© 1996 American Heart Association, Inc.
Articles |
Effects of Thyroid Hormone on Left Ventricular Performance and Regulation of Contractile and Ca2+-Cycling Proteins in the Baboon
Implications for the Force-Frequency and Relaxation-Frequency Relationships
the Division of Cardiology, University of Cincinnati (Ohio) Medical Center.
The transcriptional, posttranscriptional, and related functional effects of thyroid hormone on primate myocardium are poorly understood. Therefore, we studied the effects of thyroid hormone on sarcoplasmic reticulum (SR) Ca2+-cycling proteins and myosin heavy chain (MHC) composition at the steady state mRNA and protein level and associated alterations of left ventricular (LV) performance in 8 chronically instrumented baboons. The force-frequency and relaxation-frequency relations were assessed as the response of LV isovolumic contraction (dP/dtmax) and relaxation (Tau), respectively, to incremental atrial pacing. Both the heart rate at which dP/dtmax was maximal and Tau was minimal (critical heart rates) in response to pacing were increased significantly after thyroid hormone. Postmortem LV tissue from 5 thyroid-treated and 4 additional control baboons was assayed for steady state mRNA levels with cDNA probes to MHC isoforms and SR Ca2+-cycling proteins. Steady state SR Ca2+-ATPase and phospholamban mRNA increased in the hyperthyroid state, and 
-MHC mRNA appeared de novo, whereas ß-MHC mRNA decreased. Western analysis (4 thyroid-treated and 4 control baboons) showed directionally similar changes in MHC isoforms and a slight increase in SR Ca2+-ATPase. In contrast, there was a statistically nonsignificant decrease in phospholamban protein, which resulted in a significant 40% decrease in the ratio of phospholamban to SR Ca2+-ATPase. Thus, thyroid hormone increases the transcription of Ca2+-cycling proteins and shifts MHC isoform expression in the primate LV. Our data suggest that both transcriptional and posttranslational mechanisms determine the levels of these proteins in the hyperthyroid primate heart and mediate, in part, the observed enhanced basal and frequency-dependent LV performance.
Key Words: sarcoplasmic reticulum • hyperthyroidism • myosin • muscle contraction • muscle relaxation
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