MECHANISMS OF REFEEDING HYPERTENSION IN DIETARY OBESITY

饮食性肥胖的再喂养高血压机制

• 批准号: 3356272
• 负责人: DOUGLAS O NELSON
• 金额: $ 14.33万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-07-01 至 1988-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3356272
• 关键词: action potentials; adrenal hypertension; aldosterone; appetite regulatory center; autoradiography; blood chemistry; blood pressure; body composition; body weight; brain mapping; cardiovascular pharmacology; catecholamines; chemical binding; computer data analysis; diet; disease /disorder model; eating; electrodes; heart function; hormone regulation /control mechanism; hypothalamus; insulin; kidney function; liver function; model design /development; nutrient intake activity; nutrition related tag; obesity; renin; sympathetic nervous system; ultrasound blood flow measurement; vasopressins; weight control

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.

尽管高血压与肥胖增加有关 人类，迄今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。 这些初步研究奠定了基础 这个建议。 该提案的目标有三个： 1. 继续开展旨在开发动物的前期工作 可能有助于研究人类机制的模型 肥胖高血压进一步表征了其发病和进展 高血压及其与体重和食物的关系 使用长期仪器测量的动物摄入量 全身血流动力学。 该大鼠模型基于 观察到肥胖的人表现出不稳定的特征 食物摄入量的波动，导致体重大幅快速下降 恢复。 该提案中提供的初步数据表明 肥胖大鼠出现持续、轻度高血压 与肥胖人群中观察到的情况相似。 2. 调查潜在的机制 肥胖高血压啮齿动物模型中的高血压。 我们将 评估交感神经系统（SNS）的假定作用， 各种血管活性体液剂和胰岛素治疗高血压 通过直接测定这些物质并通过 使用已知的拮抗剂和激动剂进行药物干预 物质。 此外，我们还会直接测量一些 心血管血流动力学参数直接记录 动物的交感神经流出在之前、期间和 高血压发展后。 我们将分析使用 各种定量受体结合方法的变化 器官肾上腺素受体。 3. 本提案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 检查特定功能的可能改变 下丘脑核已知参与中枢神经系统自主神经 SNS 和喂养的控制。 总之，拟议的研究将尝试发展和完善 一种可用于研究人类肥胖的潜在新啮齿动物模型 高血压并彻底评估 SNS 的可能作用 和胰岛素在高血压发展中的作用。 另外，可能的角色 这种病理生理学中特定的下丘脑结构 状态将被检查。 此类研究的结果可能会提供 与人类肥胖高血压相关的重要新信息 并为未来的动物研究提供一种手段 问题。