Hyperactive ENaC identifies hypertensive individuals amenable to amiloridetherapy

Pathophysiological features of both primary aldosteronism and pseudohyperal dosteronism are hyperactive amiloride-sensitive epithelial Na+ channels (EN aC) and refractory hypertension. Peripheral blood lymphocytes express ENaC, which functions and is regulated similarly to ENaC expressed by renal prin cipal cells. Thus it was hypothesized that individuals with either of these hypertensive etiologies could be identified by assessment of the function and regulation of peripheral blood lymphocyte ENaC, by whole cell patch cla mp. We also tested the hypothesis that specific inhibition of hyperactive E NaC with amiloride could ameliorate the hypertension. To test these hypothe ses, we solicited blood samples from normotensive, controlled hypertensive, and refractory hypertensive individuals. Lymphocytes were examined electro physiologically to determine whether ENaC was hyperactive. All positive fin dings were from refractory hypertensive individuals. Nine refractory hypert ensive patients had amiloride added to their hypertensive therapy. Amilorid e normalized the blood pressure of four subjects. These individuals all had hyperactive ENaC. Amiloride had no effect on individuals with normal ENaC. These findings suggest that whole-cell patch clamp of peripheral blood lym phocytes can be used to identify accurately and rapidly hypertensive indivi duals who will respond to amiloride therapy.