ANGIOTENSIN, SODIUM AND GENES IN PRIMATE HYPERTENSION

灵长类高血压的血管紧张素、钠和基因

• 批准号: 7957889
• 负责人: ROBERT E SHADE
• 金额: $ 15.69万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-06 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7957889
• 关键词: Aldosterone; Angiotensins; Animals; Automobile Driving; Blood Pressure; Computer Retrieval of Information on Scientific Projects Database; Data; Defect; Dietary Sodium; Experimental Models; Family; Funding; Genes; Genetic; Goals; Grant; Human; Hypertension; Individual; Institution; Intake; Lithium; Modeling; Neuraxis; Papio; Patients; Peripheral; Phenotype; Plasma; Primates; Process; Regulation; Renal function; Renin-Angiotensin-Aldosterone System; Research; Research Personnel; Resources; Role; Sodium; Source; Sympathetic Nervous System; System; Testing; United States National Institutes of Health; Work; experience; nonhuman primate; pressure; research study; response; salt sensitive

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 依赖钠的高血压长期与肾功能的缺陷有关。实验模型以及人类研究也表明，遗传表达的改变可能有助于高血压过程。硫乙烷逆转录（SLC）活性是一种有助于维持细胞内钠浓度的机制，在某些高血压患者中，SLC活性增加。这些人还对钠挑战的反应不当，这似乎是由于缺乏抑制肾素 - 血管紧张素 - 醛固酮系统（RAAS）而导致的。 SLC活性与高血压之间的关联是基因确定的，因为它发生在家族中。尚不确定这是否反映了SLC基因的改变，可能会增加RAAS功能的基因之一，或两个系统基因之间的相互作用。拟议的研究的目的是检查SLC表型高或低的非人类灵长类动物模型中SLC活性与RAA之间的关系。要测试的假设是，高SLC活性与不适当的RAAS功能和对饮食钠的动脉压敏感有关。在三个目的中，将研究外周和中央RAAS成分对依赖钠的高血压的贡献，这些高血压将在具有高和低SLC表型的狒狒中进行。在第一个目的中，在钠摄入量的逐步增加期间，将在高和低SLC动物中检查RAA的调节。这些实验将确定具有较高SLC活性的动物是否具有抑制RAAS和发展盐敏感性高血压的能力。第二个目标将研究血管紧张素和醛固酮在钠刺激高血压及其在高和低SLC动物中升高的能力。这个目标将通过提高血浆血管紧张素或醛固酮来确定高SLC动物更有可能变得高血压。第三个目标将集中于与高和低SLC动物中不当高的RAAS相关的中枢神经系统机制。这些研究将确定高SLC活性是否导致更敏感的中心机制推动交感神经系统升高动脉压。这些研究将有助于提供数据，以确定不适当的RAAS活性是否会导致高血压。重要的是，这项工作还将揭示高SLC的遗传确定的表型是否在使动物易于钠依赖性高血压中很重要。