STUDIES ON THE NEGATIVE CHRONOTROPIC RESPONSE TO VAGAL STIMULATION IN HYPERTHYROID RATS

¹ University of Pennsylvania School of Medicine, Department of Pharmacology, Philadelphia, Pennsylvania

The mechanism for the decreased negative chronotropic response to vagal stimulation in hyperthyroid rats was investigated. It was found that in thyroxine-treated animals, blockade of sympathetic activity by administration of bretylium (5 mg/kg) and/or elimination of circulating catecholamines through adrenal demedullation only partially restored the chronotropic response to vagal stimulation. Since choline acetyltransferase activity, measured in vitro in atrial tissue from hyperthyroid rats, was not significantly different from that observed in atria from euthyroid animals, the impaired response to vagal excitation could not be attributed to an alteration in concentration of this enzyme. Free plasma calcium, determined anaerobically with the Orion Calcium Activity Flow Thru System, was 6% below normal in hyperthyroid rats. Temporal separation of the effects of thyroxine on free plasma calcium from the appearance of impaired responses to vagal stimulation indicated that the reduction in free plasma calcium was not the cause of the defect in the response of the heart to vagal excitation. Infusion of choline chloride (10 mM) into thyrotoxic rats restored to normal the negative chronotropic response produced by vagal stimulation. Possible mechanisms for the action of choline are suggested.