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 accu mulates in inflamed airways. However its physiological role has not be en fully elucidated. In this study, we investigated a role for endogen ous NO in allergen-induced airway responses. Sensitised guinea-pigs we re treated with N-G-nitro-L-arginine methyl eater L-NAME (2.0 mM) or a minoguanidine (AG) (2.0 mM) 30 min before the allergen challenge, and 3 and 4 h after the challenge. Alternatively, L-arginine (2.4 mM) trea tment 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 p erformed, and airway responses, NO production, infiltration of inflamm atory 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 increas e in exhaled NO. Treatment with L-NAME and AG did not affect IAR while they significantly blocked LAR (72% and 80% inhibition compared to ve hicle) and production of NO (35% and 40% inhibition). On the other han d, treatment with L-arginine did not affect IAR but potentiated LAR (7 4% augmentation). 3 In bronchoalveolar lavage (BAL) fluid, allergen-in duced increases in eosinophils were reduced by 48% for L-NAME treatmen t compared to vehicle, and increased by 56% for L-arginine treatment. 4 Treatment with L-NAME significantly decreased airway microvascular p ermeability to both Monastral blue (MB) and Evans blue (EB) dye (50.6% and 44% inhibition). 5 We conclude that allergen-induced LAR is close ly associated with NO production, and that NO plays a critical role in inflammatory cell infiltration and plasma exudation in the allergic c ondition.