Fellowship for Jason Collett: GRA Spring 2011 ONE YEAR Predoctoral Fellowship: Interactions Among the Renin-Angiotensin System, Mitochondrial and Nuclear Genomes and the Development of Hypertension

The goal of this fellowship proposal is to evaluate angiotensin II, type 1 receptor (AT1r) receptor mediated physiological and genetic mechanisms of heritable hypertension in a Spontaneously Hypertensive Rat (SHR)/ Brown Norway (BN) backcross rat. We have developed and identified a unique experimental model of hypertension in rats that is expected to provide critical insight into underlying mechanisms of essential hypertension. Physiological and genetic interactions are hypothesized to contribute to elevated arterial pressure and spontaneous hypertension. Specific Aim 1 will determine tissue AT1r protein expression in normotensive (NT) and hypertensive (HT) SHR/BN rats. Specific Aim 2 will identify differentially expressed mitochondrial genes contributing to genetic hypertension in SHR/BN rats. Specific Aim 3 will determine the significance of several loci linked to hypertension utilizing nuclear genome-wide linkage analysis and quantitative trait loci (QTL) identification in SHR/BN rats. The combined results from Aims 1, 2, and 3 will provide new and critical data into AT1 receptor mediated physiological and genetic mechanisms of heritable hypertension. The experiments in this research proposal will provide novel insight into the interactions between RAS, mitochondrial and nuclear genomes that are likely involved in the pathophysiology of hypertension.