Plasma NOx Research Articles

Dysregulation of hepatic one-carbon metabolism in classical homocystinuria: Implications of redox-sensitive DHFR repression and tetrahydrofolate depletion for pathogenesis and treatment.

Cystathionine beta-synthase-deficient homocystinuria (HCU) is a life-threatening disorder of sulfur metabolism. HCU can be treated by using betaine to lower tissue and plasma levels of homocysteine (Hcy). Here, we show that mice with severely elevated Hcy and potentially deficient in the folate species tetrahydrofolate (THF) exhibit a very limited response to betaine indicating that THF plays a critical role in treatment efficacy. Analysis of a mouse model of HCU revealed a 10-fold increase in hepatic levels of 5-methyl -THF and a 30-fold accumulation of formiminoglutamic acid, consistent with a paucity of THF. Neither of these metabolite accumulations were reversed or ameliorated by betaine treatment. Hepatic expression of the THF-generating enzyme dihydrofolate reductase (DHFR) was significantly repressed in HCU mice and expression was not increased by betaine treatment but appears to be sensitive to cellular redox status. Expression of the DHFR reaction partner thymidylate synthase was also repressed and metabolomic analysis detected widespread alteration of hepatic histidine and glutamine metabolism. Many individuals with HCU exhibit endothelial dysfunction. DHFR plays a key role in nitric oxide (NO) generation due to its role in regenerating oxidized tetrahydrobiopterin, and we observed a significant decrease in plasma NOx (NO2 + NO3) levels in HCU mice. Additional impairment of NO generation may also come from the HCU-mediated induction of the 20-hydroxyeicosatetraenoic acid generating cytochrome CYP4A. Collectively, our data shows that HCU induces dysfunctional one-carbon metabolism with the potential to both impair betaine treatment and contribute to multiple aspects of pathogenesis in this disease.

Critical Considerations in Power Measurements for the Precise Estimation of Energy Costs in Plasma NOx Synthesis

Critical Considerations in Power Measurements for the Precise Estimation of Energy Costs in Plasma NOx Synthesis

Blockade of sympathetic ganglia improves vascular dysfunction in septic shock.

Sepsis/septic shock activates the sympathetic nervous system (SNS) to deal with the infection stress. However, an imbalanced or maladaptive response due to excessive or uncontrolled activation characterizes autonomic dysfunction. Our hypothesis was that reducing this excessive activation of the autonomic nervous system would impact positively in sepsis. Using ganglionic blockers as a pharmacological approach, the main aim of the present report was to assess the role of ganglionic transmission in the vascular dysfunction associated with sepsis.Sepsis was induced in rats by cecal ligation and puncture (CLP). One hour after CLP surgery, rats were treated subcutaneously with hexamethonium (15 mg/kg; ganglionic blocker), pentolinium (5 mg/kg; a blocker with a higher selectivity for sympathetic ganglia compared to hexamethonium), or vehicle (PBS). Basal blood pressure and the response to adrenergic agonists were evaluated at 6 and 24 h after CLP surgery. Reactivity to vasoconstrictors, nitric oxide (NO) synthase 2 (NOS-2) expression, IL-1 and TNF plasma levels, and density of α1 adrenergic receptors were evaluated in the aorta 24 h after CLP.Septic shock resulted in hypotension and hyporesponsiveness to norepinephrine and phenylephrine, increased plasma cytokine levels and NOS-2 expression in the aorta, and decreased α1 receptor density in the same vessel. Pentolinium but not hexamethonium recovered responsiveness and α1 adrenergic receptor density in the aorta. Both blockers normalized the in vivo response to vasoconstrictors, and reduced plasma IL-1 and NOx levels and NOS-2 expression in the aorta.Blockade of ganglionic sympathetic transmission reduced the vascular dysfunction in experimental sepsis. This beneficial effect seems to be, at least in part, due to the preservation of α1 adrenergic receptor density and to reduced NOS-2 expression and may lead to adjuvant ways to treat human sepsis.

Sodium valproate treatment reverses endothelial dysfunction in aorta from rabbits with acute myocardial infarction

Sodium valproate (VPA), a histone deacetylase (HDAC) inhibitor, could be a promising candidate to treat acute myocardial infarction (AMI). In this study, AMI was induced in New Zealand White rabbits by occluding the left circumflex coronary artery for 1 h, followed by reperfusion. The animals were distributed into three experimental groups: the sham-operated group (SHAM), the AMI group and the AMI + VPA group (AMI treated with VPA 500 mg/kg/day). After 5 weeks, abdominal aorta was removed and used for isometric recording of tension in organ baths or protein expression by Western blot, and plasma for the determination of nitrate/nitrite (NOx) levels by colorimetric assay. Our results indicated that AMI induced a reduction of the endothelium-dependent response to acetylcholine without modifying the endothelium-independent response to sodium nitroprusside, leading to endothelial dysfunction. VPA treatment reversed AMI-induced endothelial dysfunction and even increased NO sensitivity in vascular smooth muscle. This response was consistent with an antioxidant effect of VPA, as it was able to reverse the superoxide dismutase 1 (SOD 1) down-regulation induced by AMI. Our experiments also ruled out that the VPA mechanism was related to eNOS, iNOS, sGC and arginase expression or changes in NOx plasma levels. Therefore, we conclude that VPA improves vasodilation by increasing NO bioavailability, likely due to its antioxidant effect. Since endothelial dysfunction was closely related to AMI, VPA treatment could increase aortic blood flow, making it a potential agent in reperfusion therapy that can prevent the vascular damage.

Effects of Acute Beetroot Juice and Sodium Nitrate on Selected Blood Metabolites and Response to Transient Ischemia: A Crossover Randomized Clinical Trial

BackgroundModification of the nitrate (NO3)–nitrite (NO2)–nitric oxide (NO) pathway can be induced by oral intake of inorganic NO3 (NIT) or NO3-rich products, such as beetroot juice (BRJ). ObjectivesThe primary aim of this study was to evaluate the plasma changes in betaine, choline, trimethylamine (TMA), trimethylamine N-oxide (TMAO), and NO3/NO2 (NOx) concentrations over 4 h after single oral ingestion of NIT or BRJ. The flow-mediated skin fluorescence (FMSF) method was applied to measure the changes in nicotinamide adenine dinucleotide reduced form (NADH) in response to transient ischemia and reperfusion. We hypothesized that various sources of NO3 may differently affect endothelial and mitochondrial functions in healthy human subjects. MethodsIn a randomized crossover trial, 8 healthy young adults ingested 800 mg NO3 from either NIT or BRJ on 2 separate days with ≥3 d apart. Venous blood samples were collected every hour, and FMSF determination was applied bihourly. ResultsPlasma betaine and choline concentrations peaked at 1 h after BRJ ingestion, and remained significantly higher than baseline values at all time points (P < 0.001 and P < 0.001, compared to preingestion values). Over time, BRJ was more effective in increasing NOx compared with NIT (fixed-trial effect P < 0.001). Baseline fluorescence decreased after both NIT and BRJ consumption (fixed-time effect P = 0.005). Transient ischemia and reperfusion response increased because of NO3 consumption (fixed-time effect P = 0.003), with no differences between trials (P = 0.451; P = 0.912; P = 0.819 at 0, 2, and 4 h, respectively). ConclusionsAcute ingestion of BRJ elevated plasma betaine and choline, but not TMA and TMAO. Moreover, plasma NOx levels were higher in the BRJ trial than in the NIT trial. Various sources of NO3 positively affected endothelial and mitochondrial functions.This trial was registered at clinicaltrials.gov as NCT05004935.

Red mud and foundry sand industry wastes for reducing NOx in plasma activated diesel exhaust

Solid waste in association with plasma was explored as an alternate to commercial catalyst/adsorbents. We have demonstrated reuse of foundry sand and red mud wastes for adsorption of gaseous pollutant from plasma treated diesel exhaust. A novel dielectric barrier discharge reactor with dual metal film is designed to explore the oxidation potential of surface discharge plasma effect onto the exhaust. The metal film was subjected to high voltage pulse/AC energization to assess the effect of plasma in oxidising NO to NO2. A separate reactor filled with industry wastes was cascaded with plasma reactor to test its efficacy in NO2 adsorption. It was observed that some amount of NO was also reduced owing to some visible light-enabled photocatalytic activity. About 85 % NOx (oxides of nitrogen) reduction was observed with red mud waste compared to half of that with foundry sand.

Mechanism(s)-of-Action for Arginine Therapy in Children with Sickle Cell Disease and Vaso-Occlusive Pain: Results of a Pharmacokinetics/Pharmacodynamics Study

Introduction: Low L-Arginine (Arg) bioavailability is associated with sickle cell disease (SCD) mortality and morbidity, including acute pain severity. Multiple phase 2 trials support the safety and efficacy of Arg therapy in children with SCD experiencing vaso-occlusive pain. Nitric oxide (NO) is a potent vasodilator depleted in SCD due to hemolysis. As the obligate substrate for NO production, Arg's mechanism-of-action is unknown but thought to be related in part to NO production. Kyotorphin (KTP) is an endogenous opioid analgesic composed of the amino acids tyrosine and Arg. Its nociceptive effects are through induction of Met-enkephalins release in the brain. Oral administration of Arg in wild-type mice increases the levels of KTP centrally. We have previously shown that Arg supplementation increases NO metabolites (NOx), improves mitochondrial function, decreases oxidative stress, and has opioid sparing effects in children with SCD. The association between IV Arg supplementation as a precursor to KTP in SCD is unknown and may represent a novel mechanism by which Arg decreases pain in patients with SCD. Objective: To analyze the results of a pharmacokinetics/pharmacodynamics study, evaluating the association between Arg supplementation and plasma levels of KTP and other potential mechanisms-of-action related to Arg in children with SCD and vaso-occlusive pain episodes (VOE). Methods: We conducted a pharmacokinetics/pharmacodynamics study of children aged 7-21 years with SCD hospitalized for VOE and randomized to treatment utilizing one of 3 dosing arms of Arg: 1) 100mg/kg IV three times/day, standard dose (n=4); 2) loading dose (200mg/kg) followed by standard dose (n=5); or 3) loading dose (200mg/kg) followed by continuous infusion (300mg/kg/day) until discharge (n=4). Plasma amino acids (arginine, ornithine, citrulline), global arginine bioavailability ratio (GABR; Arginine/[Citrulline+Ornithine]), KTP, NOx, exhaled NO, plasma arginase activity, and arginase-1 and -2 were measured. Mean±SD, paired t-tests, and Pearson correlation analyses between groups were performed where appropriate. Results: A total of 13 patients (age 13±3 years, 56% male, 88% Hb-SS, 85% on hydroxyurea) were enrolled. Statistically significant increases in plasma arginine levels (Fig1A), plasma KTP levels (Fig1B), and GABR from pre-dose (0 hour) to 1, 1.5, and 2 hours after arginine infusion were observed, with a return to baseline 8 hours after Arg administration. Arg and KTP levels peaked between 60-90 minutes after arginine infusion in all study arms (p&amp;lt;0.001, p=0.004 respectively). There were no significant differences in peak concentration across all study arm doses. Rise in KTP levels strongly correlated with changes in plasma Arg concentration ( r=0.72, p&amp;lt;0.0001). Plasma NOx levels significantly increased from pre-dose to Tmax (Tmax= 1-2 hours; mean percent change 156±313%, p=0.02), as did exhaled NO (mean percent change 31±27%, p=0.02). Arginase activity also increased significantly after IV Arg infusion peaking at approximately 90 minutes (mean percent change 137±183%, p= 0.03) with return to baseline at 8 hours, while there was no significant change in arginase-1 or -2 concentrations over time. Conclusion: IV Arg therapy increased plasma arginine concentration 2-5 times above baseline at presentation for VOE, and GABR also increased as expected in this pharmacokinetics study with both reaching a maximum concentration within 1 hour of infusion initiation in all dosing schemes. IV Arg supplementation increases plasma NOx levels suggesting a role for vasodilation as a potential mechanism-of-action during SCD-VOE. Exhaled NO also increased significantly, consistent with previous reports. Interestingly, IV Arg supplementation acutely increased arginase activity without a significant change in arginase concentration. Most notably, we report for the first time the impact of IV Arg therapy on plasma levels of KTP in SCD. As KTP is an endogenous opioid analgesic, this may represent a novel mechanism-of-action of Arg therapy that warrants further investigation. This observation may also have implications for the potential use of arginine supplementation in pain syndromes beyond sickle cell disease.

Plasma assisted NH3 combustion and NOx reduction technologies: Principles, challenges and prospective

Combustion is the cornerstone for generating energy in various sectors and applications. The predominance of hydrocarbons combustion causes several environmental and human health issues. The ever-increasing demand for decarbonization of combustion technologies in order to reduce or eliminate undesirable emissions has created a major challenge, putting tremendous pressure on the international research community to develop alternative fuels. Ammonia has recently been explored as a promising carbon-free fuel and a great alternative to hydrocarbon fuels to achieve zero-carbon emissions. However, despite its advantages over hydrogen, ammonia combustion has some drawbacks including low burning velocity, flame stability, and high NOx emissions. This review begins with energy and environmental issues before moving on to hydrogen and ammonia as promising potential solutions, their advantages and drawbacks, and ammonia combustion kinetics. It summarises the principles of chemical kinetics of both ammonia combustion and NOx reduction coupled with the chemistry, kinetic mechanisms and impact of plasma on ammonia combustion. The effects of plasma on ammonia combustion and NOx reduction are also discussed, with a comparison of NOx reduction mechanisms and plasma approach. Finally, the review discusses the perspectives and challenges of using plasma in ammonia combustion.

Green iron oxide (GIO) utilized for reductive removal of As(III) and methyl red (MR) with non-thermal plasma via synergistic catalytic study

In this research, the suggested non-thermal plasma was used for the removal of inorganic (As(III)) and organic (MR) compounds with waste material synthesized nano-particles, such as green iron oxide (GIO) for environmental safety. The plasma-generated RONS, such as O, OH•, H2O2, and NOx, have been employed for the oxidation and reduction of As(III) and Fe3O4. These plasma reactive species H2O2 and NOx were found to be the maximum in the DI water, which are 144.24 µM and 111.86 µM, respectively. The arsenic removal capacity qmax is 4.69 mg/g. However, the yield of As(III) absorbed on the surface of GIO was discovered, which is a maximum and minimum of 14.08 and 8.53 g/kWh, respectively. Meanwhile, the GIO catalytic enhancement study was proved by the removal of organic compounds, such as MR via degradation. Although, the pH for MR was found to be 3.0–3.5 under plasma irradiation. The characterization was performed for the crystallinity, surface, elemental, functional groups, surface area, mass spectrum, and XPS. Whereas, the kinetic study and isotherms are performed at the rate-limiting constant R2 ≈ 1, which is a monolayer phenomenon. Finally, the arsenic was able to be removed lower than WHO norms, which is 0.01 mg/l. Furthermore, the arsenic removal study was conducted in industrial – wastewater. Overall, which is a potentially eco-friendly way for oxidative, reductive, adsorptive, and degradative for pollutant removal, such as organic and inorganic compounds with the recycling of waste-material (GIO) synthesized nanoparticles for environmental safety.

PS-BPC12-8: ASSOCIATION OF URIC ACID WITH BLOOD PRESSURE LEVEL IN ESSENTIAL HYPERTENSION: DIFFERENCES ACCORDING TO DIPPING PATTERN OF NOCTURNAL BLOOD PRESSURE

Objective: In essential hypertensive patients, independent of the degree of hypertension, a non-dipping blood pressure pattern is a risk factor for the development of cardiovascular diseases. Serum uric acid level was demonstrated to be an independent predictor of developing hypertension. The increase of uric acid promotes oxidative stress and inflammation, which then enhances endothelial dysfunction. In this study, the association of serum uric acid with 24 hour average blood pressure level was investigated from differences in patterns of circadian blood pressure in patients with essential hypertensive patients. Design and method: In 154 untreated essential hypertensive patients (86 males, average age 56 ± 12 years) without chronic kidney disease (urinary albumin excretion less than 300 mg/g of creatinine and estimated glomerular filtration rate 60 mL/min/1.73m2 or more), 24 hour ambulatory blood pressure monitoring and blood sampling were performed. In blood samples, biochemical parameters including highly sensitive CRP (hsCRP) and nitric oxide metabolites (NOx) were measured. Non-dipper status was defined as a decrease in nocturnal systolic blood pressure &lt; 10 %. The patients were divided into two groups according to their nocturnal systolic blood pressure status: 56 patients with non-dipper status and 98 patients with dipper status. Results: 24 hour systolic blood pressure was higher in the non-dipper patients than in the dipper group (148 ± 17 vs 139 ± 16 mmHg, p &lt; 0.001), whereas diastolic blood pressure and pulse rate did not differ between the two groups. The non-dipper group was characterized by increased serum uric acid and hsCRP and decreased plasma NOx level compared with the dipper group (6.0 ± 1.7 mg/dL, 0.10 ± 0.15 mg/dL, 41.4 ± 25.3 μmol/L in the non-dipper group vs 5.5 ± 1.5, 0.07 ± 0.11, 50.1 ± 31.3 in the dipper group, p &lt; 0.05, respectively). 24 hour systolic blood pressure correlated positively with serum uric acid and hsCRP and negatively with plasma NOx in the non-dipper group (r = 0.25, 0.32, -0.25, p &lt; 0.05, respectively), but did not so in the dipper group. Furthermore, in the non-dipper group, multiple regression analysis revealed that serum uric acid was an independent determinant for 24 hour systolic blood pressure level together with hsCRP, and plasma NOx (R2 0.25, p &lt; 0.01). Conclusions: These data indicate that the elevation of serum uric acid could associate with persistently elevated blood pressure accompanied with micro-inflammation and vascular endothelial dysfunction in essential hypertensive patients with an attenuated nocturnal blood pressure dipping.

205. IL-1 β gene (+3954C/T, exon 5, rs1143634) and NOS2 (exon 22) polymorphisms associate with early aseptic loosening of hip and knee arthroplasties but not with implants infection

Abstract Background Aseptic prosthetic loosening (APL) and prosthetic joint infections (PJI) are frequent complications of hip and knee implants. Polymorphisms of cytokines and nitric oxide (NO), key inflammatory molecules in APL and PJI pathogenesis, could explain individual susceptibility to these complications. Methods Three cytokines (IL-1-a, IL-1-β, TNF-α) and two nitric oxide synthase (NOS2, NOS3) genes polymorphisms were genotyped in 77 APL and 117 PJI patients and 145 controls with aseptic hip or knee implants lasting &amp;gt; 16 years. Plasma cytokines and nitrate-nitrite (NOx) levels were measured. Results The TT genotype and T allele of the (+3954C/T, exon 5, rs1143634) IL-1β polymorphism were more frequent in APL patients compared to controls (p=0.03 and p=0.02, respectively). No genotypic associations in PJI patients were observed. S. epidermidis was their most frequently isolated microorganism (39.3%). Plasma IL-6, TNF-α and NOx were significantly different between APL and controls (p&amp;lt; 0.0001). Plasma IL-1β and IL-6 were significantly higher in APL T allele carriers vs. non-carriers (p&amp;lt; 0.03). Knee implant (HR 2.488, 95% CI 1.307-4.739, p=0.005), male gender (HR 2.252, 95% CI 1.121-4.525, p=0.023), carriages of the TT genotype of the (+3954C/T) IL-1β polymorphism (HR 3.704, 95% CI 1.274-10.753, p=0.016) and AA genotype of the (exon 22) NOS2 polymorphism (HR 3.509, 95% CI 1.266-9.709, p=0.016) were independently associated with a shorter implant survival by Cox regression. Conclusion Genotyping of IL-1β (+3954C/T, exon 5, rs1143634) and NOS2 (exon 22) polymorphisms could be useful as predictors of early hip or knee APL. Disclosures All Authors: No reported disclosures.

Low-temperature filamentary plasma for ignition-stabilized combustion

In this work, an experimental study investigating dielectric barrier discharge (DBD) plasma-assisted ignition in methane-air flows at near-atmospheric pressure is presented. Discharges are produced using 10 ns duration high voltage pulses at maximum 3 kHz pulse repetition rate. The goal is to check the feasibility of plasma as an ignition source for ignition-stabilized combustion in a wide range of equivalence ratio, pressure, and flow speed conditions. To that end, four important characteristics are investigated: 1) Ignition dynamics, 2) Minimum number of pulses required for ignition, 3) Plasma energy per pulse, gas temperature, and the effective reduced electric field, and 4) Plasma NOx production. In continuous plasma mode, we observe an elongated flame outside of the discharge region when a methane-air mixture flows through the discharge. The elongated flame is due to repetitively ignited kernels moving downstream with the flow. High-speed intensified imaging is used to explore plasma morphology and ignition dynamics. Plasma has a filamentary nature which is perceived as moving with the flow due to pulse-to-pulse memory effects. For fuel-air mixtures, ignition is followed by kernel expansion and splitting, flame propagation, and consecutive ignition. The time delay between consecutive ignition events is found to be a function of flow speed, because ignition is achieved only when a previously ignited kernel moves out of the plasma region, which happens faster at higher flow speeds. We performed optical emission spectroscopy in burst mode to further characterise plasma and ignition parameters. In air, plasma gas temperature and hence the reduced electric field increases because of pulse-to-pulse effects. By comparing the air plasma temperature with the methane auto-ignition temperature, we conclude that the observed ignition is low-temperature ignition. Parametric studies of NOx measurements suggest that plasma NOx emissions are higher for low flow speeds, high pulse repetition rates, and low-pressure conditions. Overall, our DBD filamentary plasma is found to be a fast, repetitive, and low-temperature ignition source that can be used for ignition-stabilized combustion at near atmospheric conditions.

IL-1 β gene (+3954 C/T, exon 5, rs1143634) and NOS2 (exon 22) polymorphisms associate with early aseptic loosening of arthroplasties

Aseptic prosthetic loosening (APL) and prosthetic joint infections (PJI) are frequent complications of hip and knee implants. Polymorphisms of cytokines and nitric oxide (NO), key inflammatory molecules in APL and PJI pathogenesis, could explain individual susceptibility to these complications. Three cytokines (IL-1-a, IL-1-β, TNF-α) and two nitric oxide synthase (NOS2, NOS3) genes polymorphisms were genotyped in 77 APL and 117 PJI patients and 145 controls with aseptic hip or knee implants that were implanted for > 16 years. Plasma cytokines and nitrate-nitrite (NOx) levels also were measured. The TT genotype and T allele of (+3954 C/T, exon 5, rs1143634) IL-1β polymorphism were more frequent in APL patients compared to controls (P = 0.03 and P = 0.02, respectively). No genotypic associations in PJI patients were observed. Plasma IL-6, TNF-α and NOx were significantly different between APL and controls (P < 0.0001). Plasma IL-1β and IL-6 were significantly higher in APL T allele carriers vs. non-carriers (P < 0.03). Knee implant (HR 2.488, 95% CI 1.307–4.739, P = 0.005), male gender (HR 2.252, 95% CI 1.121–4.525, P = 0.023), carriages of the TT genotype of the (+3954 C/T) IL-1β polymorphism (HR 3.704, 95% CI 1.274–10.753, P = 0.016) and AA genotype of the (exon 22) NOS2 polymorphism (HR 3.509, 95% CI 1.266–9.709, P = 0.016) were independently associated with a shorter implant survival by Cox regression. No genotypic associations in PJI patients were observed. Genotyping of IL-1β (+3954 C/T, exon 5, rs1143634) and NOS2 (exon 22) polymorphisms could be useful as predictors of early hip or knee APL.

The Evaluation of Plasma Vitamin E and Plasma Nitrite/Nitrate Anion Levels in Newly Diagnosed Type 2 Diabetes Mellitus Patients

Aim: Oxidative stress induces the onset of type 2 Diabetes mellitus (T2DM). Both plasma vitamin E (VE) and nitrite/nitrate anion&#x0D; (NOx) levels might be crucial factors to determine diabetes induced endothelial damage through different mechanisms. Therefore, in&#x0D; this study, we aimed to evaluate plasma VE and NOx concentrations of newly diagnosed T2DM patients and to understand whether any&#x0D; correlation exists with the patients’ lipid profiles.&#x0D; Material and Methods: Blood samples were taken when the patients (n=15) and the controls (n=15) first came to our university’s&#x0D; diabetes policlinic for investigation and were used to detect plasma VE and NOx levels. Patients’ files were evaluated to record both the&#x0D; demographic data and biochemical parameters. The data was distributed normally according to Kolmogorov-Smirnov test. Therefore,&#x0D; Student t test was chosen to compare patient and control data and Pearson test was applied for correlation analysis.&#x0D; Results: In newly diagnosed T2DM patients, total cholesterol (TC) and triglyceride levels were found to be significantly elevated&#x0D; (p=0.036, and p

Circulating nitrate-nitrite reduces oxygen uptake for improving resistance exercise performance after rest time in well-trained CrossFit athletes

This study aimed to determine the effects of circulating nitrate plus nitrite (NOx) concentrations on resistance exercise performance, VO2 and biomarkers of muscle damage. Eleven well-trained male CrossFit athletes (29.2 ± 3.7 years, 78.9 ± 5.4 kg, 175.1 ± 6.3 cm) carried out a resistance exercise test after drinking 140 mL of beetroot juice (BJ) or placebo. The test consisted of repeating the same resistance exercise routine twice: wall ball shots plus full back squat with 3-min rest (1st routine) or without rest (2nd routine) between the two exercises. Higher NOx plasma levels were verified after BJ than placebo in the pretest and post-test (p < 0.001). A higher number of repetitions was observed after BJ intake compared to placebo in the full back squat exercise during the first routine (p = 0.004). A significantly reduced VO2 was detected after BJ intake compared to placebo during rest and full back squat execution in the first routine (p < 0.05). Plasma myoglobin concentrations were significantly increased with BJ compared to placebo (p = 0.036). These results showed that plasma NOx levels reduced VO2 after BJ intake during rest time. These reduced VO2 was a key factor for improving full back squat performance during the first routine.

The effect of Nigella sativa oil on vascular dysfunction assessed by flow-mediated dilation and vascular-related biomarkers in subject with cardiovascular disease risk factors: A randomized controlled trial.

Cardiovascular diseases (CVD) are the leading causes of mortality worldwide. Flow-mediated dilation (FMD) is a marker of vascular function. Beneficial cardiometabolic effects of Nigella sativa (N. sativa) have been observed. We evaluated the effect of N. sativa oil on FMD, plasma nitrite, and nitrate (NOx) as nitric oxide (NO) metabolites, and inflammatory markers in subjects with CVD risk factors. Fifty participants were randomly assigned to either the N. sativa (two capsules of 500 mg N. sativa oil) or the placebo group (two capsules of 500 mg mineral oil), for 2 months. The brachial FMD, plasma NOx, vascular cellular adhesion molecule-1 (VCAM-1), and intracellular adhesion molecule-1 (ICAM-1) were measured. FMD and plasma NOx levels was significantly increased in the N. sativa group compared to the placebo group (changes: 2.97 ± 2.11% vs. 0.71 ± 3.19%, p < 0.001 for FMD and 4.73 ± 7.25 μmol/L vs. 0.99 ± 5.37 μmol/L, p=0.036 for plasma NOx). However, there was no significant difference in ICAM-1 and VCAM-1 levels between groups. Therefore, N. sativa oil improves vascular NO and FMD in subjects with cardiovascular risk factors. However, more studies are warranted to confirm the beneficial impacts of the N. sativa oil on vascular inflammation.

Poly I:C and R848 facilitate nitric oxide production via inducible nitric oxide synthase in chicks

Nitric oxide (NO) is a gaseous bioactive molecule associated with many physiological functions including vasodilation and neurotransmission. NO also plays an important role in immune responses during viral infections in mammals. However, there is a paucity of knowledge regarding the involvement of NO in viral infections in birds. Therefore, the purpose of the present study was to determine if intraperitoneal (IP) injection of poly I:C and R848 (resiquimod), which are analogues of virus component, affects NO production in chicks (Gallus gallus) as a bird model. The involvement of inducible NO synthase (iNOS) in poly I:C- and R848-induced anorexia and corticosterone release was also investigated. These virus analogues significantly increased plasma NO metabolites (NOx) concentrations. IP injection of poly I:C and R848 significantly increased iNOS mRNA expression in several organs including the liver. On the other hand, poly I:C and R848 significantly decreased mRNA expressions of endothelial NOS and neural NOS in several organs, indicating that induction of iNOS might be responsible for increased NOx levels in plasma. This finding was further confirmed by using a selective iNOS inhibitor, S-methylisothiourea sulfate (SMT), which abolished the poly I:C- and R848-induced increase in plasma NOx concentration. In addition, SMT partly attenuated the poly I:C- and R848-induced increase in plasma corticosterone concentration, suggesting that corticosterone release induced by these virus analogues may be partly mediated by iNOS. Collectively, the present results suggest that viral infections facilitate NO production by inducing iNOS. The liver would play an important role in the NO production because the response in iNOS mRNA expression to poly I:C and R848 was remarkable. The present results also suggest that NO is associated with corticosterone release in birds under viral infection.

Anti-diabetic efficacy of combination treatment with the nitric oxide metabolite nitrite and the endogenous antioxidant glutathione in diabetic mice: glutathione combination does not hamper the anti-diabetic effect of nitrite.

The nitric oxide (NO) metabolite nitrite has been shown to attenuate hyperglycemia via its increase in insulin sensitivity and glucose uptake. However, the oral use of nitrite is limited due to its potential formation of the carcinogenic N-nitrosamines via reaction of acidic nitrite and the secondary amines. We investigated the anti-diabetic effect of sodium nitrite (SN) combined with glutathione (GSH) in streptozotocin (STZ)-induced diabetic mice for potential use of GSH as a protective agent in future nitrite therapy. STZ-induced diabetic mice were orally treated for 5 weeks with vehicle, SN, GSH or SN + GSH. Oral glucose tolerance test and the measurement of fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) levels were carried out to evaluate anti-diabetic effects of SN and SN + GSH. Plasma levels of total NO metabolites (NOx) were measured to confirm nitrite absorption. SN and SN + GSH significantly improved the glucose tolerance (p < 0.05), but GSH alone did not. The efficacy of combination treatment with SN and GSH in improving the glucose tolerance was higher than that of SN alone. Oral treatment with SN or SN + GSH significant reduced FBG and HbA1c levels (p < 0.05). Interestingly, daily oral administration of SN + GSH was more effective in reducing FBG and HbA1c levels than that of SN alone. Administration of SN or SN + GSH significantly increased plasma NOx levels (p < 0.05), and combination treatment with SN + GSH was more effective in increasing plasma NOx levels than that with SN alone. Combination treatment with SN and GSH is more effective in controlling hyperglycemia and increasing the plasma NOx levels in an experimental mouse model of diabetes. Since oral administration of GSH has been shown to be non-toxic in humans, the combination of SN and GSH may be important in potential future nitrite therapy.

The effect of purple-black barberry (Berberis integerrima) on blood pressure in subjects with cardiovascular risk factors: a randomized controlled trial

Ethnopharmacological relevanceBerberis integerrima commonly known as “barberry” belongs to the Berberidaceae family and has been used as a medicinal plant in Iranian traditional medicine. Aim of the studyOur aim in this study was to investigate the effects of barberry consumption on blood pressure (BP). Materials and methodsEighty-four medicated hypertensive patients were selected and randomly allocated to barberry and placebo groups. The barberry group received 10 g/day dried purple-black barberry powder, once daily, for 2-months. Systolic, diastolic, and mean arterial BP was assessed through 24-h ambulatory BP monitoring before and after 2-month treatment. The estimation of sodium and potassium intake was done through measurement of sodium and potassium in 24-h urinary samples. Plasma and urinary nitrite, and nitrate (NOx) levels, as well as plasma angiotensin-converting enzyme (ACE) activity, were also determined. ResultsSeventy-eight participants with an average age of 54.12 ± 10.32 years and BMI of 27.93 ± 2.22 kg/m2 completed the study. There was no significant difference in body weight, physical activity, and the 24-h urinary sodium and potassium excretion between the two groups before and after the study. After adjusting for baseline values and changes in sodium intake, systolic, and mean arterial BP decreased significantly in the barberry group compared to the placebo group (p = 0.015 and p = 0.008, respectively). Plasma NOx levels and ACE activity were not different between the two groups, but urinary NOx was increased significantly in the barberry group compared to the placebo group (p = 0.008). ConclusionsIn patients treated with antihypertensive drugs, daily consumption of purple-black barberry can be effective in improving systolic BP control.

Vasoactive Biomarkers in Patients With Vasovagal Syncope During Head-Up Tilt Test: A Case-Control Study.

Background:Vasovagal syncope (VVS) is the most common cause of syncope. Some stages of its pathophysiological mechanisms remain unclear. Vasoactive substances such as nitric oxide metabolites (NOx) and endothelin (ET) may be involved during acute orthostatic stress.Objective:To analyze plasma changes in NOx and ET and heart rate variability (HRV) in the supine positions (T1) and during the head-up tilt test (HUTT) (T2), in patients with VVS (case group) and control group.Methods:Thirty-seven patients (17 in the case group and 20 in the control group), matched for age and sex (mean aged 31.8 years) underwent HUTT with simultaneous HRV recording and venipuncture. Blood samples were collected during phases T1 and T2 and the analysis was performed without knowledge of the HUTT result.Results:In the total sample, there was an increase in NOx values (P = .014), however there was no increase in ET values from phase T1 to phase T2. Patients with VVS tended to increase plasma NOx values (P = .057) and had significantly higher plasma values compared to ET (P = .033) between phases T1 to T2. In the control group, there was no significant change in the values of these vasoactive substances. Regarding HRV, there were a decrease in the component HF (high frequency) and increased of the LF (low frequency)/HF ratio during HUTT.Conclusions:There was an increase in ET during HUTT occurred only in the case group. These patients are more likely to have an imbalance between antagonistic vasoactive biomarkers during orthostatic stress.