Metabolically-modulated growth and phenotype of the rat heart.

Abstract

Heart muscle reacts to work overload and various neuroendocrine stimuli by inducing myocyte growth. A novel type of hypertrophy can be induced in the rat heart by etomoxir, which reduces fatty acid oxidation. This hypoglycaemic drug inhibits the mitochondrial carnitine palmitoyltransferase 1, and thus reduces the long-chain fatty acid uptake of mitochondria; in a compensatory manner, the glycolytic flux is enhanced. In rats, etomoxir induced a harmonious growth of the left and right ventricles of normal and pressure-overloaded hearts. To characterize the protein phenotype, myosin expression and sarcoplasmic reticulum (SR) Ca2+ pump activity were determined. In contrast to pressure-overloaded hearts, etomoxir increased the proportion of myosin V1, Ca(2+)-stimulated SR ATPase activity and the rate of SR Ca2+ uptake. Since etomoxir did not increase blood pressure, heart rate or circulating thyroid hormones, it appears that established mechanisms of other models of cardiac hypertrophy were not involved. The etomoxir-induced changes thus seem closely linked to the shift in energy metabolism.