Effect of inhaled L-arginine on exhaled nitric oxide in normal and asthmatic subjects

被引:72
|
作者
Sapienza, MA [1 ]
Kharitonov, SA [1 ]
Horvath, I [1 ]
Chung, KF [1 ]
Barnes, PJ [1 ]
机构
[1] Natl Heart & Lung Inst, Dept Thorac Med, Natl Heart & Lung Inst, Imperial Coll Sch Med, London SW3 6LY, England
关键词
nitric oxide; L-arginine; asthma;
D O I
10.1136/thx.53.3.172
中图分类号
R56 [呼吸系及胸部疾病];
学科分类号
摘要
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 0.75g (six normal and six asthmatic subjects), 1.5 g (six normal and six asthmatic subjects), and 3g (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) sand compared with the effect of placebo (0.9% NaCl), was significantly higher (mean 0.11 an; 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 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 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.
引用
收藏
页码:172 / 175
页数:4
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