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: 10663833
• 负责人: Shannon Lennon
• 金额: $ 56.44万
• 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/10663833
• 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; 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; Oxidative Stress Induction; 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 为了减少盐分，已经做出了重大的公共卫生努力，但大多数已经遇到了失败。饮食 高钠/低钾饮食等因素有助于心血管疾病的发展 （CVD），例如动脉粥样硬化和高血压（BP）。这很重要，因为CVD是第一 杀手在美国，尽管这两种营养素在BP中的作用被广泛接受，但它们对脉管系统的影响 受到更少的关注。内皮功能障碍的特征是扩张受损，是一个重要的非 - 动脉粥样硬化的传统危险因素。我们已经表明，高钠饮食会引起内皮功能障碍， 独立于BP的变化（通过用耐盐BP测试成年人来完成）。证据支持 钾在血管健康上的有益作用尚不清楚，尽管它可能在 钠饮食的存在。负责钠引起的血管功能障碍的声称的机制 是活性氧（ROS）的过量生产，导致一氧化氮降低（NO） 生产/生物利用度。有人建议钾可以通过减少来抵消钠的作用 罗斯。此外，已经显示出高钠饮食可通过增加丰度来使内皮变硬 内皮钠通道（ENNAC）虽然钾在ENNAC上的作用尚不清楚。我们的中心假设 是，饮食中的钾会通过保存NO和 减少氧化应激和内皮细胞刚度。我们将使用三种10天饮食来检验我们的假设 （受控喂养研究，跨界设计，饮食顺序序列随机用饮食之间的擦洗）。我们 将比较中等钾/高钠饮食（MK/HS； 65 mmol/300 mmol）与高钾/高钾/高 钠（HK/HS; 120 mmol/300 mmol）评估固定期间钾对脉管系统的保护作用 钠摄入量。我们还将比较中等的钾/低钠（MK/LS； 65 mmol/50 mmol）饮食与 MK/HS饮食单独确认耐盐的BP状态。专注于耐盐的成年人使我们能够分离 血管效应，没有BP变化的混淆（即独立于BP）。严格将得到增强 通过在每种饮食状况下利用二十四小时的门诊BP和尿液收集；男人，女人和 少数民族将进行测试。臂动脉流介导的扩张将用于评估导管内皮 - 依赖的扩张。对局部加热的皮肤血管舒张，使用激光多普勒流量指标耦合 用皮内微透析用于评估微血管功能。静脉内皮细胞将是 通过原子力显微镜和氧化应激的标志物收集以直接评估细胞刚度。 我们希望饮食中钾可以保护内皮免受高高影响 通过减少氧化应激和内皮细胞刚度并保留NO。这些研究是新颖的 因为他们将是第一个全面评估饮食钾对血管功能的作用的人 独立于BP。

项目成果

Acrolein, an environmental toxicant and its applications to in vivo and in vitro atherosclerosis models: An update.

丙烯醛，一种环境毒物及其在体内和体外动脉粥样硬化模型中的应用：更新。

• DOI: 10.1016/j.etap.2022.103890
• 发表时间: 2022
• 期刊: Environmental toxicology and pharmacology
• 影响因子: 4.3
• 作者: Crowley,LianaN;Le,BrandyL;Cicalo,Cara;Brown,Justin;Li,Yali;Kim,YoungJun;Lee,JinHyup;Pan,JeongHoon;Lennon,ShannonL;Han,BokKyung;Kim,JaeKyeom
• 通讯作者: Kim,JaeKyeom

Melatonin supplementation reduces nighttime blood pressure but does not affect blood pressure reactivity in normotensive adults on a high-sodium diet.

补充褪黑激素可降低夜间血压，但不会影响高钠饮食的血压正常成年人的血压反应性。

• DOI: 10.1152/ajpregu.00101.2023
• 发表时间: 2023
• 期刊: American journal of physiology. Regulatory, integrative and comparative physiology
• 作者: RamosGonzalez,Macarena;Axler,MichaelR;Kaseman,KathrynE;Lobene,AndreaJ;Farquhar,WilliamB;Witman,MelissaA;Kirkman,DanielleL;Lennon,ShannonL
• 通讯作者: Lennon,ShannonL