Divergent roles of purinergic 2X receptors in the pressor response to treadmill exercise in male and female rats

Abstract

Our objective was to investigate the role played by ATP sensitive purinergic 2X (P2X) receptors in evoking the pressor response to treadmill running in male and female rats with and without simulated peripheral artery disease (PAD). We hypothesized that PPADS (P2X receptor antagonist, 10 mg i.v.), would reduce the pressor and end-exercise plasma norepinephrine (NE) response to four minutes of treadmill exercise (15 m×min−1; 1° incline) in male and female rats with a greater magnitude of effect in rats with simulated PAD compared to sham-operated rats. Methods: Ten rats had both femoral arteries ligated ~72 hours prior to experimental protocols. Fourteen rats had sham procedures performed in which the femoral arteries were exposed, and 5-0 suture was passed under the arteries but not tied. These groups are referred to as “ligated” and “sham”, respectively. In all rats, the right carotid artery was cannulated (PE-25) for blood pressure measurement and arterial blood samples and the right jugular vein was cannulated (PE-25) for administration of PPADS. After the rats recovered (~2 hrs), treadmill exercise was initiated (15 m·min−1, 1° incline) and the rat completed a four minute exercise bout. While the rat was still running, an arterial blood sample (~100 μl) was drawn for plasma NE assessment. Following a 20 minute rest, PPADS (10 mg, dissolved in 0.2 mL saline) was infused into the jugular vein over 10 min. After PPADS infusion, a second treadmill exercise bout and blood collection were performed as described for the control condition. The pressor and plasma NE responses to submaximal treadmill running before and after the injection of PPADS (10 mg) were compared. Data are expressed as mean ± SD. Statistical significance was defined as P≤0.05. Results: In male rats, PPADS significantly reduced the mean arterial pressure (MAP) response to exercise in both sham ( n=6, Peak ΔMAP control: 19±6; PPADS: 11±9 mmHg; P=0.033) and ligated rats ( n=4; control: 24±3 mmHg; PPADS: 16±6 mmHg; P=0.021) with a similar magnitude of effect observed between groups (p=0.544). In female rats, PPADS had no effect on the MAP response to exercise in either sham (n=6, 13±8; PPADS: 10±5 mmHg; P=0.171) or ligated (n=6, 17±5; PPADS: 18±6 mmHg; P=0.375) rats. When NE values were grouped by sex independent of ligation/sham status, PPADS significantly reduced end-exercise plasma NE concentration in both male (n=11, 200±131; PPADS: 139±61 pg/mL; P=0.016) and female (n=10, 199±133; PPADS: 140±101 pg/mL; P=0.027) rats. Conclusions: The data indicate that P2X receptors contribute to the sympathetic response to exercise in both male and female sham and ligated rats, but that sympathoexcitatory roles for P2X receptors translates into an obligatory role in the blood pressure response to treadmill exercise in male but not female rats. National Institutes of Health R01HL161160. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.