ALLERGEN-INDUCED EARLY AND LATE ASTHMATIC RESPONSES ARE NOT AFFECTED BY INHIBITION OF ENDOGENOUS NITRIC-OXIDE

Endogenous exhaled nitric oxide (NO) is increased during the late resp onse to inhaled allergen in patients with asthma and may be bronchopro tective in asthma or have a deleterious effect when generated in exces s under inflammatory conditions. To investigate this, we evaluated the effect of inhibiting endogenous NO production with nebulized N-G-nitr o-L-arginine methyl ester (r-NAME), a nonselective NO synthase (NOS) i nhibitor, on early and late asthmatic responses to inhaled allergen in patients with mild allergic asthma. After a screening allergen challe nge (AC), 22 male patients attended two visits conducted in a double-b lind, randomized, placebo-controlled, crossover manner. Twelve patient s demonstrating an early asthmatic response only (single responders) i nhaled either L-NAME 170 mg or 0.9% saline 20 min before AC, with exha led NO and FEV1 measured for 3 h. Ten patients demonstrating both earl y and late asthmatic responses (dual responders) were studied in a sim ilar fashion but inhaled two further doses of L-NAME or placebo 3.5 an d 7 h after the initial dose, with exhaled NO and FEV1 measured for 10 h. L-NAME reduced exhaled NO levels by 77 +/- 5% (p < 0.01) and 71 +/ - 7% (p < 0.01) in single and dual responders, respectively, but had n o significant effect on early or late asthmatic responses. Following A C in single responders, the mean (+/- SEM) maximum fall in FEV1 after L-NAME and saline was 21.2 +/- 2.9% and 23.8 +/- 3.0%, respectively, a nd in dual responders, 31.2 +/-1 4.5% and 31.8 +/- 5.8% during the ear ly asthmatic responses, and 27.4 +/- 3.9% and 30.6 +/- 4.5% during the late asthmatic responses, respectively. Area under the curve (AUC) di d not significantly differ. AUC(0-2) (h) in single responders after L- NAME and saline was 20.2 +/- 3.9 and 24.9 +/- 4.4 Delta% FEV1/h, and i n dual responders, 37.6 +/- 8.4 and 36.7 +/- 8.4 Delta% FEV1/h, respec tively, and 106.2 +/- 18.9 and 117.1 +/- 22.4 Delta% FEV1/h, respectiv ely, for the AUC(4-10) (h). This study suggests that in mild allergic asthma, endogenous NO neither protects against nor contributes to the processes underlying airway responses to inhaled allergen.