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European Heart Journal 1995 16(Supplement C):15-19; doi:10.1093/eurheartj/16.suppl_C.15
Copyright © 1995 by the European Society of Cardiology.
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© 1995 The European Society of Cardiology

Differential influences of carnitine palmitoyltranferase-1 inhibition and hyperthyroidism on cardiac growth and sarcoplasmic reticulum phosphorylation

R. Vetter*,, M. Kott* and H. Rupp{dagger}

* Max Delbriick Center for Molecular Medicine Berlin-Buch
{dagger} University of Tuübingen, Institute of Physiology Tuübingen, Germany

Correspondence: Dr Roland Vetter, Max-Delbruck-Centrum fuür molekulare Medizin, Robert-Rossle-Strasse 10, 13122 Berlin-Buch, Germany

To characterize interventions resulting in ‘physiological’ growth of the heart, Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) had hyperthyroidism induced (005 mg.kg–1 day–1 triiodothyronine for 6 days) or were treated with a high dose of the carnitine palmitoyltransferase-1 inhibitor, etomoxir (15 mg.kg–1.day–1 for 5 weeks). Etomoxir increased cardiac growth evenly, but hyperthyroidism resulted in an over-proportional higher right ventricular weight. Both interventions increased the proportion of the myosin isozyme V1. The rate of sarcoplasmic reticulum (SR) Ca2+ uptake was increased to a greater extent in hyperthyroid rats than in etomoxir-treated rats (P >0.05). Left ventricular levels of immunoreactive phospholamban (semiquantitative ELISA) were moderately decreased (P < 0.05) in hyperthyroid rats but not in etomoxir-treated rats. The protein kinase A-catalyzed in vitro 32P-incorporation into the SR Ca2+ pump modulator phospholamban was greatly reduced (P < 0.05) in hyperthyroid rats, indicating an increased in vivo phosphorylation. Etomoxir did not affect phospholamban phosphorylation in WKY rats. Thus, both a higher in vivo phospholamban phosphorylation state and a greater number of active Ca2+ pumps contributed to an increased rate of SR Ca2+ uptake in hyperthyroidism. The etomoxir treatment primarily increased the number of active Ca2+ pumps. A scheme is proposed focusing on long-term vs short-term regulation of the SR Ca2+ pump/phospholamban system in diseased states.

Key Words: Hypertrophy • hyperthyroidism • fuel utilization • calcium adenosinetriphosphatase • phospholamban • sarcoplasmic reticulum • carnitime palmitoyltransferase • hypertension


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