Angiotensin II Promotes Skeletal Muscle Angiogenesis Induced by Volume-Dependent Aerobic Exercise Training: Effects on miRNAs-27a/b and Oxidant-Antioxidant Balance.

Aerobic exercise training (ET) produces beneficial adaptations in skeletal muscles, including angiogenesis. The renin-angiotensin system (RAS) is highly involved in angiogenesis stimuli. However, the molecular mechanisms underlying capillary growth in skeletal muscle induced by aerobic ET are not completely understood. This study aimed to investigate the effects of volume-dependent aerobic ET on skeletal muscle angiogenesis involving the expression of miRNAs-27a and 27b on RAS and oxidant-antioxidant balance. Eight-week-old female Wistar rats were divided into three groups: sedentary control (SC), trained protocol 1 (P1), and trained protocol 2 (P2). P1 consisted of 60 min/day of swimming, 5×/week, for 10 weeks. P2 consisted of the same protocol as P1 until the 8th week, but in the 9th week, rats trained 2×/day, and in the 10th week, trained 3×/day. Angiogenesis and molecular analyses were performed in soleus muscle samples. Furthermore, to establish ET-induced angiogenesis through RAS, animals were treated with an AT1 receptor blocker (losartan). Aerobic ET promoted higher VO2 peak and exercise tolerance values. In contrast, miRNA-27a and -27b levels were reduced in both trained groups, compared with the SC group. This was in parallel with an increase in the ACE1/Ang II/VEGF axis, which led to a higher capillary-to-fiber ratio. Moreover, aerobic ET induced an antioxidant profile increasing skeletal muscle SOD2 and catalase gene expression, which was accompanied by high nitrite levels and reduced nitrotyrosine concentrations in the circulation. Additionally, losartan treatment partially re-established the miRNAs expression and the capillary-to-fiber ratio in the trained groups. In summary, aerobic ET promoted angiogenesis through the miRNA-27a/b-ACE1/Ang II/VEGF axis and improved the redox balance. Losartan treatment demonstrates the participation of RAS in ET-induced vascular growth. miRNAs and RAS components are promising potential targets to modulate angiogenesis for combating vascular diseases, as well as potential biomarkers to monitor training interventions and physical performance.

Effects of postexercise cooling on heart rate recovery in normotensive and hypertensive men.

BACKGROUND: Postexercise heart rate recovery (HRR) is determined by cardiac autonomic restoration after exercise and is reduced in hypertension. Postexercise cooling accelerates HRR in healthy subjects, but its effects in a population with cardiac autonomic dysfunction, such as hypertensives (HT), may be blunted. This study assessed and compared the effects of postexercise cooling on HRR and cardiac autonomic regulation in HT and normotensive (NT) subjects. METHODS: Twenty-three never-treated HT (43 ± 8 years) and 25 NT (45 ± 8 years) men randomly underwent two exercise sessions (30 min of cycling at 70% VO2peak ) followed by 15 min of recovery. In one randomly allocated session, a fan was turned on in front of the subject during the recovery (cooling), while in the other session, no cooling was performed (control). HRR was assessed by heart rate reductions after 60 s (HRR60s) and 300 s (HRR300s) of recovery, short-term time constant of HRR (T30) and the time constant of the HRR after exponential fitting (HRRτ). HRV was assessed using time- and frequency-domain indices. RESULTS: HRR and HRV responses in the cooling and control sessions were similar between the HT and NT. Thus, in both groups, postexercise cooling equally accelerated HRR (HRR300s = 39±12 versus 36 ± 10 bpm, P≤0·05) and increased postexercise HRV (lnRMSSD = 1·8 ± 0·7 versus 1·6 ± 0·7 ms, P≤0·05). CONCLUSION: Differently from the hypothesis, postexercise cooling produced similar improvements in HRR in HT and NT men, likely by an acceleration of cardiac parasympathetic reactivation and sympathetic withdrawal. These results suggest that postexercise cooling equally accelerates HRR in hypertensive and normotensive subjects.

Metaboreflex activation delays heart rate recovery after aerobic exercise in never-treated hypertensive men.

KEY POINTS: Recent evidence indicates that metaboreflex regulates heart rate recovery after exercise (HRR). An increased metaboreflex activity during the post-exercise period might help to explain the reduced HRR observed in hypertensive subjects. Using lower limb circulatory occlusion, the present study showed that metaboreflex activation during the post-exercise period delayed HRR in never-treated hypertensive men compared to normotensives. These findings may be relevant for understanding the physiological mechanisms associated with autonomic dysfunction in hypertensive men. ABSTRACT: Muscle metaboreflex influences heart rate (HR) regulation after aerobic exercise. Therefore, increased metaboreflex sensitivity may help to explain the delayed HR recovery (HRR) reported in hypertension. The present study assessed and compared the effect of metaboreflex activation after exercise on HRR, cardiac baroreflex sensitivity (cBRS) and heart rate variability (HRV) in normotensive (NT) and hypertensive (HT) men. Twenty-three never-treated HT and 25 NT men randomly underwent two-cycle ergometer exercise sessions (30 min, 70% V̇O2 peak ) followed by 5 min of inactive recovery performed with (occlusion) or without (control) leg circulatory occlusion (bilateral thigh cuffs inflated to a suprasystolic pressure). HRR was assessed via HR reduction after 30, 60 and 300 s of recovery (HRR30s, HRR60s and HRR300s), as well as by the analysis of short- and long-term time constants of HRR. cBRS was assessed by sequence technique and HRV by the root mean square residual and the root mean square of successive differences between adjacent RR intervals on subsequent 30 s segments. Data were analysed using two- and three-way ANOVA. HRR60s and cBRS were significant and similarly reduced in both groups in the occlusion compared to the control session (combined values: 20 ± 10 vs. 26 ± 9 beats min-1 and 2.1 ± 1.2 vs. 3.2 ± 2.4 ms mmHg-1 , respectively, P < 0.05). HRR300s and HRV were also reduced in the occlusion session, although these reductions were significantly greater in HT compared to NT (-16 ± 11 vs. -8 ± 15 beats min-1 for HRR300s, P < 0.05). The results support the role of metaboreflex in HRR and suggest that increased metaboreflex sensitivity may partially explain the delayed HRR observed in HT men.