Objectives: This review addresses the role of central purinergic receptors in the operation of the cardiovascular reflexes.Methods: Potential physiological role of purinergic receptors operating in the nucleus of the solitary tract (NTS) was assessed via comparison of the regional patterns of hemodynamic and sympathetic responses evoked by selective stimulation/inhibition of NTS purinergic receptor subtypes, with the patterns evoked by stimulation and unloading of arterial baroreceptors, and other known patterns of autonomic responses. The effects of sino-aortic denervation plus vagotomy and ionotropic glutamatergic blockade of NTS mechanisms on the patterns of the responses were also considered.Results: Selective stimulation of NTS A1 receptors with CPA evoked a pattern of regional autonomic responses consistent with inhibition of baroreflex mechanisms and facilitation/ disinhibition of chemoreflex mechanisms. Selective stimulation of NTS A2a receptors with CGS 21680-evoked pattern of the responses different than that evoked by stimulation of baroreflex afferents what remains in contrast to previous reports suggesting that NTS A2a receptors facilitate baroreflex transmission. The pattern of the responses was similar to that observed during hypotensive hemorrhage. Preferential, b -adrenergic iliac vasodilation evoked by stimulation of adenosine A2a receptors and preferential activation of sympathetic output to the adrenal medulla by both adenosine A1 and A2a receptors are consistent with contribution of these receptors to the defense response, stress and exercise. These observations support previous findings that NTS A1 receptors contribute to the hypothalamic defense response. The effects of stimulation and blockade of NTS P2x receptors with α, β-methylene ATP and suramin, respectively, suggested that neuronally-released ATP operating via P2x receptors may be a crucial co-transmitter with glutamate in mediating baroreflex responses.Discussion: The above observations strongly suggest that purinergic receptor subtypes operating in NTS circuitry are linked to specific afferent and descending mechanisms primarily integrated in the NTS.