HYPERTENSION & HYPERTROPHY IN THE NON-HUMAN PRIMATE

高血压

• 批准号: 3345607
• 负责人: Richard A. Walsh
• 金额: $ 43.74万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-05-01 至 1995-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3345607
• 关键词: adenosinetriphosphatase; baboons; cineangiocardiography; collagen; congestive heart failure; disease /disorder model; echocardiography; guinea pigs; heart contraction; heart dimension /size; intracardiac pressure; intracardiac volume; isozymes; molecular biology; myosins; neurohormones; remission /regression; renal hypertension; ventricular hypertrophy

Ventricular hypertrophy is an important adaptive mechanism which accompanies systemic arterial hypertension. However, at some point in time, this compensatory process results in congestive heart failure. The major objectives of our research program, is to define the fundamental mechanical, biochemical and molecular biologic properties of pressure overload hypertrophy and hypertrophy regression in a unique model of gradual onset renal hypertension in the non-human primate (baboon). Parallel studies in a smaller mammal (guinea pig) are proposed to elucidate species differences, to facilitate development of analytic techniques, and to examine cardiac chamber mechanics of pressure overload hypertrophy in the isolated heart which is devoid of the influences of neurohumoral factors and ventricular vascular coupling. Using this approach, we propose to test the following specific hypotheses: 1) pressure overload hypertrophy is associated with unchanged systolic chamber elastance, load independent reduced velocities of ejection and filling and elevated passive chamber and muscle stiffness; 2) regression of pressure overload hypertrophy is characterized by normalization of velocities of ejection and filling and residually elevated cardiac muscle stiffness; 3) pressure overload hypertrophy is associated with diminished high-energy phosphate reserves in response to physiologic stress which is reversible upon hypertrophy regression; 4) reversibly reduced myosin ATPase activity underlies diminished velocities of shortening and relaxation during pressure overload hypertrophy and is caused by transcriptional and/or translational alterations in beta myosin heavy chains; 5) coordinate transcriptional and translational alteration of myosin light chains exert a modulatory role on myosin ATPase activity and mechanical behavior in pressure overload hypertrophy and regression; and 6) transcriptional alterations in collagen amount distribution and type largely determine intrinsic passive chamber properties of hypertrophied and hypertrophy regressed myocardium.

心室肥大是一种重要的自适应机制 伴随系统性动脉高血压。 但是，在某个时候 时间，这种补偿过程会导致充血性心力衰竭。 这 我们研究计划的主要目标是定义基本 压力的机械，生化和分子生物学特性 在独特的模型中超负荷肥大和肥大回归 非人类灵长类动物（狒狒）的逐渐发作肾脏高血压。 提出了在较小的哺乳动物（豚鼠）中的平行研究以阐明 物种差异，促进分析技术的发展和 检查压力超负荷肥大的心脏腔室力学 没有神经肿瘤的影响的孤立心脏 因素和心室血管耦合。 使用这种方法，我们建议 测试以下特定假设：1）压力超负荷 肥大与不变的收缩室弹性，负载有关 独立降低弹出速度，填充和升高的被动速度 腔室和肌肉僵硬； 2）压力超负荷的回归 肥大的特征是射血速度的标准化和 填充和残留的心脏肌肉刚度； 3）压力 超负荷肥大与高能磷酸盐降低有关 响应生理压力的储备，这是可逆的 肥大回归； 4）可逆降低肌球蛋白ATPase活性 基础缩短了缩短和放松的速度 压力超负荷肥大，是由转录和/或 β肌球蛋白重链的翻译变化； 5）协调 肌球蛋白光链的转录和翻译变化施加 在肌球蛋白ATPase活性和机械行为上的调节作用 压力超负荷肥大和回归；和6）转录 胶原蛋白分布和类型的改变很大程度上确定 肥大和肥厚的内在被动室特性 回归心肌。