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

项目总结/摘要-耐盐性BP患者中膳食盐的血管效应 心血管疾病仍然是一个主要的公共卫生问题，是美国的主要死亡原因。 饮食限盐被认为是高血压患者重要的生活方式改变; 然而，由于许多人没有“盐”， 敏感的”血压。事实上，绝大多数血压正常的成年人都有耐盐性BP。然而，我们最近 显示过量的饮食盐负荷导致导管动脉功能和微血管功能的降低， 功能，独立于BP的变化。一氧化氮（NO）生物利用度降低与氧化性增加有关 应激是其中一种作用机制，然而活性氧（ROS）的来源还没有确定。 被阐明。此外，高盐摄入量已被证明会增加来自周边的波反射， 左心室后负荷。内皮细胞的改变可能通过改变搏动性 心脏的动脉负荷基于上述情况，我们的总体假设是，饮食限盐会降低 氧化应激，改善内皮功能，并改善中心动脉脉动血流动力学。我们 研究限盐饮食对心血管功能和左心室搏动负荷的影响 男性和女性。具体地说，我们假设饮食限盐会改善中枢神经系统的功能。 血流动力学、动脉硬度、内皮依赖性舒张和NO介导的皮肤血管舒张。我们 我还假设，在饮食限盐期间，氧化应激会减少，NADPH氧化酶是 这些ROS的来源。年轻和中年耐盐成年人将接受饮食咨询， 低钠饮食30天将在术前和术后进行动态血压、尿液采集和血管测量。 干预后。反射幅度、前向波幅、主动脉特性阻抗和刚度 将进行评估，以表征中枢血流动力学。肱动脉的血流介导扩张将是 用于评估导管内皮依赖性扩张和皮肤血管对局部加热的反应 使用激光多普勒血流仪和皮内微透析进行评估，以评价微血管系统。 将在Ringers研究中心（对照）、L-NAME研究中心评估局部加热引起的皮肤血管舒张 (NO作用）、抗坏血酸位点（氧化应激的作用）、夹竹桃素位点（NADPH氧化酶的作用）和 Tempol位点（超氧化物的作用）。还将获得内皮细胞以评估氧化损伤以及 氧化剂和抗氧化酶含量。这种对中枢血流动力学的综合评估， 在饮食钠限制干预期间，人类的内皮功能将使我们能够确定 降低饮食中的盐含量可以改善中枢血流动力学和内皮依赖性血管舒张， 对饮食盐限制的反应存在特定差异。调查结果将分发给科学家， 社区和其他人通过实施一项全面的传播计划。

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.