GENETIC ISOLATION OF A REGION OF CHROMOSOME-8 THAT EXERTS MAJOR EFFECTS ON BLOOD-PRESSURE AND CARDIAC MASS IN THE SPONTANEOUSLY HYPERTENSIVE RAT

The spontaneously hypertensive rat (SHR) is the most widely studied an imal model of essential hypertension. Despite > 30 yr of research, the primary genetic lesions responsible for hypertension in the SHR remai n undefined. In this report, we describe the construction and hemodyna mic characterization of a congenic strain of SHR (SHR-Lx) that carries a defined segment of chromosome 8 from a normotensive strain of Brown -Norway rats (BN-Lx strain). Transfer of this segment of chromosome 8 from the BN-Lx strain onto the SHR background resulted in substantial reductions in systolic and diastolic blood pressure and cardiac mass. Linkage and comparative mapping studies indicate that the transferred chromosome segment contains a number of candidate genes for hypertensi on, including genes encoding a brain dopamine receptor and a renal epi thelial potassium channel. These findings demonstrate that BP regulato ry gene(s) exist within the differential chromosome segment trapped in the SHR-Lx congenic strain and that this region of chromosome 8 plays a major role in the hypertension of SHR vs. BN-Lx rats.