Angiotensin, Sodium and Genes in Primate Hypertension

灵长类高血压中的血管紧张素、钠和基因

• 批准号: 6479485
• 负责人: Joseph R Haywood
• 金额: $ 53.08万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6479485
• 关键词: angiotensin /renin /aldosterone hypertension; baboons; dietary sodium; genetic susceptibility; hypertension; ion transport; lithium; nutrition related tag; renin angiotensin system; sodium ion

DESCRIPTION (provided by applicant): Sodium-dependent hypertension has long been associated with a defect in renal function. Experimental models as well as human studies have also suggested that an alteration in genetic expression may contribute to the hypertensive process. Sodium-lithium countertransport (SLC) activity is one mechanism that helps maintain intracellular sodium concentrations, and in some hypertensive patients, SLC activity is increased. These individuals also experience an inappropriate response to sodium challenges that appears to result from a lack of suppression of the renin-angiotensin-aldosterone system (RAAS). The association between SLC activity and hypertension is genetically determined since it occurs in families. It is uncertain whether this reflects an alteration in the gene for SLC, one of the genes that may increase RAAS function, or an interaction between genes for the two systems. The goal of the proposed studies is to examine the relationship between SLC activity and the RAAS in a non-human primate model in which the SLC phenotype is high or low. The hypothesis to be tested is that a high SLC activity is associated with inappropriately high RAAS function and a greater arterial pressure sensitivity to dietary sodium. In three aims, the contributions of peripheral and central RAAS components to sodium-dependent hypertension will be studied in baboons with the high and low SLC phenotypes. In the first aim, regulation of the RAAS will be examined in high and low SLC animals during a step-wise increase in sodium intake. These experiments will determine whether animals with high SLC activity have a reduced ability to suppress the RAAS and develop salt-sensitive hypertension. The second aim will investigate the role of angiotensin and aldosterone in the stimulation of hypertension by sodium and their ability to cause blood pressure to rise in high and low SLC animals. This aim will determine whether by raising plasma angiotensin or aldosterone the high SLC animals are more likely to become hypertensive. The third aim will focus on central nervous system mechanisms associated with an inappropriately high RAAS in high and low SLC animals. These studies will determine whether the high SLC activity results in more sensitive central mechanisms driving the sympathetic nervous system to raise arterial pressure. These studies will help provide data to determine whether an inappropriately high RAAS activity can cause hypertension. Importantly, this work will also reveal whether the genetically determined phenotype of high SLC is important in predisposing an animal to sodium-dependent hypertension.

描述（由申请人提供）：钠依赖性高血压长期以来 与肾功能缺陷有关。实验模型以及 人类研究还表明，基因表达的改变可能 有助于高血压的过程。钠锂逆向转运 (SLC) 活性是帮助维持细胞内钠的一种机制 浓度，并且在一些高血压患者中，SLC 活性增加。 这些人也会对钠产生不适当的反应 挑战似乎是由于缺乏对 肾素-血管紧张素-醛固酮系统（RAAS）。 SLC之间的关联 活动和高血压是由基因决定的，因为它发生在 家庭。尚不确定这是否反映了基因的改变 SLC，可能增加 RAAS 功能的基因之一，或相互作用 两个系统的基因之间。拟议研究的目标是 检查非人类中 SLC 活性与 RAAS 之间的关系 SLC表型高或低的灵长类动物模型。假设为 经测试，高 SLC 活性与不适当的高 RAAS 相关 功能和动脉压对膳食钠的敏感性更高。在 三个目标，外围和中央 RAAS 组件对 将在狒狒身上研究钠依赖性高血压 SLC表型。第一个目标是，将对 RAAS 的监管进行审查 高和低 SLC 动物在逐步增加钠摄入量的过程中。这些 实验将确定具有高 SLC 活性的动物是否具有 抑制 RAAS 的能力降低并发展成盐敏感性高血压。 第二个目标是研究血管紧张素和醛固酮在 钠刺激高血压及其引起血压的能力 在高和低 SLC 动物中升高。这个目标将决定是否通过提高 血浆血管紧张素或醛固酮水平较高的 SLC 动物更有可能 变得高血压。第三个目标将集中于中枢神经系统 与高和低 SLC 中不适当的高 RAAS 相关的机制 动物。这些研究将确定高 SLC 活性是否会导致 更敏感的中枢机制驱动交感神经系统 提高动脉压。这些研究将有助于提供数据来确定 RAAS 活性过高是否会导致高血压。 重要的是，这项工作还将揭示基因是否决定了 高 SLC 表型对于动物易感性很重要 钠依赖性高血压。