Inhibition of endothelin A receptor protects brain microvascular endothelial cells against hypoxia‑induced injury

  • Authors:
    • Xi Liu
    • Fen Deng
    • Zhen Yu
    • Yunlan Xie
    • Changlin Hu
    • Lifen Chen
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  • Published online on: April 16, 2014     https://doi.org/10.3892/ijmm.2014.1744
  • Pages: 313-320
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Abstract

Endothelin-1 (ET-1)-induced cell damage is commonly involved in ischemia/hypoxia-associated diseases. PD155080 [sodium 2-benzo (1.3)dioxol-5-yl-3-benzyl-4-(4‑metho­xyphenyl)-4-oxobut-2-enoate] is a selective endothelin A receptor (ETAR) antagonist that inhibits ET-1‑induced cell damage. The aim of this study was to investigate the effects of PD155080 on hypoxia-induced rat brain microvascular endothelial cell (BMEC) injury. BMECs were isolated from the cerebral cortex of Wistar rats and cultured in an anoxia chamber, containing 95% N2 and 5% CO2 for 12 h. BMEC injury was assessed by determining cellular ultra-microstructural changes and cell viability by MTT assay, trypan blue (TB) staining and measuring the lactate dehydrogenase (LDH) levels. ET-1 mRNA expression was detected by in situ hybridization and reverse transcription PCR (RT-PCR); the ET-1 protein level was measured by radioimmunoassay. Following exposure to hypoxic conditions, the viability of the BMECs was markedly decreased and the ultrastructure of the BMECs was damaged, as demonstrated by chromatin margination, chromatin agglutination, plasma edema, the increased number of intracellular liposomes and vacuoles, mitochondrial swelling and the expansion of a rough surfaced endoplasmic reticulum. The levels of ET-1 and ET-1 mRNA expression in the BMECs were increased following exposure to hypoxic conditions. Of note, the administration of PD155080 greatly enhanced the viability of the BMECs and ameliorated hypoxia-induced cellular injury. PD155080 also inhibited hypoxia-induced ET-1 production by the BMECs. In conclusion, PD155080 exerts protective effects against hypoxia-induced BMEC injury.
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July 2014
Volume 34 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

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APA
Liu, X., Deng, F., Yu, Z., Xie, Y., Hu, C., & Chen, L. (2014). Inhibition of endothelin A receptor protects brain microvascular endothelial cells against hypoxia‑induced injury. International Journal of Molecular Medicine, 34, 313-320. https://doi.org/10.3892/ijmm.2014.1744
MLA
Liu, X., Deng, F., Yu, Z., Xie, Y., Hu, C., Chen, L."Inhibition of endothelin A receptor protects brain microvascular endothelial cells against hypoxia‑induced injury". International Journal of Molecular Medicine 34.1 (2014): 313-320.
Chicago
Liu, X., Deng, F., Yu, Z., Xie, Y., Hu, C., Chen, L."Inhibition of endothelin A receptor protects brain microvascular endothelial cells against hypoxia‑induced injury". International Journal of Molecular Medicine 34, no. 1 (2014): 313-320. https://doi.org/10.3892/ijmm.2014.1744