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The effect of thyroidectomy on the responsiveness of rat atria to adrenergic amines

University of British Columbia

To examine effects of thyroid state on cardiac adrenoceptor sensitivity, left and right atria isolated from male euthyroid and hypothyroid rats were exposed to the agonists methoxamine, isoproterenol and phenylephrine and to the antagonists (10⁻⁶M) phenoxybenzamine, phentolamine and propranolol. Isoproterenol and phenylephrine increased rate and force of both euthyroid and hypothyroid atria. Methoxamine also increased force of euthyroid and hypothyroid atria, but increased the rate of hypothyroid atria only. In all cases in which a response was observed, the hypothyroid state increased the potency of methoxamine and of phenylephrine, and decreased the potency of isoproterenol. The hypothyroid state also increased the inotropic and chronotropic effectiveness of methoxamine, but did not alter the maximum responses to phenylephrine or isoproterenol. Phenoxybenzamine abolished all responses to methoxamine, but only partially inhibited the effects of phenylephrine. Propranolol had no effect on the responses to methoxamine, blocked the chronotropic response to phenylephrine, and blocked the inotropic and chronotropic responses to isoproterenol. In the presence of the cholinergic agonist carbachol, the basal rate and force of euthyroid right and left atria, respectively, were decreased to the basal level observed in the hypothyroid controls. Methoxamine was found to increase both rate and force in the treated euthyroid atria similar to that observed in the hypothyroid controls. Conversely, in the presence of the adrenergic agonist isoproterenol, the basal rate and force of hypothyroid right and left atria, respectively, were increased to the basal level observed in the euthyroid controls. The hypothyroid atria then responded to methoxamine as was observed in the euthyroid right and left atria. Methoxamine was found to have no effect on cyclic AMP production in either the euthyroid or hypothyroid left or right atria, even though a greater increase in both rate and force was observed in the hypothyroid right and left atria, respectively, as compared to the euthyroid atria. While the hypothyroid state decreased the potency of isoproterenol on the force of contraction and atrial rate, it did not affect the cyclic AMP response to this beta adrenoceptor agonist. Isoproterenol increased cyclic AMP production, rate and force to the same extent in both the euthyroid and hypothyroid right and left atria. The data of the present study do not support the hypothesis that rat heart adrenoceptors undergo a conversion from beta to alpha in the hypothyroid state, in terms of cyclic AMP production, atrial rate and force development. The data do, however, support the hypothesis that there is an increased alpha adrenoceptor responsiveness in the hypothyroid state as compared to the euthyroid state.

Text

2010-03-23

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http://hdl.handle.net/2429/22378

Pharmaceutical Sciences

University of British Columbia

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