OBESITY HYPERTENSION

肥胖 高血压

• 批准号: 3350236
• 负责人: Albert P Rocchini
• 金额: $ 13.18万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-12-01 至 1986-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3350236
• 关键词: aldosterone; angiotensin II; biological models; blood volume; cardiac output; hyperinsulinism; hypertension; kidney circulation; obesity; pathology; salt intake; sympathetic nervous system

Despite the strong association between obesity and hypertension, little is known about the mechanism. The lack of knowledge into the pathogenesis of obesity hypertension is not surprising since few animals have been developed. Based on our previous research and the development of an animal model of obesity hypertension we postulate that obesity hypertension is primarily related to increased sodium retention by the kidney. We also speculate that this increased sodium retention is due to the combined effects of increased sympathetic nervous system activity, hyperinsulinemia and hyperaldosteronism. The following experiments will test this hypothesis: 1. The role of sodium retention on blood pressure in obesity will be assessed by measuring the change in sodium balance, plasma volume, cardiac output, regional blood flow (using radiolabeled microspheres) and blood pressure that occur in the dog with the development of obesity. 2. We speculate that weight gain will cause the dog to become "salt sensitive" (ie greater than 10% change in mean pressure will occur when the dog is switched from a low to high salt). We wxpect this "salt-sensitivity" will be associated with: both a decreased urinary sodium excretion and a negative correlation between urinary sodium excretion and the increment of change in mean pressure during a high sodium regimen; a greater loss of sodium on a low salt diet; and an increased renal blood flow, plasma aldosterone, insulin and catecholamines when the dogs become obese. 3. The role of hyperinsulinemia on blood pressure in obesity will be evaluated using a euglycemic insulin clamp. In addition, we will administer a chronic hyperinsulinemia to ten dogs. We believe that chronic hyperinsulinemia (independent of weight gain) will result in sodium retention and an increased pressure, heart rate and cardiac output. 4. The role of aldosterone will be evaluated by observing the effect of adrenalectomy on the developmemt of obesity hypertension. We expect to find that adrenalectomy will blunt but not eliminate obesity hypertension. We will also determine if increased adrenal sensitivity to angiotensin ll occurs with the development of obesity by administering graded infusions of angiotensin ll both before and after the development of obesity. 5. Finally, the role of the sympathetic nervous system will be evaluated by measuring the changes in catecholamines that occur with the development of obesity and with euglycemic hyperinsulinemia.

尽管肥胖症和高血压之间有很强的联系，但几乎没有 已经知道了这个机制。缺乏对其发病机制的认识 肥胖高血压并不令人惊讶，因为很少有动物 发展起来的。基于我们之前的研究和一种动物的发展 肥胖性高血压模型我们假设肥胖性高血压 主要与增加肾脏对钠的滞留有关。我们也 推测这种钠滞留的增加是由于联合 交感神经系统活动增强、高胰岛素血症的影响 和醛固酮过多症。下面的实验将验证这一点 假设：1.钠滞留对肥胖患者血压的影响 将通过测量钠平衡、血浆容量、 心输出量、局部血流量(使用放射性标记微球)和 随着肥胖的发展，狗的血压也会发生变化。2. 我们推测，体重增加会导致狗变得对盐敏感 (即当狗处于低血压状态时，平均压力变化将超过10% 从低盐改为高盐)。我们期待这种“盐敏性”将 与：尿钠排泄减少和 尿钠排泄与尿钠排泄量增加呈负相关 高钠饮食期间平均压力的变化； 低盐饮食中的钠；以及增加肾脏血流量，血浆 当狗变得肥胖时，醛固酮、胰岛素和儿茶酚胺。3. 将评估高胰岛素血症对肥胖患者血压的影响。 使用正常血糖胰岛素夹。此外，我们将管理一个 给10只狗造成慢性高胰岛素血症。我们认为慢性病 高胰岛素血症(与体重增加无关)将导致钠 并使血压、心率和心输出量增加。4. 醛固酮的作用将通过观察 肾上腺切除术对肥胖性高血压发病的影响我们希望 发现肾上腺切除将钝化但不能消除肥胖高血压。 我们还将确定肾上腺对血管紧张素II的敏感性是否增加。 随着肥胖症的发展而发生，通过分级输注 血管紧张素Ⅱ在肥胖发生之前和之后都有。5. 最后，交感神经系统的作用将通过 测量儿茶酚胺在发育过程中的变化 肥胖和正糖性高胰岛素血症。