A unique pressor response to isoprenaline in the pithed rat during triiodo-L-thyronine(T3)-induced hyperthyroidism.

Thyroid hormone appears to be involved in the regulation of beta-adrenoceptors affecting cardiovascular performance. In the present study, the influence of hyperthyroidism on beta-adrenoceptor-mediated response of the cardiovascular system was investigated in vivo using the pithed rat preparation. Hyperthyroidism was induced by triiodothyronine injections (500 micrograms/kg, i.p.) for 6 days. A markedly accelerated basal heart rate and a wider pulse pressure with a significantly elevated systolic blood pressure were observed in hyperthyroid pithed rats. Although the basal and the maximal heart rates were increased in hyperthyroid rats, EC50 of the heart rate response to isoprenaline did not significantly differ between euthyroid and hyperthyroid pithed animals. Markedly different responses of blood pressure to isoprenaline were obtained in the two groups; isoprenaline caused a dose-dependent decrease in diastolic pressure in euthyroid pithed rats, whereas it produced pressor response in hyperthyroid pithed rats. This unique pressor response to isoprenaline observed in hyperthyroid pithed rats was abolished by the beta 1-adrenoceptor selective antagonist metoprolol but not by the alpha-adrenoceptor antagonist phenoxybenzamine. The density of myocardial binding sites of the beta-type was markedly increased after T3 treatment (65%), whereas that of the mesenteric artery was not altered. The results indicate that thyroid hormone exerts different effects on cardiac and vascular beta-adrenoceptors, and this different susceptibility to thyroid hormone may in part be responsible for the altered response of blood pressure to isoprenaline seen in hyperthyroid pithed rats.