title: Plaque-stabilizing effect of angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker in a rabbit plaque model.
abstract: OBJECTIVE
  Previous studies have revealed that blockade of the renin angiotensin system attenuates plaque vulnerability and reduces cardiovascular events; however, few studies have compared the effects of an angiotensin-converting enzyme inhibitor (ACEI) with an angiotensin receptor blocker (ARB) and evaluated combination therapy. The objective of this study was to compare the efficacy and mechanisms of plaque stabilization by ACEI or ARB and to determine the effects of combination therapy.
  
  
  METHODS
  Twenty-eight male Japanese white rabbits were fed a high-cholesterol diet after balloon injury of the carotid arteries, then separated into ACEI (n= 7; imidapril 0.5 mg/kg/day), ARB (n= 7; TA606 4.5 mg/kg/day), combination (n= 7; imidapril 0.5 mg/kg/day+TA606 4.5 mg/kg/day), and vehicle (n= 7) groups.
  
  
  RESULTS
  No difference in plaque volume was identified among the 4 groups. ACEI or ARB increased the thickness of the fibrous cap, collagen content and the number of smooth muscle cells in the intima (% smooth muscle cell in intima: ACEI, 36.3%; ARB, 36.4%; vehicle, 14.9%), and reduced the accumulation of macrophages (% macrophages in intima: ACEI, 20.1%; ARB, 24.0%; vehicle, 37.9%), suggesting the plaque-stabilizing effects of each drug. ACEI reduced matrix metalloproteinase (MMP)-9 expression and gelatinolytic activity in the intima. While ARB did not change gelatinolytic activity, accumulation ot T cell in the intima was suppressed. Combination therapy did not show additive effects.
  
  
  CONCLUSIONS
  These results suggest that ACEIs and ARBs have similar, but not additive, plaque-stabilizing effects. Each agent showed specific effects, with ACEIs decreasing gelatinolytic activity and ARBs suppressing T cell accumulation.
authors.affiliation: Department of Internal Medicine I, Osaka Medical College, Osaka, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Hotchi
authors.forename: Masaaki
authors.initials: M
authors.lastname: Hoshiga
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Takeda
authors.forename: Takahito
authors.initials: T
authors.lastname: Yuki
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Fujisaka
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ishihara
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Hanafusa
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure; D007150:Immunohistochemistry; D008055:Lipids / Q000097:blood; D008297:Male; D058226:Plaque, Atherosclerotic / Q000188:drug therapy*; D011817:Rabbits
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D008055:Lipids