Activation of adenosine 2A receptors (A2ARs) enhances norepinephrine (NE) transport into perivenous sympathetic nerves in normotensive, but not DOCA‐salt hypertensive rats

NE and ATP are released from perivascular sympathetic nerves to control peripheral resistance and blood pressure. NE is cleared from the neuroeffector junction by the NE transporter (NET). Adenosine, a product of ATP hydrolysis, inhibits NE release via an action at adenosine A 1 receptors (A 1 Rs). A 2A Rs are also expressed on perivascular sympathetic nerves, but their function is unclear. We determined the role of A 2A Rs in modulating NE release and tested if A 2A R function is impaired in DOCA‐salt rats. Electrically‐evoked NE release was measured in vitro using amperometry. The amplitude, rise slope, and decay slope of NE oxidation currents were measured in the absence or presence of drugs. CGS21680 (1–100 nM, A 2A R agonist) increased the decay slope in mesenteric veins, but not arteries. The effect was antagonized by an A 2A R antagonist ( SCH58261 400 nM), and a NET blocker (cocaine 10 μM). This effect was mimicked by adenylate cyclase activation (forkolin, 1μM), but not PKC activation (PDBu 100 nM, or PMA 100 nM). A PKA inhibitor, H‐89 (1 μM) blocked the CGS‐induced effect. In mesenteric veins from DOCA‐salt rats, forskolin but not CGS21680 increased the decay slope of NE current. These data indicate that A 2A R activation enhances NE transport into perivenous sympathetic nerves through activation of adenylate cyclase/cAMP/PKA pathway and A 2A R function is impaired in DOCA‐salt veins.