenesis of this disease can be explained on the basis of the 'oxidative-modification hypothesis,' which proposes that low-density lipoprotein (LDL) oxidation represents a key early event. Nitric oxide (*NO) regulates critical lipid membrane and lipoprotein oxidation events by a) contributing to the formation of more potent secondary oxidants from superoxide (i.e.: peroxynitrite), and b) its antioxidant properties through termination reactions with lipid radicals to possibly less reactive secondary nitrogen-containing products (LONO, LOONO). Relative rates of production and steady state concentrations of superoxide and *NO and cellular sites of production will profoundly influence the expression of differential oxidant injury-enhancing and protective effects of *NO. Full understanding of the physiological roles of *NO, coupled with detailed insight into *NO regulation of oxygen radical-dependent reactions, will yield a more rational basis for intervention strategies directed toward oxidant-dependent atherogenic processes. PMID:15693284

  1. Cigarette smoking impairs nitric oxide-mediated cerebral blood flow increase: Implications for Alzheimer's disease.

    Science.gov (United States)

    Toda, Noboru; Okamura, Tomio

    2016-08-01

    Cerebral blood flow is mainly regulated by nitrergic (parasympathetic, postganglionic) nerves and nitric oxide (NO) liberated from endothelial cells in response to shear stress and stretch of vasculature, whereas sympathetic vasoconstrictor control is quite weak. On the other hand, peripheral vascular resistance and blood flow are mainly controlled by adrenergic vasoconstrictor nerves; endothelium-derived NO and nitrergic nerves play some roles as vasodilator factors. Cigarette smoking impairs NO synthesis in cerebral vascular endothelial cells and nitrergic nerves leading to interference with cerebral blood flow and glucose metabolism in the brain. Smoking-induced cerebral hypoperfusion is induced by impairment of synthesis and actions of NO via endothelial nitric oxide synthase (eNOS)/neuronal NOS (nNOS) inhibition and by increased production of oxygen radicals, resulting in decreased actions of NO on vascular smooth muscle. Nicotine acutely and chronically impairs the action of endothelial NO and also inhibits nitrergic nerve function in chronic use. Impaired cerebral blood supply promotes the synthesis of amyloid β that accelerates blood flow decrease. This vicious cycle is thought to be one of the important factors involving in Alzheimer's disease (AD). Quitting smoking is undoubtedly one of the important ways to prevent and delay the genesis or slow the progress of impaired cognitive function and AD. PMID:27530818

  2. Inflammatory cytokines promote inducible nitric oxide synthase-mediated DNA damage in hamster gallbladder epithelial cells

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To investigate the link between chronic biliary inflammation and carcinogenesis using hamster gallbladder epithelial cells.METHODS: Gallbladder epithelial cells were isolated from hamsters and cultured with a mixture of inflammatory cytokines including interleukin-1β, interferon-γ, and tumor necrosis factor-α. Inducible nitric oxide synthase (iNOS) expression, nitric oxide (NO) generation, and DNA damage were evaluated.RESULTS: NO generation was increased significantly following cytokine stimulation, and suppressed by an iNOS inhibitor. iNOS mRNA expression was demonstrated in the gallbladder epithelial cells during exposure to inflammatory cytokines. Furthermore, NO-dependent DNA damage, estimated by the comet assay, was significantly increased by cytokines, and decreased to control levels by an iNOS inhibitor.CONCLUSION: Cytokine stimulation induced iNOS expression and NO generation in normal hamster gallbladder epithelial cells, which was sufficient to cause DNA damage. These results indicate that NO-mediated genotoxicity induced by inflammatory cytokines through activation of iNOS may be involved in the process of biliary carcinogenesis in response to chronic inflammation of the biliary tree.

  3. Inducible nitric oxide synthase in heart tissue and nitric oxide in serum of Trypanosoma cruzi-infected rhesus monkeys: association with heart injury.

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    Cristiano Marcelo Espinola Carvalho

    Full Text Available BACKGROUND: The factors contributing to chronic Chagas' heart disease remain unknown. High nitric oxide (NO levels have been shown to be associated with cardiomyopathy severity in patients. Further, NO produced via inducible nitric oxide synthase (iNOS/NOS2 is proposed to play a role in Trypanosoma cruzi control. However, the participation of iNOS/NOS2 and NO in T. cruzi control and heart injury has been questioned. Here, using chronically infected rhesus monkeys and iNOS/NOS2-deficient (Nos2(-/- mice we explored the participation of iNOS/NOS2-derived NO in heart injury in T. cruzi infection. METHODOLOGY: Rhesus monkeys and C57BL/6 and Nos2(-/- mice were infected with the Colombian T. cruzi strain. Parasite DNA was detected by polymerase chain reaction, T. cruzi antigens and iNOS/NOS2(+ cells were immunohistochemically detected in heart sections and NO levels in serum were determined by Griess reagent. Heart injury was assessed by electrocardiogram (ECG, echocardiogram (ECHO, creatine kinase heart isoenzyme (CK-MB activity levels in serum and connexin 43 (Cx43 expression in the cardiac tissue. RESULTS: Chronically infected monkeys presented conduction abnormalities, cardiac inflammation and fibrosis, which resembled the spectrum of human chronic chagasic cardiomyopathy (CCC. Importantly, chronic myocarditis was associated with parasite persistence. Moreover, Cx43 loss and increased CK-MB activity levels were primarily correlated with iNOS/NOS2(+ cells infiltrating the cardiac tissue and NO levels in serum. Studies in Nos2(-/- mice reinforced that the iNOS/NOS2-NO pathway plays a pivotal role in T. cruzi-elicited cardiomyocyte injury and in conduction abnormalities that were associated with Cx43 loss in the cardiac tissue. CONCLUSION: T. cruzi-infected rhesus monkeys reproduce features of CCC. Moreover, our data support that in T. cruzi infection persistent parasite-triggered iNOS/NOS2 in the cardiac tissue and NO overproduction might contribute

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

    International Nuclear Information System (INIS)

    Exposure of mice to lipopolysaccharide (LPS) plus interferon-γ (IFN-γ) 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-γ were compared. Male mice (8-10 weeks) were exposed to LPS (1.2 mg/kg) + IFN-γ (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-α (TNF-α), 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-γ were characterized by significantly decreased TAC, increased BAL AMs and PMNs, LDH, albumin, TNF-α, 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-α, 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-γ is anti-inflammatory, and this becomes evident over time

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

    Science.gov (United States)

    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

  6. Techniques for quantifying effects of dietary antioxidants on transcription factor translocation and nitric oxide production in cultured cells

    OpenAIRE

    Ewins, B. A.; Vassiliadou, M.; Minihane, A. M.; Rimbach, G. H.; Weinberg, P.D.

    2006-01-01

    Dietary antioxidants can affect cellular processes relevant to chronic inflammatory diseases such as atherosclerosis. We have used non-standard techniques to quantify effects of the antioxidant soy isoflavones genistein and daidzein on translocation of Nuclear Factor-KB (NF-KB) and nitric oxide (NO) production, which are important in these diseases. Translocation was quantified using confocal immunofluoresecence microscopy and ratiometric image analysis. NO was quantified by an electrochemica...

  7. How to protect liver graft with nitric oxide

    Institute of Scientific and Technical Information of China (English)

    Hassen Ben Abdennebi; Mohamed Amine Zaoualí; Izabel Alfany-Fernandez; Donia Tabka; Joan Roselló-Catafau

    2011-01-01

    Organ preservation and ischemia reperfusion injury associated with liver transplantation play an important role in the induction of graft injury. One of the earliest events associated with the reperfusion injury is endothelial cell dysfunction. It is generally accepted that endothelial nitric oxide synthase (e-NOS) is cell-protective by mediating vasodilatation, whereas inducible nitric oxide synthase mediates liver graft injury after transplantation. We conducted a critical review of the literature evaluating the potential applications of regulating and promoting e-NOS activity in liver preservation and transplantation, showing the most current evidence to support the concept that enhanced bioavailability of NO derived from e-NOS is detrimental to ameliorate graft liver preservation, as well as preventing subsequent graft reperfusion injury. This review deals mainly with the beneficial effects of promoting "endogenous" pathways for NO generation, via e-NOS inducer drugs in cold preservation solution, surgical strategies such as ischemic preconditioning, and alternative "exogenous" pathways that focus on the enrichment of cold storage liquid with NO donors. Finally, we also provide a basic bench-to-bed side summary of the liver physiology and cell signalling mechanisms that account for explaining the e-NOS protective effects in liver preservation and transplantation.

  8. Nitric Oxide-Mediated Posttranslational Modifications: Impacts at the Synapse

    Directory of Open Access Journals (Sweden)

    Sophie A. Bradley

    2016-01-01

    Full Text Available Nitric oxide (NO is an important gasotransmitter molecule that is involved in numerous physiological processes throughout the nervous system. In addition to its involvement in physiological plasticity processes (long-term potentiation, LTP; long-term depression, LTD which can include NMDAR-mediated calcium-dependent activation of neuronal nitric oxide synthase (nNOS, new insights into physiological and pathological consequences of nitrergic signalling have recently emerged. In addition to the canonical cGMP-mediated signalling, NO is also implicated in numerous pathways involving posttranslational modifications. In this review we discuss the multiple effects of S-nitrosylation and 3-nitrotyrosination on proteins with potential modulation of function but limit the analyses to signalling involved in synaptic transmission and vesicular release. Here, crucial proteins which mediate synaptic transmission can undergo posttranslational modifications with either pre- or postsynaptic origin. During normal brain function, both pathways serve as important cellular signalling cascades that modulate a diverse array of physiological processes, including synaptic plasticity, transcriptional activity, and neuronal survival. In contrast, evidence suggests that aging and disease can induce nitrosative stress via excessive NO production. Consequently, uncontrolled S-nitrosylation/3-nitrotyrosination can occur and represent pathological features that contribute to the onset and progression of various neurodegenerative diseases, including Parkinson’s, Alzheimer’s, and Huntington’s.

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

    Science.gov (United States)

    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

  10. Applications of plasma sources for nitric oxide medicine

    Science.gov (United States)

    Vasilets, Victor; Shekhter, Anatoly; Pekshev, Alexander

    2013-09-01

    Nitric oxide (NO) has important roles in the function of many tissues and organs. Wound healing processes are always accompanying by the increase of nitric oxide concentration in wound tissue. These facts suggest a possible therapeutic use of various NO donors for the acceleration of the wound healing and treatment of other diseases. Our previous studies indicated that gaseous NO flow produced by air-plasma generators acts beneficially on the wound healing. This beneficial effect could be caused by the mechanism involving peroxynitrite as an intermediate. As a result of mobilization of various antioxidant reactions more endogenous NO molecules become available as signaling molecules. to regulate the metabolic processes in wound tissue. In this paper different air plasma sources generated therapeutic concentrations of NO are discussed. The concentration of NO and other therapeutically important gas products are estimated by thermodynamic simulation. Synergy effects of NO with other plasma components are discussed as a factor enhancing therapeutic results. Some new medical application of plasma devices are presented. Advanced Plasma Therapies Inc.

  11. Hyperbaric oxygen upregulates cochlear constitutive nitric oxide synthase

    Directory of Open Access Journals (Sweden)

    Kao Ming-Ching

    2011-02-01

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

  12. Nitric Oxide and eNOS Gene in Essential Hypertension

    Directory of Open Access Journals (Sweden)

    Kamna Srivastava

    2009-04-01

    Full Text Available Background: Currently hypertension grips around 25% of the entire world population. More than 90% of the hypertensive patients suffer from essential hypertension. In Asian Indians hypertension is the predominant risk factor for Coronary Artery Disease among others. Nitric Oxide (NO is synonymous with endothelial derived relaxation factor. Acting via cGMP (cyclic guanosine monophosphate it causes smooth muscle relaxation, prevents platelet aggregation and acts as an anti-inflammatory agent. iNOS (inducible Nitric oxide synthase, nNOS(neuronal nitric oxide synthase and eNOS (endothelial nitric oxide synthase are the three enzymes producing the gas nitric oxide in the human body. eNOS is the main source of NO under physiological conditions. It is known to have a number of polymorphisms. The most well known ones being the G to T polymorphism in exon 7, the T to C polymorphism in the promoter region and the a/b polymorphism in the intron 4. While the G to T polymorphism has been associated with hypertension in many races including the north Indian population, the association of other polymorphisms has been more of a controversy. Not much study has been done on the Asians especially those in India regarding these polymorphisms. Aims: To elucidate the association between the intron4a/b polymorphism in the eNOS gene and nitric oxide levels and essential hypertension. Objectives: 1. To determine the genotype frequencies of the above mentioned polymorphism in patients and controls2. To study the levels of NO in the plasma of the patients and controls3. To find out correlation if any between this polymorphism and plasma NO levels4. To find a correlation if any between this polymorphism and essential hypertension Materials and Methods: The study design was a case control study. 10 ml of venous blood was taken from 45 patients (selected from the department of Cardiology All India Institute of Medical Sciences, ages between 25 to 55 yrs and not on any

  13. Environmental Effects on Fractional Exhaled Nitric Oxide in Allergic Children

    Directory of Open Access Journals (Sweden)

    Stefania La Grutta

    2012-01-01

    Full Text Available Fractional exhaled nitric oxide (FeNO is a non-invasive marker of airway inflammation in asthma and respiratory allergy. Environmental factors, especially indoor and outdoor air quality, may play an important role in triggering acute exacerbations of respiratory symptoms. The authors have reviewed the literature reporting effects of outdoor and indoor pollutants on FeNO in children. Although the findings are not consistent, urban and industrial pollution—mainly particles (PM2.5 and PM10, nitrogen dioxide (NO2, and sulfur dioxide (SO2—as well as formaldehyde and electric baseboard heating have been shown to increase FeNO, whilst ozone (O3 tends to decrease it. Among children exposed to Environmental Tobacco Smoke (ETS with a genetic polymorphisms in nitric oxide synthase genes (NOS, a higher nicotine exposure was associated with lower FeNO levels. Finally, although more studies are needed in order to better investigate the effect of gene and environment interactions which may affect the interpretation of FeNO values in the management of children with asthma, clinicians are recommended to consider environmental exposures when taking medical histories for asthma and respiratory allergy. Further research is also needed to assess the effects of remedial interventions aimed at reducing/abating environmental exposures in asthmatic/allergic patients.

  14. Antioxidant and nitric oxide inhibition activities of Thai medicinal plants.

    Science.gov (United States)

    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

  15. Effects of nitric oxide on stem cell therapy.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    Seyffarth Gunter

    2004-06-01

    Full Text Available Abstract 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.

  19. The use of aminoguanidine, a selective inducible nitric oxide synthase inhibitor, to evaluate the role of nitric oxide on periapical healing

    OpenAIRE

    Ali Reza Farhad; Seyed Mohammad Razavi; Parnian Alavi Nejad

    2011-01-01

    Background: Nitric oxide (NO) is one of the many chemical mediators involved in inflammatory processes. In addition to periapical inflammation, NO can have a role in periapical healing. The purpose of this study was to evaluate the effect of aminoguanidine (AG) as a selective inhibitor of inducible nitric oxide synthase (iNOS) on the degree of healing response of periapical lesions of the canine teeth of cats. Methods: In this interventional experimental study, the root canals of 48 cat c...

  20. Nitric oxide mediates the stress response induced by diatom aldehydes in the sea urchin Paracentrotus lividus.

    Directory of Open Access Journals (Sweden)

    Giovanna Romano

    Full Text Available 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.

  1. Nitric oxide mediates the stress response induced by diatom aldehydes in the sea urchin Paracentrotus lividus.

    Science.gov (United States)

    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

  2. Neuronal nitric oxide synthase-deficient mice have impaired Renin release but normal blood pressure

    DEFF Research Database (Denmark)

    Sällström, Johan; Carlström, Mattias; Jensen, Boye L;

    2008-01-01

    BackgroundNitric oxide deficiency is involved in the development of hypertension, but the mechanisms are currently unclear. This study was conducted to further elucidate the role of neuronal nitric oxide synthase (nNOS) in blood pressure regulation and renin release in relation to different sodium...

  3. Expression of inducible nitric oxide synthase in trigeminal ganglion cells during culture

    DEFF Research Database (Denmark)

    Jansen-Olesen, Inger; Zhou, MingFang; Zinck, Tina Jovanovic;

    2005-01-01

    Nitric oxide (NO) is an important signalling molecule that has been suggested to be a key molecule for induction and maintenance of migraine attacks based on clinical studies, animal experimental studies and the expression of nitric oxide synthase (NOS) immunoreactivity within the trigeminovascular...

  4. Polymorphisms In The Nitric-Oxide Synthase 2 Gene And Prostate Cancer Pathogenesis

    Directory of Open Access Journals (Sweden)

    Charlotta Ryk

    2015-08-01

    Conclusions: Nitric oxide can induce proliferation as well as apoptosis depending on cellular context. Our results suggest that NOS2 polymorphisms may influence the risk of aggressive prostate cancer and that these polymorphisms could have an impact on disease pathogenesis, possibly by affecting intracellular nitric oxide levels.

  5. Behavioral impairments and changes of nitric oxide and inducible nitric oxide synthase in the brains of molarless KM mice.

    Science.gov (United States)

    Pang, Qian; Hu, Xingxue; Li, Xinya; Zhang, Jianjun; Jiang, Qingsong

    2015-02-01

    More studies showed that as a common disorder in senior population, loss of teeth could adversely affect human cognitive function, and nitric oxide (NO) might play an important role in the cognitive function. However, the underlying mechanism has not yet been well-established. The objectives of this study are to evaluate behavior changes of KM mice after loss of molars, and levels of NO and inducible nitric oxide synthase (iNOS) in the brain in molarless condition. It is hypothesized that loss of molars of the mice tested results in the cognitive impairments and that the process is mediated by NO in the brain through the signaling pathways. Morris water maze is used to test the behavioral changes after 8 weeks of the surgery. The changes of NO and iNOS are evaluated by using Griess assay, western blot, and immunohistochemistry method. The results show that 8 weeks after loss of molars, the spatial learning and memory of KM mice impair and the levels of NO and iNOS in mice hippocampus increase. These findings suggest that molar extraction is associated with the behavioral impairment, and that the changes of NO and iNOS in the hippocampus may be involved in the behavioral changes in the molarless condition. PMID:25447296

  6. Effect of nitric oxide synthase inhibition on the exchange of glucose and fatty acids in human skeletal muscle

    DEFF Research Database (Denmark)

    Heinonen, Ilkka; Saltin, Bengt; Kemppainen, Jukka;

    2013-01-01

    The role of nitric oxide in controlling substrate metabolism in humans is incompletely understood.......The role of nitric oxide in controlling substrate metabolism in humans is incompletely understood....

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

    Science.gov (United States)

    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.

  8. Nitrones: not only extraordinary spin traps, but also good nitric oxide sources in vivo.

    Science.gov (United States)

    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.

  9. Nitrones are able to release nitric oxide in aqueous environment under hydroxyl free radical attack.

    Science.gov (United States)

    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.

  10. DMPD: Regulation of nitric oxide synthesis and apoptosis by arginase and argininerecycling. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17513437 Regulation of nitric oxide synthesis and apoptosis by arginase and arginine...on of nitric oxide synthesis and apoptosis by arginase and argininerecycling. PubmedID 17513437 Title Regula...tion of nitric oxide synthesis and apoptosis by arginase and argininerecycling. A

  11. Regulation of Injury-Induced Neurogenesis by Nitric Oxide

    Directory of Open Access Journals (Sweden)

    Bruno P. Carreira

    2012-01-01

    Full Text Available 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.

  12. Solar cycle variation of thermospheric nitric oxide at solstice

    Science.gov (United States)

    Gerard, J.-C.; Fesen, C. G.; Rusch, D. W.

    1990-01-01

    A coupled, two-dimensional, chemical-diffusive model of the thermosphere is used to study the role of solar activity in the global distribution of nitric oxide. The model calculates self-consistently the zonally averaged temperature, circulation, and composition for solstice under solar maximum and solar minimum conditions. A decrease of the NO density by a factor of three to four in the E region is predicted from solar maximum to solar minimum. It is found that the main features of the overall morphology and the changes induced by the solar cycle are well reproduced in the model, although some details are not satisfactorily predicted. The sensitivity of the NO distribution to eddy transport and to the quenching of metastable N(2D) atoms by atomic oxygen is also described.

  13. Nitric oxide: a newly discovered function on wound healing

    Institute of Scientific and Technical Information of China (English)

    Jian-dong LUO; Alex F CHEN

    2005-01-01

    Wound healing impairment represents a particularly challenging clinical problem to which no efficacious treatment regimens currently exist. The factors ensuring appropriate intercellular communication during wound repair are not completely understood. Although protein-type mediators are well-established players in this process, emerging evidence from both animal and human studies indicates that nitric oxide (NO) plays a key role in wound repair. The beneficial effects of NO on wound repair may be attributed to its functional influences on angiogenesis,inflammation, cell proliferation, matrix deposition, and remodeling. Recent findings from in vitro and in vivo studies of NO on wound repair are summarized in this review. The unveiled novel mechanisms support the use of NO-containing agents and/or NO synthase gene therapy as new therapeutic regimens for impaired wound healing.

  14. Reactive Oxygen Species and Nitric Oxide in Cutaneous Leishmaniasis

    Directory of Open Access Journals (Sweden)

    Maria Fátima Horta

    2012-01-01

    Full Text Available Cutaneous leishmaniasis affects millions of people around the world. Several species of Leishmania infect mouse strains, and murine models closely reproduce the cutaneous lesions caused by the parasite in humans. Mouse models have enabled studies on the pathogenesis and effector mechanisms of host resistance to infection. Here, we review the role of nitric oxide (NO, reactive oxygen species (ROS, and peroxynitrite (ONOO− in the control of parasites by macrophages, which are both the host cells and the effector cells. We also discuss the role of neutrophil-derived oxygen and nitrogen reactive species during infection with Leishmania. We emphasize the role of these cells in the outcome of leishmaniasis early after infection, before the adaptive Th-cell immune response.

  15. Nitric oxide induces caspase activity in boar spermatozoa.

    Science.gov (United States)

    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 (Pboar sperm damage. PMID:18433854

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

    Directory of Open Access Journals (Sweden)

    Xiaoqing Hu

    2015-12-01

    Full Text Available 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.

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

    Science.gov (United States)

    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.

  18. Erythropoietin and cerebral vascular protection: role of nitric oxide

    Institute of Scientific and Technical Information of China (English)

    Anantha Vijay R SANTHANAM; Zvonimir S KATUSIC

    2006-01-01

    Cerebral vasospasm after subarachnoid hemorrhage (SAH) is a major clinical problem causing cerebral ischemia and infarction.The pathogenesis of vasospasm is related to a number of pathological processes including endothelial damage and alterations in vasomotor function leading to narrowing of artefial diameter and a subsequent decrease in cerebral blood flow.Discovery of the tissue protective effects of erythropoietin (EPO) stimulated the search for therapeutic application of EPO for the prevention and treatment of cerebrovascular disease.Recent studies have identified the role of EP0 in vascular protection mediated by the preservation of endothelial cell integrity and stimulation of angiogenesis.In this review, we discuss the EPO-induced activation of endothelial nitric oxide (NO) synthase and its contribution to the prevention of cerebral vasospasm.

  19. Weaning of inhaled nitric oxide: is there a best strategy?

    Directory of Open Access Journals (Sweden)

    Anita M. Ware

    2015-04-01

    Full Text Available Background: Inhaled nitric oxide (iNO has been used in the treatment of pulmonary hypertension in neonates for many years. iNO was approved by the FDA in 1999 for hypoxic respiratory failure (HRF in term and near term infants, defined as > 34 weeks gestational age (GA. iNO is used for persistent pulmonary hypertension of the newborn (PPHN, secondary pulmonary hypertension caused by congenital heart disease (CHD, congenital diaphragmatic hernia (CDH, meconium aspiration syndrome (MAS, pneumonia, respiratory distress syndrome (RDS, and other pathologies. iNO has its effect locally on the pulmonary vasculature and has been studied extensively regarding its effect on morbidities such as: need for extracorporeal membrane oxygenation (ECMO, oxygen requirements, and mechanical ventilatory support. However, protocols for weaning iNO and for the duration of iNO weaning have not been studied extensively. It has been shown that an abrupt discontinuation leads to rebound pulmonary hypertension.Methods: Electronic literature search and review of published articles on the use of iNO in the neonate.Results: Electronic databases including Medline and PubMed were searched from the years 1995-2015, using the keywords "iNO", "nitric oxide", "neonate", and "weaning nitric oxide." This search revealed 2,124 articles. Articles were determined to be eligible for review if they included a specific protocol for weaning iNO, and were published in English. 16 articles with specific protocols for iNO weaning have been identified and reviewed. The studies had enrolled a total of 1,735 neonates either at term either preterm and with a mean birth weight of 3.3 kg (± 2 kg. Main diagnoses included MAS, CHD (total anomalous pulmonary venous return [TAPVR], d-transposition of the great vessels [DTGV], atrial septal defect [ASD], pulmonary atresia [PA], hypoplastic left heart syndrome [HLH], pneumonia, RDS, hyaline membrane disease (HMD, PPHN, CDH, sepsis, pulmonary hypoplasia

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

    Science.gov (United States)

    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

  1. Nitric Oxide Regulates Neurogenesis in the Hippocampus following Seizures

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    Bruno P. Carreira

    2015-01-01

    Full Text Available 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.

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

    Science.gov (United States)

    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

  3. Nitric Oxide and Major Depressive Disorder: Pathophysiology and Treatment Implications.

    Science.gov (United States)

    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

  4. Modulation of endothelial nitric oxide by plant-derived products.

    Science.gov (United States)

    Schmitt, Christoph A; Dirsch, Verena M

    2009-09-01

    Nitric oxide (NO), produced by endothelial nitric oxide synthase (eNOS), is recognised as a central anti-inflammatory and anti-atherogenic principle in the vasculature. Decreased availability of NO in the vasculature promotes the progression of cardiovascular diseases. Epidemiological and clinical studies have demonstrated that a growing list of natural products, as components of the daily diet or phytomedical preparations, may improve vascular function by enhancing NO bioavailability. In this article we first outline common pathways modulating endothelial NO production or bioavailability to provide a basis for subsequent mechanistic discussions. Then we comprehensively review natural products and plant extracts known to positively influence eNOS activity and/or endothelial function in vitro or in vivo. We will discuss red wine, highlighting polyphenols, oligomeric procyanidins (OPC) and resveratrol as modulators of endothelial NO production. Other dietary products and their active components known to activate eNOS include cocoa (OPC and its monomer (-)-epicatechin), pomegranates (polyphenols), black and green tea (flavanoids, especially epigallocatechin gallate), olive oil (oleic acid and polyphenols), soy (genistein), and quercetin, one of the most abundant flavonoids in plants. In addition, phytomedical preparations made from ginkgo, hawthorn and ginseng, as well as formulations used in traditional Chinese Medicine, have been shown to affect endothelial NO production. Recurring phytochemical patterns among active fractions and purified compounds are discussed. In summary, there is increasing evidence that several single natural products and plant extracts influence endothelial NO production. Identification of such compounds and characterisation of their cellular actions may increase our knowledge of the regulation of endothelial NO production and could provide valuable clues for the prevention or treatment of cardiovascular diseases. PMID:19497380

  5. Estetrol modulates endothelial nitric oxide synthesis in human endothelial cells

    Directory of Open Access Journals (Sweden)

    Maria Magdalena eMontt-Guevara

    2015-07-01

    Full Text Available 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 ageing 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.

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

    Science.gov (United States)

    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

  7. Inducible nitric oxide synthase and guinea-pig ileitis induced by adjuvant

    Directory of Open Access Journals (Sweden)

    N. D. Seago

    1995-01-01

    Full Text Available We sought to establish a model of inflammatory bowel disease by augmenting the activity of the local immune system with Freund's complete adjuvant, and to determine if inducible nitric oxide synthase (iNOS expression and peroxynitrite formation accompanied the inflammatory condition. In anaesthetized guinea-pigs, a loop of distal ileum received intraluminal 50% ethanol followed by Freund's complete adjuvant. Control animals were sham operated. When the animals were killed 7 or 14 days later, loop lavage fluid was examined for nitrite and PGE2 levels; mucosal levels of granulocyte and macrophages were estimated by myeloperoxidase (MPO and N-acetyl-D-glucosaminidase (NAG activity, respectively. Cellular localization if iNOS and peroxynitrite formation were determined by immunohistochemistry with polyclonal antibodies directed against peptide epitopes of mouse iNOS and nitrotyrosine, respectfully. Adjuvant administration resulted in a persistent ileitis, featuring gut thickening, crypt hyperplasia, villus tip swelling and disruption, and cellular infiltration. Lavage levels of PGE2 and nitrite were markedly elevated by adjuvant treatment. Immunoreactive iNOS and nitrotyrosine bordered on detectability in normal animals but were markedly evident with adjuvant treatment at day 7 and particularly day 14. Immunohistochemistry suggested that enteric neurons and epithelia were major sites of iNOS activity and peroxynitrite formation. We conclude that local administration of adjuvant establishes a chronic ileitis. Inducible nitric oxide synthase may contribute to the inflammatory process.

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

    Science.gov (United States)

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

    2010-04-01

    Endometritis is an inflammation of the endometrial lining of the uterus without systemic signs, which is associated with chronic postpartum infection of the uterus with pathogenic bacteria. Nitric oxide (NO) is an inflammatory mediator that among other effects causes smooth muscle relaxation and mediated cytoimmunity and inflammation toxicity. To see if the nitric oxide concentration in plasma and uterine secrets is related with postpartum endometritis, NO concentrations in plasma and uterine secrets were measured in dairy cows with puerperal endometritis (clinical endometritis (n = 60) and subclinical endometritis (n = 58)). Cows with clinical or subclinical endometritis showed higher concentrations of NO in both plasma and uterine secrets when compared with normal cows and the highest concentrations of NO in plasma and uterine secrets were found in dairy cows with clinical endometritis. Expression level of NOS2 mRNA in endometrial biopsies from cows with puerperal endometritis was also higher and the highest expression of NOS2 mRNA was found in cows with clinical endometritis. The results showed that concentrations of NO in plasma and uterine fluid are related with the degree of endometritis which may be useful to diagnose the endometritis in dairy cows. PMID:20414720

  9. New nitric oxide donors based on ruthenium complexes

    Directory of Open Access Journals (Sweden)

    C.N. Lunardi

    2009-01-01

    Full Text Available Nitric oxide (NO donors produce NO-related activity when applied to biological systems. Among its diverse functions, NO has been implicated in vascular smooth muscle relaxation. Despite the great importance of NO in biological systems, its pharmacological and physiological studies have been limited due to its high reactivity and short half-life. In this review we will focus on our recent investigations of nitrosyl ruthenium complexes as NO-delivery agents and their effects on vascular smooth muscle cell relaxation. The high affinity of ruthenium for NO is a marked feature of its chemistry. The main signaling pathway responsible for the vascular relaxation induced by NO involves the activation of soluble guanylyl-cyclase, with subsequent accumulation of cGMP and activation of cGMP-dependent protein kinase. This in turn can activate several proteins such as K+ channels as well as induce vasodilatation by a decrease in cytosolic Ca2+. Oxidative stress and associated oxidative damage are mediators of vascular damage in several cardiovascular diseases, including hypertension. The increased production of the superoxide anion (O2- by the vascular wall has been observed in different animal models of hypertension. Vascular relaxation to the endogenous NO-related response or to NO released from NO deliverers is impaired in vessels from renal hypertensive (2K-1C rats. A growing amount of evidence supports the possibility that increased NO inactivation by excess O2- may account for the decreased NO bioavailability and vascular dysfunction in hypertension.

  10. Subclinical mastitis causes alterations in nitric oxide, total oxidant and antioxidant capacity in cow milk.

    Science.gov (United States)

    Atakisi, Onur; Oral, Hasan; Atakisi, Emine; Merhan, Oguz; Metin Pancarci, S; Ozcan, Ayla; Marasli, Saban; Polat, Bulent; Colak, Armagan; Kaya, Semra

    2010-08-01

    The aim of this study was to investigate total antioxidant (TAC), and oxidant capacity (TOC) and nitric oxide (NO) levels in milk of cows with subclinical mastitis. Brown Swiss and Holstein breed cows were screened with California Mastitis Test (CMT) to determine mammary glands with subclinical mastitis. Moreover, somatic cell counts (SCC) were determined electronically in all milk samples. Mammary quarters were classified as healthy (n=25) or subclinical mastitis (n=35) based on CMT scores and somatic cell count (SCC: 200,000/ml) in milk. Nitric oxide, TOC and SCC levels were significantly higher (pmastitis compared to those from healthy mammary quarters. In conclusion, subclinical mastitis results in higher NO concentrations, TOC and SCC, and NO and TOC were positively correlated with SCC. Moreover, alterations in NO levels and TOC in milk could be used as an alternative diagnostic tool to screen for subclinical mastitis. PMID:20132956

  11. The influence of organic peroxides on platelet aggregation and sensitivity to nitric oxide.

    Science.gov (United States)

    Naseem, K M; Bruckdorfer, K R

    1999-01-01

    The effects of oxidative stress, induced by water-soluble and lipid peroxides, on platelet reactivity and platelet sensitivity to nitric oxide were investigated. Hydrogen peroxide and cumene hydroperoxide potentiated thrombin-induced platelet aggregation. In contrast, 15(S)-hydroperoxyeicosatetraenoic acid had no such effect, while 12(S)-hydroperoxyeicosatetraenoic acid inhibited platelet reactivity. All of the peroxides tested were found to decrease platelet sensitivity to nitric oxide, although the mechanisms by which the various peroxides altered platelet sensitivity to nitric oxide were different. The water-soluble peroxides opposed the actions of nitric oxide without affecting cyclic GMP levels, while 15(S)-hydroperoxyeicosatetraenoic acid caused a significant reduction in the concentration of cyclic GMP formed in response to NO. The data from this study demonstrate that water-soluble and lipid peroxides both affect platelet reactivity and regulation, but by different mechanisms. Thus, caution should be exercised when selecting peroxides to be used as models of oxidative stress. PMID:16801085

  12. Sensing nitric oxide with a carbon nanofiber paste electrode modified with a CTAB and nafion composite

    International Nuclear Information System (INIS)

    We describe an electrochemical sensor for nitric oxide that was obtained by modifying the surface of a nanofiber carbon paste microelectrode with a film composed of hexadecyl trimethylammonium bromide and nafion. The modified microelectrode displays excellent catalytic activity in the electrochemical oxidation of nitric oxide. The mechanism was studied by scanning electron microscopy and cyclic voltammetry. Under optimal conditions, the oxidation peak current at a working voltage of 0.75 V (vs. SCE) is related to the concentration of nitric oxide in the 2 nM to 0.2 mM range, and the detection limit is as low as 2 nM (at an S/N ratio of 3). The sensor was successfully applied to the determination of nitric oxide released from mouse hepatocytes. (author)

  13. Nitric oxide synthase inhibitor improves de novo and long-term L-DOPA-induced dyskinesia in hemiparkinsonian rats

    Directory of Open Access Journals (Sweden)

    Fernando Eduardo Padovan-Neto

    2011-06-01

    Full Text Available Inhibitors of neuronal and endothelial nitric oxide synthase decrease l-3,4-dihidroxifenilalanine (L-DOPA-induced dyskinesias in rodents. The mechanism of nitric oxide inhibitor action is unknown. The aims of the present study were to investigate the decrease of L-DOPA-induced abnormal involuntary movements in 6-hydroxydopamine (6-OHDA-lesioned rats by nitric oxide inhibitors following either acute or chronic treatment. The primary findings of this study were that NG-nitro-L-Arginine, an inhibitor of endothelial and neuronal nitric oxide synthase, attenuated abnormal involuntary movements induced by chronic and acute L-DOPA. In contrast, rotational behavior was attenuated only after chronic L-DOPA. L-DOPA improved stepping test performance, and its chronic administration did not alter open field behavior. Our results indicated a correlation between apomorphine-induced rotation and the decrease in the number of adjusting steps performed with the contralateral forepaw in the 6-OHDA-lesioned rats.The 6-OHDA lesion and the L-DOPA treatment induced a bilateral increase (1.5 times in the nNOS protein and nNOS mRNA in the striatum and in the frontal cortex. There was a parallel increase, bilaterally, of the FosB/ΔFosB, primarily in the ipsilateral striatum. The exception was in the contralateral striatum and the ipsilateral frontal cortex, where chronic L-DOPA treatment induced an increase of approximately 10 times the nNOS mRNA. Our results provided further evidence of an anti-dyskinetic effect of NOS inhibitor. The effect appeared under L-DOPA acute and chronic treatment. The L-DOPA treatment also revealed an over-expression of the neuronal NOS in the frontal cortex and striatum. Our results corroborated findings that L-DOPA-induced rotation differs between acute and chronic treatment. The effect of the NOS inhibitor conceivably relied on the L-DOPA structural modifications in the parkinsonian brain. Taken together, these data provided a rationale

  14. Lipid Peroxidation and Nitric Oxide Levels in Male Smokers' Spermatozoa and their Relation with Sperm Motility

    OpenAIRE

    Ghaffari, Mohammad Ali; Rostami, Morad

    2012-01-01

    Background Nitric oxide (NO) is synthesized from L-arginine by a family of enzymes known as nitric oxide synthases. Low concentrations of NO is essential in biology and physiology of spermatozoa, but high amounts of NO is toxic and has negative effects on sperm functions. Moreover, sperm membrane contains high concentrations of polyunsaturated fatty acids that are highly susceptible to oxidative damage that interferes with fertilization ability. Therefore, we investigated the correlation betw...

  15. Role of nitric oxide and inducible nitric oxide synthase in human abdominal aortic aneurysms: a preliminary study

    Institute of Scientific and Technical Information of China (English)

    LIAO Ming-fang; LI Xiao-yan; JING Zai-ping; BAO Jun-min; ZHAO Zhi-qing; MEI Zhi-jun; LU Qing-shen; Feng Xiang; FENG Rui; ZHANG Su-zen

    2006-01-01

    Background Nitric oxide (NO) is an important mediator in the pathophysiology of many vascular diseases. However, the definite role of NO in human abdominal aortic aneurysm (AAA) formation is unclear. The aim of this study was to investigate production of NO and expression of inducible nitric oxide synthase (iNOS), and their possible role in AAA.Methods A total of 28 patients with AAA, 10 healthy controls, and 8 patients with arterial occlusive disease were enrolled into this study. Standard colorimetric assay was used to examine NO concentration in plasma from patients with AAA and normal controls, and in cultured smooth muscle cells (SMCs). Expression of iNOS in aortas and cultured SMCs were detected by immunochemistry. The correlation of iNOS expression with age of the patient, size of aneurysm, and degree of inflammation was also investigated by Cochran-Mantel-Haenszelχ2 test and Kendall' Tau correlation.Results Expression of iNOS increased significantly in the wall of aneurism in the patients with AAA compared to the healthy controls (P<0.05) and the patients with occlusive arteries (P<0.05). iNOS protein and media NOx (nitrite+nitrate) also increased in cultured SMCs from human AAA (n=4, P<0.05), while plasma NOx decreased in patients with AAA (n=25) compared to the healthy controls (n=20). There was a positive correlation between iNOS protein and degree of inflammation in aneurismal wall (Kendall coefficient=0.5032, P=0.0029)Conclusions SMCs and inflammatory cells were main cellular sources of increased iNOS in AAA, and NO may play a part in pathogenesis in AAA through inflammation.

  16. Fractional exhaled nitric oxide measurement with a handheld device.

    Science.gov (United States)

    Magori, Erhard; Hiltawsky, Karsten; Fleischer, Maximilian; Simon, Elfriede; Pohle, Roland; von Sicard, Oliver; Tawil, Angelika

    2011-06-01

    A sensing system for fractional exhaled nitric oxide (FeNO) measurement is presented, which is characterized by a compact setup and a cost potential to be made available for the patient at home. The sensing is based on the work function measurement of a phthalocyanine-type sensing material, which is shown to be sufficiently sensitive for NO(2) in the ppb range. The transducer used to measure the work function is a field effect transistor with a suspended gate electrode. Selectivity is given with respect to other breath components including typically metabolic by-products. The measurement system includes breath treatments in a simple setup, which essentially are dehumidification and a quantitative conversion of NO to NO(2) with a conversion rate of approx. 95%, using a disposable oxidation catalyst. The accomplishment of the correct exhalation maneuver and feeding of the suited portion of exhaled air to the sensor is provided by breath sampling means. The sensor is not gas consuming. This allows us to fill the measurement chamber once, instead of establishing a gas flow for the measurement. This feature simplifies the device architecture. In this paper, we report on sensor characteristics, system architecture and measurement with artificial breath-gas as well as with human breath with the device. PMID:21646688

  17. Molecular basis for arsenic-induced alteration in nitric oxide production and oxidative stress: implication of endothelial dysfunction.

    Science.gov (United States)

    Kumagai, Yoshito; Pi, Jingbo

    2004-08-01

    Accumulated epidemiological studies have suggested that prolonged exposure of humans to arsenic in drinking water is associated with vascular diseases. The exact mechanism of how this occurs currently unknown. Nitric oxide (NO), formed by endothelial NO synthase (eNOS), plays a crucial role in the vascular system. Decreased availability of biologically active NO in the endothelium is implicated in the pathophysiology of several vascular diseases and inhibition of eNOS by arsenic is one of the proposed mechanism s for arsenic-induced vascular diseases. In addition, during exposure to arsenic, overproduction of reactive oxygen species (ROS) can occur, resulting in oxidative stress, which is another major risk factor for vascular dysfunction. The molecular basis for decreased NO levels and increased oxidative stress during arsenic exposure is poorly understood. In this article, evidence for arsenic-mediated alteration in NO production and oxidative stress is reviewed. The results of a cross-sectional study in an endemic area of chronic arsenic poisoning and experimental animal studies to elucidate a potential mechanism for the impairment of NO formation and oxidative stress caused by prolonged exposure to arsenate in the drinking water are also reviewed.

  18. Inhibition of inducible nitric oxide synthase expression and nitric oxide production in plateau pika (Ochotona curzoniae) at high altitude on Qinghai-Tibet Plateau.

    Science.gov (United States)

    Xie, Ling; Zhang, Xuze; Qi, Delin; Guo, Xinyi; Pang, Bo; Du, Yurong; Zou, Xiaoyan; Guo, Songchang; Zhao, Xinquan

    2014-04-30

    Nitric oxide (NO), a potent vasodilator, plays an important role in preventing hypoxia induced pulmonary hypertension. Endogenous NO is synthesized by nitric oxide synthases (NOSs) from l-arginine. In mammals, three different NOSs have been identified, including neuronal NOS (nNOS), endothelial NOS (eNOS) and inducible NOS (iNOS). Plateau pika (Ochotona curzoniae) is a typical hypoxia tolerant mammal that lives at 3000-5000 m above sea level on the Qinghai-Tibet Plateau. The aim of this study was to investigate whether NOS expression and NO production are regulated by chronic hypoxia in plateau pika. Quantitative real-time PCR and western blot analyses were conducted to quantify relative abundances of iNOS and eNOS transcripts and proteins in the lung tissues of plateau pikas at different altitudes (4550, 3950 and 3200 m). Plasma NO metabolites, nitrite/nitrate (NO(x)⁻) levels were also examined by Ion chromatography to determine the correlation between NO production and altitude level. The results revealed that iNOS transcript levels were significantly lower in animals at high altitudes (decreased by 53% and 57% at altitude of 3950 and 4550 m compared with that at 3200 m). Similar trends in iNOS protein abundances were observed (26% and 41% at 3950 and 4550 m comparing with at 3200 m). There were no significant differences in eNOS mRNA and protein levels in the pika lungs among different altitudes. The plasma NO(x)⁻ levels of the plateau pikas at high altitudes significantly decreased (1.65±0.19 μg/mL at 3200 m to 0.44±0.03 μg/mL at 3950 m and 0.24±0.01 μg/mL at 4550 m). This is the first evidence describing the effects of chronic hypoxia on NOS expression and NO levels in the plateau pika in high altitude adaptation. We conclude that iNOS expression and NO production are suppressed at high altitudes, and the lower NO concentration at high altitudes may serve crucial roles for helping the plateau pika to survive at hypoxic environment.

  19. Quiescent interplay between inducible nitric oxide synthase and tumor necrosis factor-alpha: influence on transplant graft vasculopathy in renal allograft dysfunction.

    Science.gov (United States)

    Elahi, Maqsood M; Matata, Bashir M; Hakim, Nadey S

    2006-06-01

    A healthy endothelium is essential for vascular homeostasis, and preservation of endothelial cell function is critical for maintaining transplant allograft function. Damage to the microvascular endothelial cells is now regarded as a characteristic feature of acute vascular rejection, an important predictor of graft loss. It is also linked with transplant vasculopathy, often associated with chronic allograft nephropathy. Large bursts of nitric oxide in infiltrating monocytes/macrophages modulated by inducible nitric oxide synthase are considered pivotal in driving this mechanism. Indeed, it has been shown recently that increased circulating levels of tumor necrosis factor-alpha in the rejecting kidneys are largely responsible for triggering inducible nitric oxide synthase expression. This in turn suggests that several structural and functional features of graft rejection could be mediated by tumor necrosis factor-alpha. Despite the large body of evidence that supports immunologic involvement, knowledge concerning the cellular and biochemical mechanisms for nephritic cell dysfunction and death is incomplete. The role of tumor necrosis factor-alpha in mediating pathophysiological activity of inducible nitric oxide synthase during transplant vasculopathy remains contentious. Here, we discuss the effect of inducible nitric oxide synthase and tumor necrosis factor-alpha interaction on progressive damage to glomerular and vascular structures during renal allograft rejection. Selective inhibition of inducible nitrous oxide synthase and tumor necrosis factor-alpha as a potential therapy for ameliorating endothelial dysfunction and transplant graft vasculopathy is also discussed.

  20. The Mycobacterium tuberculosis proteasome active site threonine is essential for persistence yet dispensable for replication and resistance to nitric oxide.

    Directory of Open Access Journals (Sweden)

    Sheetal Gandotra

    Full Text Available Previous work revealed that conditional depletion of the core proteasome subunits PrcB and PrcA impaired growth of Mycobacterium tuberculosis in vitro and in mouse lungs, caused hypersusceptibility to nitric oxide (NO and impaired persistence of the bacilli during chronic mouse infections. Here, we show that genetic deletion of prcBA led to similar phenotypes. Surprisingly, however, an active site mutant proteasome complemented the in vitro and in vivo growth defects of the prcBA knockout (Delta prcBA as well as its NO hypersensitivity. In contrast, long-term survival of M. tuberculosis in stationary phase and during starvation in vitro and in the chronic phase of mouse infection required a proteolytically active proteasome. Inhibition of inducible nitric oxide synthase did not rescue survival of Delta prcBA, revealing a function beyond NO defense, by which the proteasome contributes to M. tuberculosis fitness during chronic mouse infections. These findings suggest that proteasomal proteolysis facilitates mycobacterial persistence, that M. tuberculosis faces starvation during chronic mouse infections and that the proteasome serves a proteolysis-independent function.

  1. Oxidative stress markers in neurological diseases and disorders: electrochemical detection of hydrogen peroxide and nitric oxide

    OpenAIRE

    O'Riordan, Saidhbhe

    2013-01-01

    The aim of this thesis is to further demonstrate the electrochemical detection of nitric oxide (NO) and hydrogen peroxide (H2O2) in-vitro, to advance the previously demonstrated detection of brain NO and to demonstrate the novel in-vivo detection of H2O2 using a paired catalase-based biosensor. We have recently successfully demonstrated the real-time detection of brain NO using a previously characterised Nafion®-modified platinum (Pt) electrochemical sensor. Additionally, th...

  2. Nitric Oxide Improves Internal Iron Availability in Plants1

    Science.gov (United States)

    Graziano, Magdalena; Beligni, María Verónica; Lamattina, Lorenzo

    2002-01-01

    Iron deficiency impairs chlorophyll biosynthesis and chloroplast development. In leaves, most of the iron must cross several biological membranes to reach the chloroplast. The components involved in the complex internal iron transport are largely unknown. Nitric oxide (NO), a bioactive free radical, can react with transition metals to form metal-nitrosyl complexes. Sodium nitroprusside, an NO donor, completely prevented leaf interveinal chlorosis in maize (Zea mays) plants growing with an iron concentration as low as 10 μm Fe-EDTA in the nutrient solution. S-Nitroso-N-acetylpenicillamine, another NO donor, as well as gaseous NO supply in a translucent chamber were also able to revert the iron deficiency symptoms. A specific NO scavenger, 2-(4-carboxy-phenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, blocked the effect of the NO donors. The effect of NO treatment on the photosynthetic apparatus of iron-deficient plants was also studied. Electron micrographs of mesophyll cells from iron-deficient maize plants revealed plastids with few photosynthetic lamellae and rudimentary grana. In contrast, in NO-treated maize plants, mesophyll chloroplast appeared completely developed. NO treatment did not increase iron content in plant organs, when expressed in a fresh matter basis, suggesting that root iron uptake was not enhanced. NO scavengers 2-(4-carboxy-phenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide and methylene blue promoted interveinal chlorosis in iron-replete maize plants (growing in 250 μm Fe-EDTA). Even though results support a role for endogenous NO in iron nutrition, experiments did not establish an essential role. NO was also able to revert the chlorotic phenotype of the iron-inefficient maize mutants yellow stripe1 and yellow stripe3, both impaired in the iron uptake mechanisms. All together, these results support a biological action of NO on the availability and/or delivery of metabolically active iron within the plant. PMID:12481068

  3. Adrenoreceptors and nitric oxide in the cardiovascular system

    Directory of Open Access Journals (Sweden)

    Valeria eConti

    2013-11-01

    Full Text Available Nitric Oxide (NO is a small molecule that continues to attract much attention from the scientific community.Since its discovery, it has been evident that NO has a crucial role in the modulation of vascular tone. NO is involved in multiple signal transduction pathways thus contributing to the regulation of many cellular functions. NO effects can be either dependent or independent on cGMP, and rely also upon several mechanisms such as the amount of NO, the compartmentalisation of the enzymes responsible for its biosynthesis (NOS, and the local redox conditions. Several evidences highlighted the correlation among adrenoreceptors activity, vascular redox status and NO bioavailability. It was suggested a possible crosstalk between NO and oxidative stress hallmarks in the endothelium function and adaptation, and in sympathetic vasoconstriction control. Adrenergic vasoconstriction is a balance between a direct vasoconstrictive effect on smooth muscle and an indirect vasorelaxant action caused by α2- and β-adrenergic endothelial receptor-triggered NO release. An increased oxidative stress and a reduction of NO bioavailability shifts this equilibrium causing the enhanced vascular adrenergic responsiveness observed in hypertension.The activity of NOS contributes to manage the adrenergic pathway, thus supporting the idea that the endothelium might control or facilitate β-adrenergic effects on the vessels and the polymorphic variants in β2-receptors and NOS isoforms could influence aging, some pathological conditions and individual responses to drugs. This seems to be dependent, almost in part, on differences in the control of vascular tone exerted by NO. Given its involvement in such important mechanisms, the NO pathway is implicated in aging process and in both cardiovascular and non-cardiovascular conditions. Thus, it is essential to pinpoint NO involvement in the regulation of vascular tone for the effective clinical/therapeutic management of

  4. Modeling toxic compounds from nitric oxide emission measurements

    Science.gov (United States)

    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.

  5. Nitric oxide emissions from soils amended with municipal waste biosolids

    International Nuclear Information System (INIS)

    Land spreading nitrogen-rich municipal waste biosolids (NO3--N-1 dry weight, NH3-N∼23,080mg Nkg-1 dry weight, Total Kjeldahl N∼41,700mg Nkg-1 dry weight) to human food and non-food chain land is a practice followed throughout the US. This practice may lead to the recovery and utilization of the nitrogen by vegetation, but it may also lead to emissions of biogenic nitric oxide (NO), which may enhance ozone pollution in the lower levels of the troposphere. Recent global estimates of biogenic NO emissions from soils are cited in the literature, which are based on field measurements of NO emissions from various agricultural and non-agricultural fields. However, biogenic emissions of NO from soils amended with biosolids are lacking. Utilizing a state-of-the-art mobile laboratory and a dynamic flow-through chamber system, in-situ concentrations of nitric oxide (NO) were measured during the spring/summer of 1999 and winter/spring of 2000 from an agricultural soil which is routinely amended with municipal waste biosolids. The average NO flux for the late spring/summer time period (10 June 1999-5 August 1999) was 69.4±34.9ngNm-2s-1. Biosolids were applied during September 1999 and the field site was sampled again during winter/spring 2000 (28 February 2000-9 March 2000), during which the average flux was 3.6±l.7ngNm-2s-1. The same field site was sampled again in late spring (2-9 June 2000) and the average flux was 64.8±41.0ng Nm-2s-1. An observationally based model, developed as part of this study, found that summer accounted for 60% of the yearly emission while fall, winter and spring accounted for 20%, 4% and 16% respectively. Field experiments were conducted which indicated that the application of biosolids increases the emissions of NO and that techniques to estimate biogenic NO emissions would, on a yearly average, underestimate the NO flux from this field by a factor of 26. Soil temperature and % water filled pore space (%WFPS) were observed to be significant

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

    Science.gov (United States)

    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.

  7. Gluten Intolerance and Neurodevelopmental Disorders: Is Nitric Oxide the Common Biomarker Linking These Conditions?

    Science.gov (United States)

    Fluegge, Keith

    2016-01-01

    Cruchet et al. attempt to tease out the myths and facts surrounding the growing popularity of certain dietary approaches in the management of neurodevelopmental disorders, like attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorders (ASDs). The authors identify a particular exclusionary-type approach that seeks to eliminate dietary gluten. Although the relationship between celiac disease (CD) and ADHD/ASD is not well established, a repeated clinical feature noted in CD is the elevated levels of nitric oxide in serum and urine. Elevated oxidative stress has also been observed in neurodevelopmental conditions, and the author of this correspondence has been the first to propose that chronic, environmental exposure to the air pollutant, nitrous oxide may contribute to these oxidative stress profiles through neural cholinergic perturbation. Therefore, the purpose of this correspondence is to highlight this biochemical connection between these conditions so as to identify the clinical populations who may realize the greatest benefit of these dietary approaches, while minimizing any potential risk of nutrient deficiencies. PMID:27498299

  8. Pharmacology and potential therapeutic applications of nitric oxide-releasing non-steroidal anti-inflammatory and related nitric oxide-donating drugs

    Science.gov (United States)

    Keeble, J E; Moore, P K

    2002-01-01

    This review examines the biological significance, therapeutic potential and mechanism(s) of action of a range of nitric oxide-releasing non-steroidal anti-inflammatory drugs (NO-NSAID) and related nitric oxide-releasing donating drugs (NODD). The slow release of nitric oxide (NO) from these compounds leads to subtle changes in the profile of pharmacological activity of the parent, non-steroidal anti-inflammatory drugs (NSAID). For example, compared with NSAID, NO-NSAID cause markedly diminished gastrointestinal toxicity and improved anti-inflammatory and anti-nociceptive efficacy. In addition, nitroparacetamol exhibits hepatoprotection as opposed to the hepatotoxic activity of paracetamol. The possibility that NO-NSAID or NODD may be of therapeutic benefit in a wide variety of disease states including pain and inflammation, thrombosis and restenosis, neurodegenerative diseases of the central nervous system, colitis, cancer, urinary incontinence, liver disease, impotence, bronchial asthma and osteoporosis is discussed. PMID:12237248

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

    Science.gov (United States)

    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. Supplementation with l-arginine stabilizes plasma arginine and nitric oxide metabolites, suppresses elevated liver enzymes and peroxidation in sickle cell anaemia.

    Science.gov (United States)

    Jaja, S I; Ogungbemi, S O; Kehinde, M O; Anigbogu, C N

    2016-06-01

    The effect of l-arginine on liver function in SCD has received little or no attention. The effect of a chronic, oral, low-dose supplementation with l-arginine (1gm/day for 6 weeks) on some liver enzymes, lipid peroxidation and nitric oxide metabolites was studied in 20 normal (non-sickle cell anaemia; NSCA) subjects and 20 sickle cell anaemia (SCA) subjects. Ten milliliters of blood was withdrawn from an ante-cubital vein for the estimation of plasma arginine concentration ([R]), alanine aminotransaminase (ALT), aspartate aminotransaminase (AST) and alkaline phosphatase (ALP), plasma total bilirubin concentration [TB], malondialdehyde concentration [MDA] and nitric oxide metabolites concentration [NOx]. Before supplementation, ALT, AST, ALP (pconcentration and nitric oxide metabolites levels in NSCA and SCA subjects. Responses in SCA subjects to l-arginine were more sensitive than in NSCA subjects.

  11. Absorption of nitric oxide into aqueous solutions of ferrous chelates accompanied by instantaneous reaction

    NARCIS (Netherlands)

    Demmink, J.F; vanGils, I.C.F.; Beenackers, A.A C M

    1997-01-01

    The absorption of nitric oxide (NO) into aqueous solutions of ferrous chelates of nitrilotriacetic acid (NTA), ethylene diaminetetraacetic acid (EDTA), hydroxyethylenediaminetriacetic acid (HEDTA), and diethylenetriaminepentaacetic acid (DTPA) was studied in a stirred cell reactor. Experimental cond

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

    Science.gov (United States)

    Brüning, G; Hattwig, K; Mayer, B

    1996-04-01

    Neuronal nitric oxide synthase was located in various organs of the goldfish by NADPH-diaphorase histochemistry and immunohistochemistry. Positive cells were detected throughout the digestive tract. A particularly dense plexus of nitric-oxide-synthase-containing fibers was present at the opening of the pneumatic duct into the esophagus and at the intestinal sphincter separating the esophagus and the intestinal bulb. The nitroxergic innervation was mainly confined to the muscularis. The muscular layer of the swim bladder and of the pneumatic duct was densely equipped with stained neurons and fibers. In the heart, the majority of small neurons located at the sinu-atrial junction was found to be positive for nitric oxide synthase. The muscularis of the urinary duct was supplied by fibers originating from many intramural ganglia harboring intensely stained neurons. These results suggest that nitric oxide represents a widespread transmitter in the peripheral nervous system of teleost species. PMID:8601299

  13. The Effect of Nitric Oxide on the Growth of Marine Phytoplankton

    Institute of Scientific and Technical Information of China (English)

    ZHANG Zhengbin; LIN Cai; LIU Chunying; SUN Mingyi; DING Haibing

    2003-01-01

    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 grovth 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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  16. Lipid Peroxidation, Antioxidant Enzymes and Levels of Nitric Oxide in Sheep Infected with Fasciola hepatica

    OpenAIRE

    BENZER, Fulya; OZAN, Sema TEMİZER

    2003-01-01

    In this study, the levels of malondialdehyde and activities of catalase and glutathione peroxidase, two antioxidant enzymes, and the levels of nitric oxide in sheep infected with Fasciola hepatica were measured. The level of malondialdehyde in plasma and tissue was measured according to the Yagi and Ohkawa methods, respectively. The activities of catalase and glutathione peroxidase were measured according to the methods of Aebi and Beutler, respectively. The level of nitric oxide was deter...

  17. Nitric oxide synthase and neuronal NADPH diaphorase are identical in brain and peripheral tissues.

    OpenAIRE

    Dawson, T. M.; Bredt, D S; M Fotuhi; Hwang, P M; Snyder, S. H.

    1991-01-01

    NADPH diaphorase staining neurons, uniquely resistant to toxic insults and neurodegenerative disorders, have been colocalized with neurons in the brain and peripheral tissue containing nitric oxide synthase (EC 1.14.23.-), which generates nitric oxide (NO), a recently identified neuronal messenger molecule. In the corpus striatum and cerebral cortex, NO synthase immunoreactivity and NADPH diaphorase staining are colocalized in medium to large aspiny neurons. These same neurons colocalize with...

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

    Directory of Open Access Journals (Sweden)

    Ismail Sari

    2013-01-01

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

  19. Conversion of nitrite to nitric oxide at zinc via S-nitrosothiols.

    Science.gov (United States)

    Cardenas, Allan Jay P; Abelman, Rebecca; Warren, Timothy H

    2014-01-01

    Nitrite is an important reservoir of nitric oxide activity in the plasma and cells. Using a biomimetic model, we demonstrate the conversion of zinc-bound nitrite in the tris(pyrazolyl)borate complex (iPr2)TpZn(NO2) to the corresponding S-nitrosothiol RSNO and zinc thiolate (iPr2)TpZn-SR via reaction with thiols H-SR. Decomposition of the S-nitrosothiol formed releases nitric oxide gas. PMID:24217415

  20. Effects of Smokeless Tobacco “Maras Powder” Use on Nitric Oxide and Cardiovascular Risk Parameters

    OpenAIRE

    Aytekin Guven, Fatma Tolun

    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 ...

  1. Serum nitric oxide status in patients with type 2 diabetes mellitus in Sikkim

    OpenAIRE

    Ghosh, Amrita; Sherpa, Mingma L.; Bhutia, Yazum; Pal, Ranabir; Dahal, Sanjay

    2011-01-01

    Background: Serum nitric oxide (NO) has emerged as a fundamental signal associated with the endothelial dysfunction in type 2 diabetes. Aims: To compare serum nitric oxide level among type 2 diabetic patients along with other biochemical parameters and to compare it with that of normal population in Sikkim. Settings and Design: This prospective study was carried out in the Biochemistry Department in a tertiary care teaching hospital in Sikkim on 50 type 2 diabetics compared to 100 non-diabeti...

  2. Nitric oxide secretion in human conjunctival fibroblasts is inhibited by alpha linolenic acid

    OpenAIRE

    Erdinest, Nir; Shohat, Noam; Moallem, Eli; Yahalom, Claudia; Mechoulam, Hadas; Anteby, Irene; Ovadia, Haim; Solomon, Abraham

    2015-01-01

    Purpose It is known that both human conjunctival fibroblasts (HCF) and corneal epithelial (HCE) cells contribute to the inflammatory process in the ocular surface by releasing inflammatory cytokines. In addition, nitric oxide (NO) has an important role in inflammatory responses in the ocular surface. In the present study, we aimed to characterize the capacity of these cells to release nitric oxide in response to cytokines and Lipopolysaccharide (LPS), and show that Alpha-linoleic acid (ALA) i...

  3. A specific method for measurement of nitric oxide synthase enzymatic activity in peritoneal biopsies.

    OpenAIRE

    Combet, S.; Balligand, Jean-Luc; Lameire, N.; Goffin, Eric; Devuyst, Olivier

    2000-01-01

    A specific method for measurement of nitric oxide synthase enzymatic activity in peritoneal biopsies. BACKGROUND: Nitric oxide (NO) is synthesized by NO synthase (NOS) isoforms that are expressed in the peritoneum. Thus far, NOS activity in the peritoneum has been assessed by nonspecific methods. We describe the application of a specific method for determination of NOS activity in rat and human peritoneal biopsies. METHODS: The L-citrulline assay is based on the stoechiometric production of N...

  4. Effect of Korean red ginseng on blood pressure and nitric oxide production

    Institute of Scientific and Technical Information of China (English)

    JEON Byeong Hwa; KIM Cuk Seong; KIM Hoe-Suk; PARK Jin-Bong; NAM Ki Yeul; CHANG Seok Jong

    2000-01-01

    AIM: To investigate the effect of crude saponin and nonsaponin fraction of Korean red ginseng (KRG) on the blood pressure and nitric oxide (NO) production in the conscious rats and cultured endothelial cell line, FCV 304 cells. METHODS: Systolic blood pressure and heart rate were monitored in the conscious rats. Nitric oxide levels and the expression of nitric oxide synthase were measured by a spectrophotometric assay using Griess reagents and Western blotting, respectively. Nitric-oxide synthase activity was measured based on the conversion rate of [3H]arginine to [3H]citmlline. RESUITS: Systolic blood pressure was decreased by crude saponin (100 mg/kg, iv) of KRG in the conscious control and one-kidney, one-clip Goldblatt hypertensive (1K, 1C-GBH) rats. The hypotensive effect induced by crude saponin of KRG reached maximum at 2 - 4 min and slowly recovered after 20 min to the initial level in both groups. Crude saponin of KRG induced tacliycardia in the conscious rats but induced bradycardia in the anesthetized rats. In contrast to crude saponin of KRG, hypotensive effect induced by saponin-free fraction was minimal. Nitric oxide concentrations were increased by the treaunent of crude saponin in conscious rats as well as in the cultured FCV 304 cells. The protein expression level of endothelial constitutive nitric-oxide synthase (eNOS) in the aorta of rats was not increased by crude saponin (100 mg/kg, ip for 3 d). However, nitric-oxide synthase activity was increased by crude saponin of KRG in the aortic homogenate of rats. CONCLUSION: The hypotensive effect of red ginseng is mainly due to saponin fraction of KRG in the conscious rats, and this effect may be due to an increase in the nitric-oxide production by KRG.

  5. Comparison Between the Acute Pulmonary Vascular Effects of Oxygen with Nitric Oxide and Sildenafil

    Directory of Open Access Journals (Sweden)

    Ronald W. Day

    2015-03-01

    Full Text Available Objective. Right heart catheterization is performed in patients with pulmonary arterial hypertension to determine the severity of disease and their pulmonary vascular reactivity. The acute pulmonary vascular effect of inhaled nitric oxide is frequently used to identify patients who will respond favorably to vasodilator therapy. This study sought to determine whether the acute pulmonary vascular effects of oxygen with nitric oxide and intravenous sildenafil are similar. Methods. A retrospective, descriptive study of 13 individuals with pulmonary hypertension who underwent heart catheterization and acute vasodilator testing was performed. The hemodynamic measurements during five phases (21% to 53% oxygen, 100% oxygen, 100% oxygen with 20 ppm nitric oxide, 21% to 51% oxygen, and 21% to 51% oxygen with 0.05 mg/kg to 0.29 mg/kg intravenous sildenafil of the procedures were compared.Results. Mean pulmonary arterial pressure and pulmonary vascular resistance acutely decreased with 100% oxygen with nitric oxide, and 21% to 51% oxygen with sildenafil. Mean pulmonary arterial pressure (mm Hg, mean ± standard error of the mean was 38 ± 4 during 21% to 53% oxygen, 32 ± 3 during 100% oxygen, 29 ± 2 during 100% oxygen with nitric oxide, 37 ± 3 during 21% to 51% oxygen, and 32 ± 2 during 21% to 51% oxygen with sildenafil. There was not a significant correlation between the percent change in pulmonary vascular resistance from baseline with oxygen and nitric oxide, and from baseline with sildenafil (r2 = 0.011, p = 0.738. Conclusions. Oxygen with nitric oxide and sildenafil decreased pulmonary vascular resistance. However, the pulmonary vascular effects of oxygen and nitric oxide cannot be used to predict the acute response to sildenafil. Additional studies are needed to determine whether the acute response to sildenafil can be used to predict the long-term response to treatment with an oral phosphodiesterase V inhibitor.

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

    Science.gov (United States)

    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

  7. Regulation between nitric oxide and MAPK signal transduction in mammals

    Institute of Scientific and Technical Information of China (English)

    TAO Yong; ZHANG Meijia; HONG Haiyan; XIA Guoliang

    2005-01-01

    Nitric oxide (NO) is an important biological messenger in the regulation of tissue homeostasis. It exhibits a wide range of effects during physiological and pathophysiological processes. Typical beneficial properties of NO include the regulation of vascular tone,the protection of cells against apoptosis, the modulation of immune responses, and the killing of microbial pathogens. On the other hand,NO may cause severe vasodilation and myocardial depression during bacterial sepsis or act as a cytotoxic and tissue-damaging molecule in autoimmune diseases. Mitogen-activated protein kinase (MAPK) is a family of serine/threonine protein kinases that are widely distributed in mammalian cells. MAPK cascade plays pivotal roles in gene expression, cell proliferation, differentiation, neuronal survival and programmed cell death under a variety of experimental conditions. MAPKs transduce the signal for the cellular response to extracellular stresses or stimuli. The relation between them, however, has never been reviewed. Based on our researches and other reports in the field, we review their reciprocal regulatory functions.

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    Ling Cui

    2015-09-01

    Full Text Available 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.

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

    Science.gov (United States)

    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

  11. Solar cycle variations of thermospheric nitric oxide at solstice

    International Nuclear Information System (INIS)

    A coupled two-dimensional chemical-diffusive model of the thermosphere is used to system the role of solar activity in the global distribution of nitric oxide. The model calculates self-consistently the zonally averaged temperature, circulation, and composition for solstice under solar maximum (F10.7 = 200) and solar minimum (F10.7 = 80) conditions. A decrease of the NO density by a factor of 3 to 4 in the E region is predicted from solar maximum to solar minimum. These results are compared with the global NO distribution observed with the Solar Mesosphere Explorer (SME) satellite in 1982 and 1985. It is found that the main features of the overall morphology and the changes induced by the solar cycle are well reproduced in the model, although some details are not satisfactorily predicted. The observed increase of the E region concentration with solar activity by a factor of 2.5 is slightly overpredicted by the model, but the SME data show a smaller solar cycle variation above 120 km than does the model. The sensitivity of the NO distribution to eddy transport and to the quenching of metastable N(2D) atoms by atomic oxygen is also described

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

    Science.gov (United States)

    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

  13. Asenapine modulates nitric oxide release and calcium movements in cardiomyoblasts

    Directory of Open Access Journals (Sweden)

    Elena Grossini

    2016-01-01

    Full Text Available Objective: To examine the effects of asenapine on nitric oxide (NO release and Ca2+ transients in H9C2 cell line, which were either subjected to peroxidation or not. Materials and Methods: H9C2 were treated with asenapine alone or in presence of intracellular kinase blockers, serotoninergic and dopaminergic antagonists, and voltage Ca2+ channels inhibitors. Experiments were also performed in H9C2 treated with hydrogen peroxide. NO release and intracellular Ca2+ were measured through specific probes. Results: In H9C2, asenapine differently modulated NO release and Ca2+ movements depending on peroxidative condition. The Ca2+ pool mobilized by asenapine mainly originated from the extracellular space and was slightly affected by thapsigargin. Moreover, the effects of asenapine were reduced or prevented by kinases blockers, dopaminergic and serotoninergic receptors inhibitors, and voltage Ca2+ channels blockers.Conclusions: On the basis of our findings, we can conclude that asenapine by interacting with its specific receptors, exerts dual effects on NO release and Ca2+ homeostasis in H9C2; this would be of particular clinical relevance when considering their role in cardiac function modulation.

  14. Nitric oxide-releasing NSAIDs: GI-safe antithrombotics.

    Science.gov (United States)

    Wallace, J L; Del Soldato, P; Cirino, G; Muscará, M N

    1999-04-01

    Aspirin is increasingly being used for long-term prophylaxis of myocardial infarction and stroke, but its use is limited by toxicity in the gastrointestinal tract. Even very low doses of aspirin can markedly increase the risk of gastrointestinal bleeding and ulceration. While proven effective in prophylaxis of stroke and myocardial infarction, the efficacy of aspirin is limited. Addition of a nitric oxide-releasing moiety to several non-steroidal anti-inflammatory drugs results in a profound reduction in their toxicity in the gastrointestinal tract and kidney. A similar derivatization of aspirin has recently been shown to result in a more potent, gastrointestinal-sparing antithrombotic drug. Two such compounds (NCX-4215 and NCX-4016; NicOx SA) have undergone detailed evaluation thus far. In each case, the NO-aspirin has shown improved anti-aggregatory activity while not inducing detectable gastric damage. The compounds have also been shown to exert protective effects in the gastrointestinal tract exposed to other injurious agents. The NO-aspirin derivatives significantly inhibit leukocyte adherence to the vascular endothelium, which may contribute to their anti-thrombotic activity. NO-releasing derivatives of aspirin and naproxen also exhibit beneficial effects in experimental hypertension, which would also contribute to improved anti-thrombotic activity. NO-releasing derivatives of NSAIDs offer great potential as gastrointestinal-sparing anti-thrombotic drugs. PMID:16158351

  15. Reference values for exhaled nitric oxide (reveno study

    Directory of Open Access Journals (Sweden)

    Mutti Antonio

    2006-06-01

    Full Text Available Abstract Background Despite the widespread use of fractional exhaled nitric oxide (FENO as a biomarker of airways inflammation, there are no published papers describing normal FENO values in a large group of healthy adults. Objective The aim of this study was to establish adult FENO reference values according to the international guidelines. Methods FENO was measured in 204 healthy, non-smoking adults with normal spirometry values using the on-line single-breath technique, and the results were analysed chemiluminescently. Results The main result of the study was the significant difference in FENO values between men and women, thus indicating that gender-based reference FENO values are necessary. The FENO levels obtained at expiratory flows of 50 ml/s ranged from 2.6 to 28.8 ppb in men, and from 1.6 to 21.5 ppb in women. Conclusion We propose reference FENO values for healthy adult men and women that could be used for clinical and research purposes.

  16. Increased amount of nitric oxide in exhaled air of asthmatics.

    Science.gov (United States)

    Alving, K; Weitzberg, E; Lundberg, J M

    1993-10-01

    The presence of nitric oxide (NO) in the exhaled air of humans has recently been described. We wanted to assess at what level exhaled NO originates in normal airways, and to determine whether airway inflammation induces changes in the levels of exhaled NO. Exhaled NO was continuously measured by chemiluminescence technique during normal tidal breathing through the nose or mouth, with a detection limit of 1 part per billion (ppb). Twelve control subjects were compared to eight patients with mild atopic asthma and rhinitis caused by occupational allergen. In control subjects, the major part of NO in exhaled air (up to 30 ppb) seemed to originate in the nasal airways, with only minor contribution from the lower airways and the oral cavity. However, in mild asthmatics, the level of exhaled NO during oral breathing, indicating the involvement of the lower airways, was increased 2-3 fold. Since increased production of NO in the lower airways may involve activated macrophages or neutrophils, we suggest that exhaled NO may be used to instantly monitor ongoing bronchial inflammation, at least when involving inducible NO synthase. PMID:7507065

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  19. Porins facilitate nitric oxide-mediated killing of mycobacteria.

    Science.gov (United States)

    Fabrino, Daniela Leite; Bleck, Christopher K E; Anes, Elsa; Hasilik, Andrej; Melo, Rossana C N; Niederweis, Michael; Griffiths, Gareth; Gutierrez, Maximiliano Gabriel

    2009-09-01

    Non-pathogenic mycobacteria such us Mycobacterium smegmatis reside in macrophages within phagosomes that fuse with late endocytic/lysosomal compartments. This sequential fusion process is required for the killing of non-pathogenic mycobacteria by macrophages. Porins are proteins that allow the influx of hydrophilic molecules across the mycobacterial outer membrane. Deletion of the porins MspA, MspC and MspD significantly increased survival of M. smegmatis in J774 macrophages. However, the mechanism underlying this observation is unknown. Internalization of wild-type M. smegmatis (SMR5) and the porin triple mutant (ML16) by macrophages was identical indicating that the viability of the porin mutant in vivo was enhanced. This was not due to effects on phagosome trafficking since fusion of phagosomes containing the mutant with late endocytic compartments was unaffected. Moreover, in ML16-infected macrophages, the generation of nitric oxide (NO) was similar to the wild type-infected cells. However, ML16 was significantly more resistant to the effects of NO in vitro compared to SMR5. Our data provide evidence that porins render mycobacteria vulnerable to killing by reactive nitrogen intermediates within phagosomes probably by facilitating uptake of NO across the mycobacterial outer membrane. PMID:19460455

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

    Science.gov (United States)

    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.

  1. Molecular dynamics simulation of nitric oxide in myoglobin

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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 thetaNODLNO 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 thetaNO. 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 thetaNO [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 thetaNO=4.5 ml NO.(min.Torr.ml blood)(-1) for calculation of DM(NO) and pulmonary capillary blood volume from DLNO and DLCO.

  3. Differential modulation of nitric oxide synthases in aging: therapeutic opportunities

    Directory of Open Access Journals (Sweden)

    Stêfany Bruno De Assis Cau

    2012-06-01

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

  4. Nitric oxide synthetase and Helicobacter pylori in patients undergoing appendicectomy.

    LENUS (Irish Health Repository)

    Kell, M R

    2012-02-03

    BACKGROUND: This study was designed to determine whether Helicobacter pylori forms part of the normal microenvironment of the appendix, whether it plays a role in the pathogenesis of acute appendicitis, and whether it is associated with increased expression of inducible nitric oxide synthetase (iNOS) in appendicular macrophages. METHODS: Serology for H. pylori was performed on 51 consecutive patients undergoing emergency appendicectomy. Appendix samples were tested for urease activity, cultured and stained for H. pylori, graded according to the degree of inflammatory infiltrate, and probed immunohistochemically for iNOS expression. RESULTS: The mean age of the patients was 21 (range 7-51) years. Seventeen patients (33 per cent) were seropositive for H. pylori but no evidence of H. pylori was found in any appendix specimen. However, an enhanced inflammatory cell infiltration was observed in seropositive patients (P < 0.04) and the expression of macrophage iNOS in the mucosa of normal and inflamed appendix specimens was increased (P < 0.01). CONCLUSION: H. pylori does not colonize the appendix and is unlikely to be a pathogenic stimulus for appendicitis. Priming effects on mucosal immunology downstream from the foregut may occur after infection with H. pylori.

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

    Science.gov (United States)

    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. PMID:25079268

  6. Nitric Oxide: A Multitasked Signaling Gas in Plants

    KAUST Repository

    Domingos, Patricia

    2014-12-01

    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 Ca2+ 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.

  7. Possible involvement of nitric oxide mechanism in the protective effect of Melatonin against sciatic nerve ligation induced behavioral and biochemical alterations in rats

    Directory of Open Access Journals (Sweden)

    Meena, Seema

    2011-03-01

    Full Text Available Introduction: Neuropathic pain is a debilitating disease afflicting wider population now days. Peripheral nerve injury produces a persistent neuropathic pain. Recently, oxidative stress nitric oxide pathway has been proposed in the pathogenesis of such type of painful conditions. Melatonin, the secretory product of the pineal gland, has potent antioxidant properties. The objective of the present study was to explore possible nitric oxide mechanism in the protective effect of melatonin against sciatic nerve ligation induced behavioral and biochemical alterations in rats Materials and Methods: Sciatic nerve ligation was performed in Wistar male rats. Various behavioral parameters (thermal hyperalgesia, cold allodynia as well as biochemical parameters (lipid peroxidation, reduced glutathione, catalse, and nitrite were assessed in sciatic nerve. Drugs were administered for 21 consecutive days from the day of surgery. Results: Sciatic nerve ligation (CCI significantly caused thermal hyeralgesia, cold allodynia and oxidative damage as compared to naïve and sham control. Chronic administration of melatonin (2.5 mg/kg and 5 mg/kg, ip significantly reversed hyperalgesia, cold allodynia and attenuated oxidative damage (as indicated by reduced lipid peroxidation, nitric concentration, restoration of reduced glutathione and catalse activity in sciatic nerve as compared to control (CCI. Further, L-NAME (5 mg/kg (nitric oxide synthase inhibitor pretreatment with effective doses of melatonin (2.5mg/kg and 5.0 mg/kg, ip potentiated the protective effect of melatonin which was significant as compared to their effect per se in sciatic nerve. However, L-arginine (100 mg/kg (nitric oxide precursor pretreatment with melatonin (2.5mg/kg and 5.0 mg/kg, ip significantly reversed the protective effects of melatonin in sciatic nerve. Conclusion- Result of present study suggests that nitric oxide mechanism might be involved in the protective effect of melatonin against

  8. Uso do óxido nítrico em pediatria Inhaled nitric oxide in pediatrics

    Directory of Open Access Journals (Sweden)

    José R. Fioretto

    2003-11-01

    persistent pulmonary hypertension and hypoxia of the newborn, acute respiratory distress syndrome, primary pulmonary hypertension, heart surgery, chronic obstructive pulmonary disease, sickle cell anemia, and bronchospastic disease. CONCLUSIONS: Inhaled nitric oxide is a therapeutic approach with wide clinical applications in pediatrics. Its use is safe when administered in pediatric intensive care units under strict monitoring. As a pulmonary vasodilator, nitric oxide has beneficial effects on gas exchange and ventilation. Controlled trials, focusing on early gas administration should be performed under many clinical conditions, especially acute respiratory distress syndrome.

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

    Energy Technology Data Exchange (ETDEWEB)

    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. Potential neurogenic and vascular roles of nitric oxide in migraine headache and aura.

    Science.gov (United States)

    Myers, D E

    1999-02-01

    It has long been known that nitrate and nitrite medications consistently cause significant headache as a side effect. Classical research has shown that cerebral vasodilation accompanies the use of these medications. More modern studies suggest that these vasodilators exert their action on blood vessels via nitric oxide and its second messenger, cyclic guanosine monophosphate. This paper reviews research studies and theoretical articles which address the concept that nitric oxide plays a major role in the vasodilation associated with the headache phase of migraine with aura. A brief discussion of nitric oxide biochemistry and pharmacology follows. In addition, there is a review of evidence examining the possible contributions of nitric oxide to the neurogenic and vascular events associated with spreading cortical depression, an animal model of migraine aura. The paradoxical hypotheses that nitric oxide may contribute to both the propagation of spreading cortical depression and its limitation are presented. Finally, a rationale for the experimental use of nitric oxide agonists and antagonists in the abortion of migraine aura is introduced. PMID:15613204

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

    Science.gov (United States)

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

    2013-07-01

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

  12. Negative association of endothelial nitric oxide gene polymorphism with hypertension in Turkish patients: effect of ecNOS polymorphism on left ventricular hypertrophy

    OpenAIRE

    Arslan Erol; Barcin Cem; Sezer Murat; Ozbek Ugur; Ekmekci C Gokhan; Olcay Ayhan; Boztosun Bilal; Nisanci Yilmaz

    2006-01-01

    Abstract Background Endothelial nitric oxide synthase produces nitric oxide which is involved in many physiologic regulatory functions. Variable number of tandem repeats in intron 4 of endothelial nitric oxide synthase gene are reported to be associated with blood pressure regulation. Nitric oxide is involved in regulation of cardiomyocyte genes but it is not known If endothelial nitric oxide synthase 4 gene polymorphisms are related with left ventricular hypertrophy. We studied endothelial n...

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

    Science.gov (United States)

    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.

  14. Piper sarmentosum increases nitric oxide production in oxidative stress: a study on human umbilical vein endothelial cells

    Directory of Open Access Journals (Sweden)

    Azizah Ugusman

    2010-01-01

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

  15. Effect of glutathione on brain nitric oxide levels in an experimental epilepsy mouse model

    Institute of Scientific and Technical Information of China (English)

    Aylin Akcali; Sadrettin Pence; Naciye Kurtul; Mehmet Bosnak; Munife Neyal

    2009-01-01

    BACKGROUND: Oxidative stress plays an important role in the pathophysiology of epilepsy. Glutathione, known as one of the compounds of antioxidant defense, has been shown to inhibit convulsions. Nitric oxide has a proconvulsant effect on a pentylenetetrazole-induced animal model. OBJECTIVE: To evaluate the effects of glutathione administration on nitric oxide levels in brain regions of convulsive and kindling pentylenetetrazole-induced seizure models. DESIGN, TIME, AND SETTING: A randomized, controlled, animal experiment. The study was performed at the Department of Physiology, Gaziantep University and Department of Chemistry-Biochemistry, Kahramamaras Sutcu Imam University in 2006.MATERIALS: Pentylenetetrazole and glutathione were purchased from Sigma, USA. METHODS: A total of 80 mice were assigned to 8 groups (n=10): normal control, saline control (1 mL normal saline), convulsive pentylenetetrazole (single intraperitoneal administration of pentylenetetrazole, 60 mg/kg), convulsive pentylenetrazole plus glutathione (single administration of 60 mg/kg pentylenetetrazole and 200 mg/kg glutathione), five-dose glutathione (intraperitoneal injection of 200 mg/kg glutathione respectively at 1, 3, 5, 7, and 10 days), single-dose glutathione (single administration of 200 mg/kg glutathione), pentylenetetrazole kindling (intraperitoneal administration of pentylenetetrazole of 40 mg/kg at 1, 3, 5, 7, and 10 days), and pentylenetetrazole kindling plus glutathione group (intraperitoneal injection of 40 mg/kg pentylenetetrazole and 200 mg/kg glutathione respectively at 1, 3, 5, 7, and 10 days). MAIN OUTCOME MEASURES: All mice were sacrificed 1 hour after the last administration. Brain nitric oxide levels were determined by spectrophotometry. RESULTS: There were no significant differences in nitric oxide levels between the normal control, saline control, five-dose glutathione, and single-dose glutathione groups (P>0.05). Nitric oxide levels in the cerebral hemisphere and

  16. Endothelial nitric oxide synthase gene haplotypes and circulating nitric oxide levels significantly associate with risk of essential hypertension.

    Science.gov (United States)

    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 (Phypertension (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 (Phypertension and served as protective haplotypes (Ppolymorphisms showed marginal association with NO(x) level; however, the susceptible haplotype H2 associated significantly with lower NO(x) levels in patients (Ppolymorphisms were identified as the determinants modifying the risk of hypertension. This study identifies the NOS3 variants and haplotypes as genetic risk factors and as useful markers of increased susceptibility to the risk of essential hypertension. PMID:18325347

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

    Science.gov (United States)

    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

  18. Is endothelial-nitric-oxide-synthase-derived nitric oxide involved in cardiac hypoxia/reoxygenation-related damage?

    Indian Academy of Sciences (India)

    A Rus; Ma Peinado; S Blanco; Ml Del Moral

    2011-03-01

    Nitric oxide (NO) has been reported to act both as a destructive and a protective agent in the pathogenesis of the injuries that occur during hypoxia/reoxygenation (H/R). It has been suggested that this dual role of NO depends directly on the isoform of NO synthase (NOS) involved. In this work, we investigate the role that NO derived from endothelial NOS (eNOS) plays in cardiac H/R-induced injury.Wistar rats were submitted to H/R (hypoxia for 30 min; reoxygenation of 0 h, 12 h and 5 days), with or without prior treatment using the selective eNOS inhibitor L-NIO (20 mg/kg). Lipid peroxidation, apoptosis and protein nitration, as well as NO production (NOx), were analysed. The results showed that L-NIO administration lowered NOx levels in all the experimental groups. However, no change was found in the lipid peroxidation level, the percentage of apoptotic cells or nitrated protein expression, implying that eNOS-derived NO may not be involved in the injuries occurring during H/R in the heart. We conclude that L-NIO would not be useful in alleviating the adverse effects of cardiac H/R.

  19. Diazeniumdiolate mediated nitrosative stress alters nitric oxide homeostasis through intracellular calcium and S-glutathionylation of nitric oxide synthetase.

    Directory of Open Access Journals (Sweden)

    Yefim Manevich

    Full Text Available BACKGROUND: PABA/NO is a diazeniumdiolate that acts as a direct nitrogen monoxide (NO donor and is in development as an anticancer drug. Its mechanism of action and effect on cells is not yet fully understood. METHODOLOGY/PRINCIPAL FINDINGS: We used HPLC and mass spectrometry to identify a primary nitroaromatic glutathione metabolite of PABA/NO and used fluorescent assays to characterize drug effects on calcium and NO homeostasis, relating these to endothelial nitric oxide synthase (eNOS activity. Unexpectedly, the glutathione conjugate was found to be a competitive inhibitor of sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA presumably at the same site as thapsigargin, increasing intracellular Ca2+ release and causing auto-regulation of eNOS through S-glutathionylation. CONCLUSIONS/SIGNIFICANCE: The initial direct release of NO after PABA/NO was followed by an eNOS-mediated generation of NO as a consequence of drug-induced increase in Ca2+ flux and calmodulin (CaM activation. PABA/NO has a unique dual mechanism of action with direct intracellular NO generation combined with metabolite driven regulation of eNOS activation.

  20. Effect of aging on expression of nitric oxide synthase I and activity of nitric oxide synthase in rat penis

    Institute of Scientific and Technical Information of China (English)

    Jun-PingSHI; Yong-MeiZHAO; Yu-TongSONG

    2003-01-01

    Aim: To investigate the effect of aging on the expression of nitric oxide synthase I (NOS I) and the activity of NOS in rat penis. Methods: Sixty male rats from 3 age groups (adult, old and senescent) were investigated.The expression of NOS I protein and mRNA in rat penis were detected by Western blot and RT-PCR respectively and the NOS activity, with ultraviolet spectrophotometry. Results: In the old and senescent group, NOS I protein expression was significantly decreased as compared with the adult. NOS I mRNA expression was well correlated with the protein expression. NOS activity was not statistically different between the adult and old groups, but it was significantly reduced in the senescent compared with the adult group (P<0.01). Conclusion: The aging-induced decreases in NOS I expression and NOS activity may be one of the main mechanisms leading to erectile dysfunctionin the senescent rats. ( Asian J Androl 2003 Jun; 5: 117-120)

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

    Science.gov (United States)

    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.

  2. Nitric oxide-dependent activation of CaMKII increases diastolic sarcoplasmic reticulum calcium release in cardiac myocytes in response to adrenergic stimulation.

    Directory of Open Access Journals (Sweden)

    Jerry Curran

    Full Text Available Spontaneous calcium waves in cardiac myocytes are caused by diastolic sarcoplasmic reticulum release (SR Ca(2+ leak through ryanodine receptors. Beta-adrenergic (β-AR tone is known to increase this leak through the activation of Ca-calmodulin-dependent protein kinase (CaMKII and the subsequent phosphorylation of the ryanodine receptor. When β-AR drive is chronic, as observed in heart failure, this CaMKII-dependent effect is exaggerated and becomes potentially arrhythmogenic. Recent evidence has indicated that CaMKII activation can be regulated by cellular oxidizing agents, such as reactive oxygen species. Here, we investigate how the cellular second messenger, nitric oxide, mediates CaMKII activity downstream of the adrenergic signaling cascade and promotes the generation of arrhythmogenic spontaneous Ca(2+ waves in intact cardiomyocytes. Both SCaWs and SR Ca(2+ leak were measured in intact rabbit and mouse ventricular myocytes loaded with the Ca-dependent fluorescent dye, fluo-4. CaMKII activity in vitro and immunoblotting for phosphorylated residues on CaMKII, nitric oxide synthase, and Akt were measured to confirm activity of these enzymes as part of the adrenergic cascade. We demonstrate that stimulation of the β-AR pathway by isoproterenol increased the CaMKII-dependent SR Ca(2+ leak. This increased leak was prevented by inhibition of nitric oxide synthase 1 but not nitric oxide synthase 3. In ventricular myocytes isolated from wild-type mice, isoproterenol stimulation also increased the CaMKII-dependent leak. Critically, in myocytes isolated from nitric oxide synthase 1 knock-out mice this effect is ablated. We show that isoproterenol stimulation leads to an increase in nitric oxide production, and nitric oxide alone is sufficient to activate CaMKII and increase SR Ca(2+ leak. Mechanistically, our data links Akt to nitric oxide synthase 1 activation downstream of β-AR stimulation. Collectively, this evidence supports the hypothesis

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

    Directory of Open Access Journals (Sweden)

    K. Yanar

    2016-01-01

    Full Text Available 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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

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

    2000-08-01

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

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

    Directory of Open Access Journals (Sweden)

    Ketab E. Al-Otaibi

    2012-01-01

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

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

    Science.gov (United States)

    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

  8. Skeletal Muscle Function during Exercise—Fine-Tuning of Diverse Subsystems by Nitric Oxide

    Directory of Open Access Journals (Sweden)

    Wilhelm Bloch

    2013-03-01

    Full Text Available Skeletal muscle is responsible for altered acute and chronic workload as induced by exercise. Skeletal muscle adaptations range from immediate change of contractility to structural adaptation to adjust the demanded performance capacities. These processes are regulated by mechanically and metabolically induced signaling pathways, which are more or less involved in all of these regulations. Nitric oxide is one of the central signaling molecules involved in functional and structural adaption in different cell types. It is mainly produced by nitric oxide synthases (NOS and by non-enzymatic pathways also in skeletal muscle. The relevance of a NOS-dependent NO signaling in skeletal muscle is underlined by the differential subcellular expression of NOS1, NOS2, and NOS3, and the alteration of NO production provoked by changes of workload. In skeletal muscle, a variety of highly relevant tasks to maintain skeletal muscle integrity and proper signaling mechanisms during adaptation processes towards mechanical and metabolic stimulations are taken over by NO signaling. The NO signaling can be mediated by cGMP-dependent and -independent signaling, such as S-nitrosylation-dependent modulation of effector molecules involved in contractile and metabolic adaptation to exercise. In this review, we describe the most recent findings of NO signaling in skeletal muscle with a special emphasis on exercise conditions. However, to gain a more detailed understanding of the complex role of NO signaling for functional adaptation of skeletal muscle (during exercise, additional sophisticated studies are needed to provide deeper insights into NO-mediated signaling and the role of non-enzymatic-derived NO in skeletal muscle physiology.

  9. Targets of nitric oxide in a mouse model of liver inflammation by Corynebacterium parvum.

    Science.gov (United States)

    Chamulitrat, W; Jordan, S J; Mason, R P; Litton, A L; Wilson, J G; Wood, E R; Wolberg, G; Molina y Vedia, L

    1995-01-10

    Treatment of mice with Corynebacterium parvum induces chronic inflammation. This treatment followed by an injection of lipopolysaccharide (LPS) produces hepatic necrosis and death. We examined liver tissue by using electron paramagnetic resonance (EPR) spectroscopy and found that, in addition to the previously reported nonheme nitrosyl complexes, heme nitrosyl complexes were also formed. Hemoglobin nitrosyl complexes measured in the whole blood of mice treated with C. parvum were not increased after additional LPS treatment. However, this treatment significantly increased the heme nitrosyl complexes in the liver, whereas the nonheme nitrosyl complex concentration was unaffected. EPR signals from whole blood and liver tissues from mice treated with C. parvum and C. parvum + LPS were inhibited by prolonged treatment with NG-monomethyl-L-arginine (L-NMA). Nitric oxide (.NO) is known to bind to cytochrome P450 heme, and we consistently found a suppression of EPR signals attributable to ferric low-spin cytochrome P450/P420 peaks in the livers of mice treated with C. parvum and C. parvum + LPS. By performing analyses of EPR spectra obtained from hepatocytes exposed to .NO, we were able to unambiguously identify EPR signals attributable to cytochrome P420 and nonheme nitrosyl complexes in the livers of both treatments. Deconvolution of the composite in vivo EPR spectra indicated that hemoglobin nitrosyl complexes contributed weakly in the C. parvum livers, but threefold more in the C. parvum + LPS livers, suggesting that hemorrhage may have occurred. Experiments with L-NMA treatment revealed that this additional .NO production did not correlate with hepatic necrosis and onset of death. Immunoprecipitation of liver cytosols from C. parvum- and (C. parvum + LPS)-treated mice using an antibody against mouse inducible nitric oxide synthase showed that this enzyme was indeed present in the cytosolic fractions and was absent in those from control livers. Our novel detection of

  10. Metabolism via arginase or nitric oxide synthase: two competing arginine pathways in macrophages

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    Meera eRath

    2014-10-01

    Full Text Available Macrophages play a major role in the immune system, both as antimicrobial effector cells and as immunoregulatory cells, which induce, suppress or modulate adaptive immune responses. These key aspects of macrophage biology are fundamentally driven by the phenotype of macrophage arginine metabolism that is prevalent in an evolving or ongoing immune response. M1 macrophages express the enzyme nitric oxide synthase (NOS, which metabolizes arginine to nitric oxide (NO and citrulline. NO can be metabolized to further downstream reactive nitrogen species, while citrulline might be reused for efficient NO synthesis via the citrulline-NO cycle. M2 macrophages are characterized by expression of the enzyme arginase, which hydrolyzes arginine to ornithine and urea. The arginase pathway limits arginine availability for NO synthesis and ornithine itself can further feed into the important downstream pathways of polyamine and proline syntheses, which are important for cellular proliferation and tissue repair. M1 versus M2 polarization leads to opposing outcomes of inflammatory reactions, but depending on the context, M1 and M2 macrophages can be both pro- and antiinflammatory. Notably, M1/M2 macrophage polarization can be driven by microbial infection or innate danger signals without any influence of adaptive immune cells, secondarily driving the T helper (Th1/Th2 polarization of the evolving adaptive immune response. Since both arginine metabolic pathways cross-inhibit each other on the level of the respective arginine break-down products and Th1 and Th2 lymphocytes can drive or amplify macrophage M1/M2 dichotomy via cytokine activation, this forms the basis of a self-sustaining M1/M2 polarization of the whole immune response. Understanding the arginine metabolism of M1/M2 macrophage phenotypes is therefore central to find new possibilities to manipulate immune responses in infection, autoimmune diseases, chronic inflammatory conditions and cancer.

  11. Liposome-encapsulated ISMN: a novel nitric oxide-based therapeutic agent against Staphylococcus aureus biofilms.

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    Camille Jardeleza

    Full Text Available BACKGROUND: Staphylococcus aureus in its biofilm form has been associated with recalcitrant chronic rhinosinusitis with significant resistance to conventional therapies. This study aims to determine if liposomal-encapsulation of a precursor of the naturally occurring antimicrobial nitric oxide (NO enhances its desired anti-biofilm effects against S. aureus, in the hope that improving its efficacy can provide an effective topical agent for future clinical use. METHODOLOGY: S. aureus ATCC 25923 biofilms were grown in-vitro using the Minimum Biofilm Eradication Concentration (MBEC device and exposed to 3 and 60 mg/mL of the NO donor isosorbide mononitrate (ISMN encapsulated into different anionic liposomal formulations based on particle size (unilamellar ULV, multilamellar MLV and lipid content (5 and 25 mM at 24 h and 5 min exposure times. Biofilms were viewed using Live-Dead Baclight stain and confocal scanning laser microscopy and quantified using the software COMSTAT2. RESULTS: At 3 and 60 mg/mL, ISMN-ULV liposomes had comparable and significant anti-biofilm effects compared to untreated control at 24 h exposure (p = 0.012 and 0.02 respectively. ULV blanks also had significant anti-biofilm effects at both 24 h and 5 min exposure (p = 0.02 and 0.047 respectively. At 5 min exposure, 60 mg/mL ISMN-MLV liposomes appeared to have greater anti-biofilm effects compared to pure ISMN or ULV particles. Increasing liposomal lipid content improved the anti-biofilm efficacy of both MLV and ULVs at 5 min exposure. CONCLUSION: Liposome-encapsulated "nitric oxide" is highly effective in eradicating S. aureus biofilms in-vitro, giving great promise for use in the clinical setting to treat this burdensome infection. Further studies however are needed to assess its safety and efficacy in-vivo before clinical translation is attempted.

  12. Temporal expression of hepatic inducible nitric oxide synthase in liver cirrhosis

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

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

  13. Expression of nitric oxide synthases and effects of L-arginine and L-NMMA on nitric oxide production and fluid transport in collagenous colitis

    DEFF Research Database (Denmark)

    Perner, A; Andresen, Lars; Normark, M;

    2001-01-01

    Luminal nitric oxide (NO) is greatly increased in the colon of patients with collagenous and ulcerative colitis. To define the source and consequence of enhanced NO production we have studied expression of NO synthase (NOS) isoforms and nitrotyrosine in mucosal biopsies from these patients...

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

    Science.gov (United States)

    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...

  15. Expression of nitric oxide synthases and effects of L-arginine and L-NMMA on nitric oxide production and fluid transport in collagenous colitis

    DEFF Research Database (Denmark)

    Perner, A; Andresen, L; Normark, M;

    2001-01-01

    BACKGROUND AND AIMS: Luminal nitric oxide (NO) is greatly increased in the colon of patients with collagenous and ulcerative colitis. To define the source and consequence of enhanced NO production we have studied expression of NO synthase (NOS) isoforms and nitrotyrosine in mucosal biopsies from ...

  16. Evidence for the participation of nitric oxide in pemphigus

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    Siebra M.X.

    2006-01-01

    Full Text Available Pemphigus is an inflammatory autoimmune disorder of the skin. Nitric oxide (NO is an inflammatory mediator linked to a variety of physiological and pathophysiological phenomena that include skin tumors, psoriasis, urticaria, and atopic dermatitis. Inflammatory cells present in pemphigus lesions are important sources of NO production. We investigated whether NO is involved in pemphigus. A prospective cohort study was conducted at the Dermatology Service of the Hospital Universitário Walter Cantídio of the Federal University of Ceará. All patients seen at the outpatient clinic between August 2000 and July 2001, with a clinically and histologically confirmed diagnosis of pemphigus were included. The median age was 42.5 years (range: 12-69 years with a male to female ratio of 3:2. Total serum nitrite levels, used as a marker for NO production, were determined by the Griess reaction. Skin biopsies from pemphigus and breast surgery (control patients were used for the detection of the inducible NO synthase (iNOS by immunohistochemistry. Twenty-two (22 patients with pemphigus and eight (8 controls who did not differ in demographic characteristics were included. Total serum nitrite levels were significantly higher (>7 µmol/L in pemphigus patients compared to controls (<6 µmol/L, regardless of the severity of the clinical activity of pemphigus (P < 0.0001. All pemphigus biopsies presented increased immunostaining for iNOS that was not detected in normal skin samples. These data are the first to demonstrate that pemphigus patients display increased serum NO levels that are associated with increased iNOS expression in the affected skin.

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

    Science.gov (United States)

    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.

  18. Nitric oxide inhibitory substances from Curcuma mangga rhizomes

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    Kanidta Kaewkroek

    2009-08-01

    Full Text Available Curcuma mangga Val. & Zijp. is a member of the Zingiberaceae family commonly grown in Thailand. It is locally known as mango tumeric because of its mango-like smell when the fresh rhizomes are cut. C. mangga is a popular vegetable, the tips of the young rhizomes and shoots are consumed raw with rice. Medicinally, the rhizomes are used as a stomachic and for chest pains, fever, and general debility. It is also used in postpartum care. In the present study, we investigated the anti-inflammatory effect of the extract and compounds from C. mangga rhizomes against lipopolysaccharide (LPS-induced nitric oxide (NO production in RAW 264.7 cell line. From bioassay-guided fractionation, the chloroform fraction exhibited the most potent inhibitory activity with an IC50 value of 2.1 g/ml, followed by the hexane fraction (IC50 = 3.8 g/ml and the ethyl acetate fraction (IC50 = 23.5 g/ml, respectively. Demethoxycurcumin (1 and 3-buten-2-one, 4-[(1R, 4aR, 8aR-decahydro-5, 5, 8a-trimethyl-2-methylene-1-naphthalenyl]-, (3E-rel- (2 were isolated from the chloroform- and hexane fractions, respectively. Bisdemethoxycurcumin (3 whose structure is similar to that of 1 was also tested for NO inhibitory activity. Of the tested compounds, compound 1 exhibited the highest activity with an IC50 value of 12.1 μM, followed by 3(IC50 = 16.9 M and 2 (IC50 = 30.3 M. These results suggest that C. mangga and its compounds exert NO inhibitory activity and have a potential to be developed as a pharmaceutical preparation for treatment of inflammatory-related diseases. Moreover, this is the first report of compound 2 that was isolated from C. mangga rhizomes.

  19. From synaptically localized to volume transmission by nitric oxide.

    Science.gov (United States)

    Garthwaite, John

    2016-01-01

    Nitric oxide (NO) functions widely as a transmitter/diffusible second messenger in the central nervous system, exerting physiological effects in target cells by binding to specialized guanylyl cyclase-coupled receptors, resulting in cGMP generation. Despite having many context-dependent physiological roles and being implicated in numerous disease states, there has been a lack of clarity about the ways that NO operates at the cellular and subcellular levels. Recently, several approaches have been used to try to gain a more concrete, quantitative understanding of this unique signalling pathway. These approaches have included analysing the kinetics of NO receptor function, real-time imaging of cellular NO signal transduction in target cells, and the use of ultrasensitive detector cells to record NO as it is being generated from native sources in brain tissue. The current picture is that, when formed in a synapse, NO is likely to act only very locally, probably mostly within the confines of that synapse, and to exist only in picomolar concentrations. Nevertheless, closely neighbouring synapses may also be within reach, raising the possibility of synaptic crosstalk. By engaging its enzyme-coupled receptors, the low NO concentrations are able to stimulate physiological (submicromolar) increases in cGMP concentration in an activity-dependent manner. When many NO-emitting neurones or synapses are active simultaneously in a tissue region, NO can act more like a volume transmitter to influence, and perhaps coordinate, the behaviour of cells within that region, irrespective of their identity and anatomical connectivity. PMID:26486504

  20. Modulation of nitric oxide synthase isoenzymes inreperfused skeletal muscle

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To investigate the modulation of nitric oxide synthnse (NOS) isoenzymes in skeletal muscle during 3 h ischemia/reperfusion (I/R, 3 h ischemia followed by 3 h reperfusion). Methods: The extensor digitorum longuses (EDLs)from 20 adult rats were divided into 4 groups: the normal,the sham operation, the ischemia (3 h), and the ischemia/reperfusion group. One normal EDL from each rat was used as the non-operated control, and the opposite ones are distributed into the 3 remaining groups. All the samples were studied with Western blotting technique and immumohistochemistry staining. Results: Three sizes of protein bands verified with the proteins of relative molecule to be of 155 000, 140 000and 135 000, were detected in the EDL homogenate by Western blotting, which were comparable with the positive controls for nNOS, eNOS and iNOS, respectively. Immunostaining demonstrated that nNOS was present in the muscle fiber, with a similar location of the muscle stria, eNOS was found apparently in microvascular endothelia,but not found in muscle fibers, and iNOS was found in the leukocytes around the muscle fiber and some endothelia cells. Immunostaining paralleled the Western blotting results. Conclusions: It suggests that the constitutive nNOS and eNOS protein can be regulated by I/R, and I/R results in a down regulation of nNOS and up-regulation of eNOS and iNOS in reperfused skeletal muscle. The fact that nNOS is present around stria suggests that nNOS may have a close relationship with muscle function. The localization of eNOS in endothelial cell indicates its role in regulating blood supply of the muscle. Based on these findings, it is possible that NO produced by distinct NOS may play a different role in I/R injury.

  1. Carnosine facilitates nitric oxide production in endothelial f-2 cells.

    Science.gov (United States)

    Takahashi, Satoru; Nakashima, Yukiko; Toda, Ken-Ichi

    2009-11-01

    We examined the effect of carnosine (beta-alanyl-histidine) on nitric oxide (NO) production and endothelial NO synthase (eNOS) activation in endothelial F-2 cells. Carnosine enhanced NO production in a dose-dependent manner, and the stimulatory effect of carnosine was observed at concentrations exceeding 5 mM. The carnosine-stimulated NO production was inhibited by N(G)-nitro-L-arginine methyl ester, but not by N(G)-nitro-D-arginine methyl ester. In contrast, beta-alanine, histidine (carnosine components) and anserine (N-methyl carnosine) failed to increase NO production. Carnosine had no effect on NO production for the initial 5 min, but thereafter resulted in a gradual increase in NO production up to 15 min. Carnosine did not induce phosphorylation of eNOS at Ser1177. The carnosine-induced increase in NO production was observed even when extracellular Ca2+ was depleted by ethylene glycol bis(2-aminoethyl ether)-N,N,N'-N'-tetraacetic acid however, the effect was abolished upon depletion of intracellular Ca2+ by BAPTA. After F-2 cells were incubated with carnosine for 4 min, intracellular Ca2+ concentration gradually increased. The carnosine-induced increase in intracellular Ca2+ concentration occurred even in the absence of extracellular Ca2+. These results indicate that carnosine facilitates NO production in endothelial F-2 cells. It is also suggested that eNOS is activated by Ca2+, which might be released from intracellular Ca2+ stores in response to carnosine. PMID:19881293

  2. Cerebral ischemia—induced neuronal apoptosis mediated by nitric oxide

    Institute of Scientific and Technical Information of China (English)

    NomuY

    2002-01-01

    To elucidate the cellular and molecular mechanism of cerebral ischemia-induced neuronal apoptosis mediated by nitric oxide (NO) in the brain,we investigated:(1)cell death in hippocampal CA1 neurons of rats after a rransient four vessel occlusion (4VO)/reperfusion and (2) apoptosis induced by NOC18(NO releaser) using SHSY5Y cells,a human neuroblastoma cell line.We found that 4VO caused expression of inducible type of NO synthase (iNOS) in glial cells and neuronal apoptosis in CA1 region of rats.Next we examined in vitro apoptotic effects of NOC18 on SHSY5Y cells and suggest that NO decrease mitochondrial membrane potential,release cytochrome C from mitochondria,activates caspase-3,degrade inhibitor of caspase-activated DNase(Icad),and activated DNase translocate into nucleus and induce DNA fragmentation.Thus we conclude that the excess amount of NO produced by glial iNOS at cerebral ischemia could be involved in neuronal apoptosis in CA1 region.Regarding NO action on neurons,we further obtained that NO propects neuronal apoptosis in PC12 cells perhaps by nitrosylation of caspase,subsequent reduction of proteolytic activity.Taken together,we suggest that NO seem to exert dual effects(toxic and beneficial) on neuronal apoptosis,the one (toxic);apoptosis-induction throuth the decrease in mitochondrial membrane potentials and cytochrome C release and the othe (beneficial);protection against apoptosis through the inhibition of caspase activity.

  3. Values in Elderly People for Exhaled Nitric Oxide Study.

    Science.gov (United States)

    Malerba, Mario; Damiani, Giovanni; Carpagnano, Giovanna E; Olivini, Alessia; Radaeli, Alessandro; Ragnoli, Beatrice; Foschino, Maria Pia; Olivieri, Mario

    2016-06-01

    Ageing population is constantly increasing due to rising life expectancy; consequently, the percentage of the elderly patients with asthma is increasing, as well. Fractional exhaled nitric oxide (FeNO) is a biomarker of lung inflammation, and currently it is widely used in clinical practice for asthma diagnosis and monitoring. Yet, there are no data about normal values of FeNO in patients of more than 65 years of age with normal lung function. The aim of this study was to establish adult FeNO reference values for subjects older than 65 years, according to the international guidelines. FeNO was measured in 303 healthy, nonsmoking adults more than 65 years of age, with normal spirometry values measured using the online single-breath technique. The results were analyzed by chemiluminescent detection. The FeNO levels obtained range from 5.00 to 29.9 ppb, with a mean value of 12.48 ± 2.80 ppb. A significant association of FeNO levels with age (p < 0.05) was observed. There was no difference in FeNO values between men and women unlike what was observed in younger patients. FeNO levels in healthy controls over 65 years of age are influenced by age as in younger adults. However, there is no difference in FeNO values in male and female seniors, in contrast with what was found in younger adults in other studies. These data can be useful for the clinician to interpret the values of FeNO assessed during clinical practice. PMID:26414479

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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). 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.

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    Luciano eFreschi

    2013-10-01

    Full Text Available Nitric oxide (NO is currently considered a ubiquitous signal in plant systems, playing significant roles in a wide range of plant 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.

  10. Choosing the right chondrocyte cell line: Focus on nitric oxide.

    Science.gov (United States)

    Santoro, Anna; Conde, Javier; Scotece, Morena; Abella, Vanessa; López, Verónica; Pino, Jesús; Gómez, Rodolfo; Gómez-Reino, Juan Jesús; Gualillo, Oreste

    2015-12-01

    Nitric oxide (NO) has been considered a catabolic factor that contributes to OA pathology by inducing chondrocytes apoptosis, matrix metalloproteinases synthesis, and pro-inflammatory cytokines expression. Thus, the research on NO regulation in chondrocytes represents a relevant field which needs to be explored in depth. However, to date, only the murine ATDC-5 cell line and primary chondrocytes are well-established cells to study NO production in cartilage tissues. The goal of this study is to determine whether two commonly used human chondrocytic cell lines: SW-1353 and T/C-28a2 cell lines are good models to examine lipopolysaccharide and/or pro-inflammatory cytokine-driven NO release and iNOS expression. To this aim, we carefully examined NO production and iNOS protein expression in human T/C-28a2 and SW-1353 chondrocytes stimulated with LPS and interleukin (IL)-1 alone or in combination. We also use ATDC-5 cells as a positive control for NO production. NO accumulation has been determined by colorimetric Griess reaction, whereas NOS type II expression was determined by Western Blot analysis. Our results clearly demonstrated that neither human T/C-28a2 nor SW-1353 chondrocytes showed a detectable increase in NO production or iNOS expression after bacterial endotoxin or cytokines challenge with IL-1. Our study demonstrated that T/C-28a2 and SW-1353 human cell lines are not suitable for studying NO release and iNOS expression confirming that ATDC5 and human primary cultured chondrocytes are the best in vitro cell system to study the actions derived from this mediator. PMID:26016689

  11. Adenosine preconditioning attenuates hepatic reperfusion injury in the rat by preventing the down-regulation of endothelial nitric oxide synthase

    Science.gov (United States)

    Serracino-Inglott, Ferdinand; Virlos, Ioannis T; Habib, Nagy A; Williamson, Robin CN; Mathie, Robert T

    2002-01-01

    Background Previous work has suggested that in the liver, adenosine preconditioning is mediated by nitric oxide. Whether the endothelial isoform of nitric oxide synthase plays a part in this mechanism has however not yet been investigated. Methods Wistar rats were used (6 in each group) – Groups: (1) sham, (2) ischemia-reperfusion, (3) adenosine + ischemia-reperfusion, (4) endothelial isoform inhibitor + adenosine + ischemia-reperfusion. Results Using immunohistochemistry, this study has revealed a decrease in the expression of endothelial nitric oxide synthase following hepatic ischemia-reperfusion. This was prevented by adenosine pre-treatment. When an inhibitor of endothelial nitric oxide synthase was administered prior to adenosine pre-treatment, pre-conditioning did not occur despite normal expression of endothelial nitric oxide synthase. Conclusions These findings suggest that adenosine attenuates hepatic injury by preventing the downregulation of endothelial nitric oxide synthase that occurs during ischemia-reperfusion. PMID:12241560

  12. Biliverdin Reductase-A correlates with inducible nitric oxide synthasein in atorvastatin treated aged canine brain

    Institute of Scientific and Technical Information of China (English)

    Fabio Di Domenico; Marzia Perluigi; Eugenio Barone

    2013-01-01

    Alzheimer’s disease is a neurodegenerative disorder characterized by progressive cognitive impairment and neuropathology. Recent preclinical and epidemiological studies proposed statins as a possible therapeutic drug for Alzheimer’s disease, but the exact mechanisms of action are stil unknown. Biliverdin reductase-A is a pleiotropic enzyme involved in cel ular stress responses. It not only transforms biliverdin-IX alpha into the antioxidant bilirubin-IX alpha but its serine/threonine/tyrosine kinase activity is able to modulate cel signaling networks. We previously reported the beneficial effects of atorvastatin treatment on biliverdin reductase-A and heme oxygenase-1 in the brains of a well characterized pre-clinical model of Alzheimer’s disease, aged beagles, together with observed improvement in cognition. Here we extend our knowledge of the effects of atorvastatin on inducible nitric oxide synthase in parietal cortex, cerebel um and liver of the same animals. We demonstrated that atorvastatin treatment (80 mg/day for 14.5 months) to aged beagles selectively increased inducible nitric oxide synthase in the parietal cortex but not in the cerebel um. In contrast, inducible nitric oxide synthase protein levels were significantly decreased in the liver. Significant positive correlations were found between biliverdin reductase-A and inducible nitric oxide synthase as wel as heme oxygenase-1 protein levels in the parietal cortex. The opposite was observed in the liver. Inducible nitric oxide synthase up-regulation in the parietal cortex was positively associated with improved biliverdin reductase-A functions, whereas the oxidative-induced impairment of biliverdin reductase-A in the liver negatively affected inducible nitric oxide synthase expression, thus suggesting a role for biliverdin reductase-A in atorvastatin-dependent inducible nitric oxide synthase changes. Interestingly, increased inducible nitric oxide synthase levels in the parietal cortex were not

  13. Wt-1 Expression Linked to Nitric Oxide Availability during Neonatal Obstructive Nephropathy

    Directory of Open Access Journals (Sweden)

    Luciana Mazzei

    2013-01-01

    Full Text Available The wt-1 gene encodes a zinc finger DNA-binding protein that acts as a transcriptional activator or repressor depending on the cellular or chromosomal context. The wt-1 regulates the expression of a large number of genes that have a critical role in kidney development. Congenital obstructive nephropathy disrupts normal renal development and causes chronic progressive interstitial fibrosis, which contributes to renal growth arrest, ultimately leading to chronic renal failure. Wt-1 is downregulated during congenital obstructive nephropathy, leading to apoptosis. Of great interest, nitric oxide bioavailability associated with heat shock protein 70 (Hsp70 interaction may modulate wt-1 mRNA expression, preventing obstruction-induced cell death during neonatal unilateral ureteral obstruction. Moreover, recent genetic researches have allowed characterization of many of the complex interactions among the individual components cited, but the realization of new biochemical, molecular, and functional experiments as proposed in our and other research labs allows us to establish a deeper level of commitment among proteins involved and the potential pathogenic consequences of their imbalance.

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

    Science.gov (United States)

    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.

  15. Nitric oxide and coronary vascular endothelium adaptations in hypertension

    Directory of Open Access Journals (Sweden)

    Andrew S Levy

    2009-12-01

    Full Text Available Andrew S Levy*, Justin CS Chung*, Jeffrey T Kroetsch*, James WE RushDepartment of Kinesiology, University of Waterloo, Waterloo, Ontario, Canada; *These authors contributed equally to this workAbstract: 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 Ca2+ control and eNOS expression and activity. In hypertension models, the coronary vasculature has not been

  16. Role of Nitric Oxide Dependence on Nitric Oxide Synthase-like Activity in the Water Stress Signaling of Maize Seedling

    Institute of Scientific and Technical Information of China (English)

    Gang-Ping Hao; Yu Xing; Jian-Hua Zhang

    2008-01-01

    Nitric oxide (NO) has been known as an important signal in plant antioxidative defense but its production and roles in water stress are less known. The present study investigated whether NO dependence on a NO synthase-lika (NOS) activity is involved in the signaling of drought-induced protective responses in maize seedlings. NOS activity, rate of NO release and drought responses were analyzed when NO donor sodium nitroprusside (SNP), NO scavenger c-PTIO (2-(4-carboxyphenyl)-4,4,5,5-tetramathylimidazoline-1-oxyl-3-oxide) and NOS inhibitor L-NAME (NG-nitro-L-arginine methyl ester) were applied to both detached maize leaves and whole plants. Both NOS activity and the rate of NO release increased substantially under dehydration stress. The high NOS activity induced by c-PTIO as NO scavenger and NO accumulation Inhibited by NOS inhibitor L-NAME In dehydration-treated maize seedlings Indicated that most NO production under water deficit stress may be generated from NOS-like activity. After dehydration stress for 3 h, detached maize leaves pretreated with NO donor SNP maintained more water content than that of control leaves pretreated with water. This result was consistent with the decrease in the transpiration rate of SNP-treated leaves subjected to drought treatment for 3 h. Membrane permeability, a cell injury index, was lower in SNP-trested maize leaves under dehydration stress for 4 h when compared with the control leaves. Also, superoxide dismutsse (SOD) activity of SNP combined drought treatment maize leaves was higher than that of drought treatment alone, indicating that exogenous NO treatment alleviated the water loss and oxidative damage of maize leaves under water deficit stress. When c-PTIO as a specific NO scavenger was applied, the effects of applied SNP were overridden. Treatment with L-NAME on leaves also led to higher membrane permeability, higher transpiration rate and lower SOD activities than those of control leaves, indicating that NOS-like activity

  17. Nitric oxide production by polymorphonuclear leukocytes in sputum from cystic fibrosis patients with chronic lung infection

    DEFF Research Database (Denmark)

    Kolpen, Mette; Bjarnsholt, Thomas; Moser, Claus;

    2010-01-01

    Objective: Chronic Pseudomonas aeruginosa lung infection in CF patients is characterized by persisting mucoid biofilm in hypoxic endobronchial mucus. These biofilms are surrounded by numerous polymorphonuclear leukocytes (PMNs), which are the major consumers of O2 for production of O2-. In this s...

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

    Science.gov (United States)

    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.

  19. Pentylentetrazole-induced loss of blood-brain barrier integrity involves excess nitric oxide generation by neuronal nitric oxide synthase.

    Science.gov (United States)

    Danjo, Sonoko; Ishihara, Yasuhiro; Watanabe, Masatomo; Nakamura, Yu; Itoh, Kouichi

    2013-09-12

    Dysfunction of the blood-brain barrier (BBB) is one of the major pathophysiological consequences of epilepsy. The increase in the permeability caused by BBB failure is thought to contribute to the development of epileptic outcomes. We developed a method by which the BBB permeability can be demonstrated by gadolinium-enhanced T1 weighted imaging (GdET1WI). The present study examined the changes in the BBB permeability in mice with generalized convulsive seizures (GCS) induced by acute pentylentetrazole (PTZ) injection. At 15min after PTZ-induced GCS, the BBB temporarily leaks BBB-impermeable contrast agent into the parenchyma of the diencephalon, hippocampus and cerebral cortex in mice, and the loss of BBB integrity was gradually recovered by 24h. The temporary BBB failure is a critical link to the glutamatergic activities that occur following the injection of PTZ. PTZ activates the glutamatergic pathway via the NMDA receptor, then nitric oxide (NO) is generated by NMDA receptor-coupled neuronal NO synthase (nNOS). To examine the influence of nNOS-derived NO induced by PTZ on the increases of the BBB permeability, GdET1WI was performed using conventional nNOS gene-deficient mice with or without PTZ injection. The failure of the BBB induced by PTZ was completely protected by nNOS deficiency in the brain. These results suggest that nNOS-derived excess NO in the glutamatergic pathway plays a key role in the failure of the BBB during PTZ-induced GCS. The levels of NO synthetized by nNOS in the brain may represent an important target for the future development of drugs to protect the BBB. PMID:23831997

  20. Intracellular conversion of environmental nitrate and nitrite to nitric oxide with resulting developmental toxicity to the crustacean Daphnia magna.

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    Bethany R Hannas

    Full Text Available BACKGROUND: Nitrate and nitrite (jointly referred to herein as NO(x are ubiquitous environmental contaminants to which aquatic organisms are at particularly high risk of exposure. We tested the hypothesis that NO(x 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 (NO(3(- and nitrite (NO(2(- to nitric oxide using amperometric real-time nitric oxide detection. Both NO(3(- and NO(2(- 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 NO(2(- to nitric oxide. Next, daphnids were continuously exposed to concentrations of the nitric oxide-donor sodium nitroprusside (positive control and to concentrations of NO(3(- and NO(2(-. 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.

  1. Nitrate as a source of nitrite and nitric oxide during exercise hyperemia in rat skeletal muscle.

    Science.gov (United States)

    Piknova, Barbora; Park, Ji Won; Kwan Jeff Lam, Kai; Schechter, Alan N

    2016-05-01

    The presence of nitric oxide (NO) synthase enzymes, mainly the NOS1 isoform, in skeletal muscle had been well established; however in the last decade it has been realized that NO may also be produced by reduction of nitrate and tissue nitrite. We have recently shown that rodent skeletal muscle contains unusually high concentrations of nitrate, compared to blood and other tissues, likely produced by oxidation of NOS1-produced NO. In the present study we measured nitrate and nitrite levels in Wistar rat leg tissue before and after acute and chronic exercise of the animals on a treadmill. We found a very large decrease of muscle nitrate levels immediately after exercise accompanied by a transient increase of nitrite levels. A significant decrease in blood nitrate levels accompanied the changes in muscle levels. Using skeletal muscle tissue homogenates we established that xanthine oxidoreductase (XOR) is at least partially responsible for the generation of nitrite and/or NO from nitrate and that this effect is increased by slight lowering of pH and by other processes related to the exercise itself. We hypothesize that the skeletal muscle nitrate reservoir contributes significantly to the generation of nitrite and then, probably via formation of NO, exercise-induced functional hyperemia. A model for these metabolic interconversions in mammals is presented. These reactions could explain the muscle-generated vasodilator causing increased blood flow, with induced contraction, exercise, or hypoxia, postulated more than 100 years ago. PMID:27000467

  2. A Potential Concept In The Management of Tumors With Modulation of Prostaglandin, Nitric Oxide and Antioxidants

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    Noori S. Al-Waili

    2007-01-01

    Full Text Available Prostaglandins (PGs, nitric oxide (NO, free radicals and chronic inflammation play a major role in tumorogenesis. We have found in vivo that PGs suppress antibody production; reduce serum iron, and modulate bone marrow function. Tumors are associated with immunosuppression and anemia. We have hypothesized that the over-production of PGs is responsible for immunosuppression and anemia in conditions associated with increased production of PG such as tumor, and that PG inhibitors might help reversing immunosuppression and anemia, and play a role in eradication and prevention of tumors. This is supported by reports that demonstrate the immunosuppressive effects of PGs in tumors. PG inhibitors have also been shown to be crucial in the prevention of tumors such as esophageal and colon cancers. Others and we have found that high NO production was encountered in patients with cancer while antioxidants are decreased. Evidence supports the efficacy of PG inhibition in malignancies, and the concept of PG inhibition, NO modulation, anti-oxidants, immunotherapy with antibody or immune cells, and anti-inflammatory agents when used in the prevention and management of malignancies are discussed.

  3. Evaluation of Serum Nitric Oxide level in Patients with Oral Lichen Planus

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    Mehdipour M.

    2014-06-01

    Full Text Available Statement of Problem: Oral lichen planus (OLP is a chronic inflammatory oral mucosal disease with indefinite etiology. In recent researches, free radicals have been deliberated as the possible etiology of inflammatory and autoimmune diseases. Purpose: This study aimed to evaluate the stress oxidative status with the nitric oxide (NO index in a sample of Iranian population. Materials and Method: In this descriptive-comparative study; serum NO level was assessed in 20 OLP patients as the case group and 20 healthy individuals as the control group. Collected data were analyzed by adopting two Sample t-test; using SPSS 16 software. Statistical significance level was set at p < 0.05. Results: The mean serum NO levels in OLP patients and healthy controls were 17.1±3.4 ng/ml and 14.5±2.7 ng/ml respectively; which revealed a significant statistic-al difference (p= 0.009. Conclusions: The results of the current study with its limitation may support the premise that higher serum levels of NO in patients with OLP might activate the process of lymphocytes and cellular immunity system; hence, possibly endorsing the effect of serum NO in pathogenesis of lichen planus.

  4. 75 FR 43535 - NIH Consensus Development Conference on Inhaled Nitric Oxide Therapy for Premature Infants

    Science.gov (United States)

    2010-07-26

    ... Oxide Therapy for Premature Infants Notice Notice is hereby given of the National Institutes of Health (NIH) ``NIH Consensus Development Conference on Inhaled Nitric Oxide Therapy for Premature Infants'' to... premature infants who still require supplemental oxygen 36 weeks after conception are diagnosed...

  5. Nitric oxide levels in the anterior chamber of vitrectomized eyes with silicon oil

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    Paulo Escarião

    2013-10-01

    Full Text Available PURPOSE: To investigate the nitric oxide levels in the anterior chamber of eyes who underwent pars plana vitrectomy (PPV with silicone oil. METHODS: Patients who underwent PPV with silicon oil injection, from february 2005 to august 2007, were selected. Nine patients (nine eyes participated in the study (five women and four men. Nitric oxide concentration was quantified after the aspiration of aqueous humor samples during the procedure of silicon oil removal. Data such as: oil emulsification; presence of oil in the anterior chamber; intraocular pressure and time with silicone oil were evaluated. Values of p <0.05 were considered to be statistically significant. RESULTS: A positive correlation between nitric oxide concentration and time with silicon oil in the vitreous cavity (r=0.799 was observed. The nitric oxide concentration was significantly higher (p=0.02 in patients with silicon oil more than 24 months (0.90µmol/ml ± 0.59, n=3 in the vitreous cavity comparing to patients with less than 24 months (0.19µmol/ml ± 0.10, n=6. CONCLUSION: A positive correlation linking silicone oil time in the vitreous cavity with the nitric oxide concentration in the anterior chamber was observed.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  8. Nitric oxide and coronary vascular endothelium adaptations in hypertension.

    Science.gov (United States)

    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

  9. Involvement of nitric oxide in inflammation of ovaries in gilts.

    Science.gov (United States)

    Jana, Barbara; Andronowska, Aneta; Kucharski, Jan

    2002-03-01

    NADPH-diaphorase (NADPH-d) and an inducible type of nitric oxide synthase (iNOS) were demonstrated in porcine ovaries after unilateral infusion of bacteria into the hilus of an ovary. In group I one ml of saline was infused into the hilus of each ovary from the 15th day to the 19th day of the estrous cycle. In group II one ml of bacterial suspension (10(9) colony forming units of Escherichia coli, Staphylococcus aureus and Corynebacterium pyogenes, in a proportion 1:1:1, respectively) in saline was infused into the hilus of one ovary on days corresponding to those of the control group (gr. I), whereas saline was infused into the contralateral ovary. The ovaries were collected on the 7th day of the next estrous cycle. In the bacteria-treated ovary, the activity of NADPH-d was higher in the endothelium of blood vessels, corpora lutea and follicular walls in comparison to that observed in the respective structures of the contralateral ovary. The highest activity of NADPH-d was found in the vascular endothelium in the bacteria-infused ovary. Vascular smooth muscle cells found in both ovaries of the bacteria-treated gilts were more intensely stained for NADPH-d than those in control animals. After bacteria administration, the intensity of NADPH-d reaction in all the structures of both ovaries in group II was higher than in control group. The strongest immunostaining for iNOS was observed in all structures of the bacteria-infused ovary. In the contralateral ovary, iNOS-immunoreactivity was weaker but still stronger than that in control group. The present results revealed that infusions of bacteria into the hilus of one ovary enhanced the activity of NADPH-d and immunoreactivity for iNOS in both porcine ovaries. However, the activity of both enzymes was higher in the bacteria-infused ovary than in the contralateral one. These data suggest that locally synthesized NO can mediate an inflammatory effect of bacteria in the porcine ovaries. PMID:14666163

  10. Inhaled nitric oxide in cardiac surgery: Evidence or tradition?

    Science.gov (United States)

    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

  11. Inhaled nitric oxide in cardiac surgery: Evidence or tradition?

    Science.gov (United States)

    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

  12. Nitric oxide-releasing polymeric nanoparticles against Trypanosoma cruzi

    Science.gov (United States)

    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

  13. Oxygen-sensing under the influence of nitric oxide.

    Science.gov (United States)

    Berchner-Pfannschmidt, Utta; Tug, Suzan; Kirsch, Michael; Fandrey, Joachim

    2010-03-01

    The transcription factor complex Hypoxia inducible factor 1 (HIF-1) controls the expression of most genes involved in adaptation to hypoxic conditions. Oxygen-dependency is maintained by prolyl- and asparagyl-4-hydroxylases (PHDs/FIH-1) belonging to the superfamily of iron(II) and 2-oxoglutarate dependent dioxygenases. Hydroxylation of the HIF-1alpha subunit by PHDs and FIH-1 leads to its degradation and inactivation. By hydroxylating HIF-1alpha in an oxygen-dependent manner PHDs and FIH-1 function as oxygen-sensing enzymes of HIF signalling. Besides molecular oxygen nitric oxide (NO), a mediator of the inflammatory response, can regulate HIF-1alpha accumulation, HIF-1 activity and HIF-1 dependent target gene expression. Recent studies addressing regulation of HIF-1 by NO revealed a complex and paradoxical picture. Acute exposure of cells to high doses of NO increased HIF-1alpha levels irrespective of the residing oxygen concentration whereas prolonged exposure to NO or low doses of this radical reduced HIF-1alpha accumulation even under hypoxic conditions. Several mechanisms were found to contribute to this paradoxical role of NO in regulating HIF-1. More recent studies support the view that NO regulates HIF-1 by modulating the activity of the oxygen-sensor enzymes PHDs and FIH-1. NO dependent HIF-1alpha accumulation under normoxia was due to direct inhibition of PHDs and FIH-1 most likely by competitive binding of NO to the ferrous iron in the catalytically active center of the enzymes. In contrast, reduced HIF-1alpha accumulation by NO under hypoxia was mainly due to enhanced HIF-1alpha degradation by induction of PHD activity. Three major mechanisms are discussed to be involved in enhancing the PHD activity despite the lack of oxygen: (1) NO mediated induction of a HIF-1 dependent feedback loop leading to newly expressed PHD2 and enhanced nuclear localization, (2) O2-redistribution towards PHDs after inhibition of mitochondrial respiration by NO, (3

  14. Effects of nitric oxide on gastric ulceration induced by nicotine and cold-restraint stress

    Institute of Scientific and Technical Information of China (English)

    Bo-Sheng Qui; Qi-Bing Mei; Li Liu; Kam-Meng Tchou-Wong

    2004-01-01

    AIM: Stress induces gastric ulceration in human and experimental animals. People tend to smoke more cigarettes when under stress. Nitric oxide (NO) and nicotine have opposing effects on gastric integrity. The present study examined the possible therapeutic benefit of NO in nicotinetreated rats with stress-induced gastric ulceration.METHODS: Rats drank a nicotine solution while control rats drank tap water for 20 days. The alkoloid was then replaced by water with or without supplementation of isosorbide dinitrate (NO donor) for an additional 10 days. Isosorbide dinitrate was given twice shortly before experiments (acute)or three times daily by oral gavages for 10 days after the rats stopped drinking nicotine solution. At the end of experiments,ulcer index, gastric adhesion mucus content and MPO activity were measured and analysed.RESULTS: Nicotine treatment decreased gastric mucus content and intensified stress-induced gastric ulcer. A higher ulcer index persisted even after the rats stopped drinking nicotine solution for 10 days. Acute NO donor showed no benefit on both mucus and ulcer index in nicotine treatment or/and stress condition. Chronic NO donor treatment reversed the worsening action of nicotine in stomach. Stress increased gastric mucosal myeloperoxidase (MPO) activity, which was antagonized by chronic NO treatment. However, nicotine was unlikely to change mucosal MPO activity.CONCLUSION: The intensifying action of nicotine on stressinduced gastric ulceration persists for 10 days after cessation.Nicotine treatment significantly decreases gastric mucus content that can be restored by chronic NO donor treatment.The present study suggests that NO antagonizes the ulcerogenic action of nicotine through a cytoprotective way.

  15. Suppression of PKG by PDGF or nitric oxide in differentiated aortic smooth muscle cells: obligatory role of protein tyrosine phosphatase 1B

    OpenAIRE

    Zhuang, Daming; Balani, Poonam; Pu, Qinghua; Thakran, Shalini; Hassid, Aviv

    2010-01-01

    Treatment of aortic smooth muscle cells with PDGF induces the upregulation of protein tyrosine phosphatase 1B (PTP1B). PTP1B, in turn, decreases the function of several growth factor receptors, thus completing a negative feedback loop. Studies have reported that PDGF induces the downregulation of PKG as part of a repertoire of dedifferentiation of vascular smooth muscle cells. Other studies have reported that chronic nitric oxide (NO) treatment also induces the downregulation of PKG. In the p...

  16. Azospirillum lectin – induced changes in the content of nitric oxide in wheat seedling roots

    Directory of Open Access Journals (Sweden)

    Alen’kina S.A.

    2010-11-01

    Full Text Available The lectin of Azospirillum brasilense Sp7 at 40 μg ml-1 elicited two peaks of induction of nitric oxide synthesis in the roots of wheat seedlings after 3 and 26 h of coincubation. The lectin of A. brasilense Sp7.2.3, a mutant defective in lectin activity, produced the same effect, but the activation of nitric oxide synthesis in the roots was less in the case of 26-h incubation. Exposure to the lectins for 3 h increased citrulline synthesis in the plant cell to the same extent. This finding indicated that the Azospirillum lectins activate nitric oxide production through the NO signal system of plants, thereby acting as inducers of adaptation processes in the roots of wheat seedlings.

  17. Nitric oxide production by chicken macrophages activated by Acemannan, a complex carbohydrate extracted from Aloe vera.

    Science.gov (United States)

    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.

  18. Study of Nitric Oxide production by murine peritoneal macrophages induced by Brucella Lipopolysaccharide

    Directory of Open Access Journals (Sweden)

    Kavoosi G

    2001-07-01

    Full Text Available Brueclla is a gram negative bacteria that causes Brucellosis. Lipopolysaccharide (LPS ", the pathogenic agent of Brucella is composed of O-chain, core oligosaccharide and lipid A. in addition, the structural and biological properties of different LPS extracted from different strains are not identical. The first defense system against LPS is nonspecific immunity that causes macrophage activation. Activated macrophages produce oxygen and nitrogen radicals that enhance the protection against intracellular pathogens.In this experiment LPS was extracted by hot phenol- water procedure and the effect of various LPSs on nitric oxide prodution by peritoneal mouse macrophages was examined.Our results demonstrated that the effect of LPS on nitric oxide production is concentration-dependent we observed the maximum response in concentration of 10-20 microgram per milliliter. Also our results demonstrate that LPS extracted from vaccine Brucella abortus (S 19 had a highe effect on nitric oxide production than the LPS from other strains

  19. Behaviour of nitric oxide trails deposited in the mesosphere and stratosphere

    Science.gov (United States)

    Eberstein, I. J.; Aikin, A. C.

    1975-01-01

    The transient behavior of a nitric oxide trail deposited at approximately 60 km altitude is studied by the solution of the appropriate multidimensional diffusion equation which includes terms representing the effects of wind shear. Similar analysis is then carried out for the situation in the stratosphere. Trail behavior is found to be relatively independent of altitude and background ozone, but strongly dependent on the magnitude of eddy diffusity and the initial nitric oxide concentration. The nitric oxide trail reacts with ambient ozone to form nitrogen dioxide. For a trail 100 m initial radius, an ozone hole will form to a maximum size in 4 to 6 hours and then decay. The overall recovery time of the atmosphere following the creation of the trail is less than 12 hours.

  20. Negative Inotropic Effects of Cytokines on the Heart Mediated by Nitric Oxide

    Science.gov (United States)

    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.

  1. Progesterone modulates the LPS-induced nitric oxide production by a progesterone-receptor independent mechanism.

    Science.gov (United States)

    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.

  2. The role of nitric oxide and lipid peroxidation in patients with Plasmodium vivax malaria

    Directory of Open Access Journals (Sweden)

    Polat G.

    2002-12-01

    Full Text Available In this study, we investigated the role of nitric oxide metabolism and lipid peroxidation in patients with P. vivax malaria. The levels of nitrite and nitrate were analyzed using a procedure based on the Griess reaction and malondialdehyde levels which index of lipid peroxidation was determined by thiobarbituric acid reaction. The levels of nitrite/nitrate and malondialdehyde in patients were higher than controls and found to be statistically significant (p < 0.001. We performed this study to determine whether nitric oxide and lipid peroxidation is produced during blood-stage P. vivax malaria. This present study shows that lipid peroxidation occurs in P. vivax malaria. The levels of nitric oxide are associated with lipid peroxidation in this disease.

  3. Cyclic nitroxides inhibit the toxicity of nitric oxide-derived oxidants: mechanisms and implications

    Directory of Open Access Journals (Sweden)

    Ohara Augusto

    2008-03-01

    Full Text Available The substantial therapeutic potential of tempol (4-hydroxy-2,2,6,6-tetramethyl-1-piperidinyloxy and related cyclic nitroxides as antioxidants has stimulated innumerous studies of their reactions with reactive oxygen species. In comparison, reactions of nitroxides with nitric oxide-derived oxidants have been less frequently investigated. Nevertheless, this is relevant because tempol has also been shown to protect animals from injuries associated with inflammatory conditions, which are characterized by the increased production of nitric oxide and its derived oxidants. Here, we review recent studies addressing the mechanisms by which cyclic nitroxides attenuate the toxicity of nitric oxidederived oxidants. As an example, we present data showing that tempol protects mice from acetaminophen-induced hepatotoxicity and discuss the possible protection mechanism. In view of the summarized studies, it is proposed that nitroxides attenuate tissue injury under inflammatory conditions mainly because of their ability to react rapidly with nitrogen dioxide and carbonate radical. In the process the nitroxides are oxidized to the corresponding oxammonium cation, which, in turn, can be recycled back to the nitroxides by reacting with upstream species, such as peroxynitrite and hydrogen peroxide, or with cellular reductants. An auxiliary protection mechanism may be down-regulation of inducible nitric oxide synthase expression. The possible therapeutic implications of these mechanisms are addressed.O considerável potencial terapêutico de tempol (4-hidroxi-2,2, 6,6-tetrametil-1piperiniloxila e nitróxidos cíclicos relacionados como antioxidantes tem estimulado inúmeros estudos de suas reações com espécies reativas derivadas de oxigênio. Em comparação, as reações de nitróxidos com oxidantes derivados do óxido nítrico têm sido investigadas menos frequentemente. Todavia, essas reações são relevantes porque o tempol é também capaz de proteger

  4. Nitric Oxide Synthetic Pathway in Patients with Microvascular Angina and Its Relations with Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Benedetta Porro

    2014-01-01

    Full Text Available A decreased nitric oxide (NO bioavailability and an increased oxidative stress play a pivotal role in different cardiovascular pathologies. As red blood cells (RBCs participate in NO formation in the bloodstream, the aim of this study was to outline the metabolic profile of L-arginine (Arg/NO pathway and of oxidative stress status in RBCs and in plasma of patients with microvascular angina (MVA, investigating similarities and differences with respect to coronary artery disease (CAD patients or healthy controls (Ctrl. Analytes involved in Arg/NO pathway and the ratio of oxidized and reduced forms of glutathione were measured by LC-MS/MS. The arginase and the NO synthase (NOS expression were evaluated by immunofluorescence staining. RBCs from MVA patients show increased levels of NO synthesis inhibitors, parallel to that found in plasma, and a reduction of NO synthase expression. When summary scores were computed, both patient groups were associated with a positive oxidative score and a negative NO score, with the CAD group located in a more extreme position with respect to Ctrl. This finding points out to an impairment of the capacity of RBCs to produce NO in a pathological condition characterized mostly by alterations at the microvascular bed with no significant coronary stenosis.

  5. Nitric oxide scavenging by hemoglobin or nitric oxide synthase inhibition by N-Nitro-L-arginine induces cortical spreading ischemia when K+0+ is increased in the subarachnoid space

    DEFF Research Database (Denmark)

    Dreier, J.P.; Körner, K.; Ebert, Nathalie;

    1998-01-01

    Cerebral blood flow, nitric oxide, potassium, spreading depression, vasospasm, migraine, migrainous stroke, mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS)......Cerebral blood flow, nitric oxide, potassium, spreading depression, vasospasm, migraine, migrainous stroke, mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS)...

  6. Effects of Smokeless Tobacco “Maras Powder” Use on Nitric Oxide and Cardiovascular Risk Parameters

    Directory of Open Access Journals (Sweden)

    Aytekin Guven, Fatma Tolun

    2012-01-01

    Full Text Available 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.

  7. Inhibition of endogenous nitric oxide in the heart enhances matrix metalloproteinase-2 release

    OpenAIRE

    Wang, Wenjie; Viappiani, Serena; Sawicka, Jolanta; Schulz, Richard

    2005-01-01

    Matrix metalloproteinase (MMP) activity is upregulated in pathologies such as atherosclerosis during which endogenous nitric oxide (NO) biosynthesis is reduced. Diminished levels of NO, an antioxidant species, may result in higher oxidative stress. Oxidants are capable of activating MMPs from their zymogen forms. We examined whether basal biosynthesis of NO in the coronary circulation regulates MMP-2 activity.In isolated rat hearts perfused with Krebs–Henseleit buffer at a constant flow of 10...

  8. Modulation of fibrosis in systemic sclerosis by nitric oxide and antioxidants.

    OpenAIRE

    Audrey Dooley; K. Richard Bruckdorfer; Abraham, David J.

    2012-01-01

    Systemic sclerosis (scleroderma: SSc) is a multisystem, connective tissue disease of unknown aetiology characterized by vascular dysfunction, autoimmunity, and enhanced fibroblast activity resulting in fibrosis of the skin, heart, and lungs, and ultimately internal organ failure, and death. One of the most important and early modulators of disease activity is thought to be oxidative stress. Evidence suggests that the free radical nitric oxide (NO), a key mediator of oxidative stress, can prof...

  9. Modulation of Fibrosis in Systemic Sclerosis by Nitric Oxide and Antioxidants

    OpenAIRE

    2012-01-01

    Systemic sclerosis (scleroderma: SSc) is a multisystem, connective tissue disease of unknown aetiology characterized by vascular dysfunction, autoimmunity, and enhanced fibroblast activity resulting in fibrosis of the skin, heart, and lungs, and ultimately internal organ failure, and death. One of the most important and early modulators of disease activity is thought to be oxidative stress. Evidence suggests that the free radical nitric oxide (NO), a key mediator of oxidative stress, can prof...

  10. Studies on the Compounds of d4T Combined with Nitric Oxide Donors and Nitric Oxide Synthase Inhibitors and their Anti-HIV and AIDS Activity

    Institute of Scientific and Technical Information of China (English)

    KWALE MOLIME GUITREMBI Blaise(Central African); YAO Qi-zheng

    2004-01-01

    Stavudine, a potent anti-HIV and AiDS-related complex, is one of the Nucleoside Analogue Reverse Transcriptase Inhibitors (NARTIs). It is phosphorylated intracellularly and then inhibits the viral reverse transcriptase by acting as a false substrate. Modifications made on the hydrogen labile at the 5'-position on the sugar is an interesting template for the elaboration of new potent anti-HIV and AIDS drugs. The expected advantages of the modified stavudine prodrugs can be multiple: synergistic drug activities, enhancement of stavudine intracellular uptake, increase of stavudine brain delivery, and bypass of the first stavudine phosphorylation step into the cells. Nitric oxide synthase inhibitors of stavudine and nitric oxide donors of stavudine may hold significant promise for the treatment of HIV and AIDS.

  11. Sex affects the feeling of pain in the mice, possible involvement of nitric oxide

    OpenAIRE

    Zahra Fatehi-Hassanabad; Mostafa Jafarzadeh; Mohammad Fatehi; Mohammad Taghi Razavi-Tossi"

    2005-01-01

    It has been shown that nitric oxide is a mediator with a major role in pain signaling at the level of dorsal root ganglion neurons of the spinal cord. The main objective of the present study was to elucidate the influence of sex on the effects of nitric oxide on pain mediation in mice. Painful stimuli such as heat induced by light beam focused on tail and hot plate chamber were applied. Animals were injected with either morphine (0.5, 5 and 50 mg/100g body weight) or L-NAME (0.1, 0.5 and 1 mg...

  12. Nitric oxide compounds have different effects profiles on human articular chondrocyte metabolism

    OpenAIRE

    de Andrés, María C.; Maneiro, Emilia; Martín, Miguel A.; Arenas, Joaquín; Francisco J Blanco

    2013-01-01

    Introduction The pathogenesis of osteoarthritis (OA) is characterized by the production of high amounts of nitric oxide (NO), as a consequence of up-regulation of chondrocyte-inducible nitric oxide synthase (iNOS) induced by inflammatory cytokines. NO donors represent a powerful tool for studying the role of NO in the cartilage in vitro. There is no consensus about NO effects on articular cartilage in part because the differences between the NO donors available. The aim of this work is to com...

  13. Iptakalim rescues human pulmonary artery endothelial cells from hypoxia-induced nitric oxide system dysfunction

    OpenAIRE

    Zong, Feng; Zuo, Xiang-Rong; Wang, Qiang; ZHANG, SHI-JIANG; Xie, Wei-Ping; Wang, Hong

    2011-01-01

    The aim of this study was to assess whether hypoxia inhibits endothelial nitric oxide synthase (eNOS) activity and nitric oxide (NO) production, and whether iptakalim may rescue human pulmonary artery endothelial cells (HPAECs) from hypoxia-induced NO system dysfunction. HPAECs were cultured under hypoxic conditions in the absence or presence of 0.1, 10 and 1,000 μM iptakalim or the combination of 10 μM iptakalim and 1, 10 and 100 μM glibenclamide for 24 h, and the eNOS activity and NO levels...

  14. Fe-Chlorophyllin Promotes the Growth of Wheat Roots Associated with Nitric Oxide Generation

    OpenAIRE

    Hui Jiang; Yong Ren; Liefeng Zhang; Yifan Wang; Min Tong

    2010-01-01

    : Effects of Fe-chlorophyllin on the growth of wheat root were investigated in this study. We found that Fe-chlorophyllin can promote root growth. The production of nitric oxide in wheat root was detected using DAF-2DA fluorescent emission. The intensity of fluorescent in the presence of 0.1 mg/L Fe-chlorophyllin was near to that observed with the positive control of sodium nitroprusside (SNP), the nitric oxide donor. IAA oxidase activity decreased with all treatments of Fe-chlorophyllin from...

  15. Effects of aerosolized ketamine on the level of nitric oxide and nitric oxide synthetase in the lung tissue of rat with asthma

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective: To explore the effects of aerosolized ketamine on the level of nitric oxide and nitric oxide synthetase in the lung tissue in rat asthma model. Methods: Forty SD rats were randomly assigned to five groups: control group (group N), asthma model group (group A), two pretreated groups of different concentrations of ketamine (group K1, K2)and dexamethasone group(group D) with eight rats in each group. The rats in group A were sensitized by injection of ovalbumin (OA) together with aluminum hydroxide and bordetella pertussis as adjuvants. Two weeks after the sensitization, aerosolized OA was used to cause asthma. The rats in group K1 and K2 were sensitized with OA as group A , and then exposed to aerosol of ketamine , with the concentration of 25 g/L and 50 g/L respectively. Before using aerosolized OA, the rats in group D were exposed to aerosol of 0.01% dexamethasone . The level of NO2-/NO3- in lung tissues, inducible nitric oxide synthetase(iNOS) and constitute nitric oxide synthetase(cNOS) was measured in all groups. Results: The level of NO2-/NO3- and the activity of iNOS in lung tissues in group A were signiticantly higher than those in the other groups. The iNOS activity and the level of NO2-/NO3- in lung tissues were highly positively correlated. Conclusion: NO can induce airway hyperreactivity that may worsen asthma. Aerosolized ketamine can decrease the iNOS expression and reduce the level of NO in the lung tissue in rat asthma model.

  16. Pressure-related activation of inducible nitric oxide synthase

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    A lot of reports suggested that inducible nitric oxide synthase (iNOS) has a very different nature from constitutive NOS including endothelial NOS (eNOS) and neural NOS (nNOS). When exposed to cytokines or bacterial products, iNOS could be greatly activated and produces hundreds or thousands fold more NO than it does usually. Whether iNOS activation is arterial pressure related is not clear. In the present experiment, we studied three groups(n=6) of Sprague Dawley (SD) rats with implanted aorta and venous catheters that were maintained on 1 mEq/d, 12.5 mEq/d and 25 mEq/d of sodium intake respectively. Pulsatile arterial pressure signals from the amplifier were sent to a digital computer and the urine samples were taken every other day for nitrate/nitrite excretion (UNOx) assay using Greiss Reaction. After 6 days infusion, the rats were euthanized with an overdose of sodium pentobarbital, and the renal medullas were rapidly removed and frozen on dry ice for iNOS activity assay. Morever separate groups of hypertensive rats including spontaneously hypertensive rat (SHR, n=6) and High NaCl-induced hypertensive rat (NaHR, n=6) were used to measure renal iNOS protein by Western Blotting. The results showed that the mean arterial pressure (MAP) were significantly increased with the increase intake of sodium, the MAP (mmHg) at day 6 were 99.6±3.5,116.65±4.2 and 125.43±4.5, and the iNOS activity (nmol*g-1 protein*min-1) were 122.3±23.4, 342.4±35.6 and 623.9±65.4 in 1 mEq/d, 12.5 mEq/d and 25 mEq/d of sodium intake-rats respectively. At the same time, UNOx at day 6 were also increased, in turn, to 5 865.6±343.0 (for 12.5 mEq/d intake-rats) and (9 642.8±1 045.3) (for 25 mEq/d sodium intake-rats) nmol/d from (3 834.9±234.8) nmol/d of 1 mEq/d sodium intake-rats respectively. Western blotting showed that the renal medullary iNOS protein in SHR and NaHR were increased by 178%±13% and 104%±9% of normal Wistar rats. The data indicates that elevated arterial pressure

  17. Regulation of prostaglandin generation in carrageenan-induced pleurisy by inducible nitric oxide synthase in knockout mice.

    NARCIS (Netherlands)

    Rossi, A.; Cuzzocrea, S.; Mazzon, E.; Serraino, I.; Sarro, A. de; Dugo, L.; Felice, M.R.; Loo, F.A.J. van de; Rosa, M. Di; Musci, G.; Caputi, A.P.; Sautebin, L.

    2003-01-01

    In the present study, by comparing the responses in wild-type mice (iNOSWT) and mice lacking (iNOSKO) the inducible (or type 2) nitric oxide synthase (iNOS), we investigated the correlation between endogenous nitric oxide (NO) and prostaglandin (PG) generation in carrageenan-induced pleurisy. The in

  18. Nitric oxide synthase in the gill of Atlantic salmon: colocalization with and inhibition of Na+,K+-ATPase

    DEFF Research Database (Denmark)

    Ebbesson, Lars O E; Tipsmark, Christian K; Holmqvist, Bo;

    2005-01-01

    We investigated the relationship between nitric oxide (NO) and Na(+),K(+)-ATPase (NKA) in the gill of anadromous Atlantic salmon. Cells containing NO-producing enzymes were revealed by means of nitric oxide synthase (NOS) immunocytochemistry and nicotinamide adenine dinucleotide phosphate...

  19. L-Arginine is not the limiting factor for nitric oxide synthesis by human alveolar macrophages in vitro

    NARCIS (Netherlands)

    Muijsers, RBR; ten Hacken, NHT; Van Ark, [No Value; Folkerts, G; Nijkamp, FP; Postma, DS

    2001-01-01

    Unlike murine mononuclear phagocytes, human macrophages do not release high amounts of nitric oxide (NO) in vitro despite the presence of nitric oxide synthase (NOS). To determine whether this limited NO synthesis in vitro is due to limited availability of the NOS substrate L-arginine, and putative

  20. Neuronal Nitric-Oxide Synthase Deficiency Impairs the Long-Term Memory of Olfactory Fear Learning and Increases Odor Generalization

    Science.gov (United States)

    Pavesi, Eloisa; Heldt, Scott A.; Fletcher, Max L.

    2013-01-01

    Experience-induced changes associated with odor learning are mediated by a number of signaling molecules, including nitric oxide (NO), which is predominantly synthesized by neuronal nitric oxide synthase (nNOS) in the brain. In the current study, we investigated the role of nNOS in the acquisition and retention of conditioned olfactory fear. Mice…

  1. Nitric oxide as a fumigant for postharvest pest control and its safety to postharvest quality of fresh products

    Science.gov (United States)

    Nitric oxide fumigation under ultralow oxygen atmospheres was discovered recently to be effective for pest control. It is effective against all life stages of insects and mites and against both external and internal feeders. Nitric oxide fumigation comes with additional but acceptable costs associ...

  2. Nitric oxide mitigates arsenic-induced oxidative stress and genotoxicity in Vicia faba L.

    Science.gov (United States)

    Shukla, Pratiksha; Singh, A K

    2015-09-01

    The protective effects of nitric oxide (NO) against arsenic (As)-induced structural disturbances in Vicia faba have been investigated. As treatment (0.25, 0.50, and 1 mM) resulted in a declined growth of V. faba seedlings. Arsenic treatment stimulates the activity of SOD and CAT while the activities of APX and GST content were decreased. The oxidative stress markers such as superoxide radical, hydrogen peroxide and malondialdehyde (lipid peroxidation) contents were enhanced by As. Overall results revealed that significant accumulation of As suppressed growth, photosynthesis, antioxidant enzymes (SOD, CAT, APX, and GST activity), mitotic index, and induction of different chromosomal abnormalities, hence led to oxidative stress. The concentration of SNP (0.02 mM) was very effective in counteracting the adverse effect of As toxicity. These abnormalities use partially or fully reversed by a simultaneous application of As and NO donor and sodium nitroprusside and has an ameliorating effect against As-induced oxidative stress and genotoxicity in V. faba roots.

  3. Catalytic studies of nitric oxide: A. Reduction of nitric oxide with methane over alumina supported rhidium. B. Characterization of alumina supported cobalt molybdate for olefin metathesis

    Energy Technology Data Exchange (ETDEWEB)

    Hardee, J.R.

    1978-01-01

    Kinetic studies at 300/sup 0/-400/sup 0/C in a gradientless recirculating reactor showed that nitric oxide reduction was first order in methane and -0.63 order in nitric oxide, with an activation energy of 18.4 kcal/mole, and a deuterium kinetic isotope effect of 1.9, suggesting that dissociative methane adsorption is the rate-determining step. Nitrogen-15 tracer studies showed that the reaction involves N/sub 2/O as a surface intermediate, and a mechanism is proposed involving two-step dissociation of adsorbed NO to adsorbed N/sub 2/O and N/sub 2/ and surface oxygen atoms, which rapidly poison the catalyst unless removed by methane. Propylene metathesis to ethylene and 2-butene over cobalt molybdate was studied by nitric oxide poisoning and shown to follow Langmuir-Hinshelwood kinetics. Two different dual-site mechanisms, one involving propylene adsorption on adjacent molybdenum atoms and the other involving adsorption of two propylene molecules on one molybdenum atom, fit the data equally well. An upper limit to the active site density was determined as 2.5 x 10/sup 13//sq cm at 27/sup 0/C, i.e., only 9Vertical Bar3< of the surface molybdenum atom density.

  4. The endothelial nitric oxide synthase/nitric oxide system is involved in the defective quality of bovine oocytes from low mid-antral follicle count ovaries.

    Science.gov (United States)

    Tessaro, I; Luciano, A M; Franciosi, F; Lodde, V; Corbani, D; Modina, S C

    2011-08-01

    In a previous survey concerning cows of reproductive age, we demonstrated that oocytes isolated from ovaries with ovaries; Lo) show less developmental competence than oocytes collected from ovaries with >10 medium antral follicles (high ovaries; Hi). The aim of the present study was to evaluate whether a defective endothelial nitric oxide synthase/nitric oxide (eNOS/NO) system and vasculature in healthy medium antral follicles is likely to reduce oocyte competence from Lo ovaries. Thus, experiments were conducted to 1) immunolocalize eNOS protein during folliculogenesis; 2) quantify eNOS protein/vasculature in the follicle wall; and 3) verify if NO donor, S-nitroso acetyl penicillamine (SNAP) administration during in vitro maturation affects developmental competence of oocytes isolated from Lo ovaries. Endothelial nitric oxide synthase protein was detected in granulosa and theca cells, as well as in blood vessels from primordial to antral follicles. Quantitative analysis indicated that in medium antral follicles from Lo ovaries, eNOS protein expression and vasculature were reduced (P ovaries, promoting a percentage similar to oocytes from Hi ovaries, and reduced the percentage of apoptotic nuclei in in vitro-produced blastocysts (P bovine ovaries with small mid antral follicle number, a defective eNOS/NO system is related to a reduced follicle vasculature and may affect oocyte quality, thus inducing a premature decline of fertility. PMID:21421835

  5. Exhaled Nitric Oxide as a Biomarker in COPD and Related Comorbidities

    Directory of Open Access Journals (Sweden)

    Mario Malerba

    2014-01-01

    Full Text Available Chronic Obstructive Pulmonary Disease (COPD is defined as a disease characterized by persistent, progressive airflow limitation. Recent studies have underlined that COPD is correlated to many systemic manifestations, probably due to an underlying pattern of systemic inflammation. In COPD fractional exhaled Nitric Oxide (FeNO levels are related to smoking habits and disease severity, showing a positive relationship with respiratory functional parameters. Moreover FeNO is increased in patients with COPD exacerbation, compared with stable ones. In alpha-1 antitrypsin deficiency, a possible cause of COPD, FeNO levels may be monitored to early detect a disease progression. FeNO measurements may be useful in clinical setting to identify the level of airway inflammation, per se and in relation to comorbidities, such as pulmonary arterial hypertension and cardiovascular diseases, either in basal conditions or during treatment. Finally, some systemic inflammatory diseases, such as psoriasis, have been associated with higher FeNO levels and potentially with an increased risk of developing COPD. In these systemic inflammatory diseases, FeNO monitoring may be a useful biomarker for early diagnosis of COPD development.

  6. In vivo measurement of nitric oxide production in porcine gut, liver and muscle during hyperdynamic endotoxaemia

    Science.gov (United States)

    Bruins, Maaike J; Lamers, Wouter H; Meijer, Alfred J; Soeters, Peter B; Deutz, Nicolaas E P

    2002-01-01

    During prolonged endotoxaemia, an increase in arginine catabolism may result in limiting substrate availability for nitric oxide (NO) production. These effects were quantitated in a chronically instrumented porcine endotoxaemia model. Ten days prior to the beginning of the experiments, pigs were catheterized. On day 0, pigs received a continuous infusion of endotoxin (3 μg kg−1 h−1) over 24 h and were saline resuscitated. Blood was drawn from the catheters at 0 and 24 h during primed-infusion of 15N2-arginine and P-aminohippurate to assess 15N2-arginine to 15N-citrulline conversion and plasma flow rates, respectively, across the portal-drained viscera, liver and hindquarter. During endotoxin infusion a hyperdynamic circulation with elevated heart rate, cardiac index and decreased mean arterial pressure was achieved, characteristic of the human septic condition. Endotoxin induced NO production by the portal-drained viscera and the liver. The increased NO production was quantitatively matched by an increase in arginine disposal. Nitrite/nitrate levels remained unchanged during endotoxaemia. Despite an increased arginine production from the hindquarter and an increased whole-body arginine appearance rate during endotoxin infusion, the plasma arginine concentration was lower in endotoxin-treated animals than in controls. On a whole-body level, the muscle was found to serve as a major arginine supplier and, considering the lowered arginine plasma levels, seems critical in providing arginine as precursor for NO synthesis in the splanchnic region. PMID:12466232

  7. Nitric Oxide as a Unique Bioactive Signaling Messenger in Physiology and Pathophysiology

    Directory of Open Access Journals (Sweden)

    Tuteja Narendra

    2004-01-01

    Full Text Available Nitric oxide (NO is an intra- and extracellular messenger that mediates diverse signaling pathways in target cells and is known to play an important role in many physiological processes including neuronal signaling, immune response, inflammatory response, modulation of ion channels, phagocytic defense mechanism, penile erection, and cardiovascular homeostasis and its decompensation in atherogenesis. Recent studies have also revealed a role for NO as signaling molecule in plant, as it activates various defense genes and acts as developmental regulator. In plants, NO can also be produced by nitrate reductase. NO can operate through posttranslational modification of proteins (nitrosylation. NO is also a causative agent in various pathophysiological abnormalities. One of the very important systems, the cardiovascular system, is affected by NO production, as this bioactive molecule is involved in the regulation of cardiovascular motor tone, modulation of myocardial contractivity, control of cell proliferation, and inhibition of platelet activation, aggregation, and adhesion. The prime source of NO in the cardiovascular system is endothelial NO synthase, which is tightly regulated with respect to activity and localization. The inhibition of chronic NO synthesis leads to neurogenic and arterial hypertensions, which later contribute to development of myocardial fibrosis. Overall, the modulation of NO synthesis is associated with hypertension. This review briefly describes the physiology of NO, its synthesis, catabolism, and targeting, the mechanism of NO action, and the pharmacological role of NO with special reference to its essential role in hypertension.

  8. Anticonvulsant and proconvulsant roles of nitric oxide in experimental epilepsy models

    Directory of Open Access Journals (Sweden)

    Del-Bel E.A.

    1997-01-01

    Full Text Available The effect of acute (120 mg/kg and chronic (25 mg/kg, twice a day, for 4 days intraperitonial injection of the nitric oxide (NO synthase (NOS inhibitor NG-nitro-L-arginine (L-NOARG was evaluated on seizure induction by drugs such as pilocarpine and pentylenetetrazole (PTZ and by sound stimulation of audiogenic seizure-resistant (R and audiogenic seizure-susceptible (S rats. Seizures were elicited by a subconvulsant dose of pilocarpine (100 mg/kg only after NOS inhibition. NOS inhibition also simultaneously potentiated the severity of PTZ-induced limbic seizures (60 mg/kg and protected against PTZ-induced tonic seizures (80 mg/kg. The audiogenic seizure susceptibility of S or R rats did not change after similar treatments. In conclusion, proconvulsant effects of NOS inhibition are suggested to occur in the pilocarpine model and in the limbic components of PTZ-induced seizures, while an anticonvulsant role is suggested for the tonic seizures induced by higher doses of PTZ, revealing inhibitor-specific interactions with convulsant dose and also confirming the hypothesis that the effects of NOS inhibitors vary with the model of seizure

  9. The role of nitric oxide donors in schizophrenia: Basic studies and clinical applications.

    Science.gov (United States)

    Pitsikas, Nikolaos

    2015-11-01

    Schizophrenia is a complex and chronic mental health disease that affects nearly 1% of the population worldwide. While the current antipsychotic medications have profoundly impacted the treatment of schizophrenia over the past 50 years, the newer atypical antipsychotics have not fulfilled initial expectations, and enormous challenges remain in long-term treatment of this debilitating disease. In particular, improved treatment of the negative symptoms and cognitive dysfunction in schizophrenia which greatly impact overall morbidity is required. Nitric oxide (NO) is considered as an intra- and inter-cellular messenger in the brain. The implication of NO in the pathogenesis of schizophrenia is documented. Specifically, underproduction of NO is linked to this pathology. This, in turn, indicates that enhancement of nitrergic activity might be beneficial in this disease. Therefore, novel molecules aiming to increase NO production such as NO donors might constitute potential candidates for the treatment of schizophrenia. Here I intended to critically review advances in research of these emerging molecules for the treatment of this psychiatric disorder. Present analysis suggests that NO donors might be a promising class of compounds for the treatment of schizophrenia. However, the potential neurotoxicity and the narrow therapeutic window of NO donors would add a note of caution in this context.

  10. Hybrid inhibitor of peripheral cannabinoid-1 receptors and inducible nitric oxide synthase mitigates liver fibrosis

    Science.gov (United States)

    Liu, Ziyi; Cao, Zongxian; Jourdan, Tony; Erdelyi, Katalin; Godlewski, Grzegorz; Szanda, Gergő; Liu, Jie; Park, Joshua K.; Mukhopadhyay, Bani; Rosenberg, Avi Z.; Liow, Jeih-San; Lorenz, Robin G.; Pacher, Pal; Innis, Robert B.; Kunos, George

    2016-01-01

    Liver fibrosis, a consequence of chronic liver injury and a way station to cirrhosis and hepatocellular carcinoma, lacks effective treatment. Endocannabinoids acting via cannabinoid-1 receptors (CB1R) induce profibrotic gene expression and promote pathologies that predispose to liver fibrosis. CB1R antagonists produce opposite effects, but their therapeutic development was halted due to neuropsychiatric side effects. Inducible nitric oxide synthase (iNOS) also promotes liver fibrosis and its underlying pathologies, but iNOS inhibitors tested to date showed limited therapeutic efficacy in inflammatory diseases. Here, we introduce a peripherally restricted, orally bioavailable CB1R antagonist, which accumulates in liver to release an iNOS inhibitory leaving group. In mouse models of fibrosis induced by CCl4 or bile duct ligation, the hybrid CB1R/iNOS antagonist surpassed the antifibrotic efficacy of the CB1R antagonist rimonabant or the iNOS inhibitor 1400W, without inducing anxiety-like behaviors or CB1R occupancy in the CNS. The hybrid inhibitor also targeted CB1R-independent, iNOS-mediated profibrotic pathways, including increased PDGF, Nlrp3/Asc3, and integrin αvβ6 signaling, as judged by its ability to inhibit these pathways in cnr1−/− but not in nos2−/− mice. Additionally, it was able to slow fibrosis progression and to attenuate established fibrosis. Thus, dual-target peripheral CB1R/iNOS antagonists have therapeutic potential in liver fibrosis.

  11. Role of nitric oxide in the pathogenesis ofBarrett's-associated carcinogenesis

    Institute of Scientific and Technical Information of China (English)

    2016-01-01

    Barrett's esophagus (BE), a premalignant condition toBarrett's adenocarcinoma (BAC), is closely associatedwith chronic inflammation due to gastro-esophagealreflux. Caudal type homeobox 2 (CDX2), a representativemarker of BE, is increased during the metaplasticand neoplastic transformation of BE. Nitric oxide (NO)has been proposed to be a crucial mediator of Barrett'scarcinogenesis. We previously demonstrated that CDX2 might be induced directly under stimulation oflarge amounts of NO generated around the gastroesophagealjunction (GEJ) by activating epithelial growthfactor receptor in a ligand-independent manner. Thus,we reviewed recent developments on the role of NOin Barrett's carcinogenesis. Notably, recent studieshave reported that microbial communities in the distalesophagus are significantly different among groupswith a normal esophagus, reflux esophagitis, BE orBAC, despite there being no difference in the bacterialquantity. Considering that microorganism componentscan be one of the major sources of large amounts ofNO, these studies suggest that the bacterial compositionin the distal esophagus might play an important rolein regulating NO production during the carcinogenicprocess. Controlling an inflammatory reaction due togastro-esophageal reflux or bacterial composition aroundthe GEJ might help prevent the progression of Barrett'scarcinogenesis by inhibiting NO production.

  12. Distribution of nitric oxide synthase positive neurons in the substantia nigra of rats with liver cirrhosis

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND:Nitrogen monoxide plays an important role in the physiological activity and pathological process of striatum in substantia nigra, and the nitric oxide synthase in substantia nigra may have characteristic changes after liver cirrhosis.OBJECTIYE: To observe the distribution and forms of nitric oxide synthase (NOS) positive neurons and fibers in substantia nigra of rats with liver cirrhosis.DESIGN: A comparative observational experiment.SETTINGS: Beijing Friendship Hospital; Capital Medical University.MATERIALS: Twenty 4-month-old male Wistar rats (120 - 150 g) of clean grade, were maintained in a 12-hour light/dark cycle at a constant temperature with free access to standard diet and water. Cryostat microtome (LEICA, Germany); All the reagents were purchased from Sigma Company.METHODS: The experiment was carried out in the Department of Anatomy (key laboratory of Beijing city),Capital Medical University from July 2000 to March 2002. The rats were randomly divided into normal group (n=10) and liver fibrosis group (n=10). Rats in the liver fibrosis group were subcutaneously injected with 60% CCl4 oil at a dose of 5 mL/kg for the first time, and 3 mL/kg for the next 14 times, twice a week,totally 15 times. Liver fibrosis of grades 5 - 6 was taken as successful models. Whereas rats in the normal group were not given any treatment. Four months after CCl4 treatment, all the rats were anesthetized to remove brain, and frontal frozen serial sections were prepared. The expressions of nitric oxide synthase positive neurons in substantia nigra of rats were observed under inverted microscope. The number and gray scale of cell body of nitric oxide synthase positive neurons in substantia nigra were detected with NADPH-diaphorase staining.MAIN OUTCOME MEASURES: ①Number and gray scale of cell body of nitric oxide synthase positive neurons in substantia nigra; ②Expressions of nitric oxide synthase positive neurons in substantia nigra.RESULTS: All the 20 rats were

  13. Preparation of nitric humic acid by catalytic oxidation from Guizhou coal with catalysts

    Institute of Scientific and Technical Information of China (English)

    Yang Zhiyuan; Gong Liang; Ran Pan

    2012-01-01

    Nitric humic acid was prepared by catalytic oxidation between nitric acid and Guizhou coal,with added catalysts.We investigated catalytic oxidation processes and the factors that affect the reactions.The effects of different catalysts,including NiSO4 support on active carbon (AC-NiSO4),NiSO4 support on silicon dioxide (SiO2-NiSO4),composites of SO42-/Fe2O3,Zr-iron and vanadium-iron composite were studied.As well.we investigated nitric humic acid yields and the chemical structure of products by element analysis,FT-IR and E4/E6 (an absorbance ratio at wavelengths of 465 and 665 nm of humic acid alkaline extraction solutions).The results show that the catalytic oxidation reaction with added catalysts can increase humic acid yields by 18.7%,16.36%,12.94%,5.61% and 8.59%,respectively.The highest yield of humic acid,i.e.,36.0%,was obtained with AC-NiSO4 as the catalyst.The amounts of C and H decreased with the amount of nitrogen.The increase in the E4/E6 ratio in catalytic oxidation of (Guizhou) coal shows that small molecular weights and high yields of nitric humic acid can be obtained by catalytic oxidation reactions.

  14. Nitric oxide as a mediator of gastrointestinal mucosal injury?—Say it ain't so

    Directory of Open Access Journals (Sweden)

    Paul Kubes

    1995-01-01

    Full Text Available Nitric oxide has been suggested as a contributor to tissue injury in various experimental models of gastrointestinal inflammation. However, there is overwhelming evidence that nitric oxide is one of the most important mediators of mucosal defence, influencing such factors as mucus secretion, mucosal blood flow, ulcer repair and the activity of a variety of mucosal immunocytes. Nitric oxide has the capacity to down-regulate inflammatory responses in the gastrointestinal tract, to scavenge various free radical species and to protect the mucosa from injury induced by topical irritants. Moreover, questions can be raised regarding the evidence purported to support a role for nitric oxide in producing tissue injury. In this review, we provide an overview of the evidence supporting a role for nitric oxide in protecting the gastrointestinal tract from injury.

  15. 海马BDNF和iNOS与慢性应激性抑郁的关系%Sequental Involvement of Hippocampal BDNF and Inducible Nitric Oxide in Depression Induced by Chronic Unpredicted Mild Stress

    Institute of Scientific and Technical Information of China (English)

    王丹

    2010-01-01

    建立慢性不可预见性抑郁动物模型,采用液体消耗实验(fluid consumption test,FCT)、敞箱实验(Open field test,OFT)和强迫游泳(Forced swimming test,FST)等方法进行行为学测试,并用免疫组织化学的方法检测海马BDNF和iNOS的表达,运用腹腔注射药物的方法探索BDNF和iNOS的作用与关系.探讨了海马脑源性神经营养因子(BDNF)和诱导型一氧化氮合酶(iNOS)在慢性应激诱导的抑郁症中的关系,及抑郁症的发病机制.与对照组相比,慢性不可预见性应激(Chronic unpredicted mild stress ,CUMS)组大鼠的行为学表现能力下降,BDNF表达下降(n=8,P<0.01),iNOS的表达升高(n=8,P<0.01);阻断内源性BDNF大鼠的行为学表现能力也下降,iNOS的表达升高(n=7,P<0.01);而海马微量注射iNOS的抑制剂SMT均可反转CUMS和BDNF抑制剂所导致的行为学表现能力下降的现象.慢性不可预见性应激引起海马BDNF表达下降,NO过高而导致抑郁.BDNF对神经元具有保护作用, BDNF的抗抑郁作用可能是通过抑制iNOS的表达而起作用的.提示BDNF等神经保护因子通过抑制iNOS的过量表达而保护脑组织可能是治疗抑郁症的一个重要途径.

  16. Endothelial nitric oxide synthase (NOS) deficiency affects energy metabolism pattern in murine oxidative skeletal muscle.

    Science.gov (United States)

    Momken, Iman; Fortin, Dominique; Serrurier, Bernard; Bigard, Xavier; Ventura-Clapier, Renée; Veksler, Vladimir

    2002-01-01

    Oxidative capacity of muscles correlates with capillary density and with microcirculation, which in turn depend on various regulatory factors, including NO generated by endothelial nitric oxide synthase (eNOS). To determine the role of eNOS in patterns of regulation of energy metabolism in various muscles, we studied mitochondrial respiration in situ in saponin-permeabilized fibres as well as the energy metabolism enzyme profile in the cardiac, soleus (oxidative) and gastrocnemius (glycolytic) muscles isolated from mice lacking eNOS (eNOS(-/-)). In soleus muscle, the absence of eNOS induced a marked decrease in both basal mitochondrial respiration without ADP (-32%; P <0.05) and maximal respiration in the presence of ADP (-29%; P <0.05). Furthermore, the eNOS(-/-) soleus muscle showed a decrease in total creatine kinase (-29%; P <0.05), citrate synthase (-31%; P <0.01), adenylate kinase (-27%; P <0.05), glyceraldehyde-3-phosphate dehydrogenase (-43%; P <0.01) and pyruvate kinase (-26%; P <0.05) activities. The percentage of myosin heavy chains I (slow isoform) was significantly increased from 24.3+/-1.5% in control to 30.1+/-1.1% in eNOS(-/-) soleus muscle ( P <0.05) at the expense of a slight non-significant decrease in the three other (fast) isoforms. Besides, eNOS(-/-) soleus showed a 28% loss of weight. Interestingly, we did not find differences in any parameters in cardiac and gastrocnemius muscles compared with respective controls. These results show that eNOS knockout has an important effect on muscle oxidative capacity as well on the activities of energy metabolism enzymes in oxidative (soleus) muscle. The absence of such effects in cardiac and glycolytic (gastrocnemius) muscle suggests a specific role for eNOS-produced NO in oxidative skeletal muscle. PMID:12123418

  17. Correlation of plasma nitrite/nitrate levels and inducible nitric oxide gene expression among women with cervical abnormalities and cancer.

    Science.gov (United States)

    Sowjanya, A Pavani; Rao, Meera; Vedantham, Haripriya; Kalpana, Basany; Poli, Usha Rani; Marks, Morgan A; Sujatha, M

    2016-01-30

    Cervical cancer is caused by infection with high risk human papillomavirus (HR-HPV). Inducible nitric oxide synthase (iNOS), a soluble factor involved in chronic inflammation, may modulate cervical cancer risk among HPV infected women. The aim of the study was to measure and correlate plasma nitrite/nitrate levels with tissue specific expression of iNOS mRNA among women with different grades of cervical lesions and cervical cancer. Tissue biopsy and plasma specimens were collected from 120 women with cervical neoplasia or cancer (ASCUS, LSIL, HSIL and invasive cancer) and 35 women without cervical abnormalities. Inducible nitric oxide synthase (iNOS) mRNA from biopsy and plasma nitrite/nitrate levels of the same study subjects were measured. Single nucleotide polymorphism (SNP) analysis was performed on the promoter region and Ser608Leu (rs2297518) in exon 16 of the iNOS gene. Differences in iNOS gene expression and plasma nitrite/nitrate levels were compared across disease stage using linear and logistic regression analysis. Compared to normal controls, women diagnosed with HSIL or invasive cancer had a significantly higher concentration of plasma nitrite/nitrate and a higher median fold-change in iNOS mRNA gene expression. Genotyping of the promoter region showed three different variations: A pentanucleotide repeat (CCTTT) n, -1026T > G (rs2779249) and a novel variant -1153T > A. These variants were associated with increased levels of plasma nitrite/nitrate across all disease stages. The higher expression of iNOS mRNA and plasma nitrite/nitrate among women with pre-cancerous lesions suggests a role for nitric oxide in the natural history of cervical cancer. PMID:26435258

  18. Effect of nitric oxide on rostral ventrolateral medulla modulating cardiac sympathetic afferent reflex in rats with chronic heart failure%延髓头端腹外侧区一氧化氮对慢性心力衰竭大鼠心交感传入反射的影响

    Institute of Scientific and Technical Information of China (English)

    高兴亚; 郭瑞; 王玮; 张枫; 朱国庆

    2005-01-01

    大变化速率明显降低,左室舒张末压明显增加.②与假手术大鼠相比,慢性心力衰竭大鼠的心交感传入反射显著增强.③延髓头端腹外侧区微量注射MeTC(80 nmol)仅增强假手术大鼠的心交感传入反射,对慢性心力衰竭大鼠的心交感传入反射无显著影响.④延髓头端腹外侧区微量注射SNAP(50 nmol)同时抑制假手术和慢性心力衰竭大鼠的心交感传入反射.⑤心室前壁表面用利多卡因预处理可完全抑制心室前壁表面应用缓激肽所引起的肾交感神经活动增加.结论:延髓头端腹外侧区的一氧化氮抑制正常大鼠和慢性心力衰竭大鼠心室表面应用缓激肽引起的心交感传入反射,慢性心力衰竭大鼠心交感传入反射增强与延髓头端腹外侧区中内源性一氧化氮减少有关.%BACKGROUND: Nitric oxide in the central nervous system is involved in controlling the sympathetic outflow. The authors' recent data show that the reduction of nitric oxide in the rostral ventrolateral medulla (RVLM)enhanced the cardiac sympathetic afferent reflex (CSAR) evoked by stimulating the cardiac sympathetic afferent nerves in rats with chronic heart failure (CHF).OBJECTIVE: To further investigate the effect of nitric oxide in the RVLM on modulating the CSAR evoked by epicardial chemical stimulation in rats with CHF.DESIGN: Randomized controlled experiment.SETTING: Department of Physiology, Nanjing Medical University, and Department of Cellular and Integrative Physiology, University of Nebraska College of Medicine.MATERIALS: This study was carried out in the Department of Physiology, Nanjing Medical University from July 2003 to May 2004. A total of 52male Sprague-Dawley rats weighing 360-420 g were used, and were randomly divided into chronic heart failure group and control group with 23 in each group.METHODS: The rats were carried out either sham surgery or the left coronary artery ligation. Six to eight weeks later, all rats were

  19. Nitric oxide signals are interlinked with calcium signals in normal pancreatic stellate cells upon oxidative stress and inflammation

    Science.gov (United States)

    2016-01-01

    The mammalian diffuse stellate cell system comprises retinoid-storing cells capable of remarkable transformations from a quiescent to an activated myofibroblast-like phenotype. Activated pancreatic stellate cells (PSCs) attract attention owing to the pivotal role they play in development of tissue fibrosis in chronic pancreatitis and pancreatic cancer. However, little is known about the actual role of PSCs in the normal pancreas. These enigmatic cells have recently been shown to respond to physiological stimuli in a manner that is markedly different from their neighbouring pancreatic acinar cells (PACs). Here, we demonstrate the capacity of PSCs to generate nitric oxide (NO), a free radical messenger mediating, for example, inflammation and vasodilatation. We show that production of cytosolic NO in PSCs is unambiguously related to cytosolic Ca2+ signals. Only stimuli that evoke Ca2+ signals in the PSCs elicit consequent NO generation. We provide fresh evidence for the striking difference between signalling pathways in PSCs and adjacent PACs, because PSCs, in contrast to PACs, generate substantial Ca2+-mediated and NOS-dependent NO signals. We also show that inhibition of NO generation protects both PSCs and PACs from necrosis. Our results highlight the interplay between Ca2+ and NO signalling pathways in cell–cell communication, and also identify a potential therapeutic target for anti-inflammatory therapies. PMID:27488376

  20. Nitric oxide and geriatrics: Implications in diagnostics and treatment of the elderly

    Institute of Scientific and Technical Information of China (English)

    Ashley C Torregrossa; Mayank Aranke; Nathan S Bryan

    2011-01-01

    The nation's aging population is growing rapidly.By 2030,the number of adults age 65 and older will nearly double to 70 million.Americans are living longer and older adults can now live for many years with multiple chronic illnesses but with a substantial cost to health care.Twenty percent of the Medicare population has at least five chronic conditions i.e.,hypertension,diabetes,arthritis,etc.Studies in experimental models and even humans reveal that constitutive production of nitric oxide (NO) is reduced with aging and this circumstance may be relevant to a number of diseases that plague the aging population.NO is a multifunctional signaling molecule,intricately involved with maintaining a host of physiological processes including,but not limited to,host defense,neuronal communication and the regulation of vascular tone.NO is one of the most important signaling molecules in our body,and loss of NO function is one of the earliest indicators or markers of disease.Clinical studies provide evidence that insufficient NO production is associated with all major cardiovascular risk factors,such as hyperlipidemia,diabetes,hypertension,smoking and severity of atherosclerosis,and also has a profound predictive value for disease progression including cardiovascular and Alzheimers disease.Thirty plus years after its discovery and over 13 years since a Nobel Prize was awarded for its discovery,there have been no hallmark therapeutic breakthroughs or even NO based diagnostics.We will review the current state of the science surrounding NO in the etiology of a number of different diseases in the geriatric patient.From these observations,it can be concluded that enzymatic production of NO declines steadily with increasing age in healthy human subjects.Implementing strategies to diagnose and treat NO insufficiency may provide enormous benefit to the geriatric patient.