Robust arm and leg muscle adaptation to training despite ACE inhibition: a randomized placebo-controlled trial

Tórur Sjúrðarson, Jacob Bejder, Andreas Breenfeldt Andersen, Thomas C. Bonne, Kasper Kyhl, Martin Thomassen, Júlia Prats, Noomi Oddmarsdóttir Gregersen, May-Britt Skoradal, Pál Weihe, Nikolai B. Nordsborg, Magni Mohr

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1 Citation (Scopus)


Purpose Angiotensin-converting enzyme (ACE) inhibitor treatment is widely applied, but the fact that plasma ACE activity
is a potential determinant of training-induced local muscular adaptability is often neglected. Thus, we investigated the hypothesis that ACE inhibition modulates the response to systematic aerobic exercise training on leg and arm muscular adaptations.
Methods Healthy, untrained, middle-aged participants (40±7 yrs) completed a randomized, double-blinded, placebo-controlled trial. Participants were randomized to placebo (PLA: CaCO3) or ACE inhibitor (ACEi
: enalapril) for 8 weeks and
completed a supervised, high-intensity exercise training program. Muscular characteristics in the leg and arm were extensively evaluated pre and post-intervention.
Results Forty-eight participants (nACEi=23, nPLA =25) completed the trial. Exercise training compliance was above 99%.
After training, citrate synthase, 3-hydroxyacyl-CoA dehydrogenase and phosphofructokinase maximal activity were increased
in m. vastus lateralis in both groups (all P0.05).
In m. deltoideus, citrate synthase maximal activity was upregulated to a greater extent (time×treatment P(51 [33;69] %) than in ACEi
(28 [13;43] %), but the change in 3-hydroxyacyl-CoA dehydrogenase and phosphofructokinase
maximal activity was similar between groups. Finally, the training-induced changes in the platelet endothelial cell adhesion molecule-1 protein abundance, a marker of capillary density, were similar in both groups in m. vastus lateralis and m.
Conclusion Eight weeks of high-intensity whole-body exercise training improves markers of skeletal muscle mitochondrial
oxidative capacity, glycolytic capacity and angiogenesis, with no overall efect of pharmacological ACE inhibition in healthy
Original languageEnglish
Article numbers00421-022-05072-5
Number of pages13
JournalEuropean Journal of Applied Physiology
Publication statusPublished - 22 Oct 2022


  • Angiotensin-converting enzyme inhibitors
  • Muscle oxidative capacity
  • High-intensity interval training
  • Muscle-specifc adaptations
  • Angiogenesis


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