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.

项目总结/摘要-膳食钾与高膳食钠对 人类的血管系统 心血管疾病仍然是美国的主要公共卫生问题，并且是亚临床疾病的结果。 如动脉粥样硬化和高血压（BP）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，过量的钠摄入会增加血压，而摄入 钾具有降低血压的特性。虽然这两种营养素对BP的作用是 虽然它们被广泛接受，但它们对脉管系统的影响却较少受到关注。血管内皮功能障碍， 其特征在于受损的扩张是动脉粥样硬化的重要非传统危险因素。动物数据 模型提示，盐负荷，独立于血压的变化，导致血管内皮功能障碍 同时越来越多的证据表明钾可能有益于血管健康。潜在机制 导致钠诱导的血管功能障碍的原因包括活性氧物质的过度产生， 硬化内皮细胞导致一氧化氮（NO）产生/生物利用度降低。钾具有 被认为具有抗氧化能力，可以抵消高钠的影响， 显示软化培养的内皮细胞，该内皮细胞因高钠而变硬。我们的核心假设是钠 直接影响血管系统，同时消耗钾可以改善有害的 钠通过减少氧化应激和细胞硬度的影响，从而保持NO。 子项目，我们建议使用21天的控制喂养研究，以比较高钠饮食的影响 (300 mmol）联合高钾（120 mmol）或中钾（65 mmol），2个水平， 脉管系统、导管和微脉管系统。这些实验将在耐盐的成年人中进行， 单独研究血管效应，不依赖于血压的变化。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的盐敏感性进行个体评估。肱动脉血流- 介导的舒张将用于评估导管内皮依赖性舒张和皮肤血管舒张， 使用激光多普勒血流仪结合皮内微透析对局部加热的反应将用于 评估前臂的微血管功能将通过颈动脉-股动脉脉搏波评估动脉僵硬度 速度和波反射的主动脉增强指数。静脉刮取内皮细胞 收集用于评估氧化应激和细胞硬度。我们希望证明高钾 通过减少氧化应激和细胞凋亡，保护内皮细胞免受高钠的有害影响。 刚度这些研究的新颖之处在于，它们将是第一个批判性评估钾在体内作用的研究。 独立于BP的血管功能，并采用血管功能的综合评估（导管 来自人类受试者的动脉内皮功能、微血管功能、动脉硬度和内皮细胞） 研究高钾饮食对高钠饮食的影响。此外，从中收集的数据 建议将允许通过R 01对这一专题进行更广泛的探讨。