NEW EXPERIMENTAL MODELS OF HYPERTENSION

描述：自发性高血压大鼠(SHR)是目前应用最广泛的 研究了实验性高血压动物模型。尽管 SHR已成为研究血液机制的重要实验工具 压力(BP)调节，该菌株的研究价值已 因所谓的正常血压控制问题而严重受损 Wistar-京都(WKY)大鼠品系。SHR株和WKY株不同 在整个啮齿动物基因组中，不仅仅是在涉及 高血压的发病机制。因此，尚不清楚是否有任何 据报道，SHR和WKY株之间存在多种生物学差异 在机理上和/或基因上与BP中的菌株差异有关； 这些差异中的许多可能与糖尿病的发病机制无关。 高血压。在目前的研究中，研究人员将衍生出新颖的 SHR的菌株将：1)帮助解决许多相关的问题 与传统SHR模型中的实验研究和2)使他们能够 开始分离涉及初级染色体的特定染色体区域 自发性高血压的发病机制。为了实现这些目标，他们 将产生SHR和正常血压的BN大鼠的多个同源品系。每个人 这些新的毒株中，将不同于SHR前体毒株或BN 关于单个染色体区域的祖代菌株。 将使用无线电遥测技术来测量这些菌株的血压，以及 同源菌株将使他们能够确定哪些是 染色体区域在自发性骨质疏松症的发病机制中起作用 高血压。最后，他们将把这些菌株分发给其他 研究人员也对研究病理生理机制感兴趣 由此选择的染色体区域可能会影响心血管功能 和英国石油公司。

DESCRIPTION: The spontaneously hypertensive rat (SHR) is the most widely studied experimental animal model of essential hypertension. Although the SHR has been an important experimental tool for studying mechanisms of blood pressure (BP) regulation, the research value of this strain has been seriously compromised by problems with the so-called normotensive control strain of Wistar-Kyoto (WKY) rats. The SHR and WKY strains differ throughout the entire rodent genome, not just at loci involved in the pathogenesis of hypertension. Thus, it is unclear whether any of the multiple biological differences reported between the SHR and WKY strains are mechanistically and or genetically linked to the strain differences in BP; many of these differences may not be relevant to the pathogenesis of hypertension. In the current studies, the investigators will derive novel strains of SHR that will: 1) help to solve many of the problems associated with experimental studies in the traditional SHR model and 2) enable them to begin to isolate specific chromosome regions involved in the primary pathogenesis of spontaneous hypertension. To accomplish these goals, they will create multiple congenic strains of SHR and normotensive BN rats. Each of these new strains will differ from the SHR progenitor strain or BN progenitor strain with respect to a single chromosome region. Radiotelemetry techniques will be used to measure BP in these strains, and the congenic strains will enable them to definitively identify which chromosome regions are contributing to the pathogenesis of spontaneous hypertension. Finally, they will distribute these strains to other investigators also interested in studying pathophysiologic mechanisms whereby selected chromosome regions may influence cardiovascular function and BP.