Objectives: Although physical activity is recommended for hypertensives the effect of endurance training in hypertensives is not well understood. We observed adverse effects of free running wheel exercise in spontaneously hypertensive rats (SHR) including a higher mortality. Low-dose treatment with captopril, an ACE inhibitor, reduced but did not normalize molecular adaptations. In this study we investigated first whether the combined effect of free running wheel exercise and ACE inhibition is superior to ACE inhibition alone and second whether it improves effects of running on myocardial hypertrophy. Methods: 45 SHR and 32 normotensive rats (age: 1yr) were used in this study. Running groups revealed free access to running wheels. Running distance, time, and velocity were controlled. Captopril was administered at a dose of 30 mg/kg with tap- water. All rats were followed for 6 months. Results: Mean systolic blood pressure was 177 mmHg in SHR at the beginning. Free running did not reduce blood pressure but attenuated the additional increase of blood pressure in untreated SHR during the 6 months period (SHR: 201 mmHg; SHR running group: 179 mmHg). Captopril alone reduced blood pressure (153 mmHg) but not in the context of running (186 mmHg). Captopril reduced left ventricular weight- to-tibia length from 0.26 g/mm to 0.20 g/mm in the absence of running but not in the presence of running (0.29 g/mm). Running increased hypertrophy to 0.37 g/mm. Captopril treatment improved left ventricular developed pressure normalized to heart weight compared to non- treated running SHR from 76.8 mmHg to 107.5 mmHg and normalized the SERCA/NCX ratio. Running and captopril normalized molecular markers of hypertrophy in right ventricles more effective than captopril treatment alone. Conclusion: Combination of running and ACE inhibition made endurance training in hypertensive rats safe and evoked a more favourable reverse remodelling in the right ventricle compared to ACE inhibition alone.