PHYSIOLOGICAL EFFECTS OF DIETARY SODIUM IN SALT RESISTANT HUMANS

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 最近的证据表明，钠可能导致结构和功能异常，而不是血压(BP)。具体地说，实验动物的数据表明，钠负荷与血压变化无关，会促进心脏、血管和肾脏的损害。在自发性高血压大鼠中，已经记录了过量钠的有害生理变化，这与正常血压的Wistar-京都大鼠的这一建议特别相关。简而言之，人们越来越认识到，血压升高并不是与过量饮食钠有关的唯一问题。INBRE建议的目标是通过在人类身上探索这些问题，在这些动物研究的基础上再接再厉；这些机械性的动物研究需要转化为人类研究。我们将在一组我们认为患有耐盐性血压(平均血压从低钠饮食转变为高钠饮食的血压变化为5毫米汞)的人群中检查饮食钠的生理效应。受试者将完成为期17天的饮食试验(3天磨合，每天100毫摩尔的钠，7天的高钠(350毫摩尔/天)和7天的低钠(20毫摩尔/天)。所有食物将通过与克里斯蒂娜关怀健康系统建立的合作为受试者准备。饮食依从性将通过在每种情况的最后一天收集24小时尿液来评估；BP的盐敏感性将通过在每种情况的最后一天的24小时动态血压来单独评估。我们的总体假设是，膳食钠会对血压昼夜节律、动脉功能和静脉功能产生不利影响。血压昼夜节律将通过夜间血压下降来评估；动脉功能将通过脉搏波速度和增大指数来评估；内皮功能将通过臂部血流介导的扩张来评估；静脉功能将通过静脉闭塞体积图来评估。这项建议的优势在于，在饮食条件控制良好的情况下，对没有“盐敏感”血压的人群进行复杂的生理评估。普通人群的习惯性钠摄入量很高，因此我们的重点将放在展示高钠和低钠条件下这些变量的差异。这项建议汇集了一个多学科的团队，其中包括来自生理学、心脏病学、医疗技术、营养学和护理学的个人。特拉华州有两个不同的机构参与其中(特拉华大学和克里斯蒂娜保健保健系统)。这个团队代表着真正的合作伙伴关系。这项提案还将为本科生和研究生提供实践研究经验。根据这一供资机制收集的数据将构成R01提交的基础。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Recent evidence suggests that sodium may contribute to structural and functional abnormalities, independent of blood pressure (BP). Specifically, data in experimental animals suggest that sodium-loading  independent of changes in BP  promotes cardiac, vascular, and renal damage. Deleterious physiological changes from excess sodium have been documented in spontaneously hypertensive rats, and  with particular relevance for this proposal  in normotensive Wistar-Kyoto rats. In short, there is a growing appreciation that elevated BP is not the only problem related to excess dietary sodium. The objective of this INBRE proposal is to build upon these animal studies by exploring these issues in humans; these mechanistic animal studies need to be translated to human studies. We will examine the physiological effects of dietary sodium in a group that we characterize as having salt resistant BP ( 5 mmHg change in mean BP going from a low to high sodium diet). Subjects will complete a 17-day dietary trial (3-day run-in of 100 mmol/day of sodium, 7 days high sodium (350 mmol/day) and 7 days of low sodium (20 mmol/day). All foods will be prepared for the subjects thought an established collaboration with Christiana Care Health System. Dietary compliance will be assessed by collecting 24 hours of urine on the last day of each condition; salt sensitivity of BP will be individually assessed via 24-hour ambulatory BP on the last day of each condition. Our overall hypothesis is that dietary sodium will adversely affect circadian BP rhythm, arterial function, and venous function. Circadian BP rhythm will be assessed using the night time dip in pressure; arterial function will be assessed via pulse wave velocity and augmentation index; endothelial function will be assessed via brachial flow-mediated dilation; and venous function will be assess via venous occlusion plethysmography. The strength of this proposal is the sophisticated physiological assessment that will be performed under well-controlled dietary conditions in a group that does not have "salt sensitive" BP. Habitual sodium intake is high in the general population, therefore our focus will be on demonstrating differences in these variables between the high and low sodium conditions. This proposal brings together a multi-disciplinary team which includes individuals from Physiology, Cardiology, Medical Technology, Nutrition, and Nursing. Two different institutions in the state of Delaware are involved (University of Delaware and Christiana Care Health System). This team represents a true collaborative partnership. This proposal will also provide hands-on research experience for undergraduate and graduate students. The data collected under this funding mechanism will form the basis of an R01 submission.