Chronic real-time particulate matter exposure causes rat pulmonary arteriole hyperresponsiveness and remodeling: The role of ET B R-ERK1/2 signaling

Exposure to air pollution is associated with the incidence of respiratory diseases. The present study evaluated the pulmonary vascular system injury by chronic real-time particulate matter (PM ) exposure and investigated the underlying mechanisms. Rats were exposed to PM or filtered air for 2 to 4 months using a whole body exposure system, and intraperitoneally injected with the MEK1/2 inhibitor U0126. Right heart catheterization and myography were performed to detect lung function and pulmonary vascular reactivity, respectively. Western blotting, qRT-PCR, enzyme-linked immunosorbent assay and histological analyses were used to detect the effects and mechanisms by which PM exposure-induced pulmonary vascular dysfunction. Functional experiment results showed that PM exposure increased the pulmonary artery pressure of rats and caused endothelin B receptor (ET R)-mediated pulmonary arteriole hyperreactivity. U0126 significantly rescued these pathological changes. PM exposure upregulated the contractile ET R of pulmonary arteriolar smooth muscle, and damaged pulmonary artery endothelial cells to induce the release of more endothelin 1 (ET-1). The upregulated ET R bound to increased ET-1 induced pulmonary arteriolar hyperresponsiveness and remodeling. U0126 inhibited the PM exposure-induced upregulation of ET R in pulmonary arteriole, ET R-mediated pulmonary arterial hyperresponsiveness and vascular remodeling. In conclusion, chronic real-time particulate matter exposure can activate the ERK1/2 signaling, thereby inducing the upregulation of contractile ET R in pulmonary arteriole, which may be involved in pulmonary arteriole hyperresponsiveness and remodeling in rats. These findings provide new mechanistic evidence of PM exposure-induced respiratory diseases, and a new possible target for treatment.