Effect of oral l-arginine on airway hyperresponsiveness to histamine in asthma
- aDepartment of Pulmonology, bDepartment of Clinical Pharmacology and Toxicology, cLeiden University Medical Center, Leiden, The Netherlands
- Dr H W F M de Gouw, Lung Function Laboratory, C2-P-62, Leiden University Medical Center, P O Box 9600, NL-2300 RC Leiden, The Netherlands.
- Received 26 October 1998
- Revision requested 26 January 1999
- Revised 4 August 1999
- Accepted 4 August 1999
Abstract
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 (FEV1) occurred and the response was expressed as the provocative concentration causing a 20% fall in FEV1(PC20) and as the dose-response slope (maximal % fall in FEV1/cumulative dose (μmol)).
RESULTS Pretreatment with l-arginine did not affect PC20 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 Orall-arginine does not influence airway hyperresponsiveness to histamine as reflected by PC20, 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.
