title: Blockade of acid sensing ion channels attenuates the augmented exercise pressor reflex in rats with chronic femoral artery occlusion.
abstract: We found previously that static contraction of the hindlimb muscles of rats whose femoral artery was ligated evoked a larger reflex pressor response (i.e. exercise pressor reflex) than did static contraction of the contralateral hindlimb muscles which were freely perfused. Ligating a femoral artery in rats results in blood flow patterns to the muscles that are remarkably similar to those displayed by humans with peripheral artery disease. Using decerebrated rats, we tested the hypothesis that the augmented exercise pressor reflex in rats with a ligated femoral artery is attenuated by blockade of the acid sensing ion channel (ASIC) 3. We found that femoral arterial injection of either amiloride (5 and 50 μg kg(-1)) or APETx2 (100 μg kg(-1)) markedly attenuated the reflex in rats with a ligated femoral artery. In contrast, these ASIC antagonists had only modest effects on the reflex in rats with freely perfused hindlimbs. Tests of specificity of the two antagonists revealed that the low dose of amiloride and APETx2 greatly attenuated the pressor response to lactic acid, an ASIC agonist, but did not attenuate the pressor response to capsaicin, a TRPV1 agonist. In contrast, the high dose of amiloride attenuated the pressor responses to lactic acid, but also attenuated the pressor response to capsaicin. We conclude that ASIC3 on thin fibre muscle afferents plays an important role in evoking the exercise pressor reflex in rats with a compromised arterial blood supply to the working muscles.
authors: Penn State Heart and Vascular Institute, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
authors: Hirotsugu
authors: H
authors: Tsuchimochi
authors: Katsuya
authors: K
authors: Yamauchi
authors: Jennifer L
authors: JL
authors: McCord
authors: Marc P
authors: MP
authors: Kaufman
mesh_terms: D062565:Acid Sensing Ion Channels; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology; D003064:Cnidarian Venoms / Q000494:pharmacology; D005263:Femoral Artery / Q000503:physiopathology / Q000601:surgery; D006339:Heart Rate / Q000187:drug effects; D006614:Hindlimb; D019344:Lactic Acid / Q000494:pharmacology; D008026:Ligation; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D018482:Muscle, Skeletal / Q000098:blood supply / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018689:Sensory System Agents / Q000494:pharmacology; D062687:Sodium Channel Agonists; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000502:physiology*
chemical_list: C501880:APETx2 protein, Anthopleura elegantissima; C568269:ASIC3 protein, rat; D062565:Acid Sensing Ion Channels; D003064:Cnidarian Venoms; D009419:Nerve Tissue Proteins; D018689:Sensory System Agents; D062687:Sodium Channel Agonists; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D019344:Lactic Acid; D000584:Amiloride; D002211:Capsaicin