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

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Abstract
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 NG‐nitro‐l‐arginine methyl ester l‐NAME (2.0 mm) or aminoguanidine (AG) (2.0 mm) 30 min before the allergen challenge, and 3 and 4 h after the challenge. Alternatively, l‐arginine (2.4 mm) 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. 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). 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. Treatment with l‐NAME significantly decreased airway microvascular permeability to both Monastral blue (MB) and Evans blue (EB) dye (50.6% and 44% inhibition). 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