Effects of angiotensin converting enzyme inhibition with cilazapril on intimal hyperplasia in injured arteries and vascular grafts in the baboon.

TLDR

Angiotensin‑converting enzyme inhibition has been suggested to influence arterial proliferative lesions, but its effect on intimal hyperplasia remains uncertain. The study aimed to assess whether ACE inhibition with cilazapril reduces arterial proliferative lesions in a baboon model of vascular injury. Five baboons received oral cilazapril or no treatment and underwent carotid endarterectomy, femoral artery balloon deendothelialization, and placement of aorto‑iliac Gore‑Tex grafts, with cilazapril started one week preoperatively and continued throughout the study, and lesions were later quantified morphometrically. Cilazapril produced >96% inhibition of plasma ACE activity but did not reduce neointimal cross‑sectional areas at carotid, femoral, or graft sites after 3 months, indicating no effect on intimal hyperplasia in this primate model.

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.