NEW EXPERIMENTAL MODELS OF HYPERTENSION

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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.