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

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

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Author(s)

  • Jianwei Tian
  • Wing Tak Wong
  • Xiao Yu Tian
  • Peng Zhang
  • Nanping Wang

Detail(s)

Original languageEnglish
Pages (from-to)129-135
Journal / PublicationHypertension
Volume56
Issue number1
Publication statusPublished - Jul 2010
Externally publishedYes

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. © 2010 American Heart Association, Inc.

Research Area(s)

  • ETBR, PPAR-γ, Thiazolidinediones, Vasoconstriction

Bibliographic Note

Publication details (e.g. title, author(s), publication statuses and dates) are captured on an “AS IS” and “AS AVAILABLE” basis at the time of record harvesting from the data source. Suggestions for further amendments or supplementary information can be sent to lbscholars@cityu.edu.hk.

Citation Format(s)

Rosiglitazone attenuates endothelin-1-induced vasoconstriction by upregulating endothelial expression of endothelin b receptor. / Tian, Jianwei; Wong, Wing Tak; Tian, Xiao Yu et al.
In: Hypertension, Vol. 56, No. 1, 07.2010, p. 129-135.

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review