Endogenous nitric oxide in expired air: Effects of acute exercise in humans

doi:10.1016/0024-3205(94)00522-2

Life Sciences

Volume 55, Issue 24, 1994, Pages 1903-1909

https://doi.org/10.1016/0024-3205(94)00522-2 Get rights and content

Abstract

Nitric oxide (NO) is present in the exhaled breath of humans and experimental animals, but its physiologic role and cellular source(s) remain to be determined. Possible sites of origin are pulmonary endothelial cells and/or resident macrophages. Here we have tested the hypothesis that changes in cardiovascular status can alter the apparent pulmonary excretion of NO. Exercise on a stationary bicycle produced rapid and reversible increases in pulmonary NO excretion rate, and changes in NO excretion rate during exercise were well correlated with observed changes in heart rate. These results suggest that changes in expired NO during exercise are related to corresponding cardiovascular responses.

References (20)

L.E. Gustafsson et al.
Biochem. Biophys. Res. Commun.
(1991)
J.A. Bauer et al.
Life Sci.
(1994)
J. Pepke-Zaba et al.
Lancet
(1991)
B. Caru et al.
Chest
(1992)
S.A. Kharitonov et al.
Lancet
(1994)
S. Moncada et al.
New Engl. J. Med.
(1993)
L.J. Ignarro
Annu. Rev. Pharmacol. Toxicol.
(1990)
S. Moncada et al.
Pharmacol. Rev.
(1991)
V. Smiesko et al.
News Physiol. Sci.
(1993)
J.S. Stamler et al.
Science
(1992)

There are more references available in the full text version of this article.

Cited by (67)

Exercise and Lung Function in Child Health and Disease
2012, Kendig and Chernick's Disorders of the Respiratory Tract in Children
The effects of hyperpnea on exhaled nitric oxide synthesis in normal subjects
2005, Chest
Citation Excerpt :
Because of the time necessary to complete such a protocol, we could never have been certain if NO synthesis was changing as we measured it. Our data in both the multiple and single-breath analyses complement and extend previous studies.4, 6-13 The Ve-FeNO patterns recorded are typical of those reported in other trials with both hyperventilation1,11,13 and exercise.6,7,8,9,12,22
Study objectives: To determine if the concentration of nitric oxide (NO) in the lungs increases with hyperpnea by contrasting calculated production (ie, the product of the fractional expired NO concentration [FeNO] and minute ventilation [Ve]) [Vno] with the amount of NO in equilibrium with the conducting airways (eNOair) and the amount of NO diffusing from the alveoli (eNOalv).
Design: Observational study.
Setting: University teaching hospital.
Participants: Normal subjects.
Interventions: Measurements were made in 16 healthy people during and after 4 min of tidal breathing (10 L/min) and isocapnic hyperventilation of 60 L/min.
Measurements and results: FeNO was measured by collecting the exhaled air during the last minute of each trial and passing it through a chemiluminescence analyzer. The expired NO levels in the plateau phases of slow (30 mL/s) and fast (200 mL/s) single-breath exhalations were also obtained before and after hyperventilation. The Vno(mean ± SEM) increased from 89.8 ± 12.3 to 329.1 ± 36.2 nL/min as Verose (p < 0.001). However, neither the quantities of eNOair nor eNOalv changed with hyperventilation (eNOair range before to after, 34.9 ± 7.7 to 30.9 ± 6.4 parts per billion [ppb], p = 0.96; eNOalv range before to after, 7.3 ± 1.5 to 6.5 ± 1.1 ppb, p = 0.97).
Conclusions: These data demonstrate that the amount of NO in equilibrium with the airway walls and alveoli are not altered by hyperpnea. Rather, the apparent augmentation in Vnoin such circumstances appears to be an arithmetic artifact.
Amlodipine increases nitric oxide production in exhaled air during exercise in patients with essential hypertension
2004, American Journal of Hypertension
Endothelial production of nitric oxide (NO) is attenuated in patients with essential hypertension. We investigated whether treatment with amlodipine increased exhaled NO output (V̇NO) at rest and during exercise in patients with essential hypertension.
We studied the effect of amlodipine in seven untreated hypertensive patients. Cardiopulmonary exercise testing and NO measurement of exhaled air were performed on these patients before and after 2 months of amlodipine treatment.
Amlodipine decreased blood pressure (BP) both at rest and during exercise (at rest: 147.1 ± 6.4 [SEM]/89.9 ± 4.4 v 133.6 ± 5.4/82.7 ± 3.9 mm Hg, P < .05; at peak exercise: 224.9 ± 8.0/113.1 ± 5.3 v 207.0 ± 6.0/100.7 ± 5.0 mm Hg, P < .05) without affecting heart rate (at rest: 67.6 ± 3.9 v 70.4 ± 4.5 beats/min, P = .33; peak exercise: 146.4 ± 7.4 v 144.0 ± 7.2 beats/min, P = .49). Amlodipine did not affect minute ventilation (V̇E) at rest or during exercise. It did not alter anaerobic threshold, peak oxygen uptake (peak V̇O₂), or peak workload. However, after amlodipine treatment, V̇NO was significantly greater both at rest (130.8 ± 19.4 v 180.4 ± 24.8 nL/min, P < .05) and at peak exercise (380.0 ± 47.5 v 582.6 ± 74.3 nL/min, P < .05).
Amlodipine increased NO production, at least in the pulmonary circulation, in patients with essential hypertension. In addition to its antihypertensive effect, the enhancement of NO production by amlodipine in the vasculature of other organs may contribute to its beneficial effects on the cardiovascular system.
Exhaled nitric oxide and exercise tolerance in severe COPD patients
2002, Respiratory Medicine
To answer the question as to whether pulmonary rehabilitation programs (PRP) induced increase in exercise tolerance (ET) is associated with increased levels of exhaled nitric oxide (eNO) in COPD patients of different degrees of severity, we designed a prospective and controlled study. Forty-seven stable COPD patients underwent an 8-week outpatient multidisciplinary PRP including supervised incremental exercise. Fractional eNO concentration (FE_NO) and peak work-rate (W_peak) were assessed baseline (T−1), at the end of 1-month run-in period (T 0), and after (T 1) the PRP. Lung function, walking test, health-related quality of life (HRQL) were also recorded. Patients were divided into three groups according to disease severity: 17 severe [FEV₁ 35 (5)% pred] COPD patients, seven of them with cor pulmonale; 15 mild [FEV₁ 78 (6)% pred], and 15 moderate [FEV₁ 56 (6)% pred] COPD patients. FE_NO did not differ at T -1 and T 0 (mean absolute change (SD): 0.03 (0.09) 95% Cl-0.01, 0.16, 0.06 (1.03) 95% Cl 0.03, 0.75 and 0.05 (0.06) 95% Cl 0.02, 0.11 ppb in mild, moderate and severe patients, respectively). As compared to T 0, both W_peak (by 17, 15 and 10%, respectively) and FE_NO (by 29, 24 and 16%, respectively) significantly increased in all groups, but not in patients with corpulmonale. A significant correlation between pre- and post-PRP changes in W_peak and FE_NO was found both in mild to moderate (r=0.79, P<0.00001) and severe (r=0.76, P<0.001) COPD patients. After a PRP, improvement in ET is associated with an increase in eNO also in most severe COPD patients, but not in those with cor pulmonale.
Mixed exhaled nitric oxide and plasma nitrites and nitrates in newborn infants
2001, Life Sciences
Plasma nitrite (NO₂⁻) and nitrate (NO₃⁻) are the stable end-products of endogenous nitric oxide (NO) metabolism. NO is present in the exhaled air of humans, but it is not clear if exhaled NO may be an indicator of the systemic endogenous NO production. The aims of the study were to determine the levels of exhaled NO and plasma NO₂⁻/NO₃⁻ in healthy term and preterm newborns, and to assess if exhaled NO correlates with plasma NO₂⁻/NO₃⁻ at birth. After the stabilization of the newborn, we measured by chemiluminescence the concentration of NO in the mixed expired breath of 133 healthy newborns. Measurement of exhaled NO was repeated after 24 and 48 hours. Plasma NO₂⁻/NO₃⁻ levels at birth were measured by the Griess reaction. NO concentrations were 8.9 (CI 8.1–9.8) parts per billion (ppb), 7.7 (CI 7.2–8.3) ppb and 9.0 (CI 8.4–9.6) ppb at birth, 24 and 48 hours, respectively. At birth, exhaled NO was inversely correlated with gestational age (p=0.008) and birth weight (p<0.001). Plasma NO₂⁻/NO₃⁻ level was 27.30 (CI 24.26–30.34) μmol/L. There was no correlation between exhaled NO and plasma NO₂⁻/NO₃⁻ levels at birth (p=0.88). We speculate that the inverse correlation between exhaled NO and gestational age and birth weight may reflect a role of NO in the postnatal adaptation of pulmonary circulation. At birth, exhaled NO does not correlate with plasma NO₂⁻/NO₃⁻ and does not seem to be an index of the systemic endogenous NO production.
Nitric oxide in the nasal airway: A new dimension in otorhinolaryngology
2001, American Journal of Otolaryngology - Head and Neck Medicine and Surgery
Citation Excerpt :
Asthmatic-exercise-induced—bronchoconstriction126 might be related to NO physiology. Several studies have shown that NO concentration in exhaled air from the lower airways increases during exercise.49,127-131 This increase in NO output is probably more closely related to increasing ventilation49,129,132 than to the increased blood flow.135
The discovery that the gas nitric oxide (NO) is an important signaling molecule in the cardiovascular system earned its Nobel prize in 1998. NO has since been found to play important roles in a variety of physiologic and pathophysiologic processes in the body including vasoregulation, hemostasis, neurotransmission, immune defense, and respiration. The surprisingly high concentrations of NO in the nasal airway and paranasal sinuses has important implications for the field of otorhinolaryngology. NO provides a first-line defense against micro-organisms through its antiviral and antimicrobial activity and by its upregulation of ciliary motility. Nasal treatments such as polypectomy, sinus surgery, removal of hypertrophic adenoids and tonsils, and treatment of allergic rhinitis may alter NO output and, therefore, the microbial colonization of the upper airways. Nasal surgery aimed at relieving nasal obstruction may do the same but would also be expected to improve pulmonary function in patients with asthma and upper airway obstruction. NO output rises in a number of conditions associated with chronic airway inflammation, but not all of them. Concentrations are increased in asthma, allergic rhinitis, and viral respiratory infections, but reduced in sinusitis, cystic fibrosis, primary ciliary dysfunction, chronic cough, and after exposure to tobacco and alcohol. Therefore, NO, similar to several other inflammatory mediators, probably subserves different functions as local conditions dictate. At present, it seems that the measurement of NO in the upper airway may prove valuable as a simple, noninvasive diagnostic marker of airway pathologies. The objective of this review is to highlight some aspects of the origin, physiology, and functions of upper airway NO, and to discuss the particular methodological problems that result from the complex anatomy. (Am J Otolaryngol 2001;22:19-32. Copyright © 2001 by W.B. Saunders Company)

View all citing articles on Scopus

View full text

Endogenous nitric oxide in expired air: Effects of acute exercise in humans

Abstract

Biochem. Biophys. Res. Commun.

Life Sci.

Lancet

Chest

Lancet

New Engl. J. Med.

Annu. Rev. Pharmacol. Toxicol.

Pharmacol. Rev.

News Physiol. Sci.

Science