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Physical activity is emerging as an alternative nonpharmaceutical strategy to prevent and treat a variety of cardiovascular diseases due to its cardiac and skeletal muscle beneficial effects. Oxidative stress occurs in skeletal muscle of chronic heart failure (CHF) patients with possible impact on muscle function decline. We determined the effect of voluntary-free wheel running (VFWR) in preventing protein damage in Tgαq*44 transgenic mice (Tg) characterized by a delayed CHF progression. In the early (6 months) and transition (12 months) phase of CHF, VFWR increased the daily mean distance covered by Tg mice eliminating the difference between Tg and WT present before exercise at 12 months of age (WT Pre-EX 3.62 ± 1.66 vs. Tg Pre-EX 1.51 ± 1.09 km, P < 0.005; WT Post-EX 5.72 ± 3.42 vs. Tg Post-EX 4.17 ± 1.8 km, P > 0.005). This effect was concomitant with an improvement of in vivo cardiac performance [(Cardiac Index (mL/min/cm 2 ): 6 months, untrained-Tg 0.167 ± 0.005 vs. trained-Tg 0.21 ± 0.003, P < 0.005; 12 months, untrained-Tg 0.1 ± 0.009 vs. trained-Tg 0.133 ± 0.005, P < 0.005]. Such effects were associated with a skeletal muscle antioxidant response effective in preventing oxidative damage induced by CHF at the transition phase (untrained-Tg 0.438 ± 0.25 vs. trained-Tg 0.114 ± 0.010, P < 0.05) and with an increased expression of protein control markers (MuRF-1, untrained-Tg 1.12 ± 0.29 vs. trained-Tg 14.14 ± 3.04, P < 0.0001; Atrogin-1, untrained-Tg 0.9 ± 0.38 vs. trained-Tg 7.79 ± 2.03, P < 0.01; Cathepsin L, untrained-Tg 0.91 ± 0.27 vs. trained-Tg 2.14 ± 0.55, P < 0.01). At the end-stage of CHF (14 months), trained-Tg mice showed a worsening of physical performance (decrease in daily activity and weekly distance and time of activity) compared to trained age-matched WT in association with oxidative protein damage of a similar level to that of untrained-Tg mice (untrained-Tg 0.62 ± 0.24 vs. trained-Tg 0.64 ± 0.13, P > 0.05). Prolonged voluntary physical activity performed before the onset of CHF end-stage, appears to be a useful tool to increase cardiac function and to reduce skeletal muscle oxidative damage counteracting physical activity decline., (© 2019 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

We assessed exercise performance, coronary blood flow and cardiac reserve of female ApoE/LDLR(-/-) mice with advanced atherosclerosis compared with age-matched, wild-type C57BL6/J mice. Exercise capacity was assessed as whole body maximal oxygen consumption (V'O2max), maximum running velocity (vmax) and maximum distance (DISTmax) during treadmill exercise. Cardiac systolic and diastolic function in basal conditions and in response to dobutamine (mimicking exercise-induced cardiac stress) were assessed by Magnetic Resonance Imaging (MRI) in vivo. Function of coronary circulation was assessed in isolated perfused hearts. In female ApoE/LDLR(-/-) mice V'O2max, vmax and DISTmax were not impaired as compared with C57BL6/J mice. Cardiac function at rest and systolic and diastolic cardiac reserve were also preserved in female ApoE/LDLR(-/-) mice as evidenced by preserved fractional area change and similar fall in systolic and end diastolic area after dobutamine. Moreover, endothelium-dependent responses of coronary circulation induced by bradykinin (Bk) and acetylcholine (ACh) were preserved, while endothelium-independent responses induced by NO-donors were augmented in female ApoE/LDLR(-/-) mice. Basal COX-2-dependent production of 6-keto-PGF1α was increased. Concluding, we suggest that robust compensatory mechanisms in coronary circulation involving PGI2- and NO-pathways may efficiently counterbalance coronary atherosclerosis-induced impairment in V'O2max and exercise capacity.