Timing of sodium intake and nocturnal sodium excretion and blood pressure in obese African Americans

肥胖非裔美国人的钠摄入时间和夜间钠排泄以及血压

• 批准号: 10215613
• 负责人: Orlando M Gutierrez
• 金额: $ 71.31万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10215613
• 关键词: ARNTL gene; Acute; Address; Adult; Affect; African American; Ambulatory Blood Pressure Monitoring; Animals; Blood Pressure; Body Temperature; Cells; Circadian desynchrony; Clinical Data; Cross-Over Trials; Data; Defect; Diet; Dietary Sodium; Dyslipidemias; Eating; Endothelin; Endothelin-1; Energy Intake; Equilibrium; Excess Dietary Salt; Excretory function; Gene Expression; Genes; Glucose; Goals; Health; High Prevalence; Homeostasis; Hour; Human; Hydrocortisone; Hypertension; Impairment; Inflammatory; Intake; Kidney; Lead; Leptin; Light; Link; Lipids; Measures; Mediating; Melatonin; Metabolic; Metabolic Diseases; Molecular; Monitor; Morbidity - disease rate; Obesity; Participant; Pathway interactions; Pattern; Periodicity; Peripheral; Phase; Plasma; Randomized; Rattus; Reporting; Resistance; Risk; Risk Factors; Role; Serum; Sleep; Sodium; Sodium Chloride; Speed; Stimulus; System; Tablets; Telemetry; Testing; Time; Tissues; adiponectin; adult obesity; awake; base; blood pressure regulation; cardiometabolism; cardiovascular disorder risk; cardiovascular risk factor; circadian; circadian pacemaker; cytokine; dietary salt; feeding; high risk; high salt diet; immune activation; improved; innovation; insulin sensitivity; molecular clock; monocyte; mortality; novel strategies; obese person; obesity risk; peripheral blood; pre-clinical; preclinical study; receptor; receptor function; response; salt intake; salt sensitive; salt sensitive hypertension; saluretic; urinary; western diet

SUMMARY Timing of food intake affects a variety of pathophysiological systems. The Western diet, which is high in salt, also contributes to excess morbidity and mortality related to obesity and hypertension. Nocturnal hypertension frequently occurs in obesity and is recognized as an important consequence of hypertension risk, yet the mechanisms involved in this phenomenon are poorly understood. Experimental data from our group have shown that timing of sodium intake impacts diurnal patterns of sodium excretion. Further, we recently reported that high salt intake causes a shift in expression of circadian control genes in the kidney. Additional studies demonstrate that obese animals have an impaired response to a natriuretic stimulus. Given the established contribution of high salt intake to obesity-dependent hypertension, particularly, nocturnal hypertension, we hypothesize that the time of day for salt intake impacts (1) blood pressure rhythms and urinary sodium excretion and (2) circadian timing of factors responsible for blood pressure regulation and cardiometabolic health in obese individuals. Because of the very high prevalence of nocturnal hypertension and salt-sensitivity in black adults, we will conduct a randomized, cross-over feeding study of 55 obese black adults with non-dipping sleep blood pressure. These studies will address two aims. The first aim will test the hypothesis that limiting high salt intake prior to sleep increases day-night differences in blood pressure, improves timing of urinary sodium excretion, and improves metabolic risk factors. We will monitor 24-hour blood pressure by ambulatory blood pressure monitoring to determine the role of timing of sodium intake on diurnal blood pressure patterns. Day- and night- time sodium excretion will be used to determine whether improvements in blood pressure are mediated by enhanced sodium excretion during the day. We will also assess the effects of timing of sodium intake on lipids, leptin, adiponectin, insulin sensitivity, inflammatory cytokines, and immune cell activation over 24 hours. The second aim will test the hypothesis that limiting high salt intake prior to sleep preferentially improves rhythmicity in peripheral vs. central circadian clock factors linked to renal sodium handling. Circadian measures of plasma cortisol, dim light melatonin onset, and core body temperature (telemetry) will be used to assess the phase and amplitude of the core circadian clock. Circadian measures of peripheral clock genes in buccal cells and peripheral blood monocytes will be used to determine the phase and amplitude of the peripheral clock. The proposed hypothesis-driven studies will determine how timing of sodium intake affects diurnal blood pressure and circadian timing of factors responsible for blood pressure control and metabolic health, with the ultimate goal of identifying novel strategies to treat nocturnal hypertension and metabolic disease in obesity.

概括 食物摄入的时间影响各种病理生理系统。西方饮食很高 盐，也导致与肥胖和高血压有关的过量发病率和死亡率。夜 高血压经常发生在肥胖症中，被认为是高血压风险的重要结果， 然而，这种现象所涉及的机制知之甚少。来自我们小组的实验数据 已经表明，钠摄入的时机会影响钠排泄的昼夜模式。此外，我们最近 报道说，高盐摄入会导致肾脏中昼夜节律基因表达的转移。额外的 研究表明，肥胖动物对亚钠刺激的反应受损。 考虑到高盐摄入对肥胖依赖性高血压的既定贡献，特别是 夜间高血压，我们假设盐摄入量的一天时间（1）血压节奏 和尿钠排泄和（2）负责血压调节和 肥胖个体的心脏代谢健康。由于夜间高血压的患病率很高 和黑人成年人的盐敏感性，我们将对55个肥胖黑色的随机，交叉喂养研究 成年人不浸泡睡眠血压。 这些研究将针对两个目标。第一个目的将检验以下假设：限制先验的高盐摄入量 睡眠会增加血压的昼夜差异，改善尿钠排泄的时间，并 改善新陈代谢风险因素。我们将通过门诊血压监测24小时血压 监测以确定钠摄入量计时对昼夜血压模式的作用。日夜- 时间排泄将用于确定血压改善是否由 白天增强的钠排泄。我们还将评估钠摄入量计时对脂质的影响， 瘦素，脂联素，胰岛素敏感性，炎症细胞因子和免疫细胞活化在24小时内。 第二个目的将检验以下假设：限制在睡眠之前限制高盐的摄入量优先改善 与肾脏钠处理有关的外围与中央昼夜节律因素的节奏性。昼夜节律措施 血浆皮质醇，昏暗的光褪黑激素的发作和核心体温（遥测）将用于评估 核心昼夜节律时钟的相位和振幅。颊细胞中外围钟基因的昼夜节律测量 外周血单核细胞将用于确定外围时钟的相位和振幅。 提出的假设驱动的研究将决定钠摄入的时间如何影响昼夜血液 负责血压控制和代谢健康的因素的压力和昼夜节律，与 确定肥胖症中夜间高血压和代谢疾病的新型策略的最终目标。