Am. J. Respir. Crit. Care Med., Vol 150, No. 4, Oct 1994, 1019-1025.
Role of nitric oxide and superoxide anions in interleukin-1 beta- induced airway hyperresponsiveness to bradykinin
H Tsukagoshi, RA Robbins, PJ Barnes and KF Chung
Department of Thoracic Medicine, Royal Brompton Hospital, London, United Kingdom.
We investigated the role of endogenous nitric oxide (NO) and superoxide
anions in recombinant human interleukin-1 beta (rhIL-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
(O2-)-generating NADPH oxidase in macrophages and neutrophils, were
administered prior to administration of rhIL-1 beta (500 U)
intratracheally. Aminoguanidine in addition to another inhibitor of NO
synthase, NW-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. rhIL-1 beta-treated rats also demonstrated BHR to BK but not
to ACh, associated with neutrophilia in bronchoalveolar lavage fluid
(BALF). rhIL-1 beta-induced BHR and neutrophilia were neither further
increased by aminoguanidine nor inhibited by L-arginine. Apocynin, however,
significantly inhibited rhIL-1 beta-induced BHR but not the BALF
neutrophilia. Suppression of NO generation and generation of O2- from
macrophages and infiltrating neutrophils may be important in rhIL-1
beta-induced airway hyperresponsiveness to bradykinin.
