Cooperative action of APJ and α1A-adrenergic receptor in vascular smooth muscle cells induces vasoconstriction

Katsumasa Nagano, Chulwon Kwon, Junji Ishida, Tatsuo Hashimoto, Jun Dal Kim, Nana Kishikawa, Mei Murao, Kenjiro Kimura, Yoshitoshi Kasuya, Sadao Kimura, Yi-Ching Chen, Hirotsugu Tsuchimochi, Mikiyasu Shirai, James T. Pearson, Akiyoshi Fukamizu

Research output: Contribution to journalArticleResearchpeer-review

2 Citations (Scopus)

Abstract

The apelin receptor (APJ), a receptor for apelin and elabela/apela, induces vasodilation and vasoconstriction in blood vessels. However, the prolonged effects of increased APJ-mediated signalling, involving vasoconstriction, in smooth muscle cells have not been fully characterized. Here, we investigated the vasoactive effects of APJ gain of function under the control of the smooth muscle actin (SMA) gene promoter in mice. Transgenic overexpression of APJ (SMA-APJ) conferred sensitivity to blood pressure and vascular contraction induced by apelin administration in vivo. Interestingly, ex vivo experiments showed that apelin markedly increased the vasoconstriction of isolated aorta induced by noradrenaline (NA), an agonist for α- and β-adrenergic receptors, or phenylephrine, a specific agonist for α1-adrenergic receptor (α1-AR). In addition, intracellular calcium influx was augmented by apelin with NA in HEK293T cells expressing APJ and α1A-AR. To examine the cooperative action of APJ and α1A-AR in the regulation of vasoconstriction, we developed α1A-AR deficient mice using a genome-editing technique, and then established SMA-APJ/α1A-AR-KO mice. In the latter mouse line, aortic vasoconstriction induced by a specific agonist for α1A-AR, A-61603, were significantly less than in SMA-APJ mice. These results suggest that the APJ-enhanced response requires α1A-AR to contract vessels coordinately.

Original languageEnglish
Pages (from-to)383-392
Number of pages10
JournalJournal of Biochemistry
Volume166
Issue number5
DOIs
Publication statusPublished - 1 Nov 2019

Keywords

  • apelin
  • APJ
  • GPCRs
  • vasoconstriction
  • α1A-AR

Cite this