The Role of MAPK Pathways in Airborne Fine Particulate Matter-Induced Upregulation of Endothelin Receptors in Rat Basilar Arteries.
Airborne fine particulate matter (PM(2.5)) increases the risk of cerebrovascular diseases. However, existing experimental data do not sufficiently explain how PM(2.5) affects cerebral vessels. This study sought to examine whether PM(2.5) alters endothelin (ET) receptor expression on rat cerebral arteries and the potential underlying mechanisms. Isolated rat basilar arteries were cultured with PM(2.5) aqueous suspension in the presence of mitogen-activated protein kinase (MAPK) pathway inhibitors. ET receptor-mediated vasomotor functions were recorded by a sensitive myograph. ET(A) and ET(B) receptor mRNA and protein expressions were assessed using quantitative real-time PCR, Western blotting, and immunohistochemistry, respectively. Compared with fresh and culture alone arteries, PM(2.5) significantly enhanced ET(A) and ET(B) receptor-mediated contractions and increased receptor mRNA and protein expressions in basilar arteries, indicating PM(2.5) upregulates ET(A) and ET(B) 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 PM(2.5)-induced ETB receptor upregulation. PM(2.5)-induced enhancement of ET(A) receptor-mediated contraction and receptor expression was notably inhibited by SB386023 or U0126. However, neither SP600125 nor SB203580 had an effect on PM(2.5)-induced ET(A) receptor upregulation. In conclusion, PM(2.5) upregulates ET(A) and ET(B) receptors in rat basilar arteries. ET(B) receptor upregulation is involved in MEK/ERK1/2, JNK, and p38 MAPK pathways, and ET(A) receptors upregulation is associated with MEK/ERK1/2 pathway.
*Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China;
Xue
X
Xiao
*Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China;
Rong
R
Wang
*Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; leicao@mail.xjtu.edu.cn.
Lei
L
Cao
Department of Environmental Science and Engineering, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, China.
Zhen-xing
ZX
Shen
*Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China;
Yong-xiao
YX
Cao
D000818:Animals; D001488:Basilar Artery / Q000187:drug effects*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D052638:Particulate Matter / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A / Q000032:analysis / Q000187:drug effects* / Q000502:physiology; D044023:Receptor, Endothelin B / Q000032:analysis / Q000187:drug effects* / Q000502:physiology; D015854:Up-Regulation; D014661:Vasoconstriction / Q000187:drug effects
D052638:Particulate Matter; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B
basilar artery; endothelin receptor; fine particulate matter; rat