Angiotensin II type 2 receptor activation alleviates inflammation and oxidative stress caused by chronic exposure to air pollution.

The impact of chronic exposure to urban air (UA) on renin-angiotensin system (RAS) components and the therapeutic potential of the angiotensin type 2 receptor (AT2R) agonist, Compound 21 (C21), in mitigating pollution-induced inflammation and oxidative stress was evaluated in a mouse model exposed to UA for 14 weeks. Air pollution exposure increased pro-inflammatory cytokines and oxidative damage markers in the lungs and kidneys and upregulated angiotensin converting enzyme; ACE, and angiotensin type 1 receptor; AT1R in the lungs; while it induced a compensatory increase in Mas receptor; MasR and AT2R in the heart and kidneys. C21 treatment reduced IL-1β and TNF-α expression in the lungs and 3-nitrotyrosine levels in the lungs and kidneys, downregulated both ACE and AT1R expression in the lungs and increased renal MasR expression. Current results underscore the relevance of RAS dysregulation in pollution-induced tissue damage and positions AT2R agonism as a possibility for mitigating the health impacts of air pollution.