DIFFERENTIAL INFLUENCES OF CARNITINE PALMITOYLTRANSFERASE-1 INHIBITION AND HYPERTHYROIDISM ON CARDIAC GROWTH AND SARCOPLASMIC-RETICULUM PHOSPHORYLATION

To characterize interventions resulting in 'physiological' growth of t he heart, Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) had hyperthyroidism induced (0.05 mg . kg(-1). day(-1) triiodoth yronine for 6 days) or were treated with a high dose of the carnitine palmitoyltransferase-1 inhibitor, etomoxir (15 mg . kg(-1). day(-1) fo r 5 weeks). Etomoxir increased cardiac growth evenly, but hyperthyroid ism resulted in an over-proportional higher right ventricular weight. Both interventions increased the proportion of the myosin isozyme V-1. 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 (semiq uantitative ELISA) were moderately decreased (P<0.05) in hyperthyroid rats but not in etomoxir-treated rats. The protein kinase A-catalyzed in vitro P-32-incorporation into the SR Ca2+ pump modulator phospholam ban was greatly reduced (P<0.05) in hyperthyroid rats, indicating an i ncreased in vivo phosphorylation. Etomoxir did not affect phospholamba n phosphorylation in WKY rats. Thus, both a higher in vivo phospholamb an phosphorylation state and a greater number of active Ca2+ pumps con tributed to an increased rate of SR Ca2+ uptake in hyperthyroidism. Th e etomoxir treatment primarily increased the number of active Ca2+ pum ps. A scheme is proposed focusing on long-term vs short-term regulatio n ofthe SR Ca2+ pump/phospholamban system in diseased stares.