Mechanism of the apparent parasympathetic inhibition of adenosine induced heart rate slowing in the dog

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Abstract
The inhibitory action of intravenously administered adenosine on the sinoatrial (SA) node is not expressed in the conscious dog in the presence of normal vagal tone. After pharmacological or surgical parasympathetic blockade, however, adenosine exerts a powerful negative chronotropic effect. In order to determine the reason why this action of adenosine is blocked by the intact parasympathetic nervous system, we measured the chronotropic effects of adenosine while applying a constant cholinergic stimulus to the SA node. In conscious dogs during a systemic infusion of acetylcholine at a rate sufficient by itself to inhibit the SA node, intravenous adenosine injections caused further dose dependent reductions in heart rate. In anaesthetised, vagotomised dogs, intravenous adenosine caused similar negative chronotropic effects with or without concomitant electrical stimulation of the vagus nerve. As an example, 5 μmol·kg−1 adenosine reduced heart rate by 22 (SEM 4)% from a baseline heart rate of 172(10) beats·min−1; when heart rate was lowered to 66(1) beats·min−1 by electrical vagal stimulation, this dose of adenosine reduced heart rate by 36(8)%. Propranolol had no effect on these responses. We conclude that there is no direct cholinergic inhibition of the negative chronotropic action of adenosine on the canine SA node but rather that the inhibitory action of systemically administered adenosine on the SA node is simply masked by the withdrawal of vagal tone in response to the arterial hypotension resulting from this mode of adenosine administration.