Evidence for reduction of bradykinin-induced bronchoconstriction in guinea-pigs by release of nitric oxide.

1. In this study the influence of nitric oxide (NO) on the bronchoconstriction induced by bradykinin in anaesthetized and artifically ventilated guinea-pigs pretreated with atropine was investigated. 2. Aerosol administration of bradykinin (0.1-1 mM, 40 breaths) caused a dose-dependent increase in lung resistance (RL): maximum increase in RL was 2.5 fold the baseline value. Pretreatment with aerosolized NG-nitro-L-arginine methyl ester (L-NAME) or NG-monomethyl-L-arginine (L-NMMA) (1 mM, 10 breaths every 5 min for 30 min), NO synthase inhibitors, markedly increased the bronchoconstrictor response to bradykinin. L-Arginine, but not D-arginine, (3 mM, 10 breaths every 5 min for 30 min) reversed the hyperresponsiveness to aerosolized bradykinin caused by L-NAME and L-NMMA. 3. L-NAME (1 mM, 10 breaths every 5 min for 30 min) increased the bronchoconstriction induced by intravenous bradykinin (1-10 nmol kg-1). L-Arginine, but not D-arginine, (10 breaths every 5 min for 30 min) reversed the hyperresponsiveness to intravenous bradykinin caused by L-NAME. 4. The increase in RL induced by capsaicin, either aerosol (10 microM, 10 breaths) or i.v. (20 nmol kg-1) was not affected by L-NAME (1 mM, 10 breaths every 5 min for 30 min). Acute resection of the vagi did not affect the bronchoconstriction evoked by bradykinin in guinea-pigs, either in the absence or presence of L-NAME (1 mM, 10 breaths every 5 min for 30 min). 4. These results suggest that, irrespective of the route of administration, bradykinin releases NO or a related molecule which exerts a bronchodilator action that opposes the bronchoconstrictor mechanisms activated by bradykinin itself.