NEW EXPERIMENTAL MODELS OF HYPERTENSION

描述：自发性高血压大鼠（SHR）是最广泛的 研究原发性高血压的实验动物模型。 虽然 自发性高血压大鼠已成为研究血液调节机制的重要实验工具 压力（BP）调节，该菌株的研究价值已被 由于所谓的正常血压控制问题而严重受损 Wistar-Kyoto（WKY）大鼠品系。 SHR和WKY品系不同 在整个啮齿类动物基因组中，不仅仅是在涉及 高血压的发病机制 因此，不清楚是否有任何 SHR和WKY品系之间报道的多种生物学差异是 与BP中的菌株差异有机械和/或遗传联系; 其中许多差异可能与发病机制无关 高血压 在目前的研究中，研究人员将获得新的 SHR的菌株，将：1）有助于解决许多相关问题 在传统SHR模型中进行实验研究，2）使他们能够 开始分离参与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BN大鼠的多个同类品系。 每个 这些新菌株将不同于SHR的祖先菌株或BN 祖菌株相对于单个染色体区域。 无线电遥测技术将用于测量这些菌株的血压， 同源菌株将使他们能够明确地识别 染色体区域有助于自发性 高血压 最后，他们将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， 由此选定的染色体区域可以影响心血管功能 还有BP。

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.