HYPERTENSION & HYPERTROPHY

高血压

• 批准号: 3345609
• 负责人: Richard A. Walsh
• 金额: $ 49.08万
• 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/3345609
• 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适应性机制 伴有全身动脉高血压。 然而，在某个时刻 随着时间的推移，这种代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的 压力的机械、生化和分子生物学特性 超负荷肥大和肥大回归的独特模型 非人灵长类动物（狒狒）逐渐出现肾性高血压。 建议对较小的哺乳动物（豚鼠）进行平行研究来阐明 物种差异，以促进分析技术的发展，以及 检查压力超负荷肥大的心腔力学 不受神经体液影响的孤立心脏 因素和心室血管耦合。 使用这种方法，我们建议 测试以下具体假设：1）压力过载 肥大与收缩室弹性、负荷不变有关 独立降低喷射和填充速度以及提高被动速度 腔室和肌肉僵硬； 2）压力过载的回归 肥大的特征是射血和射血速度正常化 充盈和残余升高的心肌僵硬度； 3）压力 超负荷肥大与高能磷酸盐减少有关 储备以应对生理压力，这是可逆的 肥大回归； 4)可逆性降低肌球蛋白ATP酶活性 是缩短和松弛速度降低的基础 压力超负荷肥大是由转录和/或引起的 β肌球蛋白重链的翻译改变； 5）坐标 肌球蛋白轻链的转录和翻译改变发挥着 对肌球蛋白 ATP 酶活性和机械行为的调节作用 压力超负荷肥大和退化； 6) 转录 胶原蛋白数量分布和类型的改变很大程度上决定了 肥大和肥大的固有被动室特性 心肌退化。