The epithelial sodium channel in hypertension: genetic heterogeneity and implications for treatment with amiloride.

The epithelial sodium channel (ENaC) has a central role in sodium transport across membranes. It is expressed on the apical cell surface of renal tubular epithelia and also on other aldosterone-responsive epithelial cells. In the kidney, ENaC contributes to the regulation of blood pressure via changes in sodium balance and blood volume. Rare monogenetic disorders associated with hypertension have been described, such as Liddle syndrome, which gives rise to increased sodium reabsorption in the kidney via increased ENaC activity. There are many other variants in the genes encoding ENaC subunits, some of which occur with sufficient frequency as to be termed polymorphic variants. The Thr594Met polymorphism of the ENaC beta-subunit gene SCNN1B occurs exclusively in Black individuals, with a frequency of 6-8% in those with hypertension. It increases cAMP mediated ENaC sodium current in affected B lymphocytes, and has been associated with hypertension in a Black South London population. There is preliminary evidence that amiloride is effective as monotherapy in hypertensive individuals with the Thr594Met polymorphism and in patients with resistant hypertension, who have evidence of increased amiloride-sensitive sodium channel activity. If these preliminary studies are corroborated in larger studies, then amiloride may provide an important new strategy for blood pressure control in selected individuals.

Citation

Pauline A Swift, Graham A MacGregor. The epithelial sodium channel in hypertension: genetic heterogeneity and implications for treatment with amiloride. American journal of pharmacogenomics : genomics-related research in drug development and clinical practice. 2004;4(3):161-8

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PMID: 15174897

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