title: Blood pressure is the major driving force for plaque formation in aortic-constricted ApoE-/- mice.
abstract: OBJECTIVE
  Using an aortic constriction model in mice, we studied whether the increase in pressure or the activation of the renin-angiotensin system (RAS) and its main receptors is the main driving force for plaque progression.
  
  
  METHODS
  Male ApoE mice underwent sham surgery or placement of a suprarenal silver clip around the aorta (AoC). Half the group was treated with the selective AT1 receptor antagonist losartan (30 mg/kg per day) for 4 weeks.
  
  
  RESULTS
  Anesthetized mean arterial pressure (MAP) was increased in AoC mice compared to sham (106 +/- 3 versus 90 +/- 1 mmHg, P < 0.001). Losartan reduced MAP in sham mice (78 +/- 2 mmHg, P < 0.01) but not in AoC (AoC losartan 104 +/- 2 mmHg). Plasma renin concentration (PRC) was increased in AoC mice compared to sham [1.6 +/- 0.3 versus 0.8 +/- 0.2 milliGoldblatt units (mGU)/ml, P < 0.001]. Losartan treatment augmented this difference (18.7 +/- 3.7 versus 4.6 +/- 1.7 mGU/ml, P < 0.01). AT2 receptor mRNA expression was increased 5.8-fold by aortic constriction in thoracic aorta (P < 0.05) and the major site for expression of the AT2 receptor protein was within the plaques. The plaque area was increased in AoC mice compared to sham (0.61 +/- 0.09 versus 0.07 +/- 0.01%, P < 0.001); however, losartan did not alter plaque area.
  
  
  CONCLUSIONS
  Our data do not support a role for the AT1 receptor in the progression of atherosclerosis in this model, since blockade with losartan did not alter plaque distribution. Furthermore, we found no support for the counteraction of atherogenesis by increased activity of the RAS acting on the AT2 receptor. Our data suggest that increased pressure is the main driving force for atherosclerosis in this model.
authors.affiliation: Department of Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, Göteborg University, Göteborg, Sweden.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Johansson
authors.forename: Anna
authors.initials: A
authors.lastname: Wickman
authors.forename: Ole
authors.initials: O
authors.lastname: Skøtt
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Gan
authors.forename: Göran
authors.initials: G
authors.lastname: Bergström
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001024:Aortic Valve Stenosis / Q000378:metabolism / Q000503:physiopathology*; D050197:Atherosclerosis / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D019808:Losartan / Q000494:pharmacology; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects / Q000502:physiology*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D019808:Losartan