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.
['Xiao|Xue|X|', 'Wang|Rong|R|', 'Cao|Lei|L|', 'Shen|Zhen-xing|ZX|', 'Cao|Yong-xiao|YX|']
D000818:Animals D001488:Basilar Artery D020935:MAP Kinase Signaling System D008297:Male D052638:Particulate Matter D051381:Rats D017207:Rats, Sprague-Dawley D044022:Receptor, Endothelin A D044023:Receptor, Endothelin B D015854:Up-Regulation D014661:Vasoconstriction
endothelin receptor rat basilar artery fine particulate matter