EARLY INDUCTION OF ANGIOTENSIN I-CONVERTING ENZYME IN RAT CAROTID-ARTERY AFTER BALLOON INJURY

Several studies have demonstrated the effectiveness of angiotensin I-c onverting enzyme (ACE) inhibitors in preventing the neointima formatio n found after denudation of the rat carotid artery by balloon injury. The aim of the present study was to determine the role of ACE in this model and to compare the treatment with the ACE inhibitor ramiprilat w ith that with the angiotensin II antagonist HR 720. The endothelial la ver of the left carotid artery was removed using an inflated balloon c athetcr. Injured and control vessels were both submitted to histomorph ological analysis and DNA content quantification at 2, 4, 6, 8, 12, an d 14 days after injury. Evaluation of neointima thickening demonstrate d a slow bur steady increase of neointima that was significant after d ay 6 and reached 30% of the lumen in 2 weeks. This was paralleled by a n increase in DNA content, which was significant 4 days after injury. ACE mRNA levels were quantified by polymerase chain reaction after rev erse transcription. Measurement of ACE mRNA levels revealed a signific ant upregulation 2,and 8 days after injury, with no significant differ ence when compared with control tissue at later time points. ACE activ ity was also significantly enhanced at 2 and 8 days after injury, with no significant difference when compared with control tissue at later time points. In addition, the treatment with ramiprilat was more effic ient in reducing neointima. formation than that with HR 720. These dat a underlie the role of ACE in this model of restenosis. The early indu ction of ACE expression after endothelial injury but before significan t changes in the vessel structure suggests that ACE activity might be one of the mechanisms that trigger neointima formation in the rat.