Evered M D, Robinson M M, Richardson M A
Eur J Pharmacol. 1980 Dec 19;68(4):443-9. doi: 10.1016/0014-2999(80)90419-7.
In rats with permanent brain cannulas intracerebroventricular (i.c.v.) injections of 2 microgram captopril nearly abolished drinking responses elicited by i.c.v. injections of 1 mUnit hog renin, 10 pmol synthetic renin substrate or 10 pmol angiotensin I but did not reduce drinking elicited by 10 pmol angiotensin II. Inhibition of the response to precursors of angiotensin II was long-lasting (at least 2 h) and dose-dependent (20 ng-2 microgram captopril). Captopril was 3-5 times more potent than SQ 20,881 i.c.v. Subcutaneous injections of captopril in doses 0.1 to 1.0 mg/kg reduced pressor responses to intravenous injections of angiotensin I without attenuating drinking elicited by i.c.v. injections of angiotensin precursors. Higher doses of captopril, however, given subcutaneously (5-50 mg/kg) or by gavage (10 mg/kg) did not reduce drinking to i.c.v. injections of renin or angiotensin I (but not angiotensin II). We conclude that captopril inhibits angiotensin-converting enzyme activity in the brain even when given subcutaneously or by gavage in doses commonly used in the rat.
在具有永久性脑插管的大鼠中，脑室内（i.c.v.）注射2微克卡托普利几乎完全消除了i.c.v.注射1毫单位猪肾素、10皮摩尔合成肾素底物或10皮摩尔血管紧张素I所引发的饮水反应，但并未减少10皮摩尔血管紧张素II所引发的饮水。对血管紧张素II前体反应的抑制作用是持久的（至少2小时）且呈剂量依赖性（20纳克 - 2微克卡托普利）。脑室内注射时，卡托普利的效力比SQ 20,881强3至5倍。皮下注射0.1至1.0毫克/千克剂量的卡托普利可降低对静脉注射血管紧张素I的升压反应，而不减弱i.c.v.注射血管紧张素前体所引发的饮水。然而，皮下注射（5至50毫克/千克）或灌胃（10毫克/千克）更高剂量的卡托普利并不能减少对i.c.v.注射肾素或血管紧张素I（但不包括血管紧张素II）的饮水。我们得出结论，即使以大鼠常用剂量皮下注射或灌胃给药，卡托普利也能抑制脑中的血管紧张素转换酶活性。
