title: Effects of angiotensin converting enzyme inhibition with cilazapril on intimal hyperplasia in injured arteries and vascular grafts in the baboon.
abstract: To determine the importance of angiotensin converting enzyme (ACE) activity in the development of arterial proliferative lesions in a primate model, the response to vascular injury was studied in five baboons treated with oral cilazapril (20 mg/kg/day) and in five untreated control animals. Each animal underwent three procedures: 1) carotid artery endarterectomy, 2) balloon catheter deendothelialization of the superficial femoral artery, and 3) surgical placement of bilateral aorto-iliac expanded polytetrafluoroethylene (Gore-Tex) vascular grafts. Cilazapril therapy was initiated 1 week preoperatively and continued throughout the study interval. At 1 and 3 weeks postoperatively, plasma ACE activity was inhibited by more than 96% versus control values. After animals were killed at 3 months, injured vessel and graft segments were evaluated morphometrically. Although the response between animals was variable, average cross-sectional areas of neointima did not differ between the cilazapril-treated and control groups at sites of carotid endarterectomy (0.26 +/- 0.12 versus 0.34 +/- 0.17 mm2, respectively; p greater than 0.5), femoral artery ballooning (0.15 +/- 0.08 versus 0.11 +/- 0.01 mm2; p greater than 0.5), or at graft anastomoses (1.86 +/- 0.50 versus 1.72 +/- 0.50 mm2; p greater than 0.5). Thus, cilazapril did not reduce intimal thickening over 3 months in these primate arterial injury models. However, a possible beneficial effect of cilazapril, which might be apparent at earlier time points or with larger animal groups, cannot be excluded.
authors.affiliation: Department of Medicine (Hematology-Oncology), Emory University Atlanta, Ga. 30322.
authors.forename: S R
authors.initials: SR
authors.lastname: Hanson
authors.forename: J S
authors.initials: JS
authors.lastname: Powell
authors.forename: T
authors.initials: T
authors.lastname: Dodson
authors.forename: A
authors.initials: A
authors.lastname: Lumsden
authors.forename: A B
authors.initials: AB
authors.lastname: Kelly
authors.forename: J S
authors.initials: JS
authors.lastname: Anderson
authors.forename: A W
authors.initials: AW
authors.lastname: Clowes
authors.forename: L A
authors.initials: LA
authors.lastname: Harker
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000637:transplantation; D001158:Arteries / Q000187:drug effects / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D017315:Cilazapril; D004691:Endarterectomy / Q000009:adverse effects; D005263:Femoral Artery / Q000187:drug effects / Q000473:pathology; D006965:Hyperplasia; D007083:Iliac Artery / Q000637:transplantation; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology*; D010215:Papio; D011724:Pyridazines / Q000494:pharmacology*; D013045:Species Specificity
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D011724:Pyridazines; D017315:Cilazapril