title: α1- and α2-adrenergic responsiveness in human skeletal muscle feed arteries: the role of TRPV ion channels in heat-induced sympatholysis.
abstract: The purpose of this study was to determine if heat inhibits α2-adrenergic vasocontraction, similarly to α1-adrenergic contraction, in isolated human skeletal muscle feed arteries (SMFA) and elucidate the role of the temperature-sensitive vanilloid-type transient receptor potential (TRPV) ion channels in this response. Isolated SMFA from 37 subjects were studied using wire myography. α1 [Phenylephrine (PE)]- and α2 [dexmedetomidine (DEX)]-contractions were induced at 37 and 39°C with and without TRPV family and TRPV4-specific inhibition [ruthenium red (RR) and RN-1734, respectively]. Endothelial function [acetylcholine (ACh)] and smooth muscle function [sodium nitroprusside (SNP) and potassium chloride (KCl)] were also assessed under these conditions. Heat and TRPV inhibition was further examined in endothelium-denuded arteries. Contraction data are reported as a percentage of maximal contraction elicited by 100 mM KCl (LTmax). DEX elicited a small and variable contractile response, one-fifth the magnitude of PE, which was not as clearly attenuated when heated from 37 to 39°C (12 ± 4 to 6 ± 2% LTmax; P = 0.18) as were PE-induced contractions (59 ± 5 to 24 ± 4% LTmax; P < 0.05). Both forms of TRPV inhibition restored PE-induced contraction at 39°C (P < 0.05) implicating these channels, particularly the TRPV4 channels, in the heat-induced attenuation of α1-adrenergic vasocontraction. TRPV inhibition significantly blunted ACh relaxation while denudation prevented heat-induced sympatholysis without having an additive effect when combined with TRPV inhibition. In conclusion, physiological increases in temperature elicit a sympatholysis-like inhibition of α1-adrenergic vasocontraction in human SMFA that appears to be mediated by endothelial TRPV4 ion channels.
authors.forename: Jayson R
authors.initials: JR
authors.lastname: Gifford
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Ives
authors.forename: Song-Young
authors.initials: SY
authors.lastname: Park
authors.forename: Robert H I
authors.initials: RH
authors.lastname: Andtbacka
authors.forename: John R
authors.initials: JR
authors.lastname: Hyngstrom
authors.forename: Michelle T
authors.initials: MT
authors.lastname: Mueller
authors.forename: Gerald S
authors.initials: GS
authors.lastname: Treiman
authors.forename: Christopher
authors.initials: C
authors.lastname: Ward
authors.forename: Joel D
authors.initials: JD
authors.lastname: Trinity
authors.forename: Russell S
authors.initials: RS
authors.lastname: Richardson
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D058646:Adrenergic alpha-1 Receptor Agonists / Q000494:pharmacology*; D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D001158:Arteries / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D020927:Dexmedetomidine / Q000494:pharmacology; D005260:Female; D006358:Hot Temperature; D006801:Humans; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000098:blood supply; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D012430:Ruthenium Red / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D013565:Sympatholytics / Q000494:pharmacology*; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014661:Vasoconstriction
chemical_list: D058646:Adrenergic alpha-1 Receptor Agonists; D058647:Adrenergic alpha-2 Receptor Agonists; C544743:RN 1734; D013449:Sulfonamides; D013565:Sympatholytics; D050916:TRPV Cation Channels; D012430:Ruthenium Red; D009599:Nitroprusside; D010656:Phenylephrine; D011189:Potassium Chloride; D020927:Dexmedetomidine; D000109:Acetylcholine