GENETIC SALT SENSITIVE HYPERTENSION IN RATS

这个项目的总体目标是进一步深入了解基因 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作为遗传基因的作用 Dahl大鼠盐敏感型高血压的自发因素 高血压大鼠(SHR)和临界高血压大鼠(BHR)。的确有 来自人类高血压和遗传性高血压的大量证据 在数量性状复杂的大鼠中， 交感神经功能和血管结构起重要作用 对自发性高血压发病机制的研究一直很少 使用现代遗传学方法解决这一概念的研究。我们的目标 是为了验证这样的假设：L改变了交感神经机制 是Dahl盐中盐源性高血压的遗传决定因素- 敏感(S)大鼠，自发性高血压大鼠和高血压大鼠，2.小动脉重构的形式 与肥大不同的外部血管直径缩小的一个特征是 Dahl S大鼠和自发性高血压大鼠高血压的遗传决定因素。为了测试这些 假设，我们将1-使用分离的种群来自 以确定遗传性高血压和正常血压大鼠是否 推测的中间神经和血管结构表型 与血压相关；2.使用遗传标记识别 染色体数量性状基因座(QTL)与这些QTL分离 中间的神经和结构表型。我们还将利用- DAHL大鼠同源品系的可得性 含有11B-R或S等位基因的一段染色体 用羟基酶测试11B-羟基酶遗传变异的概念 S和R作用于中枢神经系统的基因和类固醇的产生 改变Dahl大鼠的交感神经调节和动脉压。 该项目中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。我们的工作旨在推进对生理学的洞察 可能受主效QTL调控的中间表型 对Dahl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.