Stimulatory effect of CO2 on vagal bronchopulmonary C-fiber afferents during airway inflammation

J Appl Physiol (1985). 2005 Nov;99(5):1704-11. doi: 10.1152/japplphysiol.00532.2005. Epub 2005 Jun 30.


This study investigated 1) whether pulmonary C fibers are activated by a transient increase in the CO2 concentration of alveolar gas; and 2) if the CO2 sensitivity of these afferents is altered during airway inflammation. Single-unit pulmonary C-fiber activity was recorded in anesthetized, open-chest rats. Transient alveolar hypercapnia (HPC) was induced by administering a CO2-enriched gas mixture (25-30% CO2, 21% O2, balance N2) for five to eight breaths, which increased alveolar CO2 concentration progressively to near or above 13% for 3-5 s and lowered the arterial pH transiently to 7.10 +/- 0.05. Our results showed the following. 1) HPC evoked only a mild stimulation in a small fraction (4/47) of pulmonary C fibers, and there was no significant change in fiber activity (change in fiber activity = 0.22 +/- 0.16 imp/s; P > 0.1, n = 47). 2) In sharp contrast, after airway exposure to poly-L-lysine, a cationic protein known to induce mucosal injury, the same challenge of transient HPC activated 87.5% of the pulmonary C fibers tested and evoked a distinct stimulatory effect on these afferents (change in fiber activity = 6.59 +/- 1.78 imp/s; P < 0. 01, n = 8). 3) Similar potentiation of the C-fiber response to HPC was also observed after acute exposure to ozone (n = 6) and during a constant infusion of inflammatory mediators such as adenosine (n = 15) or prostaglandin E2 (n = 12). 4) The enhanced C-fiber sensitivity to CO2 after poly-L-lysine was completely abrogated by infusion of NaHCO3 (1.82 that prevented the reduction in pH during HPC (n = 6). In conclusion, only a small percentage (<10%) of the bronchopulmonary C fibers exhibit CO2 sensitivity under control conditions, but alveolar HPC exerts a consistent and pronounced stimulatory effect on the C-fiber endings during airway inflammation. This effect of CO2 is probably mediated through the action of hydrogen ions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acidosis / physiopathology
  • Animals
  • Bronchial Hyperreactivity / physiopathology*
  • Carbon Dioxide / physiology*
  • Hypercapnia / physiopathology*
  • Lung / innervation
  • Lung / physiology
  • Male
  • Nerve Fibers, Unmyelinated / physiology*
  • Neurons, Afferent / physiology
  • Neurons, Afferent / ultrastructure
  • Pneumonia / physiopathology*
  • Rats
  • Rats, Sprague-Dawley
  • Respiratory Mucosa / innervation
  • Respiratory Mucosa / physiology
  • Vagus Nerve / cytology
  • Vagus Nerve / physiology*


  • Carbon Dioxide