GENETIC SALT SENSITIVE HYPERTENSION IN RATS

大鼠遗传性盐敏感性高血压

• 批准号: 6273125
• 负责人: ALLYN L. MARK
• 金额: $ 18.84万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-03-05 至 1999-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6273125
• 关键词: arterioles; chromosome movement; dietary sodium; disease /disorder model; efferent nerve; electrophysiology; familial hypertension; genetic mapping; genetic markers; genetic strain; histology; kidney circulation; kidney transplantation; laboratory rat; mechanical stress; microcirculation; neuroregulation; pathology; phenotype; quantitative trait loci; spontaneous hypertensive rat; sympathetic nervous system; ultrasound blood flow measurement; vasodilation

The overall goal of this project is to further insight into the genetic basis of salt-sensitive hypertension in genetically hypertensive rats. We will evaluate the role of intermediate physiologic phenotypes as genetic contributors to salt-sensitive hypertension in Dahl rats, spontaneously hypertensive rats (SHR), and borderline hypertensive rats (BHR). There is substantial evidence from both human hypertension and genetic hypertension in rats that complex quantitative traits such as alterations in sympathetic neural function and vascular structure contribute importantly to the pathogenesis of spontaneous hypertension, but there have been few studies addressing this concept using modern genetic approaches. Our aims is to test the hypotheses that: l - altered sympathetic neural mechanisms are a genetic determinant of salt-induced hypertension in Dahl salt- sensitive(S) rats, SHR and BHR, and 2. arteriolar remodeling in the form of a reduction in external vessel diameter distinct from hypertrophy is a genetic determinant of hypertension in Dahl S rats and SHR. To test these hypotheses, we will 1 - employ segregating populations from crosses of the genetically hypertensive and normotensive rats to determine if the putative intermediate neural and vascular structural phenotypes cosegregate with blood pressure, and 2. use genetic markers to identify chromosomal quantitative trait loci(QTLs) Nhat Co segregate with these intermediate neural and structural phenotypes. We will also capitalize - on the availability of congenic strains of Dahl rats that differ only in a segment of chromosome containing either the "r" or "s" allele for 11B- hydroxylase to test the concept that genetic variation in 11B-hydroxylase gene and steroid production in S and R acts in the central nervous system to alter sympathetic neural regulation and arterial pressure in Dahl rats. The studies in this project are close intertwined with Dr. Rapp's work in Project 3 aimed at identifying QTLs that influence blood pressure in the Dahl rat. Our work is aimed at advancing insight into the physiologic intermediate phenotypes that may be regulated by QTLs exerting a major influence on blood pressure in Dahl rats.

该项目的总体目标是进一步深入了解遗传 遗传性高血压大鼠中盐敏感性高血压的基础。 我们 将评估中间生理表型作为遗传的作用 自发的大鼠盐敏感高血压的贡献者 高血压大鼠（SHR）和边缘性高血压大鼠（BHR）。 有 人类高血压和遗传性高血压的大量证据 在复杂定量特征的大鼠中，例如改变 交感神经功能和血管结构贡献重要 对于自发性高血压的发病机理，但很少 使用现代遗传方法来解决这一概念的研究。 我们的目标 是测试以下假设：L-改变交感神经机制 是达尔盐中盐诱导高血压的遗传决定因素 敏感的大鼠，SHR和BHR和2。 与肥大不同的外部血管直径降低的是 Dahl S大鼠和SHR中高血压的遗传决定因素。测试这些 假设，我们将使用1-雇用隔离人群 遗传性高血压和正常的大鼠，以确定是否是否 推定的中间神经和血管结构表型 与血压进行cosegregate，2。使用遗传标记来识别 与这些 中间神经和结构表型。我们还将大写 - 关于Dahl大鼠的先天性菌株的可用性 一段11B-的染色体含有“ R”或“ S”等位基因 羟化酶测试11B-羟化酶中遗传变异的概念 S和R的基因和类固醇在中枢神经系统中起作用 改变DAHL大鼠的交感神经调节和动脉压。 该项目的研究与Rapp博士的工作紧密交织在一起 项目3旨在识别影响血压的QTL 达尔大鼠。我们的工作旨在促进对生理学的见解 QTL可能调节主要表型的中间表型 对达尔大鼠血压的影响。