The precise role of inhibitory nonadrenergic noncholinergic (iNANC) neurons and nitric oxide in airway hyperresponsiveness remains uncertain. The role of NO in the regulation of airway responsiveness was studied in anaesthetized and mechanically ventilated cats. To assess airway responsiveness, the changes in total pulmonary resistance (R(L)) produced by delivering serotonin aerosol to the airways were measured before and after N(ω)-nitro-L-arginine methyl ester (L-NAME), or a ganglionic blocker, hexamethonium, which has been reported to block iNANC. Serotonin was chosen because it causes bronchoconstriction in part by neural reflex. To further clarify the mechanism(s) involved, the effect of inhaled capsaicin was also determined in animals with sustained bronchoconstriction induced by serotonin after treatment with atropine and propranolol. Inhibition of NO synthase by L-NAME or blockade of iNANC neurons by hexamethonium significantly increased airway responsiveness. However, addition of L-NAME did not further increase airway responsiveness in animals treated with hexamethonium. In the presence of atropine and propranolol, inhaled capsaicin caused a marked bronchodilation during serotonin-induced sustained bronchoconstriction. The bronchodilation induced by capsaicin was significantly suppressed by hexamethonium and by L-NAME. These results suggest that the nitric oxide released from inhibitory nonadrenergic noncholinergic neurons is important in modulating the airway responsiveness of cats in vivo.
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