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 is olated from hypothyroid rats and euthyroid controls that had been fed diets enriched in either n-6 or n-3 fatty acids. 2 In hypothyroid anim als fed the n-6 diet, the maximum developed tension in the presence of isoprenaline was only 54% greater than resting tension compared to 16 0% 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. max imum tension was significantly greater in both hypothyroid and euthyro id animals fed the n-3 diet, but tension was depressed in the hypothyr oid state. 3 Binding of the beta-adrenoceptor antagonist [H-3]-dihydro alprenolol 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 affi nity (K-d) was higher in hypothyroid animals fed the n-6 diet. 4 The i notropic response to forskolin was the same in hypothyroid animals, ir respective of diet, but maximum developed tension was significantly gr eater in euthyroid animals fed the n-6 compared to the n-3 diet. The d ose-response curve for forskolin was shifted to the right in hypothyro id animals fed the n-3 diet indicating a decrease in sensitivity. 5 Th ese results indicate that the depressed contractility in the hypothyro id heart may be due in part to an altered lipid environment of the bet a-adrenoceptor complex and that n-3 fatty acids can significantly incr ease maximum developed tension in the hypothyLroid state.