Blockade of angiotensin II type 1 receptor improves the arrhythmia morbidity in mice with left ventricular hypertrophy.
BACKGROUND
Stimulation of angiotensin II type 1 (AT(1)) 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).


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 AT(1) receptor.
Zhang
Cuntai
C
Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Yasuno
Shinji
S
Kuwahara
Koichiro
K
Zankov
Dimitar P
DP
Kobori
Atsushi
A
Makiyama
Takeru
T
Horie
Minoru
M
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000401:mortality* / Q000503:physiopathology / Q000517:prevention & control*; D001562:Benzimidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003627:Data Interpretation, Statistical; D004452:Echocardiography; D022062:Electrophysiologic Techniques, Cardiac; D006334:Heart Function Tests; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects / Q000502:physiology; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; C081643:candesartan