Urinary Angiotensinogen Excretion and Salt-Sensitivity of Blood Pressure

项目摘要 血压的盐敏感性与高血压和心血管疾病的风险增加有关 疾病死亡率盐敏感性的潜在机制尚未完全了解。的总体目标 所提出的研究是调查血管紧张素原（AGT），激肽释放酶， 多巴胺、去甲肾上腺素和白蛋白与血压的盐敏感性和钾敏感性以及 高血压盐敏感性遗传流行病学网络（GenSalt）是一个由NHLBI赞助的饮食计划。 2003年10月至2005年7月，在中国农村地区的1,906名参与者中进行了喂养研究。的 饮食干预包括7天低钠喂养（51.3 mmol/d），7天高钠喂养 （307.8 mmol/天），以及7天高钠喂养伴口服钾补充（60 mmol/天）。BP 在基线期间的3天中的每一天和3个干预期的每一天获得测量值。 在GenSalt研究中进行了两次随访检查，以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月期间参加了培训。GenSalt复制研究 在同一地区的698名参与者中进行了相同的研究方案，从4月到 2010年11月GenSalt和GenSalt-replication研究具有高质量的数据和足够的 生物样品为以下具体目标提供了独特的机会：1.来调查 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排泄 血压敏感性; 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 将在冷冻储存的24小时内测量尿AGT，激肽释放酶，多巴胺，去甲肾上腺素和白蛋白 GenSalt和GenSalt-replication研究参与者的尿液样本;分析尿液中 基线时和饮食干预期间生物标志物的排泄与饮食钠的BP反应， 在2,604名GenSalt和GenSalt-replication研究参与者中进行钾干预;并分析 基线时和饮食干预期间生物标志物的尿排泄与 1,906名GenSalt研究参与者随后的高血压风险，并有BP随访数据。拟议 这项研究非常及时，成本效益高，因为它利用了美国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规模的调查，以检查之间的关联， 尿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会提供新的 深入了解BP盐敏感性和钾敏感性的潜在生物学机制。研究 这些发现也可能有助于确定BP盐敏感性和钾敏感性的新生物标志物， 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。

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.