GENETIC-DETERMINANTS AND RENAL MECHANISMS IN ESSENTIAL-HYPERTENSION

Human essential hypertension is a polygenic disease whose phenotypic e xpression is modulated by the environment. Though the kidney could pla y a major role in the initiation and maintainment of hypertension, man y questions remain open. Rat models of primary hypertension provided t he substantial information with experiments on kidney cross-transplant ation, showing that at least a portion of hypertension could be transp lanted with the kidney in all strains where such an experiment has bee n carried out. Data consistent with those of rats have also been obtai ned in humans. Many abnormalities in kidney function and cell membrane ion transport have been described in hypertensive rats and humans, bu t the logical sequence of events 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 sequenc e in Milan hypertensive rats using a variety of experimental technique s such as the study of isolated kidney and renal cell function, cell m embrane ion transport, cross-immunisation with membrane proteins, mole cular biology, genetic crosses and manipulation, Such study led to the identification of a polymorphism in the cytoskeletal protein adducin, Recently, alpha-adducin variants have been associated to both primary hypertension and salt sensitive hypertension. Finally, recent finding s strongly support the hypothesis that adducin variants may affect kid ney function by modulating the overall capacity of the tubular epithel ial cells to transport ions through both a modification in the assembl y of actin cytoskeleton, and a modulation of sodium pump activity.