Vagal bronchopulmonary C-fibers and acute ventilatory response to inhaled irritants

Experiments were carried out in anesthetized Sprague-Dawley rats to determine the role of vagal bronchopulmonary C-fiber afferents in regulating the respiratory responses to inhaled irritants. Spontaneous inhalation of 2 tidal breaths of a known airway irritant (sulfur dioxide, 0.5%; ammonia, 1%; cigarette smoke, 50%) into the lower airways invariably elicited an immediate and transient inhibitory effect on breathing, characterized by apnea or bradypnea and accompanied by bradycardia, which lasted for 3-8 breaths. A delayed hyperpnea was also induced by inhalation of cigarette smoke, but not by sulfur dioxide or ammonia. After perineural capsaicin treatment of both cervical vagi to selectively block the conduction of capsaicin-sensitive C-fibers, these inhaled irritants no longer evoked any inhibitory effect on breathing; conversely, an augmented inspiration was triggered within the first 3 breaths from the onset of cigarette smoke inhalation in >85% of the rats studied, but after a delay of several breaths following inhalation of ammonia or sulfur dioxide in only 30% of the rats. The augmented breaths were completely abolished when both cervical vagi were cooled to 6-7 degrees C. Bilateral vagotomy eliminated all the immediate responses to these irritants. These results suggest that both vagal C-fiber endings and irritant receptors in the airways are activated by these inhaled irritants, but the more dominant and consistent inhibitory effect on breathing is elicited primarily by stimulation of C-fiber afferents.