MECHANISMS OF REFEEDING HYPERTENSION IN DIETARY OBESITY

虽然高血压与肥胖增加有关， 到目前为止，在动物中存在类似关联的证据 缺乏 我们最近启动了旨在开发一种 基于抗抑郁药的肥胖性高血压动物模型的建立 禁食再进食 这些初步研究构成了 这个提议。 该提案的目标有三个方面： 1. 继续进行初步工作， 这一模型可能有助于研究人类的机制， 肥胖型高血压的发病和进展 高血压及其与体重和食物的关系 摄入量使用动物长期仪器测量 全身血流动力学 这种大鼠模型是基于 观察到肥胖的人表现出不稳定的 食物摄入量的波动，导致大量和快速的体重减轻， 恢复。 本提案中提供的初步数据显示， 肥胖大鼠发生持续轻度高血压 类似于肥胖的人类。 2. 研究可能的机制， 肥胖高血压的啮齿动物模型。 我们将 评估交感神经系统（SNS）的假定作用， 各种血管活性体液因子和胰岛素在高血压中的作用 通过直接测定这些物质并通过 使用已知拮抗剂和激动剂的药理学干预 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 交感神经流出的动物之前，期间和 随着高血压的发展。 我们将使用 定量受体结合方法学的变化， 器官肾上腺素能受体 3. 本提案的最终目的是开始审查 室旁核功能改变的可能作用 （PVN）。 本部分研究的目的是开始 检查特定功能的可能改变 已知参与CNS自主神经系统的下丘脑核 控制SNS和喂养。 总之，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潜在新啮齿动物模型 高血压和彻底评估SNS的可能作用 和胰岛素在高血压发展中的作用。 此外，可能的作用 在这种病理生理学上， 国家将予以审查。 这项研究的结果可以提供 人类肥胖性高血压相关重要新信息 并为未来的动物研究提供了一种手段， 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.