About 33% of American adults have hypertension. However, we can only identify and therefore target an underlying cause in 5 to 10% of cases. Although suboptimal blood pressure may be caused by many contributing factors, sympathetic nervous system activity is increased in human and animal models of hypertension. Norepinephrine and ATP are coreleased from sympathetic nerve endings onto arteries and veins, maintaining vascular tone and controlling blood pressure. Importantly, periarterial and perivenous nerves originate from different neurons in prevertebral ganglia, and these nerve fibers have neurochemical and anatomic differences. There are also differences in the adrenergic and purinergic receptor subtypes found on arterial and venous smooth muscle cells. Studies in our laboratory and others have shown that in animal models of hypertension, increased neurotransmitter release and increased sensitivity of smooth muscle cells in veins precede changes in arteries. In the present work, immunohistochemistry, contractility studies, and electrophysiologic techniques were used to study these differences between arteries and veins. To explore changes occurring at the neuroeffector junction in hypertension, we used the deoxycorticosterone acetate (DOCA)-salt model in rats. Mesenteric arteries and veins maintained in vitro were used. Perivascular nerves were stimulated electrically. These studies provide insight into (a) differential regulation of resistance arteries and capacitance veins, (b) the neurotransmitters involved in regulating vascular tone, and (c) alterations in the neuroeffector junction in salt-dependent hypertension. Data from frequency-response curves (0.2-30 Hz) confirmed that veins are more sensitive to nerve stimulation than arteries (p < .05), but there were no differences in responses between DOCA-salt and sham arteries or veins (n = 4-9, p > .05). Electophysiologic studies showed that the amplitude of excitatory junction potentials (EJPs) mediated by ATP were not different in sham and DOCA arterial smooth muscle cells. Clonidine (an α2-adrenergic receptor agonist that stimulates prejunctional autoreceptors) caused a concentration-dependent inhibition of EJPs in sham and DOCA-salt arteries, but EJPs in DOCA-salt arteries were less sensitive to inhibition by clonidine (p < .05). A better understanding of neurotransmitters released at the neuroeffector junction and changes that occur in a salt-dependent model of high blood pressure may provide novel pharmaceutical targets for hypertension in the future.