Protein kinase Cb mediates downregulated expression of glucagon-like peptide-1receptor in hypertensive rat renal arteries

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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Author(s)

  • Limei Liu
  • Jian Liu
  • Yuansheng Gao
  • Chi Fai Ng
  • Xiaoxing Yu
  • Dou Dou

Detail(s)

Original languageEnglish
Pages (from-to)784-790
Journal / PublicationJournal of Hypertension
Volume33
Issue number4
Publication statusPublished - 1 Apr 2015
Externally publishedYes

Abstract

Objective: Glucagon-like peptide-1 (GLP-1) exerts its actions via activating GLP-1 receptor (GLP-1R). Our previous study showed a reduced GLP-1R expression in spontaneously hypertensive rat (SHR) renal arteries. The present study investigated the mechanisms underlying GLP- 1R downregulation in hypertension. Methods: Intrarenal arteries of normotensive Wistar-Kyoto rat (WKY) and SHR were suspended in the myograph for force measurement. GLP-1R expression was evaluated by both immunofluorescence and western blotting. Protein kinase Ca (PKCa), PKCb, PKCd, and total PKC levels were assayed by western blotting. Results: Immunofluorescence revealed reduced GLP-1R level in SHR renal arteries compared with WKY renal arteries. GLP-1R agonist exendin-4 induced concentrationdependent relaxations in WKY arteries, which mainly depended on the presence of endothelium. GLP-1R antagonist exendin 9-39 inhibited this relaxation in WKY arteries, whereas the relaxations were significantly less in SHR arteries. Ex-vivo treatment with PKC inhibitor GFX, PKCa and PKCb inhibitor Go 6976, and PKCb inhibitor hispidin but not PKCd inhibitor rottlerin improved the impaired relaxations and restored the diminished GLP-1R expression in SHR arteries. Furthermore, PKCb level was greater in SHR than WKY arteries, with no difference in PKCa, PKCd, or total PKC expressions between two rat strains. Treatment with PKC-activating agent phorbol-12- myristate-13-acetate attenuated exendin-4-induced relaxations and reduced GLP-1R expression in WKY arteries, which were reversed by GFX, Go 6976, or hispidin. More relevantly, immunofluorescence of human renal arteries also showed a reduced GLP-1R level in hypertensive patients. Conclusion: The present results provide novel evidence that the reduced GLP-1R expression in SHR renal arteries is most likely mediated through PKCb upregulation; the latter probably contributes to the impaired GLP-1Rmediated vasorelaxations in hypertension.

Research Area(s)

  • Glucagon-like peptide-1 receptor, Hypertension, Protein kinase C, Renal artery

Bibliographic Note

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Citation Format(s)

Protein kinase Cb mediates downregulated expression of glucagon-like peptide-1receptor in hypertensive rat renal arteries. / Liu, Limei; Liu, Jian; Gao, Yuansheng; Ng, Chi Fai; Yu, Xiaoxing; Dou, Dou; Huang, Yu.

In: Journal of Hypertension, Vol. 33, No. 4, 01.04.2015, p. 784-790.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review