ASIC1a plays a key role in evoking the metabolic component of the exercise pressor reflex in rats

Abstract

The role of the acid‐sensing ion channel 1a (ASIC1a) in evoking the exercise pressor reflex is unknown despite the fact that ASIC1a is opened by decreases in pH in the physiological range. This fact prompted us to test the hypothesis that ASIC1a plays an important role in evoking the exercise pressor reflex in decerebrated rats with freely perfused hindlimb muscles. To test this hypothesis, we measured the effect of injecting two ASIC1a blockers into the arterial supply of the triceps surae muscles on the reflex pressor responses to four maneuvers, namely (1) static contraction of the triceps surae muscles (i.e., the exercise pressor reflex), (2) calcaneal tendon stretch, and (3) intra‐arterial injection of lactic acid and (4) diprotonated phosphate. We found that the two ASIC1a blockers, psalmotoxin‐1 (200 ng kg−1) and mambalgin‐1 (6.5 μg −1), decreased the pressor responses to static contraction as well as the peak pressor responses to injection of lactic acid and diprotonated phosphate. In contrast, neither ASIC1a blocker had any effect on the pressor responses to tendon stretch. Importantly, we found that ASIC1a blockade significantly decreased the pressor response to static contraction after a latency of at least 8 s. Our results support the hypothesis that ASIC1a plays a key role in evoking the metabolic component of the exercise pressor reflexSupport or Funding Information Funding for this study was provided by the National Institute of Arthritis and Muskuloskeletal and Skin Diseases (Grant R01‐AR‐059397) and National Heart, Lung, and Blood Institute (Grant P01‐HL‐134609).