Regression of thyroid hormone induced cardiac hypertrophy: effect on cardiac beta receptors and adenyl cyclase activity.
Adrenergic mechanisms may be important in the symptomatic manifestations of hyperthyroidism. The chronic administration of thyroid hormone also results in cardiac hypertrophy and increased numbers of beta-adrenergic receptors in cardiac membranes. The roles of adrenergic mechanisms in the initiation and perpetuation of this hypertrophy has been open to speculation. Rats treated chronically with L-thyroxin were sacrificed after 7 days of treatment and 1-4 days after cessation of treatment. Hearts were removed and weighed and norepinephrine measured. In other groups of identically treated rats, membranes were prepared from the left ventricle for in vitro measurements of beta-adrenergic receptor characteristics and adenyl cyclase activity. Regression of cardiac hypertrophy with a decrease in receptor number to control values was seen as early as 2 days after stopping thyroxine. Cardiac norepinephrine concentrations had also returned to control values at this time. Displacement of bound [H3] dihydroalprenolol by isoproterenol was not changed from control. Basal and isoproterenol stimulated adenyl cyclase activity was not changed by thyroxine administration or its cessation. The rapid reversal of the increased beta-adrenergic receptor number and cardiac hypertrophy raises the possibility that thyroid hormone may play a regulatory role in cardiac function. Although the enhancement of myocardial contractility by thyroid hormone may be mediated through cardiac hypertrophy this effect of thyroid hormone is independent of the catecholamine sensitive adenyl cyclase system.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced / Q000503:physiopathology*; D002462:Cell Membrane / Q000378:metabolism; D004082:Dihydroalprenolol / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D013974:Thyroxine / Q000097:blood / Q000633:toxicity*; D014284:Triiodothyronine / Q000097:blood
D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D014284:Triiodothyronine; D004082:Dihydroalprenolol; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D013974:Thyroxine