Total Amount Of Nitric Oxide Research Articles

Profile of new vascular damage biomarkers in middle-aged men with arterial hypertension

PurposeNormal endothelial function is important for the homeostasis of the cardiovascular (CV) system. The aim of the present study was to determine the profile of key parameters of endothelial dysfunction in middle-aged men that play a significant role in the functioning of endothelial vessels, which seems to be crucial for the early diagnosis of cardiovascular disorders. Materials and methodsThe study included 53 men, 20 with hypertension (HTN), 18 with HTN and related diseases, 15 healthy controls Apart from general testing (BMI, biochemical analysis, SBP, DBP), we used the Griess reaction to assess the total amount of nitric oxide (NO), and used ELISA to verify the concentrations of malondialdehyde (MDA), nitrotyrosine (NT), asymmetric dimethylarginine (ADMA), tumor necrosis factor-alpha (TNF-α), monocyte chemotactic protein 1 (MCP-1), and myeloperoxidase (MPO). Furthermore, we assessed the concentration of circulating free DNA (cfDNA) using the fluorescence method. ResultsThe values of MDA, ADMA, cfDNA, and MPO observed in samples from men with HTN were determined to be higher compared to those from men without HTN. In the group of men with HTN and other concomitant cardiovascular disorders, we observed low concentrations of NO, MDA, and ADMA with high concentrations of cfDNA. ConclusionsThe results obtained for parameters selected for the study, should be considered by cardiologists as a prompt to include in the diagnostic profile the assessment of NO and cfDNA concentrations for risk evaluation and/or diagnosis of endothelial dysfunction in patients suffering from HTN or related complications.

Nitric oxide production from nitrite by a series of zeolites produced via the ADOR route

The nitric oxide (NO) production for a series of aluminosilicate zeolites, prepared using the ADOR method, was investigated. Al-UTL and Al-IPC-2,-4 and −6 were prepared and characterised to determine their elemental composition. Positive trends were found to exist between zeolite pore size and the rate and total amount of NO produced. A trend between the number of acid sites and the initial rate of NO produced by the zeolite was also discovered.

Critical nitric oxide concentration for Pseudomonas aeruginosa biofilm reduction on polyurethane substrates.

Bacterial colonies that reside on a surface, known as biofilms, are intrinsically impenetrable to traditional antibiotics, ultimately driving research toward an alternative therapeutic approach. Nitric oxide (NO) has gained attention for its biologically beneficial properties, particularly centered around its antibacterial capabilities. NO donors that can release the molecule under physiological conditions (such as S-nitrosothiols) can be utilized in clinical settings to combat bacterial biofilm infections. Herein the authors describe determining a critical concentration of NO necessary to cause >90% reduction of a Pseudomonas aeruginosa biofilm grown on medical grade polyurethane films. The biofilm was grown under optimal culture conditions [in nutrient broth media (NBM) at 37 °C] for 24 h before the addition of the NO donor S-nitrosoglutathione (GSNO) in NBM for an additional 24 h. The cellular viability of the biofilm after the challenge period was tested using varying concentrations of NO to determine the critical amount necessary to cause at least a 90% reduction in bacterial biofilm viability. The critical GSNO concentration was found to be 10 mM, which corresponds to 2.73 mM NO. Time kill experiments were performed on the 24 h biofilm using the critical amount of NO at 4, 8, 12, and 16 h and it was determined that the 90% biofilm viability reduction occurred at 12 h and was sustained for the entire 24 h challenge period. This critical concentration was subsequently tested for total NO release via a nitric oxide analyzer. The total amount of NO released over the 12 h challenge period was found to be 5.97 ± 0.66 × 10(-6) mol NO, which corresponds to 1.49 ± 0.17 μmol NO/ml NBM. This is the first identification of the critical NO concentration needed to elicit this biological response on a medically relevant polymer.

High correlations between temperature and nitric oxide in the thermosphere.

Obtaining accurate predictions of the neutral density in the thermosphere has been a long‐standing problem. During geomagnetic storms the auroral heating in the polar ionospheres quickly raises the temperature of the thermosphere, resulting in higher neutral densities that exert a greater drag force on objects in low Earth orbit. Rapid increases and decreases in the temperature and density may occur within a couple days. A key parameter in the thermosphere is the total amount of nitric oxide (NO). The production of NO is accelerated by the auroral heating, and since NO is an efficient radiator of thermal energy, higher concentrations of this molecule accelerate the rate at which the thermosphere cools. This paper describes an improved technique that calculates changes in the global temperature of the thermosphere. Starting from an empirical model of the Poynting flux into the ionosphere, a set of differential equations derives the minimum, global value of the exospheric temperature, which can be used in a neutral density model to calculate the global values. The relative variations in NO content are used to obtain more accurate cooling rates. Comparisons with the global rate of NO emissions that are measured with the Sounding of the Atmosphere using Broadband Emission Radiometry instrument show that there is very good agreement with the predicted values. The NO emissions correlate highly with the total auroral heating that has been integrated over time. We also show that the NO emissions are highly correlated with thermospheric temperature, as well as indices of solar extreme ultraviolet radiation.

Hypoxia induces stem and leaf nitric oxide (NO) emission from poplar seedlings.

Hypoxia leads to NO formation in poplar roots. Additionally, either NO or a NO derivative is transported from the roots to the shoot causing NO emission from aboveground plant organs. Nitric oxide (NO) is involved in the response of plants to various forms of stress including hypoxia. It also seems to play an important role in stomatal closure during stress exposure. In this study, we investigated the formation of NO in roots of intact poplar (Populus×canescens) plants in response to hypoxia, as well as its dependence on nitrate availability. We further addressed the question if root hypoxia triggers NO emission from aboveground plant parts, i.e., stems and leaves of young poplar trees. Our results indicate that NO is formed in poplar roots in response to hypoxia and that this production depends on the availability of nitrate and its conversion product nitrite. As long as nitrate was available in the nutrient solution, NO emission of roots occurred; in the range of the nitrate concentrations (10-100µM) tested, NO emission was widely independent on nitrate concentration. However, the time period in which NO was emitted and the total amount of NO emitted strongly depended on the nitrate concentration of the solution. Hypoxia also led to increased NO emissions from the leaves and stems of the trees. There was a tight correlation between leaf and stem NO emission of hypoxia-treated plants. We propose that NO is produced by nitrate reductase in the roots and either NO itself, a metabolic NO precursor, or a NO derivative is transported in the xylem sap of the trees from the roots to the shoot thereby mediating NO emission from aboveground parts of the plant.

Selective binding of an imprinted polymer resulted from controlling cobalt coordination to nitric oxide

AbstractIn this article, the binding characteristics of the imprinted polymer P‐1[CoII(salen)] (salen: bis(2‐hydroxybenzaldehyde)ethylenediimine) to nitric oxide (NO) have been reported. P‐1[CoII(salen)] was characterized by Fourier transform infrared analysis, thermogravimetric analysis, and differential scanning calorimetry. Batch‐mode adsorption studies were carried out to investigate binding thermodynamics, kinetics, and selective recognition behavior of P‐1[CoII(salen)] to NO. The kinetics study indicates that binding of the polymer to NO fits the first‐order reaction kinetics with the rate constant k1 of 0.087 min−1. Langmuir and Freundlich equations were used to explain the equilibrium character of P‐1[CoII(salen)] binding to NO. The r2 and χ2 values suggest that total amount of NO bound by P‐1[CoII(salen)] can be best fitted by the Langmuir equation. The binding capacity (Bmax) of P‐1[CoII(salen)] was calculated to be 76.28 μmol/g, very close to the experimental value, 75 μmol/g. The thermodynamics and selectivity experiments showed that the affinity of P‐1[CoII(salen)] to NO was much higher than carbon dioxide (CO2) and oxygen (O2), suggesting that P‐1[CoII(salen)] is a promising functional material for NO storage and NO sensing. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013

Age-related comparative evaluation of laboratory-functional parameters of vascular endothelial dysfunction in patients with arterial hypertension

Aim. To conduct a comparative complex evaluation of the vasomotor and metabolic functions of the vascular endothelium in patients of different age groups with arterial hypertension. Methods. Examined were 98 young men and 60 elderly people with arterial hypertension of the I and II degree. The control group included 44 practically healthy young men and 45 elderly men. The endothelial function was assessed by Doppler measurements of brachial artery diameter at rest and during the test with reactive hyperemia and nitroglycerin, as well as by determining serum levels of the total amount of nitric oxide. Secondary stable products of lipid peroxidation were determined by the level of malondialdehyde. Antioxidant activity of blood was determined by evaluating the spontaneous chemiluminescence response. The diameter of the common carotid artery and the width of the intima/media complex was evaluated at rest using an ultrasound scanner. Results. Disturbance of the endothelium-dependent vasodilation in young and elderly patients with arterial hypertension of the I and II degree was accompanied by a significant decrease in production of endothelial nitric oxide. The expression of vascular endothelial dysfunction in patients of different ages with arterial hypertension of the I and II degree was in close correlation with the indicators of imbalance between the prooxidant activity and the antioxidant activity of blood, which manifested in an increase in the concentration of malondialdehyde in blood serum and in the decrease of the «antioxidant activity of blood/malondialdehyde content in blood serum» coefficient compared to groups of healthy individuals in response to pathological vasoconstriction. Conclusion. Arterial hypertension is accompanied by a progressive dysfunction of the vascular endothelium, which is more pronounced in the elderly due to reduced production of nitric oxide by the endothelium and due to the imbalance of the prooxidant-antioxidant system.

Antibacterial nitric oxide-releasing xerogels: Cell viability and parallel plate flow cell adhesion studies

The ability of nitric oxide (NO)-releasing xerogels to reduce adhesion of Pseudomonas aeruginosa under flowing conditions was evaluated using a parallel plate flow chamber. At a controlled bacterial suspension flow rate of 0.2 mL/min, the NO-releasing xerogels reduced bacterial adhesion in a flux-dependent fashion, with an NO flux of ∼21 pmol cm −2 s −1 reducing P. aeruginosa adhesion by ∼65% compared to controls. Fluorescent viability staining indicated that bacteria adhered to NO-releasing xerogels were killed within 7 h. Quantitative cell-plating viability studies showed that the extent of bactericidal activity was dependent on the total amount of NO released, with 750 nmol cm −2 killing >90% more adhered bacteria than xerogels releasing 25 nmol cm −2. Thus, NO-releasing xerogels were shown to both inhibit P. aeruginosa adhesion and kill adhered bacteria cells, two important steps toward designing anti-infective biomaterial coatings.

Hypoxia accelerates nitric oxide-dependent inhibition of mitochondrial complex I in activated macrophages.

Excess production of nitric oxide (NO) is implicated in the development of multiple organ failure, with a putative mechanism involving direct mitochondrial inhibition, predominantly affecting complex I. The persistent effects of NO on complex I may be mediated through S-nitrosylation and/or nitration. The temporal contribution of these chemical modifications to the inhibition of respiration and the influence of concurrent hypoxia have not been previously examined. We therefore addressed these questions using J774 macrophages activated by endotoxin and interferon-gamma over a 24-h period, incubated at 21% and 1% oxygen. Oxygen consumption and complex I activity fell progressively over time in the activated cells. This was largely prevented by coincubation with the nonspecific NO synthase inhibitor L-N5-(1-iminoethyl)-ornithine. Addition of glutathione ethyl ester reversed the inhibition at initial time points, suggesting an early mechanism involving nitrosylation. Thereafter, the inhibition of complex I became more persistent, coinciding with a progressive increase in mitochondrial nitration. Hypoxia accelerated the persistent inhibition of complex I, despite a reduction in the total amount of NO generated. Our results suggest that hypoxia amplified the mitochondrial inhibition induced by NO generated during inflammatory disease states.

Combination of paclitaxel and nitric oxide as a novel treatment for the reduction of restenosis.

The combination of a nitric oxide (NO) donor and a paclitaxel-NO donor conjugate coated on a vascular stent was tested in a rabbit iliac artery model of stenosis as a potential therapy for restenosis. Paclitaxel was conjugated with a NO donor at the 7-position to give compound 7. An adamantane-based NO donor 14 was synthesized and combined with 7 to provide a burst of NO in the first few critical hours following injury to the vessel wall. Both 7 and 14 demonstrated antiproliferative activity (IC(50) = 20 nM and 15 microM, respectively) and antiplatelet activity (IC(50) = 10 and 1 microM, respectively). Stents were coated with a layer of a polymer containing test compounds. The total amount of NO eluted from the stents after a 6 h implantation in the rabbit iliac artery was 35%, 95%, and 69% of the original content for the stents coated with 7, 14, and the combination of 7 and 14, respectively. The antistenotic activity of 7 and 14 was determined in a 28-day rabbit model with two control groups (uncoated stents and polymer-coated stents) and two study groups (paclitaxel-coated stents and stents coated with the combination of 7 and 14). Polymer-coated stents caused inflammation and increased stenosis by 39% when compared to the uncoated stents. The stents coated with 7 plus 14 were as good as the uncoated stents, 41% better than the polymer-coated stents and 34% better than the paclitaxel-coated stents. These data indicate a beneficial effect of adding NO to an antiproliferative agent (paclitaxel) and suggest a potential therapeutic combination for the treatment of stenotic vessel disease.

Inhaled nitric oxide improves survival rates during hypoxia in a sickle cell (SAD) mouse model.

The hallmark of sickle cell disease (SCD) is erythrocyte sickling during deoxygenation of the abnormal hemoglobin S (HbS). When HbS is deoxygenated, it aggregates into polymers, resulting in distortion of the erythrocyte structure, producing microvascular thrombosis and ischemia. The transgenic SAD mouse produces three types of human hemoglobin: S, Antilles, and D-Punjab (HbSAD) and provides an animal model for SCD. We studied the effects of nitric oxide (NO) breathing at various doses and time regimens in the presence of severe hypoxia (6% oxygen) using the SAD mouse model. Age- and sex-matched control and SAD mice were exposed to 6% oxygen breathing in an environmental chamber and assessed for survival up to 1 h. Animals received different inhaled NO concentrations before and/or during hypoxia. Blood was obtained to evaluate the oxyhemoglobin dissociation curve and measure methemoglobinemia. Pretreatment by breathing NO at 20 ppm by volume in air for 30 min, and continuing to breathe 20 ppm NO during hypoxia resulted in improvement in survival rates in the SAD mouse (75%, n = 8) as compared with control SAD mice (11%, n = 9; P < 0.001). Pretreatment alone or breathing lower doses of NO were not protective. Changes in HbSAD oxygen affinity were not detected with NO breathing, and methemoglobin levels were low in all surviving mice. Breathing NO produced a rapid, protective effect to severe hypoxic stress in SAD mice. There appears to be a required loading period between NO breathing and its beneficial effect during hypoxic stress, possibly because of the total amount of NO delivered to SAD hemoglobin, blood cell components, and endothelium. NO breathing may be beneficial as a therapeutic intervention in SCD.

In vitro comparison of two NONOates (novel nitric oxide donors) on rat pulmonary arteries

The pulmonary vasorelaxant properties of two NONOates (diazeniumdiolates) were examined because this novel group of nitric oxide (NO) donors may be useful in pulmonary hypertension. MAHMA NONOate (( Z)-1-{ N-Methyl- N-[6-( N-methylammoniohexyl)amino]} diazen-1-ium-1,2-diolate) and spermine NONOate (( Z)-1-{ N-[3-aminopropyl]- N-[4-(3-aminopropylammonio)butyl]-amino}diazen-1-ium-1,2-diolate) decomposed at different rates (half-lives 1.3 min and 73 min, respectively; 37°C, pH 7.3) but generated the same total amount of NO. They fully relaxed submaximally contracted ring preparations of main and intralobar pulmonary arteries from rats. Responses were inhibited by the guanylate cyclase inhibitor, ODQ (1 H-[1,2,4]Oxadiazolo[4,3- a]quinoxalin-1-one). Potency was not affected by choice of contractile spasmogen (phenylephrine, endothelin-1, thromboxane-mimetic) or endothelium removal, and tolerance did not develop; thus the drugs had properties important for use in pulmonary hypertension. MAHMA NONOate was 10–40-fold more potent than spermine NONOate but responses to spermine NONOate were more sustained (spermine NONOate>60 min; MAHMA NONOate<7 min). It is concluded that the differences in potency and time-course reflect the different rates of NO generation by these NONOates.

Uptake of inhaled nitric oxide in acute lung injury

Despite the widespread use of inhaled nitric oxide (NO), little is known of its pulmonary uptake in patients with acute respiratory failure. Fourteen patients with acute lung injury (ALI) and ongoing NO therapy were studied. Three doses of NO (5, 10 and 40 ppm) were given for 20 min and at each dose level the following parameters were recorded: minute ventilation, inspiratory NO conc., mixed expired NO conc., end-tidal NO conc., mixed expired CO2 conc., end-tidal CO2 conc, and arterial CO2 tension. Total uptake was calculated and correlated to the total amount of NO inhaled, the amount of NO administered to the alveolar space, and the amount of NO administered to the perfused alveolar space. About 35% of the total amount of NO delivered is taken up by the lungs, 70% of NO administered to the alveolar space is taken up, and 95-100% of the NO administered to perfused alveolar space is taken up. The size of the alveolar dead space varied between 10 and 60% of the alveolar space. At 40 ppm of inhaled NO there was no difference between inspired and mixed expired NO2 concentration, indicating that there is no significant NO2 formation taking place in the lungs during NO inhalation at the concentrations studied. Practically all NO administered to the perfused alveolar space is taken up. The total uptake differs from that of healthy persons probably because of differences in the alveolar dead space.

石炭の循環流動層燃焼におけるＮ２Ｏ生成

Parametric study was made on emission of nitric oxide (NO) and nitrous oxide (N2O) from a bench scale circulating fluidized bed combustor (CFBC) of coal. It was found that significant amount of N2O was emitted from the CFBC. N2O emission levels were dependent on the bed temperature and coal types, and were parti cularly sensitive to former. Under the condition of lower bed temperature and/or low volatile coals, the N2O emission increased. The dependency of N2O emission on the bed temperature and the coal types was opposite to that of NO.The total amount of NO and N2O was rather independent of the operating conditions except for the coal types and became large for low volatile coals.