Up-regulation of contractile endothelin receptors by airborne fine particulate matter in rat mesenteric arteries via activation of MAPK pathway.

Fine particle matters (PM) is a well-known risk factor for cardiovascular diseases. However, the underlying molecular mechanisms are largely unknown. Vascular hyper-reactivity plays an important roles in the pathogenesis of cardiovascular diseases. The present study was designed to investigate a hypothesis that PM up-regulated endothelin receptors in mesenteric artery and the potential underlying mechanisms. Rat mesenteric arteries were cultured with PM. The artery contractile responses were recorded by a sensitive myograph. ET and ET receptor expressions of mRNA and protein were assessed by quantitative real-time PCR, Western blotting, and immunohistochemistry, respectively. Results showed that ET receptor agonist, sarafotoxin 6c induced a negligible contraction in fresh artery segments, while ET receptor agonist, ET-1 induced an obvious contraction. After organ culture, the contraction curve mediated by ET and ET receptors were shifted toward the left. PM 1.0 μg/ml cultured for 16 h further enhanced ET and ET receptor-mediated contractile responses with a markedly increased maximal contraction. The organ culture enhanced ET and ET receptor mRNA and protein levels from fresh arteries, which were further increased by PM. The U0126 (MEK/ERK1/2 inhibitor) and SB203580 (p38 inhibitor) significantly attenuated both organ cultured-induced and PM-induced up-regulation of ET receptor. U0126 also suppressed organ culture-increased and PM-increased expressions of ET receptor. SB203580 only suppressed PM-induced enhanced expressions of ET receptor In conclusion, airborne PM up-regulates ET and ET receptors of mesenteric artery via p38 MAPK and MEK/ERK1/2 MAPK pathways.