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.

Endothelium‐dependent vasodilatory signalling modulates α1‐adrenergic vasoconstriction in contracting skeletal muscle of humans

“…The results from this study, in conjunction with accumulating evidence in animal models (Kurjiaka & Segal, ; Gifford et al . ), points to a critical role for EDH, independent of NO, PGs, or K IR channels, in modulating sympathetic vasoconstriction during exercise.…”

Increased endothelial shear stress improves insulin‐stimulated vasodilatation in skeletal muscle

“…; Jendzjowsky & Delorey, ; Gifford et al . ; Mizuno et al . ), it is possible that in our study direct heating and/or increased shear stress‐induced NO produced local sympatholytic effects during insulin stimulation, i.e.…”

Endothelial TRPV4 channels modulate vascular tone by Ca2+‐induced Ca2+ release at inositol 1,4,5‐trisphosphate receptors

“…TRPV4 channels are emerging as key plasmalemmal channels that mediates Ca 2+ influx and physiological functions in the endothelium (Fiorio Pla et al, ; Gao & Wang, ; Gifford et al, ; Ma et al, ; Sayed et al, ; Schierling et al, ; Sonkusare et al, ; Thodeti et al, ; Troidl et al, ). We have shown that the Ca 2+ increase in endothelial cells, arising from Ca 2+ entry via TRPV4 channels, may be amplified by a Ca 2+ ‐induced Ca 2+ release‐like mechanism acting at IP 3 Rs to generate propagating Ca 2+ waves.…”