title: ASIC3 contributes to the blunted muscle metaboreflex in heart failure.
abstract: BACKGROUND
  During exercise, the sympathetic nervous system is activated and blood pressure and HR increase. In heart failure (HF), the muscle metaboreceptor contribution to sympathetic outflow is attenuated and the mechanoreceptor contribution is accentuated. Previous studies suggest that lactic acid stimulates acid-sensing channel subtype 3 (ASIC3), inducing a neurally mediated pressor response. Thus, we hypothesized that the pressor response to ASIC3 stimulation is smaller in HF rats because of attenuation in expression and function of ASIC3 in sensory nerves.
  
  
  METHODS
  Lactic acid was injected into the arterial blood supply of the hind limb to stimulate ASIC3 in muscle afferent nerves and evoke muscle metaboreceptor response in control rats and HF rats. In addition, western blot analysis was used to examine expression of ASIC3 in dorsal root ganglion (DRG) and patch clamp to examine current response with ASIC3 activation.
  
  
  RESULTS
  Lactic acid (4 μmol·kg) increased mean arterial pressure by 28 ± 5 mm Hg in controls (n = 6) but only by 16 ± 3 mm Hg (P < 0.05 vs control) in HF (n = 8). In addition, HF decreased the protein levels of ASIC3 in DRG (optical density, 1.03 ± 0.02 in control, vs 0.79 ± 0.03 in HF; P < 0.05; n = 6 in each group). The peak current amplitude of dorsal DRG neuron in response to ASIC3 stimulation is smaller in HF rats than that in control rats.
  
  
  CONCLUSIONS
  Compared with those in controls, cardiovascular responses to lactic acid administered into the hind limb muscles are blunted in HF rats owing to attenuated ASIC3. This suggests that ASIC3 plays a role in engagement in the attenuated metaboreceptor component of the exercise pressor reflex in HF.
authors.affiliation: 1Department of Emergency Medicine, The First Hospital of Jilin University, Norman Bethune College of Medicine, Jilin University, Changchun, CHINA; and 2Heart & Vascular Institute and Department of Medicine, Pennsylvania State University College of Medicine, Hershey, PA.
authors.forename: Jihong
authors.initials: J
authors.lastname: Xing
authors.forename: Jian
authors.initials: J
authors.lastname: Lu
authors.forename: Jianhua
authors.initials: J
authors.lastname: Li
mesh_terms: D062565:Acid Sensing Ion Channels / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure; D005727:Ganglia, Spinal / Q000378:metabolism; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology*; D006339:Heart Rate; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D008465:Mechanoreceptors / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D020932:Nerve Growth Factor / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000502:physiology*; D017207:Rats, Sprague-Dawley; D014463:Ultrasonography
chemical_list: C568269:ASIC3 protein, rat; D062565:Acid Sensing Ion Channels; D019344:Lactic Acid; D020932:Nerve Growth Factor