Role of nitric oxide in the airway response to exercise in healthy and asthmatic subjects.
A role of nitric oxide (NO) has been suggested in the airway response to exercise. However, it is unclear whether NO may act as a protective or a stimulatory factor. Therefore, we examined the role of NO in the airway response to exercise by using N-monomethyl-L-arginine (L-NMMA, an NO synthase inhibitor), L-arginine (the NO synthase substrate), or placebo as pretreatment to exercise challenge in 12 healthy nonsmoking, nonatopic subjects and 12 nonsmoking, atopic asthmatic patients in a double-blind, crossover study. Fifteen minutes after inhalation of L-NMMA (10 mg), L-arginine (375 mg), or placebo, standardized bicycle ergometry was performed for 6 min using dry air, while ventilation was kept constant. The forced expiratory volume in 1-s response was expressed as area under the time-response curve (AUC) over 30 min. In healthy subjects, there was no significant change in AUC between L-NMMA and placebo treatment [28.6 +/- 17.0 and 1.3 +/- 20.4 (SE) for placebo and L-NMMA, respectively, P = 0.2]. In the asthmatic group, L-NMMA and L-arginine induced significant changes in exhaled NO (P < 0.01) but had no significant effect on AUC compared with placebo (geometric mean +/- SE: -204.3 +/- 1.5, -186.9 +/- 1.4, and -318.1 +/- 1.2%. h for placebo, L-NMMA, and L-arginine, respectively, P > 0.2). However, there was a borderline significant difference in AUC between L-NMMA and L-arginine treatment (P = 0.052). We conclude that modulation of NO synthesis has no effect on the airway response to exercise in healthy subjects but that NO synthesis inhibition slightly attenuates exercise-induced bronchoconstriction compared with NO synthase substrate supplementation in asthma. These data suggest that the net effect of endogenous NO is not inhibitory during exercise-induced bronchoconstriction in asthma.
De Gouw
H W
HW
Department of Pulmonology, Leiden University Medical Center, NL-2300 RC Leiden, The Netherlands.
Marshall-Partridge
S J
SJ
Van Der Veen
H
H
Van Den Aardweg
J G
JG
Hiemstra
P S
PS
Sterk
P J
PJ
D000280:Administration, Inhalation; D000328:Adult; D001120:Arginine / Q000008:administration & dosage / Q000494:pharmacology; D001250:Asthma, Exercise-Induced / Q000378:metabolism / Q000503:physiopathology*; D001944:Breath Tests; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D005541:Forced Expiratory Volume; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D013997:Time Factors; D019323:omega-N-Methylarginine / Q000008:administration & dosage / Q000494:pharmacology
D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine