title: Angiotensin converting enzyme inhibitor prevents left ventricular remodelling after myocardial infarction in angiotensin II type 1 receptor knockout mice.
abstract: BACKGROUND
  It is well known that angiotensin converting enzyme (ACE) inhibitors and angiotensin II type 1 (AT1) receptor blockers (ARBs) prevent left ventricular (LV) remodelling after myocardial infarction (MI). However, it is still not clear whether inhibition of the AT1 receptor is enough to prevent LV remodelling after MI.
  
  
  OBJECTIVE
  To elucidate the effects of ACE inhibitors that are not mediated by the AT1 receptor on LV remodelling, MI was experimentally induced in wild-type (WT-MI) mice and AT1 receptor knockout (KO-MI) mice.
  
  
  METHODS
  Mice were divided into six groups: WT-control, KO-control, WT-MI, KO-MI, WT-MI treated with an ACE inhibitor, and KO-MI treated with an ACE inhibitor. Four weeks after MI, cardiac function was assessed by Doppler echocardiography and non-infarcted myocardial mRNA expression by northern blot analysis.
  
  
  RESULTS
  Cardiac function decreased significantly in the MI groups compared with the sham operated groups. Additionally, in the MI groups end diastolic dimension, E wave velocity, the ratio of peak velocity of E wave to A wave, deceleration rate of E wave, and mRNA expression of atrial natriuretic peptide, brain natriuretic peptide, and collagens I and III increased significantly compared with the sham groups. LV remodelling after MI was prevented in KO-MI mice compared with WT-MI mice. ACE inhibitor administration significantly attenuated progressive LV remodelling in both WT and KO-MI groups.
  
  
  CONCLUSIONS
  ACE inhibitors can prevent the LV remodelling process that accompanies cardiac dysfunction after MI, even in AT1 KO mice. These findings suggest that ACE inhibitors prevent LV remodelling after MI by mechanisms other than inhibition of angiotensin AT1 receptor mediated effects.
authors: Department of Internal Medicine and Cardiology, Graduate School of Medicine, Osaka City University, Osaka, Japan. yoshiyama@med.osaka-cu.ac.jp
authors: M
authors: M
authors: Yoshiyama
authors: Y
authors: Y
authors: Nakamura
authors: T
authors: T
authors: Omura
authors: Y
authors: Y
authors: Izumi
authors: R
authors: R
authors: Matsumoto
authors: S
authors: S
authors: Oda
authors: K
authors: K
authors: Takeuchi
authors: S
authors: S
authors: Kim
authors: H
authors: H
authors: Iwao
authors: J
authors: J
authors: Yoshikawa
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D015152:Blotting, Northern; D015150:Echocardiography, Doppler; D006352:Heart Ventricles / Q000473:pathology; D006439:Hemodynamics / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009929:Organ Size / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D018487:Ventricular Dysfunction, Left / Q000473:pathology; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1