Adenosine A2A receptor modulates vascular response in soluble epoxide hydrolase‐null mice through cyp2j‐epoxygenases and PPARγ

The interaction between adenosine and sEH in vascular response is not known. Therefore, we hypothesized that lack of sEH enhances adenosine‐induced relaxation through A 2A AR via cyp2j‐epoxygenases and PPARγ. sEH −/− showed an increase in A 2A AR (31%), cyp2j (65%) & PPARγ (36%), and decrease in A 1 AR (30%) & PPARα (27%) vs. sEH +/+ . NECA (adenosine analog), CGS 21680 (A 2A AR‐agonist) & GW 7647 (PPARα‐agonist)‐induced responses were tested with L‐NAME (NO‐inhibitor), ZM‐241385, SCH‐58261 (A 2A AR‐antagonists), 14,15‐EEZE (EETs‐antagonist), AUDA, t‐ AUCB (sEH‐inhibitors) & T0070907 (PPARγ‐antagonist). NECA‐induced relaxation was higher in sEH −/− (+12.94 ± 3.2%) vs. sEH +/+ (−5.35 ± 5.2%), that was blocked by ZM‐241385 (−22.42 ± 1.9%) & SCH‐58261(−30.04 ± 4.2%). CGS‐21680‐induced relaxation was higher in sEH −/− (+37.4 ± 5.4%) vs. sEH +/+ (+2.14 ± 2.8%), that was not blocked by L‐NAME (p>;0.05), whereas 14,15‐EEZE did (p<0.05). Also, AUDA & t‐AUCB did not change CGS‐21680‐induced response in sEH −/− (p>;0.05), but reversed in sEH +/+ (AUDA: +45.33±4.1%, t ‐AUCB: +63.37±7.2). GW 7647 did not relax vs. CGS 21680 in sEH −/− (p<0.05), and T0070907 blocked CGS 21680 induced relaxation in sEH −/− (+9.40 ± 3.1). These data suggest that A 2A AR‐induced relaxation in sEH −/− may depend on the up‐regulation of cyp2j , PPARγ and down‐regulation of A 1 AR, PPARα. Supported (BGF‐WVU, STF‐WVU, HL027339 , HL094447 , GM31278 & z01 ES025034 ).