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1 Department of Pharmacology, School of Medicine, University of Washington, Seattle, Washington
Hyperpolarization, retardation of rate and secondary acceleration of rate are observed, following direct electrical stimulation of the isolated rabbit sinoatrial node.
The hyperpolarization and negative chronotropic effect are blocked by atropine or hemicholinium, and enhanced by physostigmine.
The positive chronotropic effect is blocked by guanethidine, bretylium, dichloroisoproterenol and pretreatment with reserpine.
Pyrogallol and cocaine augment the intensity and duration of the positive chronotropic response.
The application of nicotine to the node causes a mild inhibition and acceleration of rate. In the presence of hexamethonium the action is depressed.
It is proposed that direct electrical stimulation of the sinoatrial node simulates stimulation of the adrenergic and cholinergic nerves to the heart. The stimulation procedure induces the release of acetylcholine and norepinephrine which elicit the chronotropic phenomenon.
Submitted on February 1, 1962
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