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However, little is known about the effects of PM<jats:sub>2.5<\/jats:sub> on arteries. The present study investigated whether PM<jats:sub>2.5<\/jats:sub> alters 5\u2010hydroxytryptamine (5\u2010HT) receptor expression and inflammatory mediators on rat mesenteric arteries, and examined the underlying mechanisms. Isolated rat mesenteric arteries segments were cultured with PM<jats:sub>2.5<\/jats:sub> in the presence or absence of ERK1\/2, JNK, and p38 pathway inhibitors. Contractile reactivity was monitored by a sensitive myograph. The expression of 5\u2010HT<jats:sub>2A\/1B<\/jats:sub> receptors and inflammatory mediators were studied by a real\u2010time polymerase chain reaction and\/or by immunohistochemistry. The phosphorylation of mitogen\u2010activated protein kinases (MAPK) pathway was detected by Western blot. Compared with the fresh or culture alone groups, 1.0 \u03bcg\/mL PM<jats:sub>2.5<\/jats:sub> cultured for 16\u2009hours significantly enhanced contractile response induced by 5\u2010HT and increased 5\u2010HT<jats:sub>2A<\/jats:sub> receptor mRNA and protein expressions, indicating PM<jats:sub>2.5<\/jats:sub> upregulates 5\u2010HT<jats:sub>2A<\/jats:sub> receptor. SB203580 (p38 inhibitor) and U0126 (ERK1\/2 inhibitor) significantly decreased PM<jats:sub>2.5<\/jats:sub>\u2010induced elevated contraction and mRNA and protein expression of 5\u2010HT<jats:sub>2A<\/jats:sub> receptor. Cultured with PM<jats:sub>2.5<\/jats:sub> significantly increased the mRNA expression of inflammatory mediators (NOS2, IL\u20101\u03b2, and TNF\u2010\u03b1), while SB203580 decreased mRNA expression level of NOS2, IL\u20101\u03b2, and TNF\u2010\u03b1. SP600125 (JNK inhibitor) decreased mRNA expression level of TNF\u2010\u03b1 and IL\u20101\u03b2. After PM<jats:sub>2.5<\/jats:sub> exposure, the phosphorylation of p38 and ERK1\/2 protein were increased. SB203580 and U0126 inhibited the PM<jats:sub>2.5<\/jats:sub> caused increased phosphorylation protein of p38 and ERK1\/2. In conclusion, PM<jats:sub>2.5<\/jats:sub> induces inflammatory\u2010mediated MAPK pathway in artery which subsequently results in enhanced vascular contraction responding to 5\u2010HT via the upregulated 5\u2010HT<jats:sub>2A<\/jats:sub> receptors.<\/jats:p>","DOI":"10.1002\/tox.22810","type":"journal-article","created":{"date-parts":[[2019,6,14]],"date-time":"2019-06-14T11:13:45Z","timestamp":1560510825000},"page":"1094-1104","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["PM<sub>2.5<\/sub> upregulates rat mesenteric arteries 5\u2010HT<sub>2A<\/sub> receptor via inflammatory\u2010mediated mitogen\u2010activated protein kinases signaling pathway"],"prefix":"10.1002","volume":"34","author":[{"given":"Rong","family":"Wang","sequence":"first","affiliation":[{"name":"Shaanxi Key Laboratory of Ischemic Cardiovascular Disease Xi'an Medical University  Xi'an Shaanxi China"},{"name":"Department of Pharmacology Xi'an 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