Effect of inhaled L-arginine on exhaled nitric oxide in normal and asthmatic subjects.
BACKGROUND
Nitric oxide (NO) plays an important part in the regulation of many physiological functions and may also be involved in several pulmonary diseases. Endogenous NO is synthesised by different isoforms of NO synthase (NOS) from L-arginine.


METHODS
The effect of inhaled L-arginine 0.75 g (six normal and six asthmatic subjects), 1.5 g (six normal and six asthmatic subjects), and 3 g (seven normal and six asthmatic subjects) has been studied in a double blind placebo controlled, randomised, parallel group design study. In addition, the effect of a single dose (3 g) of inhaled L-alanine has been assessed in five normal and five asthmatic subjects.


RESULTS
L-arginine increased exhaled NO in a dose-dependent fashion with a maximum at 60 minutes. The cumulative effect of L-arginine (3 g) on NO in asthmatic subjects, expressed as the area under the curve in arbitrary units (au) and compared with the effect of placebo (0.9% NaCl), was significantly higher (mean 0.11 au; 95% confidence interval (CI) 0.03 to 0.19) than in normal subjects (0.012 au; 95% CI 0.002 to 0.022). There was a negative correlation (r = -0.72) between the increase in exhaled NO and the fall in forced expiratory volume in one second (FEV1) (0.034 au, 95% CI 0.030 to 0.038) after 3 g L-arginine in asthmatic subjects. Inhalation of 3 g of L-alanine produced a similar reduction in FEV1 (0.033 au, 95% CI 0.007 to 0.059) but no significantly different changes in exhaled NO (0.017 au, 95% CI 0.001 to 0.039) compared with placebo (0.020 au, 95% CI 0.001 to 0.042).


CONCLUSIONS
An increase in the amount of substrate for NOS increases the formation of endogenous NO. L-arginine may have therapeutic potential in diseases in which there is defective production of NO, but in asthma it may amplify the inflammatory response in the airways.
Sapienza
M A
MA
Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College School of Medicine, London, UK.
Kharitonov
S A
SA
Horvath
I
I
Chung
K F
KF
Barnes
P J
PJ
D000280:Administration, Inhalation; D000409:Alanine / Q000008:administration & dosage; D019540:Area Under Curve; D001120:Arginine / Q000008:administration & dosage*; D001249:Asthma / Q000378:metabolism* / Q000503:physiopathology; D001944:Breath Tests; D001985:Bronchial Provocation Tests; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008297:Male; D016210:Methacholine Chloride; D009569:Nitric Oxide / Q000032:analysis* / Q000378:metabolism
D016210:Methacholine Chloride; D009569:Nitric Oxide; D001120:Arginine; D000409:Alanine