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This Article Full Text Full Text (PDF) All Versions of this Article: 295/4/H1720    most recent 00623.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Hayes, S. G. Articles by Kaufman, M. P. PubMed PubMed Citation Articles by Hayes, S. G. Articles by Kaufman, M. P.

Role played by acid-sensitive ion channels in evoking the exercise pressor reflex

¹Heart and Vascular Institute, Pennsylvania State College of Medicine, Hershey; and ²Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania; and ³Department of Chemistry, University of Utah, Salt Lake City, Utah

Submitted 13 June 2008 ; accepted in final form 18 August 2008

The exercise pressor reflex arises from contracting skeletal muscle and is believed to play a role in evoking the cardiovascular responses to static exercise, effects that include increases in arterial pressure and heart rate. This reflex is believed to be evoked by the metabolic and mechanical stimulation of thin fiber muscle afferents. Lactic acid is known to be an important metabolic stimulus evoking the reflex. Until recently, the only antagonist for acid-sensitive ion channels (ASICs), the receptors to lactic acid, was amiloride, a substance that is also a potent antagonist for both epithelial sodium channels as well as voltage-gated sodium channels. Recently, a second compound, A-317567, has been shown to be an effective and selective antagonist to ASICs in vitro. Consequently, we measured the pressor responses to the static contraction of the triceps surae muscles in decerebrate cats before and after a popliteal arterial injection of A-317567 (10 mM solution; 0.5 ml). We found that this ASIC antagonist significantly attenuated by half (P < 0.05) the pressor responses to both contraction and to lactic acid injection into the popliteal artery. In contrast, A-317567 had no effect on the pressor responses to tendon stretch, a pure mechanical stimulus, and to a popliteal arterial injection of capsaicin, which stimulated transient receptor potential vanilloid type 1 channels. We conclude that ASICs on thin fiber muscle afferents play a substantial role in evoking the metabolic component of the exercise pressor reflex.

groups III and IV muscle afferents; cats; neural control of the circulation; lactic acid; mechanogated channels; transient receptor potential vanilloid type 1 channels