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 microg) into the right atrium before and during acute hypoxia (10% O(2) for approximately 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.