Mechanisms Underlying the Protective Vascular Effects of Dietary Potassium in Humans

膳食钾对人体血管保护作用的机制

• 批准号: 10221040
• 负责人: Shannon Lennon
• 金额: $ 54.57万
• 依托单位: UNIVERSITY OF DELAWARE
• 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 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10221040
• 关键词: Adult; American; Animal Model; Animals; Antioxidants; Area; Arteries; Ascorbic Acid; Atherosclerosis; Atomic Force Microscopy; Attention; Attenuated; Biological Availability; Blood Pressure; Blood Vessels; Cardiovascular Diseases; Cells; Cessation of life; Collection; Conflict (Psychology); Consumption; Coupled; Crossover Design; Cutaneous; Data; Development; Diet; Dietary Factors; Dietary Potassium; Dietary Sodium; Endothelial Cells; Endothelium; Failure; Goals; Health; Heart Diseases; Heating; Hour; Human; Hypertension; Impairment; Individual; Intake; Laser-Doppler Flowmetry; Measurement; Mediating; Meta-Analysis; Microdialysis; Minority; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nutrient; Outcome; Oxidants; Oxidative Stress; Participant; Potassium; Production; Public Health; Pulse Pressure; Randomized; Reactive Oxygen Species; Research; Resistance; Risk Factors; Role; Sodium; Sodium Channel; Sodium Chloride; Stroke; Testing; Urine; Vascular Diseases; Vascular Endothelial Cell; Vasodilation; Venous; Woman; acetovanillone; antioxidant enzyme; brachial artery; cardiovascular disorder risk; endothelial dysfunction; feeding; high salt diet; improved; men; middle age; novel; preservation; protective effect; reactive hyperemia; response; tempol

ABSTRACT/PROJECT SUMMARY Significant Public Health efforts have been made towards salt reduction but most have met with failure. Dietary factors such high sodium/low potassium diets contribute to the development of cardiovascular diseases (CVDs) such as atherosclerosis and high blood pressure (BP). This is important as CVD is the number one killer in the U.S. While the role of these two nutrients on BP is widely accepted, their impact on the vasculature has received less attention. Endothelial dysfunction, characterized by impaired dilation, is an important non- traditional risk factor for atherosclerosis. We have shown that high sodium diets cause endothelial dysfunction, independent of changes in BP (accomplished by testing adults with salt resistant BP). Evidence supporting potassium's beneficial role on vascular health remains unclear although it may be more effective in the presence of a high sodium diet. A purported mechanism responsible for sodium-induced vascular dysfunction is overproduction of reactive oxygen species (ROS) resulting in reduced nitric oxide (NO) production/bioavailability. It has been suggested that potassium can counteract sodium's effects by reducing ROS. Additionally, high sodium diets have been shown to stiffen the endothelium by increasing abundance of the endothelial sodium channel (EnNaC) while potassium's role on EnNaC is unknown. Our central hypothesis is that dietary potassium will protect the vasculature from sodium's harmful effect by preserving NO and reducing oxidative stress and endothelial cell stiffness. We will use three 10-day diets to test our hypothesis (controlled feeding study, crossover design, diet order sequence randomized with washout between diets). We will compare a moderate potassium/high sodium diet (MK/HS; 65 mmol/300 mmol) to a high potassium/high sodium (HK/HS;120 mmol/300 mmol) to assess potassium's protective effect on the vasculature during a fixed sodium intake. We will also compare a moderate potassium/low sodium (MK/LS; 65 mmol/50 mmol) diet to the MK/HS diet to individually confirm salt resistant BP status. Focusing on salt resistant adults allows us to isolate the vascular effects, without the confound of changes in BP (i.e., independent of BP). Rigor will be enhanced by utilizing twenty-four hour ambulatory BP and urine collections during each diet condition; men, women, and minorities will be tested. Brachial artery flow-mediated dilation will be used to assess conduit endothelial- dependent dilation. Cutaneous vasodilation in response to local heating using laser Doppler flowmetry coupled with intradermal microdialysis will be used to assess microvascular function. Venous endothelial cells will be collected for direct assessment of cell stiffness by atomic force microscopy and markers of oxidative stress. We expect to demonstrate that dietary potassium protects the endothelium from the deleterious effects of high sodium by reducing oxidative stress and endothelial cell stiffness and preserving NO. These studies are novel in that they will be the first to comprehensively evaluate the role of dietary potassium on vascular function independent of BP.

摘要/项目摘要 公共卫生部门为减少盐摄入量做出了重大努力，但大多数都失败了。饮食 高钠/低钾饮食等因素会导致心血管疾病的发生 （CVD），例如动脉粥样硬化和高血压（BP）。这很重要，因为 CVD 是第一 虽然这两种营养素对血压的作用已被广泛接受，但它们对脉管系统的影响 受到的关注较少。以扩张受损为特征的内皮功能障碍是一个重要的非 动脉粥样硬化的传统危险因素。我们已经证明高钠饮食会导致内皮功能障碍， 独立于血压变化（通过测试患有耐盐血压的成人来实现）。证据支持 钾对血管健康的有益作用仍不清楚，尽管它可能更有效 高钠饮食的存在。据称导致钠诱导血管功能障碍的机制 活性氧 (ROS) 产生过多，导致一氧化氮 (NO) 减少 生产/生物利用度。有人认为钾可以通过减少钠的影响来抵消钠的影响。 活性氧。此外，高钠饮食已被证明可以通过增加丰富的内皮细胞来硬化内皮细胞。 内皮钠通道 (EnNaC)，而钾对 EnNaC 的作用尚不清楚。我们的中心假设 饮食中的钾可以通过保留一氧化氮和保护血管系统免受钠的有害影响 减少氧化应激和内皮细胞硬度。我们将使用三种 10 天饮食来检验我们的假设 （控制喂养研究、交叉设计、饮食顺序随机化，并在饮食之间进行淘汰）。我们 将比较中度钾/高钠饮食（MK/HS；65 mmol/300 mmol）与高钾/高钠饮食 钠（HK/HS；120 mmol/300 mmol），以评估固定期间钾对脉管系统的保护作用 钠的摄入量。我们还将比较中钾/低钠（MK/LS；65 mmol/50 mmol）饮食与 MK/HS 饮食可单独确认耐盐血压状态。关注耐盐成人可以让我们隔离 血管效应，不与血压变化相混淆（即独立于血压）。严谨性将加强 在每种饮食条件下利用二十四小时动态血压和尿液收集；男人、女人和 少数族裔将接受测试。肱动脉血流介导的扩张将用于评估导管内皮细胞 依赖性膨胀。使用激光多普勒血流计耦合局部加热引起的皮肤血管舒张 皮内微透析将用于评估微血管功能。静脉内皮细胞将 收集用于通过原子力显微镜和氧化应激标记物直接评估细胞硬度。 我们希望证明膳食钾可以保护内皮免受高浓度钾的有害影响。 通过减少氧化应激和内皮细胞硬度并保留 NO 来抑制钠。这些研究很新颖 因为他们将是第一个全面评估膳食钾对血管功能作用的人 独立于血压。