Abstract
Direct perfusion of the sinus node artery under a constant pressure of 100mm Hg was arranged in the canine heart in vivo. The administration of dopamine, norepinephrine or epinephrine from 1 to 10μg into the sinus node artery often induced a deceleration of the sinus rhythm, but isoproterenol never caused such a paradoxical response. The higher the dose given, the more frequently was this paradoxical response observed. The participation of a cholinergic mechanism in this paradoxical response was proved by blocking it with atropine and by enhancing it with physostigmine. Furthermore such paradoxical responses were blocked by treatment with hemicholinium, hexamethonium or phenoxybenzamine, none of which blocked the muscarinic action of acetylcholine. The blocking effect of phenoxybenzamine was persistent and selective. The authors assume that naturally occurring catecholamines stimulate the cholinergic neuron at the presynaptic site through the α-receptors and thus, they are cholinergic in effect, causing the paradoxical response of the sinoatrial node.
