Activation of adenosine A_2a receptors in the NTS decreases mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) whereas increases in preganglionic adrenal sympathetic nerve activity (pre-ASNA)occur. A pattern similar to that observed during hypotensive hemorrhage. Central vasopressin V1 receptors may contribute to posthemorrhagic hypotension and bradycardia. Both V₁ and A_2a receptors are densely expressed in the NTS and both of these receptors are involved in cardiovascular control, thus they may interact. The responses elicited by NTS A_2a receptors are mediated mostly via nonglutamatergic mechanisms, possibly via release of vasopressin. Therefore we investigated if blockade of NTS V₁ receptors alters the autonomic response patterns evoked by stimulation of NTS A_2a receptors (CGS 21680, 20 pmol/50 nL) in chloralose/urethane anesthetized male Sprague-Dawley rats. In addition, we compared the regional sympathetic responses to microinjections of vasopressin (0.1-100 ng/50 nL) into the NTS. Blockade of V₁ receptors reversed the normal decreases in MAP into increases (-95.6±28.3 vs. 51.4±15.7 Integral%), virtually abolished the decreases in HR (-258.3±54.0 vs. 18.9±57.8 Integralbpm) and RSNA (-239.3±47.4 vs. 15.9±36.1 Integral%)and did not affect the increases in pre-ASNA (279.7±48.3 vs. 233.1±54.1 Integral%) evoked by A_2a receptor stimulation. The responses partially returned towards normal values approximately 90 min following the blockade. Microinjections of vasopressin into the NTS evoked dose dependent decreases in HR and RSNA and variable MAP and pre-ASNA responses with a tendency towards increases. We conclude that the decreases in MAP, HR and RSNA in response to NTS A_2a receptor stimulation may be mediated via release of vasopressin from neural terminals in the NTS. The differential effects of NTS V₁ and A_2a receptors on RSNA vs. pre-ASNA supports the hypothesis that these receptor subtypes are differentially located/expressed on NTS neurons/neural terminals controlling different sympathetic outputs.