Abstract 3630: Exercise Training Increases Cardiomyocyte Passive Stiffness and Phosphatase Activity in Progressive Pulmonary Hypertension
Objective Recently, we have demonstrated that exercise training improved exercise capacity in stable pulmonary hypertension (PH) but was detrimental in progressive PH (Handoko -Circulation 2009). Here, we investigated whether the opposite effects of exercise in vivo could be ascribed to functional changes in right ventricular cardiomyocytes.
Methods and Results Rats received a single injection of low (40 mg/kg) or high (60 mg/kg) dose monocrotaline to induce stable PH and progressive PH, respectively. Two weeks after injection, rats were randomized to a sedentary or training group (treadmill training: 4 weeks, 5x/week, 30 min, n=9 in all groups). Exercise significantly increased passive stiffness of single cardiomyocytes in progressive PH, whereas it reduced passive stiffness in stable PH (pinteraction<0.05). In addition, exercise increased maximal force in both groups, without an effect on Ca2+-sensitivity. Phosphorylation status of myosin binding protein C and troponin I were decreased by exercise in progressive PH, though increased in stable PH (pinteraction<0.05). In addition, exercise significantly increased protein levels of protein phosphatase 1 in progressive PH only (p<0.01).
Conclusions Increased exercise-induced cardiomyocyte stiffness in progressive PH may be explained by phosphatase induced hypophosphorylation of myofilament proteins. Our study indicates that the exercise induced opposite changes in cardiomyocyte stiffness might in part explain the opposite effects of exercise in vivo in PH and identifies potential novel therapeutic targets.