Excessive thyroxine enhances susceptibility to apoptosis and decreases contractility of cardiomyocytes.
Excessive thyroid hormone induces cardiac hypertrophy and promotes heart failure in patients with hyperthyroidism, but the mechanism remains elusive. Rats were orally administered with levothyroxine (100 microg/kg, T(4)) for 4 weeks to induce hyperthyroidism. The calculated stroke volume decreased and the shortening amplitude-frequency relationship in unloaded contraction of isolated cardiomyocytes was negative in T(4)-treated rats. Apoptotic rates increased and DNA laddering was also detectable in T(4)-treated rat hearts. By contrast, in primary cultured cardiomyocytes, T(3) induced dose-dependent hypertrophy but did not affect the apoptotic rate. Angiotensin II further increased the apoptotic rate of T(3)-induced hypertrophied cardiomyocytes. The apoptotic rate was dependent on the extent of cardiomyocyte hypertrophy. These results suggest that cardiac contractility is enhanced during the early stage of hyperthyroidism, but decreased during the late stage of hyperthyroidism. The hypertrophied cardiomyocytes were also susceptible to apoptotic stimulation by angiotensin II. Depressed cardiac contractility and enhanced apoptosis may lead to heart failure in hypertrophied myocardium.
Wang
Yun-Ying
YY
Key Laboratory of Aerospace Medicine, Ministry of Education, Department of Aerospace Physiology, Fourth Military Medical University, 169# Changlexi Road, Xi'an 710032, China.
Jiao
Bo
B
Guo
Wang-Gang
WG
Che
Hong-Lei
HL
Yu
Zhi-Bin
ZB
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002469:Cell Separation; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D053938:DNA Fragmentation / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006980:Hyperthyroidism / Q000473:pathology / Q000503:physiopathology; D020287:In Situ Nick-End Labeling; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D009336:Necrosis / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013318:Stroke Volume / Q000187:drug effects; D013499:Surface Properties / Q000187:drug effects; D013974:Thyroxine / Q000494:pharmacology*
D013974:Thyroxine