ACTIVATION OF PULMONARY C-FIBERS BY ADENOSINE IN ANESTHETIZED RATS - ROLE OF ADENOSINE-A(1) RECEPTORS

1. Intravenous administration of adenosine (Ado) to patients can cause dyspnoea, chest discomfort and bronchoconstriction. To assess the rol e of vagal pulmonary C fibres in evoking these adverse reactions, the effect of Ado on single pulmonary C fibres was studied in anaesthetize d and artificially ventilated rats. 2. Right-atrial injection of Ado ( 320 mu g kg(-1)) activated 68% (73/107) of pulmonary C fibres; the tot al number of action potentials during a period of 15 s increased from a baseline of 0.2 +/- 0.1 impulses to a peak of 16.4 +/- 2.6 impulses (P < 0.01, n = 107) after Ado. Inosine, the metabolite of Ado, did not activate any of eleven C fibres tested in six rats. Furthermore, C fi bres were activated only by right-atrial and not by left-ventricular i njection of the same dose of Ado. 3. Unlike the immediate and transien t stimulation of C fibres by capsaicin, the C fibre stimulation by Ado had a latency of 6.5 +/- 0.3 s (range, 3-18 s) and lasted longer. 4. The stimulation of C fibres by Ado was significantly attenuated by pre treatment with aminophylline, a non-selective Ado receptor antagonist, was completely prevented by 1,3-dipropyl-8-cyclopentylxanthine, an Ad o A(1) receptor antagonist, but was unaffected by 3,7-dimethy-1-propar gylxanthine, an A(2) receptor antagonist. None of these Ado receptor a ntagonists prevented capsaicin-induced C fibre stimulation. 5. In conc lusion, Ado stimulates pulmonary C fibre terminals through an activati on of A(1) receptors. The stimulation of pulmonary C fibres may play a n important role in Ado-induced adverse respiratory effects.