JOURNAL ARTICLE

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

Xue Xiao, Tong Yao, Shuaishuai Du, Jin Wang, Pinging Yan, Yali Lei, Lei Cao, Zhenxing Shen, Yongxiao Cao
Toxicology and Applied Pharmacology 2020 July 22, : 115154
32710959
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 (PM10 ) exposure and investigated the underlying mechanisms. Rats were exposed to PM10 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 PM10 exposure-induced pulmonary vascular dysfunction. Functional experiment results showed that PM10 exposure increased the pulmonary artery pressure of rats and caused endothelin B receptor (ETB R)-mediated pulmonary arteriolar hyperreactivity. U0126 significantly rescued these pathological changes. PM10 exposure upregulated of contractile ETB R of pulmonary arteriolar smooth muscle, and damage pulmonary artery endothelial cells to induce the release of more endothelin 1 (ET-1). The upregulated ETB R bound to increased ET-1 induced pulmonary arteriolar hyperresponsiveness and pulmonary arteriolar remodeling. U0126 inhibited the PM10 exposure-induced upregulation of ETB R in pulmonary arteriole, ETB 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 ETB R in pulmonary arteriole, which may be involved in pulmonary arteriole hyperresponsiveness and remodeling in rats. These findings provide new mechanistic evidence of PM10 exposure-induced respiratory diseases, and a new possible target for treatment.

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