Role of nitric oxide in the development and partial reversal of allergen-induced airway hyperreactivity in conscious, unrestrained guinea-pigs (original) (raw)

1998, British Journal of Pharmacology

Using a conscious, unrestrained guinea-pig model of allergic asthma, we investigated the role of endogenous nitric oxide (NO) in the regulation of airway (hyper)reactivity to histamine before and after the allergen-induced early and late asthmatic reactions, by examining the eect of inhalation of the NO synthase inhibitor N o-nitro-L-arginine methyl ester (L-NAME, 12 mM, 15 min) on the histamine-induced airway obstruction of ovalbumin-sensitized guinea-pigs before, and at 5.5 h and 23.5 h after allergen challenge. 2 Before allergen challenge, inhaled L-NAME caused a signi®cant 2.02+0.25 fold increase (P50.01) in airway reactivity to histamine; this eect was reversed within 2.5 to 6 h after administration. 3 After the allergen-induced early asthmatic reaction at 5 h after ovalbumin provocation, a signi®cant 3.73+0.67 fold increase (P50.01) of the airway reactivity to histamine was observed; subsequent inhalation of L-NAME at 5.5 h had no eect on the airway hyperreactivity, reassessed at 6 h. 4 After the late asthmatic reaction, at 23 h after ovalbumin provocation, a reduced, but still signi®cant airway hyperreactivity to histamine (2.18+0.40 fold; P50.05) was observed. Subsequent inhalation of L-NAME now signi®cantly potentiated the partially reduced airway hyperreactivity 1.57+0.19 fold (P50.05) to the level observed after the early asthmatic reaction. 5 When administered 30 min before allergen exposure, L-NAME signi®cantly enhanced the allergeninduced early asthmatic reaction. However, when administered at 5.5 h after allergen provocation, L-NAME did not aect the subsequent late asthmatic reaction. 6 These results indicate that endogenous NO is involved the regulation of histamine-and allergeninduced bronchoconstriction and that a de®ciency of cNOS-derived NO contributes to the allergeninduced airway hyperreactivity to histamine after the early asthmatic reaction, while a recovery of NO de®ciency may account for the partial reversal of the allergen-induced airway hyperreactivity after the late asthmatic reaction.