Early induction of angiotensin I-converting enzyme in rat carotid artery after balloon injury.
Several studies have demonstrated the effectiveness of angiotensin I-converting enzyme (ACE) inhibitors in preventing the neointima formation 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 with that with the angiotensin II antagonist HR 720. The endothelial layer of the left carotid artery was removed using an inflated balloon catheter. Injured and control vessels were both submitted to histomorphological analysis and DNA content quantification at 2, 4, 6, 8, 12, and 14 days after injury. Evaluation of neointima thickening demonstrated a slow but steady increase of neointima that was significant after day 6 and reached 30% of the lumen in 2 weeks. This was paralleled by an increase in DNA content, which was significant 4 days after injury. ACE mRNA levels were quantified by polymerase chain reaction after reverse transcription. Measurement of ACE mRNA levels revealed a significant upregulation 2 and 8 days after injury, with no significant difference when compared with control tissue at later time points. ACE activity 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 efficient in reducing neointima formation than that with HR 720. These data underlie the role of ACE in this model of restenosis. The early induction of ACE expression after endothelial injury but before significant changes in the vessel structure suggests that ACE activity might be one of the mechanisms that trigger neointima formation in the rat.
Fernandez-Alfonso
M S
MS
Departamento de Farmacologia, Facultad de Farmacia, Universidad Complutense, Madrid, Spain.
Martorana
P A
PA
Licka
I
I
van Even
P
P
Trobisch
D
D
Schölkens
B A
BA
Paul
M
M
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000517:prevention & control; D001713:Biphenyl Compounds / Q000494:pharmacology; D002339:Carotid Arteries / Q000201:enzymology* / Q000473:pathology; D020212:Carotid Artery Injuries; D002404:Catheterization; D004247:DNA / Q000378:metabolism; D004790:Enzyme Induction; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D017257:Ramipril / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology; D014949:Wounds, Nonpenetrating / Q000201:enzymology* / Q000473:pathology
D000806:Angiotensin-Converting Enzyme Inhibitors; D001713:Biphenyl Compounds; D007093:Imidazoles; D012333:RNA, Messenger; C094626:fonsartan; C052549:ramiprilat; D004247:DNA; D007703:Peptidyl-Dipeptidase A; D017257:Ramipril