Activation of P2x-purinoceptors in the nucleus tractus solitarius (NTS) via microinjection of alpha,beta-methylene ATP (alpha,beta-MeATP) elicits large dose-dependent decreases in mean arterial pressure (MAP) and heart rate (HR) and preferential dilation of the iliac vascular bed in comparison to renal and mesenteric vascular beds. We investigated whether sympathoinhibition contributes to the depressor responses and whether differential changes in regional sympathetic output occur. In 43 chloralose/urethane anesthetized male Sprague-Dawley rats, MAP, HR, renal (RSNA) and lumbar sympathetic nerve activity (LSNA) were recorded. Data were analyzed as both the maximum decrease and the integral of the decrease over the duration of the depressor response. Microinjection of alpha,beta-MeATP (25 and 100 pmol in 50 nl volume) into the subpostremal NTS caused significant and dose-dependent decreases in MAP, HR, RSNA and LSNA. However, the changes in RSNA were significantly greater than those observed in LSNA for both doses and both methods of analysis of data (maximum responses in delta %: 84 +/- 3 vs 62 +/- 4, and 93 +/- 3 vs 74 +/- 4 for low and high dose of alpha,beta-MeATP, respectively; integral responses in delta % x min: 32 +/- 4 vs 18 +/- 3 and 179 +/- 7 vs 134 +/- 14 for low and high dose of alpha,beta-MeATP, respectively). Blockade of P2-purinoceptors in the NTS by the specific P2-receptor antagonist suramin abolished responses to 100 pmol alpha,beta-MeATP and microinjections of vehicle did not alter neural nor hemodynamic parameters. We conclude that activation of P2x-purinoceptors in the NTS inhibits sympathetic nerve activity and evokes differential regional sympathetic responses. However, differential sympathoinhibition does not explain differential vascular responses to the activation of P2x-purinoceptors in the NTS.