Randomised double-blind placebo-controlled study of the effect of inhibition of nitric oxide synthesis in bradykinin-induced asthma

Summary Background Bronchoconstriction induced by bradykinin is reduced by the release of nitric oxide (NO) in the airways of guineapigs. Inhaled NO is known to cause broncho-dilatation in asthmatic patients. To find out the role of endogenous NO in airway response to bradykinin in asthma, we examined the effect of the NO synthase inhibitor N G -monomethyl-L-arginine (L-NMMA) on bronchoconstriction after bradykinin challenge in ten patients with mild asthma. Methods The study had a randomised, double-blind, placebo-controlled, cross-over design. Participants were studied during two phases, each consisting of 2 study days. After baseline measurements of forced expiratory volume in 1 s (FEV 1 ) participants inhaled an aerosol of L-NMMA or saline (placebo). After 5 min, saline and doubling doses of bradykinin (from 0·25 nmol) were inhaled until FEV 1 fell by at least 20% of the post-saline value. The effect of L-NMMA and placebo on airway response to doubling concentrations of methacholine (from 0·03 mg/mL) was then examined. We also assessed the effect of the inactive enantiomer of L-NMMA, D-NMMA, and placebo on bronchoconstriction after bradykinin or methacholine challenge in six of the participants. Findings The geometric mean of the provocative dose producing a 20% fall in FEV 1 to bradykinin was 138·0 nmol (range 48·2-475·2 nmol) after placebo and 11·2 nmol (range 0·9-51·3 nmol) after L-NMMA (p Interpretation The results suggest that bronchoconstriction after bradykinin inhalation is greatly inhibited by the formation of NO in airways of asthmatic patients and that NO could have a bronchoprotective role in asthma.