Acute hypoxia prolongs the apnea induced by right atrial injection of capsaicin

Inspiratory central drive is augmented by acute hypoxia that leads to a hyperventilation, but it is inhibited by capsaicin (Cap)-induced stimulation of pulmonary C fibers (PCFs) that produces an expiratory apnea. We hypothesized that acute hypoxia should shorten or eliminate the Cap-induced apnea. The ventilatory responses to bolus injection of Cap (0.2-0.5 μg) into the right atrium before and during acute hypoxia (10% O₂ for ∼1 min; Hypoxia+Cap) were compared in anesthetized and spontaneously breathing rats. We found that Cap injection during acute hypoxia produced an extremely long-lasting apnea (69.67 ± 11.97 s) that was 16-fold longer than the apnea induced by Cap alone (expiratory duration = 4.37 ± 0.53 s; P < 0.01). A similar prolonged apnea was also observed during hypoxia in anesthetized guinea pigs. Bilateral vagotomy abolished apneic responses to Cap both before and during hypoxia. Subsequent recording of single-fiber activity of PCFs (PCF_A) showed that acute hypoxia did not significantly affect baseline PCF_A but that it doubled PCF_A responses to Cap via increasing both the firing rate (3.34 ± 0.76 to 7.65 ± 1.32 impulses/s; P < 0.05) and burst duration (1.12 ± 0.18 to 2.32 ± 0.31 s; P < 0.05). These results suggest that acute hypoxia augments PCF-mediated inspiratory inhibition and thereby leads to an extremely long-lasting apnea. This interaction is partially due to hypoxic sensitization of PCF response to Cap.