HYPERTENSION & HYPERTROPHY

心室肥厚是一种重要的适应性机制， 伴随全身性动脉高血压。 然而，在某些时候， 随着时间的推移，这种代偿过程导致充血性心力衰竭。 的 我们的研究计划的主要目标，是确定基本的 压力的力学、生物化学和分子生物学特性 在一个独特的模型中， 非人灵长类动物（狒狒）中的渐进性肾性高血压。 建议在较小的哺乳动物（豚鼠）中进行平行研究，以阐明 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， 离体心脏不受神经体液的影响， 因素和心室血管耦联。 利用这种方法，我们建议 为了检验以下特定假设：1）压力过载 肥厚与收缩期室壁弹性、负荷 射血和充盈速度独立降低， 室和肌肉僵硬; 2）压力超负荷的回归 肥大的特征在于射血速度的正常化， 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 对生理应激的反应储备， 肌球蛋白ATP酶活性可逆性降低 在收缩和松弛过程中， 压力超负荷肥大，由转录和/或 β肌球蛋白重链的翻译改变; 5）协调 肌球蛋白轻链的转录和翻译改变， 对肌球蛋白ATP酶活性和机械行为的调节作用 压力超负荷肥大和消退;和6）转录 胶原蛋白数量分布和类型的改变在很大程度上决定了 肥厚型和肥厚型心脏固有的被动心腔特性 心肌退化

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.