Thyroid status and dietary fatty acids affect beta-adrenoceptor agonist stimulation of tension development in rat...

1. The inotropic responses to the beta-adrenoceptor agonists adrenaline, noradrenaline and isoprenaline were examined in papillary muscles isolated from hypothyroid rats and euthyroid controls that had been fed diets enriched in either n-6 or n-3 fatty acids. 2. In hypothyroid animals fed the n-6 diet, the maximum developed tension in the presence of isoprenaline was only 54% greater than resting tension compared to 160% in euthyroid animals. Maximum tension was 105% greater than resting in hypothyroid animals fed the n-3 diet compared to 399% in controls. Similar responses to adrenaline and noradrenaline were seen, i.e. maximum tension was significantly greater in both hypothyroid and euthyroid animals fed the n-3 diet, but tension was depressed in the hypothyroid state. 3. Binding of the beta-adrenoceptor antagonist [3H]-dihydroalprenolol to ventricular membranes was saturable and of high affinity, irrespective of thyroid state and diet. While binding site density (Bmax) was not affected by the hypothyroid state or diet, binding affinity (Kd) was higher in hypothyroid animals fed the n-6 diet. 4. The inotropic response to forskolin was the same in hypothyroid animals, irrespective of diet, but maximum developed tension was significantly greater in euthyroid animals fed the n-6 compared to the n-3 diet. The dose-response curve for forskolin was shifted to the right in hypothyroid animals fed the n-3 diet indicating a decrease in sensitivity. 5. These results indicate that the depressed contractility in the hypothyroid heart may be due in part to an altered lipid environment of the beta-adrenoceptor complex and that n-3 fatty acids can significantly increase maximum developed tension in the hypothyLroid state.