Yamaguchi N, Fujimoto K, Fujii T, Suzuki T, Kawashima K
Department of Pharmacology, Kyoritsu College of Pharmacy, Minato-ku, Tokyo, Japan.
Jpn J Pharmacol. 1997 Jan;73(1):83-91. doi: 10.1254/jjp.73.83.
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.
YM358（2,7 - 二乙基 - 5 - [[2' - (1H - 四氮唑 - 5 - 基)联苯 - 4 - 基]甲基] - 5H - 吡唑并[1,5 - b][1,2,4] - 三唑钾盐），一种新型非肽类血管紧张素AT1受体拮抗剂，对24周龄的易中风自发性高血压大鼠（SHRSP）每日给药，持续4周。通过无线电遥测技术研究了其对收缩压、平均动脉压和舒张压（SAP、MAP和DAP）、心率及运动活性的影响。观察到血压、心率和运动活性呈现明显的昼夜节律变化，与光照周期同步。每日口服剂量为10或30 mg/kg的YM358可剂量依赖性地降低血压。虽然在治疗早期观察到YM358的降压作用有轻度减弱，但每日30 mg/kg的YM358可使24小时MAP和DAP显著且持续降低，并可防止高血压的进一步发展。YM358对心率、运动活性及其昼夜节律均无影响。停用YM358治疗后，血压迅速恢复至对照水平，且无血压反跳升高的迹象。这些结果表明YM358可能对高血压治疗具有潜在的应用价值。
