Temporal nitric oxide dynamics in the paranasal sinuses during humming

2005 ◽  
Vol 98 (6) ◽  
pp. 2064-2071 ◽  
Author(s):  
Lars Menzel ◽  
Alexander Hess ◽  
Wilhelm Bloch ◽  
Olaf Michel ◽  
Klaus-Dieter Schuster ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Time Constant ◽  
Paranasal Sinuses ◽  
Compartment Model ◽  
Resonance Spectroscopy ◽  
No Production ◽  
No Emission ◽  
Experimental Conditions ◽  
Experimental Part ◽  
Three Compartment Model

In this study, the temporal shape of voice-induced nitric oxide (NO) signals in exhaled air has been investigated in eight healthy individuals by means of laser magnetic resonance spectroscopy. The results of the experimental part have been compared with calculated signals obtained by using a simple one-compartment model of the paranasal sinuses. In the experimental part, a rapidly increasing NO concentration has been found when the subjects started humming. After reaching a maximum, the emission starts to decrease with the shape of an exponential decay and finally reaches a constant level. The time constant of this decay (NO washout) is 3.0 ± 1.2 s. The peak height of the NO emission during humming increases when the time between two humming processes increases. When no voice-induced NO emission takes place, the NO concentration in the paranasal sinuses rebuilds again to a maximum concentration. The typical time constant for the NO recovery is 4.5 ± 3.2 min. A three-compartment model defining exactly the geometry and anatomy of the paranasal sinuses has been developed that is based on three main assumptions of the NO dynamics: 1) constant NO production of the epithelium in the sinuses; 2) the rate of the chemical reaction of NO with the epithelium of the paranasal sinuses is proportional to the NO concentration; and 3) the emission of NO from the sinuses (volume/s) is proportional to the NO concentration. It is shown that the three-compartment model under the experimental conditions can be reduced to a one-compartment model, which describes the complete temporal behavior of the NO exchange.

Determination of the enhancing action of HSP90 on neuronal nitric oxide synthase by EPR spectroscopy

2001 ◽  
Vol 281 (6) ◽  
pp. C1819-C1824 ◽  
Author(s):  
Yao Song ◽  
Jay L. Zweier ◽  
Yong Xia
Keyword(s):  
Nitric Oxide ◽  
Electron Paramagnetic Resonance Spectroscopy ◽  
Heat Shock Protein 90 ◽  
Tryptophan Fluorescence ◽  
Hsp90 Inhibitor ◽  
Resonance Spectroscopy ◽  
No Production ◽  
Dependent Manner ◽  
Intact Cells

Recent studies showed that heat shock protein 90 (HSP90) enhances nitric oxide (NO) synthesis from endothelial and neuronal NO synthase (eNOS and nNOS, respectively). However, these findings were based on indirect NO measurements. Moreover, although our previous studies showed that the action of HSP90 involves increased Ca2+/calmodulin (Ca2+/CaM) binding, quantitative measurements of the effect of HSP90 on CaM binding to nNOS have been lacking. With electron paramagnetic resonance spectroscopy, we directly measured NO signals from purified nNOS. HSP90 augmented NO formation from nNOS in a dose-dependent manner. Tryptophan fluorescence-quenching measurements revealed that HSP90 markedly reduced the K d of CaM to nNOS (0.5 ± 0.1 nM vs. 9.4 ± 1.8 nM in the presence and absence of HSP90, P < 0.01). Ca2+ ionophore triggered strong NO production from nNOS-transfected cells, and this was significantly reduced by the HSP90 inhibitor geldanamycin. Thus these studies provide direct evidence demonstrating that HSP90 enhances nNOS catalytic function in vitro and in intact cells. The effect of HSP90 is mediated by the enhancement of CaM binding to nNOS.

scholarly journals Depolarization of mitochondria in neurons promotes activation of nitric oxide synthase and generation of nitric oxide

2016 ◽  
Vol 310 (9) ◽  
pp. H1097-H1106 ◽  
Author(s):  
Prasad V. G. Katakam ◽  
Somhrita Dutta ◽  
Venkata N. Sure ◽  
Samuel M. Grovenburg ◽  
Angellica O. Gordon ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Cortical Neurons ◽  
Ex Vivo ◽  
Cerebral Arteries ◽  
Resonance Spectroscopy ◽  
No Production ◽  
Cultured Neurons ◽  
Mitochondrial Depolarization ◽  
Oxide Synthase

The diverse signaling events following mitochondrial depolarization in neurons are not clear. We examined for the first time the effects of mitochondrial depolarization on mitochondrial function, intracellular calcium, neuronal nitric oxide synthase (nNOS) activation, and nitric oxide (NO) production in cultured neurons and perivascular nerves. Cultured rat primary cortical neurons were studied on 7–10 days in vitro, and endothelium-denuded cerebral arteries of adult Sprague-Dawley rats were studied ex vivo. Diazoxide and BMS-191095 (BMS), activators of mitochondrial KATP channels, depolarized mitochondria in cultured neurons and increased cytosolic calcium levels. However, the mitochondrial oxygen consumption rate was unaffected by mitochondrial depolarization. In addition, diazoxide and BMS not only increased the nNOS phosphorylation at positive regulatory serine 1417 but also decreased nNOS phosphorylation at negative regulatory serine 847. Furthermore, diazoxide and BMS increased NO production in cultured neurons measured with both fluorescence microscopy and electron spin resonance spectroscopy, which was sensitive to inhibition by the selective nNOS inhibitor 7-nitroindazole (7-NI). Diazoxide also protected cultured neurons against oxygen-glucose deprivation, which was blocked by NOS inhibition and rescued by NO donors. Finally, BMS induced vasodilation of endothelium denuded, freshly isolated cerebral arteries that was diminished by 7-NI and tetrodotoxin. Thus pharmacological depolarization of mitochondria promotes activation of nNOS leading to generation of NO in cultured neurons and endothelium-denuded arteries. Mitochondrial-induced NO production leads to increased cellular resistance to lethal stress by cultured neurons and to vasodilation of denuded cerebral arteries.

Blunted respiratory responses to hypoxia in mutant mice deficient in nitric oxide synthase-3

2000 ◽  
Vol 88 (4) ◽  
pp. 1496-1508 ◽  
Author(s):  
David D. Kline ◽  
Tianen Yang ◽  
Daniel R. D. Premkumar ◽  
Agnes J. Thomas ◽  
Nanduri R. Prabhakar
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Nitric Oxide Synthase ◽  
Blood Gases ◽  
Mutant Mice ◽  
No Production ◽  
Experimental Conditions ◽  
Arterial Blood ◽  
Oxide Synthase ◽  
Respiratory Responses

In the present study, the role of nitric oxide (NO) generated by endothelial nitric oxide synthase (NOS-3) in the control of respiration during hypoxia and hypercapnia was assessed using mutant mice deficient in NOS-3. Experiments were performed on awake and anesthetized mutant and wild-type (WT) control mice. Respiratory responses to 100, 21, and 12% O2and 3 and 5% CO2-balance O2were analyzed. In awake animals, respiration was monitored by body plethysmography along with O2consumption (V˙o2) and CO2production (V˙co2). In anesthetized, spontaneously breathing mice, integrated efferent phrenic nerve activity was monitored as an index of neural respiration along with arterial blood pressure and blood gases. Under both experimental conditions, WT mice responded with greater increases in respiration during 12% O2than mutant mice. Respiratory responses to hyperoxic hypercapnia were comparable between both groups of mice. Arterial blood gases, changes in blood pressure,V˙o2, andV˙co2during hypoxia were comparable between both groups of mice. Respiratory responses to cyanide and brief hyperoxia were attenuated in mutant compared with WT mice, indicating reduced peripheral chemoreceptor sensitivity. cGMP levels in the brain stem during 12% O2, taken as an index of NO production, were greater in mutant compared with WT mice. These observations demonstrate that NOS-3 mutant mice exhibit selective blunting of the respiratory responses to hypoxia but not to hypercapnia, which in part is due to reduced peripheral chemosensitivity. These results support the idea that NO generated by NOS-3 is an important physiological modulator of respiration during hypoxia.

A simple technique to characterize proximal and peripheral nitric oxide exchange using constant flow exhalations and an axial diffusion model

2007 ◽  
Vol 102 (1) ◽  
pp. 417-425 ◽  
Author(s):  
Peter Condorelli ◽  
Hye-Won Shin ◽  
Anna S. Aledia ◽  
Philip E. Silkoff ◽  
Steven C. George
Keyword(s):  
Nitric Oxide ◽  
Diffusion Model ◽  
Healthy Subjects ◽  
Elimination Rate ◽  
Compartment Model ◽  
No Production ◽  
Constant Flow ◽  
Axial Diffusion ◽  
Common Technique ◽  
Airway Tree

The most common technique employed to describe pulmonary gas exchange of nitric oxide (NO) combines multiple constant flow exhalations with a two-compartment model (2CM) that neglects 1) the trumpet shape (increasing surface area per unit volume) of the airway tree and 2) gas phase axial diffusion of NO. However, recent evidence suggests that these features of the lungs are important determinants of NO exchange. The goal of this study is to present an algorithm that characterizes NO exchange using multiple constant flow exhalations and a model that considers the trumpet shape of the airway tree and axial diffusion (model TMAD). Solution of the diffusion equation for the TMAD for exhalation flows >100 ml/s can be reduced to the same linear relationship between the NO elimination rate and the flow; however, the interpretation of the slope and the intercept depend on the model. We tested the TMAD in healthy subjects ( n = 8) using commonly used and easily performed exhalation flows (100, 150, 200, and 250 ml/s). Compared with the 2CM, estimates (mean ± SD) from the TMAD for the maximum airway flux are statistically higher ( J′awNO = 770 ± 470 compared with 440 ± 270 pl/s), whereas estimates for the steady-state alveolar concentration are statistically lower (CANO = 0.66 ± 0.98 compared with 1.2 ± 0.80 parts/billion). Furthermore, CANO from the TMAD is not different from zero. We conclude that proximal (airways) NO production is larger than previously predicted with the 2CM and that peripheral (respiratory bronchioles and alveoli) NO is near zero in healthy subjects.

scholarly journals Monoterpenoids from the Fruits of Amomum tsao-ko Have Inhibitory Effects on Nitric Oxide Production

Plants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 257
Author(s):  
Seong Su Hong ◽  
Ji Eun Lee ◽  
Yeon Woo Jung ◽  
Ju-Hyoung Park ◽  
Jung A. Lee ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Diseases ◽  
Interleukin 1 ◽  
Resonance Spectroscopy ◽  
No Production ◽  
Dependent Manner ◽  
Interleukin 1 Beta ◽  
Inhibitory Effects ◽  
Concentration Dependent Manner ◽  
First Time

In our search for novel plant-derived inhibitors of nitric oxide (NO) with potential for treating inflammatory diseases, the phytochemicals of Amomum tsao-ko fruits were investigated, leading to the isolation of one bicyclic nonane (1), three menthene skeleton monoterpenoids (2–4), and two acyclic monoterpenoids (5 and 6). Their structures were identified using one- and two-dimensional nuclear magnetic resonance spectroscopy, and mass spectrometry. To the best of our knowledge, compounds 2–5 were obtained from the genus Amomum for the first time. All isolates were tested for their ability to inhibit lipopolysaccharide-stimulated NO overproduction in RAW264.7 cells. Compound 4 was found to inhibit NO production. Western blotting analysis indicated that active compound 4 can regulate inducible NO synthase expression. In addition, lipopolysaccharide-induced interleukin 1 beta and interleukin-6 overproduction was reduced in a concentration-dependent manner.

The Role of Nitric Oxide in Regulation of Red Blood Cell Deformability.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3730-3730
Author(s):  
Xiaojun He ◽  
Ivan Azarov ◽  
Beth Gordon ◽  
Daniel B. Kim-Shapiro ◽  
Samir K. Ballas
Keyword(s):  
Nitric Oxide ◽  
Sodium Nitroprusside ◽  
Electron Paramagnetic Resonance Spectroscopy ◽  
Flow Channel ◽  
Resonance Spectroscopy ◽  
No Production ◽  
Cell Deformability ◽  
No Donor ◽  
Physiol Heart Circ ◽  
Rbc Deformability

Abstract Nitric Oxide (NO) has been suggested to modulate the deformability of red blood cells (RBCs). Bor-Kucukatay (Bor-Kucukatay et al. Am J Physiol Heart Circ Physiol284: H1577, 2003) found that cells incubated with 1 μM of the NO donor sodium nitroprusside lead to a small but significant increase RBC deformability as measured by ektacytometry. However, no significant effect was seen at lower or higher concentrations of sodium nitroprusside or for any concentration of another NO donor, diethylenetriamine NONOate. Kleinbongard (Kleinbongard et al. Blood10; 3992, 2005) found large increases in red cell deformability as a function of added arginine (the substrate for Nitric Oxide Synthase) by measuring the flow rate through filters. On the other hand, using cell aspiration techniques, Bateman (Bateman et al. Am J Physiol Heart Circ Physiol 280; H2848 H2001) found that NO production during sepsis causes a decrease in RBC deformability. Clearly more work is needed to determine the effects of NO on RBC deformability. The present work was undertaken to further investigate the effect of NO on normal and sickle RBC deformability. ProLi NONOate, arginine, and nitrite (which can be reduced to NO by hemoglobin (Hb), were incubated with blood at various concentrations over a period of 2 hours. Nitrosyl Hb and MetHb formed due to the interaction between NO and RBCs were quantified by electron paramagnetic resonance spectroscopy. The deformability was measured using a flow channel laser diffraction similar to ektacytometry (Huang et al. Am J Hematol67; 151, 2001, Biophys J85; 2374, 2003) with a stress range from 0 to 1,000 Pa. Diffraction patterns produced by deformed cells were analyzed by Matlab®. The deformability coefficients were compared to the control (n=6 per experiment condition). Our results suggested that ProLi NONOate did not significantly effect the deformability of normal RBCs. In a single case, ProLi NONOate improved the deformability of poorly deformable sickle red cells and this result is being studied further. Using our flow channel assay, we did not find any significant affects of arginine on RBC deformability. In addition, our studies involving nitrite, performed under both oxygenated and deoxygenated conditions, suggested that nitrite has no significant effect on RBC deformability. In summary, NO didn’t significantly affect the deformability of normal RBCs, and its potential effects on sickle RBCs needs to be further investigated.

scholarly journals Erythrocyte deformability is a nitric oxide-mediated factor in decreased capillary density during sepsis

2001 ◽  
Vol 280 (6) ◽  
pp. H2848-H2856 ◽  
Author(s):  
Ryon M. Bateman ◽  
Justin E. Jagger ◽  
Michael D. Sharpe ◽  
Mary L. Ellsworth ◽  
Sanjay Mehta ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Electron Paramagnetic Resonance Spectroscopy ◽  
Cecal Ligation ◽  
Capillary Density ◽  
Erythrocyte Deformability ◽  
Resonance Spectroscopy ◽  
No Production ◽  
Nitrite Nitrate ◽  
Plasma Nitrite ◽  
Rbc Deformability

Erythrocyte deformability has been recognized as a determinant of microvascular perfusion. Because nitric oxide (NO) is implicated in the modulation of red blood cell (RBC) deformability and NO levels increase during sepsis, we tested the hypothesis that a NO-mediated decrease in RBC deformability contributes to decreased functional capillary density (CD) in remote organs. With the use of a peritonitis model of sepsis in the rat [cecal ligation and perforation (CLP)] and aminoguanidine (AG) to prevent increases in NO, we measured CD in skeletal muscle (intravital microscopy), mean erythrocyte membrane deformability ([Formula: see text]; micropipette aspiration), systemic NO production [plasma nitrite/nitrate (NOx) chemiluminescence], and NO accumulation in RBC [NO bound to hemoglobin (HbNO) detected by electron paramagnetic resonance spectroscopy]. In untreated CLP animals relative to sham, NOx increased 254% ( P < 0.05), stopped flow capillaries increased 149% ( P < 0.05), and [Formula: see text] decreased 12.7% ( P < 0.05), with a subpopulation (5%) of RBC with deformabilities below the normal range. AG prevented increases in NOx, accumulation of HbNO, and decreases in both [Formula: see text]and functional CD. We found no evidence of leukocyte plugging postcapillary venules. Our findings suggest that decreased functional CD during sepsis resulted from a NO-mediated decrease in erythrocyte deformability.

NOS Inhibitors Decrease Hypoxia-induced ATP Reductions in Respiring Cerebrocortical Slices 

1999 ◽  
Vol 90 (5) ◽  
pp. 1392-1401 ◽  
Author(s):  
Lawrence Litt ◽  
Maryceline T. Espanol ◽  
Koh Hasegawa ◽  
Lee-Hong Chang ◽  
George A. Gregory ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Adenosine Triphosphate ◽  
High Performance ◽  
Brain Parenchyma ◽  
Cellular Damage ◽  
Cell Swelling ◽  
Cresyl Violet ◽  
Resonance Spectroscopy ◽  
No Production ◽  
Nos Inhibitors

Background Excess neuronal nitric oxide (NO) production might cause adenosine triphosphate loss and cellular damage in hypoxic brain parenchyma. 31P nuclear magnetic resonance spectroscopy was used to study hypoxic intracellular responses in perfused respiring cerebrocortical slices, in which NO scavenging by hemoglobin is absent, during NO synthase blockade and NO augmentation. Methods Adenosine triphosphate concentrations were monitored at 4.7 Tesla in respiring slices before, during, and after 60 min of hypoxia (oxygen tension &lt; 5 mmHg). Slices were not treated or were pretreated with 27 microM L-nitroarginine methyl ester (L-NAME), 27 microM 7-nitroindozole (7-NI), or 27 microM L-nitroarginine. Nitrotyrosine:tyrosine ratios of slice extracts were measured using high-performance liquid chromatography. Cresyl violet-stained sections (2 microm) from random slices were examined histologically. Results After 60 min of hypoxia, adenosine triphosphate decreased to &lt; or = 3, &lt; or = 3, 65 +/- 6, and 25 +/- 4% of control in slices that were untreated or treated with L-nitroarginine, L-NAME, and 7-NI, respectively. After 120 min of hyperoxic recovery, adenosine triphosphate levels returned to control values in slices pretreated with L-NAME and 7-NI, but to only 30% of control in untreated or L-nitroarginine-treated slices. Nitric oxide donors administered during posthypoxic recovery partially antagonized the adenosine triphosphate recovery found with L-NAME and 7-NI. Nitric oxide synthase activity in slice homogenates, assayed via conversion of L-arginine to citrulline, was &lt; or = 2% of control after all inhibitory treatments. The nitrotyrosine:tyrosine ratio increased by 52% in slices treated with 7-NI and by 200-300% in all other groups. Pretreatment with L-NAME and 7-NI reduced histologic evidence of cell swelling. Conclusion Neuronal NO is associated with rapid adenosine triphosphate reductions and peroxynitrite formation in acutely hypoxic cerebrocortical slices.

scholarly journals The Functional Diversity of Nitric Oxide Synthase Isoforms in Human Nose and Paranasal Sinuses: Contrasting Pathophysiological Aspects in Nasal Allergy and Chronic Rhinosinusitis

2021 ◽  
Vol 22 (14) ◽  
pp. 7561
Author(s):  
Tomohiro Kawasumi ◽  
Sachio Takeno ◽  
Chie Ishikawa ◽  
Daisuke Takahara ◽  
Takayuki Taruya ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Chronic Rhinosinusitis ◽  
Functional Diversity ◽  
Paranasal Sinuses ◽  
Treatment Strategies ◽  
Inferior Turbinate ◽  
No Production ◽  
Nasal Allergy ◽  
Cellular Components ◽  
Nos Isoforms

The human paranasal sinuses are the major source of intrinsic nitric oxide (NO) production in the human airway. NO plays several roles in the maintenance of physiological homeostasis and the regulation of airway inflammation through the expression of three NO synthase (NOS) isoforms. Measuring NO levels can contribute to the diagnosis and assessment of allergic rhinitis (AR) and chronic rhinosinusitis (CRS). In symptomatic AR patients, pro-inflammatory cytokines upregulate the expression of inducible NOS (iNOS) in the inferior turbinate. Excessive amounts of NO cause oxidative damage to cellular components, leading to the deposition of cytotoxic substances. CRS phenotype and endotype classifications have provided insights into modern treatment strategies. Analyses of the production of sinus NO and its metabolites revealed pathobiological diversity that can be exploited for useful biomarkers. Measuring nasal NO based on different NOS activities is a potent tool for specific interventions targeting molecular pathways underlying CRS endotype-specific inflammation. We provide a comprehensive review of the functional diversity of NOS isoforms in the human sinonasal system in relation to these two major nasal disorders’ pathologies. The regulatory mechanisms of NOS expression associated with the substrate bioavailability indicate the involvement of both type 1 and type 2 immune responses.

Brisk production of nitric oxide and associated formation of S-nitrosothiols in early hemorrhage

2006 ◽  
Vol 100 (4) ◽  
pp. 1267-1277 ◽  
Author(s):  
James L. Atkins ◽  
Billy W. Day ◽  
Michael T. Handrigan ◽  
Zhe Zhang ◽  
Motilal B. Pamnani ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Electron Paramagnetic Resonance ◽  
Red Blood Cells ◽  
Blood Cells ◽  
No Synthase ◽  
Resonance Spectroscopy ◽  
No Production ◽  
Paramagnetic Resonance ◽  
Arterial Blood ◽  
Electron Paramagnetic

The results of previous inhibitor studies suggest that there is some increase in nitric oxide (NO) production from constitutive NO synthase in early hemorrhage (H), but the magnitude of NO production early after H has not been previously assessed. It is generally believed that only modest production rates are possible from the constitutively expressed NO synthases. To study this, anesthetized male Sprague-Dawley rats were subjected to 90 min of isobaric (40 mmHg) H. During this period of time, the dynamics of accumulation of NO intermediates in the arterial blood was assessed using electron paramagnetic resonance spectroscopy, chemiluminescence, fluorescence imaging, and mass spectrometry. Electron paramagnetic resonance-detectable NO adducts were also measured with spin traps in blood plasma and red blood cells. H led to an increase in the concentration of hemoglobin-NO from 0.9 ± 0.2 to 4.8 ± 0.7 μM. This accumulation was attenuated by a nonselective inhibitor of NO synthase, NG-nitro-l-argininemethyl ester (l-NAME), but not by NG-nitro-d-argininemethyl ester (d-NAME) or 1400W. Administration of l-NAME (but not 1400W or d-NAME) during H produced a short-term increase in mean arterial pressure (∼90%). In H, the level of N oxides in red blood cells increased sevenfold. S-nitrosylation of plasma proteins was revealed with “biotin switch” techniques. The results provide compelling evidence that there is brisk production of NO in early H. The results indicate that the initial compensatory response to H is more complicated than previously realized, and it involves an orchestrated balance between intense vasoconstrictor and vasodilatory components.

Sign in / Sign up

Export Citation Format

Share Document