Bing Oscar H L, Conrad Chester H, Boluyt Marvin O, Robinson Kathleen G, Brooks Wesley W
The Department of Medicine, VA Boston Healthcare System, 150 South Huntington Avenue, Boston, MA 02130, USA.
Heart Fail Rev. 2002 Jan;7(1):71-88. doi: 10.1023/a:1013753907135.
The spontaneously hypertensive rat (SHR) is an animal model of genetic hypertension which develops heart failure with aging, similar to man. The consistent pattern of a long period of stable hypertrophy followed by a transition to failure provides a useful model to study mechanisms of heart failure with aging and test treatments at differing phases of the disease process. The transition from compensated hypertrophy to failure is accompanied by changes in cardiac function which are associated with altered active and passive mechanical properties of myocardial tissue; these events define the physiologic basis for cardiac decompensation. In examining the mechanism for myocardial tissue dysfunction, studies have demonstrated a central role for neurohormonal activation, and specifically the renin-angiotensin-aldosterone system. Pharmacologic attenuation of this system at differing points in the course of the process suggests that prevention but not reversal of myocardial tissue dysfunction is possible. The roles of the extracellular matrix, apoptosis, intracellular calcium, beta-adrenergic stimulation, microtubules, and oxygen supply-demand relationships in ultimately mediating myocardial tissue dysfunction are reviewed. Studies suggest that while considerable progress has been made in understanding and treating the transition to failure, our current state of knowledge is limited in scope and we are not yet able to define specific mechanisms responsible for tissue dysfunction. It will be necessary to integrate information on the roles of newly discovered, and as yet undiscovered, genes and pathways to provide a clearer understanding of maladaptive remodeling seen with heart failure. Understanding the mechanism for tissue dysfunction is likely to result in more effective treatments for the prevention and reversal of heart failure with aging. It is anticipated that the SHR model will assist us in reaching these important goals.
自发性高血压大鼠（SHR）是一种遗传性高血压动物模型，与人类相似，随着年龄增长会发生心力衰竭。长期稳定的肥厚随后转变为衰竭的一致模式，为研究衰老相关心力衰竭的机制以及在疾病过程的不同阶段测试治疗方法提供了一个有用的模型。从代偿性肥厚向衰竭的转变伴随着心脏功能的变化，这些变化与心肌组织主动和被动力学特性的改变有关；这些事件定义了心脏失代偿的生理基础。在研究心肌组织功能障碍的机制时，研究表明神经激素激活，特别是肾素 - 血管紧张素 - 醛固酮系统起着核心作用。在该过程的不同时间点对该系统进行药理学抑制表明，心肌组织功能障碍可以预防但无法逆转。本文综述了细胞外基质、细胞凋亡、细胞内钙、β - 肾上腺素能刺激、微管以及氧供需关系在最终介导心肌组织功能障碍中的作用。研究表明，虽然在理解和治疗向衰竭的转变方面已经取得了相当大的进展，但我们目前的知识状态在范围上是有限的，我们尚未能够确定导致组织功能障碍的具体机制。有必要整合关于新发现和尚未发现的基因及信号通路作用的信息，以便更清楚地了解心力衰竭时出现的适应性不良重塑。了解组织功能障碍的机制可能会带来更有效的治疗方法，用于预防和逆转衰老相关的心力衰竭。预计SHR模型将帮助我们实现这些重要目标。
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