Beta-adrenergic receptors, adenylate cyclase activation, and myofibril enzyme activity in hypothyroid rats.
A previous study in intact animals assessed cardiovascular alterations in surgically thyroidectomized rats. Hemodynamic challenge via isoproterenol infusion identified abnormal left ventricular relaxation. Challenge by aortic occlusion revealed a latent deficiency in left ventricular contractility which was not apparent during beta-agonist challenge. The present study utilized left ventricular cardiac tissue obtained from the identical control and thyroidectomized animals from which intact heart hemodynamic information had been obtained. Biochemical systems were selected for evaluation based on demonstrated hemodynamic alterations, i.e., beta-adrenergic receptor number/function and contractile protein enzyme properties. The number of beta-receptors on hypothyroid cardiac membranes was significantly decreased, but receptor agonist affinity was not influenced. Basal adenylate cyclase activity in cardiac membranes from control and thyroidectomized rats was nearly identical; however, isoproterenol activation was diminished in hypothyroid cardiac membrane, particularly at the higher levels of beta-agonist stimulation. Adenylate cyclase enzyme activation by forskolin was not influenced by thyroidectomy; however, activation by sodium fluoride was reduced approximately 30% when compared with preparations from control rats. Cardiac myofibrillar enzyme activity for adenosinetriphosphatase (ATPase) was significantly lower in thyroidectomized rats. Despite reduced ATPase activity, myofibrillar calcium sensitivity was unaltered. Myofibrillar creatine kinase enzyme activity was not influenced by thyroidectomy; therefore, compartmentalized ATP regeneration potential via creatine kinase was enhanced relative to substrate utilization via ATPase. Thus hemodynamically significant cardiac influences of hypothyroidism are mediated, at least in part, via 1) reduced beta-receptor number, 2) diminished catecholamine-induced activation of adenylate cyclase, and 3) reduced myofibrillar ATPase activity.
Dowell
R T
RT
Department of Physiology and Biophysics, University of Kentucky, Lexington 40546-0236.
Atkins
F L
FL
Love
S
S
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D003402:Creatine Kinase / Q000378:metabolism; D004789:Enzyme Activation; D007037:Hypothyroidism / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009210:Myofibrils / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013965:Thyroidectomy
D011943:Receptors, Adrenergic, beta; D003402:Creatine Kinase; D017301:Ca(2+) Mg(2+)-ATPase; D000262:Adenylyl Cyclases