Thyroid-dependent alterations of myocardial adrenoceptors and adrenoceptor-mediated responses in the rat.
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. The density of myocardial beta-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 beta-adrenoceptor density caused by T3 was prevented by concomitant administration of cycloheximide, indicating its dependence on protein synthesis. The density of myocardial alpha 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%). KD values remained unaltered. 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. The density of adrenoceptors is known to be inversely correlated with catecholamine levels in several organs. Neither alpha- nor beta-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.(ABSTRACT TRUNCATED AT 400 WORDS)
D000818:Animals; D003513:Cycloheximide / Q000494:pharmacology; D003655:Decerebrate State; D004082:Dihydroalprenolol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006339:Heart Rate; D006980:Hyperthyroidism / Q000378:metabolism*; D007037:Hypothyroidism / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D011224:Prazosin / Q000378:metabolism; D011441:Propylthiouracil / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000378:metabolism*; D013997:Time Factors; D014284:Triiodothyronine / Q000494:pharmacology
D011941:Receptors, Adrenergic; D014284:Triiodothyronine; D004082:Dihydroalprenolol; D011441:Propylthiouracil; D003513:Cycloheximide; D009638:Norepinephrine; D011224:Prazosin