Current Hypertension Reviews

Prof. Kazuomi Kario
Jichi Medical University
School of Medicine
Tochigi
Japan

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The Epithelial Na+ Channel as a Determinant of Blood Pressure

Author(s): Timothy J. Burton, Kevin M. O'Shaughnessy, Morris J. Brown.

Abstract:

The epithelial Na+ channel (ENaC) forms the rate limiting step in transepithelial Na+ absorption across aldosterone- responsive tissues such as the distal nephron. After more than a decade of investigation it is clear that the mechanisms of ENaC regulation are complex with an array of ENaC-regulatory proteins having been identified. A variety of monogenic syndromes of low renin hypertension have been identified that serve, through different mechanisms, to upregulate distal tubular ENaC activity. One of the most extensively studied, Liddles syndrome, results predominantly from mutations in the C-termini of β and γ-ENaC subunits leading to a failure of Nedd4-2 (neuronal precursor cell-expressed and developmentally down-regulated protein 4-2) mediated channel endocytosis and an increased expression of ENaC at the cell surface. The role of ENaC subunit polymorphisms as determinants of essential hypertension has been investigated in a number of studies. The T594M mutation in the β-subunit of ENaC, for example, has been screened in large study populations and there is conflicting evidence that it co-segregates with blood pressure. Reasons for such controversies are discussed. The authors conclude that ENaC is a pivotal convergence point in blood pressure regulation and that future studies must identify better ways to measure distal tubular ENaC activity and investigate the importance of combination polymorphisms of ENaC subunits and their regulatory proteins as genetic determinants of hypertension.

Keywords: Epithelial Na+ channel, hypertension

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Article Details

VOLUME: 3
ISSUE: 1
Year: 2007
Page: [45 - 49]
Pages: 5
DOI: 10.2174/157340207779815491