Role of pulmonary C-fibers in adenosine-induced apnea

The use of adenosine (Ado) in asthmatic patients is associated with pulmonary side effects, namely dyspnea, suggesting possible involvement of pulmonary afferents. Our study aim is to characterize Ado's effects on breathing and to understand the role pulmonary afferents play in these Ado-induced effects In anesthetized and spontaneously breathing rats, we measured respiratory and cardiovascular changes upon bolus injections of Ado at therapeutic doses. Ado (0.3-0.6 mg/kg i.v.) elicited bradycardia and hypotension with a delay of 3-4 s and apnea (T_E= 499.6 ± 92.6% of baseline, BL; mean±SEM, n=21) with an additional delay of 2-3 s. In contrast, capsaicin-induced pulmonary and cardiovascular events occur almost immediately and simultaneously after injection. Perineural treatment of the cervical vagi with capsaicin (150 μg/ml for 20 min) selectively and reversibly blocks conduction through C-fibers. This blockade abolished the Ado-induced apnea (T_E= 103.5 ± 7.67% of BL) and slightly diminished the cardiovascular effects. Left ventricular administration of Ado, bypassing the pulmonary circulation, failed to elicit an apnea (T_E= 91.1 ± 5.1% of BL) and shortened the delay of the cardiovascular events. The A₁-receptor antagonist, DPCPX (10 μg/kg/min for 10 min), decreased the Ado-induced apnea by 85.6% and attenuated the cardiovascular effects. These results indicate that Ado elicits the äpneic response via stimulation of pulmonary C-fibers, and the action involves the A₁-receptor. It is unclear, however, what accounts for the exceedingly long latency (5-7 s) of the apneic response.