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Antihypertensive effect of chronic KT3-671, a structurally new nonpeptide angiotensin AT1-receptor antagonist, in stroke-prone spontaneously hypertensive rats.

Abstract
KT3-671 (2-propyl-8-oxo-1-[(2'-(1H-tetrazole-5-yl)biphenyl-4-yl)methyl]-4,5,6, 7-tetrahydrocycloheptimidazole), a structurally new nonpeptide angiotensin AT1-receptor antagonist, was administered orally and repeatedly to 15-week-old stroke-prone spontaneously hypertensive rats for 7 weeks; and its effects on blood pressure, heart rate, renal function, plasma renin concentration (PRC), plasma aldosterone concentration (PAC) and hypertension-related tissue damage in the brain, heart, kidney and mesenteric artery were investigated. KT3-671 at a dose of 3 or 10 mg/kg, p.o. per day prevented development of hypertension and produced a significant and consistent reduction of blood pressure in a dose-dependent manner. Enalapril at a dose of 10 mg/kg per day produced cardiovascular effects similar to those of KT3-671 at 10 mg/kg. Despite marked reduction in blood pressure, neither KT3-671 nor enalapril affected the heart rate. KT3-671 at 10 mg/kg produced a transient and significant reduction of urinary sodium excretion in the second week, but did not affect renal function at any other time during the experimental period. Both KT3-671 at 10 mg/kg and enalapril at 10 mg/kg produced a significant increase in PRC and showed a tendency to decrease PAC. Repeated administration of KT3-671 reduced the severity of the pathological changes in the kidney. These results suggest that KT3-671 is a potentially useful antihypertensive drug.
AuthorsH Amano, K Fujimoto, T Suzuki, T Fujii, S Mochizuki, A Tomiyama, K Kawashima
JournalJapanese journal of pharmacology (Jpn J Pharmacol) Vol. 69 Issue 3 Pg. 215-22 (Nov 1995) ISSN: 0021-5198 [Print] Japan
PMID8699629 (Publication Type: Journal Article)
Chemical References
  • Angiotensin Receptor Antagonists
  • Imidazoles
  • KT3 671
  • Tetrazoles
  • Aldosterone
  • Renin
Topics
  • Aldosterone (blood)
  • Angiotensin Receptor Antagonists
  • Animals
  • Body Weight (drug effects)
  • Heart Rate (drug effects)
  • Imidazoles (pharmacology)
  • Rats
  • Rats, Inbred SHR
  • Renin (blood)
  • Tetrazoles (pharmacology)
  • Time Factors
  • Urination (drug effects)

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