Mechanisms Underlying Sodium Intake Mediated Vascular Function

钠摄入介导血管功能的机制

• 批准号: 8101168
• 负责人: Rhonda Bentley-Lewis
• 金额: $ 16.25万
• 依托单位: MASSACHUSETTS GENERAL 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 2012-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8101168
• 关键词: Accounting; African American; Age; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Angiotensinogen; Biological Markers; Blood Pressure; Blood Vessels; Cardiovascular Diseases; Characteristics; Clinical Investigator; Coronary Arteriosclerosis; Coronary Circulation; Counseling; Data; Diabetes Mellitus; Diet; Diet Modification; Dietary Sodium; 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; Investigation; Kidney; Kidney Diseases; Lead; Measurement; Mediating; Mediator of activation protein; Medicine; Nature; Organ; Peripheral; Physicians; Physiological; Population; Prevalence; Prevention strategy; Production; Public Health; Race; Renal Plasma Flow; Renin-Angiotensin-Aldosterone System; Reporting; Research Personnel; Research Proposals; Risk; Role; Secondary to; Series; Serum; Sodium; Sodium Chloride; Sodium-Restricted Diet; Stroke; Surrogate Markers; System; Techniques; Testing; Time; Variant; Vasoconstrictor Agents; Woman; brachial artery; cardiovascular disorder prevention; cardiovascular disorder risk; cardiovascular injury; insight; instructor; kidney vascular structure; medical schools; normotensive; patient population; 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 博士是哈佛医学院的医学讲师，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，重点研究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，黑人高血压、肾病和中风的患病率更高。这些差异背后的机制尚未阐明，尽管黑人中盐敏感性高血压的患病率较高，表明膳食钠、对盐摄入做出反应的激素系统以及该人群的脉管系统之间的相互作用发生了变化。随后，当前的研究计划重点关注肾素-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调节因素的作用。该提案的具体目的是检验以下假设：1）高膳食钠会导致黑人和白人血管功能受损，但黑人受损程度更大； 2）在高钠饮食的情况下，肾素-血管紧张素-醛固酮系统（RAAS）抑制不充分，导致黑人的内皮功能损伤比白人更大； 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）通过种族和性别的钠平衡来表征血管功能； 2）研究饮食盐控制对血管功能影响的机制； 3）提供关于遗传学在调节这些影响中的作用的试点数据。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建议，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，而且有利于考虑跨性别和种族的正常血压患者的心血管疾病预防策略。

项目成果

Effect of race/ethnicity on hypertension risk subsequent to gestational diabetes mellitus.

• DOI: 10.1016/j.amjcard.2014.01.411
• 发表时间: 2014-04-15
• 期刊: AMERICAN JOURNAL OF CARDIOLOGY
• 影响因子: 2.8
• 作者: Bentley-Lewis, Rhonda;Powe, Camille;Ankers, Elizabeth;Wenger, Julia;Ecker, Jeffiey;Thadhani, Ravi
• 通讯作者: Thadhani, Ravi

Late cardiovascular consequences of gestational diabetes mellitus.

• DOI: 10.1055/s-0029-1225260
• 发表时间: 2009-07
• 期刊: Seminars in reproductive medicine
• 影响因子: 2.7
• 作者: Bentley-Lewis R