Tetraethylammonium, glibenclamide, and 4-aminopyridine modulate post-occlusive reactive hyperemia in non-glabrous human skin with no roles of NOS and COX

Naoto Fujii, Gregory W. McGarr, Masashi Ichinose, Takeshi Nishiyasu, Glen P. Kenny

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Objectives: Post-occlusive reactive hyperemia (PORH) following arterial occlusion is widely used to assess cutaneous microvascular function, though the underlying mechanisms remain to be fully elucidated. We evaluated the hypothesis that Ca2+-activated, ATP-sensitive, and voltage-gated K+ channels (KC a, KATP, and KV channels, respectively) contribute to PORH while nitric oxide synthase (NOS) and cyclooxygenase (COX) do not. Methods: On separate occasions, cutaneous blood flow (laser Doppler flowmetry) was monitored before and following 5-min arterial occlusion at forearm skin sites treated via microdialysis with the following: Experiment 1 (n = 11): (a) lactated Ringer solution (Control), (b) 10 mM Nω-nitro-L-arginine (NOS inhibitor), (c) 10 mM ketorolac (COX inhibitor), and (d) combined NOS+COX inhibition; Experiment 2 (n = 14): (a) lactated Ringer solution (Control), (b) 50 mM tetraethylammonium (non-selective KC a channel blocker), (c) 5 mM glibenclamide (non-specific KATP channel blocker), and (d) 10 mM 4-aminopyridine (non-selective KV channel blocker). Results: Separate and combined NOS and COX inhibition did not influence PORH. Conversely, tetraethylammonium and glibenclamide attenuated, whereas 4-aminopyridine augmented PORH. Conclusions: We showed that tetraethylammonium, glibenclamide, and 4-aminopyridine modulate PORH with no roles of NOS and COX in human non-glabrous forearm skin in vivo. Thus, cutaneous PORH changes could reflect altered K+ channel function.

Original languageEnglish
Article numbere12586
JournalMicrocirculation
Volume27
Issue number1
DOIs
Publication statusPublished - 1 Jan 2020

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4-Aminopyridine
Tetraethylammonium
Glyburide
Hyperemia
Prostaglandin-Endoperoxide Synthases
Nitric Oxide Synthase
Skin
KATP Channels
Forearm
Ketorolac
Voltage-Gated Potassium Channels
Laser-Doppler Flowmetry
Cyclooxygenase Inhibitors
Microdialysis
Arginine
Adenosine Triphosphate

Keywords

  • dermatology
  • endothelium
  • heat loss responses
  • hyperpolarization
  • ligand-gated ion channels

Cite this

@article{265a0b6a155548a9a365bcc48362f7f9,
title = "Tetraethylammonium, glibenclamide, and 4-aminopyridine modulate post-occlusive reactive hyperemia in non-glabrous human skin with no roles of NOS and COX",
abstract = "Objectives: Post-occlusive reactive hyperemia (PORH) following arterial occlusion is widely used to assess cutaneous microvascular function, though the underlying mechanisms remain to be fully elucidated. We evaluated the hypothesis that Ca2+-activated, ATP-sensitive, and voltage-gated K+ channels (KC a, KATP, and KV channels, respectively) contribute to PORH while nitric oxide synthase (NOS) and cyclooxygenase (COX) do not. Methods: On separate occasions, cutaneous blood flow (laser Doppler flowmetry) was monitored before and following 5-min arterial occlusion at forearm skin sites treated via microdialysis with the following: Experiment 1 (n = 11): (a) lactated Ringer solution (Control), (b) 10 mM Nω-nitro-L-arginine (NOS inhibitor), (c) 10 mM ketorolac (COX inhibitor), and (d) combined NOS+COX inhibition; Experiment 2 (n = 14): (a) lactated Ringer solution (Control), (b) 50 mM tetraethylammonium (non-selective KC a channel blocker), (c) 5 mM glibenclamide (non-specific KATP channel blocker), and (d) 10 mM 4-aminopyridine (non-selective KV channel blocker). Results: Separate and combined NOS and COX inhibition did not influence PORH. Conversely, tetraethylammonium and glibenclamide attenuated, whereas 4-aminopyridine augmented PORH. Conclusions: We showed that tetraethylammonium, glibenclamide, and 4-aminopyridine modulate PORH with no roles of NOS and COX in human non-glabrous forearm skin in vivo. Thus, cutaneous PORH changes could reflect altered K+ channel function.",
keywords = "dermatology, endothelium, heat loss responses, hyperpolarization, ligand-gated ion channels",
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year = "2020",
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Tetraethylammonium, glibenclamide, and 4-aminopyridine modulate post-occlusive reactive hyperemia in non-glabrous human skin with no roles of NOS and COX. / Fujii, Naoto; McGarr, Gregory W.; Ichinose, Masashi; Nishiyasu, Takeshi; Kenny, Glen P.

In: Microcirculation, Vol. 27, No. 1, e12586, 01.01.2020.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Tetraethylammonium, glibenclamide, and 4-aminopyridine modulate post-occlusive reactive hyperemia in non-glabrous human skin with no roles of NOS and COX

AU - Fujii, Naoto

AU - McGarr, Gregory W.

AU - Ichinose, Masashi

AU - Nishiyasu, Takeshi

AU - Kenny, Glen P.

PY - 2020/1/1

Y1 - 2020/1/1

N2 - Objectives: Post-occlusive reactive hyperemia (PORH) following arterial occlusion is widely used to assess cutaneous microvascular function, though the underlying mechanisms remain to be fully elucidated. We evaluated the hypothesis that Ca2+-activated, ATP-sensitive, and voltage-gated K+ channels (KC a, KATP, and KV channels, respectively) contribute to PORH while nitric oxide synthase (NOS) and cyclooxygenase (COX) do not. Methods: On separate occasions, cutaneous blood flow (laser Doppler flowmetry) was monitored before and following 5-min arterial occlusion at forearm skin sites treated via microdialysis with the following: Experiment 1 (n = 11): (a) lactated Ringer solution (Control), (b) 10 mM Nω-nitro-L-arginine (NOS inhibitor), (c) 10 mM ketorolac (COX inhibitor), and (d) combined NOS+COX inhibition; Experiment 2 (n = 14): (a) lactated Ringer solution (Control), (b) 50 mM tetraethylammonium (non-selective KC a channel blocker), (c) 5 mM glibenclamide (non-specific KATP channel blocker), and (d) 10 mM 4-aminopyridine (non-selective KV channel blocker). Results: Separate and combined NOS and COX inhibition did not influence PORH. Conversely, tetraethylammonium and glibenclamide attenuated, whereas 4-aminopyridine augmented PORH. Conclusions: We showed that tetraethylammonium, glibenclamide, and 4-aminopyridine modulate PORH with no roles of NOS and COX in human non-glabrous forearm skin in vivo. Thus, cutaneous PORH changes could reflect altered K+ channel function.

AB - Objectives: Post-occlusive reactive hyperemia (PORH) following arterial occlusion is widely used to assess cutaneous microvascular function, though the underlying mechanisms remain to be fully elucidated. We evaluated the hypothesis that Ca2+-activated, ATP-sensitive, and voltage-gated K+ channels (KC a, KATP, and KV channels, respectively) contribute to PORH while nitric oxide synthase (NOS) and cyclooxygenase (COX) do not. Methods: On separate occasions, cutaneous blood flow (laser Doppler flowmetry) was monitored before and following 5-min arterial occlusion at forearm skin sites treated via microdialysis with the following: Experiment 1 (n = 11): (a) lactated Ringer solution (Control), (b) 10 mM Nω-nitro-L-arginine (NOS inhibitor), (c) 10 mM ketorolac (COX inhibitor), and (d) combined NOS+COX inhibition; Experiment 2 (n = 14): (a) lactated Ringer solution (Control), (b) 50 mM tetraethylammonium (non-selective KC a channel blocker), (c) 5 mM glibenclamide (non-specific KATP channel blocker), and (d) 10 mM 4-aminopyridine (non-selective KV channel blocker). Results: Separate and combined NOS and COX inhibition did not influence PORH. Conversely, tetraethylammonium and glibenclamide attenuated, whereas 4-aminopyridine augmented PORH. Conclusions: We showed that tetraethylammonium, glibenclamide, and 4-aminopyridine modulate PORH with no roles of NOS and COX in human non-glabrous forearm skin in vivo. Thus, cutaneous PORH changes could reflect altered K+ channel function.

KW - dermatology

KW - endothelium

KW - heat loss responses

KW - hyperpolarization

KW - ligand-gated ion channels

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