Stimulation of NTS A_2a adenosine receptors elicits cardiovascular responses quite similar to those observed with rapid, severe hemorrhage including bradycardia, hypotension, inhibition of renal but activation of pre-ganglionic adrenal sympathetic nerve activity (RSNA and pre-ASNA, respectively). Since adenosine levels in the central nervous system increase during severe hemorrhage, we investigated to what extent these responses to hemorrhage may be due to activation of NTS adenosine receptors. In urethane/chloralose anesthetized male Sprague Dawley rats, rapid hemorrhage was performed before and following bilateral nonselective or selective blockade of NTS adenosine receptor subtypes (A₁ and A_2a adenosine receptor antagonist 8-(p-Sulfophenyl) theophylline; 1 nmol/100 nl and A_2a receptor antagonist, ZM 241385; 40 pmol/100 nl, respectively). The nonselective blockade reversed the response in RSNA (-21.0±9.6 % vs. +7.3±5.7 %) and attenuated the average heart rate (HR) response (-14.8±4.8 bpm vs. -4.4±3.4 bpm). The selective blockade attenuated the RSNA response (-30.4±5.2 % vs. -11.1±7.7 %) and tended to attenuate HR response (-27.5±5.3 bpm vs. -15.8±8.2 bpm). Microinjection of vehicle (100 nl ) had no significant effect on the responses. The hemorrhage-induced increases in pre-ASNA remained unchanged following either adenosine receptor antagonist. We conclude that adenosine operating in the NTS via A_2a and possibly A₁ receptors may contribute to post-hemorrhagic sympathoinhibition of RSNA but not to the sympathoactivation of pre-ASNA. The differential effects of NTS adenosine receptors on RSNA vs. pre-ASNA responses to hemorrhage supports the hypothesis that these receptors are differentially located/expressed on NTS neurons/synaptic terminals controlling different sympathetic outputs.