Clozel J P, Hess P, Schietinger K, Breu V, Fischli W, Baumgartner H R
Pharma Division, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Life Sci. 1994;54(6):PL87-92. doi: 10.1016/0024-3205(94)00706-3.
ACE inhibition has been shown to prevent neointima formation after vascular injury. However, it is not known if this effect is due to a specific inhibition of the renin angiotensin system or to another mechanism such as the accumulation of bradykinin. In order to answer this question we compared the effects of maximal effective doses of cilazapril, an angiotensin converting enzyme (ACE) inhibitor, and ciprokiren, a new renin inhibitor, in guinea pigs. Vascular injury was induced by endothelial denudation of the right carotid artery of guinea pigs treated either by saline (control group), cilazapril (30 mg/kg/day) or ciprokiren (24 mg/kg/day). Twelve days after the ballooning, the guinea pigs were sacrificed, the carotid arteries were perfused fixed and neointima formation was evaluated by quantitative morphometry. Both, ciprokiren and cilazapril prevented neointima formation to the same extent (inhibition by 42 and 49%, respectively, p < 0.05). These results suggest that, in guinea pigs, renin inhibition prevents neointima formation to a similar extent as ACE inhibition. Therefore, ACE inhibitors seem to act in this model by inhibiting the renin angiotensin system and not by other effects such as accumulation of bradykinin.
血管紧张素转换酶（ACE）抑制已被证明可预防血管损伤后的新生内膜形成。然而，尚不清楚这种作用是由于对肾素血管紧张素系统的特异性抑制，还是由于其他机制，如缓激肽的蓄积。为了回答这个问题，我们比较了豚鼠中血管紧张素转换酶（ACE）抑制剂西拉普利和新型肾素抑制剂西普罗瑞林最大有效剂量的作用。通过对豚鼠右颈动脉进行内皮剥脱来诱导血管损伤，豚鼠分别用生理盐水（对照组）、西拉普利（30mg/kg/天）或西普罗瑞林（24mg/kg/天）处理。球囊扩张12天后，处死豚鼠，灌注固定颈动脉，并通过定量形态学评估新生内膜形成。西普罗瑞林和西拉普利均在相同程度上预防了新生内膜形成（分别抑制42%和49%，p<0.05）。这些结果表明，在豚鼠中，肾素抑制与ACE抑制预防新生内膜形成的程度相似。因此，在该模型中，ACE抑制剂似乎是通过抑制肾素血管紧张素系统起作用，而不是通过缓激肽蓄积等其他效应。
