Our studies have revealed, however, that anatomically and physiologically distinct parasympathetic nerves mediate cholinergic contractions and noncholinergic (nitrergic) relaxations of the airways [36–38]. Importantly,reflexes differentially regulate these distinct parasympathetic pathways [34, 39]. The existence of two parasympathetic pathways with opposing actions on the bronchial musculature changes entirely how autonomic nerve-dependent regulation of airway caliber should be viewed. Bronchospasm could be evoked by increases in cholinergic nerve activity or withdrawal of nitrergic neural activity. Conversely, increased nitrergic nerve activity or decreased cholinergic tone could elicit bronchodilatation. The role of the autonomic nervous system in disease must also now be viewed differently.
With distinct neuronal pathways mediating contractions and relaxations of airway smooth muscle, dysfunction or dysregulation of either parasympathetic pathway could account for the alterations in airway tone associated with asthma and COPD (Figure 1).