These studies tested the hypothesis that there is impaired function of 2 adrenergic autoreceptors and increased transmitter release from sympathetic nerves associated with mesenteric arteries and veins from DOCA-salt rats. High performance liquid chromatography was used to measure overflow of ATP and norepinephrine (NE) from electrically-stimulated mesenteric artery and vein preparations in vitro. In sham arteries, nerve stimulation evoked a 1.5 -fold increase in NE release while in DOCA-salt arteries there was a 3.9-fold increase in NE release over basal levels (P<0.05). In contrast, stimulated ATP release was not different in DOCA-salt arteries compared with sham arteries. In sham veins, nerve stimulation evoked a 2.9 -fold increase in NE release whereas in DOCA-salt veins there was a 8.4-fold increase in NE release over basal levels (P<0.05). In sham rats NE release, normalized to basal levels, was greater in veins than in arteries (P<0.05). The 2 adrenergic receptor antagonist yohimbine (1 µM) increased ATP and NE release in sham but not DOCA-salt arteries. The 2- adrenergic receptor agonist, UK 14,304 (10 µM), decreased ATP release in sham but not in DOCA-salt arteries. In sham veins, UK 14,304 decreased, but yohimbine increased NE release; effects that were not observed in DOCA-salt veins. These data show that nerve stimulation causes a greater increase in NE release from nerves associated with veins compared to arteries. In addition, impairment of 2 adrenergic autoreceptor function in sympathetic nerves associated with arteries and veins from DOCA-salt rats results in increased NE release.