Ishibashi T, Tatebe S, Mitomi A, Tanaka M, Imai S
Department of Pharmacology, Niigata University School of Medicine, Japan.
Cardiovasc Drugs Ther. 1991 Jun;5(3):635-41. doi: 10.1007/BF03029732.
Hemodynamic effects and inhibitory effects on the pressor response to exogenous angiotensin I of benazepril (CGS 14824A), a new angiotensin-converting enzyme (ACE) inhibitor, were examined in conscious chronically instrumented normotensive dogs in comparison with those of captorpil. Oral administration of benazepril (1-10 mg/kg) and captopril (3 and 10 mg/kg) reduced the blood pressure and inhibited the pressor response to angiotensin I dose-dependently. The blood-pressure-lowering effect of benazepril was as potent as that of captopril. The onset of effects of benazepril was slower and the duration longer than that of captopril. There was no close correlation between the attenuation of pressor response to exogenous angiotensin I and the blood-pressure-lowering effect of these two agents. These results indicate that benazepril is a potent ACE inhibitor with a slow onset and a long duration. The slow onset of action may be explained by the necessity of prior conversion of this compound to an active metabolite. A mechanism or mechanisms other than that responsible for the inhibition of pressor response to exogenous angiotensin I must be taken into consideration to explain the blood-pressure-lowering effects of benazepril and captopril.
在清醒的、长期植入仪器的正常血压犬中,研究了新型血管紧张素转换酶(ACE)抑制剂贝那普利(CGS 14824A)对外源性血管紧张素I升压反应的血流动力学效应和抑制作用,并与卡托普利进行了比较。口服贝那普利(1 - 10 mg/kg)和卡托普利(3和10 mg/kg)可降低血压,并剂量依赖性地抑制对外源性血管紧张素I的升压反应。贝那普利的降压效果与卡托普利相当。贝那普利的起效较慢,持续时间比卡托普利长。对外源性血管紧张素I升压反应的减弱与这两种药物的降压效果之间没有密切相关性。这些结果表明,贝那普利是一种起效缓慢、作用持续时间长的强效ACE抑制剂。作用起效缓慢可能是由于该化合物需要先转化为活性代谢产物。为了解释贝那普利和卡托普利的降压作用,必须考虑除抑制对外源性血管紧张素I升压反应之外的一种或多种机制。