Noncholinergic airway constriction: role of axon reflex and oxygen radicals

In the airways and lungs, activated afferent C-fibers release tachykinins, which induce noncholinergic bronchoconstriction. We have, for several years, focused our research on the role of axon reflex and oxygen radicals in noncholinergic airway constriction in guinea pigs. In this species, the noncholinergic bronchial constriction is not affected by administration of a ganglionic blocking agent, chlorisondamine, indicating that only the afferent C-fiber, not a complete reflex arc, is required for this constriction. Accordingly, we investigated the role of axon reflex by using tetrodotoxin (TTX) and bupivacaine to block impulse conduction in the axon. For the role of oxygen radicals, superoxide dismutase (SOD), catalase (CAT), and dimethylthiourea (DMTU) were employed to scavenge superoxide anion, hydrogen peroxide, and hydroxyl radical, respectively. We used capsaicin, resiniferatoxin (RTX), or hyperventilation to activate afferent C-fibers which, in turn, release tachykinins and lead to noncholinergic airway constriction. The constriction was quantified by measuring the maximal expiratory flow rate (Vmax) and dynamic compliance (Crs). Both capsaicin and RTX caused an immediate decrease in Vmax and Crs, indicating severe bronchoconstriction. This constriction decreased gradually with time. Tachykinin depletion abolished neurotoxin-induced airway constriction, suggesting that tachykinins mediate the constriction. Both TTX and bupivacaine significantly attenuated the constriction at 15-20 min after neurotoxin administration. Therefore, these data suggest that the axon reflex plays an important role in noncholinergic bronchial constriction. In other studies, capsaicin- or hyperventilation-induced bronchoconstriction was abolished by tachykinin depletion, as well as significantly ameliorated by the administration of antioxidants. These data indicate that oxygen radicals modulate the tachykinin-mediated noncholinergic airway constriction.