Restoration of normal ventricular electrophysiology in renovascular hypertensive rabbits after treatment with losartan

Left ventricular hypertrophy (LVH) is associated with abnormal ventricular electrophysiology. We have shown complete regression of LVH and normalizati on of ventricular electrophysiology in renovascular hypertensive rabbits tr eated with captopril. To determine if angiotensin II type 1 receptor (AT(1) ) blockade produces the same benefit, we treated hypertensive rabbits with losartan for 3 months. LVH was evaluated by heart-to-body weight ratio (HW/ BW). Vulnerability to ventricular arrhythmia was assessed by ventricular fi brillation threshold (VFT) and dispersion of effective refractory period (E RP). The electrical properties of single left ventricular myocytes were cha racterized by action potential duration at 90% repolarization (APD(90)) and inward rectifier K+ current (I-K1) density. Hypertensive rabbits treated w ith vehicle (LVH/Vehicle) had higher mean arterial pressure (MAP, 81 +/- 2 vs. 60 +/- 2 mm Hg) and HW/BW (2.71 +/- 0.07 vs. 1.97 +/- 0.04 g/kg), lower VFT (20 +/- 1 vs. 39 +/- 2 mA), larger dispersion of ERP (34 a 3 vs. 1 1 a 3 ms), longer APD(90) (187 +/- 6 vs. 162 +/- 6 ms) and lower I-K1 density compared with control rabbits. Hypertensive rabbits treated with losartan ( LVH/Losartan) had HW/BW (2.36 +/- 0.06 g/kg) between those of LVH/Vehicle a nd control rabbits. whereas MAP (65 +/- 2 mm Hg), VFT (34 +/- 2 mA), disper sion of ERP (19 +/- 1 ms), APD(90) (160 +/- 6 ms), and I-K1 density were si gnificantly different from LVH/Vehicle but similar to control. We conclude that AT(1) blockade in renovascular hypertensive rabbits normalizes ventric ular electrophysiology.