BETA-ADRENOCEPTOR ANTAGONISM AND THE HYPERTHYROID RAT-HEART

beta-Adrenoceptor antagonists such as propranolol and atenolol amelior ate the symptoms of human hyperthyroidism. We wished to define whether the cardiac changes of hyperthyroidism are attenuated by treatment wi th the beta-adrenoceptor antagonist atenolol. Rats were treated with t riiodothyronine (T-3) [1 mg/kg/day subcutaneously (s.c.) for 14 days] together with oral atenolol (100 mg/day on days 8-14); physiological p arameters, inotropic and chronotropic responses in isolated cardiac ti ssues to compounds that increase intracellular cyclic AMP, and ventric ular beta(1)- and beta(2)-adrenoceptors were measured. Administration of T-3 produced marked hyperthyroidism, leading to increased metabolis m, cardiac hypertrophy, tachycardia, hypertension, marked decrease in or loss of positive inotropic responses to calcium chloride, norepinep hrine (NE), forskolin, and theophylline and increased ventricular beta (1)- and beta(2)-adrenoceptor density. Atenolol treatment of hyperthyr oid rats attenuated the increases in heart rate (HR), rectal temperatu re, and O-2 consumption but did not alter cardiac hypertrophy, hyperte nsion, decreased positive inotropic responses or increased beta-adreno ceptor density. We conclude that beta-adrenoceptor antagonists produce only limited changes in hyperthyroidism-induced cardiovascular respon ses; furthermore, beta-adrenoceptor antagonists are unlikely to attenu ate the cardiovascular risk factors of hyperthyroidism.