Role of endogenous nitric oxide in allergen‐induced airway responses in guinea‐pigs

1 Endogenous nitric oxide (NO) can be detected in exhaled air and accumulates in inflamed airways. However its physiological role has not been fully elucidated. In this study, we investigated a role for endogenous NO in allergen‐induced airway responses. Sensitised guinea‐pigs were treated with N G ‐nitro‐ l ‐arginine methyl ester l ‐NAME (2.0 m m ) or aminoguanidine (AG) (2.0 m m ) 30 min before the allergen challenge, and 3 and 4 h after the challenge. Alternatively, l ‐arginine (2.4 m m ) treatment was performed 30 min before, and 2 and 3 h after the challenge. In all groups, ovalbumin (OVA) challenge (2 mg ml −1 for 2 min) was performed, and airway responses, NO production, infiltration of inflammatory cells, plasma exudation and histological details were examined. 2 Allergen‐challenged animals showed an immediate airway response (IAR) and a late airway response (LAR), which synchronised with an increase in exhaled NO. Treatment with l ‐NAME and AG did not affect IAR while they significantly blocked LAR (72% and 80% inhibition compared to vehicle) and production of NO (35% and 40% inhibition). On the other hand, treatment with l ‐arginine did not affect IAR but potentiated LAR (74% augmentation). 3 In bronchoalveolar lavage (BAL) fluid, allergen‐induced increases in eosinophils were reduced by 48% for l ‐NAME treatment compared to vehicle, and increased by 56% for l ‐arginine treatment. 4 Treatment with l ‐NAME significantly decreased airway microvascular permeability to both Monastral blue (MB) and Evans blue (EB) dye (50.6% and 44% inhibition). 5 We conclude that allergen‐induced LAR is closely associated with NO production, and that NO plays a critical role in inflammatory cell infiltration and plasma exudation in the allergic condition.British Journal of Pharmacology (1998) 124 , 1019–1028; doi: 10.1038/sj.bjp.0701951