Aerobic Exercise Attenuates Pressure Overload-Induced Cardiac Dysfunction through Promoting Skeletal Muscle Microcirculation and Increasing Muscle Mass

Abstract

Background: Aerobic exercise has been proven to have a positive effect on cardiac function after hypertension; however, the mechanism is not entirely clarified. Skeletal muscle mass and microcirculation are closely associated with blood pressure and cardiac function.

Objective: This study was designed to investigate the effects of aerobic exercise on the skeletal muscle capillary and muscle mass, to explore the possible mechanisms involved in exercise-induced mitigation of cardiac dysfunction in pressure overload mice.

Methods: In this study, 60 BALB/C mice aged 8 weeks were randomly divided into 3 groups: control (CON), TAC, and TAC plus exercise (TAE) group and utilized transverse aortic constriction (TAC) to establish hypertensive model; meanwhile, treadmill training is used for aerobic exercise. After 5 days of recovery, mice in the TAE group were subjected to 10-week aerobic exercise. Carotid pressure and cardiac function were examined before mice were executed by Millar catheter and ultrasound, respectively. Muscle mass of gastrocnemius was weighed; cross-sectional area and the number of capillaries of gastrocnemius were detected by HE and immunohistochemistry, respectively. The mRNA and protein levels of VEGF in skeletal muscle were determined by RT-PCR and western blot, respectively.

Results: We found that ① 10-week aerobic exercise counteracted hypertension and attenuated cardiac dysfunction in TAC-induced hypertensive mice; ② TAC decreased muscle mass of gastrocnemius and resulted in muscle atrophy, while 10-week aerobic exercise could reserve transverse aortic constriction-induced the decline of muscle mass and muscle atrophy; and ③ TAC reduced the number of capillaries and the protein level of VEGF in gastrocnemius, whereas 10-week aerobic exercise augmented the number of capillaries, the mRNA and protein levels of VEGF in mice were subjected to TAC surgery.

Conclusions: This study indicates that 10-week aerobic exercise might fulfill its blood pressure-lowering effect via improving skeletal muscle microcirculation and increasing muscle mass.

Figure 1

Exercise attenuated TAC-induced hypertension. The carotid pressure was determined after exercise was finished by Millar catheter. Compared with the CON group, TAC surgery significantly increased the carotid blood pressure, indicating the successful establishment of hypertension; compared with the TAC group, the carotid blood pressure of the TAE group was lowered, which suggested that aerobic exercise was an effective method to prevent elevated blood pressure. CON: control, TAC: transverse aortic constriction, and TAE: transverse aortic constriction plus exercised. n = 6–7 per group.  ^∗∗p < 0.01 vs. CON; ^#p < 0.05 vs. TAC.

Figure 2

Exercise mitigated cardiac structure and dysfunction in TAC-induced hypertensive mice. Cardiac LVIDs, LVIDd, and ejection fraction were detected by ultrasound; the respective pictures of cardiac ultrasound in CON, TAC, and TAE were shown (a), and the results of LVIDs, LVIDd, and ejection fraction were calculated (b, c), heart muscle cross-sectional area was determined by HE staining, five views of each section were chosen, and pictures were captured by light microscope at 400× magnification (d). Total area and the number of cell nuclear were examined by Leica Qwin Plus software, and the muscle cross-sectional area was calculated (e). CON: control, TAC: transverse aortic constriction, and TAE: transverse aortic constriction plus exercised. n = 6 per group. ^∗p < 0.05 vs. CON;  ^∗∗p < 0.01 vs. CON; ^#p < 0.05 vs. TAC.

Figure 3

Aerobic exercise augmented the number of skeletal muscle capillaries in TAC-induced hypertensive mice. Skeletal muscle capillaries were determined by immunostaining with anti-CD31 antibody, platelet endothelial cell adhesion molecule-1. The positive spots that the arrows indicated represented capillary (a). Five views of each section were chosen, and the number of capillaries were counted under the light microscope at 400× magnification and analyzed by independent t-test (b). CON: control, TAC: transverse aortic constriction, and TAE: transverse aortic constriction plus exercised. n = 6 per group.  ^∗∗p < 0.01 vs. CON; ^#p < 0.05 vs. TAC.

Figure 4

Aerobic exercise increased the mRNA and protein levels of VEGF in skeletal muscle of TAC-induced hypertensive mice. The relative mRNA (a) and protein (b) levels of VEGF in skeletal muscle were examined by RT-PCR and western blot, respectively. CON: control, TAC: transverse aortic constriction, and TAE: transverse aortic constriction plus exercised. n = 6 per group.  ^∗∗p < 0.01 vs. CON; ^#p < 0.05 vs. TAC.

Figure 5

Aerobic exercise totally reversed relative skeletal muscle mass loss and alleviated muscle atrophy induced by TAC. (a) The body weight was weighed at different time points after TAC surgery. (b) The value of relative skeletal muscle mass was calculated by the formula: = the mass of gastrocnemius divided by body weight. (c) Skeletal muscle morphology was determined by HE staining; five views of each section were chosen; and pictures were captured by light microscope at ×400 magnification. (d) Total area and the number of cell nuclear were examined by Leica Qwin Plus software, and the muscle cross-sectional area was calculated. CON: control, TAC: transverse aortic constriction, and TAE: transverse aortic constriction plus exercised. n = 6 per group. ^∗p < 0.05 and  ^∗∗p < 0.01 vs. CON; ^#p < 0.05 vs. TAC.

Figure 6

Proposed mechanism underlying the effects of aerobic exercise attenuates pressure overload-induced cardiac dysfunction.