THYROID STATUS AND DIETARY FATTY-ACIDS AFFECT BETA-ADRENOCEPTOR AGONIST STIMULATION OF TENSION DEVELOPMENT IN RAT MYOCARDIUM

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 [H-3]-dihydroalprenolol to ventricular membranes was saturable and of high affinity, irrespective of thyroid state and diet. While binding site density (B-max) was not affected by the hypothyroid state or diet, binding affinity (K-d) 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.