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 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. 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.
Department of Pulmonary Medicine, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan.
H
H
Iijima
Y
Y
Uchida
T
T
Endo
A
A
Xiang
M
M
Shirato
A
A
Nomura
S
S
Hasegawa
D000485:Allergens / Q000276:immunology*; D000818:Animals; D001980:Bronchi / Q000276:immunology* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005119:Extravasation of Diagnostic and Therapeutic Materials; D005260:Female; D006146:Guanidines / Q000494:pharmacology; D006168:Guinea Pigs; D008854:Microscopy, Electron; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D014132:Trachea / Q000276:immunology* / Q000503:physiopathology / Q000648:ultrastructure
D000485:Allergens; D004791:Enzyme Inhibitors; D006146:Guanidines; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester