Aerobic Endurance Training Exerts Cardioprotective Effects by Regulating Metalloproteinases 2 and 9 Activities And Cardiac Angiotensin Levels In Stressed Rats

We aimed to investigate the effects of combining endurance aerobic training and chronic stress on systemic responses and cardiac remodeling. We hypothesize that endurance training not only improves systemic and cardiac renin angiotensin system (RAS) profiles but also modulates metalloproteinases (MMPs) activity by reducing angiotensin (Ang) II levels and MMP-9 activity, while concurrently increasing Ang 1-7 levels and MMP-2 activity. We hypothesize that endurance training not only improves systemic and cardiac RAS profiles but also modulates MMP activity by reducing Ang II levels and MMP-9 activity, while concurrently increasing Ang 1-7 levels and MMP-2 activity. Trained rats (T and TS) were submitted to 8-weeks endurance training regimen on treadmill. Non-trained rats (NT and NTS) were also submitted to identical procedures except for physical training. Three weeks after the onset of endurance training, stress protocol was applied for 3 weeks. TS and NTS rats were exposed to stressors, including restraint stress, cage tilting, overnight lighting, damp bedding, and light-dark cycle reversion. Blood was collected and the heart was isolated for biochemical analysis. Our results unveiled the chronic stress effect elevated in 130% the myocardial activity of MMP-2 and 125% the Ang 1-9 levels, with a concomitant reduction in the cardiac and systemic levels of Ang 1-7 (55% lower than NT rats). Chronic stress reduced the circulating levels of Ang 1-9 and Ang 1-5 (71% and 76 % lower, respectively: vs. NT) along with an increase in 13% of Ang III (2-8) levels that may produce physiologically relevant effects that are similar to those produced by Ang II. Training and stress elevated the circulating levels of MMP-2 (1313% higher in TS vs. NT) and MMP-9 (1114% higher in TS vs. NT), but endurance training conferred cardioprotective effects by reducing 118% the myocardial activity of MMP-2 along with reduction in the myocardial levels of Ang 3-7 (37% and 33% lower than NT and T, respectively). Although higher circulating levels of MMP-2 and MMP-9 was observed in response to aerobic endurance training, we conclude that aerobic endurance training exerts cardioprotective effects by alleviating the stress-induced higher cardiac MMP-2 activity along with reduction in the cardiac levels of Ang 3-7. Funding: This work was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP Processes 2021/06090-8 and 2017/17027-0). This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.