| First Author | Magalhães GS | Year | 2016 |
| Journal | Am J Physiol Lung Cell Mol Physiol | Volume | 311 |
| Issue | 6 | Pages | L1141-L1148 |
| PubMed ID | 27815255 | Mgi Jnum | J:237510 |
| Mgi Id | MGI:5812837 | Doi | 10.1152/ajplung.00029.2016 |
| Citation | Magalhaes GS, et al. (2016) Chronic allergic pulmonary inflammation is aggravated in angiotensin-(1-7) Mas receptor knockout mice. Am J Physiol Lung Cell Mol Physiol 311(6):L1141-L1148 |
| abstractText | The angiotensin-(1-7) [ANG-(1-7)]/Mas receptor pathway is currently recognized as a counterbalancing mechanism of the renin-angiotensin system in different pathophysiological conditions. We have previously described that treatment with ANG-(1-7) attenuates lung inflammation and remodeling in an experimental model of asthma. In the present study, we investigated whether lack of the Mas receptor could alter the inflammatory response in a model of chronic allergic lung inflammation induced by ovalbumin (OVA). Mas receptor wild-type (MasWT) and knockout (MasKO) mice were subjected to four doses of OVA (20 mug/mice ip) with a 14-day interval. At the 21st day, nebulization with OVA (1%) was started, three times per week until the 46th day. Control groups received saline (0.9% ip) and were nebulized with saline (0.9%). MasWT-OVA developed a modest inflammatory response and minor pulmonary remodeling to OVA challenge. Strikingly, MasKO-OVA presented a significant increase in inflammatory cell infiltrate, increase in extracellular matrix deposition, increase in thickening of the alveolar parenchyma, increase in thickening of the smooth muscle layer of the pulmonary arterioles, increase in proinflammatory cytokine and chemokine levels in the lungs, characteristic of chronic asthma. Additionally, MasKO-OVA presented an increase in ERK1/2 phosphorylation compared with MasWT-OVA. Furthermore, MasKO-OVA showed a worse performance in a test of maximum physical exercise compared with MasWT-OVA. Our study shows that effects triggered by the Mas receptor are important to attenuate the inflammatory and remodeling processes in a model of allergic lung inflammation in mice. Our data indicate that impairment of the ANG-(1-7)/Mas receptor pathway may lead to worsening of the pathophysiological changes of asthma. |
