title: AVE 0991, a non-peptide mimic of angiotensin-(1-7) effects, attenuates pulmonary remodelling in a model of chronic asthma.
abstract: OBJECTIVE
  AVE 0991 (AVE) is a non-peptide compound, mimic of the angiotensin (Ang)-(1-7) actions in many tissues and pathophysiological states. Here, we have investigated the effect of AVE on pulmonary remodelling in a murine model of ovalbumin (OVA)-induced chronic allergic lung inflammation.
  
  
  METHODS
  We used BALB/c mice (6-8 weeks old) and induced chronic allergic lung inflammation by OVA sensitization (20 μg·mouse(-1) , i.p., four times, 14 days apart) and OVA challenge (1%, nebulised during 30 min, three times per·week, for 4 weeks). Control and AVE groups were given saline i.p and challenged with saline. AVE treatment (1 mg·kg(-1) ·per day, s.c.) or saline (100 μL·kg(-1) ·per day, s.c.) was given during the challenge period. Mice were anaesthetized 72 h after the last challenge and blood and lungs collected. In some animals, primary bronchi were isolated to test contractile responses. Cytokines were evaluated in bronchoalveolar lavage (BAL) and lung homogenates.
  
  
  RESULTS
  Treatment with AVE of OVA sensitised and challenged mice attenuated the altered contractile response to carbachol in bronchial rings and reversed the increased airway wall and pulmonary vasculature thickness and right ventricular hypertrophy. Furthermore, AVE reduced IL-5 and increased IL-10 levels in the BAL, accompanied by decreased Ang II levels in lungs.
  
  
  CONCLUSIONS
  AVE treatment prevented pulmonary remodelling, inflammation and right ventricular hypertrophy in OVA mice, suggesting that Ang-(1-7) receptor agonists are a new possibility for the treatment of pulmonary remodelling induced by chronic asthma.
authors.affiliation: National Institute of Science and Technology in Nanobiopharmaceutics (INCT-NANOBIOFAR), Department of Physiology and Biophysics, Biological Sciences Institute, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: M G
authors.initials: MG
authors.lastname: Rodrigues-Machado
authors.forename: G S
authors.initials: GS
authors.lastname: Magalhães
authors.forename: J A
authors.initials: JA
authors.lastname: Cardoso
authors.forename: L M
authors.initials: LM
authors.lastname: Kangussu
authors.forename: A
authors.initials: A
authors.lastname: Murari
authors.forename: M V
authors.initials: MV
authors.lastname: Caliari
authors.forename: M L
authors.initials: ML
authors.lastname: Oliveira
authors.forename: D C
authors.initials: DC
authors.lastname: Cara
authors.forename: M L M
authors.initials: ML
authors.lastname: Noviello
authors.forename: F D
authors.initials: FD
authors.lastname: Marques
authors.forename: J M
authors.initials: JM
authors.lastname: Pereira
authors.forename: R Q
authors.initials: RQ
authors.lastname: Lautner
authors.forename: R A S
authors.initials: RA
authors.lastname: Santos
authors.forename: M J
authors.initials: MJ
authors.lastname: Campagnole-Santos
mesh_terms: D056151:Airway Remodeling / Q000187:drug effects*; D000803:Angiotensin I / Q000494:pharmacology*; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016084:Bronchoconstriction / Q000187:drug effects; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D017380:Hypertrophy, Right Ventricular / Q000378:metabolism / Q000517:prevention & control; D007093:Imidazoles / Q000494:pharmacology*; D008168:Lung / Q000098:blood supply / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018716:Molecular Mimicry; D010047:Ovalbumin; D010446:Peptide Fragments / Q000494:pharmacology*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000378:metabolism; D011651:Pulmonary Artery / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D011667:Pulmonary Veins / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
chemical_list: C469726:AVE 0991; D018927:Anti-Asthmatic Agents; D016207:Cytokines; D007093:Imidazoles; D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D000804:Angiotensin II; D010047:Ovalbumin; D000803:Angiotensin I; C118790:angiotensin I (1-7)
keywords: AVE 0991; Mas receptor; airway remodelling; allergic lung inflammation; angiotensin-(1-7); asthma; cytokines
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