title: Acute hypoxia prolongs the apnea induced by right atrial injection of capsaicin.
abstract: 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.
authors.affiliation: Department of Physiology, University of Kentucky, Lexington, Kentucky 40536, USA. fxu@lrri.org
authors.forename: Fadi
authors.initials: F
authors.lastname: Xu
authors.forename: Qi-Hai
authors.initials: QH
authors.lastname: Gu
authors.forename: Tongrong
authors.initials: T
authors.lastname: Zhou
authors.forename: Lu-Yuan
authors.initials: LY
authors.lastname: Lee
mesh_terms: D000208:Acute Disease; D000818:Animals; D001049:Apnea / Q000097:blood / Q000139:chemically induced* / Q000150:complications / Q000503:physiopathology*; D001158:Arteries; D002211:Capsaicin / Q000008:administration & dosage*; D005740:Gases / Q000097:blood; D006168:Guinea Pigs; D006321:Heart / Q000503:physiopathology; D006325:Heart Atria; D000860:Hypoxia / Q000150:complications*; D007267:Injections; D008168:Lung / Q000294:innervation; D036421:Nerve Fibers, Unmyelinated; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration / Q000187:drug effects; D014628:Vagotomy
chemical_list: D005740:Gases; D002211:Capsaicin