Cigarette smoke‐inhibition of neurogenic bronchoconstriction in guinea‐pigs in vivo : involvement of exogenous and endogenous nitric oxide

1 We investigated the effect of acute inhalation of cigarette smoke on subsequent non‐adrenergic, non‐cholinergic (NANC) neural bronchoconstriction in anaesthetized guinea‐pigs in vivo by use of pulmonary insufflation pressure (PIP) as an index of airway tone. The contribution of endogenous nitric oxide (NO) was investigated with the NO synthase inhibitor N G ‐nitro‐ L ‐arginine methyl ester ( L ‐NAME). The contribution of plasma exudation to the response was investigated with Evans blue dye as a plasma marker. 2 Inhalation of 50 tidal volumes of cigarette smoke or air had no significant effect on baseline PIP. In the presence of propranolol and atropine (1 mg kg −1 each), electrical stimulation of the vagus nerves in animals given air 30 min previously induced a frequency‐dependent increase in PIP above sham stimulated controls (16 fold increase at 2.5 Hz, 24 fold increase at 10 Hz). In contrast, in smoke‐exposed animals, the increase in subsequent vagally‐induced PIP was markedly less than in the air controls (90% less at 2.5 Hz, 76% less at 10 Hz). 3 L ‐NAME (10 mg kg −1 ), given 10 min before air or smoke, potentiated subsequent vagally‐induced (2.5 Hz) NANC bronchoconstriction by 338% in smoke‐exposed animals, but had no significant effect in air‐exposed animals. The inactive enantiomer D ‐NAME (10 mg kg −1 ) had no effect, and the potentiation by L ‐NAME was partially reversed by the NO‐precursor L ‐arginine (100 mg kg −1 ). Vagal stimulation did not affect the magnitude of vagally‐induced bronchoconstriction 30 min later. 4 Cigarette smoke exposure reduced the magnitude of subsequent bronchoconstriction induced by neurokinin A (NKA) by 37% compared with the effect of NKA in air‐exposed animals. L ‐NAME had no significant effect on the smoke‐induced inhibition of NKA‐induced bronchoconstriction. 5 Vagally‐induced plasma exudation in the main bronchi was greater in smoke‐exposed animals compared with air‐exposed animals (120% greater at 2.5 Hz, 82% greater at 10 Hz). 6 We conclude that cigarette smoke‐induced inhibition of subsequent NANC neurogenic bronchoconstriction is not associated with inhibition of airway plasma exudation and is mediated in part via exogenous smoke‐derived NO, or another bronchoprotective molecule, and by endogenous NO.British Journal of Pharmacology (1997) 122 , 779–785; doi: 10.1038/sj.bjp.0701440