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AVE 0991, a non‐peptide mimic of angiotensin‐(1–7) effects, attenuates pulmonary remodelling in a model of chronic asthma
Author(s) -
RodriguesMachado M G,
Magalhães G S,
Cardoso J A,
Kangussu L M,
Murari A,
Caliari M V,
Oliveira M L,
Cara D C,
Noviello M L M,
Marques F D,
Pereira J M,
Lautner R Q,
Santos R A S,
CampagnoleSantos M J
Publication year - 2013
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.12318
Subject(s) - ovalbumin , bronchoalveolar lavage , lung , angiotensin ii , saline , medicine , pulmonary hypertension , inflammation , muscle hypertrophy , vascular remodelling in the embryo , receptor , endocrinology , bradykinin , asthma , immunology , immune system
Background and Purpose AVE 0991 ( AVE ) is a non‐peptide compound, mimic of the angiotensin ( A ng)‐(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 A ng II levels in lungs. Conclusions and Implications AVE treatment prevented pulmonary remodelling, inflammation and right ventricular hypertrophy in OVA mice, suggesting that A ng‐(1–7) receptor agonists are a new possibility for the treatment of pulmonary remodelling induced by chronic asthma.