Mechanisms Underlying Sodium Intake Mediated Vascular Function

简介（由申请人提供）：朗达·本特利-刘易斯博士是哈佛医学院医学讲师，也是布莱根妇女医院内分泌、糖尿病和高血压科的副医师。Bentley-Lewis博士的长期目标是成为一名独立的临床研究者，专注于影响心血管疾病风险的激素机制，并了解种族/民族、性别和遗传如何影响这种风险。据报道，心血管疾病的种族差异，如高血压、肾病和中风在黑人中的患病率高于白人。这些差异背后的机制尚未被阐明，尽管黑人中盐敏感性高血压的更大患病率表明饮食钠、对盐摄入有反应的激素系统和该人群的血管系统之间的相互作用发生了变化。随后，目前的研究建议侧重于肾素-血管紧张素-醛固酮系统作为钠摄入量对血管功能影响的种族差异的潜在中介的作用。本研究的具体目的是验证以下假设：1)高钠饮食会导致黑人和白人的血管功能受损，但黑人的损伤程度更大；2)与白人相比，高钠饮食环境下肾素-血管紧张素-醛固酮系统（RAAS）抑制不足是黑人内皮功能受损更严重的原因；3)黑人中RAAS介导的血管功能差异是继发于黑人和白人之间已知的RAAS基因遗传差异。这些研究结果将使我们能够：1)钠平衡中不同种族和性别的血管功能特征；2)探讨饮食盐调控对血管功能影响的机制；3)提供基因在调节这些效应中的作用的先导数据。公共卫生影响是巨大的，因为我们将能够在饮食调整方面适当地咨询我们不同的患者群体，从而优化健康并最大限度地降低心血管疾病的风险。此外，这些见解不仅有利于高血压患者的血压管理，而且有助于考虑跨性别和种族的血压正常者的心血管疾病预防策略。

DESCRIPTION (provided by applicant): Dr. Rhonda Bentley-Lewis is an Instructor in Medicine at Harvard Medical School and an Associate Physician in the Division of Endocrinology, Diabetes, and Hypertension at Brigham and Women's Hospital. Dr. Bentley-Lewis' long-term goal is to become an independent clinical investigator with a focus on the hormonal mechanisms that influence cardiovascular disease risk and to understand how race/ethnicity, gender, and genetics influence this risk. Racial differences in cardiovascular disease have been reported, such as a higher prevalence of hypertension, renal disease, and stroke, in blacks as compared to whites. Mechanisms underlying these differences have not yet been elucidated, although the greater prevalence of salt-sensitive hypertension in blacks suggests an alteration in the interaction of dietary sodium, the hormonal systems reponsive to salt intake, and the vasculature in this population. Subsequently, the current research proposal focuses on the role of the renin-angiotensin-aldosterone system as a potential mediator of the racial differences in the effect of sodium intake on vascular function. The specific aims of this proposal are to test the hypotheses that: 1) high dietary sodium will lead to impairment in vascular function in both blacks and whites but to a greater degree among the blacks; 2) the inadequate suppression of renin-angiotensin-aldosterone system (RAAS) in the setting of high dietary sodium is responsible for the greater impairment in endothelial function seen in blacks compared to whites; and 3) the RAAS-mediated differences in vascular function in blacks are secondary to known genetic differences in RAAS genes between blacks and whites. The results of these investigations would enable us: 1) to characterize vascular function by race and gender in sodium balance; 2) to investigate mechanisms underlying the influence of dietary salt manipulation on vascular function; and 3) to provide pilot data on the role of genetics in mediating these effects. The public health impact is great in that we will be able to appropriately counsel our different patient populations with respect to dietary modifications, thereby optimizing health and minimizing cardiovascular disease risk. Moreover, these insights will benefit not only the management of blood pressure in hypertensives, but also the consideration of cardiovascular disease prevention strategies in normotensives across gender and race.