Aldosterone and Sodium Regulation in Postural Tachycardia Syndrome

体位性心动过速综合征中醛固酮和钠的调节

• 批准号: 8494682
• 负责人: SATISH R RAJ
• 金额: $ 45.07万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8494682
• 关键词: Adrenal Glands; Age; Aldosterone; Angiotensin II; Angiotensins; Blood Plasma Volume; Blood Volume; Child; Chronic; Chronic Obstructive Airway Disease; Chronic Orthostatic Intolerance; Clinical; Congestive Heart Failure; Data; Diet; Disease; Excretory function; Female of child bearing age; Functional disorder; Heart Rate; Hormones; Hypovolemia; Incidence; Individual; Intake; Kidney; Lead; Light; Mediating; Mineralocorticoid Receptor; Mineralocorticoids; Patients; Physiological; Play; Posture; Predisposition; Publishing; Quality of life; Regulation; Role; Sodium; Stress; Symptoms; Syndrome; Tachycardia; Testing; Time; Woman; disability; functional disability; health related quality of life; improved; men; patient population; public health relevance; receptor; response; saluretic

DESCRIPTION (provided by applicant): Postural Tachycardia Syndrome (POTS) is a debilitating clinical condition characterized by intolerance to upright posture of at least 6 months duration, associated with consistent orthostatic tachycardia of at least 30 bpm, and with orthostatic symptoms relieved by lying down. POTS is primarily a disorder of women (4-5 fold incidence over men) with predisposition for younger individuals, often of child-bearing age. We and others have found that patients with POTS have significantly diminished health-related quality of life, to levels comparable to patients with congestive heart failure or chronic obstructive pulmonary disease. While grossly elevated heart rates are the hallmark physiologic findings in POTS, there are several other important physiological abnormalities. We have found low plasma volume in the majority of patients with POTS. This can trigger the sympathetic activation that drives the tachycardia. The exact cause of the hypovolemia has not been elucidated, but our preliminary studies indicate that aldosterone levels are paradoxically diminished, and this likely contributes to the low blood volume. Quite surprisingly in light of the low aldosterone and blood volume, angiotensin II levels were elevated in patients with POTS. These data suggest a decreased adrenal sensitivity to angiotensin II in patients with POTS. Perturbations in the Angiotensin-Aldosterone Axis may play a critical role in the pathophysiology of POTS. Our preliminary studies also indicate that patients with POTS have an impaired ability to retain sodium at times of stress or depletion. In addition to an inadequate level of circulating aldosterone in POTS, there could be diminished renal sensitivity to mineralocorticoid stimulation in these patients. Given the low plasma volume in many patients with POTS, a common strategy in their management is to ask patients to follow a high sodium diet, in an effort to increase their plasma volume. Unfortunately, there are no published data demonstrating that this simple strategy is effective in this patient population. Our overarching hypothesis is that problems in aldosterone and sodium handling lead to reduced plasma volume and that these factors play an important role in the pathophysiology of POTS. To the test these hypotheses we propose the following Specific Aims: 1. To test the hypothesis that in patients with POTS that AT1 Receptor mediated aldosterone release is blunted. 2. To determine the anti-natriuretic response to aldosterone in patients with POTS. 3. To test the hypothesis that patients with POTS have a blunted (inadequate) plasma volume expansion in response to a high sodium diet. 4. To test the hypothesis that chronic mineralocorticoid stimulation can restore blood volume in POTS.

描述（由申请人提供）：姿势心动过速综合征（POTS）是一种使人衰弱的临床状况，其特征在于至少6个月的直立姿势不宽容，与一致的直立性心动过速至少为30 bpm，并且与原位的症状相关。锅主要是女性（男性的4-5倍发病率），对年轻人（通常是育儿年龄）的易感性。我们和其他人发现，盆栽患者的生活质量显着降低，其水平与充血性心力衰竭或慢性阻塞性肺部疾病的患者相当。 虽然心率严重升高是盆中的标志性生理发现，但还有其他一些重要的生理异常。我们发现大多数POTS患者的血浆体积较低。这可以触发驱动心动过速的交感神经激活。尚未阐明低血容量的确切原因，但是我们的初步研究表明，醛固酮水平矛盾地降低，这可能导致血液量低。鉴于低醛固酮和血容量，血管紧张素II的水平升高了。这些数据表明盆腔患者对血管紧张素II的肾上腺敏感性降低。血管紧张素 - 醛固酮轴的扰动可能在盆的病理生理学中起关键作用。我们的初步研究还表明，盆栽患者在压力或耗尽时保持钠的能力受损。除了盆中的循环醛固酮水平不足外，这些患者对矿物皮质激素刺激的敏感性可能会降低。鉴于许多花盆患者的血浆量低，管理中的一种常见策略是要求患者遵循高钠饮食，以增加血浆量。不幸的是，没有公开的数据表明这种简单的策略在该患者人群中有效。 我们的总体假设是，醛固酮和钠处理的问题导致血浆量减少，并且这些因素在盆栽的病理生理学中起重要作用。为了测试这些假设，我们提出了以下特定目的：1。检验以下假设：在AT1受体介导的醛固酮释放的盆中患者中。 2。为了确定盆患者对醛固酮的抗钠尿素反应。 3。检验以下假设：盆栽患者对高钠饮食的钝化血浆体积膨胀（不足）的膨胀。 4。为了测试慢性盐皮质激素刺激可以恢复盆中的血液体积的假设。