Research efforts of this Program Project are designed to identify and map genes in newly discovered quantitative trait loci (QTL) and to elucidate their contributions to susceptibility to genetic hypertension and target organ damage. Four projects supported by five cores comprise this Program. The Program theme emphasizes genomics of the effect of stressors on aberrant cardiovascular responses in the SHR, unique genetic rodent models, including the only colony of HXB-BXH rat Recombinant Inbred (RI) strains outside of Europe, and the pursuit of genes which (a) determine resting arterial pressure, (b) determine autonomic responses to environmental and behavioral stress, or (c) determine susceptibility to hypertension from repeated episodes of stress. The first subproject will seek candidate genes in new QTL discovered for mild airpuff startle stress-elicited tachycardia and pressor responses, for bradycardia associated with the Orienting Response, and for a cluster of blood pressure QTL on chromosome 2. Dr. Kurtz's subproject will build on its studies of the genes, Srebp-1 and CD36, and their role in abnormal lipid, glucose and plasma insulin in the SHR. Dr. Nigam's subproject will study the cell biology and mechanisms of action of new and unknown factors which exert inhibition on the formation of the developing ureteric tree and ultimately nephron number. Dr. Taylor's subproject will continue studies of hyper-responsiveness of spinal nicotinic receptors in the SHR and define the gene structure of nicotinic receptor subunit genes, which are in close proximity to a blood pressure locus. Cores will provide the folkowing functions: administration; breeding of rodents; telemetry and phenotyping, statistical genetic analyses, gene discovery, informatics and genotyping. The contributions of this Program should enhance our knowledge of genes, which determine susceptibility to repeated stress, to hypertension, to metabolic risk factors and to target organ damage.
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