Effects of adenosine and its analogues on ventricular automaticity induced by a local injury: role of catecholamines and of cyclic AMP.

The effect of adenosine and its analogues, 5'-N-ethyl-carboxamide adenosine (NECA), L-N6-phenylisopropyladenosine (L-PIA) and 2-chloroadenosine (CADO) on ventricular automaticity induced by a local injury, has been studied in the isolated right ventricle of the rat. Adenosine had both excitatory and inhibitory actions on ventricular automaticity, the excitatory action being observed with lower concentrations of adenosine. The adenosine analogues NECA and CADO, mimicked the excitatory action of adenosine on ventricular automaticity, with NECA being much more potent than CADO. NECA and CADO also had inhibitory effects on ventricular automaticity, with CADO being more potent than NECA. L-PIA only caused inhibitory effects on ventricular automaticity. In reserpinized animals, adenosine did not cause any excitatory effect on ventricular automaticity, and the inhibitory action of adenosine was potentiated. In the presence of propranolol, adenosine also did not exhibit its excitatory effect on ventricular automaticity. In reserpinized rats, noradrenaline restored the excitatory action of adenosine on ventricular automaticity. In the presence of dibutyryl cyclic AMP, adenosine only caused excitatory effects on ventricular automaticity in reserpinized rats. The results suggest the involvement of catecholamines in the excitatory action of adenosine on ventricular automaticity, an effect probably linked to accumulation of intracellular cyclic AMP.