Stimulatory effect of CO2 on vagal bronchopulmonary C-fiber afferents during airway inflammation.
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 mmol.kg(-1).min(-1)) 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.
Dept. of Physiology, Univ. of Kentucky Medical Center, 800 Rose St., Lexington, KY 40536-0298, USA.
Ruei-Lung
RL
Lin
Qihai
Q
Gu
You-Shuei
YS
Lin
Lu-Yuan
LY
Lee
D000138:Acidosis / Q000503:physiopathology; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000503:physiopathology*; D002245:Carbon Dioxide / Q000502:physiology*; D006935:Hypercapnia / Q000503:physiopathology*; D008168:Lung / Q000294:innervation / Q000502:physiology; D008297:Male; D036421:Nerve Fibers, Unmyelinated / Q000502:physiology*; D009475:Neurons, Afferent / Q000502:physiology / Q000648:ultrastructure; D011014:Pneumonia / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020545:Respiratory Mucosa / Q000294:innervation / Q000502:physiology; D014630:Vagus Nerve / Q000166:cytology / Q000502:physiology*
D002245:Carbon Dioxide