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

作者：Rodrigues Machado M G; Magalhaes 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; Campagnole Santos M J^*

来源：British Journal of Pharmacology, 2013, 170(4): 835-846.

DOI：10.1111/bph.12318

• AVE 0991
• angiotensin-(1-7)
• allergic lung inflammation
• asthma
• airway remodelling
• cytokines
• Mas receptor

Background and PurposeAVE 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. %26lt;br%26gt;Experimental ApproachWe used BALB/c mice (6-8 weeks old) and induced chronic allergic lung inflammation by OVA sensitization (20gmouse(-1), i.p., four times, 14 days apart) and OVA challenge (1%, nebulised during 30min, three times perweek, for 4 weeks). Control and AVE groups were given saline i.p and challenged with saline. AVE treatment (1mgkg(-1)per day, s.c.) or saline (100Lkg(-1)per day, s.c.) was given during the challenge period. Mice were anaesthetized 72h 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. %26lt;br%26gt;Key ResultsTreatment 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. %26lt;br%26gt;Conclusions and ImplicationsAVE 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.

• 出版日期2013-10