The theme of this Program will continue to be focused on identifying the genetic bases for both hypertension and resultant target organ damage. Efforts are designed to identify and map genes responsible for elevated arterial pressure, for the new airpuff-stress phenotype, for renal function traits important to the hypertension phenotype and for receptor and signal transduction mechanisms potentially contributors to the phenotype of the spontaneously hypertensive rat (SHR). Project 1 will extend studies of cellular, pharmacological and neurophysiological importance of a new stress phenotype to genetic hypertension and seek additional QTLs in the new Colony of Recombinant Inbred Rat strains. Project 2 will extend studies of new congenic strains which they developed to identify and test the significance of blood pressure QTLs and to map blood pressure regulating genes important for full expression of the hypertension phenotype. Project 3 will develop congenics for chromosome 7 and 2 to test newly discovered QTLs for plasma and urinary calcium and examine their relationship to blood pressure, renal function and electrolyte homeostasis. Project 4 will extend studies of the regulation and function of stress activated signaling pathways that control the activity of the transcriptional factors AP-1 and NF-kappaB and evaluate their importance to the hypertension phenotype. Project 5 will extend studies into the role and genetic basis of hyper-excitability of spinal nicotinic and excitatory amino acid receptor mechanisms to hypertension and the stress response of the SHR. The Program contains three Cores. A continuing Breeder Core will provide SHR(LJ), WKY(LJ) and Program-derived congenics to Projects. An expanded Molecular Genetics Core will consist of three Subcores designed to conduct phenotyping, statistical genetics and genotyping. The Molecular Genetics Core will continue its efforts on genetic analysis of the phenotyped SHR x WKY cross, will assist with Program studies of the Recombinant Inbred Rat strains and with the development of congenics.
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