HYPERTROPHY OF CULTURED SHR CARDIAC MYOCYTE

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Our objectives are to determine if primary cultures of cardiac muscle cells from normal and hypertrophied hearts retain their patterns of substrate preference, adrenergic responsiveness, myosin isozyme transcription and translation and morphological characteristics and to determine if hypertrophy of the left ventricle of the spontaneously hypertensive rat (SHR) is due to a genetic defect in the heart muscle cell per se, represents an adaptive response to the systemic hypertension or is a consequence of both of these factors. In order to accomplish these objectives we will isolate and culture cardiac muscle cells from the adult SHR rat and determine if they retain in culture certain biochemical and morphological characteristics observed in the intact animal and in perfused hearts from SHR rats. A multidisciplinary approach will be taken in that both metabolic and morphological studies are planned. Several drugs will be used to dissociate the cardiac hypertrophy from the systemic hypertension, and myocardial cells cultured from these animals will also be characterized. We also plan to culture cardiac muscle cells from neonatal SHR rats to determine if they will develop "SHR-Characteristics" in culture. These experiments should allow us to determine if the hypertrophy is a consequence of the level and duration of hypertension or is an intrinsic genetic defect in the muscle cell. Studies of cultured cardiac muscle cells from hearts of normal and hypertensive rats should allow us to better define the specific defects which are responsible for this condition and may allow us to develop a model of the adult hypertrophied cardiac muscle cell in culture. Such an in vitro model would provide a system to more precisely determine what factors are responsible for enlargement of the heart muscle cell and the molecular mechanisms involved.