Salt modulates vascular response through adenosine A2A receptor in eNOS-null mice: Role of CYP450 epoxygenase and soluble epoxide hydrolase

Mohammed A. Nayeem, Darryl C. Zeldin, Matthew A. Boegehold, J R Falck

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

High salt (HS) intake can change the arterial tone in mice, and the nitric oxide (NO) acts as a mediator to some of the receptors mediated vascular response. The main aim of this study was to explore the mechanism behind adenosine-induced vascular response in HS-fed eNOS+/+ and eNOS -/- mice The modulation of vascular response by HS was examined using aortas from mice (eNOS+/+ and eNOS-/-) fed 4% (HS) or 0.45% (NS) NaCl-diet through acetylcholine (ACh), NECA (adenosine-analog), CGS 21680 (A2A AR-agonist), MS-PPOH (CYP epoxygenase-blocker; 10 -5 M), AUDA (sEH-blocker; 10-5 M), and DDMS (CYP4A-blocker; 10-5 M). ACh-response was greater in HS-eNOS +/+ (+59.3 ± 6.3%) versus NS-eNOS+/+ (+33.3 ± 8.0%; P < 0.05). However, there was no response in both HS-eNOS -/- and NS-eNOS-/-. NECA-response was greater in HS-eNOS-/- (+37.4 ± 3.2%) versus NS-eNOS-/- (+7.4.0 ± 3.8%; P < 0.05). CGS 21680-response was also greater in HS-eNOS-/- (+45.4 ± 5.2%) versus NS-eNOS-/-(+5.1 ± 5.0%; P < 0.05). In HS-eNOS-/-, the CGS 21680-response was reduced by MS-PPOH (+7.3 ± 3.2%; P < 0.05). In NS-eNOS -/-, the CGS 21680-response was increased by AUDA (+38.2 ± 3.3%; P < 0.05) and DDMS (+30.1 ± 4.1%; P < 0.05). Compared to NS, HS increased CYP2J2 in eNOS+/+ (35%; P < 0.05) and eNOS -/- (61%; P < 0.05), but decreased sEH in eNOS+/+ (74%; P < 0.05) and eNOS-/- (40%; P < 0.05). Similarly, CYP4A decreased in HS-eNOS+/+ (35%; P < 0.05) and HS-eNOS-/- (34%; P < 0.05). These data suggest that NS causes reduced-vasodilation in both eNOS+/+ and eNOS-/- via sEH and CYP4A. However, HS triggers possible A2AAR-induced relaxation through CYP epoxygenase in both eNOS+/+ and eNOS-/-.

Original languageEnglish (US)
Pages (from-to)101-111
Number of pages11
JournalMolecular and Cellular Biochemistry
Volume350
Issue number1-2
DOIs
StatePublished - Apr 2011

Keywords

  • Adenosine
  • CYP2J2
  • Relaxation
  • Salt
  • eNOS
  • sEH

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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