Mechanisms Underlying Sodium Intake Mediated Vascular Function

描述（由申请人提供）：Rhonda Bentley-Lewis博士是哈佛医学院的医学讲师，也是布里格姆妇女医院内分泌、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，性别和遗传学如何影响这种风险。据报道，心血管疾病存在种族差异，例如，与白人相比，黑人的高血压、肾病和中风患病率更高。这些差异背后的机制尚未阐明，虽然盐敏感性高血压在黑人中的更大患病率表明，在饮食中的钠，激素系统responsive盐的摄入量的相互作用的改变，在这个人群中的血管。随后，目前的研究建议集中在肾素-血管紧张素-醛固酮系统的作用，作为一个潜在的调解人的种族差异，钠摄入量对血管功能的影响。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血管功能受损，但黑人的程度更大; 2）高钠饮食对肾素-血管紧张素-醛固酮系统（RAAS）的抑制不足是导致黑人内皮功能受损程度大于白人的原因;和3）黑人中RAAS介导的血管功能差异继发于黑人和白人之间RAAS基因的已知遗传差异。这些研究的结果将使我们能够：1）通过种族和性别来表征钠平衡中的血管功能; 2）研究饮食盐操纵对血管功能影响的潜在机制; 3）提供遗传学在介导这些影响中的作用的初步数据。公共卫生的影响是巨大的，因为我们将能够适当地咨询我们不同的患者群体关于饮食的改变，从而优化健康和最大限度地减少心血管疾病的风险。此外，这些见解不仅有利于高血压患者的血压管理，而且有利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.