Blockade of acid sensing ion channels attenuates the exercise pressor reflex in cats.
Although thin fibre muscle afferents possess acid sensing ion channels (ASICs), their contribution to the exercise pressor reflex is not known. This lack of information is partly attributable to the fact that there is no known selective in vivo antagonist for ASICs. Although amiloride has been shown to antagonize ASICs, it also has been shown to antagonize voltage-gated sodium channels, thereby impairing impulse conduction in sensory nerves. Our aim was to test the hypothesis that lactic acid accumulation in exercising muscle acted on ASICs located on thin fibre muscle afferents to evoke the metabolic component of the exercise pressor reflex. To test this hypothesis, we determined in decerebrate cats if amiloride attenuated the pressor and cardioaccelerator responses to static contraction, to tendon stretch and to arterial injections of lactic acid and capsaicin. We found a dose of amiloride (0.5 microg kg(-1); i.a.) that attenuated the pressor and cardioaccelerator responses to both contraction and lactic acid injection, but had no effect on the responses to stretch and capsaicin. A higher dose of amiloride (5 microg kg(-1), i.a.) not only blocked the pressor and cardioaccelerator responses to lactic acid and contraction, but also attenuated the responses to stretch and to capsaicin, manoeuvers in which ASICs probably play no significant role. In addition, we found that the low dose of amiloride (0.5 microg kg(-1)) had no effect on the responses of muscle spindles to tendon stretch and to succinylcholine, whereas the high dose (5 microg kg(-1)) attenuated the responses to both. Our data suggest the low dose of amiloride used in our experiments selectively blocked ASICs, whereas the high dose blocked ASICs and impulse conduction in muscle afferents. We conclude that ASICs play a role in the metabolic component of the exercise pressor reflex.
Hayes
Shawn G
SG
Division of Cardiovascular Medicine, University of California, Davis 95616, USA. shayes1@hmc.psu.edu
Kindig
Angela E
AE
Kaufman
Marc P
MP
D062565:Acid Sensing Ion Channels; D000200:Action Potentials / Q000187:drug effects; D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology; D002415:Cats; D003655:Decerebrate State; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D019344:Lactic Acid / Q000378:metabolism* / Q000494:pharmacology; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009431:Neural Conduction / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects* / Q000378:metabolism; D005082:Physical Exertion / Q000502:physiology*; D012018:Reflex / Q000187:drug effects*; D012026:Reflex, Stretch / Q000187:drug effects; D015222:Sodium Channels / Q000378:metabolism
D062565:Acid Sensing Ion Channels; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D015222:Sodium Channels; D019344:Lactic Acid; D000584:Amiloride; D002211:Capsaicin