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.