Shirota M, Iijima M, Ushijima T, Kajiwara Y, Kitabatake K
Central Research Laboratories, Asahi Breweries, Ltd., Tokyo, Japan.
Arzneimittelforschung. 1990 Dec;40(12):1303-9.
The hypotensive effects of N-[8-amino-1(S)-carboxyoctyl] -L-alanyl-L-proline (AB-47, CAS 120008-53-9) were examined in normotensive rats and various hypertensive rat models. The hemodynamic effect of AB-47 was also examined in anesthetized spontaneously hypertensive rats (SHR). In 2-kidney, 1-clip renal hypertensive rats (2K, 1C-RHR) and SHR, the single administration of AB-47 (10 mg/kg, p.o.) induced potent and long-lasting hypotensive effects. The repeated administration of AB-47 (1 to 10 mg/kg, p.o.) to SHR for 29 days produced a dose-dependently and sustained hypotensive effect of 20 to 70 mmHg. AB-47 (10 mg/kg, p.o.) had a weak hypotensive effect in DOCA-salt hypertensive rats but no effects in normotensive and 1-kidney, 1-clip renal hypertensive rats (1K, 1C-RHR). AB-47 (3 mg/kg, p.o.) reduced blood pressure in intact SHR but not in bilateral nephrectomized SHR. The single intravenous injection of AB-47 (10 to 100 micrograms/kg) dose-dependently lowered systemic blood pressure, left ventricular systolic pressure (LVSP) and dp/dtmax without affecting heart rate (HR) and these effects of AB-47 were more potent than those of captopril and enalaprilat. These results suggest that AB-47 is a potent and long-lasting hypotensive agent and may be useful for the therapy of both hypertension and congestive heart failure.
在正常血压大鼠和各种高血压大鼠模型中研究了N-[8-氨基-1(S)-羧基辛基]-L-丙氨酰-L-脯氨酸（AB-47，CAS 120008-53-9）的降压作用。还在麻醉的自发性高血压大鼠（SHR）中研究了AB-47的血流动力学效应。在二肾一夹肾性高血压大鼠（2K，1C-RHR）和SHR中，单次给予AB-47（10 mg/kg，口服）可产生强效且持久的降压作用。对SHR重复给予AB-47（1至10 mg/kg，口服）29天，产生了剂量依赖性且持续的20至70 mmHg的降压作用。AB-47（10 mg/kg，口服）在DOCA-盐性高血压大鼠中具有较弱的降压作用，但在正常血压大鼠和一肾一夹肾性高血压大鼠（1K，1C-RHR）中无作用。AB-47（3 mg/kg，口服）可降低完整SHR的血压，但对双侧肾切除的SHR无效。单次静脉注射AB-47（10至100微克/千克）可剂量依赖性地降低全身血压、左心室收缩压（LVSP）和dp/dtmax，而不影响心率（HR），且AB-47的这些作用比卡托普利和依那普利拉更强。这些结果表明，AB-47是一种强效且持久的降压药物，可能对高血压和充血性心力衰竭的治疗均有用。
