Dietary medium-chain triglycerides can prevent changes in myosin
and sarcoplasmic reticulum due to cpt-1 inhibition by etomoxir.
Rupp, Heinz, Wolfgang Schulze, and Roland Vetter.
Molecular Cardiology Lab, Centre of Internal Medicine, University
of Marburg, 35033 Marburg and Molecular Cardiology Unit, Max
-Delbr[umlaut]uck Centre for Molecular Medicine, 13122 Berlin-Buch,
Germany
APStracts 2:0092R, 1995.
To define determinants of subcellular structures of heart, Wistar
-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were
treated for 5 weeks with 15 mg/kg/d etomoxir (reduces mitochondrial
carnitine palmitoyltransferase-1 (CPT-1) activity and fatty acid
synthesis). To bypass CPT-1 inhibition, etomoxir-treated rats were
fed a medium-chain fatty acid (MCFA) diet. Etomoxir induced a
proportionate growth of heart which could partially (WKY, P<0.05)
or completely (SHR, P<0.05) be prevented by the MCFA diet. Also the
etomoxir-induced increase in myosin V1 was partially prevented
(P<0.05). Etomoxir increased (P<0.05) rate of SR Ca2+ uptake of
WKY and SHR ventricular homogenates in the presence or absence of the
SR Ca2+ release inhibitor ruthenium red. The MCFA diet resulted in SR
Ca2+ uptake rates that were inbetween those of etomoxir-treated and
untreated rats. The in vitro 32P incorporation into phospholamban and
troponin-I did not differ significantly in WKY. Etomoxir induced,
however, an increase (P<0.05) in the phosphorylated intermediate of
the Ca2+ ATPase in WKY that was prevented by the MCFA diet. In SHR,
etomoxir increased the in vitro phospholamban phosphorylation which
was reduced when compared with WKY. The data show that myosin and SR
are affected by a chronically altered substrate utilization of heart.
Received 21 April 1994; accepted in final form 30 March 1995.
APS Manuscript Number R209-4.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 10 April 1995.