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

Author:

Gifford Jayson R.12,Ives Stephen J.13,Park Song-Young12,Andtbacka Robert H. I.4,Hyngstrom John R.4,Mueller Michelle T.56,Treiman Gerald S.56,Ward Christopher56,Trinity Joel D.16,Richardson Russell S.126

Affiliation:

1. Geriatric Research, Education, and Clinical Center, Salt Lake City Veterans Affairs Medical Center, Salt Lake City, Utah;

2. Department of Exercise and Sport Science, University of Utah, Salt Lake City, Utah;

3. Department of Health and Exercise Sciences, Skidmore College, Saratoga Springs, New York;

4. Department of Surgery, Huntsman Cancer Hospital, University of Utah, Salt Lake City, Utah;

5. Division of Surgery, Salt Lake City Veterans Affairs Medical Center, Salt Lake City, Utah; and

6. Department of Internal Medicine, University of Utah, Salt Lake City, Utah

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.

Publisher

American Physiological Society

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine,Physiology

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