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

Department of Physiology, University of Kentucky Medical Center, Lexington, Kentucky Submitted 6 May 2005 ; accepted in final form 21 June 2005 This study investigated 1 ) whether pulmonary C fibers are activated by a transient increase in the CO 2 concentration of alveolar gas; and 2 ) if the CO 2 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 CO 2 -enriched gas mixture (25–30% CO 2 , 21% O 2 , balance N 2 ) for five to eight breaths, which increased alveolar CO 2 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 E 2 ( n = 12). 4 ) The enhanced C-fiber sensitivity to CO 2 after poly- L -lysine was completely abrogated by infusion of NaHCO 3 (1.82 mmol·kg –1 ·min –1 ) that prevented the reduction in pH during HPC ( n = 6). In conclusion, only a small percentage (