Purinergic 2X receptors play a role in evoking the exercise pressor reflex in rats with peripheral artery insufficiency

Purinergic 2X (P2X) receptors on the endings of thin fiber afferents have been shown to play a role in evoking the exercise pressor reflex in cats. In this study, we attempted to extend this finding to decerebrated, unanesthetized rats whose femoral arteries were either freely perfused or were ligated 72 h before the start of the experiment. We first established that our dose of pyridoxal phosphate-6-azophenyl-2', 4'-disulfonic acid (PPADS; 10 mg/kg), a P2X receptor antagonist, attenuated the pressor response to alpha,beta-methylene ATP (10 mu g/kg), a P2X receptor agonist. We then compared the exercise pressor reflex before and after infusing PPADS into the arterial supply of the hindlimb muscles that were statically contracted. In rats with freely perfused femoral arteries, the peak pressor responses to contraction were not significantly attenuated by PPADS (before PPADS: 19 +/- 2 mmHg, 13 min after PPADS: 17 +/- 2 mmHg, and 25 min after PPADS: 17 +/- 3 mmHg). Likewise, the cardioaccelerator and renal sympathetic nerve responses were not significantly attenuated. In contrast, we found that in rats whose femoral arteries were ligated PPADS significantly attenuated the peak pressor responses to contraction (before PPADS: 37 +/- 5 mmHg, 13 min after PPADS: 27 +/- 6 mmHg, and 25 min after PPADS: 25 +/- 5 mmHg; P < 0.05). Heart rate was not significantly attenuated, but renal SNA was at certain time points over the 30-s contraction period. We conclude that P2X receptors play a substantial role in evoking the exercise pressor reflex in rats whose femoral arteries were ligated but play only a minimal role in evoking the reflex in rats whose femoral arteries were freely perfused.