1. AVE 0991, a non-peptide mimic of angiotensin-(1-7) effects, attenuates pulmonary remodelling in a model of chronic asthma.
- Author
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Rodrigues-Machado MG, Magalhães GS, Cardoso JA, Kangussu LM, Murari A, Caliari MV, Oliveira ML, Cara DC, Noviello ML, Marques FD, Pereira JM, Lautner RQ, Santos RA, and Campagnole-Santos MJ
- Subjects
- Angiotensin II metabolism, Animals, Asthma chemically induced, Asthma immunology, Asthma metabolism, Asthma physiopathology, Bronchoalveolar Lavage Fluid immunology, Bronchoconstriction drug effects, Chronic Disease, Cytokines metabolism, Disease Models, Animal, Hypertrophy, Right Ventricular metabolism, Hypertrophy, Right Ventricular prevention & control, Lung blood supply, Lung immunology, Lung metabolism, Lung physiopathology, Male, Mice, Mice, Inbred BALB C, Molecular Mimicry, Ovalbumin, Proto-Oncogene Mas, Proto-Oncogene Proteins drug effects, Proto-Oncogene Proteins metabolism, Pulmonary Artery immunology, Pulmonary Artery metabolism, Pulmonary Artery physiopathology, Pulmonary Veins immunology, Pulmonary Veins metabolism, Pulmonary Veins physiopathology, Receptors, G-Protein-Coupled drug effects, Receptors, G-Protein-Coupled metabolism, Time Factors, Airway Remodeling drug effects, Angiotensin I pharmacology, Anti-Asthmatic Agents pharmacology, Asthma drug therapy, Imidazoles pharmacology, Lung drug effects, Peptide Fragments pharmacology, Pulmonary Artery drug effects, Pulmonary Veins drug effects
- Abstract
Background and Purpose: 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., Experimental Approach: 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., Key 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 and Implications: 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., (© 2013 The British Pharmacological Society.)
- Published
- 2013
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