The effect of the nitric oxide synthase inhibitor, L-NMMA, on sodium metabisulphite-induced bronchoconstriction and refractoriness in asthma

Refractoriness to indirect bronchoconstrictor stimuli, is a feature of asth ma but the mechanism is poorly understood. This study tested the hypothesis that endogenous nitric oxide (NO) produced during a first bronchoconstrict or challenge protects against subsequent challenge and therefore has a role in the refractory process. The effect of an NO synthase inhibitor, NG-mono-methyl-L-arginine (L-NMMA), on refractoriness to sodium metabisulphite (MBS) was investigated in 20 su bjects with mild asthma. On visit one, the dose of MBS which caused a 20% f all in forced expiratory volume in one second (FEV1) (PD20) was determined. On visit two, the refractory index (RI) to MBS was determined by challengi ng the subjects twice with their PD20 of MBS, the second challenge proceedi ng after recovery from the first. Those showing a refractory index of simil ar to 30% (10 subjects) inhaled either L-NMMA or placebo followed 5 min lat er by two challenges with their PD20 of MBS in a double-blind cross over st udy at two further visits. The dose of L-NMMA used was shown to reduce exhaled NO for a duration suffi cient to cover the second MBS challenge However, no significant difference was found between L-NMMA and placebo in maximum fall in FEV1% and area unde r the curve (AUC) during first or second MBS challenges or in RI on the two study days, It is concluded that subjects with mild asthma show refractoriness to sodiu m metabisulphite, but that endogenous nitric oxide is unlikely to be involv ed either in the refractory process or in the response to sodium metabisulp hite per se.