Effect of oral L-arginine on airway hyperresponsiveness to histamine in asthma

Background-Nitric oxide (NO) may exert protective properties within the air ways of asthmatic patients. It was postulated that airways obstruction in a sthma may be associated with endogenous NO deficiency caused by limited ava ilability of NO synthase substrate. Methods-In a double blind, crossover study 14 asthmatic patients received p retreatment 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 wa s expressed as the provocative concentration causing a 20% fall in FEV1 (PC 20) and as the dose-response slope (maximal % fall in FEV1/cumulative dose (mu mol)). Results-Pretreatment with L-arginine did not affect PC20 histamine (mean ch ange 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 t o histamine as reflected by PC20, although the dose-response slope is sligh tly reduced in patients with asthma. This indicates only marginal, clinical ly unimportant limitation of NO synthase substrate in asthma.