Beta-adrenoceptor antagonism and the hyperthyroid rat heart.
beta-Adrenoceptor antagonists such as propranolol and atenolol ameliorate the symptoms of human hyperthyroidism. We wished to define whether the cardiac changes of hyperthyroidism are attenuated by treatment with the beta-adrenoceptor antagonist atenolol. Rats were treated with triiodothyronine (T3) [1 mg/kg/day subcutaneously (s.c.) for 14 days] together with oral atenolol (100 mg/day on days 8-14); physiological parameters, inotropic and chronotropic responses in isolated cardiac tissues to compounds that increase intracellular cyclic AMP, and ventricular beta 1- and beta 2-adrenoceptors were measured. Administration of T3 produced marked hyperthyroidism, leading to increased metabolism, cardiac hypertrophy, tachycardia, hypertension, marked decrease in or loss of positive inotropic responses to calcium chloride, norepinephrine (NE), forskolin, and theophylline and increased ventricular beta 1- and beta 2-adrenoceptor density. Atenolol treatment of hyperthyroid rats attenuated the increases in heart rate (HR), rectal temperature, and O2 consumption but did not alter cardiac hypertrophy, hypertension, decreased positive inotropic responses or increased beta-adrenoceptor density. We conclude that beta-adrenoceptor antagonists produce only limited changes in hyperthyroidism-induced cardiovascular responses; furthermore, beta-adrenoceptor antagonists are unlikely to attenuate the cardiovascular risk factors of hyperthyroidism.
Amos
G
G
Department of Physiology and Pharmacology, University of Queensland, Australia.
Kerr
D
D
Sernia
C
C
Brown
L
L
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects*; D006980:Hyperthyroidism / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000032:analysis; D013268:Stimulation, Chemical
D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D001262:Atenolol