Subcellular remodeling and heart dysfunction in cardiac hypertrophy due to pressure overload

Rats were treated with etomoxir, an inhibitor of palmitoyltransferase-1, to examine the role of a shift in myocardial metabolism in cardiac hypertrophy, Pressure overload was induced by abdominal aorta banding for 8 weeks. Sham operated animals served as control. Left ventricular dysfunction, as reflected by decreased LVDP, +dP/dt, -dP/dt, and elevated LVEDP In the pressure overloaded animals, was improved by treatment with etomoxir, Cardiac hypertrophy in pressure-overload rats decreased the sarcoplasmic reticular (SR) Ca2+ uptake and Ca2+ release as well as myofibrillar Ca2+ stimulated ATPase and myosin Ca2+-ATPase activities; these changes were attenuated by treatment with etomoxir. Steady-state mRNA levels for alpha- and beta-myosin heavy chains, SR Ca2+-pump, and protein content of SR Ca2+-pump were reduced in hypertrophied hearts; these alterations were prevented by etomoxir treatment, The results indicate that modification of changes in myocardial metabolism by etomoxir may prevent remodeling of myofibrils and SR membrane and thereby improve cardiac function in hypertrophied heart.