The Role of MAPK Pathways in Airborne Fine Particulate Matter-Induced Upregulation of Endothelin Receptors in Rat Basilar Arteries

Airborne fine particulate matter (PM2.5) increases the risk of cerebrovascular diseases. However, existing experimental data do not sufficiently explain how PM2.5 affects cerebral vessels. This study sought to examine whether PM2.5 alters endothelin (ET) receptor expression on rat cerebral arteries and the potential underlying mechanisms. Isolated rat basilar arteries were cultured with PM2.5 aqueous suspension in the presence of mitogen-activated protein kinase (MAPK) pathway inhibitors. ET receptor-mediated vasomotor functions were recorded by a sensitive myograph. ETA and ETB receptor mRNA and protein expressions were assessed using quantitative real-time PCR, Western blotting, and immunohistochemistry, respectively. Compared with fresh and culture alone arteries, PM2.5 significantly enhanced ETA and ETB receptor-mediated contractions and increased receptor mRNA and protein expressions in basilar arteries, indicating PM2.5 upregulates ETA and ETB receptors. Culturing with SB386023 (MEK/ERK1/2 inhibitor), U0126 (ERK1/2 inhibitor), SP600125 [c-Jun N-terminal kinase (JNK) inhibitor], or SB203580 (p38 inhibitor) attenuated PM2.5-induced ETB receptor upregulation. PM2.5-induced enhancement of ETA receptor-mediated contraction and receptor expression was notably inhibited by SB386023 or U0126. However, neither SP600125 nor SB203580 had an effect on PM2.5-induced ETA receptor upregulation. In conclusion, PM2.5 upregulates ETA and ETB receptors in rat basilar arteries. ETB receptor upregulation is involved in MEK/ERK1/2, JNK, and p38 MAPK pathways, and ETA receptors upregulation is associated with MEK/ERK1/2 pathway.