Airborne fine particulate matter alters the expression of endothelin receptors in rat coronary arteries

Exposure to airborne fine particulate matter (PM_2.5) is associated with cardiovascular diseases. However, a comprehensive understanding of the underlying mechanisms by which PM_2.5 induces or aggravates these diseases is still insufficiently clear. The present study investigated whether PM_2.5 alters the expression of the endothelin subtype B (ET_B) and endothelin subtype A (ET_A) receptors in the coronary artery and examined the underlying mechanisms. Rat coronary artery segments were cultured with PM_2.5 in the presence or absence of MEK/ERK1/2, JNK, and p38 pathway inhibitors. Contractile reactivity was measured by myography. ET_B and ET_A receptor expression was evaluated using RT-PCR, western blot and immunohistochemistry. Compared with fresh arteries, the cultured coronary arteries showed a significantly enhanced contraction mediated by the ET_B receptor and an unaltered contraction mediated by the ET_A receptor. Culture with PM_2.5 significantly enhanced the contraction and the mRNA and protein expression levels of the ET_B and ET_A receptors in the coronary arteries, suggesting that PM_2.5 induces an upregulation of ET_A and ET_B receptors. In addition, the PM_2.5-induced increases in ET_B- and ET_A-mediated vasoconstriction and receptor expressions could be notably decreased by MEK1/2 inhibitor, U0126 and Raf inhibitor, SB386023, suggesting that the upregulation of ET_B and ET_A receptors is related with MEK/ERK1/2 pathway. In conclusion, PM_2.5 induces the ET_B and ET_A receptor upregulation in rat coronary arteries, and the MEK/ERK1/2 pathway may be involved in this process.