The importance of the epithelial sodium channel in determining salt sensitivity in people of African origin

Abstract

Hypertension is highly prevalent in Black Africans and has been found to be associated with worse blood pressure (BP) control and more cardiovascular disease. Black Africans are more salt sensitive with low renin and aldosterone levels. This can be explained in part by variants in the epithelial sodium channel (ENaC) causing an increase in channel activity resulting in sodium and water retention. These variants in the ENaC are increased in the Black African populations presumably due to selective pressure for sodium retention in traditionally low-salt diets. Furthermore, increased endothelial sodium channel activity contributes to the risk of vascular stiffness, which may also result in more difficult to control hypertension. Patients with increased activity of the ENaC are more likely to respond to amiloride (a selective sodium channel antagonist), which has implications for the management of severe and resistant hypertension in Black Africans. A large-scale controlled trial on the use of amiloride compared to usual care is warranted in Blacks with severe or resistant hypertension.

Keywords: ENaC; Genetics; Hypertension; Renin and aldosterone; Salt sensitivity; Sodium channel.