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

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Abstract

Fine particle matters (PM2.5) 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 PM2.5 up-regulated endothelin receptors in mesenteric artery and the potential underlying mechanisms. Rat mesenteric arteries were cultured with PM2.5. The artery contractile responses were recorded by a sensitive myograph. ETB and ETA receptor expressions of mRNA and protein were assessed by quantitative real-time PCR, Western blotting, and immunohistochemistry, respectively. Results showed that ETB receptor agonist, sarafotoxin 6c induced a negligible contraction in fresh artery segments, while ETA receptor agonist, ET-1 induced an obvious contraction. After organ culture, the contraction curve mediated by ETB and ETA receptors were shifted toward the left. PM2.5 1.0 μg/ml cultured for 16 h further enhanced ETB and ETA receptor-mediated contractile responses with a markedly increased maximal contraction. The organ culture enhanced ETB and ETA receptor mRNA and protein levels from fresh arteries, which were further increased by PM2.5. The U0126 (MEK/ERK1/2 inhibitor) and SB203580 (p38 inhibitor) significantly attenuated both organ cultured-induced and PM2.5-induced up-regulation of ETB receptor. U0126 also suppressed organ culture-increased and PM2.5-increased expressions of ETA receptor. SB203580 only suppressed PM2.5-induced enhanced expressions of ETA receptor In conclusion, airborne PM2.5 up-regulates ETB and ETA receptors of mesenteric artery via p38 MAPK and MEK/ERK1/2 MAPK pathways.

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Funding

This work is supported by the national natural science foundation of China (Grant No.81670001), the research fund for doctor from Xi’an Medical University (Grant No. 2016D0C04), Shaanxi provincial research center for the project of prevention and treatment of respiratory diseases (Grant No. 2017GCKF05), and the national science foundation of breeding program (Grant No. 2017GJFY13).

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Authors and Affiliations

  1. Department of Pharmacology, Xi’an Medical University, 1 Xin Wang Road, Xi’an, Shaanxi, 710021, China

    Rong Wang

  2. Department of Pharmacology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, 76 Yanta West Road, Xi’an, Shaanxi, 710061, China

    Lei Cao & Yongxiao Cao

  3. Department of Environmental Science and Engineering, Xi’an Jiaotong University, Xi’an, Shaanxi, China

    Zhenxing Shen

Authors
  1. Rong Wang
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  2. Lei Cao
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  3. Zhenxing Shen
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  4. Yongxiao Cao
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Correspondence to Rong Wang or Yongxiao Cao.

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The authors declare that they have no conflicts of interest.

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Responsible editor: Philippe Garrigues

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Wang, R., Cao, L., Shen, Z. et al. Up-regulation of contractile endothelin receptors by airborne fine particulate matter in rat mesenteric arteries via activation of MAPK pathway. Environ Sci Pollut Res 25, 14713–14725 (2018). https://doi.org/10.1007/s11356-018-1694-y

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  • DOI: https://doi.org/10.1007/s11356-018-1694-y

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