Consequences of capsaicin treatment on pulmonary vagal reflexes and chemoreceptor activity in lambs

The aim of this study was to test the hypothesis that capsaicin treatment in lambs selectively inhibits bronchopulmonary C-fiber function but does not alter other vagal pulmonary receptor functions or peripheral and central chemoreceptor functions. Eleven lambs were randomized to receive a subcutaneous injection of either 25 mg/kg capsaicin (6 lambs) or solvent (5 lambs) under general anesthesia. Capsaicin-treated lambs did not demonstrate the classical ventilatory response consistently observed in response to capsaicin bolus intravenous injection in control lambs. Moreover, the ventilatory responses to stimulation of the rapidly adapting pulmonary stretch receptors (intratracheal water instillation) and slowly adapting pulmonary stretch receptors (Hering-Breuer inflation reflex) were similar in both groups of lambs. Finally, the ventilatory responses to various stimuli and depressants of carotid body activity and to central chemoreceptor stimulation (CO2 rebreathing) were identical in control and capsaicin-treated lambs. We conclude that 25 mg/kg capsaicin treatment in lambs selectively inhibits bronchopulmonary C-fiber function without significantly affecting the other vagal pulmonary receptor functions or that of peripheral and central chemoreceptors.

CO2-sensitive olfactory and pulmonary receptor modulation of episodic breathing in bullfrogs

Breathing was monitored during normocarbia, hypercarbia (6% CO2 in air), and the period immediately after the return to normocarbic conditions in intact, olfactory-denervated, and vagotomized bullfrogs. In intact frogs, ventilation increased during hypercarbia, but the breathing pattern remained episodic. Immediately upon return to air, there was a further paradoxical increase in breathing frequency, and breathing became continuous in most frogs. Results obtained from animals after olfactory receptor denervation indicate that tonic stimulation of olfactory receptors by airway CO2 inhibited breathing during hypercarbia. Measurements of the kinetics of changes in airway and arterial blood CO2 levels support the suggestion that the sudden release of this inhibition on the return to normocarbic conditions was responsible for the posthypercarbic hyperpnea. Vagotomy increased ventilation during normocarbia. Hypercarbia now caused a change in breathing pattern but had no net effect on total ventilation, suggesting that pulmonary vagal feedback inhibited ventilation during normocarbia but stimulated ventilation during hypercarbia. Although olfactory and pulmonary receptor feed-back shape the breathing pattern, they were not responsible for initiating or terminating the episodes of breathing.

Laryngeal Regulation of Airway Resistance

The response of laryngeal airway resistance to pulmonary receptor stimulation was studied in 20 mongrel dogs anesthetized with α-chloralose (80 mg/kg). Stimulation of pulmonary stretch receptors by lung inflation inhibited the phasic variation of laryngeal resistance during respiration and produced a sustained reduction of laryngeal resistance, which was related to lung inflation pressure. Stimulation of pulmonary J-receptors with capsaicin produced apnea and a large increase in laryngeal resistance. Capsaicin produced this reflex when injected into the pulmonary circulation but not when injected into the systemic circulation. Irritant receptor stimulation with histamine hydrochloride produced tachypnea and a reduction in inspiratory laryngeal resistance. Pulmonary receptor reflexes were abolished by dividing the vagus nerves distal to the origin of the recurrent laryngeal nerves. Laryngeal reflexes may be important in the regulation of respiration and the production of physiologic and pathologic alterations in pulmonary function.