Stimulation of vagal pulmonary C-fibers by adenosine in rats

Adenosine (Ado) causes bronchoconstriction in asthmatic patients and other respiratory complications such as dyspnea. Our recent study has demonstrated that Ado elicits apnea in rats and suggested that vagal afferent C-fibers mediate the response. The present study aimed to determine the effect of Ado on pulmonary C-fibers and the subtypes) of Ado receptors (R) involved. Ado (95-380 μg/kg) injected into the right atrium increased afferent activity in 76% (36/47) of single pulmonary C-fibers in a dose-dependent manner (baseline: 0.01±0.01 imp/s; peak: 4.1±0.6 imp/s; P<0.05). Unlike an immediate-onset (<1.5 s), intense, and short-lasting response to capsaicin (0.5-2 μ5/kg), the response to Ado had a latency of ∼7 s and usually consisted of one to several recurring and milder bursts of action potentials separated by a few seconds. The same dose of Ado injected into the left ventricle either failed to elicit any response or triggered a significantly weaker response (n=6, P<0.08) after an additional delay of 3-6 s, probably caused by recirculating Ado. Aminophylline (20-40 mg/kg, iv), a non-selective Ado-R antagonist, significantly reduced the response to Ado (n=6, P<0.05). DPCPX (10 μg kg^-1 min^-1×10 min, iv), a potent and selective A₁-R antagonist, completely blocked the response (n=4), whereas DMPX (0.1 mg kg^-1 min^-1×10 min, iv), an A₂-R antagonist, was ineffective (n=3). These results provide the first direct evidence that Ado at therapeutic doses stimulates pulmonary C-fiber endings and that A₁-R is involved. This effect of Ado may play a role in the Ado-induced bronchoconstriction and other respiratory complications.