Measured NO Levels Research Articles

Evaluation of sympathetic adrenergic branch of cutaneous neural control throughout thermography and its relationship to nitric oxide levels in patients with fibromyalgia.

Fibromyalgia syndrome is defined as a complex disease, characterized by chronic widespread musculoskeletal pain and other symptoms. The factors underlying physiopathology of fibromyalgia are not well understood, complicating its diagnosis and management. To evaluate the peripheral vascular blood flow of the skin of the hands and the core body temperature as indirect measures of sympathetic adrenergic activity of the nervous system and its relationship to nitric oxide levels (NO) in women with fibromyalgia compared with healthy controls. Forty-two women with fibromyalgia and 52 healthy women were enrolled in this observational pilot study. We used infrared thermography of the hands and an infrared dermal thermometer to evaluate the peripheral vascular blood flow and tympanic and axillary core body temperature, respectively. We measured NO levels using the ozone chemiluminescence-based method. Two-way analysis of covariance (ANCOVA) showed that the tympanic (P=0.002) and hand temperatures were significantly higher in the patients with fibromyalgia than in the controls (P≤0.001). Significant associations were also found between serum NO levels and minimum temperatures at the dorsal center of the dominant hand (β=-3.501; 95% confidence interval [CI] -6.805, ‑0.198; P= 0.038), maximum temperature (β=-5.594; 95% CI ‑10.106, ‑1.081; P=0.016), minimum temperature (β=-4.090; 95% CI ‑7.905, ‑0.275; P=0.036), and mean temperature (β=-5.519; 95% CI ‑9.933, ‑1.106; P=0.015) of the center of the palm of the non-dominant hand, maximum temperature at the thenar eminence of the dominant hand (β=-5.800; 95% CI ‑10.508, ‑1.092; P=0.017), and tympanic temperature (β=-9.321; 95% CI ‑17.974, ‑0.669; P=0.035) in the controls. Our findings indicate that the women with fibromyalgia showed higher tympanic core body and hand temperature than the healthy controls. Moreover, there were negative associations between hand peripheral vasodilation and NO in the healthy women but not in those with fibromyalgia, suggesting a dysfunction of sympathetic cutaneous neural control.

PKA and Epac activation mediates cAMP-induced vasorelaxation by increasing endothelial NO production

Vascular relaxation induced by 3′,5′-cyclic adenosine monophosphate (cAMP) is both endothelium-dependent and endothelium-independent, although the underlying signaling pathways are not fully understood. Aiming to uncover potential mechanisms, we performed contraction–relaxation experiments on endothelium-denuded and intact rat aorta rings and measured NO levels in isolated human endothelial cells using single cell fluorescence imaging. The vasorelaxant effect of forskolin, an adenylyl cyclase activator, was decreased after selective inhibitor of protein kinase A (PKA), a cAMP-activated kinase, or L-NAME, an endothelial nitric oxide synthase (eNOS) inhibitor, only in intact aortic rings. Both selective activation of PKA with 6-Bnz-cAMP and exchange protein directly activated by cAMP (Epac) with 8-pCPT-2′–O-Me-cAMP significantly relaxed phenylephrine-induced contractions. The vasorelaxant effect of the Epac activator, but not that of the PKA activator, was reduced by endothelium removal. Forskolin, dibutyryl cAMP (a cAMP analogue), 6-Bnz-cAMP and 8-pCPT-2′–O-Me-cAMP increased NO levels in endothelial cells and the forskolin effect was significantly inhibited by inactivation of both Epac and PKA, and eNOS inhibition. Our results indicate that the endothelium-dependent component of forskolin/cAMP-induced vasorelaxation is partially mediated by an increase in endothelial NO release due to an enhanced eNOS activity through PKA and Epac activation in endothelial cells.

Abstract 5651: Apelin Deficient Mice Demonstrate Worsening Pulmonary Hypertension in a Nitric Oxide Dependent Manner

Recent studies have shown high expression of the GPCR APJ and its ligand apelin in the pulmonary vasculature. Given its known vasodilatory properties and pulmonary expression, we hypothesize that disruption of this pathway leads to worsening of pulmonary hypertension in the murine hypoxia model, and that the pathway is abnormally regulated in patients with pulmonary arterial hypertension (PAH). Right ventricular systolic pressures were assessed in apelin deficient (KO) mice after 2 weeks of hypoxia. Lungs were perfused with contrast agent (Microfil), and imaged using micro-computed tomography (CT) imaging. We measured NO levels in the serum and evaluated the lungs for expression of endothelial nitric oxide synthase (eNOS) using quantitative real-time polymerase chain reaction (RT-PCR) and western blots. We found that apelin KO mice developed more severe pulmonary hypertension in response to hypoxia compared to wildtype mice (34.1 vs. 28.3 mmHg, p<0.001). Micro-CT of the lungs demonstrated vascular abnormalities in the apelin KO mice including pruning of smaller vessels and increased tortuosity of the larger vessels. Apelin KO mice had decreased levels of serum NO (p=0.02) and had lower expression of eNOS in the lungs, as determined by RT-PCR and western blots. We also performed ELISA assays to determine apelin levels in patients with PAH. Apelin levels from PAH patients were significantly lower compared to healthy controls (1.25 vs. 0.89 ng/mL, p=0.037). These data suggest that disruption of apelin signaling can exacerbate pulmonary hypertension, and identify this pathway as a potential therapeutic target for treatment of this refractory human disease.

A study of [formula omitted] formation in hydrogen flames

The aim of this work is to improve the knowledge of modeling NO x formation in hydrogen flames. Four different detailed reaction mechanisms have been tested for eight laminar flames, and two of these mechanisms have been tested for a turbulent jet flame. The numerical results have been compared with experimental data from the literature. Sensitivity and integral reaction flow analyses are applied to identify important reaction steps. Formation of NO through NNH radicals was found to be important in the hydrogen-air flames investigated. This work suggests that the H 2/O 2 mechanism of Li et al. for pure hydrogen combustion may be combined with the N/H/O subset from Glarborg et al. for prediction of NO x in hydrogen-air flames. However, the pressure-dependency of the reaction N 2 O + M ⇌ N 2 + O + M should be further investigated and accounted for. For the turbulent hydrogen jet flame, the agreement between the predicted and measured NO levels was better with the mechanism of Glarborg et al.

Scalar profiles and NO formation in laminar opposed-flow partially premixed methane/air flames

Measurements of temperature, the major species (N 2, O 2, CH 4, CO 2, H 2O, CO, and H 2), OH, and NO are obtained in steady laminar opposed-flow partially premixed flames of methane and air, using the non-intrusive techniques of Raman scattering and laser-induced fluorescence. Flames having fuel-side equivalence ratios of φ = 3.17, 2.17, and 1.8 are stabilized on a porous cylindrical burner (Tsuji burner) in a low-velocity flow of air. Results are compared with calculations using a version of the Sandia laminar flame code that is formulated for the Tsuji geometry and includes an optically thin treatment of radiation. Because velocity profiles are not measured, the strain rate in each calculation is adjusted to match the measured profile of the mixture fraction. Measured profiles of temperature and species mass fractions are then compared with results of calculations using the GRI-Mech 2.11 and 3.0 chemical mechanisms, as well as a detailed mechanism from Miller. All three mechanisms give agreement with experimental results for the major species that is generally within experimental uncertainty. With regard to NO formation, the relative performance of the three mechanisms depends on the fuel-side equivalence ratio. GRI-Mech 2.11 gives reasonably good agreement with measured NO levels in lean and near-stoichiometric conditions, but it under predicts NO levels in fuel-rich conditions. GRI-Mech 3.0 significantly over predicts the peak NO levels the φ = 3.17 and 2.17 flames, but it yields relatively good agreement with measurements in the φ = 1.8 flame. The Miller mechanism gives good agreement with measured NO levels in the φ = 3.17 flame, but it progressively over predicts peak NO levels in the leaner flames. Comparisons of adiabatic and radiative calculations show that radiation can have a significant effect on the width and structure of partially premixed flames, as well as on the levels of NO produced.

Relationships among nitric oxide, temperature, and mixture fraction in hydrogen jet flames

Simultaneous point measurements of NO, the major species, mixture fraction, temperature, and OH are obtained in nonpremixed turbulent hydrogen jet flames, using the combination of spontaneous Raman scattering, Rayleigh scattering, and laser-induced fluorescence. Results are presented for an undiluted hydrogen flame at Reynolds number 10,000 and for flames with 20% and 40% helium dilution, with emphasis on the relationships among nitric oxide, mixture fraction, and temperature. Conditional statistics are used to extract information on the coupling between reaction zone structure and measured NO levels. Fluctuations of the NO mole fraction conditional on mixture fraction are greatest near the base of the flame, where NO formation rates and concentrations are sensitive to local strain. Similarly, when NO levels are averaged conditional on both mixture fraction and temperature, the temperature dependence is strongest near the flame base, where reaction zones are thin. The radial dependence of the conditional mean NO mole fraction (conditional on mixture fraction) is shown to be small at upstream locations and negligible at the downstream locations that contribute most to the overall NO emission. These results combined with previously reported data on the present hydrogen flames provide a detailed basis for evaluation and refinement of turbulent combustion models for thermal NO x formation in jet flames.

Raman/Rayleigh/LIF measurements of nitric oxide formation in turbulent hydrogen jet flames

Simultaneous, time-resolved measurements of NO, major species, mixture fraction, temperature, and OH are obtained in nonpremixed turbulent hydrogen jet flames, using the combination of spontaneous Raman scattering, Rayleigh scattering, and laser-induced fluorescence. Results are presented for an undiluted hydrogen flame at Reynolds number 10,000 and for flames with 20 percent and 40 percent helium dilution. Scatter plots and conditional averages of NO mole fraction show gradual increases with streamwise distance. The width in mixture fraction coordinates of the zone of high NO mole fractions decreases with increasing streamwise distance. At a given mixture fraction, the fluctuation in NO mole fraction relative to the mean is greatest near the nozzle and decreases toward the flame tip. These effects are related to the streamwise evolution of turbulent flame structure from thin reaction layers near the nozzle to broad, near-equilibrium zones at the flame tip. Dilution with helium significantly reduces the measured NO levels and causes a slight shift of the curves of conditional average NO mole fraction toward the fuel-lean side of the stoichiometric mixture fraction. Favre averages and ensemble averages show significant bias, relative to conditional averages, in the relationship between NO mole fraction and mixture fraction. This suggests that the “rich shift” observed in some sampling-probe studies may results from the averaging process itself.

Effects of turbulent mixing and chemical kineticson nitric oxide production in a jet-stirred reactor

A conical jet-stirred reactor was utilized to study the formation of nitric oxide under nearstoichiometric conditions, and at pressures varying from 0.25 to 1 atm. Measurements of temperature, mass-flow rate, equivalence ratio, nitric oxide and oxygen concentrations were made and compared with perfectly stirred reactor (PSR) predictions, based on kinetic rate data and mechanisms chosen to maximize predicted NO formation and to correctly predict reactor blowout conditions. Observed blowout flow rates were greater by a factor of 2 than that predicted using PSR assumptions and rate data and mechanisms due to Marteney and due to Seery and Bowman. Measured NO levels were higher by a factor of 3 to 10 than predicted by the PSR computer model. A one-parameter “two-environment” mixing model was unsuccessfully applied to the analytical model, in an attempt to correct for imperfect stirring. Since factors controlling formation of NO by the Zeldovich mechanism were suppressed (short residence time and low combustion temperature), the high levels of NO observed are postulated to be due to fast NO-producing reactions occurring during pyrolysis steps of the reaction mechanism.