Effect of oral L-arginine on airway hyperresponsiveness to histamine in asthma.
BACKGROUND
Nitric oxide (NO) may exert protective properties within the airways of asthmatic patients. It was postulated that airways obstruction in asthma may be associated with endogenous NO deficiency caused by limited availability of NO synthase substrate.


METHODS
In a double blind, crossover study 14 asthmatic patients received pretreatment with oral L-arginine (50 mg/kg body weight) or placebo prior to histamine challenge. Histamine challenge was performed until a 50% fall in forced expiratory volume in one second (FEV(1)) occurred and the response was expressed as the provocative concentration causing a 20% fall in FEV(1) (PC(20)) and as the dose-response slope (maximal % fall in FEV(1)/cumulative dose (micromol)).


RESULTS
Pretreatment with L-arginine did not affect PC(20) histamine (mean change in doubling dose 0.18 (95% confidence interval (CI) -0.36 to 0.71), p = 0.5) but the dose-response slope to histamine was slightly reduced (mean change: 0.7 (95% CI 0.6 to 0. 9), p = 0.016).


CONCLUSIONS
Oral L-arginine does not influence airway hyperresponsiveness to histamine as reflected by PC(20), although the dose-response slope is slightly reduced in patients with asthma. This indicates only marginal, clinically unimportant limitation of NO synthase substrate in asthma.
de Gouw
H W
HW
Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands.
Verbruggen
M B
MB
Twiss
I M
IM
Sterk
P J
PJ
D000704:Analysis of Variance; D001120:Arginine / Q000008:administration & dosage / Q000494:pharmacology*; D001249:Asthma / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000188:drug therapy* / Q000378:metabolism; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005541:Forced Expiratory Volume / Q000187:drug effects; D006632:Histamine; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism*
D009569:Nitric Oxide; D006632:Histamine; D001120:Arginine