Multiple mechanisms of reflex bronchospasm in guinea pigs

The mechanisms of histamine- and bradykinin-induced reflex bronchospasm wer e determined in anesthetized guinea pigs. With intravenous administration, both autacoids evoked dose-dependent increases in trachea cholinergic tone. Vagotomy or atropine prevented these tracheal reflexes. When delivered as an aerosol, bradykinin readily increased tracheal cholinergic tone, whereas histamine aerosols were much less effective at inducing tracheal reflexes. Also, unlike histamine, bradykinin could evoke profound increases in choli nergic tone without directly or indirectly (e.g., prostanoid dependent) ind ucing measurable airway smooth muscle contraction resulting in bronchospasm . Neither autacoid required de novo synthesis of prostanoids or nitric oxid e to induce reflex tracheal contractions. Combined cyclooxygenase inhibitio n and tachykinin-receptor antagonism did, however, abolish all effects of b radykinin in the airways, whereas responses to histamine were unaffected by these pretreatments. The data indicate that histamine and bradykinin initi ate reflex bronchospasm by differential activation of vagal afferent nerve subtypes. We speculate that selective activation of either airway C fibers or airway rapid adapting receptors can initiate reflex bronchospasm.