Dietary sodium, inflammation, and salt sensitivity of blood pressure

膳食钠、炎症和血压的盐敏感性

• 批准号: 10452631
• 负责人: NORRINA Bai ALLEN
• 金额: $ 81.26万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10452631
• 关键词: Adult; Affect; Ambulatory Blood Pressure Monitoring; Biochemical; Biological Markers; Blood Pressure; Blood Vessels; Cardiovascular Diseases; Cardiovascular system; Cells; Cerebrovascular Disorders; Cessation of life; Chicago; Chronic; Clinical; Communities; Coronary Artery Risk Development in Young Adults Study; Crossover Design; Data; Dietary Sodium; Epidemiology; Equilibrium; Excess Dietary Salt; Excretory function; Experimental Models; Fibrosis; Foundations; Functional disorder; Future; Hour; Human; Hypertension; Hypotension; Immune; Immune response; Impairment; In Vitro; Individual; Inflammation; Inflammatory; Inflammatory Response; Insulin Resistance; Intake; Interleukin-10; Interleukin-17; Interleukin-6; Investigation; Kidney; Kidney Diseases; Measures; Medical Genetics; Modeling; Morbidity - disease rate; National Heart, Lung, and Blood Institute; Natriuresis; Neurohormones; Outcome; Oxidative Stress; Participant; Pathogenesis; Pathogenicity; Pathway interactions; Persons; Pharmaceutical Preparations; Phenotype; Physiological; Predisposition; Prognosis; Randomized; Recommendation; Resistance; Signal Transduction; Sodium; Sodium Chloride; Sodium-Restricted Diet; Standardization; T-Lymphocyte; Testing; Translating; Vasodilation; Work; base; blood pressure elevation; cardiovascular risk factor; circulating biomarkers; clinical application; cohort; cytokine; diagnostic strategy; dietary salt; follow-up; high salt diet; hypertensive; immunoregulation; inflammatory marker; insight; middle age; mortality; normotensive; novel; polarized cell; pressure; prospective; response; salt intake; salt sensitive; urinary; vascular inflammation

PROJECT SUMMARY/ABSTRACT Salt sensitivity of blood pressure (SSBP) is defined as the change in blood pressure (BP) in relation to change in salt intake. An increase in BP from low- to high-salt diet is common and associated with an increased risk of cardiovascular morbidity and mortality, even among normotensive individuals. Yet, the pathophysiology of SSBP is not well understood. The prevailing paradigm is that abnormalities of neurohormones that regulate sodium (Na+) retention and excretion and/or Na+ transporting pathways create Na+ imbalances that underlie susceptibility to SSBP. As a homeostatic mechanism, BP fluctuates to maintain Na+ balance, i.e. higher BP is needed for pressure natriuresis to excrete excess Na+. An alternate framework emphasizes vascular dysregulation as the inciting mechanism. In both constructs, how Na+ itself influences BP remains incompletely understood. Our preliminary work suggests that excess Na+ induces a pro-inflammatory state that sustains higher BP. Interleukin-6 (IL-6) drives the induction of interleukin-17 (IL-17) secreting T helper 17 cells that were recently demonstrated to be pathogenic in response to Na+ exposure. IL-6, IL-17 and related cytokines regulate renal Na+ transporters and raise BP through vascular inflammation, fibrosis, and impaired vasodilation. The immune response to high- and low-salt diet in humans, however, is not completely understood, emphasizing the need for more detailed human studies, with deeper immune profiling under controlled salt conditions and with neurohormonal assessment. Our overarching postulate is that the inflammatory response to excess dietary salt intake is associated with SSBP. The Coronary Artery Risk Development in Young Adults (CARDIA) study is the ideal cohort in which to translate our preliminary findings. We propose to investigate SSBP in CARDIA using standardized low- and high-salt diets and 24-hour ambulatory BP monitoring. We will quantify SSBP in a total of 500 participants from the Chicago and Birmingham field centers during the upcoming year 35 exam (beginning in 2020). Our specific aims are: 1) to define the distribution of SSBP and its clinical correlates in a contemporary community-based US cohort of middle-aged individuals; 2) to investigate the immune response to dietary salt loading, and 3) to investigate the association between the immune and BP responses to dietary salt loading. The proposed study represents a unique opportunity to leverage a large, well-phenotyped cohort to test novel hypotheses regarding SSBP. Phenotyping SSBP using standardized high- and low-salt diets in CARDIA will be novel as this has never been performed in any of the existing US based NHLBI sponsored cardiovascular epidemiologic cohorts. The proposed work has the potential to yield a more readily available approach for differentiating an individual as salt-sensitive or resistant. New insights into the pathophysiology of SSBP should also provide a foundation for investigating high-impact clinical applications, by informing future studies of therapies directed at SSBP. The scientific rigor is further enhanced by the rich clinical, genetic, and biochemical data available in CARDIA.

项目摘要/摘要 血压盐敏感性(SSBP)被定义为与血压变化相关的血压变化 在盐分摄入量方面。从低盐饮食到高盐饮食，血压升高是很常见的，并与患高血压的风险增加有关。 心血管发病率和死亡率，即使在血压正常的人中也是如此。然而，这一疾病的病理生理学 SSBP还没有被很好地理解。流行的范式是调节神经激素的异常 钠(Na+)滞留和排泄和/或钠离子转运途径造成了钠离子失衡 对SSBP的敏感性。作为一种体内平衡机制，血压波动以维持钠离子平衡，即较高的血压是 压力钠排泄过量的钠离子所必需的。另一种框架强调血管 作为激励机制的调控失调。在这两种结构中，Na+本身如何影响BP仍然存在 不完全理解。我们的初步工作表明，过量的Na+会导致促炎状态 这支撑了更高的BP。白介素6(IL-6)诱导分泌IL-17的辅助性T细胞 最近被证明是对Na+暴露作出反应的致病细胞。IL-6、IL-17及其相关因子 细胞因子通过血管炎症、纤维化和受损调节肾脏Na+转运体和升高血压 血管扩张。然而，人类对高盐和低盐饮食的免疫反应并不完全。 理解，强调需要更详细的人体研究，并在以下条件下进行更深入的免疫分析 控制盐分条件，并进行神经激素评估。我们最重要的假设是 食盐摄入过多引起的炎症反应与SSBP有关。冠状动脉风险 青年发展研究(CARDIA)是翻译我们初步发现的理想队列。 我们建议使用标准化的低盐和高盐饮食和24小时来研究心脏病患者的SSBP 动态血压监测。我们将量化来自芝加哥的500名参与者的SSBP 在即将到来的35年级考试(从2020年开始)期间，伯明翰球场将成为中心。我们的具体目标是：1) 确定SSBP在当代以社区为基础的美国队列中的分布及其临床相关性 2)调查饮食盐负荷的免疫反应；3)调查 饮食盐负荷引起的免疫反应和血压反应之间的关系。拟议的研究代表了一项 利用一个大型的、表型良好的队列来测试关于SSBP的新假设的独特机会。 在CARDIA中使用标准化的高盐和低盐饮食对SSBP进行表型鉴定将是前所未有的 在任何现有的美国NHLBI赞助的心血管流行病学队列中进行。这个 拟议的工作有可能产生一种更容易获得的方法来区分个体AS 耐盐的对盐敏感或耐盐的对SSBP病理生理学的新见解也应该为 通过告知针对SSBP的治疗方法的未来研究，调查高影响的临床应用。这个 CARDIA提供的丰富的临床、遗传和生化数据进一步增强了科学的严谨性。