Abstract
The role of the ASIC1a in evoking the exercise pressor reflex in rats with simulated peripheral artery disease is unknown. This prompted us to determine whether ASIC1a plays a role in evoking the exaggerated exercise pressor reflex in decerebrated rats with simulated peripheral artery disease. To simulate peripheral artery disease, we ligated the left femoral artery 72 h before the experiment. The right femoral artery was freely perfused and used as a control. To test our hypothesis, we measured the effect of injecting two ASIC1a blockers into the arterial supply of the triceps surae muscles with and without the femoral artery ligated on the reflex pressor responses to 1) static contraction of the triceps surae muscles, 2) calcaneal tendon stretch, and 3) intra-arterial injection of diprotonated phosphate (pH 6.0). We found that the ASIC1a blockers psalmotoxin-1 (200 ng/kg) and mambalgin-1 (6.5 μg/kg) decreased the pressor responses to static contraction as well as the peak pressor responses to injection of diprotonated phosphate when these responses were evoked from the freely perfused hindlimb. In contrast, ASIC1a blockers only decreased the peak pressor responses evoked by injection of diprotonated phosphate in the hindlimb circulation with simulated peripheral artery disease. This inhibitory effect was less than the one measured from the healthy hindlimb. Independently of the hindlimb of interest, ASIC1a blockers had no effect on the pressor responses to tendon stretch. Our results do not support the hypothesis that ASIC1a play a role in evoking the exercise pressor reflex arising from a hindlimb with simulated peripheral artery disease.NEW & NOTEWORTHY The role of ASIC1a in evoking the metabolic component of the exercise pressor reflex in peripheral artery disease is unknown. Using a within-rat experimental design, we found that the contribution of ASIC1a decreased in a rat model of peripheral artery disease. These results have key implications to help finding better treatments and improve morbidity, quality of life, and mortality in patients with peripheral artery disease.