Mas Antagonist Prevents the Anti‐inflammatory Effect of Exercise in a Model of Chronic Allergic Lung Inflammation

Abstract

Aerobic exercise training attenuates asthma‐induced airway inflammation, pulmonary remodelling and bronchial hyperresponsiveness. In addition, aerobic exercise increase circulating and tissue levels of angiotensin‐(1–7) [Ang‐(1–7)], which was shown to attenuate inflammation in different diseases. In the present study, we evaluated whether Ang‐(1–7) is involved in the beneficial effects of aerobic training in an experimental model of chronic allergic lung inflammation (asthma). BALB/c mice were subjected to a chronic protocol of asthma induced by ovalbumine (OVA) immunization (4 i.p. injections of OVA 14 days apart) and sensitization (OVA inhalation, 3 times a week during 4 weeks). Simultaneously to sensitization period, part of the animals were treated with the antagonist of Ang‐(1–7) receptor Mas (A779, 1μg/h; for 28 days) and trained in a treadmill (TRE; 60% of the maximal capacity, 1h/day, 5 days/week during 4 weeks). Non‐asthmatic and sedentary mice (controls) received saline i.p. and inhalation with saline at same time points of experimental groups. The serum IgE levels were determined by ELISA, the airway remodelling by histology, infiltration of inflammatory cells in the lung by enzymatic activity assay. The gene expression of PGC‐1α was determined by qRT‐PCR and the protein expression of fibronectin in the lung by Western blotting. Treatment of asthmatic and trained animals with A779 prevented: i) the reduction in serum IgE levels (23±10 U/ml vs 0±0 U/ml in OVA‐TRE); ii) the reduction in extracellular matrix deposition in the airways (32±1% vs 17±2% in OVA‐TRE); iii) the reduction in the alveolar wall thickening (3±0.3 μm2 vs 1.8±0.1 μm2 in OVA‐TRE); iv) the reduction in MPO enzyme activity (neutrophils infiltration; 1.51±0.11 D.O./mg vs 1.01±0.06 D.O./mg in OVA‐TRE); v) the decrease in protein expression of fibronectin in the lung. Physical training was confirmed by the increase in PGC1‐α in OVA‐TRE (1.85±0.14 a.u.) and OVA‐TRE‐A779 (1.62±0.48 a.u.) in comparison to sedentary animals (0.96±0.15 a.u.). These data suggest that Mas receptor activation is involved, at least in part, in the anti‐inflammatory and anti‐fibrotic effect of aerobic training in animals subjected to an experimental model of chronic pulmonary lung inflammation. FINNANCIAL SUPPORT: FAPEMIG, CAPES, CNPq, INCT‐NanobiofarSupport or Funding InformationFAPEMIG, CAPES, CNPq, INCT‐Nanobiofar