1. α1- and α2-Adrenergic responsiveness in human skeletal muscle feed arteries: the role of TRPV ion channels in heat-induced sympatholysis.
- Author
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Gifford, Jayson R., Ives, Stephen J., Park, Song-Young, Andtbacka, Robert H. I., Hyngstrom, John R., Mueller, Michelle T., Treiman, Gerald S., Ward, Christopher, Trinity, Joel D., and Richardson, Russell S.
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SKELETAL muscle ,ADRENERGIC mechanisms ,SMOOTH muscle ,SYMPATHOMIMETIC agents ,ENDOTHELIAL cells ,ION channels - Abstract
The purpose of this study was to determine if heat inhibits α
2 -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 PEinduced 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. [ABSTRACT FROM AUTHOR]- Published
- 2014
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