Rosiglitazone attenuates endothelin-1-induced vasoconstriction by upregulating endothelial expression of endothelin b receptor

Jianwei Tian, Wing Tak Wong, Xiao Yu Tian, Peng Zhang, Yu Huang, Nanping Wang

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Thiazolidinediones improve insulin resistance and endothelial dysfunction. However, the mechanisms underlying the vasoprotective effects of thiazolidinediones remain to be fully elucidated. The present study aimed to examine the molecular mechanism for the anti-vasoconstrictive effects of rosiglitazone in response to endothelin (ET) 1. Mouse aortas were treated with rosiglitazone for 24 hours, and ET-1-induced vasoconstriction was assessed by wire myography. The results showed that rosiglitazone attenuated ET-1-induced contraction in mouse aortas; this effect was abolished by ET-B receptor (ETBR) antagonist, NO synthase inhibitor, and by the removal of endothelium. By using Northern blotting, real-time RT-PCR, Western blotting, and immunohistochemical techniques, we found that rosiglitazone upregulated expression of ETBR at both mRNA and protein levels in mouse aortas and human vascular endothelial cells. The induction of ETBR was prevented by peroxisome proliferator-activated receptor-γ antagonism. Luciferase reporter assay showed that rosiglitazone enhanced ETBR gene promoter activity. Furthermore, chromatin immunoprecipitation assays demonstrated that peroxisome proliferator-activated receptor-γ can directly bind to ET BR gene promoter. Furthermore, in vivo treatment with rosiglitazone also attenuated the ET-1-induced vasoconstrictions and increased the ET BR expression in mouse aortas and mesenteric arteries. In conclusion, these results demonstrate that rosiglitazone attenuated ET-1-induced vasoconstriction through the upregulation of endothelial ETBR, which is a peroxisome proliferator-activated receptor-γ direct target.

Original languageEnglish (US)
Pages (from-to)129-135
Number of pages7
JournalHypertension
Volume56
Issue number1
DOIs
StatePublished - Jul 2010

Keywords

  • ETR
  • PPAR-γ
  • Thiazolidinediones
  • Vasoconstriction

ASJC Scopus subject areas

  • Internal Medicine

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