Increased sympathetic nervous system activity contributes to DOCA‐salt hypertension in rats. ATP and norepinephrine (NE) are released from sympathetic nerves. NE acts at prejunctional α2 adrenoceptors to inhibit NE release and prejunctional α2 adrenoceptor function is impaired in DOCA‐salt rats. Adenosine is a product of ATP hydrolysis and adenosine acts at prejunctional A1 adenosine receptors to inhibit NE release. We tested the hypothesis that prejunctional A1 receptor function is impaired in sympathetic nerves associated with mesenteric arteries (MA) and veins (MV) of DOCA‐salt rats. Electrically‐evoked NE release and constrictions of MA and MV were measured in vitro using amperometry and video microscopy, respectively. Adenosine and N6‐cyclopentyl‐adenosine (CPA, A1 receptor agonist) constricted MV but not MA. Adenosine and CPA caused concentration‐dependent (0.001‐10 μM) inhibition of MA constrictions. Adenosine and CPA concentration responses curves (CRCs) in DOCA‐salt MA were right shifted (P<0.05) compared to control MA. CPA inhibited NE release in MA and MV. The CPA CRC in DOCA‐salt MA, but not MV, was right shifted compared to control MA. These data indicate that there are prejunctional A1 receptors in MA and pre and postjunctional A1 receptors in MV. Prejunctional A1 receptor function is impaired in MA, but not MV, from DOCA‐salt rats. These data indicate that prejunctional α2 adrenoceptors are not selectively affected in DOCA‐salt hypertension. There is a more general disruption of prejunctional mechanisms controlling sympathetic neurotransmitter release.