AVE 0991, a non-peptide mimic of angiotensin-(1-7) effects, attenuates pulmonary remodelling in a model of chronic asthma.

Autor: Rodrigues-Machado MG; 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., Magalhães GS, Cardoso JA, Kangussu LM, Murari A, Caliari MV, Oliveira ML, Cara DC, Noviello ML, Marques FD, Pereira JM, Lautner RQ, Santos RA, Campagnole-Santos MJ
Jazyk: angličtina
Zdroj: British journal of pharmacology [Br J Pharmacol] 2013 Oct; Vol. 170 (4), pp. 835-46.
DOI: 10.1111/bph.12318
Abstrakt: 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.)
Databáze: MEDLINE
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