CHANGES IN ENZYME LEVELS IN HYPERTENSIVE HEART-TISSUE

The levels of activity of some enzymes involved in oxidative metabolis m have been determined in left ventricular tissue from spontaneously h ypertensive rats compared with those in normotensive controls. Levels of pyruvate kinase were increased about 1.3 fold indicative of elevate d glycolytic activity. Similarly, enhanced levels of lactate dehydroge nase were found, consistent with a requirement for increased oxidation of cytosolically-generated NADH. In addition a more active malate-asp artate shuttle, which in heart provides the major route for transfer o f reducing equivalents to the mitochondria, was suggested by elevated levels of the cytosolic isoenzyme of aspartate aminotransferase; malat e dehydrogenase did not increase but the activity of this enzyme is ve ry high and unlikely to be rate-limiting in the shuttle. The levels of expression of mRNAs for three of these enzymes (pyruvate kinase, aspa rtate aminotransferase and malate dehydrogenase) were also determined and correlated well with the extent of change, if any, in the changes in enzymatic activity. Thus it seems that one response to development of hypertension in rats is an increase in expression of the genes for certain key enzymes involved in oxidative metabolism.