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: 10200882
• 负责人: NORRINA Bai ALLEN
• 金额: $ 73.47万
• 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/10200882
• 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; Prognosis; 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; 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.

项目总结/摘要 血压的盐敏感性（SSBP）定义为血压（BP）的变化与盐浓度变化的关系。 盐的摄入量。从低盐饮食到高盐饮食的血压升高是常见的，并与以下风险增加有关： 心血管疾病的发病率和死亡率，甚至在血压正常的个体中。然而， SSBP并没有被很好地理解。流行的观点是，调节神经系统的神经激素异常 钠（Na+）潴留和排泄和/或Na+转运途径造成Na+失衡， 对SSBP的敏感性。作为一种自我平衡机制，血压波动以维持Na+平衡，即较高的血压 需要加压尿钠排泄来排出过量的Na+。替代框架强调血管 作为刺激机制的失调。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+诱导促炎状态 维持较高的血压白细胞介素-6（IL-6）驱动分泌白细胞介素-17（IL-17）的辅助性T细胞17的诱导 最近被证明是响应于Na+暴露的致病细胞。IL-6、IL-17及相关 细胞因子调节肾Na+转运蛋白，并通过血管炎症、纤维化和受损 血管舒张然而，人类对高盐和低盐饮食的免疫反应并不完全相同。 理解，强调需要进行更详细的人体研究，根据 控制盐条件和神经激素评估。我们的首要假设是， 对过量饮食盐摄入的炎症反应与SSBP相关。冠状动脉风险 青年人发展（CARDIA）研究是转化我们初步研究结果的理想队列。 我们建议使用标准化的低盐和高盐饮食以及24小时的 动态血压监测。我们将量化来自芝加哥和 伯明翰场中心在即将到来的一年35考试（从2020年开始）。我们的具体目标是：1） 定义SSBP及其临床相关因素在当代以社区为基础的美国队列中的分布， 中年人; 2）研究对饮食盐负荷的免疫反应，3）研究 饮食盐负荷的免疫和BP反应之间的关联。拟议的研究是一项 这是一个独特的机会，可以利用一个大型的，表型良好的队列来测试关于SSBP的新假设。 在CARDIA中使用标准化的高盐和低盐饮食对SSBP进行表型分析将是新颖的，因为这是前所未有的 在任何现有的美国NHLBI申办的心血管流行病学队列中进行。的 拟议的工作有可能产生一个更容易获得的方法来区分个人， 盐敏感或耐盐。对SSBP病理生理学的新认识也应该为以下方面提供基础： 调查高影响力的临床应用，通过告知未来针对SSBP的治疗研究。的 CARDIA中丰富的临床、遗传和生化数据进一步增强了科学的严谨性。