The exercise pressor reflex is inhibited by Brilliant Blue G in freely perfused and femoral artery ligated rats following intrathecal, but not hindlimb, treatment.

The exercise pressor reflex (EPR) is mediated in part by purinergic(P)2X receptors which are compromised of seven subtypes. Blockade of the P2X3 subtype on the peripheral endings of group III and IV muscle afferents attenuates the EPR. We investigated whether other P2X receptors were involved in the EPR arc in decerebrate Sprague Dawley rats whose femoral arteries were either patent or were ligated. We antagonized P2X receptors with Brilliant Blue G (BBG), which has highest affinity for P2X7 receptors. We injected BBG in both group of rats either intrathecally (50mg/mL; 25–50uL) or into the superficial epigastric artery, which is a side branch of the femoral artery. Intrathecal injection of BBG attenuated the magnitude of the EPR in both rats with patent femoral arteries and in rats with ligated femoral arteries (P<0.05). Intrathecal injection of BBG had no effect on the pressor response to intra‐carotid injection of sodium cyanide (2ug), which is a potent and selective stimulant to carotid chemoreceptors. This latter finding indicates that intrathecal injection of BBG did not ascend to the medulla and did not impact the spinal sympathetic outflow. BBG injected either into the superficial epigastric artery or intravenously (5mg) had no appreciable effect on the EPR. In addition the effect of intrathecal BBG could not be explained by “neural fatigue” caused by repetitive contractions in rats with ligated femoral arteries. We conclude that intrathecal BBG treatment inhibits the EPR by antagonizing P2X4 or P2X7 receptors within the dorsal horn of the spinal cord. Support or Funding Information This study was funded by NIH grants R01 AR 059397 and P01 HL 134609.