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Salt induced vascular response through adenosine A 2A receptor: role of CYP epoxygenase and soluble epoxide hydrolase
Author(s) -
Nayeem Mohammed A,
Zeldin Darryl C.,
Boegehold Mathew A,
Ponnoth Dovenia S,
Roush Kevin P,
Falck John R
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.977.4
Subject(s) - cgs 21680 , chemistry , epoxide hydrolase 2 , glibenclamide , adenosine , agonist , medicine , endocrinology , channel blocker , epoxygenase , receptor , adenosine receptor , pharmacology , arachidonic acid , biochemistry , enzyme , organic chemistry , diabetes mellitus , calcium
High salt intake can change the effect of adenosine on arterial tone in mice. The aim of this study was to clarify the mechanism by which this occurs. Using aortas from mice fed a 4% (HS) or 0.45% (NS) NaCl diet for 4–5 wks, concentration response curves for NECA (adenosine analog) and CGS 21680 (A 2A AR agonist) were obtained with glibenclamide (Glib, K ATP channel blocker; 10 −5 M), 5‐hydroxydecanoate (5‐HD, mito‐K ATP channel blocker; 10 −4 M), MS‐PPOH (CYP2J2 blocker; 10 −5 M), AUDA (sEH blocker; 10 −5 M) and DDMS (CYP4A blocker; 10 −5 M). Relaxation to 10 −6 M NECA was greater in the HS group (28.4 ± 3.9%) than in the NS group (4.1 ± 2.3%). Relaxation to 10 −6 M CGS 21680 was also greater in HS (27.9 ± 4.5%) than in NS (4.9 ± 2.2%). In HS, the CGS 21680 response was greatly reduced by MS‐PPOH (to 4.7 ± 2.0%) and 5‐HD (to 8.9 ± 2.2%), and abolished by Glib (−1.0 ± 5.9%). In NS, the CGS 21680 response was increased by AUDA (to 29.2 ± 3.1%) and DDMS (to 27.2 ± 3.0%). Compared to NS, HS vessels showed increased CYP2J2 expression (46% higher) but decreased sEH and CYP4A expression (60% and 30% lower, respectively). These data suggest that in mice fed normal diet, activation of arterial A 2A receptors causes constriction via increased sEH activity and formation of CYP4A metabolites. However, in mice fed high salt, activation of these receptors triggers relaxation via formation of CYP2J2 metabolites. HL027339 , HL094447 , z01‐ES‐025034, AHA2250298, GM‐31278