Effect of angiotensin-converting enzyme inhibition on intimal thickening in rabbit collared carotid artery.
The positioning of a nonocclusive silicone collar around the rabbit carotid artery results in the formation of a neointima under a morphologically continuous endothelium. We wished to determine whether oral treatment with angiotensin-converting enzyme (ACE) inhibitors prevents or retards intimal thickening and whether this is related to the blood pressure (BP) lowering effects of such drugs. Silicone collars were placed around the left carotid artery of 104 male New Zealand white rabbits for 14 days. The contralateral carotid artery was sham-operated. Three ACE inhibitors were administered from 7 days before collar placement until the end of the experiment: zabicipril (0, 0.03, 0.10, or 0.30 mg/kg/day), moexipril (0, 0.3, 1, or 3 mg/kg twice daily, b.i.d.), and enalapril (0 or 3 mg/kg/day). Each group consisted of 6-12 animals. BP and plasma ACE activity were measured in the nonanesthetized rabbits after 3-week treatment. To evaluate intimal thickening, we measured the cross-sectional area of intima and media. The positioning of the collar led to significant intimal thickening after 14 days. Although the ACE inhibitors decreased BP (zabicipril, 9, 16, 16%; moexipril, 10, 22, 31%; enalapril, 15%) and plasma ACE activity (zabicipril, 87, 88, 92%; moexipril, 79, 92, 93%; enalapril, 88%) significantly and dose dependently, they did not reduce intimal thickening or the cross-sectional area of the media. Angiotensin II does not play a dominant role in collar-induced intimal thickening in rabbits. Furthermore, reducing the BP of normotensive rabbits does not alter neointima formation in this model.
De Meyer
G R
GR
Division of Pharmacology, University of Antwerp, Belgium.
Bult
H
H
Kockx
M M
MM
Herman
A G
AG
D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002339:Carotid Arteries / Q000187:drug effects* / Q000473:pathology; D004656:Enalapril / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000097:blood*; D011817:Rabbits; D012828:Silicones; D044005:Tetrahydroisoquinolines; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology
D000806:Angiotensin-Converting Enzyme Inhibitors; D019086:Bridged Bicyclo Compounds, Heterocyclic; D007546:Isoquinolines; D012828:Silicones; D044005:Tetrahydroisoquinolines; C065499:zabicipril; D004656:Enalapril; D007703:Peptidyl-Dipeptidase A; C058302:moexipril