High salt diet modulates vascular response in A<inf>2A</inf>AR<sup>+/+</sup> and A<inf>2A</inf>AR<sup>−/−</sup> mice: role of sEH, PPARγ, and K<inf>ATP</inf> channels

Isha Pradhan, Catherine Ledent, S. Jamal Mustafa, Christophe Morisseau, Mohammed A. Nayeem

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

This study aims to investigate the signaling mechanism involved in HS-induced modulation of adenosine-mediated vascular tone in the presence or absence of adenosine A<inf>2A</inf> receptor (A<inf>2A</inf>AR). We hypothesized that HS-induced enhanced vascular relaxation through A<inf>2A</inf>AR and epoxyeicosatrienoic acid (EETs) is dependent on peroxisome proliferator-activated receptor gamma (PPARγ) and ATP-sensitive potassium channels (K<inf>ATP</inf> channels) in A<inf>2A</inf>AR<sup>+/+</sup> mice, while HS-induced vascular contraction to adenosine is dependent on soluble epoxide hydrolase (sEH) that degrades EETs in A<inf>2A</inf>AR<sup>−/−</sup> mice. Organ bath and Western blot techniques were conducted in HS (4 % NaCl) and normal salt (NS, 0.45 % NaCl)-fed A<inf>2A</inf>AR<sup>+/+</sup> and A<inf>2A</inf>AR<sup>−/−</sup> mouse aorta. We found that enhanced vasodilation to A<inf>2A</inf>AR agonist, CGS 21680, in HS-fed A<inf>2A</inf>AR<sup>+/+</sup> mice was blocked by PPARγ antagonist (T0070907) and K<inf>ATP</inf> channel blocker (Glibenclamide). Also, sEH inhibitor (AUDA)-dependent vascular relaxation was mitigated by PPARγ antagonist. PPARγ agonist (Rosiglitazone)-induced relaxation in HS-A<inf>2A</inf>AR<sup>+/+</sup> mice was attenuated by K<inf>ATP</inf> channel blocker. Conversely, HS-induced contraction in A<inf>2A</inf>AR<sup>−/−</sup> mice was attenuated by sEH inhibitor. Overall, findings from this study that implicates the contribution of EETs, PPARγ and K<inf>ATP</inf> channels downstream of A<inf>2A</inf>AR to mediate enhanced vascular relaxation in response to HS diet while, role of sEH in mediating vascular contraction in HS-fed A<inf>2A</inf>AR<sup>−/−</sup> mice.

Original languageEnglish (US)
Pages (from-to)87-96
Number of pages10
JournalMolecular and Cellular Biochemistry
Volume404
Issue number1-2
DOIs
StatePublished - Mar 5 2015

Keywords

  • A<inf>2A</inf>AR
  • EETs
  • High salt
  • K<inf>ATP</inf> channel
  • PPARγ
  • Soluble epoxide hydrolase

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Cell Biology

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