MECHANISM OF OBESITY HYPERTENSION IN ADOLESCENTS

青少年肥胖高血压的机制

• 批准号: 3349967
• 负责人: Albert P Rocchini
• 金额: $ 23.77万
• 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/3349967
• 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; sodium potassium exchanging ATPase; 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存在密切联系，但很少有研究表明 了解该机制。 由于部分混乱 肥胖高血压的机制可能是由于长期的并发症 长期高血压，我们已将调查工作转向 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 研究中我们假设肥胖引起的高血压主要是 与肾脏钠潴留增加有关。 我们推测 交感神经系统活动增加的综合影响， 高胰岛素血症和醛固酮增多症不仅导致肾脏保留 钠还可以重新适应新的和升高的血容量， 压力。 以下实验将检验这一假设： 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血压的影响 减肥前后的血压。 我们推测减肥 会降低钠对压力的敏感性程度。 这一变化在 钠敏感性也会伴随肾脏的适应 允许重新调整至较低的血容量和心输出量。 我们的 先前证明红细胞协同转运活性增加 体重减轻表明这可能是肾小管变化的标志 运输能力。 我们现在将关联红细胞协同转运活动 减肥前后的肾小管转运能力。 2）我们 将确定肥胖症中是否存在以 抵抗胰岛素对葡萄糖代谢的影响，即 胰岛素的钠保留功能保持完整。 3）自从我们 有文献记载，肥胖青少年的血浆醛固酮水平升高 随着体重减轻，压力的降低与压力的降低相关 在醛固酮方面，我们现在将评估醛固酮分泌的控制 通过测量醛固酮的尿排泄及其代谢（ 醛固酮分泌指数）并通过测量肾上腺反应性 血管紧张素II，使用卡托普利阻断血管紧张素II的产生。 4) 交感神经系统的作用将通过以下方式评估 测量静息时和血糖正常期间的血浆儿茶酚胺 高胰岛素血症并通过测量去甲肾上腺素的释放、清除和 血管反应性。