scholarly journals Airway Thiol-NO Adducts as Determinants of Exhaled NO

Antioxidants ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1527
Author(s):  
Megan Pophal ◽  
Zachary W. Grimmett ◽  
Clara Chu ◽  
Seunghee Margevicius ◽  
Thomas Raffay ◽  
...  

Thiol-NO adducts such as S-nitrosoglutathione (GSNO) are endogenous bronchodilators in human airways. Decreased airway S-nitrosothiol concentrations are associated with asthma. Nitric oxide (NO), a breakdown product of GSNO, is measured in exhaled breath as a biomarker in asthma; an elevated fraction of expired NO (FENO) is associated with asthmatic airway inflammation. We hypothesized that FENO could reflect airway S-nitrosothiol concentrations. To test this hypothesis, we first studied the relationship between mixed expired NO and airway S-nitrosothiols in patients endotracheally intubated for respiratory failure. The inverse (Lineweaver-Burke type) relationship suggested that expired NO could reflect the rate of pulmonary S-nitrosothiol breakdown. We thus studied NO evolution from the lungs of mice (GSNO reductase −/−) unable reductively to catabolize GSNO. More NO was produced from GSNO in the −/− compared to wild type lungs. Finally, we formally tested the hypothesis that airway GSNO increases FENO using an inhalational challenge model in normal human subjects. FENO increased in all subjects tested, with a median t1/2 of 32.0 min. Taken together, these data demonstrate that FENO reports, at least in part, GSNO breakdown in the lungs. Unlike GSNO, NO is not present in the lungs in physiologically relevant concentrations. However, FENO following a GSNO challenge could be a non-invasive test for airway GSNO catabolism.

1998 ◽  
Vol 85 (2) ◽  
pp. 653-666 ◽  
Author(s):  
Nikolaos M. Tsoukias ◽  
Steven C. George

The relatively recent detection of nitric oxide (NO) in the exhaled breath has prompted a great deal of experimentation in an effort to understand the pulmonary exchange dynamics. There has been very little progress in theoretical studies to assist in the interpretation of the experimental results. We have developed a two-compartment model of the lungs in an effort to explain several fundamental experimental observations. The model consists of a nonexpansile compartment representing the conducting airways and an expansile compartment representing the alveolar region of the lungs. Each compartment is surrounded by a layer of tissue that is capable of producing and consuming NO. Beyond the tissue barrier in each compartment is a layer of blood representing the bronchial circulation or the pulmonary circulation, which are both considered an infinite sink for NO. All parameters were estimated from data in the literature, including the production rates of NO in the tissue layers, which were estimated from experimental plots of the elimination rate of NO at end exhalation (ENO) vs. the exhalation flow rate (V˙E). The model is able to simulate the shape of the NO exhalation profile and to successfully simulate the following experimental features of endogenous NO exchange: 1) an inverse relationship between exhaled NO concentration and V˙E, 2) the dynamic relationship between the phase III slope andV˙E, and 3) the positive relationship between ENO andV˙E. The model predicts that these relationships can be explained by significant contributions of NO in the exhaled breath from the nonexpansile airways and the expansile alveoli. In addition, the model predicts that the relationship between ENO and V˙E can be used as an index of the relative contributions of the airways and the alveoli to exhaled NO.


2019 ◽  
Vol 8 (11) ◽  
pp. 1783 ◽  
Author(s):  
Valentina Agnese Ferraro ◽  
Stefania Zanconato ◽  
Eugenio Baraldi ◽  
Silvia Carraro

Background: In the context of the so-called unified airway theory, chronic rhinosinusitis (CRS) and asthma may coexist. The inflammation underlying these conditions can be studied through the aid of biomarkers. Main body: We described the main biological mediators that have been studied in pediatric CRS and asthma, and, according to the available literature, we reported their potential role in the diagnosis and management of these conditions. As for CRS, we discussed the studies that investigated nasal nitric oxide (nNO), pendrin, and periostin. As for asthma, we discussed the role of fractional exhaled nitric oxide (feNO), the role of periostin, and that of biological mediators measured in exhaled breath condensate (EBC) and exhaled air (volatile organic compounds, VOCs). Conclusion: Among non-invasive biomarkers, nNO seems the most informative in CRS and feNO in asthma. Other biological mediators seem promising, but further studies are needed before they can be applied in clinical practice.


1995 ◽  
Vol 88 (2) ◽  
pp. 135-139 ◽  
Author(s):  
Sergei A. Kharitonov ◽  
Gert Lubec ◽  
Barbara Lubec ◽  
Magnus Hjelm ◽  
Peter J. Barnes

1. Endogenous nitric oxide plays an important physiological role and is synthesized by several isoforms of nitric oxide synthase from the semiessential amino acid l-arginine. Nitric oxide is detectable in the exhaled air of normal individuals and may be used to monitor the formation of nitric oxide in the respiratory tract. 2. We have investigated the effect of orally administered l-arginine (0.05, 0.1, 0.2 g/kg) compared with matched placebo on the concentration of nitric oxide in the exhaled air in 23 normal individuals. 3. l-Arginine caused significant increases in the concentration of nitric oxide in exhaled air at doses of 0.1 and 0.2 mg/kg, which was maximal 2 h after administration. This was associated with an increase in the concentration of l-arginine and nitrate in plasma. There were no significant changes in heart rate, blood pressure or forced expiratory volume in 1 s. 4. These results suggest that an increase in the amount of substrate for nitric oxide synthase can increase the formation of endogenous nitric oxide. This may have therapeutic relevance in diseases in which there is defective production of nitric oxide.


2002 ◽  
Vol 109 (1) ◽  
pp. S234-S234
Author(s):  
Michael Wechsler ◽  
Aaron Deykin ◽  
Paul E Daniel ◽  
Anthony F Massaro ◽  
Elliot Israel

1991 ◽  
Vol 71 (6) ◽  
pp. 2122-2126 ◽  
Author(s):  
D. J. Newham ◽  
T. McCarthy ◽  
J. Turner

The extent of voluntary activation in fresh and fatigued quadriceps muscles was investigated during isometric and isokinetic voluntary contractions at 20 and 150 degrees/s in 23 normal human subjects. The muscles were fatigued by a total of 4 min of maximal knee extension at an angular velocity of 85 degrees/s. Voluntary activation was determined by the superimposition of tetanic electrical stimulation at 100 Hz for 250 ms, initiated at a constant knee angle. The relationship between voluntary and stimulated force was similar to that found with the established twitch superimposition technique used on isometric contractions. In fresh muscle all the subjects showed full voluntary activation during isometric contractions. Some activation failure was seen in five subjects at 20 degrees/s [2.0 +/- 0.9 degrees (SE)] and in two subjects at 150 degrees/s (0.7 +/- 0.5). After fatigue all subjects showed some activation failure at 0 and 20 degrees/s (36.4 +/- 3.1 and 28.8 +/- 4.1 degrees, respectively), but only two showed any at 150 degrees/s (1.4 +/- 5.7). We conclude that brief high-intensity dynamic exercise can cause a considerable failure of voluntary activation. This failure was most marked during isometric and the lower-velocity isokinetic contractions. Thus a failure of voluntary activation may have greater functional significance than previous studies of isometric contractions have indicated.


1996 ◽  
Vol 135 (5) ◽  
pp. 543-547 ◽  
Author(s):  
Márta Korbonits ◽  
Peter J Trainer ◽  
Giuseppe Fanciulli ◽  
Osvaldo Oliva ◽  
Alessandra Pala ◽  
...  

Korbonits M, Trainer PJ, Fanciulli G, Oliva O, Pala A, Dettori A, Besser GM, Delitala G, Grossman AB. l-Arginine is unlikely to exert neuroendocrine effects in humans via the generation of nitric oxide. Eur J Endocrinol 1996;135:543–7. ISSN 0804–4643 There is now considerable evidence that nitric oxide is an important neuroregulatory agent, but there has been very little investigation of its possible role in neuroendocrine mechanisms in humans. We have investigated the effects of two nitric oxide precursors, l-arginine and molsidomine, under basal conditions on the pituitary hormones growth hormone (GH), prolactin, luteinizing hormone, folliclestimulating hormone, thyrotrophin, adrenocorticotrophin (ACTH) and vasopressin, and also on serum cortisol; we have also studied the effect of l-arginine on circulating prolactin, ACTH and cortisol in normal human subjects under hypoglycaemic stress. l-Arginine stimulated both GH and prolactin release under basal conditions but had no effect on the other hormones studied, while the nitric oxide donor molsidomine showed no effect on any hormone studied. l-Arginine potentiated the hypoglycaemia-stimulated release of ACTH but did not influence the rise in GH. The current studies suggest that the effects of l-arginine on the stimulation of GH and prolactin release are unlikely to be mediated via the generation of nitric oxide. A Grossman, Department of Endocrinology, St Bartholomew's Hospital, West Smithfield, London EC1A 7BE, UK


1981 ◽  
Vol 59 (2) ◽  
pp. 173-179 ◽  
Author(s):  
E. E. Daniel ◽  
J. E. T. Fox ◽  
S. M. Collins ◽  
T. D. Lewis ◽  
M. Meghji ◽  
...  

The hypothesis that acid, emptied intermittently from the stomach during fasting, might initiate the duodenal phase of the migrating motor complex was tested in normal human subjects, in addition, the relationship between plasma motilin concentrations and the initiation of migrating motor complexes was examined. Migrating complexes occurred spontaneously in the absence of acid in the duodenal bulb and in the presence of duodenal bulb neutralization with sodium bicarbonate. Thus duodenal bulb acidification is not necessary for initiation of the duodenal phase of the migrating motor complexes. Further-more, cyclical increases in plasma motilin concentrations were not closely correlated with the initiation of the gastric phase of maximal activity of the migrating motor complexes. However, motilin concentrations were decreased significantly following onset of the duodenal phase III. We conclude that neither duodenal acidification nor increases in motilin concentration are necessary to initiate migrating motor complexes in man.


1980 ◽  
Vol 32 (1) ◽  
pp. 3-25 ◽  
Author(s):  
Michael I. Posner

Bartlett viewed thinking as a high level skill exhibiting ballistic properties that he called its “point of no return”. This paper explores one aspect of cognition through the use of a simple model task in which human subjects are asked to commit attention to a position in visual space other than fixation. This instruction is executed by orienting a covert (attentional) mechanism that seems sufficiently time locked to external events that its trajectory can be traced across the visual field in terms of momentary changes in the efficiency of detecting stimuli. A comparison of results obtained with alert monkeys, brain injured and normal human subjects shows the relationship of this covert system to saccadic eye movements and to various brain systems controlling perception and motion. In accordance with Bartlett's insight, the possibility is explored that similar principles apply to orienting of attention toward sensory input and orienting to the semantic structures used in thinking.


Author(s):  
W. Bedingham ◽  
W.G. Tatton

ABSTRACT:The relationship between the segmented EMG activity in flexor carpi radialis evoked by imposed angular wrist displacement was studied with respect to the level of pre-existing background activity in 30 normal human subjects. Input-output response planes demonstrate that the magnitude of the Ml & M2-3 segments is dependent on both the displacement parameters and the level of pre-existing EMG activity in the stretched muscle. If the level of background activity exceeded 4-5% of the maximum voluntary contraction, the onset latency of the M1 segment and duration of the Ml and the M2-3 segments remained constant (within ± 2 msec) for different magnitudes of step load displacements, despite marked variation in the range of the displacement’s amplitude, duration, velocity, and acceleration. We propose that the dependency of the relationship between reflex magnitude and imposed movement parameters on tonic motoneuron activity, as represented by pre-existing EMG levels, may reflect an automatic adjustment mechanism that could be utilized in servo compensation of movements requiring markedly different force levels.


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