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Thyroid-dependent alterations of myocardial adrenoceptors and adrenoceptor-mediated responses in the rat

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Summary

Cardiovascular alterations in hypo- and hyperthyroidism have been ascribed to changes of noradrenergic neurotransmission. In the present study the influence of thyroid hormones on adrenoceptors in the rat heart was further characterized. The effect of artificial hypothyroidism (induced by feeding 6-propyl-2-thiouracil, PTU) and hyperthyroidism (induced by daily injections of triiodothyronine, T3) on myocardial adrenoceptor binding, catecholamines, some physiological responses, and their interdependence was examined.

  1. 1.

    The density of myocardial β-adrenergic binding sites (3H-dihydroalprenolol, 3H-DHA) was reduced after PTU (by 38%) and enhanced after T3 treatment (by up to 82%). The increase was dose- and time-dependent and reversible within 4 days. No changes of the affinity of 3H-DHA to its binding sites were observed. Only L-T3 and L-T4 proved to be active, D-T3 and reverse T3 had no effect. The rise in β-adrenoceptor density caused by T3 was prevented by concomitant administration of cycloheximide, indicating its dependence on protein synthesis.

  2. 2.

    The density of myocardial α 1-adrenergic binding sites (3H-prazosin) was significantly reduced in the PTU group (by up to 28%) and even more distinctly by T3 treatment (by up to 50%). K D values remained unaltered.

  3. 3.

    The noradrenaline content and turnover of rat hearts was significantly reduced by T3-induced hyperthyroidism. PTU treatment had no influence on content and turnover of noradrenaline. Plasma noradrenaline as well as adrenaline levels in freely moving rats were increased by PTU treatment 9- and 5-fold, respectively. In T3-injected animals no significant changes were measured.

  4. 4.

    The density of adrenoceptors is known to be inversely correlated with catecholamine levels in several organs. Neither α- nor β-adrenoceptor changes in the myocardium of dysthyroid rats could be attributed to such a homologous regulation, since they still occurred after chemical sympathectomy with 6-hydroxydopamine and adrenalectomy.

  5. 5.

    Hypertrophy of the heart due to T3 could not be explained by prolonged β-adrenergic stimulation because it was not inhibited by 6-hydroxydopamine or high doses of propranolol. A T3-induced tachycardia was recorded in pithed and in intact rats. It was not reduced to normal levels by the β-adrenoceptor antagonist sotalol and, thus, was independent of sympathetic influence. Hypothyroid pithed rats displayed a marked bradycardia, whereas in intact hypothyroid animals a normal heart rate was measured at rest. Obviously, an enhanced availability of catecholamines which seems to reflect an increased release and/or a central nervous compensatory mechanism was responsible for the maintenance of the normal heart rate.

  6. 6.

    In pithed rats the β-adrenoceptor-mediated increase in heart rate was attenuated by PTU treatment. The isoprenaline dose-response curve was shifted to the right, the maximal response was reduced. After T3 injections, the sensitivity to isoprenaline was not affected, but the maximal heart rate that could be obtained was increased. These results are compatible with the β-adrenoceptor changes described above.

It is concluded that cardiovascular signs of hypo- and hyperthyroidism can only be explained by a complex interaction of several factors. Beside the changes of adrenoceptor density and an altered sensitivity to noradrenaline, a central nervous regulation and subsequent changes of catecholamine release as well as effects independent of the sympathetic nervous system have to be considered.

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  1. Pharmakologisches Institut des Universitätsklinikums Essen, Hufelandstrasse 55, D-4300, Essen 1, Federal Republic of Germany

    Gerhard Gross & Inge Lues

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  1. Gerhard Gross
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This work was supported by the Deutsche Forschungsgemeinschaft

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Gross, G., Lues, I. Thyroid-dependent alterations of myocardial adrenoceptors and adrenoceptor-mediated responses in the rat. Naunyn-Schmiedeberg's Arch. Pharmacol. 329, 427–439 (1985). https://doi.org/10.1007/BF00496378

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