Previously we showed that pressor and differential regional sympathoexcitatory responses (adrenal>renallumbar) evoked by stimulation of A₁ adenosine receptors located in the nucleus of the solitary tract (NTS) were attenuated/abolished by baroreceptor denervation or blockade of glutamatergic transmission in the NTS, suggesting A₁ receptor-elicited inhibition of glutamatergic transmission in baroreflex pathways. Therefore we tested the hypothesis that stimulation of NTS A₁ adenosine receptors differentially inhibits/resets baroreflex responses of preganglionic-adrenal (pre-ASNA), renal (RSNA) and lumbar (LSNA) sympathetic nerve activity. In urethane/chloralose anesthetized male Sprague Dawley rats (n=65) we compared baroreflex-response curves (i.v. nitroprusside/phenylephrine) evoked before and after bilateral microinjections into the NTS of A₁ adenosine receptor agonist (N⁶cyclopentyladenosine, CPA, 0.033 - 330 pmol/50 nl). CPA evoked typical dose dependent pressor and differential sympathoexcitatory responses and similarly shifted baroreflex curves for pre-ASNA, RSNA and LSNA toward higher mean arterial pressure (MAP) in dose dependent manner; the maximal shifts were: 52.6±2.8, 48.0±3.6, and 56.8±6.7 mmHg for pre-ASNA, RSNA and LSNA, respectively. These shifts were not a result of simple baroreceptor resetting as they were 2-3 times greater than respective increases in baseline MAP evoked by CPA. Baroreflex curves for pre-ASNA were additionally shifted upwards: the maximal increases of upper and lower plateaus were 41.8±16.4% and 45.3±8.7%, respectively. Maximal gain (%/mmHg) measured before vs. after CPA increased for pre-ASNA (3.0±0.6 vs. 4.9±1.3), decreased for RSNA (4.1±0.6 vs. 2.3±0.3) and remained unaltered for LSNA (2.1±0.2 vs. 2.0±0.1). Vehicle control did not alter the baroreflex curves. We conclude that the activation of NTS A₁ adenosine receptors differentially inhibits/resets baroreflex control of regional sympathetic outputs.