Modulation of vascular response by high salt intake depends on the presence or absence of adenosine A2A receptor using A2A AR‐null mice

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).