Static contraction of skeletal muscle evokes increases in BP and HR. Previous studies suggest that the dorsal horn of the spinal cord is the first synaptic site responsible for those cardiovascular responses. In this study, we examined the role of ATP sensitive-P2X receptors in the cardiovascular responses to contraction by microdialyzing the P2X receptor antagonist pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS) into the L7 level of the dorsal horn of eight anesthetized cats. Contraction was elicited by electrical stimulation of the L7 and S1 ventral roots. Blockade of P2X receptor attenuated the contraction induced-pressor response (MAP = 16 ± 4 mmHg after 10 mM of PPADS vs. 42 ± 8 mmHg in controls, P<0.05). Additionally, the pressor response to muscle stretch was also blunted by PPADS (MAP = 27 ± 5 mmHg after PPADS vs. 49 ± 8 mmHg in controls, P<0.05). Finally, activation of P2X receptor by microdialyzing 0.5 mM of ,-methylene into the dorsal horn significantly augmented the pressor response to contraction. This effect was antagonized by prior PPADS dialysis. These data demonstrate that blockade of P2X receptors in the dorsal horn attenuates the pressor response to activation of muscle afferents and that stimulation of P2X receptors enhance the reflex response, indicating that P2X receptors play a role in mediating the muscle pressor reflex at the first synaptic site of this reflex.