GENETIC SALT SENSITIVE HYPERTENSION IN RATS

该项目的总体目标是进一步深入了解遗传 遗传性高血压大鼠盐敏感性高血压的基础。 我们 将评估中间生理表型的作用， Dahl大鼠盐敏感性高血压的自发性贡献者 高血压大鼠（SHR）和临界高血压大鼠（BHR）。 有 来自人类高血压和遗传性高血压的大量证据 在大鼠中，复杂的数量性状，如 交感神经功能和血管结构对 自发性高血压的发病机制，但很少有 使用现代遗传学方法研究这一概念。 我们的目标 是为了验证假设：l -改变交感神经机制 是达尔盐中盐引起的高血压的遗传决定因素 敏感（S）大鼠、SHR和BHR;小动脉重塑 与肥大不同的是， Dahl S大鼠和SHR高血压的遗传决定因素测试这些 假设，我们将1 -采用分离的人口从杂交的 遗传性高血压和正常血压大鼠，以确定是否 假定的中间神经和血管结构表型 与血压共分离; 2.用遗传标记来识别 染色体数量性状位点（QTL）Nhat Co与这些分离 中间神经和结构表型。我们还将利用- Dahl大鼠的同类品系的可用性， 含有11B的“r”或“s”等位基因的染色体片段- 羟化酶，以测试11B-羟化酶的遗传变异的概念， S和R中的基因和类固醇产生作用于中枢神经系统 改变Dahl大鼠的交感神经调节和动脉压。 该项目的研究与拉普博士在 项目3旨在确定影响血压的QTL， 达尔老鼠。我们的工作旨在深入了解 中间表型，可能是由QTL发挥主要作用， 对达尔大鼠血压的影响。

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.