Abstract :
In animal models of hypertension, traditional physiologic and biochemical studies have identified a host of complex pathways that may contribute to increased blood pressure. Just as pharmacologic perturbations of these pathways can alter blood pressure, it is now well-established that artificially engineered genetic lesions in many of these pathways can also alter blood pressure. However, little is known about the contribution of naturally occurring genetic variation in any of these pathways to inherited variation in blood pressure. Recent linkage studies in segregating populations derived from crosses of genetically hypertensive rats and normotensive rats have identified multiple chromosome regions that may contain genes involved in the pathogenesis of spontaneous hypertension. New genetic models for hypertension research, including recombinant inbred strains, congenic strains, and transgenic strains, are beginning to provide important opportunities for investigating whether certain candidate genes contribute to inherited variations in blood pressure and related cardiovascular phenotypes. The use of linkage studies and the new genetic models for dissecting primary mechanisms of spontaneous hypertension will be the focus of this presentation. The applications and limitations of these genetic approaches will be discussed and the use of combined physiologic and genetic strategies will be emphasized.
