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 using the cesium-induced arrhythmia model, which has been widely used as an afterdepolarization and triggered activity model.


METHODS
Eighteen adult mongrel dogs of either sex weighing 9.6-23.0 kg were studied. The dogs were randomly divided into three groups. In the control group (n=6), the subjects received intravenous saline solution at a 0.45 ml/kg/h, and intravenous bolus injections of cesium (0.25, 0.5, 1.0 mmol/kg) were given at 20-min intervals. In the captopril-treated group (n=6), captopril was administered intravenously at 15 microg/kg/min, and cesium was injected as above. After the infusion 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 to 1.0 ng/kg/min, and the same procedure was repeated. The remaining six dogs were simultaneously infused with captopril (15 microg/kg/min), angiotensin II (1.0 ng/kg/min), and U-73122 (10 microg/kg/min), a selective phospholipase C blocker, and injected with cesium (1.0 mmol/kg). Forty minutes after termination of U-73122 infusion, the dogs were injected with the same dose of cesium.


RESULTS
Sustained ventricular tachycardia or ventricular fibrillation was induced by cesium in all of the dogs in the control group. In the captopril-treated group, none of the dogs showed these arrhythmias when only captopril was infused. The treatment of captopril significantly reduced lethal 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 angiotensin II (1.0 ng/kg/min), the surviving three dogs died following induced ventricular fibrillation. The additional infusion of angiotensin II (0.1 and 1.0 ng/kg/min) significantly increased fatal arrhythmias (P<0.01 vs. only captopril- infused period, respectively). None of the dogs in the third group exhibited ventricular tachycardia during the infusion of U-73122, and ventricular fibrillations were recorded in all six dogs in the absence of U-73122. 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 calcium release from sarcoplasmic reticulum in myocytes via activation of a phosphatidylinositol response.
Gondo
N
N
Department of Second Internal Medicine, School of Medicine, Fukuoka University, 7-45-1, Nanakuma, Jonan-ku, 814-0180, Fukuoka, Japan.
Kumagai
K
K
Nakashima
H
H
Saku
K
K
D000200:Action Potentials / Q000187:drug effects; D000704:Analysis of Variance; D000804:Angiotensin II / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use; D002216:Captopril / Q000627:therapeutic use*; D002586:Cesium / Q000494:pharmacology; D004285:Dogs; D004562:Electrocardiography / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D004963:Estrenes / Q000627:therapeutic use; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D023421:Models, Animal; D011760:Pyrrolidinones / Q000627:therapeutic use; D011897:Random Allocation; D017180:Tachycardia, Ventricular / Q000188:drug therapy / Q000209:etiology*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
D000806:Angiotensin-Converting Enzyme Inhibitors; D000889:Anti-Arrhythmia Agents; D004791:Enzyme Inhibitors; D004963:Estrenes; D011760:Pyrrolidinones; D000804:Angiotensin II; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D002586:Cesium; D002216:Captopril; D010738:Type C Phospholipases