MODULATION OF ACE2 AND THE MAIN COMPONENTS OF THE RENIN-ANGIOTENSIN SYSTEM IN HUMAN SKELETAL MUSCLE BY BLOOD FLOW RESTRICTION WALKING TRAINING.

Author(s): GARCIA-GONZALEZ, E.1, THOMPSON, K.M.A.2, GALVAN ALVAREZ, V.1, MARTINEZ-CANTON, M.1, GALLEGO-SELLES, A.1, GARCIA-PEREZ, G.1, MORALES-ALAMO, D.1, SKATTEBO, Ø.3, DE PAZ, J.A.4, BOUSHEL, R.5, HALLEN, J.3, MARTIN-RINCON, M.1, BURR, J.F.2, CALBET, J.A.L.1,3, Institution: PHYSICAL EDUCATION DEPARTMENT, Country: SPAIN, Abstract-ID: 2425

INTRODUCTION:
Blood Flow Restriction (BFR) added to any intensity endurance training improves the aerobic capacity of young healthy individuals and trained athletes, likely by acting as a major stressor on fluid regulating systems, as well as on vessel and cardiovascular function. An acute BFR session increases the concentration of blood volume (BV) regulating-hormones such as renin and copeptin, which could be mediated by changes in the main components of the Renin Angiotensin System (RAS). Furthermore, Angiotensin-converting enzyme 2 (ACE2) is a critical modulator of the hyperemic response to exercise and/or BFR. The aim of the study was to assess the changes in maximal aerobic capacity (VO2max) and to determine the effects on basal skeletal muscle (SM) expression of ACE2, its regulatory protein ADAM17 and key components of the RAS elicited by BFR added to walking training in highly trained athletes.
METHODS:
Ten highly trained athletes (31.5 ± 5.1yr; 59.2 ± 8.9ml.kg-1, min-1; 7M/3F) were divided into BFR training group (BFR, 100% lowest occlusion pressure) (N=6) and control (CON) (N=4). Both groups performed 6 weeks (3x/week) of 5x3min at 5km/h and 5% incline separated by 1min rest. Resting biopsies were taken from m. vastus lateralis at PRE and POST. Protein expression was measured by WB. Statistics analysis: ANOVA and t-test.
RESULTS:
At POST, BFR group showed a significant increase in VO2max (+4.1%, p=0.017), that was not present in CON. The protein levels of ACE2 were upregulated in BFR by 25% (p=0.05), while remained unchanged in CON (time*group; p=0.026). The protein levels of ACE were not modified by training (t-test; p>0.05), regardless of group (time*group; p=0.72). Similarly, there were no significant changes from PRE to POST for AT1R or AT2R in any groups (t-test; p>0.05), with a similar response across groups (time*group; P>0.31). The levels of ADAM17 were not significantly reduced by 12.6% in BFR (p=0.16), while remained unchanged in CON (time*group; p=0.26).
CONCLUSION:
This study shows that BFR added to walking improves VO2max and increases the expression levels of ACE2, without apparent changes in other components of the RAS nor ADAM17 in SM of highly trained athletes. We have recently shown a linear association between SM ACE2 and VO2max, which might imply that high levels of ACE2 are present in this population. Nonetheless, data shows that BFR training during walking can be a sufficient stimulus to increase ACE2 in SM, which may facilitate muscle perfusion, oxygen delivery and explain the observed increase in VO2max. Besides a higher ACE2 expression, increasing the conversion of Angiotensin 2 to Angiotensin 1-7 may limit the BV expansion stimulation elicited by activation of the RAS in the context of BFR. It remains to be elucidated what are the effects of BFR training on the expression of ACE2 in less fit individuals and whether it plays role in performance or hemodynamical adaptations.
GRANTS: PID2021-125354OB-C21, CSD EXP_75097