Mammalian synthesis of nitrite, nitrate, nitric oxide, and N-nitrosating agents

1988 ◽  
Vol 1 (5) ◽  
pp. 249-257 ◽  
Author(s):  
Michael A. Marletta
Keyword(s):  
Nitric Oxide ◽  
Nitrite Nitrate

scholarly journals Cold Atmospheric Pressure Plasma-Activated Medium Induces Selective Cell Death in Human Hepatocellular Carcinoma Cells Independently of Singlet Oxygen, Hydrogen Peroxide, Nitric Oxide and Nitrite/Nitrate

2021 ◽  
Vol 22 (11) ◽  
pp. 5548
Author(s):  
Yan Li ◽  
Tianyu Tang ◽  
Haejune Lee ◽  
Kiwon Song
Keyword(s):  
Nitric Oxide ◽  
Cell Death ◽  
Singlet Oxygen ◽  
Atmospheric Pressure ◽  
Atmospheric Pressure Plasma ◽  
Proliferative Effect ◽  
Huh7 Cells ◽  
Anti Cancer ◽  
Cold Atmospheric Pressure Plasma ◽  
Nitrite Nitrate

Cold atmospheric pressure plasma (CAP) and plasma-activated medium (PAM) induce cell death in diverse cancer cells and may function as powerful anti-cancer agents. The main components responsible for the selective anti-cancer effects of CAP and PAM remain elusive. CAP or PAM induces selective cell death in hepatocellular carcinoma cell lines Hep3B and Huh7 containing populations with cancer stem cell markers. Here, we investigated the major component(s) of CAP and PAM for mediating the selective anti-proliferative effect on Hep3B and Huh7 cells. The anti-proliferative effect of CAP was mediated through the medium; however, the reactive oxygen species scavenger N-acetyl cysteine did not suppress PAM-induced cell death. Neither high concentrations of nitrite or nitrite/nitrate nor a low concentration of H2O2 present in the PAM containing sodium pyruvate affected the viability of Hep3B and Huh7 cells. Inhibitors of singlet oxygen, superoxide anions, and nitric oxide retained the capacity of PAM to induce anti-cancer effects. The anti-cancer effect was largely blocked in the PAM prepared by placing an aluminum metal mesh, but not a dielectric PVC mesh, between the plasma source and the medium. Hence, singlet oxygen, hydrogen peroxide, nitric oxide, and nitrite/nitrate are not the main factors responsible for PAM-mediated selective death in Hep3B and Huh7 cells. Other factors, such as charged particles including various ions in CAP and PAM, may induce selective anti-cancer effects in certain cancer cells.

Effects of Early Neuronal and Delayed Inducible Nitric Oxide Synthase Blockade on Cardiovascular, Renal, and Hepatic Function in Ovine Sepsis

2010 ◽  
Vol 113 (6) ◽  
pp. 1376-1384 ◽  
Author(s):  
Matthias Lange ◽  
Atsumori Hamahata ◽  
Daniel L. Traber ◽  
Yoshimitsu Nakano ◽  
Aimalohi Esechie ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Nitric Oxide Synthase Inhibitor ◽  
Nitrite Nitrate ◽  
Synthase Inhibitor ◽  
Plasma Nitrite ◽  
Oxide Synthase ◽  
Organ Dysfunctions ◽  
Inducible Nitric Oxide

Background Recent evidence suggests that nitric oxide produced via the neuronal nitric oxide synthase is involved mainly in the early response to sepsis, whereas nitric oxide derived from the inducible nitric oxide synthase is responsible during the later phase. We hypothesized that early neuronal and delayed inducible nitric oxide synthase blockade attenuates multiple organ dysfunctions during sepsis. Methods Sheep were randomly allocated to sham-injured, nontreated animals (n = 6); injured (48 breaths of cotton smoke and instillation of Pseudomonas aeruginosa into the lungs), nontreated animals (n = 7); and injured animals treated with a neuronal nitric oxide synthase inhibitor from 1 to 12 h and an inducible nitric oxide synthase inhibitor from 12 to 24 h postinjury (n = 6). Results The injury induced arterial hypotension, vascular leakage, myocardial depression, and signs of renal and hepatic dysfunctions. The treatment significantly attenuated, but did not fully prevent, the decreases in mean arterial pressure and left ventricular stroke work index. Although the elevation of creatinine levels was partially prevented, the decreases in urine output and creatinine clearance were not affected. The injury-related increases in bilirubin levels, international normalized ratio, and lipid peroxidation in liver tissue were significantly attenuated. Although plasma nitrite/nitrate levels were significantly increased versus baseline from 12-24 h in controls, plasma nitrite/nitrate levels were not increased in treated animals. Conclusions The combination treatment shows potential benefit on sepsis-related arterial hypotension and surrogate parameters of organ dysfunctions in sheep. It may be crucial to identify the time course of expression and activation of different nitric oxide synthase isoforms in future investigations.

scholarly journals Blood asymmetric dimethylarginine and nitrite/nitrate concentrations in short-stature children born small for gestational age with and without growth hormone therapy

2017 ◽  
Vol 46 (2) ◽  
pp. 761-772 ◽  
Author(s):  
Hironori Nagasaka ◽  
Ichiro Morioka ◽  
Mayuko Takuwa ◽  
Mariko Nakacho ◽  
Mayumi Yoshida ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Growth Hormone ◽  
Asymmetric Dimethylarginine ◽  
Therapy Group ◽  
Adma Level ◽  
Gh Therapy ◽  
Normal Children ◽  
Group A ◽  
Group B ◽  
Nitrite Nitrate

Objective To investigate the basal amino acid metabolism and impact of growth hormone (GH) therapy in short-stature children born small for gestational age (short SGA children). Methods In this age-matched case-control study, the basal blood levels of amino acids, asymmetric dimethylarginine (ADMA), and nitrite/nitrate (NOx) were compared between 24 short SGA children and 25 age-matched normal children. Changes in these parameters were assessed for 12 months in 12 short SGA children initiating GH therapy (Group A) and 12 age-matched short SGA children without GH therapy (Group B). Results The arginine levels were significantly lower in the short SGA than in normal children. The ADMA levels were significantly higher and NOx levels were significantly lower in the short SGA than normal children. In Group A, the ADMA level was significantly lower and NOx level was significantly higher at 6 months than at baseline. At 12 months, the ADMA level in Group A began to increase, but the NOx level remained the same. Group B showed no significant changes. Conclusions This study is the first to show that ADMA is promoted and nitric oxide is suppressed in short SGA children and that GH therapy affects the production of ADMA and nitric oxide.

scholarly journals Cholesterol induces renal vasoconstriction and anti-natriuresis by inhibiting nitric oxide production in anesthetized rats

2009 ◽  
Vol 297 (6) ◽  
pp. F1606-F1613 ◽  
Author(s):  
Libor Kopkan ◽  
Md Abdul H. Khan ◽  
Agnieszka Lis ◽  
Mouhamed S. Awayda ◽  
Dewan S. A. Majid
Keyword(s):  
Nitric Oxide ◽  
Sodium Reabsorption ◽  
No Production ◽  
Sprague Dawley ◽  
Appreciable Change ◽  
Renal Vasoconstriction ◽  
Sprague Dawley Rats ◽  
Nitrite Nitrate ◽  
Synthase Inhibitor ◽  
Renal Responses

Although hypercholesterolemia is implicated in the pathophysiology of many renal disorders as well as hypertension, its direct actions in the kidney are not yet clearly understood. In the present study, we evaluated renal responses to administration of cholesterol (8 μg·min−1·100 g body wt−1; bound by polyethylene glycol) into the renal artery of anesthetized male Sprague-Dawley rats. Total renal blood flow (RBF) was measured by a Transonic flow probe, and glomerular filtration rate (GFR) was determined by Inulin clearance. In control rats ( n = 8), cholesterol induced reductions of 10 ± 2% in RBF [baseline (b) 7.6 ± 0.3 μg·min−1·100 g−1], 17 ± 3% in urine flow (b, 10.6 ± 0.9 μg·min−1·100 g−1), 29 ± 3% in sodium excretion (b, 0.96 ± 0.05 μmol·min−1·100 g−1) and 24 ± 2% in nitrite/nitrate excretion (b, 0.22 ± 0.01 nmol·min−1·100 g−1) without an appreciable change in GFR (b, 0.87 ± 0.03 ml·min−1·100 g−1). These renal vasoconstrictor and anti-natriuretic responses to cholesterol were absent in rats pretreated with nitric oxide (NO) synthase inhibitor, nitro-l-arginine methylester (0.5 μg·min−1·100 g−1; n = 6). In rats pretreated with superoxide (O2−) scavenger tempol (50 μg·min−1·100 g−1; n = 6), the cholesterol-induced renal responses remained mostly unchanged, although there was a slight attenuation in anti-natriuretic response. This anti-natriuretic response to cholesterol was abolished in furosemide-pretreated rats (0.3 μg·min−1·100 g−1; n = 6) but remained unchanged in amiloride-pretreated rats (0.2 μg·min−1·100 g−1; n = 5), indicating that Na+/K+/2Cl− cotransport is the dominant mediator of this effect. These data demonstrate that cholesterol-induced acute renal vasoconstrictor and antinatriuretic responses are mediated by a decrease in NO production. These data also indicate that tubular effect of cholesterol on sodium reabsorption is mediated by the furosemide sensitive Na+/K+/2Cl− cotransporter.

scholarly journals Dietary Nitrite: from menace to marvel

2016 ◽  
Vol 6 (11) ◽  
pp. 691 ◽  
Author(s):  
Nathan S. Bryan
Keyword(s):  
Nitric Oxide ◽  
Health Benefits ◽  
Biomedical Science ◽  
No Production ◽  
Positive Health ◽  
Therapeutic Benefits ◽  
Rigorous Research ◽  
Science Community ◽  
Nitrite Nitrate ◽  
Nutrition Epidemiology

Background: There are now indisputable health benefits of nitrite when administered in a clinical setting for specific diseases.  Most of the published reports identify the production of nitric oxide (NO) as the mechanism of action for nitrite.  Basic science as well as clinical studies demonstrates nitrite and/or nitrate can restore NO homeostasis as an endothelium independent source of NO that may be a redundant system for endogenous NO production.  Nitrate must first be reduced to nitrite by oral commensal bacteria and then nitrite further reduced to NO along the physiological oxygen gradient.  Despite decades of rigorous research on its safety and efficacy as a curing agent, sodium nitrite is still regarded by many as a toxic undesirable food additive.  However, research within the biomedical science community has revealed enormous therapeutic benefits of nitrite that is currently being developed as novel therapies for conditions associated with nitric oxide insufficiency.  This review will highlight the fundamental biochemistry of nitrite and nitrate in human physiology and provide evidence that nitrite and nitrate be considered essential nutrients.  Foods or diets enriched with nitrite can have profound positive health benefits. Keywords: nitrite, nitrate, nitric oxide, curing, nutrition, epidemiology, cardiovascular, cancer, diet, nitrosamines, antioxidants

scholarly journals Effect of ACEI and ARB treatment on nitric oxide-dependent endothelial function

VASA ◽  
2021 ◽  
Author(s):  
Kangbo Li ◽  
Claudia Zemmrich ◽  
Peter Bramlage ◽  
Anja Bondke Persson ◽  
Mesud Sacirovic ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nitric Oxide ◽  
Angiotensin Converting Enzyme ◽  
Endothelial Function ◽  
Mononuclear Cells ◽  
Mrna Level ◽  
Converting Enzyme ◽  
Bradykinin Receptors ◽  
Artery Disease ◽  
Nitrite Nitrate

Summary: Background: Angiotensin-converting-enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) are widely used as a first-line therapy for the treatment of cardiovascular disease. Here, ACEI modulate the bradykinin receptor (BDKRB1 and BDKRB2) system and NO-dependent endothelial function, thus determining cardiovascular health and regenerative arteriogenesis. The current study aims at evaluating nitric oxide-dependent endothelial function, and gene expression of bradykinin receptors in peripheral blood mononuclear cells (PBMC) from patients with ACEI or ARB treatment. Patients and methods: The WalkByLab has been established to screen cardiovascular patients for peripheral artery disease and coronary artery disease. In total 177 patients from WalkByLab with heterogenous disease and risk status were randomly selected, divided according to their medication history into the following groups: 1. ACEI group, 2. ARB group or 3. non-ACE/ARB group. Total plasma nitrite/nitrate (NO) levels were measured, endothelial function was evaluated by assessing flow meditated dilation (FMD). PBMC were isolated from peripheral whole blood, and gene expression (qRT-PCR) of bradykinin receptors and angiotensin converting enzyme were assessed. Results: Plasma total NO concentration in the ACEI group (24.66±16.28, µmol/l) was increased as compared to the ARB group (18.57±11.58, µmol/l, P=0.0046) and non-ACE/ARB group (16.83±8.64, µmol/l, P=0.0127) in patients between 40 to 90 years of age. However, FMD values (%) in the ACEI group (7.07±2.40, %) were similar as compared to the ARB (6.35±2.13, %) and non-ACE/ARB group (6.51±2.15, %), but significantly negatively correlated with age. Interestingly, BDKRB1 mRNA level was significantly higher and BDKRB2 mRNA level lower in the ACEI group (BDKRB1 3.88-fold±1.05, BDKRB2 0.22-fold±0.04) as compared to the non-ACE/ARB group (BDKRB1 1.00-fold±0.39, P<0.0001, BDKRB2 1.00-fold±0.45, P=0.0136). Conclusions: ACEI treatment enhances total nitrite/nitrate concentration, furthermore, upregulates BDKRB1 in PBMC, but downregulates BDKRB2 mRNA expression. FMD is a strong determinant of vascular aging and is sensitive to underlying heterogenous cardiovascular diseases.

scholarly journals Lipid Peroxidation, Nitric Oxide Metabolites, and Their Ratio in a Group of Subjects with Metabolic Syndrome

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Gregorio Caimi ◽  
Rosalia Lo Presti ◽  
Maria Montana ◽  
Davide Noto ◽  
Baldassare Canino ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Metabolic Syndrome ◽  
Lipid Peroxidation ◽  
Hdl Cholesterol ◽  
Thiobarbituric Acid ◽  
Entire Group ◽  
Inflammatory Status ◽  
Nitric Oxide Metabolites ◽  
Nitrite Nitrate ◽  
Normal Controls

Our aim was to evaluate lipid peroxidation, expressed as thiobarbituric acid-reactive substances (TBARS), nitric oxide metabolites (nitrite + nitrate) expressed asNOx, and TBARS/NOxratio in a group of subjects with metabolic syndrome (MS). In this regard we enrolled 106 subjects with MS defined according to the IDF criteria, subsequently subdivided into diabetic (DMS) and nondiabetic (NDMS) and also into subjects with a low triglycerides/HDL-cholesterol (TG/HDL-C) index or with a high TG/HDL-C index. In the entire group and in the four subgroups of MS subjects we found an increase in TBARS andNOxlevels and a decrease in TBARS/NOxratio in comparison with normal controls. Regarding all these parameters no statistical difference between DMS and NDMS was evident, but a significant increase inNOxwas present in subjects with a high TG/HDL-C index in comparison with those with a low index. In MS subjects we also found a negative correlation between TBARS/NOxratio and TG/HDL-C index. Considering the hyperactivity of the inducible NO synthase in MS, these data confirm the altered redox and inflammatory status that characterizes the MS and suggest a link between lipid peroxidation, inflammation, and insulin resistance, evaluated as TG/HDL-C index.

Monosodium urate crystal interleukin-1β release is dependent on Toll-like receptor 4 and transient receptor potential V1 activation

Rheumatology ◽  
2019 ◽  
Author(s):  
Mateus F. Rossato ◽  
Carin Hoffmeister ◽  
Gabriela Trevisan ◽  
Fabio Bezerra ◽  
Thiago M. Cunha ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Synovial Fluid ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Acute Gout ◽  
Toll Like Receptor ◽  
Wild Type ◽  
Toll Like Receptor 4 ◽  
Transient Receptor ◽  
Nitrite Nitrate

AbstractObjectiveThe present study aimed to elucidate the mechanisms involved in MSU-induced IL-1β release in a rodent animal model of acute gout arthritis.MethodsPainful (mechanical and thermal hypersensitivity, ongoing pain and arthritis score) and inflammatory (oedema, plasma extravasation, cell infiltration and IL-1β release) parameters were assessed several hours after intra-articular injection of MSU (100 µg/articulation) in wild-type or knockout mice for Toll-like receptor 4 (TLR4), inducible nitric oxide synthase (iNOS), transient receptor potential (TRP) V1 and the IL-1 receptor (IL-1R). Also, wild-type animals were treated with clodronate, lipopolysaccharide from Rhodobacter sphaeroides (LPS-RS) (TLR4 antagonist), spleen tyrosine kinase (SYK) inhibitor (iSYK), aminoguanidine (AMG, an iNOS inhibitor) or SB366791 (TRPV1 antagonist). Nitrite/nitrate and IL-1β levels were measured on the synovial fluid of wild-type mice, 2 h after intra-articular MSU injections, or medium from macrophages stimulated for MSU (1000 μg) for 2 h.ResultsIntra-articular MSU injection caused robust nociception and severe inflammation from 2 up to 6 h after injection, which were prevented by the pre-treatment with clodronate, LPS-RS, iSYK, AMG and SB366791, or the genetic ablation of TLR4, iNOS, TRPV1 or IL-1R. MSU also increased nitrite/nitrate and IL-1β levels in the synovial fluid, which was prevented by clodronate, LPS-RS, iSYK and AMG, but not by SB366791. Similarly, MSU-stimulated peritoneal macrophages released nitric oxide, which was prevented by LPS-RS, iSYK and AMG, but not by SB366791, and released IL-1β, which was prevented by LPS-RS, iSYK, AMG and SB366791.ConclusionOur data indicate that MSU may activate TLR4, SYK, iNOS and TRPV1 to induce the release of IL-1β by macrophages, triggering nociception and inflammation during acute gout attack.

scholarly journals Effects of long-term orall-arginine on esophageal motility and gallbladder dynamics in healthy humans

1998 ◽  
Vol 274 (6) ◽  
pp. G984-G991 ◽  
Author(s):  
Y. C. Luiking ◽  
B. L. A. M. Weusten ◽  
P. Portincasa ◽  
R. Van Der Meer ◽  
A. J. P. M. Smout ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Esophageal Motility ◽  
Oral Intake ◽  
Crossover Design ◽  
Gallbladder Motility ◽  
Healthy Male ◽  
Healthy Humans ◽  
Esophageal Sphincter ◽  
Nitrite Nitrate

Inhibitory nitrergic neurons are known to play a role in the regulation of motility patterns of the distal esophagus, the lower esophageal sphincter (LES), and the gallbladder. Our study aim was to investigate the effects of “long-term” (i.e., prolonged) oral intake ofl-arginine (l-Arg), the endogenous source for nitric oxide (NO) synthesis, on postprandial LES pressure (LESP), esophageal motility, gastroesophageal reflux, and gallbladder motility. l-Arg (30 g/day) or glycine (placebo; 13 g/day; isosmolar) was given orally to 10 healthy male volunteers for 8 days, according to a randomized, crossover design. Twenty-four-hour urinary nitrite/nitrate excretion was measured to indicate NO synthesis. Basal early postprandial LESP was lower after l-Arg ingestion (2.2 kPa) than after glycine ingestion (2.7 kPa) ( P < 0.05).l-Arg abolished the physiological late postprandial rise in LESP. Transient LES relaxations were longer lasting after l-Arg ingestion ( P < 0.02). Esophageal motility and reflux were not affected (not significant). Fasting and residual gallbladder volumes were greater afterl-Arg ingestion ( P < 0.05). Urinary nitrite/nitrate excretion was higher after l-Arg intake ( P < 0.05). In conclusion, long-term oral l-Arg suppresses late postprandial LESP increase, prolongs transient LES relaxations, and increases fasting and residual gallbladder volumes. These effects may be mediated by increased NO synthesis.

Nitric oxide synthesis by rat pleural mesothelial cells: induction by cytokines and lipopolysaccharide

1993 ◽  
Vol 265 (2) ◽  
pp. L110-L116 ◽  
Author(s):  
M. W. Owens ◽  
M. B. Grisham
Keyword(s):  
Nitric Oxide ◽  
Mononuclear Cells ◽  
Interleukin 1 ◽  
Mesothelial Cells ◽  
No Production ◽  
Nitrate Accumulation ◽  
Pleural Mesothelial Cells ◽  
Nitrate Production ◽  
Close Proximity ◽  
Nitrite Nitrate

The close proximity of pleural mesothelial cells (PMC) and mononuclear cells during pleural inflammation suggests that leukocyte-derived products (e.g., cytokines) may play an important role in modulating PMC function. The purpose of this study was to determine whether certain cytokines and bacterial products induce PMC to produce nitric oxide (NO). Confluent monolayers of rat PMC were exposed to tumor necrosis factor (TNF), interleukin-1 beta (IL-1), gamma-interferon (IFN), or lipopolysaccharide (LPS) individually and in various double and triple combinations for 6–72 h. Concentrations of nitrite and nitrate were quantified and used as indirect indices of NO production. Nitrite/nitrate accumulation was maximal at 72 h, with most of the increase occurring from 48 to 72 h. Maximal nitrite/nitrate production was observed with triple combinations with the combination of LPS, IL-1, and TNF giving the highest concentration (137.4 +/- 2.8 microM). Nitrite/nitrate production was significantly inhibited by NG-nitro-L-arginine methyl ester, suggesting that nitrite and nitrate were derived from the L-arginine-dependent formation of NO. These data indicate that PMC can be induced to produce large amounts of NO in response to specific combinations of proinflammatory cytokines and LPS.

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