title: Inhibition of AAA in a rat model by treatment with ACEI perindopril.
abstract: BACKGROUND
  The purpose of the present study was to evaluate the effect of a new angiotensin converting enzyme inhibitor perindopril on the formation of experimental abdominal aortic aneurysms (AAAs) in a rat model induced by intraluminal elastase infusion and extraluminal calcium chloride (CaCl2) application.
  
  
  METHODS
  Thirty-six male Sprague-Dawley rats were randomly distributed into three groups (n = 12 per group): model (A), sham (B), and perindopril (C). Rats in model and perindopril groups underwent intra-aortic elastase perfusion and extraluminal CaCl2 application to induce AAAs. Rats in the sham group received aortic perfusion and extraluminal application of saline. A dose of 3 mg/kg/d of perindopril was fed orally in the perindopril group. The maximum abdominal aortic diameter was measured in vivo on days 0 and 28 and by ultrasound on days 7, 14, and 21. The arterial blood pressure was measured directly using a pressure transducer after cannulation in surgery and before death. AAA tissue samples were harvested at day 28 and evaluated using normal hematoxylin and eosin stain, Verhoeff-van Gieson stain for elastin, and image analysis technique.
  
  
  RESULTS
  Aortic diameters of rats in the model group consistently increased within 28 d, coinciding with the development of a transmural inflammatory response, thickening of intima, and destruction of the elastic media. Without alteration in blood pressure, the AAA formation rate and mean maximal diameter of aorta at day 28 were significantly lower in the perindopril group compared with the control group (1.71 ± 0.20 versus 2.70 ± 0.69 mm, P < 0.001; 0% versus 90.91%, P < 0.001) and were similar to those in the sham group (1.79 ± 0.29 mm, P = 0.175; 0%, P = 1). The thickness of intima in the perindopril group was lower than that in the model group (20.68 ± 9.96 versus 58.49 ± 32.01 μm, P = 0.001), but higher than that in the sham group (7.23 ± 2.68 μm, P = 0.005). The intensity of elastin fiber showed the opposite trend (0.8541 ± 0.0495 in sham group versus 0.7376 ± 0.1024 in perindopril group versus 0.5413 ± 0.0912 in model group, P < 0.001).
  
  
  CONCLUSIONS
  Perindopril inhibited the aortic degeneration and AAA formation in the experimental AAA model induced by elastase and CaCl2. This effect, which was independent of its influence on hemodynamics, appeared to be induced by the suppression of the inflammatory cell influx and intimal thickening and the preservation of aortic medial elastin.
authors.affiliation: Department of Vascular Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Xiong
authors.affiliation: Department of Vascular Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China. Electronic address: zhaojc3@163.com.
authors.forename: Jichun
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Vascular Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
authors.forename: Guojun
authors.initials: G
authors.lastname: Zeng
authors.affiliation: Department of Vascular Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Huang
authors.affiliation: Department of Vascular Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
authors.forename: Ding
authors.initials: D
authors.lastname: Yuan
authors.affiliation: Department of Vascular Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000473:pathology / Q000517:prevention & control*; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D008297:Male; D020913:Perindopril / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D020913:Perindopril
keywords: Abdominal aortic aneurysm; Angiotensin converting enzyme inhibitor; Calcium chloride; Elastase; Elastin; Image analysis; Inflammation; Intimal hyperplasia; Rat model