Izumi H, Hayashi S
Department of Physiology, Tohoku University School of Dentistry, Miyagi, Japan.
Jpn J Pharmacol. 1990 Jul;53(3):367-74. doi: 10.1254/jjp.53.367.
Subcutaneous (s.c.) injection of Hoe 498, an angiotensin converting enzyme (ACE) inhibitor, at the doses of 0.1, 0.5, 1.0 and 4.0 mg/kg produced a dose-related inhibition of compound 48/80-induced hypovolemic thirst in rats. A significant time-response relationship was observed between the pretreatment time of Hoe 498 at a dose of 4.0 mg/kg and the inhibition of compound 48/80-induced water intake. Nearly 90% of plasma ACE activity was inhibited by Hoe 498 at all doses used, and this inhibition at the dose of 4.0 mg/kg of Hoe 498 continued for more than 4 hr. Intracerebroventricular (i.c.v.) or s.c. injection of Hoe 498 in doses ranging from 0.5 to 20 micrograms comparably inhibited plasma ACE activity in a dose-dependent manner. The compound 48/80-induced water intake was significantly reduced by i.c.v. injection of Hoe 498 (20 micrograms) 30 min after compound 48/80 administration, but not reduced when the drug was given 15 min prior to injection of dipsogen. The inhibition of water intake by Hoe 498 seems to be dependent on the dose and time between administration of Hoe 498 and compound 48/80. The present data suggest that brain ACE is more involved in compound 48/80-induced water intake than peripheral systemic ACE.
皮下（s.c.）注射血管紧张素转换酶（ACE）抑制剂Hoe 498，剂量为0.1、0.5、1.0和4.0 mg/kg，对化合物48/80诱导的大鼠低血容量性口渴产生剂量依赖性抑制作用。观察到剂量为4.0 mg/kg的Hoe 498预处理时间与化合物48/80诱导的水摄入量抑制之间存在显著的时间反应关系。在所使用的所有剂量下，Hoe 498均可抑制近90%的血浆ACE活性，且4.0 mg/kg剂量的Hoe 498的这种抑制作用持续超过4小时。脑室内（i.c.v.）或皮下注射剂量范围为0.5至20微克的Hoe 498以剂量依赖性方式同等程度地抑制血浆ACE活性。在给予化合物48/80后30分钟，脑室内注射Hoe 498（20微克）可显著降低化合物48/80诱导的水摄入量，但在给予致渴剂前15分钟给予该药物时则不会降低。Hoe 498对水摄入量的抑制作用似乎取决于Hoe 498与化合物48/80给药之间的剂量和时间。目前的数据表明，脑ACE比外周系统性ACE更参与化合物48/80诱导的水摄入。
