Limitations of Angiotensin-Converting Enzyme Inhibitor in Restenosis of a Deep Arterial Injury Model

Cilazapril (CLZ) has been reported to reduce intimal hyperplasia in a rat carotid model of restenosis. The purpose of this study was to determine whether CLZ inhibits restenosis after deep arterial injury in lathyritic rats. The lathyritic rat was used as a model of deep arterial injury; in this model the internal elastic lamina is easily broken by balloon injury because of the fragility of the connective tissue. Deep arterial injury is defined as rupture of the internal elastic lamina with damage to both the intima and the media. The rats were divided into 4 groups (n = 40): mild injury (intimal damage with intact internal elastic lamina), mild injury +CLZ, deep injury, and deep injury +CLZ. In the CLZ-treated groups, the drug was administered orally (10 mg/day) from 7 days before balloon injury until the time of sacrifice 21 days after balloon injury. The intimal hyperplasia was determined histologically using a computerized morphometry program. At sacrifice, blood pressure was lower in the CLZ-treated groups than in the untreated (control) rats (p < 0.05). In the mild injury model, CLZ decreased intimal hyperplasia markedly. In contrast, CLZ failed to reduce intimal hyperplasia in the rats with deep injury. CLZ markedly decreased neointimal hyperplasia in mild injury. In contrast, CLZ failed to reduce intimal area in deep injury. The type of arterial injury seems to determine the effectiveness of CLZ.