Epithelial sodium channel inhibition by amiloride on blood pressure and cardiovascular disease risk in young prehypertensives

Abstract

Overactivity of the epithelial sodium channel (ENaC) is considered to be one mechanism underlying obesity-related blood pressure (BP) elevation. In an open-labeled, nonplacebo-controlled clinical trial (Clinicaltrials.gov: NCT-01308983), the authors aimed to comprehensively evaluate the effects of amiloride monotherapy, an ENaC blocker, on BP and cardiovascular risk in young adults with prehypertension (n=17). The mean body mass index of participants was 28.45±1.30 kg/m(2) . Following 10 mg daily amiloride for 4 weeks, peripheral systolic BP (SBP), central SBP, and carotid-radial pulse wave velocity were significantly reduced by -7.06±2.25 mm Hg, -7.68±2.56 mm Hg, and -0.72±0.33 m/s, respectively, whereas flow-mediated dilation was significantly increased by 2.2±0.9%. Following amiloride monotherapy for 4 weeks, a significant increase in serum aldosterone was observed (5.85±2.45 ng/dL). ENaC inhibition by amiloride may be used as an early intervention to halt the progression to full hypertension and cardiovascular disease in young adults with prehypertension.

Trial registration: ClinicalTrials.gov NCT01308983.

©2013 Wiley Periodicals, Inc.

Figures

Figure 1

Effects of amiloride on peripheral systolic blood pressure (SBP), central SBP, flow‐mediated dilation (FMD), and carotid‐radial pulse wave velocity (CR‐PWV) in all participants (N=17). *P value <.05. (A) Effects of amiloride on peripheral SBP. (B) Effects of amiloride on central SBP. (C) Effects of amiloride on FMD. (D) Effects of amiloride on CR‐PWV.

Figure 2

Effects of amiloride on peripheral and central systolic blood pressure (SBP) reduction in stage 2 prehypertensive participants (N=6). *P value <.01. (A) Effects of amiloride on peripheral SBP in stage 2 prehypertensive participants. (B) Effects of amiloride on central SBP in stage 2 prehypertensive participants.