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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.

Abstract
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.
AuthorsM Murakami, Y Inada, S Tazawa, K Nakao, H Komatsu
JournalArzneimittel-Forschung (Arzneimittelforschung) Vol. 47 Issue 10 Pg. 1099-103 (Oct 1997) ISSN: 0004-4172 [Print] Germany
PMID9368701 (Publication Type: Journal Article)
Chemical References
  • Angiotensin Receptor Antagonists
  • Benzimidazoles
  • Biphenyl Compounds
  • KRH 594
  • Tetrazoles
  • Thiadiazoles
  • candesartan cilexetil
Topics
  • Acute Disease
  • Angiotensin Receptor Antagonists
  • Animals
  • Benzimidazoles (pharmacology)
  • Biphenyl Compounds (pharmacology)
  • Cardiomegaly (drug therapy, physiopathology)
  • Dogs
  • Female
  • Hemodynamics (drug effects)
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Tetrazoles (therapeutic use)
  • Thiadiazoles (therapeutic use)
  • Ventricular Dysfunction, Left (drug therapy, physiopathology)

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