MECHANISM OF OBESITY HYPERTENSION IN ADOLESCENTS

青少年肥胖高血压的机制

• 批准号: 3349966
• 负责人: Albert P Rocchini
• 金额: $ 22.89万
• 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: 1985-09-30 至 1990-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3349966
• 关键词: adolescence (12-20); angiotensin /renin /aldosterone hypertension; erythrocytes; homeostasis; human subject; hyperaldosteronism; hyperinsulinism; hypertension; norepinephrine; obesity; renal tubular transport; salt intake; saluresis; sympathetic nervous system; weight control

Despite the strong association between obesity and hypertension little is known about the mechanism. Since part of the confusion as to the mechanisms of obesity hypertension may be due to complications of long standing hypertension, we have directed our investigative efforts into studying the pathogenesis of hypertension in obese adolescents, a population that represents an early stage of the disease. Based on these studies we will postulate that the hypertension of obesity is primarily related to increased sodium retention by the kidney. We speculate that the combined effects of increased sympathetic nervous system activity, hyperinsulinemia and hyperaldosteronism cause the kidney not only to retain sodium but also to readapt to a new and elevated blood volume and pressure. The following experiments will test this hypothesis: 1) Since our preliminary data suggests that obese adolescents are sodium-sensitive with regards to blood pressure, we will assess the role of sodium intake on blood pressure before and after weight loss. We speculate that weight loss will decrease the degree of sodium-sensitivity of pressure. This change in sodium-sensitivity also will be accompanied by an adaptation of the kidney permitting readjustment to a lower blood volume and cardiac output. Our previous demonstration of increased red cell cotransport activity after weight loss suggest it may be a marker of a change in renal tubular transport capacity. We will now correlate red cell cotransport activity with renal tubular transport capacity before and after weight loss. 2) We will determine if, in obesity, a hyperinsulinemic state marked by resistance to the effects of insulin on glucose metabolism, that the sodium-retaining function of insulin is maintained intact. 3) Since we have documented that obese adolescents have an increased plasma aldosterone and with weight loss the decrease in pressure correlates with the decrease in aldosterone, we will now evaluate the control of aldosterone secretion by measuring urinary excretion of aldosterone and its metabolities (an index of aldosterone secretion) and by measuring adrenal responsiveness to angiotensin II, using Captopril to block the production of angiotensin II. 4) The role of the sympathetic nervous system will be evaluated by measuring plasma catecholamines at rest and during euglycemic hyperinsulinemia and by measuring norepinephrine release, clearance and vascular reactivity.

尽管肥胖和高血压之间有很强的联系， 了解机制。 由于部分的混乱， 肥胖高血压的机制可能是由于长期的并发症， 长期高血压，我们已经把我们的调查工作， 研究肥胖青少年高血压的发病机制， 代表疾病早期阶段的人群。 基于这些 研究我们将假设肥胖的高血压主要是 与肾脏钠潴留增加有关。 我们推测 交感神经系统活性增加的综合作用， 高胰岛素血症和高醛固酮血症不仅使肾脏保留 钠，但也重新适应新的和升高的血容量， 压力 以下实验将验证这一假设：1）由于 我们的初步数据表明肥胖青少年对钠敏感， 关于血压，我们将评估钠摄入量对 减肥前后的血压 我们推测减肥 将降低压力的钠敏感度。 的这种变化 钠敏感性也将伴随着肾脏的适应 允许重新调整以适应较低的血容量和心输出量。 我们 先前证明红细胞共转运活性增加， 体重减轻表明它可能是肾小管变化的标志 运输能力。 我们现在将红细胞共转运活性 与体重减轻前后肾小管转运能力的关系。 2)我们 将决定肥胖者是否处于高胰岛素血症状态， 抵抗胰岛素对葡萄糖代谢的影响， 胰岛素的钠保持功能保持完整。3)既然我们 已经证实肥胖青少年的血浆醛固酮增加 随着体重的减轻，压力的降低与 在醛固酮中，我们现在将评估对醛固酮分泌的控制 通过测量尿中醛固酮的排泄及其代谢（一种 醛固酮分泌指数），并通过测量肾上腺对 血管紧张素II，使用Captopril来阻断血管紧张素II的产生。 4)交感神经系统的作用将通过 测量静息时和血糖正常时的血浆儿茶酚胺 高胰岛素血症和通过测量去甲肾上腺素释放，清除和 血管反应性