VASCULAR EFFECTS OF DIETARY SALT IN HUMANS WITH SALT-RESISTANT BP

项目摘要/摘要-食盐对患有耐盐性BP的人的血管效应 心血管疾病仍然是一个主要的公共卫生问题，也是美国主要的死亡原因。 限制饮食盐被认为是高血压患者重要的生活方式改变； 然而，鉴于许多人没有“盐”，人们对食盐的影响存在争议。 敏感的“BP。事实上，绝大多数血压正常的成年人都有耐盐的BP。然而，我们最近 研究表明，过量的饮食盐负荷会导致导管动脉功能和微血管的减少 功能，与BP的变化无关。一氧化氮(NO)生物利用度降低与氧化增加有关 应激是致病机制之一，但活性氧(ROS)的来源尚不清楚。 将被澄清。此外，高盐摄入量已被证明增加了来自外围的波反射和 左心室后负荷。内皮细胞的改变可能通过改变脉搏而导致这种情况。 心脏上的动脉负荷。基于上述，我们的全球假设是，限制饮食中的食盐将降低 氧化应激，改善内皮功能，改善中心动脉搏动性血流动力学。我们 建议研究饮食盐限制对血管功能和左心室脉动负荷的影响。 在男人和女人身上。具体地说，我们假设限制饮食中的盐分将改善中枢 血流动力学、动脉僵硬、内皮依赖性扩张和一氧化氮介导的皮肤血管扩张。我们 还假设在饮食盐限制期间氧化应激会减少，并且NADPH氧化酶是 这些RO的来源。青年和中年耐盐成年人将接受饮食咨询 30天的低钠饮食。动态血压、尿液采集和血管测量将在 干预后。反射幅度、前向波幅、主动脉特性阻抗和僵硬 将被评估以表征中枢血流动力学。血流介导的肱动脉扩张将是 用于评估局部加热对导管内皮依赖性扩张和皮肤血管扩张的影响 使用激光多普勒血流仪和皮内微渗析来评估微血管。 对局部加热的皮肤血管扩张反应将在林格斯点(对照)进行评估，L点名的点 (无贡献)、抗坏血酸部位(氧化应激作用)、载脂蛋白部位(NADPH氧化酶作用)和 Tempol位点(超氧化物的作用)。还将获得内皮细胞以评估氧化剂损伤以及 氧化剂和抗氧化物酶含量。这项对中枢血流动力学和 人类在饮食钠限制干预期间的内皮功能将使我们能够确定 降低饮食盐分可改善中枢血流动力学和内皮依赖性血管扩张，以及性别 对食盐限制的反应存在特定的差异。研究结果将分发给科学工作者 通过实施一项全面的传播计划，加强社区和其他方面的能力。

PROJECT SUMMARY/ABSTRACT - Vascular Effects of Dietary Salt in Humans with Salt-Resistant BP Cardiovascular disease remains a major Public Health problem and is the leading cause of death in the US. Dietary salt restriction is considered an important lifestyle modification for individuals with hypertension; however, there is controversy about the effects of dietary salt given that many individuals do not have “salt sensitive” BP. Indeed, the vast majority of normotensive adults have salt resistant BP. Yet, we have recently shown that excess dietary salt loading causes a reduction in conduit artery function and microvascular function, independent of changes in BP. Reduced nitric oxide (NO) bioavailability linked to increased oxidative stress is one of the contributing mechanisms, however the source of reactive oxygen species (ROS) has yet to be elucidated. Further, a high salt intake has been shown to increase wave reflection from the periphery and left ventricular (LV) afterload. Alterations in the endothelium likely contribute to this by altering the pulsatile arterial load on the heart. Based on the foregoing, our global hypothesis is that dietary salt restriction will lower oxidative stress, improve endothelial function, and improve central arterial pulsatile hemodynamics. We propose to investigate the effects of dietary salt restriction on vascular function and the pulsatile load on the LV in men and women. Specifically, we hypothesize that dietary salt restriction will improve central hemodynamics, arterial stiffness, endothelial–dependent dilation and NO-mediated cutaneous vasodilation. We also hypothesize that oxidative stress will decrease during dietary salt restriction, and that NADPH oxidase is the source of these ROS. Young and middle-aged salt resistant adults will undergo dietary counseling to follow a low sodium diet for 30-days. Ambulatory BP, urine collections, and vascular measures will occur pre- and post-intervention. Reflection magnitude, forward wave amplitude, aortic characteristic impedance and stiffness will be assessed to characterize central hemodynamics. Flow mediated dilation of the brachial artery will be used to assess conduit endothelial–dependent dilation and cutaneous vasodilation in response to local heating using laser Doppler flowmetry and intradermal microdialysis will be assessed to evaluate the microvasculature. Cutaneous vasodilation in response to local heating will be assessed at a Ringers site (control), L-NAME site (NO contribution), an ascorbic acid site (role of oxidative stress), an apocynin site (role of NADPH oxidase) and a tempol site (role of superoxide). Endothelial cells will be also obtained to assess oxidant damage as well as oxidant and antioxidant enzyme content. This comprehensive assessment of central hemodynamics and endothelial function in humans during a dietary sodium restriction intervention will allow us to determine if lowering dietary salt improves central hemodynamics and endothelial-dependent vasodilation and whether sex specific differences exist in response to dietary salt restriction. Findings will be distributed to the scientific community and others through implementation of a comprehensive dissemination plan.