α1- and α2-Adrenergic responsiveness in human skeletal muscle feed arteries: The role of TRPV ion channels in heat-induced sympatholysis

Jayson R. Gifford, Stephen J. Ives, Song Young Park, Robert H.I. Andtbacka, John R. Hyngstrom, Michelle T. Mueller, Gerald S. Treiman, Christopher Ward, Joel D. Trinity, Russell S. Richardson

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)H1288-H1297
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume307
Issue number9
DOIs
StatePublished - Nov 1 2014
Externally publishedYes

Keywords

  • Alpha adrenergic
  • Feed arteries
  • Heat
  • Sympatholysis
  • TRPV ion channels

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Fingerprint

Dive into the research topics of 'α<sub>1</sub>- and α<sub>2</sub>-Adrenergic responsiveness in human skeletal muscle feed arteries: The role of TRPV ion channels in heat-induced sympatholysis'. Together they form a unique fingerprint.

Cite this