Rials S J, Xu X, Wu Y, Liu T, Marinchack R A, Kowey P R
Healthcare, Inc., Columbus, Ohio, USA.
J Cardiovasc Pharmacol. 2001 Mar;37(3):317-23. doi: 10.1097/00005344-200103000-00010.
Left ventricular hypertrophy (LVH) is associated with abnormal ventricular electrophysiology. We have shown complete regression of LVH and normalization of ventricular electrophysiology in renovascular hypertensive rabbits treated with captopril. To determine if angiotensin II type 1 receptor (AT1) 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 fibrillation threshold (VFT) and dispersion of effective refractory period (ERP). The electrical properties of single left ventricular myocytes were characterized by action potential duration at 90% repolarization (APD90) and inward rectifier K+ current (I(K1)) density. Hypertensive rabbits treated with 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+/-3 vs. 14+/-3 ms), longer APD90 (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 and control rabbits, whereas MAP (65+/-2 mm Hg), VFT (34+/-2 mA), dispersion of ERP (19+/-1 ms), APD90 (160+/-6 ms), and I(K1) density were significantly different from LVH/Vehicle but similar to control. We conclude that AT1 blockade in renovascular hypertensive rabbits normalizes ventricular electrophysiology.
左心室肥厚（LVH）与心室电生理异常有关。我们已经证明，用卡托普利治疗的肾血管性高血压兔的LVH完全消退，心室电生理恢复正常。为了确定1型血管紧张素II受体（AT1）阻断是否产生相同的益处，我们用氯沙坦治疗高血压兔3个月。通过心脏与体重比（HW/BW）评估LVH。通过心室颤动阈值（VFT）和有效不应期（ERP）离散度评估心室心律失常易感性。通过复极化90%时的动作电位持续时间（APD90）和内向整流钾电流（I(K1)）密度来表征单个左心室肌细胞的电特性。用赋形剂治疗的高血压兔（LVH/赋形剂组）平均动脉压（MAP，81±2对60±2 mmHg）和HW/BW（2.71±0.07对1.97±0.04 g/kg）较高，VFT较低（20±1对39±2 mA），ERP离散度较大（34±3对14±3 ms），APD90较长（187±6对162±6 ms），I(K1)密度低于对照兔。用氯沙坦治疗的高血压兔（LVH/氯沙坦组）的HW/BW（2.36±0.06 g/kg）介于LVH/赋形剂组和对照兔之间，而MAP（65±2 mmHg）、VFT（34±2 mA）、ERP离散度（19±1 ms）、APD90（160±6 ms）和I(K1)密度与LVH/赋形剂组有显著差异，但与对照组相似。我们得出结论，肾血管性高血压兔的AT1阻断可使心室电生理恢复正常。
