Chronic Allergic Pulmonary Inflammation is Aggravated in Angiotensin‐(1‐7) Mas Receptor Knockout Mice

Abstract

Angiotensin‐(1‐7)/Mas receptor axis of the renin‐angiotensin system is associated with attenuation of different inflammatory processes. In this study, we investigated the involvement of Mas receptor in the inflammation and airway remodelling in a model of chronic allergic pulmonary inflammation induced by ovalbumin (OVA). FVBN mice groups: Mas KO control (Mas‐/‐CTRL), Mas KO sensitized with OVA (Mas‐/‐OVA), WT control (Mas+/+CTRL) and WT sensitized with OVA (Mas+/+OVA). The allergic groups received 4 doses of OVA (20µg/mice, i.p.) 14 days apart. After the 2nd sensitization, mice were nebulized with OVA (1% for 30 min; 3 times/week for 4 weeks) or saline (CTRL). Mice were sacrificed 72h after the last nebulization. Mas+/+OVA did not develop inflammation or pulmonary remodelling, as it is observed with this protocol in BalbC mice. However, Mas‐/‐OVA showed a worse performance in the maximum load exercise test and presented a significant increase in inflammatory cell infiltrate in the lung, collagen deposition in the airways, increased thickening of the alveolar parenchyma, increased thickening of the smooth muscle layer of the pulmonary arterioles and hypertrophy of the cardiomyocyte of the right ventricle. Furthermore, Mas‐/‐OVA showed an increase in ERK1/2 and SAPK/JNK phosphorylation and an increase in pro‐inflammatory cytokine (IL13) and chemokines (MCP‐1/CCL2 and RANTES/CCL5) in the lungs. These data indicate that genetic deletion of Mas receptor aggravates lung inflammation and remodelling in mice subjected to a model of chronic asthma.