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 - 膳食钾与高膳食钠的相互作用 人体脉管系统 心血管疾病仍然是美国的一个主要公共卫生问题，并且是亚临床疾病的结果 动脉粥样硬化和高血压（BP）等疾病。多种饮食因素有关 作为危险因素。事实上，众所周知，过量摄入钠会导致血压升高，而摄入过量钠会导致血压升高。 钾已被证明具有降低血压的特性。而这两种营养素对血压的作用是 尽管它们被广泛接受，但它们对脉管系统的影响却很少受到关注。血管内皮功能障碍， 以扩张受损为特征的动脉粥样硬化的重要非传统危险因素。动物数据 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 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 钠引起的血管功能障碍的原因包括活性氧的过度产生和 内皮细胞硬化，导致一氧化氮 (NO) 产生/生物利用度降低。钾有 有人认为具有抗氧化能力，可以抵消高钠的影响，并且已被证实 显示可以软化因高钠而僵硬的培养内皮细胞。我们的中心假设是钠 直接影响脉管系统，同时消耗钾可以改善不利的情况 钠通过降低氧化应激和细胞硬度来发挥作用，从而保留一氧化氮。在这个 COBRE 子项目中，我们建议使用 21 天的控制喂养研究来比较高钠饮食的影响 (300 mmol) 与高量 (120 mmol) 或中等量 (65 mmol) 钾结合，分为 2 个水平 脉管系统、导管和微脉管系统。这些实验将在耐盐成人身上进行 单独研究血管效应，与血压变化无关。 24 小时动态血压和尿液采集 在每种饮食条件下，将允许对血压的盐敏感性进行单独评估。肱动脉血流- 介导的扩张将用于评估导管内皮依赖性扩张和皮肤血管舒张 使用激光多普勒血流计结合皮内微透析对局部加热的响应将用于 评估前臂的微血管功能。通过颈动脉-股动脉脉搏波评估动脉僵硬度 通过主动脉增强指数测量速度和波反射。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保护内皮免受高钠的有害影响 刚性。这些研究的新颖之处在于，它们将是第一个批判性评估钾对健康的作用的研究。 独立于血压的血管功能并采用血管功能的综合评估（导管 动脉内皮功能、微血管功能、动脉僵硬度和来自人类受试者的内皮细胞） 研究高钠饮食中高钾饮食的影响。此外，从本次收集的数据 提案将允许通过 R01 对这个主题进行更广泛的探索。