Triiodothyronine, beta-adrenergic receptors, agonist responses, and exercise capacity.
Although thyroid hormone excess results in increased beta-adrenergic receptor density or agonist responses in some cells of experimental animals, the role of these effects in contributing to clinical manifestations of hyperthyroidism in human subjects is unclear. To shed further light on this issue, we characterized the effect of 2 weeks of excess triiodothyronine administration on cardiac and metabolic responses to graded-dose isoproterenol infusion, skeletal muscle beta-adrenergic receptor density, and physiologic determinants of exercise capacity in young healthy subjects. The slope of the heart rate response to isoproterenol was 36% greater (p < 0.05) after triiodothyronine administration. In addition, beta-adrenergic receptor density was increased (p < 0.01) in all types of skeletal muscle fibers. Maximal oxygen uptake during treadmill exercise declined 5% (p < 0.001) after triiodothyronine administration because of a decrease in the arteriovenous oxygen difference (p < 0.05). The plasma lactate response to submaximal exercise was 25% greater (p < 0.01) in the hyperthyroid state. These effects were paralleled by a decrement in skeletal muscle oxidative capacity and a decrease in cross-sectional area of type 2A skeletal myocytes. Thus, thyroid hormone excess enhances cardiac beta-adrenergic sensitivity under in vivo conditions in human subjects. Nevertheless, exercise capacity is diminished in the hyperthyroid state, an effect that may be related to reduced skeletal muscle oxidative capacity and type 2A fiber atrophy.
Department of Medicine, Irene Walter Johnson Institute of Rehabilitation, Washington University School of Medicine, St. Louis, Missouri 63110.
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D000328:Adult; D000818:Animals; D017079:Exercise Tolerance; D005260:Female; D006321:Heart / Q000502:physiology* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006980:Hyperthyroidism / Q000503:physiopathology; D007545:Isoproterenol / Q000494:pharmacology*; D007773:Lactates / Q000378:metabolism; D008297:Male; D009132:Muscles / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects; D010101:Oxygen Consumption; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D014284:Triiodothyronine / Q000494:pharmacology / Q000502:physiology*; D016277:Ventricular Function, Left / Q000187:drug effects
D007773:Lactates; D011943:Receptors, Adrenergic, beta; D014284:Triiodothyronine; D007545:Isoproterenol