Mechanisms Underlying Sodium Intake Mediated Vascular Function

描述(申请人提供)：朗达·本特利·刘易斯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科、糖尿病和高血压科的副内科医生。Bentley-Lewis博士的长期目标是成为一名独立的临床研究员，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，与白人相比，黑人在心血管疾病方面的种族差异，如高血压、肾脏疾病和中风的患病率更高。这些差异背后的机制尚未阐明，尽管黑人中盐敏感型高血压的较高患病率表明饮食钠的相互作用、对盐摄入量作出反应的激素系统以及这一人群中的血管系统发生了变化。随后，目前的研究建议集中在肾素-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。这项建议的具体目的是检验以下假设：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)在高钠饮食的背景下，肾素-血管紧张素-醛固酮系统(RAAS)抑制不足是导致黑人比白人更大的内皮功能损害的原因；以及3)RAAS介导的黑人血管功能差异是次要于黑人和白人之间已知的RAAS基因差异。这些研究的结果将使我们能够：1)根据种族和性别来表征钠平衡中的血管功能；2)调查饮食盐操作对血管功能影响的潜在机制；3)提供关于遗传在调节这些影响中的作用的初步数据。这对公共健康的影响是巨大的，因为我们将能够就饮食调整向不同的患者群体提供适当的咨询，从而优化健康并将心血管疾病风险降至最低。此外，这些见解不仅有利于高血压患者的血压管理，还有助于考虑不同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.