Jpn. J. Pharmacol. 73 (1), 83-91 (1997)
Antihypertensive Effect of Repeatedly Administered YM358, an Angiotensin
AT1-Receptor Antagonist, in Stroke-Prone Spontaneously Hypertensive Rats
Norikazu Yamaguchi, Kazuko Fujimoto, Takeshi Fujii, Takeshi Suzuki and Koichiro
Kawashima (*)
Department of Pharmacology, Kyoritsu College of Pharmacy, Minato-ku,
Tokyo 105, Japan
(*) To whom correspondence should be addressed.
Abstract: YM358 (2,7-diethyl-5-[[2'-(1H-tetrazole-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole
potassium salt), a novel nonpeptide angiotensin AT1-receptor antagonist,
was administered daily for 4 weeks to 24-week-old stroke-prone spontaneously
hypertensive rats (SHRSP). Its effects on systolic, mean and diastolic arterial
pressure (SAP, MAP and DAP), heart rate and locomotor activity were investigated
by using radiotelemetry. A clear diurnal variation in blood pressure, heart
rate and locomotor activity was observed in synchrony with the light cycle.
YM358 at a daily oral dose of 10 or 30 mg/kg produced a reduction of blood
pressure in a dose-dependent manner. Although a mild attenuation of the
antihypertensive effect of YM358 was observed during the early stage of
therapy, YM358 at 30 mg/kg per day produced a significant and consistent
decrease in 24-hr MAP and DAP, and it prevented the further development
of hypertension. YM358 did not affect either heart rate or locomotor activity
or their diurnal variations. After the discontinuation of therapy with YM358,
the blood pressure recovered promptly to the control level while there was
no sign of a rebound increase in blood pressure. These results suggest that
YM358 may be potentially useful for the treatment of hypertension.
Keywords: YM358, Angiotensin AT1-receptor antagonist, Antihypertensive
effect, Stroke-prone spontaneously hypertensive rats, Radiotelemetry
Copyright© The Japanese Pharmacological Society 1997
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