Role of nitric oxide in the airway response to exercise in healthy and asthmatic subjects

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Abstract
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 betweenl-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.