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/项目总结 为了减少盐的摄入，公共卫生部门做出了大量努力，但大多数都失败了。膳食 高钠/低钾饮食等因素有助于心血管疾病的发展 心血管疾病（CVD），如动脉粥样硬化和高血压（BP）。这一点很重要，因为CVD是第一位 虽然这两种营养素对血压的作用被广泛接受，但它们对血管系统的影响 受到的关注较少。以扩张受损为特征的内皮功能障碍是一种重要的非血管性疾病， 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BP的变化（通过测试具有耐盐BP的成年人来完成）。证据支持 钾对血管健康的有益作用尚不清楚，尽管它可能在心脏病中更有效。 存在高钠饮食。钠诱导血管功能障碍的一种假定机制 是过量产生活性氧（ROS），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 罗斯此外，高钠饮食已被证明会通过增加内皮细胞的丰度而使内皮硬化。 内皮钠通道（EnNaC），而钾对EnNaC的作用尚不清楚。我们的核心假设 饮食中的钾可以保护血管系统免受钠的有害影响， 降低氧化应激和内皮细胞硬度。我们将使用三个10天的饮食来验证我们的假设 （对照饲养研究，交叉设计，饮食顺序序列随机化，饮食之间有洗脱）。我们 将比较中等钾/高钠饮食（MK/HS; 65 mmol/300 mmol）与高钾/高钠饮食（MK/HS; 65 mmol/300 mmol）。 钠（HK/HS;120 mmol/300 mmol），以评估钾在固定时间内对血管系统的保护作用。 钠摄入量我们还将比较中等钾/低钠（MK/LS; 65 mmol/50 mmol）饮食与 MK/HS饮食以单独确认耐盐BP状态。专注于耐盐的成年人可以让我们分离出 血管效应，没有BP变化的混杂（即，独立于BP）。尸体的僵硬程度会提高 通过在每种饮食条件下利用24小时动态BP和尿液收集;男性、女性和 少数民族将受到考验。肱动脉血流介导的扩张将用于评估管道内皮- 依赖膨胀激光多普勒血流仪联合局部加热对皮肤血管舒张的影响 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直接评估细胞硬度。 我们希望证明，膳食钾保护内皮细胞免受高钾的有害影响。 钠通过减少氧化应激和内皮细胞硬度和保护NO。这些研究是新颖的 因为他们将是第一个全面评估膳食钾对血管功能的作用的人 独立于BP