MECHANISMS OF REFEEDING HYPERTENSION IN DIETARY OBESITY

尽管高血压与肥胖增加有关，但 人类，到目前为止，在动物身上也有类似关联的证据 缺乏。我们最近启动了旨在开发一种 基于间歇性的人类肥胖高血压动物模型 禁食和重新进食。这些初步研究构成了 这项提议。这项提议的目标有三个： 1.继续进行旨在培育动物的前期工作 可能对研究人类机制有用的模型 肥胖性高血压的发生和发展进一步表现为 高血压及其与体重和食物的关系 使用长期用仪器测量的动物摄入量 全身血流动力学。这种大鼠模型是基于 观察到肥胖的人典型地表现出反复无常的行为 食物摄入量的波动，导致体重大幅快速下降和 重获新生。本提案中提供的初步数据显示， 肥胖大鼠发生持续性轻度高血压的研究 与肥胖人类的情况相似。 2.调查可能导致 高血压在这个肥胖高血压的啮齿动物模型中。我们会 评估交感神经系统(SNS)的假定作用， 多种血管活性体液药与胰岛素在高血压中的作用 通过直接检测这些物质和通过 使用已知拮抗剂和激动剂的药理干预 物质。此外，我们还将直接测量几个 心血管血流动力学参数和直接记录 动物交感神经在前、中、后的流出 随着高血压的发展。我们将使用以下工具进行分析 定量受体结合方法学在不同领域的变化 器官肾上腺素能受体。 3.这项建议的最终目标是开始审查 室旁核功能改变的可能作用 (PVN)。这部分研究的目的是开始 检查特定设备的功能可能发生的变化 已知的下丘脑核团参与中枢自主神经 控制SNS和喂养。 总而言之，拟议的研究将试图发展和完善 一种可用于研究人类肥胖的新型啮齿动物模型 并彻底评估SNS的可能作用 和胰岛素与高血压的发展。此外，可能扮演的角色 一种特殊的下丘脑结构在这种病理生理学中 将对该州进行审查。这种研究的结果可能会提供 与人类肥胖性高血压相关的重要新信息 并为未来的动物研究提供了一种手段 有问题。

Although hypertension is associated with increased adiposity in humans, evidence for a similar association in animals is thus far lacking. We recently initiated studies aimed at developing an animal model of human obese hypertension based on intermittant fasting and refeeding. These preliminary studies form the basis of this proposal. The goals of this proposal are threefold: 1. To continue preliminary work aimed at developing an animal model which may be useful in studying mechanisms of human obese hypertension further characterize the onset and progression of the hypertension and its relationship to body weight and food intake using animals chronically instrumented for measurement of systemic hemodynamics. This rat model is based on the observation that fat humans characteristically exhibit erratic swings in food intake, resulting in large and rapid weight loss and regain. Preliminary data presented in this proposal shows the development of a sustained, mild hypertension in obese rats similar to that seen in obese humans. 2. To investigate potential mechanisms responsible for the hypertension in this rodent model of obese hypertension. We will assess the putative role of the sympathetic nervous system (SNS), various vasoactive humoral agents and insulin in hypertension development by directly assaying these substances and through pharmacological interventions using known antagonist and agonist substances. In addition, we will directly measure several cardiovascular hemodynamic parameters and directly records sympathetic neural outflow in animals before, during and following hypertension development. We will analyze using quantitative receptor binding methodology changes in various organ adrenergic receptors. 3. The final aim of this proposal is to begin to examine the possible role of altered function of the paraventricular nucleus (PVN). The aims of this portion of the study are to begin to examine the possible alteration in function of a specific hypothalamic nucleus known to be involved in CNS autonomic control of the SNS and feeding. In summary, the proposed study will attempt to develop and refine a potential new rodent model useful in studying human obese hypertension and to thoroughly assess the possible role of the SNS and insulin in hypertension development. Also, the possible role of a specific hypothalamic structure in this pathophysiological state will be examined. The results of such a study may provide important new information related to human obese hypertension as well as provide a means for future animal studies of this problem.