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 dysthyroid states on the beta-adrenoceptor system in rat heart left ventricle. Therefore, the influence of acute and chronic hyper- and hypothyroidism on beta-adrenoceptor-induced left ventricular responses, beta-adrenoceptor density, cardiac noradrenaline tissue concentrations, Gs alpha-proteins, and basal and stimulated adenylate cyclase 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 the drinking water. Rats of varying ages were used in order to compensate for the differences in the duration of the treatments. Rats were aged 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 ventricular beta-adrenoceptor density was increased only in rats treated with T4 for 1 week. This transient effect of hyperthyroidism on cardiac beta-adrenoceptor density was not observed in older rats. The PTU treatment resulted in a stable decrease of cardiac beta-adrenoceptor density. 4. Left ventricular tissue noradrenaline concentrations were unaffected by hyperthyroidism, where a decrease was observed in hypothyroid rats. Density of Gs alpha proteins was increased in hearts from chronic hyperthyroid rats. 5. These results indicate that the increased sensitivity to beta-adrenoceptor-mediated stimulation in chronic hyperthyroidism cannot be attributed to changes in cardiac beta-adrenoceptor density, but is probably caused by an enhanced content of Gs alpha. Accordingly, in hyperthyroidism, the beta-adrenoceptor system is influenced time-dependently, whereas hypothyroidism affects the beta-adrenoceptor system independent of time.
Zwaveling
J
J
Department of Pharmacotherapy, University of Amsterdam, The Netherlands.
Batink
H D
HD
Taguchi
K
K
de Jong
J
J
Michel
M C
MC
Pfaffendorf
M
M
van Zwieten
A
A
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D005576:Colforsin / Q000378:metabolism / Q000494:pharmacology; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000276:immunology / Q000378:metabolism; D006352:Heart Ventricles; D006980:Hyperthyroidism / Q000378:metabolism*; D007037:Hypothyroidism / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D015290:Second Messenger Systems; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects
D011943:Receptors, Adrenergic, beta; D005576:Colforsin; D019205:GTP-Binding Protein alpha Subunits, Gs; D000262:Adenylyl Cyclases; D009638:Norepinephrine