The aim was to investigate the potential role of the renin-angiotensin system in the electromechanical changes associated with left ventricular hypertrophy (LVH) induced by thoracic aortic constriction, and its regression. LVH was induced by placing a plastic clip (2mm diameter) around the ascending aorta under anaesthesia (30 mg/kg methohexitone sodium, followed by inhalation of a 49%/49%/2%, N₂O/O₂/halothane mixture). After 42±3 days, animals underwent a second thoracotomy, with an identical anaesthetic procedure, and the plastic clip was either removed (regressed group) or left in place (age-matched LVH group). Following the second operation animals were fed losartan (10 mg/kg/day) or placebo in the drinking water for 42±3 days. Sham-operated and unoperated animals were controls. In another group, angiotensin II (200 ng/kg/min) or saline was infused by subcutaneous osmotic mini-pumps for 42±3 days. After humane killing, the heart was removed, heart-to-body weight ratio (HBR) recorded, and papillary muscles superfused in Tyrode solution at 37°C. Isometric tension and action potential (AP) characteristics were recorded as previously described (Botchway et al. 2004). The force-frequency relationship was quantified as the ratio of peak tensions generated at stimulation frequencies of 1.6 and 0.8 Hz (T_1.6/0.8). Results are given as mean±SD and statistical significance from control (p<0.05) assessed using Student's t tests. Compared with sham and unoperated animals (n =16), significant changes to the LVH group (n=11) were: an increased HBR; (3.89±0.41 vs 2.75±0.41 g/kg); a decline in the force-frequency response (T_1.6/0.8) 1.33±0.14 vs 1.52±0.09); a reduction of longitudinal conduction velocity (58.9±3.8 vs 70.9±3.4 cm/s); an increase of transverse conduction velocity (24.2±4.6 vs 19.4±2.7cm/s); and prolongation of the action potential duration (APD) at 1Hz (221.7±14.9 vs 209.4±11.7 ms). With removal of the constriction (n=10) HBR and conduction velocity decreased towards control values (3.15±0.39 g/kg, p<0.05 and 66.7±4.7 cm/s, p<0.05 respectively) and T_1.6/0.8 recovered completely (1.52±0.17. Losartan had no effect on these variables in either the LVH or regressed animals. Angiotensin II infusion (n=7) was also accompanied by an increase of HBR (3.57±0.44 vs 2.66±0.24 g/kg), a decline of T_1.6/0.8 (1.23±0.04 vs 1.55±0.05), but no change to longitudinal conduction velocity (72.2±4.1 vs 73.2±2.1 cm/s) or APD (206.4±17.9 vs 209.4±11.7ms) compared to saline infusion (n=6). Transverse conduction velocity increased from 17.5±1.8 to 23.2±3.9 cm/s). We conclude that electromechanical changes to hypertrophied myocardium are different in these two models of LVH. Furthermore, angiotensin II receptor blockade has no effect on the electromechanical changes induced by thoracic aortic constriction.