A 10-mg dose of amiloride increases time to failure during blood-flow-restricted plantar flexion in healthy adults without influencing blood pressure

Author:

Stavres Jon12ORCID,Luck J. Carter2ORCID,Hamaoka Takuto2ORCID,Blaha Cheryl2,Cauffman Aimee2,Dalton Paul C.2,Herr Michael D.2,Ruiz-Velasco Victor3,Carr Zyad J.4,Janicki Piotr3,Cui Jian2ORCID

Affiliation:

1. School of Kinesiology and Nutrition, University of Southern Mississippi, Hattiesburg, Mississippi

2. Penn State Heart and Vascular Institute, Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey, Pennsylvania

3. Department of Anesthesiology and Perioperative Medicine, Penn State University College of Medicine, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania

4. Department of Anesthesiology, Yale School of Medicine, Yale New Haven Hospital, New Haven, Connecticut

Abstract

Amiloride has been shown to inhibit acid-sensing ion channels (ASICs), which contribute to ischemia-related muscle pain during exercise. The purpose of this study was to determine if a single oral dose of amiloride would improve exercise tolerance and attenuate blood pressure during blood-flow-restricted (BFR) exercise in healthy adults. Ten subjects (4 females) performed isometric plantar flexion exercise with BFR (30% maximal voluntary contraction) after ingesting either a 10-mg dose of amiloride or a volume-matched placebo (random order). Time to failure, time-tension index (TTI), and perceived pain (visual analog scale) were compared between the amiloride and placebo trials. Mean blood pressure, heart rate, blood pressure index (BPI), and BPI normalized to TTI (BPInorm) were also compared between trials using both time-matched (TM50 and TM100) and effort-matched (T50 and T100) comparisons. Time to failure (+69.4 ± 63.2 s, P < 0.01) and TTI (+1,441 ± 633 kg·s, P = 0.02) were both significantly increased in the amiloride trial compared with placebo, despite no increase in pain (+0.4 ± 1.7 cm, P = 0.46). In contrast, amiloride had no significant influence on the mean blood pressure or heart rate responses, nor were there any significant differences in BPI or BPInorm between trials when matched for time (all P ≥ 0.13). When matched for effort, BPI was significantly greater in the amiloride trial (+5,300 ± 1,798 mmHg·s, P = 0.01), likely owing to an increase in total exercise duration. In conclusion, a 10-mg oral dose of amiloride appears to significantly improve the tolerance to BFR exercise in healthy adults without influencing blood pressure responses.

Funder

Penn State University College of Medicine

HHS | NIH | National Heart, Lung, and Blood Institute

HHS | NIH | National Center for Advancing Translational Sciences

University of Southern Mississippi

Publisher

American Physiological Society

Subject

Physiology (medical),Physiology

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