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.