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

总结 食物摄入的时间影响各种病理生理系统。西方饮食，其中高， 盐也是导致肥胖和高血压发病率和死亡率过高的原因。夜间 高血压经常发生在肥胖症中并且被认为是高血压风险的重要后果， 然而，人们对这一现象所涉及的机制知之甚少。我们小组的实验数据 已经表明，钠摄入的时间会影响钠排泄的昼夜模式。此外，我们最近 高盐摄入导致肾脏中昼夜节律控制基因表达的变化。额外 研究表明肥胖动物对利尿钠刺激的反应受损。 鉴于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，我们假设一天中的盐摄入时间影响（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， 肥胖个体的心脏代谢健康。由于夜间高血压的发病率很高， 和盐敏感性，我们将对55名肥胖黑人进行随机交叉喂养研究。 成人睡眠血压不下降。 这些研究将针对两个目标。第一个目标是检验限制高盐摄入量优先于 睡眠增加血压的昼夜差异，改善尿钠排泄的时间， 改善代谢危险因素。我们将通过动态血压监测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。不分昼夜- 将使用钠排泄时间来确定血压的改善是否由以下因素介导： 白天增加钠排泄。我们还将评估钠摄入时间对脂质的影响， 瘦素、脂联素、胰岛素敏感性、炎性细胞因子和免疫细胞活化。 第二个目标是检验睡眠前限制高盐摄入量优先改善 与肾钠处理相关的外周与中枢生物钟因素的节律性。昼夜节律测量 血浆皮质醇、昏暗光褪黑激素起效和核心体温（遥测）将用于评估 核心生物钟的相位和振幅。颊黏膜细胞外周时钟基因的昼夜节律测定 外周血单核细胞将用于确定外周时钟的相位和幅度。 这些假设驱动的研究将确定钠摄入的时间如何影响昼夜血液 压力和昼夜节律的因素，负责血压控制和代谢健康，与 最终目标是确定治疗肥胖症患者夜间高血压和代谢性疾病的新策略。

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.