The Effect of Amiloride (10mg) on the Blood Pressure Response to Ischemic Exercise: Preliminary Observations
Authors: Stavres Jon , Luck J. C. , Hamaoka Takuto , Blaha Cheryl , Cauffman Aimee , Herr Mick , Sarraf Elie , Farrag Mohamed , Janicki Piotr , Sinoway Lawrence I. , Cui Jian , Ruiz‐Velasco Victor 
Published: May 2022

Background

During exercise, blood pressure increases via augmented central command and stimulation of mechano‐ and metabosensitive muscle afferents (i.e., the exercise pressor reflex). Recent evidence has reported a strong role of acid sensing ion channels (ASIC’s) in mediating this reflex, as well as exercise induced muscle pain. Therefore, it is logical to suspect that inhibiting ASIC’s would mitigate the exaggerated blood pressure responses and exercise related muscle pain observed in individuals with peripheral artery disease (PAD).

Purpose

. We tested the hypothesis that a single 10mg dose of amiloride (a K+‐sparing diuretic known to inhibit ASIC’s) would attenuate the pressor response to blood flow restricted (BFR) plantar flexion exercise in young healthy adults.

Methods

Six healthy subjects (5 male, 26 ± 2 y/o, 180.8 ± 12.1 cm, 79.7 ± 12.9 Kg) completed three separate visits. Each visit included two bouts of isometric plantar flexion, both performed until failure at 30% of the predetermined maximal voluntary isometric contraction. During one bout, blood flow to the limb was restricted via a pressurized cuff placed around the proximal portion of the lower leg (BFR); the other bout was performed under free flow conditions. In the first visit, subjects performed these two exercise bouts (in random order) under normal, non‐treated conditions. In the second and third visits, subjects performed these exercise bouts (same order as in visit 1) ~3 hrs after oral ingestion of 10mg of amiloride, or ingestion of a placebo (random order). Blood pressure and heart rate were continuously recorded throughout exercise, and time to fatigue and muscle pain (on a 12cm visual analog scale) was recorded at the end of each exercise bout. Only data from the placebo and amiloride conditions are presented here.

Results

The addition of BFR reduced total exercise time by ~40.8% (t=2.99, p=0.03), but had no significant effect on peak muscle pain (p>0.10). Due to the preliminary nature of these data, no significant main effects of treatment (amiloride vs. placebo) were observed for free flow or BFR exercise (all p>0.05). However, we did observe a net decrease in the average heart rate response (+10.7 ± 3.0 bpm vs. +11.3 ± 3.7 bpm, ηp2=0.539, p>0.47), the total blood pressure response (5477.5 ± 373.7 mmHg*sec vs. 5841.3 ± 518.9 mmHg*sec, ηp2=0.250, p>0.30), the total time‐tension index (595.9 ± 406.5 Kg*sec vs. 691.6 ± 394.2 Kg*sec, ηp2=0.211, p>0.30), and the blood pressure to time‐tension index relationship (9.09 ± 4.40 mmHg/Kg vs. 11.38 ± 6.30 mmHg/Kg, ηp2=0.08, p>0.50) in the amiloride condition compared to the placebo condition during BFR exercise.

Conclusions

While these preliminary findings do not indicate significant effects of treatment, these observations serve as strong pilot data to support the continued investigation of amiloride as a method of attenuating the pressor response to ischemic exercise.