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Current Pharmaceutical Design

Volume 12 Issue 18
ISSN: 1381-6128
eISSN: 1873-4286

 

   All Titles

  The Renal Epithelial Sodium Channel: Genetic Heterogeneity and Implications for the Treatment of High Blood Pressure
  pp.2221-2234 (14) Authors: G. A. Sagnella, P. A. Swift
 
 
      Abstract

The renal epithelial sodium channel (ENaC) is of fundamental importance in the control of sodium reabsorption through the distal nephron. ENaC is an important component in the overall control of sodium balance, blood volume and thereby of blood pressure. This is clearly demonstrated by rare genetic disorders of sodium channel activity (Liddle's Syndrome and Pseudohypoaldosteronism type 1 associated with contrasting effects on blood pressure). Subtle dysregulation of ENaC however may also be important in essential hypertension - a common condition and a major cause of cardiovascular morbidity and mortality.

The epithelial sodium channel is formed from three partly homologous subunits. In this review we deals firstly with current views of structural and functional features of the renal epithelial sodium channel with particular emphasis on mechanisms and processes involved in the control of sodium channel activity at the biochemical and cellular levels. We then focus on genetic aspects with reference to the significance of genetic variation in the sodium channel genes in relation to blood pressure. In particular, we review recent investigations on the potential clinical significance of mutations within the genes encoding ENaC subunits in individuals with high blood pressure. Lastly, we also examine the potential value of pharmacological targeting of the renal epithelial sodium channel with the sodium channel inhibitor amiloride for the treatment of hypertension.

 
  Keywords: Neural Cell Expressed Developmentally Down Regulated 4 (Nedd4), aldosterone, Channel activating protease (CAP), amiloride, hypertension, Afro-Caribbeans
  Affiliation: Blood Pressure Unit, St.George's, University of London, Cranmer Terrace, London, SW17 0RE,UK.
 
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