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: 10649700
• 负责人: Orlando M Gutierrez
• 金额: $ 56.03万
• 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/10649700
• 关键词: ARNTL gene; Acute; Adult; Affect; African American; African American population; Ambulatory Blood Pressure Monitoring; Animal Feed; Animals; Blood Pressure; Body Temperature; Cells; Circadian desynchrony; Cross-Over Trials; Data; Defect; Diet; Dietary Sodium; Dyslipidemias; Eating; Endothelin; 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; Leptin; Light; Link; Lipids; Measures; Mediating; Melatonin; Metabolic; Metabolic Diseases; Molecular; Monitor; Morbidity - disease rate; Nocturnal Hypertension; 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; Time Factors; Tissues; adiponectin; adult obesity; awake; blood pressure control; 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.

摘要 食物摄入的时间会影响各种病理生理系统。西方饮食，这是高含量的 与肥胖和高血压相关的过量发病率和死亡率也是由盐引起的。夜间活动 高血压经常出现在肥胖中，并被认为是高血压风险的重要后果， 然而，人们对这一现象涉及的机制知之甚少。来自我们小组的实验数据 研究表明，钠的摄入时间会影响每天的钠排泄模式。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。其他内容 研究表明，肥胖的动物对利钠刺激的反应受损。 鉴于高盐摄入量对肥胖依赖型高血压的既定贡献，尤其是， 夜间高血压，我们假设一天中摄入盐分的时间影响(1)血压节律 和尿钠排泄以及(2)血压调节因素的昼夜节律和 肥胖者的心脏代谢健康。因为夜间高血压的发病率很高 和盐敏感性，我们将对55名肥胖的黑人进行随机交叉喂养研究 成年人睡眠时血压不会下降。 这些研究将解决两个目标。第一个目标将检验这样一种假设，即限制高盐摄入量 睡眠增加血压的昼夜差异，改善尿钠排出的时间，以及 改善代谢风险因素。我们将通过动态血压24小时监测血压 监测以确定钠摄入时机对昼夜血压模式的影响。日日夜夜- 钠排泄时间将被用来确定血压的改善是否通过 白天钠排泄增加。我们还将评估钠摄取时机对血脂的影响， 瘦素、脂联素、胰岛素敏感性、炎症细胞因子和免疫细胞在24小时内的激活。 第二个目标将检验这样的假设，即睡前限制高盐摄入量会优先改善效果。 与肾脏钠处理有关的外周与中枢昼夜节律时钟因素的节律性。昼夜节律测量 血浆皮质醇、暗光褪黑素开始和核心体温(遥测)将被用来评估 核心昼夜节律时钟的相位和幅度。颊细胞外周时钟基因的昼夜节律测量 外周血单核细胞将被用来确定外周时钟的相位和幅度。 拟议的假设驱动的研究将确定钠的摄入时间如何影响每天的血液。 血压和昼夜节律因素对血压控制和新陈代谢健康的影响 最终目标是确定治疗夜间高血压和肥胖症代谢性疾病的新策略。