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Notes: Summary The influence of thyroid hormones on the concentration and properties of α1-adrenoceptors in a crude membrane fraction obtained from the rat cerebral cortex was investigated using the [3H]-WB 4101 binding assay. Animals were made hypothyroid by feeding 6-propyl-2-thiouracil for 8 weeks. Hyperthyroidism was induced by triiodothyronine injections (50 μg/100 g body weight) for 9 days. 1. The binding of [3H]-WB 4101 was saturable and of high affinity in controls as well as in hyper- and hypothyroid animals. The maximal number of binding sites (B max), which amounted to 95 fmol/mg protein in control animals, was increased by 27% in cortical membranes from hyperthyroid rats and reduced by 23% in the hypothyroid group. 2. The reduction in [3H]-WB 4101 binding due to 6-propyl-2-thiouracil feeding was reversible by triiodothyronine treatment. 3. Dissociation constants (K D) calculated from saturation experiments (0.25 nM) or kinetic data (0.21 nM) remained unchanged in altered thyroid states. 4. Inhibition of [3H]-WB 4101 binding by adrenergic agonists and antagonists revealed no differences between euthyroid and hypothyroid animals. The higher affinity of prazosin to the binding sites compared with yohimbine indicated that [3H]-WB 4101 predominantly labeled α1-adrenoceptors. It is concluded that thyroid hormones regulate the number of α1-adrenoceptors in membranes of the rat cerebral cortex, leaving their affinities unchanged.

Notes: 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. 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. 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. 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. 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. 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. 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.

Notes: Summary Altered thyroid states are known to produce profound changes in sympathetic mechanisms. The influence of thyroid hormones on plasma catecholamines, adrenal catecholamines and on circulatory parameters were studied in pithed rats. Animals were made hypothyroid by feeding 6-propyl-2-thiouracil for 6 weeks. Hyperthyroidism was induced by triiodothyronine injections (0.5 mg/kg body weight) for 7 days. 1. The basal heart rate was decreased in hypothyroidism and accelerated in hyperthyroidism. Basal diastolic blood pressure was reduced in both dysthyroid states. 2. Electrical stimulation of autonomic outflow from the spinal cord induced tachycardia and increased diastolic blood pressure. The increase in heart rate due to electrical stimulation was reduced in hypo- and hyperthyroidism. In hyperthyroid animals this may be due to the already accelerated basal heart rate. The initial rise in diastolic blood pressure was decreased in the hypothyroid and increased in the hyperthyroid state. 3. Basal adrenaline plasma levels were higher than control values in hypothyroidism and unaltered in hyperthyroidism. Basal noradrenaline levels were not significantly influenced by either thyroid state. 4. The increase in plasma noradrenaline during electrical stimulation was enhanced in hyperthyroid animals and remained unaltered by hypothyroidism. 5. The increase in plasma adrenaline during electrical stimulation was significantly changed in both dysthyroid states. Hyperthyroidism reduced the initial peak of adrenaline release. Hypothyroidism raised plasma adrenaline in the steady state after sustained stimulation. 6. Elevated basal and stimulated adrenaline plasma levels corresponded to an increased adrenaline content and enhanced phenylethanolamine-N-methyltransferase activity in adrenal glands of hypothyroid rats. The significant influence of thyroid hormones on plasma catecholamines seems to contribute but cannot explain completely the circulatory changes in hypo- and hyperthyroidism. The role of additional factors such as receptor changes and central nervous mechanisms is discussed.