Antihypertensive Effect of Chronic KT3-671, a Structurally New Nonpeptide Angiotensin AT1-Receptor Antagonist, in Stroke-Prone Spontaneously Hypertensive Rats

Hideto Amano, Kazuko Fujimoto, Takeshi Suzuki, Takeshi Fujii, Koichiro Kawashima, Seiichiro Mochizuki, Akira Tomiyama

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

KT3-671 (2-propyl-8-oxo-1-[(2′-(1H-tetrazole-5-yl)bibhenyl-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.

Original languageEnglish
Pages (from-to)215-222
Number of pages8
JournalThe Japanese Journal of Pharmacology
Volume69
Issue number3
DOIs
Publication statusPublished - 1995 Jan 1

Keywords

  • AT-receptor antagonist
  • Antihypertensive effect
  • KT3-671
  • Renal lesion
  • Stroke-prone spontaneously hypertensive rat

ASJC Scopus subject areas

  • Pharmacology

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