Blockade of Angiotensin II Type 1 Receptor Improves the Arrhythmia Morbidity in Mice With Left Ventricular Hypertrophy

• Published in: Circulation Journal 2006, Vol.70(3), pp.335-341
• Main Authors: Zhang, Cuntai, Yasuno, Shinji, Kuwahara, Koichiro, Zankov, Dimitar P., Kobori, Atsushi, Makiyama, Takeru, Horie, Minoru
• Format: Article
• Language: English
• Subjects: Angiontensin II; Angiotensin II Type 1 Receptor Blockers - pharmacology; Angiotensin II Type 1 Receptor Blockers - therapeutic use; Animals; Arrhythmias, Cardiac - etiology; Arrhythmias, Cardiac - mortality; Arrhythmias, Cardiac - physiopathology; Arrhythmias, Cardiac - prevention & control; Atrial fibrillation; Benzimidazoles - pharmacology; Benzimidazoles - therapeutic use; Blood Pressure - drug effects; Blood Pressure - physiology; Data Interpretation, Statistical; Echocardiography; Electrophysiologic Techniques, Cardiac; Heart Function Tests; Heart Ventricles - drug effects; Heart Ventricles - physiopathology; Hypertrophy, Left Ventricular - complications; Hypertrophy, Left Ventricular - drug therapy; Hypertrophy, Left Ventricular - physiopathology; Male; Mice; Mice, Inbred C57BL; Receptor, Angiotensin, Type 1 - drug effects; Receptor, Angiotensin, Type 1 - physiology; Tetrazoles - pharmacology; Tetrazoles - therapeutic use; Ventricular Function, Left - drug effects; Ventricular Function, Left - physiology; Ventricular hypertrophy; Ventricular tachycardia
• ISSN: 1346-9843; 1347-4820
• DOI: 10.1253/circj.70.335

Background Stimulation of angiotensin II type 1 (AT1) receptors has been shown to generate the arrhythmogenic substrate in ventricular hypertrophy. We examined whether candesartan, an AT1 receptor blocker, has antiarrhythmic effects on mouse model of left ventricular hypertrophy created by transverse aorta constriction (TAC). Methods and Results Forty-eight male mice were divided into 3 groups: TAC, candesartan (TAC plus candesartan) and control groups. Echocardiographic examination was performed before the operation and 2 and 4 weeks after the operation. Four weeks after the operation, electrophysiological studies were conducted by inserting a 1.7 F octapolar electrode catheter through the right external jugular vein into the right ventricle. The effective refractory period of the atrioventricular node (AVNERP) in TAC group was significantly prolonged, and short episodes of ventricular tachycardia (VT) and atrial fibrillation (AF) could be induced in 12 of 16 mice (75%) and 8 of 16 (50%), respectively. In contrast, in candesartan group, the incidence of VT was significantly reduced (12.5%) and no AF was induced. Moreover, the drug produced a significant left ventricular hypertrophy regression and restored the AVNERP to normal. Conclusions Candesartan reduced both ventricular and atrial arrhythmias in the TAC mice, presumably by preventing the electrical remodeling by inhibiting the AT1 receptor. (Circ J 2006; 70: 335 - 341)