The renin-angiotensin system (RAS) plays a major role in development of heart failure primarily through its systemic effects but also through local cardiac RAS signalling involving the angiotensin II type 1 (AT1) receptor (Reudelhuber et al. 2007). We developed a transgenic mouse line that expresses constitutively active human AT1 (hAT1) receptors, which can be regulated in differentiated cardiac myocytes. Previously we demonstrated that this transgenic line displays significant ventricular hypertrophy in the absence of pressure overload (Sedo et al. 2005). To investigate the consequence of prolonged activation of cardiac AT1 receptors on cardiac function we examined the effects of moderate exercise training in these mice. Male mice, 6 transgenic (Tg) 7 nontransgenic (NTg), were implanted with telemetry probes (TA11PA-C20; under Isoflurane anaesthesia; 5% induction, 1.5% maintenance) to allow acquisition of blood pressure and heart rate. After implantation and following stable recordings, mice were subjected to an exercise training regime. Mice were allowed free access to voluntary running wheels and the distance run was recorded on a daily basis. Treadmill exercise consisted of two weeks acclimatization, following this animals were run for 30mins per day, four days per week, for eight weeks at 18 mmin^-1 5 deg incline. Continuous blood pressure and heart rate recordings were obtained immediately upon cessation of treadmill exercise. Daily recordings of distance run demonstrated no significant difference in running ability between the two groups (3.3±1.3 (NTg) 3.4±0.9 (Tg) kmday^-1, P>0.05 unpaired t test). The NTg animals showed a typical training response with resting heart rate decreasing from 436±15 to 372±16 beats min^-1 (P<0.05 paired t test). This contrasts with an impaired response observed in the Tg animals where no significant decrease in heart rate was obtained 454±16 to 431±17 beats min^-1 P>0.05 paired t test). In addition in response to treadmill exercise the maximum heart rate and systolic blood pressure were significantly reduced in Tg animals (688±20 (NTg) and 613±16 (Tg) beats min^-1 P<0.02; 160±5 (NTg) and 142±5 (Tg) mmHg P<0.03 unpaired t test). In man, studies suggest that impaired response to exercise training is a predictor of sudden death (Jouven et al., 2005). We conclude that over expression of the hAT1 receptor in murine cardiac myocytes results in an impaired cardiovascular response to moderate exercise training and this may suggest that these animals are undergoing adverse cardiac remodelling.