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Molecular and Cellular Biochemistry

, Volume 350, Issue 1–2, pp 101–111 | Cite as

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

  • Mohammed A. NayeemEmail author
  • Darryl C. Zeldin
  • Matthew A. Boegehold
  • John R. Falck
Article

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−/−.

Keywords

Salt eNOS CYP2J2 sEH Relaxation Adenosine 

Abbreviations

EDRF

Endothelium-derived relaxing factors

EDHF

Endothelium-derived hyperpolarizing factor

L-NAME

NG-nitro-l-arginine methyl ester

sEH

Soluble epoxide hydrolase

eNOS

Endothelial nitric oxide synthase

EET

Eicosatrienoic acid

NECA

5′-N-ethylcarboxamidoadenosine

MS-PPOH

Methylsulfonyl-propargyloxyphenylhexanamide

AUDA

12-(3-adamantan-1-yl-ureido)dodecanoic acid

DDMS

Dibromo-dodecenyl-methylsulfimide

Notes

Acknowledgments

The authors would like to thank Dr. Mustafa for his support (HL 027339 and MAN is Co-Investigator in HL 094447), AHA 2250298 (MAB), GM 31278 (JRF), and the Intramural Research Program of the NIEHS/NIH-Z01 ES025034 (DCZ).

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Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Mohammed A. Nayeem
    • 1
    Email author
  • Darryl C. Zeldin
    • 2
  • Matthew A. Boegehold
    • 1
  • John R. Falck
    • 3
  1. 1.Department of Physiology and PharmacologyCenter for Cardiovascular and Respiratory Sciences, West Virginia UniversityMorgantownUSA
  2. 2.Division of Intramural ResearchNIEHS/NIHDurhamUSA
  3. 3.Department of BiochemistryUTSWMCDallasUSA

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