Direct action of T3 on phosphorylation potential in the sheep heart in vivo.
Thyroid acting through ligand binding to nuclear receptors modifies myocardial respiratory kinetics and oxidative phosphorylation in the heart. Direct nongenomic action of thyroid hormone on high-energy phosphate concentrations and respiratory kinetics has never been proven in vivo but might be responsible for observed changes in oxygen utilization efficiency immediately after triiodothyronine (T3) administration. We tested the hypothesis that T3 directly and rapidly modifies myocardial high-energy phosphate concentrations and phosphorylation potential in vivo. Anesthetized sheep (age 28-40 days) thyroidectomized shortly after birth (Thy) and euthyroid age-matched controls (Con) underwent median sternotomy and received T3 infusion (0.8 microg/kg), followed by epinephrine infusion to increase myocardial oxygen consumption (MVo2). 31P magnetic resonance spectra were monitored via a surface coil over the left ventricle. T3 increased phosphocreatine (PCr)/ATP and decreased ADP in Thy animals without causing a change in MVo2. T3 produced no changes in high-energy phosphates in Con animals. T3 did not modify the PCr/ATP or ADP response to epinephrine and elevation in MVo2 in either group. Cardiac mitochondria isolated from Thy and Con animals showed no change in respiratory rate or ADP/ATP exchange efficiency after T3 incubation. T3 infusion in a hypothyroid state decreases ADP concentration, thereby altering the equilibrium between phosphorylation potential and myocardial respiratory rate. These T3-induced effects are not due to changes in ADP/ATP exchange efficiency through action at the adenine nucleotide translocator but may be due to T3 mediation of substrate utilization, confirmed in other models.
Portman
Michael A
MA
Division of Cardiology, Department of Pediatrics, University of Washington School of Medicine, Seattle, Wahington 98105, USA. michael.portman@seattlechildrens.org
Qian
Kun
K
Krueger
Julia
J
Ning
Xue-Han
XH
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003326:Coronary Circulation / Q000502:physiology; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology*; D009682:Magnetic Resonance Spectroscopy; D008928:Mitochondria / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption / Q000502:physiology; D010725:Phosphocreatine / Q000378:metabolism; D010759:Phosphorus Isotopes; D010766:Phosphorylation; D012756:Sheep; D013965:Thyroidectomy; D014284:Triiodothyronine / Q000378:metabolism* / Q000494:pharmacology
D010759:Phosphorus Isotopes; D010725:Phosphocreatine; D014284:Triiodothyronine; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate