Effect of knock out of ASIC3 on cardiovascular reflexes arising from hindlimb muscle in ligated rats

Abstract

The exercise pressor reflex (EPR) arises from contracting the skeletal muscle and is manifested by increases in arterial pressure, heart rate and blood flow to working muscles. Group III and IV afferents comprise the sensory arm of the exercise pressor reflex. The exercise pressor reflex is exaggerated in patients with peripheral artery disease, which is an atherosclerotic process that occludes blood flow to working muscles. The exaggeration of the exercise pressor reflex is believed to be caused by a metabolite whose concentration is increased when the working muscles are inadequately perfused. Previous work has shown that pharmacological blockade of acid‐sensing ion channel 3, which is found on the endings of group III and IV afferents, prevents the exaggeration of the exercise pressor reflex in rats with simulated peripheral artery disease. In the present experiments, we compared the magnitude of the exercise pressor reflex in decerebrated rats with a functional knockout of the ASIC3 (KO) with the magnitude of the reflex in their decerebrated wild type counterparts (WT). We found that the exercise pressor reflex in ASIC3 KO rats was significantly smaller than the exercise pressor reflex in their WT counterparts (p<0.05). In addition, ASIC 3 KO rats demonstrated significantly smaller pressor responses to injection of diprotonated phosphate (86mM; pH 6.0), lactic acid (12mM; pH 2.85), and capsaicin (0.2μg; pH 7.2) into the arterial supply of the hindlimb (p< 0.05). In contrast, both ligated WT and ASIC3 KO rats displayed similar pressor responses to calcaneal tendon stretch (p>0.05). We conclude that ASIC3 plays an important role in evoking the exaggerated exercise pressor reflex seen in rats with peripheral artery disease.Support or Funding InformationNIH Grants R01‐AR‐059397 and P01‐HL‐134609