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Modulation of vascular response by high salt intake depends on the presence or absence of adenosine A2A receptor using A2A AR‐null mice
Author(s) -
Pradhan Isha,
Mustafa Jamal S,
Zeldin Darryl C,
Ledent Catherine,
Falck John R,
Nayeem Mohammed A
Publication year - 2013
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.27.1_supplement.1092.4
Subject(s) - adenosine , chemistry , agonist , downregulation and upregulation , cgs 21680 , endocrinology , medicine , adenosine receptor , antagonist , adenosine a2a receptor , contraction (grammar) , ccpa , receptor , biology , biochemistry , gene
High salt (HS) has been shown to modulate adenosine‐induced vascular response through A 2A AR. We hypothesized that HS enhances adenosine‐induced relaxation through cyp‐epoxygenases in the presence of A 2A AR, but exaggerates contraction in the absence of A 2A AR. Organ bath and western blot studies were conducted with 4% (HS) and 0.18% NaCl (NS) diet fed A 2A AR −/− and A 2A AR +/+ mice. Non‐selective adenosine analog (NECA) produced significantly higher relaxation in HS‐A 2A AR +/+ vs. NS‐A 2A AR +/+ , NS & HS‐A 2A AR −/− . Also, CGS 21680, selective A 2A AR agonist, enhanced relaxation in HS‐A 2A AR +/+ vs. NS‐A 2A AR +/+ which was blocked by an EET antagonist (14,15‐EEZE) but not by L‐NAME (NOS inhibitor) and indomethacin (COX inhibitor). NECA induced contraction in NS & HS‐A 2A AR −/− was reversed by A 1 AR antagonist, DPCPX. Also, CCPA, a selective A 1 AR agonist yielded higher contraction in NS & HS‐A 2A AR −/− vs. NS & HS‐A 2A AR +/+ mice. Compared with NS‐A 2A AR +/+ , HS‐A 2A AR +/+ demonstrated upregulation of A 2A AR (60%), cyp2c29 (64%) and downregulation of A 1 AR (17%) & cyp4a (46%). A 1 AR (20 %) & cyp4a (50%) were upregulated and cyp2c29 (54%) was downregulated in HS‐A 2A AR −/− vs. HS A 2A AR +/+ . Our data suggest HS elicited enhanced A 2A AR‐induced relaxation through cyp‐epoxygenases in A 2A AR +/+ is abolished in the A 2A AR −/− , further exaggerating contraction via A 1 AR. Supported (BGF‐WVU, STF‐WVU, HL027339, HL094447, GM31278 & z01 ES025034).