title: Renal genetic mechanisms of essential hypertension.
abstract: Human essential hypertension is a polygenic disease whose phenotypic expression is modulated by the environment. Though the kidney could play a major role in the initiation and maintainment of hypertension, many questions remain open. Rat models of primary hypertension provided the substantial information with experiments on kidney cross-transplantation showing that at least a portion of hypertension could be transplanted with the kidney in all strains where such experiment has been carried out. Data consistent with those of rats have also been obtained in humans. Many abnormalities in kidney function and cell membrane on transport have been described in hypertensive rats and humans but the logical sequence of events going from a genetic-molecular abnormality to a cellular abnormality which causes hypertension via a modification of kidney function is difficult to prove. We established this sequence in Milan hypertensive rats using a variety of experimental techniques such as the study of isolated kidney and renal cell function, cell membrane ion transport, cross-immunisation with membrane proteins, molecular biology, genetic crosses and manipulation. Such study led to the identification of a polymorphism in the cytoskeletal protein adducin and to the demonstration of its role in blood pressure control. Recently, alpha-adducin variants have been associated to both human primary hypertension and salt sensitive hypertension. Finally, recent findings strongly support the hypothesis that adducin variants may affect kidney function by modulating the overall capacity of the tubular epithelial cells to transport ions through both a modification in the assembly of actin cytoskeleton, and a modulation of sodium pump activity.
authors.affiliation: Chair of Nephrology and Postgraduate School of Nephrology, University of Milan, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Manunta
authors.forename: R
authors.initials: R
authors.lastname: Cerutti
authors.forename: L
authors.initials: L
authors.lastname: Bernardi
authors.forename: P
authors.initials: P
authors.lastname: Stella
authors.forename: G
authors.initials: G
authors.lastname: Bianchi
mesh_terms: D000818:Animals; D002148:Calmodulin-Binding Proteins / Q000235:genetics* / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000235:genetics; D004195:Disease Models, Animal; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D017136:Ion Transport; D007668:Kidney / Q000503:physiopathology*; D008954:Models, Biological; D011110:Polymorphism, Genetic; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase; D000099291:Adducins
chemical_list: D002148:Calmodulin-Binding Proteins; D003598:Cytoskeletal Proteins; D000254:Sodium-Potassium-Exchanging ATPase; D000099291:Adducins