Cardiac hypertrophy is a fundamental adaptation of the heart to hemodynamic overload, and it is often accompanied by changes in myocardial contractility. The direction and magnitude of change are determined by the type, duration, and severity of the stimulus to hypertrophy. Considerable evidence suggest that these chronic changes in contractile function may be mediated in part by alterations in the activity of myosin adenosine triphosphatase (ATPase). This enzyme provides energy for muscle contraction, and its activity correlates closely with the maximal velocity of muscle shortening. It is the specific purpose of this research to investigate the molecular mechanism(s) by which changes in myosin ATPase activity occur during the development of cardiac hypertrophy. Available evidence in the rat and rabbit suggests that myosin may exist as at least three electrophoretically distinct isoenzymes in these species, each with its own intrinsic ATPase activity. The relative propostions of the three isoenzymes may determine the total ATPase activity of the myosin pool. The working hypothesis is that different stimuli to cardiac hypertrophy (e.g., pressure overload and thyroid hormone) may promote the synthesis of different myosin isoenzymes depending upon the functional requirements placed upon the myocardium. This hypothesis will be tested by directly measuring rates of synthesis, degradation, and half-lives of cardiac myosin isoenzymes. These measurements will be made in normal rats, and compared to values obtained in thyroidectomized animals, hyperthyroid animals, and animals with left ventricular pressure overload produced by aortic banding. In this way the effects of different hypertrophic stimuli on myosin isoenzyme turnover and the resulting distribution of isoenzymes within the myocardium will be investigated. These experiments are intended to provide further information about the role of myosin isoenzymes in the adaptation of the heart to different hemodynamic conditions, and may bear upon the important clinical problem of congestive heart failure. Future research will be aimed at defining myosin isoenzyme patterns in the human heart, and studying the effect of human cardiac diseases such as cardiomyopathies on myosin isoenzyme distribution.