Prescott M F, Webb R L, Reidy M A
Research Department, Ciba-Geigy Corporation, Summit, New Jersey 07901.
Am J Pathol. 1991 Dec;139(6):1291-6.
The angiotensin-converting enzyme (ACE) inhibitor, benazeprilat and the angiotensin II (Ang II), AT1-specific receptor antagonist, DuP753, were compared for their effects on intimal lesion formation as well as smooth muscle cell (SMC) proliferation and migration in Sprague Dawley rats after carotid balloon injury. Both the ACE inhibitor (benazeprilat, 3 mg/kg/day) and the AT1 antagonist (DuP 753, 10 mg/kg/day) significantly reduced intimal lesion formation after balloon injury (by 35% and 49%, respectively). Medial SMC proliferation after injury was reduced 53% by the AT1 antagonist; however, the ACE inhibitor had no effect on SMC proliferation. SMC migration was reduced 94% by the AT1 antagonist and 68% by the ACE inhibitor. These data demonstrate the importance of Ang II in SMC proliferation and migration after balloon injury. They also demonstrate that in the balloon injury model, the ACE inhibitor reduced intimal lesion size by inhibiting SMC migration alone without affecting SMC proliferation. A more pronounced reduction in lesion size was obtained after AT1 antagonism, however, when both SMC migration and proliferation were inhibited.
在颈动脉球囊损伤后的Sprague Dawley大鼠中，比较了血管紧张素转换酶（ACE）抑制剂苯那普利拉和血管紧张素II（Ang II）、AT1特异性受体拮抗剂DuP753对内膜损伤形成以及平滑肌细胞（SMC）增殖和迁移的影响。ACE抑制剂（苯那普利拉，3毫克/千克/天）和AT1拮抗剂（DuP 753，10毫克/千克/天）均显著减少了球囊损伤后的内膜损伤形成（分别减少了35%和49%）。AT1拮抗剂使损伤后中膜SMC增殖减少了53%；然而，ACE抑制剂对SMC增殖没有影响。AT1拮抗剂使SMC迁移减少了94%，ACE抑制剂使其减少了68%。这些数据证明了Ang II在球囊损伤后SMC增殖和迁移中的重要性。它们还表明，在球囊损伤模型中，ACE抑制剂仅通过抑制SMC迁移而不影响SMC增殖来减少内膜损伤大小。然而，当SMC迁移和增殖均受到抑制时，AT1拮抗后损伤大小的减少更为显著。
