title: Transient receptor potential A1 channel contributes to activation of the muscle reflex.
abstract: This study was undertaken to elucidate the role played by transient receptor potential A1 channels (TRPA1) in activating the muscle reflex, a sympathoexcitatory drive originating in contracting muscle. First, we tested the hypothesis that stimulation of the TRPA1 located on muscle afferents reflexly increases sympathetic nerve activity. In decerebrate rats, allyl isothiocyanate, a TRPA1 agonist, was injected intra-arterially into the hindlimb muscle circulation. This led to a 33% increase in renal sympathetic nerve activity (RSNA). The effect of allyl isothiocyanate was a reflex because the response was prevented by sectioning the sciatic nerve. Second, we tested the hypothesis that blockade of TRPA1 reduces RSNA response to contraction. Thirty-second continuous static contraction of the hindlimb muscles, induced by electrical stimulation of the peripheral cut ends of L(4) and L(5) ventral roots, increased RSNA and blood pressure. The integrated RSNA during contraction was reduced by HC-030031, a TRPA1 antagonist, injected intra-arterially (163 ± 24 vs. 95 ± 21 arbitrary units, before vs. after HC-030031, P < 0.05). Third, we attempted to identify potential endogenous stimulants of TRPA1, responsible for activating the muscle reflex. Increases in RSNA in response to injection into the muscle circulation of arachidonic acid, bradykinin, and diprotonated phosphate, which are metabolic by-products of contraction and stimulants of muscle afferents during contraction, were reduced by HC-030031. These observations suggest that the TRPA1 located on muscle afferents is part of the muscle reflex and further support the notion that arachidonic acid metabolites, bradykinin, and diprotonated phosphate are candidates for endogenous agonists of TRPA1.
authors.affiliation: Penn State Heart and Vascular Institute, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA. skoba@med.tottori-u.ac.jp
authors.forename: Satoshi
authors.initials: S
authors.lastname: Koba
authors.forename: Shawn G
authors.initials: SG
authors.lastname: Hayes
authors.forename: Lawrence I
authors.initials: LI
authors.lastname: Sinoway
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D017487:Ankyrins / Q000502:physiology*; D015220:Calcium Channels / Q000502:physiology*; D006614:Hindlimb / Q000187:drug effects / Q000502:physiology; D017879:Isothiocyanates / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels
chemical_list: D017487:Ankyrins; D015220:Calcium Channels; D017879:Isothiocyanates; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; C480976:Trpa1 protein, rat; C037152:isothiocyanic acid