Urinary Angiotensinogen Excretion and Salt-Sensitivity of Blood Pressure

尿血管紧张素原排泄和血压的盐敏感性

• 批准号: 8697725
• 负责人: JING CHEN
• 金额: $ 69.27万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-01 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8697725
• 关键词: Albumins; Angiotensinogen; Animal Model; Biological; Biological Markers; Blood Pressure; Cardiovascular Diseases; Cessation of life; China; Clinical; Clinical Research; Data; Data Quality; Development; Diet; Dietary Intervention; Dietary Potassium; Dietary Sodium; Dopamine; Excretory function; Freezing; Hour; Hypertension; Hypotension; Incidence; Individual; Intake; Intervention; Intervention Studies; Investigation; Kallikrein-Kinin System; Kidney; Kininogenase; Lead; Life; Measurement; Measures; National Heart, Lung, and Blood Institute; Norepinephrine; Oral; Outcome; Participant; Patients; Pharmacologic Substance; Potassium; Prospective Studies; Protocols documentation; Public Health; Randomized Controlled Trials; Rattus; Renin-Angiotensin System; Research; Research Infrastructure; Resources; Risk; Rural; Sampling; Sodium; Sodium Chloride; Supplementation; Urinary Kallikrein; cost; cost effective; epidemiology study; feeding; follow-up; genetic epidemiology; insight; mortality; novel; premature; prospective; public health relevance; response; salt sensitive; salt sensitive hypertension; urinary

Project Summary Salt-sensitivity of blood pressure (BP) is associated with increased risk of hypertension and cardiovascular disease mortality. The underlying mechanism of salt-sensitivity is not fully understood. The overall objective of the proposed study is to investigate the association of urinary excretion of angiotensinogen (AGT), kallikrein, dopamine, norepinephrine, and albumin with salt-sensitivity and potassium-sensitivity of BP and risk of hypertension. The Genetic Epidemiology Network of Salt Sensitivity (GenSalt) is an NHLBI-sponsored dietary feeding-study conducted among 1,906 participants living in rural China during October 2003-July 2005. The dietary interventions included a 7-day low-sodium feeding (51.3 mmol/day), a 7-day high-sodium feeding (307.8 mmol/day), and a 7-day high-sodium feeding with oral potassium supplementation (60 mmol/day). BP measurements were obtained on each of 3 days during the baseline and each of the 3 intervention periods. Two follow-up examinations to investigate the incidence of hypertension were conducted in the GenSalt study participants during August 2008-December 2009 and August 2011-May 2012. The GenSalt-replication study was conducted among 698 participants living in the same region using an identical study protocol from April to November of 2010. The GenSalt and GenSalt-replication studies with high quality data and sufficient biosamples provide a unique opportunity for the following specific aims: 1. to investigate the association of urinary excretion of AGT, kallikrein, dopamine, norepinephrine, and albumin with salt- and potassium- sensitivity of BP, and 2. to study the prospective association of urinary excretion of AGT, kallikrein, dopamine, norepinephrine, and albumin with subsequent incidence of hypertension. To achieve these specific aims, we will measure urinary AGT, kallikrein, dopamine, norepinephrine, and albumin in the frozen-stored 24-hour urinary samples from the GenSalt and GenSalt-replication study participants; analyze the association of urinary excretion of biomarkers at baseline and during dietary interventions with BP responses to dietary sodium and potassium interventions in 2,604 GenSalt and GenSalt-replication study participants; and analyze the prospective relationship of urinary excretion of biomarkers at baseline and during dietary interventions with subsequent risk of hypertension in 1,906 GenSalt study participants with follow-up data on BP. The proposed study is very timely and cost-effective, because it uses the rich resources and research infrastructure of the GenSalt study. This study will be the first large investigation to examine the association between multiple urinary biomarkers and risk of salt-sensitive hypertension. The findings from this study may provide novel insights into the underlying biologic mechanisms of salt-sensitivity and potassium-sensitivity of BP. The study findings may also help to identify novel biomarkers for salt-sensitivity and potassium-sensitivity of BP and for the prediction of hypertension risk. Finally, the findings from this study may help to develop new pharmaceutical treatments for salt-sensitive hypertension.

项目概要 血压 (BP) 的盐敏感性与高血压和心血管疾病风险增加相关 疾病死亡率。盐敏感性的潜在机制尚不完全清楚。总体目标 拟议的研究旨在调查血管紧张素原 (AGT)、激肽释放酶、 多巴胺、去甲肾上腺素和白蛋白对血压的盐敏感性和钾敏感性以及罹患糖尿病的风险 高血压。盐敏感性遗传流行病学网络 (GenSalt) 是 NHLBI 赞助的饮食 2003 年 10 月至 2005 年 7 月期间，对居住在中国农村的 1,906 名参与者进行了喂养研究。 饮食干预包括 7 天低钠喂养（51.3 mmol/天）、7 天高钠喂养 （307.8 mmol/天），以及 7 天高钠喂养并口服补钾（60 mmol/天）。血压 在基线期间的每一天和 3 个干预期间的每一天都获得测量结果。 GenSalt 研究中进行了两次随访检查来调查高血压的发生率 2008年8月至2009年12月和2011年8月至2012年5月期间的参与者。GenSalt复制研究 从 4 月到 2019 年，使用相同的研究方案对居住在同一地区的 698 名参与者进行了 2010 年 11 月。GenSalt 和 GenSalt 复制研究具有高质量的数据和足够的数据 生物样本为实现以下特定目标提供了独特的机会： 1. 调查 AGT、激肽释放酶、多巴胺、去甲肾上腺素和白蛋白与盐和钾的尿液排泄 BP 的敏感性，以及 2. 研究 AGT、激肽释放酶、多巴胺、 去甲肾上腺素和白蛋白随后发生高血压。为了实现这些具体目标，我们 将测量冷冻保存24小时的尿AGT、激肽释放酶、多巴胺、去甲肾上腺素和白蛋白 GenSalt 和 GenSalt 复制研究参与者的尿液样本；分析泌尿系统的相关性 基线和饮食干预期间生物标志物的排泄，以及血压对饮食钠和饮食的反应 对 2,604 名 GenSalt 和 GenSalt 复制研究参与者进行钾干预；并分析 基线和饮食干预期间生物标志物尿液排泄的前瞻性关系 通过血压随访数据，了解 1,906 名 GenSalt 研究参与者的后续高血压风险。拟议的 研究非常及时且具有成本效益，因为它利用了丰富的资源和研究基础设施 GenSalt 研究。这项研究将是第一个大型调查，旨在检验多个因素之间的关联 尿液生物标志物和盐敏感性高血压的风险。这项研究的结果可能提供新颖的 深入了解 BP 盐敏感性和钾敏感性的潜在生物学机制。研究 研究结果还可能有助于确定血压盐敏感性和钾敏感性的新生物标志物以及 高血压风险的预测。最后，这项研究的结果可能有助于开发新的 盐敏感性高血压的药物治疗。