Effects of the new angiotensin receptor antagonist dipotassium (Z)-2-[[5-ethyl-3-[2'-(1H-tetrazol-5-yl)biphenyl-4-yl] methyl-1,3,4-thiadiazoline-2-ylidene]aminocarbonyl]-1-cy clopentencarbox ylate on experimental cardiac hypertrophy and acute left ventricular failure.
The cardiovascular effects of dipotassium (Z)-2-[[5-ethyl-3-[2'-(1H-tetrazol-5-yl)biphenyl-4-yl] methyl-1,3,4-thiadiazoline-2-ylidene]aminocarbonyl]-1-cyc lopentencarboxylate CAS 169328-25-0, KRH-594), a new angiotensin II type 1 (AT1) receptor antagonist, on pressure-overload cardiac hypertrophy in rats and on acute left ventricular failure in dogs were investigated. In rats with a 2-week abdominal aorta constriction, left ventricular weight (LVW) and systolic blood pressure (SBP) were significantly greater than in sham-operated rats. Oral administration of KRH-594 (10 or 30 mg/kg/day for 2 weeks) reduced the increases in both LVW and SBP. Another AT1 receptor antagonist, candesartan cilexetil (1 or 3 mg/kg/day for 2 weeks), also prevented this type of cardiac hypertrophy. In anesthetized dogs with a 60-min coronary ligation, left ventricular end-diastolic pressure (LVEDP) and total peripheral resistance (TPR) were raised, whereas the maximum first derivative of left ventricular pressure and cardiac output were both decreased. Intravenous administration of KRH-594 (3 mg/kg) significantly attenuated the increases in both LVEDP and TPR after coronary ligation. These results suggest that KRH-594, by reducing the cardiac afterload, may ameliorate pressure-overload cardiac hypertrophy in rats and produce an improvement in the hemodynamic status of dogs with acute left ventricular failure.
Murakami
M
M
Pharmacological Laboratories, Kissei Pharmaceutical Co., Ltd., Nagano, Japan.
Inada
Y
Y
Tazawa
S
S
Nakao
K
K
Komatsu
H
H
D000208:Acute Disease; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D006332:Cardiomegaly / Q000188:drug therapy* / Q000503:physiopathology; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000627:therapeutic use*; D013830:Thiadiazoles / Q000627:therapeutic use*; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy* / Q000503:physiopathology
D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; C108799:KRH 594; D013777:Tetrazoles; D013830:Thiadiazoles; C077793:candesartan cilexetil