Angiotensin II provokes cesium-induced ventricular tachyarrhythmias

Objective: The purpose of this study was to investigate whether angiotensin II provokes ventricular tachyarrhythmias and to clarify its mechanism usin g the cesium-induced arrhythmia model, which has been widely used as an aft erdepolarization and triggered activity model. Methods: Eighteen adult mong rel dogs of either sex weighing 9.6-23.0 kg were studied. The dogs were ran domly divided into three groups. In the control group (n=6), the subjects r eceived intravenous saline solution at a 0.45 ml/kg/h, and intravenous bolu s injections of cesium (0.25, 0.5, 1.0 mmol/kg) were given at 20-min interv als. In the captopril-treated group (n=6), captopril was administered intra venously at 15 mug/kg/min, and cesium was injected as above. After the infu sion of only captopril, in the captopril-treated group, angiotensin II was simultaneously infused at a dose of 0.1 ng/kg/min, and cesium was injected as above. When the dog survived, the dose of angiotensin II was increased t o 1.0 ng/kg/min, and the same procedure was repeated. The remaining six dog s were simultaneously infused with captopril (15 mug/kg/min), angiotensin I I (1.0 ng/kg/min), and U-73122 (10 mug/kg/min), a selective phospholipase C blocker, and injected with cesium (1.0 mmol/kg). Forty minutes after termi nation of U-73122 infusion, the dogs were injected with the same dose of ce sium. Results: Sustained ventricular tachycardia or ventricular fibrillatio n was induced by cesium in all of the dogs in the control group. In the cap topril-treated group, none of the dogs showed these arrhythmias when only c aptopril was infused. The treatment of captopril significantly reduced leth al arrhythmias (P<0.01 vs, control group). During the simultaneous infusion of captopril and angiotensin II (0.1 ng/kg/min), cesium produced sustained ventricular tachycardia in all six dogs and the arrhythmia developed into ventricular fibrillation in three dogs. By increasing the dose of angiotens in II (1.0 ng/kg/min), the surviving three dogs died following induced vent ricular fibrillation. The additional infusion of angiotensin II (0.1 and 1. 0 ng/kg/min) significantly increased fatal arrhythmias (P<0.01 vs, only cap topril- infused period, respectively). None of the dogs in the third group exhibited ventricular tachycardia during the infusion of U-73122, and ventr icular fibrillations were recorded in all six dogs in the absence of U-7312 2. The treatment of U-73122 significantly reduced lethal arrhythmias. (P<0. 01 vs, control period). Conclusions: These results suggest that angiotensin II provokes cesium-induced ventricular tachyarrhythmias by increasing calc ium release from sarcoplasmic reticulum in myocytes via activation of a pho sphatidylinositol response. (C) 2001 Elsevier Science B.V. All rights reser ved.