ROLE OF NITRIC-OXIDE AND SUPEROXIDE ANIONS IN INTERLEUKIN-1-BETA-INDUCED AIRWAY HYPERRESPONSIVENESS TO BRADYKININ

We investigated the role of endogenous nitric oxide (NO) and superoxide anions in recombinant human interleukin-1 beta (rhlL-1 beta)-induced bronchial hyperresponsiveness (BHR) and neutrophilia in Brown-Norway rats. Aminoguanidine (100 mg/kg/d) administered subcutaneously for 3 d, an inhibitor of inducible NO synthase, L-arginine (100 mg/kg/d administered subcutaneously for 3 d, a specific precursor for the synthesis of NO and apocynin (5 mg/kg/orally), an inhibitor of superoxide anion (O-2(-))-generating NADPH oxidase in macrophages and neutrophils, were administered prior to administration of rhlL-1 beta (500 U) intratracheally. Aminoguanidine in addition to another inhibitor of NO synthase, N-W-nitro-L-arginine methyl ester (L-NAME) 100 mg kg/d administered subcutaneously for 3 d augmented bronchial responsiveness to inhaled bradykinin (BK) but not to acetylcholine (ACh), an effect reversed by L-arginine. rhlL-1 beta-treated rats also demonstrated BHR to BK but not to ACh, associated with neutrophilia in bronchoalveolar lavage fluid (BALF). rhlL-1 beta-induced BHR and neutrophilia were neither further increased by aminoguanidine nor inhibited by L-arginine. Apocynin, however, significantly inhibited rhlL-1 beta-induced BHR but not the BALF neutrophilia. Suppression of NO generation and generation of O-2(-) from macrophages and infiltrating neutrophils may be important in rhlL-1 beta-induced airway hyperresponsiveness to bradykinin.