Contribution of sympathetic activation to antihypertrophic memory after regression of exercise-induced physiological myocardial hypertrophy in mice

Abstract

To investigate whether anti-hypertrophic memory exists after regression of exercise-induced physiological myocardial hypertrophy (PMH) and explore the contribution of sympathetic activation to hypertrophic memory formation. Seventy-two mice were randomized equally into 6 groups, including sedentary sham-operated group, exercise hypertrophic preconditioning (EHP) + sham operation group, bisoprolol (an adrenergic β1 receptor blocker) + EHP + sham operation group (biso+Exe+Sham group), sedentary group with transverse aortic constriction (TAC) (Sed+TAC group), EHP+ TAC group (Exe+TAC group), and bisoprolol+EHP+TAC group (biso+Exe+TAC group). The mice in the EHP groups were subjected to 3 weeks of swimming training, and in the bisoprolol groups, bisoprolol was administered by gavage once daily from two days before till the end of the training. One week after the training, TAC or sham surgery was performed. Echocardiography and hemodynamic measurements were performed to evaluate cardiac function of the mice, and the myocardial tissues were examined histologically to detect cardiac remodeling. Compared with the sedentary group, the mice receiving 3 weeks of swimming training had significantly increased heart weight to body weight ratio (HW/BW), HW to tibia length ratio (HW/TL), and the cross-sectional area of the cardiomyocytes (P < 0.05). One week after the training, exercise-induced PMH rapidly diminished and both HW/BW and HW/TL recovered the baseline levels. Treatment with bisoprolol obviously prevented the occurrence of PMH. Four weeks after TAC, the left ventricular posterior wall thickness, HW/BW, HW/TL, left ventricular end diastolic pressure and cross-sectional area of cardiomyocytes were all significantly lower (P < 0.05) while the left ejection fraction and maximal change rate of left ventricular pressure were significantly higher (P < 0.05) in Exe + TAC group than in Sed + TAC group. No significant difference was found in these parameters between biso + Exe + TAC group and Sed + TAC group. Anti-hypertrophic memory exists even after the regression of exercise-induced PMH, which may be attributed to the activation of sympathetic nervous system during exercise.