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Effect of isoproterenol on physiological and biochemical changes in euthyroid and hyperthyroid rat hearts

University of British Columbia

The effect of triiodothyronine pretreatment on the physiological and biochemical properties of the rat heart was Investigated In a number of cardiac preparations. Pretreatment with triiodothyronine for three days produced an increased chronotropic effect in the isolated right atrium, and a decreased Inotropic effect In the isolated left atrium and Langendorff heart. Following administration of isoproterenol there was a dose-dependent increase in rate of the right atrium. The absolute increase in rate was similar in euthyroid, and hyperthyrold. tissues; the hyperthyroid atria maintained a higher rate than the euthyroid atria, with no sign of supersensitivity. In the electrically stimulated left atrium and right ventricle, isoproterenol produced a dose-dependent increase in tension. The absolute increase in tension was slightly greater in the euthyroid tissues than in the hyperthyrold tissues. In all three preparations, the contractile changes produced by isoproterenol were accompanied by an increase in phosphorylase activity which was similar in euthyroid and hyperthyrold animals. Five nanograms of isoproterenol produced a similar increase in tension in euthyroid and hyperthyrold Langendorff rat hearts. The increase in tension was accompanied by an increase in phosphorylase a activity. This effect of isoproterenol on phosphorylase activation was potentiated in the hyperthyroid hearts. The possibility that the potentiation of phosphorylase activation in the perfused. heart was a result of the increase in coronary blood flow, noted in hearts from hyperthyroid animals, was investigated. Coronary blood flow was reduced in a group of hearts from hyperthyroid animals to the same level as that of hearts from euthyroid animals, and the phosphorylase-activating effect of isoproterenol was again tested. Under these conditions the phosphorylase-actlvating effect of isoproterenol was still enhanced. A pA₂ study carried out on the rat right atrium showed that beta-adrenoceptors in the euthyroid and hyperthyroid state were similar. The data obtained in the present study suggest that the actions of thyroid hormones on the heart do not result in a supersensitivity to the chronotropic or inotropic effects of isoproterenol. In the Langendorff heart preparation a supersensitivity to the phosphorylase-activating effect of isoproterenol was detected, but this same potentiation could not be demonstrated in the right atrium or right ventricle. The reason for the absence of an isoproterenol-induced potentiation of phosphorylase activation in these two preparations, when it can be readily demonstrated in the isolated perfused heart, is not clearly understood but maybe due to tissue damage incurred during dissection. It is suggested that the greater resting rate of hyperthyroid myocardial tissue might be due to a direct action of the thyroid hormones on calcium movements in the sino-atrial node.

Text

2010-02-24

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http://hdl.handle.net/2429/20827

Pharmaceutical Sciences

University of British Columbia

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