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: 9978945
• 负责人: NORRINA Bai ALLEN
• 金额: $ 74.29万
• 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 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9978945
• 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; Diagnostic; 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; Pharmaceutical Preparations; Phenotype; Physiological; Predisposition; Randomized; Recommendation; Resistance; Signal Transduction; Sodium; Sodium Chloride; Sodium-Restricted Diet; Standardization; T-Lymphocyte; Testing; Translating; Vasodilation; Work; base; cardiovascular risk factor; circulating biomarkers; clinical application; cohort; cytokine; dietary salt; follow-up; high salt diet; immunoregulation; inflammatory marker; insight; middle age; mortality; normotensive; novel; outcome forecast; 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（SSBP）的盐灵敏度定义为与变化有关的血压变化（BP） 在盐的摄入量中。 BP从低盐饮食的增加很常见，并且与增加的风险有关 心血管发病率和死亡率，即使在正常的个体中也是如此。然而， SSBP不太了解。流行的范式是调节神经激素的异常 钠（Na+）保留和排泄和/或Na+运输途径产生的Na+不平衡是构成基础的 对SSBP的敏感性。作为一种体内稳态机制，BP波动以维持Na+平衡，即较高的BP为 压力纳地尿需要排出多余的Na+所需的。一个替代框架强调血管 失调作为煽动机制。在这两个结构中，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，多余的NA+诱导了促炎状态 维持更高的BP。白介素-6（IL-6）驱动介绍白介素17（IL-17）分泌T助手17 最近证明对Na+暴露的细胞是致病性的。 IL-6，IL-17及相关 细胞因子调节肾脏Na+转运蛋白，并通过血管炎症，纤维化和受损而提高BP 血管舒张。然而，人类对高盐和低盐饮食的免疫反应并非完全 理解，强调需要进行更详细的人类研究，并具有更深的免疫分析 受控的盐条件和神经激素评估。我们的总体假设是 SSBP对过量饮食盐摄入的炎症反应与SSBP有关。冠状动脉风险 年轻人的发展（CARDIA）研究是转化我们初步发现的理想人群。 我们建议使用标准化的低盐和高盐饮食和24小时来研究Cardia中的SSBP 卧床BP监测。我们将在来自芝加哥的总共500名参与者中量化SSBP，并 在即将到来的35年级考试（从2020年开始）中，伯明翰野战中心。我们的具体目的是：1） 定义SSBP的分布及其临床相关性 中年人； 2）研究对饮食盐负荷的免疫反应，3）研究 免疫和BP对饮食盐负荷的反应之间的关联。拟议的研究代表 利用大型，良好的同类队列来检验有关SSBP的新假设的独特机会。 使用标准化的高盐饮食Cardia中的表型SSBP将是新颖的，因为这从未有过 在现有的美国NHLBI赞助的心血管流行病学队列中进行。这 拟议的工作有可能产生更容易获得的方法，以区分个人 盐敏感或抗性。对SSBP病理生理学的新见解也应为 通过告知针对SSBP的疗法的未来研究，研究高影响力的临床应用。这 CADCIA可用的丰富临床，遗传和生化数据进一步增强了科学严谨性。