Abstract
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 P < 0.05) without statistical differences between them (all time × treatment P > 0.05). In m. deltoideus, citrate synthase maximal activity was upregulated to a greater extent (time × treatment P < 0.05) in PLA (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. deltoideus.
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 effect of pharmacological ACE inhibition in healthy adults.
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Data availability
The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
Abbreviations
- ACE:
-
Angiotensin-converting enzyme
- COX4I1:
-
Cytochrome c oxidase isoform 1
- COX4I2:
-
Cytochrome c oxidase isoform 2
- CS:
-
Citrate synthase
- HAD:
-
3-Hydroxyacyl-CoA dehydrogenase
- HIF-1α:
-
Hypoxia-inducible factor 1-alpha
- PECAM-1:
-
Platelet endothelial cell adhesion molecule-1
- PFK:
-
Phosphofructokinase
- VEGF:
-
Vascular endothelial growth factor
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Acknowledgements
We would like to thank Katrin D. Apol for her help with the recruitment of study participants, and Toni R. Dam, Ólavur Weihe and Magnus Norðberg for their supervision of the exercise sessions. Furthermore, the authors would like to express their appreciation of the commitment and enthusiastic participation of the participants.
Funding
This work was supported by grants from the Research Council Faroe Islands (project number 0352) and the Novo Nordisk Foundation (NNF17OC0029134).
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NBN, TS, JB and MM conceived and designed research. TS, JB, ABA, TB, KK, NOG, MS, MT, JP, PW, MM and NBN performed experiments. TS, JB, MM and NBN analyzed data. TS, JB, MM, KK and NBN interpreted results of experiments. TS prepared figures. TS, MM and NBN drafted manuscript. All authors edited and revised manuscript and approved the final version of the manuscript.
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Sjúrðarson, T., Bejder, J., Breenfeldt Andersen, A. et al. Robust arm and leg muscle adaptation to training despite ACE inhibition: a randomized placebo-controlled trial. Eur J Appl Physiol 123, 325–337 (2023). https://doi.org/10.1007/s00421-022-05072-5
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DOI: https://doi.org/10.1007/s00421-022-05072-5