EFFECT OF INHALED L-ARGININE ON EXHALED NITRIC-OXIDE IN NORMAL AND ASTHMATIC SUBJECTS

Background--Nitric oxide (NO) plays an important part in the regulatio n 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 0.75g (six normal and six asthmatic subjects), 1.5 g (six n ormal and six asthmatic subjects), and 3g (seven normal and six asthma tic subjects) has been studied in a double blind placebo controlled, r andomised, parallel group design study. In addition, the effect of a s ingle 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 cumulat ive effect of L-arginine (3 g) on NO in asthmatic subjects, expressed as the area under the curve in arbitrary units (au) sand compared with the effect of placebo (0.9% NaCl), was significantly higher (mean 0.1 1 an; 95% confidence interval (CI) 0.03 to 0.19) than in normal subjec ts (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 0.0 38) after 3g 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 t o 0.059) but no significantly different changes in exhaled NO (0.017 a u, 95% CI 0.001 to 0.039) compared with placebo (0.020 au, 95% CI 0.00 1 to 0.042). Conclusions-An increase in the amount of substrate for NO S increases the formation of endogenous NO. L-arginine may have therap eutic potential in diseases in which there is defective production of NO, but in asthma it may amplify the inflammatory response in the airw ays.