Objective: Since we showed recently that T causes time-dependent changes on brain RAS and oxidative stress of hypertensive rats, we sought now to investigate the sequential effects of T on ACE2-Ang(1-7)-MasR axis and reactive oxygen species (ROS) production in the left ventricle (LV) of SHRs.
Methods: Male SHR and WKY aged 12 weeks underwent maximal exercise test (ET) and were allocated to T (50-60% of maximum exercise capacity, 1 h/day, 5 days/week) or sedentary (S) groups for 8 weeks. Subgroups of rats were cannulated at weeks 0 (S0), 1 (T1), 2 (T2), 4 (T4) and 8 (S8 and T8) for measurement of resting pressure (AP) and heart rate (HR), followed by saline perfusion and harvesting of the heart. ACE2 and MasR expression (Western Blotting) and ROS production (Dihydroethidium staining) were measured in the LV.
Results: At the beginning of protocols SHR vs WKY exhibited higher MAP and HR (169±1 mmHg, 351±9 b/min, corresponding to 44% and 7% increases), elevated MasR (1,22±0,03 vs 1,00± 0,01 AU) but similar ACE2 expression (1,06±0,04 AU). ROS production was higher in SHR vs WKY (78±4 x 103 vs 66±1 x 103 AU). T increased treadmill performance (+0,87±0.10 km/h) and decreased resting HR (-15% at T4-T8) in both groups; MAP was only reduced in SHR (-10% at T8). T caused no change in the WKY group but increased ACE2 expression in the SHR (~1.14±0.03 au, T1-T4 P<0.05 vs WKY), with a biphasic response in Mas receptor expression: an early fall and a late increase (1,02±0,07 AU at T2-T4 and 1,20±0,04 AU at T8, respectively, P<0.05). In the SHR, T also caused an early normalization in ROS production (65±1 x 103 AU at T2) which was maintained up to T8. Again T did not change ROS production in the WKY group.
Conclusions: Augmented ACE2 expression and reduced ROS production in the heart of the SHR are early responses to training, which are followed by a late increase in MasR expression. Data suggest that the prompt normalization of ROS production is mediated by ACE2-induced reduction of angiotensin II content in the LV of the trained SHR.