Sex differences in the purinergic 2 receptor mediated blood pressure response to treadmill exercise in rats with simulated peripheral artery disease.

We investigated the role played by ATP sensitive purinergic 2 (P2) receptors in evoking the pressor response to treadmill exercise in male and female rats with and without femoral arteries that were ligated for ~72 hours to induce simulated peripheral artery disease (PAD). We hypothesized that PPADS (P2 receptor antagonist, 10 mg i.v.) would reduce the pressor response to four minutes of treadmill exercise (15 m×min-1 , 1° incline) and steady-state exercise plasma norepinephrine (NE) values in male and female rats, and that the magnitude of effect of PPADS would be greater in rats with simulated PAD ("ligated") than in sham-operated rats. In males, PPADS significantly reduced the difference between steady-state exercise and baseline mean arterial pressure (ΔMAP) response to treadmill exercise in sham ( n =8, pre-PPADS: 12±2, post-PPADS: 1±5 mmHg; P=0.037) and ligated ( n =4; pre-PPADS: 20±2, post-PPADS: 11±3 mmHg; P=0.028) rats with a similar magnitude of effect observed between groups (P=0.720). In females, PPADS had no effect on the ∆MAP response to treadmill exercise in sham ( n =6, pre-PPADS: 9±2, post-PPADS: 7±2 mmHg; P=0.448) or ligated ( n =6, pre-PPADS: 15±2, post-PPADS: 16±3 mmHg; P=0.684) rats. When NE values were grouped by sex independent of ligation/sham status, PPADS significantly reduced plasma NE in male (P=0.016) and female (P=0.027) rats. The data indicate that P2 receptors contribute to the sympathetic response to exercise in both male and female rats, but that the sympathoexcitatory role for P2 receptors translates into an obligatory role in the blood pressure response to exercise in male but not female rats.