Interaction of Dietary Potassium with High Dietary Sodium on the Vasculature of Humans

膳食钾与高膳食钠对人体脉管系统的相互作用

• 批准号: 9432533
• 负责人: Shannon Lennon
• 金额: $ 32.72万
• 依托单位: UNIVERSITY OF DELAWARE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9432533
• 关键词: Acute; Adult; Affect; Animal Model; Antioxidants; Area; Arteries; Atherosclerosis; Atomic Force Microscopy; Attention; Biological Availability; Blood Pressure; Blood Vessels; Cardiovascular Diseases; Cattle; Cells; Centers of Research Excellence; Clinical Trials; Collection; Consumption; Coupled; Cutaneous; Data; Diet; Dietary Factors; Dietary Potassium; Dietary Sodium; Disease; Endothelial Cells; Endothelium; Forearm; Goals; Health; Heating; Hour; Human; Hyperemia; Hypertension; Impairment; Individual; Intake; Laser-Doppler Flowmetry; Mediating; Microdialysis; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nutrient; Outcome; Oxidative Stress; Participant; Physiologic pulse; Positioning Attribute; Potassium; Production; Property; Public Health; Reactive Oxygen Species; Resistance; Risk Factors; Rodent; Role; Sodium; Sodium Chloride; Superoxides; Time; Translating; Urine; Vascular Diseases; Vasodilation; Venous; arterial stiffness; brachial artery; cardiovascular disorder risk; cardiovascular health; endothelial dysfunction; experimental study; extracellular; feeding; high salt diet; human subject; indexing; middle age; novel; protective effect; response; salt sensitive; vascular endothelial dysfunction

PROJECT SUMMARY/ABSTRACT - Interaction of Dietary Potassium with High Dietary Sodium on the Vasculature of Humans Cardiovascular disease remains a major Public Health problem in the U.S. and is the result of sub-clinical diseases such as atherosclerosis and high blood pressure (BP). Several dietary factors have been implicated as risk factors. Indeed, it is well known that excess sodium consumption can increase BP while consumption of potassium has been shown to have BP lowering properties. While the role of these two nutrients on BP is widely accepted, their impact on the vasculature has received less attention. Vascular endothelial dysfunction, characterized by impaired dilation is an important non-traditional risk factor for atherosclerosis. Data in animal models suggest that salt loading, independent of changes in BP, results in vascular endothelial dysfunction while evidence is mounting that potassium may be beneficial to vascular health. Potential mechanisms responsible for sodium induced vascular dysfunction include overproduction of reactive oxygen species and stiffening of endothelial cells resulting in reduced nitric oxide (NO) production/bioavailability. Potassium has been suggested to have antioxidant capabilities that may counteract the effects of high sodium and has been shown to soften cultured endothelial cells stiffened from high sodium. Our central hypothesis is that sodium directly affects the vasculature and simultaneous consumption of potassium can ameliorate the detrimental effects of sodium by reducing oxidative stress and cell stiffness, thereby preserving NO. In this COBRE subproject, we propose to use a 21-day controlled feeding study to compare the effects of a high sodium diet (300 mmol) combined with either a high (120 mmol) or moderate (65 mmol) amount of potassium on 2 levels of the vasculature, conduit and microvasculature. These experiments will be performed in salt-resistant adults to study the vascular effects alone, independent of changes in BP. 24-hour ambulatory BP and urine collections during each diet condition will permit the individual assessment of salt sensitivity of BP. Brachial artery flow- mediated dilation will be used to assess conduit endothelial-dependent dilation and cutaneous vasodilation in response to local heating using laser Doppler flowmetry coupled with intradermal microdialysis will be used to assess microvascular function in the forearm. Arterial stiffness will be assessed by carotid-femoral pulse wave velocity and wave reflection by aortic augmentation index. A venous scraping of endothelial cells will be collected for assessment of oxidative stress and cell stiffness. We expect to demonstrate that high potassium protects the endothelium from the deleterious effects of high sodium by reducing oxidative stress and cell stiffness. These studies are novel in that they will be the first to critically evaluate the role of potassium on vascular function independent of BP and employ a comprehensive assessment of vascular function (conduit artery endothelial function, microvascular function, arterial stiffness, and endothelial cells from human subjects) to study the effect of a high potassium diet in the presence of high sodium. Further, the data collected from this proposal would allow for a larger exploration of this topic through a R01.

项目摘要/摘要-日粮钾与高钠之间的相互作用 人类的血管系统 心血管疾病在美国仍然是一个主要的公共卫生问题，是亚临床疾病的结果 动脉粥样硬化和高血压等疾病。有几个饮食因素与此有关。 作为风险因素。事实上，众所周知，过量的钠摄入量会增加血压，而摄入量 已被证明具有降血压的特性。而这两种营养素对BP的作用是 被广泛接受的是，它们对血管系统的影响却没有得到太多关注。血管内皮功能障碍， 以扩张受损为特征的动脉粥样硬化是一种重要的非传统危险因素。动物中的数据 模型表明，盐负荷与血压变化无关，会导致血管内皮功能障碍 而越来越多的证据表明，钾可能对血管健康有益。潜在机制 导致钠致血管功能障碍的原因包括产生过多的活性氧和 内皮细胞僵硬导致一氧化氮(NO)的产生/生物利用度降低。钾有 被认为具有抗氧化能力，可以抵消高钠的影响，并已被 可软化因高钠而僵硬的培养内皮细胞。我们的中心假设是钠 直接影响血管系统和同时摄入钾可以改善有害的 钠通过降低氧化应激和细胞硬度，从而保护NO。在这个科布雷 子项目，我们建议使用21天的受控喂养研究来比较高钠饮食的效果 (300 MmoL)与高(120 MmoL)或中(65 MmoL)的钾结合在两个水平上 血管系统、导管和微血管系统。这些实验将在耐盐成年人身上进行，以 单独研究血管效应，不受血压变化的影响。24小时动态血压和尿液采集 在每种饮食条件下，将允许对BP的盐敏感性进行个别评估。臂动脉血流- 介导性扩张将被用来评估导管内皮依赖性扩张和皮肤血管扩张 使用激光多普勒血流仪与皮内微透析相结合对局部加热的反应将用于 评估前臂的微血管功能。动脉僵硬将通过颈动脉-股动脉脉搏波来评估 用主动脉增厚指数评价血流速度和反射波。静脉刮取内皮细胞将是 收集用于评估氧化应激和细胞硬度。我们希望能证明高钾 通过减少氧化应激和细胞保护内皮免受高钠的有害影响 僵硬。这些研究是新颖的，因为他们将是第一个批判性地评估钾在 独立于血压的血管功能，并采用血管功能(导管)的综合评估 动脉内皮功能、微血管功能、动脉僵硬和人体内皮细胞) 目的：研究高钾饮食对高钠饮食的影响。此外，从这一事件中收集的数据 提案将允许通过R01对这一主题进行更大规模的探索。