Mechanisms Underlying Sodium Intake Mediated Vascular Function

钠摄入介导血管功能的机制

• 批准号: 7321420
• 负责人: Rhonda Bentley-Lewis
• 金额: $ 16.25万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7321420
• 关键词: Accounting; African American; Age; Aldosterone; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Angiotensinogen; Angiotensins; Biological Markers; Blood Pressure; Blood Vessels; Cardiovascular Diseases; Characteristics; Clinical Investigator; Condition; Coronary Arteriosclerosis; Coronary Circulation; Counseling; Data; Diabetes Mellitus; Diet; Diet Modification; Dietary Sodium; Disease; Endocrine system; Endocrinology; Equilibrium; Ethnic Origin; Forearm; Frequencies; Gender; Genes; Genetic; Genetic Polymorphism; Genotype; Goals; Gold; Health; High Prevalence; Hormonal; Hormones; Hospitals; Hypertension; Impairment; Individual; Infusion procedures; Intake; Interruption; Invasive; Investigation; Kidney; Kidney Diseases; Lead; Measurement; Mediating; Mediator of activation protein; Medicine; Nature; Organ; Patients; Peripheral; Physicians; Physiological; Population; Prevalence; Prevention strategy; Production; Public Health; Race; Renal Hypertension; Renal Plasma Flow; Renin; Renin-Angiotensin-Aldosterone System; Reporting; Research Personnel; Research Proposals; Risk; Role; Secondary to; Series; Serum; Sodium; Sodium Chloride; Sodium-Restricted Diet; Standards of Weights and Measures; Stroke; Surrogate Markers; System; Techniques; Testing; Time; Variant; Vasoconstrictor Agents; Woman; brachial artery; cardiovascular disorder prevention; cardiovascular disorder risk; cardiovascular injury; dietary control; insight; instructor; kidney vascular structure; medical schools; normotensive; racial difference; response; salt intake; salt sensitive; vascular bed

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.

描述（由申请人提供）：Rhonda Bentley-Lewis博士是哈佛医学院医学的讲师，也是内分泌学，糖尿病和杨氏妇女医院的内分泌学，糖尿病和高血压的副医师。 Bentley-Lewis博士的长期目标是成为一名独立的临床研究者，重点是影响心血管疾病风险的激素机制，并了解种族/种族，族裔和遗传学如何影响这种风险。已经报道了心血管疾病的种族差异，例如与白人相比，黑人的高血压，肾脏疾病和中风的患病率更高。尽管黑人对盐敏感的高血压的较高患病率表明，饮食中钠的相互作用改变，荷尔蒙系统对盐的摄入量的相互作用发生了改变，并且该人群中的脉管系统发生了变化，但尚未阐明这些差异的机制。随后，当前的研究建议着重于肾素 - 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介体。该提案的具体目的是检验以下假设：1）高饮食钠将导致黑人和白人的血管功能受损，但在黑人中的程度更大； 2）在高饮食钠的情况下，肾素 - 血管紧张素 - 醛固酮系统（RAAS）的抑制不足，与白人相比，黑人在黑人中看到的内皮功能的损害更大。 3）黑人血管功能的RAAS介导的差异是黑人和白人之间的RAAS基因的已知遗传差异的继发。这些调查的结果将使我们能够：1）在钠平衡中通过种族和性别来表征血管功能； 2）研究饮食盐操纵对血管功能影响的机制； 3）提供有关遗传学在介导这些作用中作用的试验数据。公共卫生的影响很大，因为我们将能够就饮食修改适当地为不同的患者人群提供咨询，从而优化健康并最大程度地降低心血管疾病的风险。此外，这些见解不仅将受益于高血压的血压管理，而且还会使人们对性别和种族正常敏化的心血管疾病预防策略的考虑。