Involvement of renal apical Na transport systems in the control of blood pressure

Human genetic studies and gene targeting techniques in mice suggest that th e genes encoding renal apical Na transport proteins play an essential role in the control of extracellular fluid volume and blood pressure. Particular ly, very significant advancements in understanding the role of these genes in Mendelian forms of hypertension or hypotension have been achieved in rec ent years. However, much progress still needs to be made in understanding t he more common forms of human essential hypertension. In addition to the mo use models that should be very useful for investigating the mechanisms by w hich a mutation provokes the hypertensive phenotype, improved clinical phen otyping of patients is needed as well as the use of DNA chip techniques to unravel global gene interactions. Indeed, it is likely that most chronic bl ood pressure disturbances in a given environment result from a specific com bination of polymorphisms or mutations rather than from unique genetic vari ants. Of equal importance will be definition of the various factors that re gulate the expression and activity of the Na transport systems. These regul atory pathways and the responses to environmental factors such as dietary s alt, stress, etc, may play a central role in determining the appearance, se verity, and complications of essential hypertension. (C) 2001 by the Nation al Kidney Foundation, Inc.