Der Einflu� der Schilddr�senfunktion auf die chronotropen und einige metabolische Wirkungen von Theophyllin und Coffein

Abstract

1. Hyperthyroidism was induced in male rats by daily injections of 0.1 mg/kg triiodothyronine for 3 days, and hypothyroidism by exstirpation of the thyroid gland. Oxygen consumption and heart rate in the hyperthyroid rats were increased by 44 and 30%, respectively, and in the hypothyroid rats decreased by 32 and 10%, respectively. 2. Administration of theophylline (6.6, 20, and 60 mg/kg i.p.) and caffeine (60 mg/kg i.p.) to anaesthetized rats (1.2 g/kg urethane i.m.) lead to a long-lasting increase of oxygen consumption and heart rate. When compared with the effects in euthyroid control animals, the calorigenic and chronotropic actions of theophylline and caffeine were greater in hyperthyroid but smaller in hypothyroid rats. 3. The direct actions of theophylline and caffeine were separated from indirect sympathomimetic effects by experiments in sympathectomized rats (adrenal demedullation and 2 mg/kg reserpine i.p.). Triiodothyronine primarily increased the direct calorigenic and chronotropic actions of the methylxanthines; it enhanced the indirect sympathomimetic actions of caffeine only moderately but did not enhance those of theophyllme. 4. The positive chronotropic actions of theophyllme and caffeine were the same in the isolated atria of euthyroid, hyperthyroid and hypothyroid rats. 5. The different actions of theophyllme and caffeine in eu-, hyper-and hypothyroid rats cannot be explained by differences in the concentration of these methylxanthines hi serum, liver and heart between these groups. 6. Theophyllme and caffeine (60 mg/kg i.p.) increased blood glucose levels in euthyroid and hypothyroid rats by about 50%. However, in hyperthyroid rats theophylline and caffeine (60 mg/kg i.p.) had no effect on the blood glucose concentration. In euthyroid rats, serum free fatty acids were increased by 60 and 77% after theophylline and caffeine, respectively, whereas in hypothyroid rats they were decreased by 41 and 22%, respectively. There was no change in serum free fatty acids after theophylline and caffeine in hyperthyroid animals. 7. We conclude that the thyroid enhances the calorigenic response to the methylxanthines by activation of adenylcyclase and/or inhibition of phosphodiesterase. Cardiac reactions are probably the consequence of altered calorigenio activities.