THYROID STATUS AFFECTS THE RAT CARDIAC BETA-ADRENOCEPTOR SYSTEM TRANSIENTLY AND TIME-DEPENDENTLY

1 The aim of this study was to investigate the time-dependency of the influence of dysthryoid states on the beta-adrenoceptor system in rat heart left ventricle. Therefore, the influence of acute and chronic hy per- and hypothyroidism on beta-adrenoceptor-induced left ventricular responses, beta-adrenoceptor density, cardiac noradrenaline tissue con centrations, G(S)alpha-proteins, and basal and stimulated adenylate cy clase activities was determined. 2 Hyperthyroid rats were obtained by feeding with thyroxine (T4)-containing rat-chow for 1, 4 and 8 weeks. Hypothyroidism was induced by adding 0.05% propylthiouracil (PTU) to t he drinking water. Rats of varying ages were used in order to compensa te for the differences in the duration of the treatments. Rats were ag ed 3 and 5 months at the end of the experiments. 3 Thyroxine treatment for 4 and 8 weeks increased the cardiac sensitivity to isoprenaline, but maximal induced inotropic responses were decreased. Cardiac ventri cular beta-adrenoceptor density was increased only in rats treated wit h T4 for 1 week. This transient effect of hyperthyroidism on cardiac b eta-adrenoceptor density was not observed in older rats, The PTU treat ment resulted in a stable decrease of cardiac beta-adrenoceptor densit y. 4 Left ventricular tissue noradrenaline concentrations were unaffec ted by hyperthyroidism, where a decrease was observed in hypothyroid r ats. Density of G(S)alpha proteins was increased in hearts from chroni c hyperthyroid rats. 5 These results indicate that the increased sensi tivity to beta-adrenoceptor-mediated stimulation in chronic hyperthyro idism cannot be attributed to changes in cardiac beta-adrenoceptor den sity, but is probably caused by an enhanced content of G(S)alpha. Acco rdingly, in hyperthyroidism, the beta-adrenoceptor system is influence d time-dependently, whereas hypothyroidism affects the beta- adrenocep tor system independent of time.