help button home button
AJRCCM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by TAYLOR, D. A.
Right arrow Articles by BARNES, P. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by TAYLOR, D. A.
Right arrow Articles by BARNES, P. J.

Am. J. Respir. Crit. Care Med., Volume 158, Number 1, July 1998, 99-106

Allergen-induced Early and Late Asthmatic Responses Are Not Affected by Inhibition of Endogenous Nitric Oxide

DAVID A. TAYLOR, JENNIFER L. MCGRATH, BRIAN J. O'CONNOR, and PETER J. BARNES

Royal Brompton Clinical Studies Unit, Department of Thoracic Medicine, Imperial College School of Medicine at the National Heart and Lung Institute, London, United Kingdom

Endogenous exhaled nitric oxide (NO) is increased during the late response to inhaled allergen in patients with asthma and may be bronchoprotective in asthma or have a deleterious effect when generated in excess under inflammatory conditions. To investigate this, we evaluated the effect of inhibiting endogenous NO production with nebulized NG-nitro-L-arginine methyl ester (L-NAME), a nonselective NO synthase (NOS) inhibitor, on early and late asthmatic responses to inhaled allergen in patients with mild allergic asthma. After a screening allergen challenge (AC), 22 male patients attended two visits conducted in a double-blind, randomized, placebo-controlled, crossover manner. Twelve patients demonstrating an early asthmatic response only (single responders) inhaled either L-NAME 170 mg or 0.9% saline 20 min before AC, with exhaled NO and FEV1 measured for 3 h. Ten patients demonstrating both early and late asthmatic responses (dual responders) were studied in a similar fashion but inhaled two further doses of L-NAME or placebo 3.5 and 7 h after the initial dose, with exhaled NO and FEV1 measured for 10 h. L-NAME reduced exhaled NO levels by 77 ± 5% (p < 0.01) and 71 ± 7% (p < 0.01) in single and dual responders, respectively, but had no significant effect on early or late asthmatic responses. Following AC in single responders, the mean (± SEM) maximum fall in FEV1 after L-NAME and saline was 21.2 ± 2.9% and 23.8 ± 3.0%, respectively, and in dual responders, 31.2 ± 4.5% and 31.8 ± 5.8% during the early asthmatic responses, and 27.4 ± 3.9% and 30.6 ± 4.5% during the late asthmatic responses, respectively. Area under the curve (AUC) did not significantly differ. AUC0-2 h in single responders after L-NAME and saline was 20.2 ± 3.9 and 24.9 ± 4.4 Delta % FEV1/h, and in dual responders, 37.6 ± 8.4 and 36.7 ± 8.4 Delta % FEV1/h, respectively, and 106.2 ± 18.9 and 117.1 ± 22.4 Delta % FEV1/h, respectively, for the AUC4-10 h. This study suggests that in mild allergic asthma, endogenous NO neither protects against nor contributes to the processes underlying airway responses to inhaled allergen.




This article has been cited by other articles:


Home page
 ChestHome page
C. Brindicci, K. Ito, O. Torre, P. J. Barnes, and S. A. Kharitonov
Effects of Aminoguanidine, an Inhibitor of Inducible Nitric Oxide Synthase, on Nitric Oxide Production and Its Metabolites in Healthy Control Subjects, Healthy Smokers, and COPD Patients
Chest, February 1, 2009; 135(2): 353 - 367.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
D. Singh, D. Richards, R. G. Knowles, S. Schwartz, A. Woodcock, S. Langley, and B. J. O'Connor
Selective Inducible Nitric Oxide Synthase Inhibition Has No Effect on Allergen Challenge in Asthma
Am. J. Respir. Crit. Care Med., November 15, 2007; 176(10): 988 - 993.
[Abstract] [Full Text] [PDF]

Home page
 ChestHome page
C. Brindicci, K. Ito, P. J. Barnes, and S. A. Kharitonov
Effect of an Inducible Nitric Oxide Synthase Inhibitor on Differential Flow-Exhaled Nitric Oxide in Asthmatic Patients and Healthy Volunteers
Chest, August 1, 2007; 132(2): 581 - 588.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
F. L. M. Ricciardolo, P. J. Sterk, B. Gaston, and G. Folkerts
Nitric Oxide in Health and Disease of the Respiratory System
Physiol Rev, July 1, 2004; 84(3): 731 - 765.
[Abstract] [Full Text] [PDF]

Home page
 ThoraxHome page
F L M Ricciardolo
Multiple roles of nitric oxide in the airways
Thorax, February 1, 2003; 58(2): 175 - 182.
[Abstract] [Full Text] [PDF]

Home page
 ChestHome page
M. Shinkai, S. Suzuki, A. Miyashita, H. Kobayashi, T. Okubo, and Y. Ishigatsubo
Analysis of Exhaled Nitric Oxide by the Helium Bolus Method*
Chest, June 1, 2002; 121(6): 1847 - 1852.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
H. E. Marshall and J. S. Stamler
NO Waiting to Exhale in Asthma
Am. J. Respir. Crit. Care Med., March 1, 2000; 161(3): 685 - 687.
[Full Text] [PDF]

Home page
 JEMHome page
G. T. De Sanctis, J. A. MacLean, K. Hamada, S. Mehta, J. A. Scott, A. Jiao, C. N. Yandava, L. Kobzik, W. W. Wolyniec, A. J. Fabian, et al.
Contribution of Nitric Oxide Synthases 1, 2, and 3 to Airway Hyperresponsiveness and Inflammation in a Murine Model of Asthma
J. Exp. Med., May 17, 1999; 189(10): 1621 - 1630.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Proc. Am. Thorac. Soc. Am. J. Respir. Cell Mol. Biol.
Copyright © 1998 American Thoracic Society