Using a guinea‐pig model of allergic asthma, we investigated the role of nitric oxide (NO) in allergen‐induced airway hyperreactivity after the early asthmatic reaction, by examining the effects of the NO‐synthase inhibitor Nω‐nitro‐L‐arginine methyl ester (L‐NAME) on the responsiveness to methacholine and histamine of isolated perfused tracheae from unchallenged (control) animals and from animals 6 h after ovalbumin challenge.

All animals developed airway hyperreactivity to inhaled histamine at 6 h after ovalbumin challenge, with a mean 3.11 ± 0.45 fold increase in sensitivity to the agonist (P < 0.001).

In perfused tracheal preparations from the ovalbumin‐challenged guinea‐pigs, the maximal responses (E_max) to methacholine and histamine were significantly enhanced compared to controls, both after intraluminal (IL) and extraluminal (EL) administration of the contractile agonists. In addition, a small but significant increase in the pD₂ (‐log₁₀ EC₅₀) for IL and EL methacholine and for IL histamine was observed. As a consequence, the ΔpD₂ (EL‐IL) for histamine was slightly decreased from 1.67 ± 0.13 to 1.23 ± 0.14 (P < 0.05). However, the ΔpD₂ for methacholine was unchanged (1.85 ± 0.11 and 1.77 ± 0.12, respectively; NS).

Incubation of control tracheae with 100 μm L‐NAME (IL) significantly enhanced the E_max for both IL and EL methacholine and histamine to approximately the same degree as observed after ovalbumin challenge, with no effect on the pD₂ and ΔpD₂ for both agonists. On the contrary, L‐NAME had no effect on E_max and pD₂ values of tracheal preparations from ovalbumin‐challenged guinea‐pigs.

L‐NAME (10 μm‐l mM) had no effect on methacholine‐induced contraction of isolated tracheal strip preparations obtained from control animals, indicating that L‐NAME has no antimuscarinic effect on tracheal smooth muscle.

Histological examination of the intact tracheal preparations indicated epithelial and subepithelial infiltration of eosinophils after ovalbumin challenge. However, no apparent damage of the airway epithelium was observed in these preparations.

The results indicate that a deficiency of NO contributes to allergen‐induced airway hyperreactivity after the early asthmatic reaction and that this deficiency appears not to be due to epithelial shedding.