HYPERTROPHY OF CULTURED SHR CARDIAC MYOCYTE

我们的目标是确定心肌细胞的原代培养 来自正常和肥厚的心脏保留了它们的底物图案 偏好、肾上腺素能反应性、肌球蛋白同工酶转录和 翻译和形态特征，并确定是否 自发性高血压大鼠左室肥厚的实验研究 (SHR)是由于心肌细胞本身的遗传缺陷， 代表对系统性高血压的适应性反应，或者是一种 这两个因素的后果。为了实现这些目标 目的分离培养成人心肌细胞。 并确定它们在培养中是否保留了某些生化和 在完整动物和灌流动物中观察到的形态特征 来自SHR大鼠的心脏。在这方面将采取多学科的方法 代谢和形态研究都在计划中。几种药物会 用来分离心肌肥厚与全身性 高血压，而从这些动物培养的心肌细胞也将 特色化的。我们还计划培养新生儿的心肌细胞。 以确定SHR大鼠是否会在 文化。这些实验应该能让我们确定肥大是否 是高血压水平和持续时间的结果，还是 肌肉细胞固有的遗传缺陷。培养心脏的研究进展 来自正常和高血压大鼠心脏的肌肉细胞应该可以让我们 更好地定义导致这种情况的特定缺陷 并可能使我们开发出一种成人肥厚心脏模型 培养中的肌肉细胞。这样的体外模型将提供一种系统来 更准确地确定是什么因素导致了 心肌细胞及其涉及的分子机制。

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.