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 食物摄入时间影响多种病理生理系统。西方饮食中含有大量 盐也会导致与肥胖和高血压相关的发病率和死亡率过高。夜 肥胖经常发生高血压，并被认为是高血压风险的重要后果， 然而，人们对这种现象所涉及的机制知之甚少。我们组的实验数据 研究表明，摄入钠的时间会影响钠排泄的昼夜模式。此外，我们最近 报道称，高盐摄入会导致肾脏中昼夜节律控制基因的表达发生变化。额外的 研究表明，肥胖动物对利尿钠刺激的反应受损。 考虑到高盐摄入对肥胖依赖性高血压的影响已明确，特别是， 夜间高血压，我们假设一天中盐摄入的时间会影响 (1) 血压节律 和尿钠排泄以及（2）负责血压调节的因素的昼夜节律时间和 肥胖个体的心脏代谢健康。由于夜间高血压的患病率非常高 和黑人成人的盐敏感性，我们将对 55 名肥胖黑人进行随机、交叉喂养研究 睡眠血压不下降的成年人。 这些研究将解决两个目标。第一个目标将检验以下假设：首先限制高盐摄入量 睡眠会增加血压的昼夜差异，改善尿钠排泄的时间，并且 改善代谢危险因素。我们会通过动态血压监测24小时血压 监测以确定钠摄入时间对昼夜血压模式的作用。日夜- 钠排泄的时间将用于确定血压的改善是否是由 白天加强钠排泄。我们还将评估钠摄入时间对血脂的影响， 24 小时内瘦素、脂联素、胰岛素敏感性、炎症细胞因子和免疫细胞激活。 第二个目标将检验以下假设：睡前限制高盐摄入量优先改善睡眠质量 与肾钠处理相关的外周生物钟因素与中枢生物钟因素的节律性。昼夜节律措施 血浆皮质醇的浓度、弱光褪黑激素的产生和核心体温（遥测）将用于评估 核心生物钟的相位和幅度。口腔细胞外周时钟基因的昼夜节律测量 外周血单核细胞将用于确定外周时钟的相位和幅度。 拟议的假设驱动研究将确定钠摄入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时间， 最终目标是确定治疗夜间高血压和肥胖代谢性疾病的新策略。