Effects of angiotensin II type 1 receptor antagonist, YM358, on cardiac hypertrophy and dysfunction after myocardial infarction in rats.
This study was undertaken to investigate the effects of an angiotensin II type 1 receptor antagonist, YM358 (2,7-diethyl-5-[[2'(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo [1,5-b] [1,2,4]triazole potassium salt monohydrate), on cardiac hypertrophy and dysfunction in rats with heart failure after myocardial infarction (MI). One day after the coronary ligation, rats were randomized, and administered YM358 or vehicle for 2, 4 or 8 weeks. In MI rats, mean blood pressure, left ventricular (LV) systolic pressure, and the first derivative of LV pressure significantly decreased, and LV end-diastolic pressure (LVEDP) markedly increased after 2 to 8 week treatment of YM358. From 2 weeks after the ligation, ratios of cardiac weight and lung weight to body weight (BW) significantly increased, which indicated the progression of cardiac hypertrophy and lung congestion in MI rats. Two weeks after the ligation, YM358 did not improve LV function, although it decreased the elevated LVEDP and cardiac weights/BW ratios 8 weeks after the ligation. These results indicated that long-term treatment with YM358 improves the reduced cardiac function and reduces cardiac hypertrophy after MI, and may be useful for the treatment of congestive heart failure.
Biometrics Department, Yamanouchi Pharmaceutical Co., Ltd, Tokyo, Japan. tokioka@yamanouchi.co.jp
Tomoko
T
Oka-Akagi
Akira
A
Fujimori
Masayuki
M
Shibasaki
Yasuko
Y
Matsuda-Satoh
Osamu
O
Inagaki
Isao
I
Yanagisawa
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001393:Azoles / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D006333:Heart Failure / Q000188:drug therapy / Q000209:etiology; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy* / Q000209:etiology; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D009929:Organ Size; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy* / Q000209:etiology
D057911:Angiotensin Receptor Antagonists; D001393:Azoles; D001713:Biphenyl Compounds; D044140:Receptor, Angiotensin, Type 1; C105489:YM358