KCa and KV channels modulate the venoarteriolar reflex in non-glabrous human skin with no roles of KATP channels, NOS, and COX

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

Research output: Contribution to journalArticle

Abstract

The venoarteriolar reflex is a local mechanism that induces vasoconstriction during venous congestion in various tissues, including skin. This response is thought to play a critical role in minimizing capillary damage or edema resulting from overperfusion, though factors that modulate this response remain largely unknown. Here, we hypothesized that nitric oxide synthase (NOS), cyclooxygenase (COX), and Ca2+-activated, ATP-sensitive, and voltage-gated K+ channels (KCa, KATP, and KV channels, respectively) modulate the venoarteriolar reflex in human skin. Cutaneous blood flow (laser-Doppler flowmetry) was monitored during a 3-min pre-occlusion baseline and following a 3-min venous occlusion of 45 mmHg, the latter maneuver was used to induce the venoarteriolar reflex. The venoarteriolar reflex was assessed at the following forearm skin sites: Experiment 1 (n = 11): 1) lactated Ringer solution (Control), 2) 10 mM Nω-nitro-L-arginine (NOS inhibitor), 3) 10 mM ketorolac (COX inhibitor), and 4) combined NOS + COX inhibition; Experiment 2 (n = 15): 1) lactated Ringer solution (Control), 2) 50 mM tetraethylammonium (KCa channel blocker), 3) 5 mM glybenclamide (KATP channel blocker), and 4) 10 mM 4-aminopyridine (KV channel blocker). Separate and combined NOS and COX inhibition as well as KATP channel blocker had no effect on venoarteriolar reflex. Conversely, venoarteriolar reflex was attenuated by KCa channel blockade (36–38%) and augmented by KV channel blockade (38–55%). We showed that KCa and KV channels modulate the venoarteriolar reflex with minimum roles of NOS, COX, and KATP channels in human non-glabrous forearm skin in vivo. Thus, cutaneous venoarteriolar reflex changes could reflect altered K+ channel function.

Original languageEnglish
Article number172828
JournalEuropean Journal of Pharmacology
Volume866
DOIs
Publication statusPublished - 5 Jan 2020

Fingerprint

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

Keywords

  • Dermatology
  • Endothelium
  • Heat loss responses
  • Hyperpolarization
  • Ligand-gated ion channels

Cite this

Fujii, Naoto ; McGarr, Gregory W. ; McNeely, Brendan D. ; Ichinose, Masashi ; Nishiyasu, Takeshi ; Kenny, Glen P. / KCa and KV channels modulate the venoarteriolar reflex in non-glabrous human skin with no roles of KATP channels, NOS, and COX. In: European Journal of Pharmacology. 2020 ; Vol. 866.
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KCa and KV channels modulate the venoarteriolar reflex in non-glabrous human skin with no roles of KATP channels, NOS, and COX. / Fujii, Naoto; McGarr, Gregory W.; McNeely, Brendan D.; Ichinose, Masashi; Nishiyasu, Takeshi; Kenny, Glen P.

In: European Journal of Pharmacology, Vol. 866, 172828, 05.01.2020.

Research output: Contribution to journalArticle

TY - JOUR

T1 - KCa and KV channels modulate the venoarteriolar reflex in non-glabrous human skin with no roles of KATP channels, NOS, and COX

AU - Fujii, Naoto

AU - McGarr, Gregory W.

AU - McNeely, Brendan D.

AU - Ichinose, Masashi

AU - Nishiyasu, Takeshi

AU - Kenny, Glen P.

PY - 2020/1/5

Y1 - 2020/1/5

N2 - The venoarteriolar reflex is a local mechanism that induces vasoconstriction during venous congestion in various tissues, including skin. This response is thought to play a critical role in minimizing capillary damage or edema resulting from overperfusion, though factors that modulate this response remain largely unknown. Here, we hypothesized that nitric oxide synthase (NOS), cyclooxygenase (COX), and Ca2+-activated, ATP-sensitive, and voltage-gated K+ channels (KCa, KATP, and KV channels, respectively) modulate the venoarteriolar reflex in human skin. Cutaneous blood flow (laser-Doppler flowmetry) was monitored during a 3-min pre-occlusion baseline and following a 3-min venous occlusion of 45 mmHg, the latter maneuver was used to induce the venoarteriolar reflex. The venoarteriolar reflex was assessed at the following forearm skin sites: Experiment 1 (n = 11): 1) lactated Ringer solution (Control), 2) 10 mM Nω-nitro-L-arginine (NOS inhibitor), 3) 10 mM ketorolac (COX inhibitor), and 4) combined NOS + COX inhibition; Experiment 2 (n = 15): 1) lactated Ringer solution (Control), 2) 50 mM tetraethylammonium (KCa channel blocker), 3) 5 mM glybenclamide (KATP channel blocker), and 4) 10 mM 4-aminopyridine (KV channel blocker). Separate and combined NOS and COX inhibition as well as KATP channel blocker had no effect on venoarteriolar reflex. Conversely, venoarteriolar reflex was attenuated by KCa channel blockade (36–38%) and augmented by KV channel blockade (38–55%). We showed that KCa and KV channels modulate the venoarteriolar reflex with minimum roles of NOS, COX, and KATP channels in human non-glabrous forearm skin in vivo. Thus, cutaneous venoarteriolar reflex changes could reflect altered K+ channel function.

AB - The venoarteriolar reflex is a local mechanism that induces vasoconstriction during venous congestion in various tissues, including skin. This response is thought to play a critical role in minimizing capillary damage or edema resulting from overperfusion, though factors that modulate this response remain largely unknown. Here, we hypothesized that nitric oxide synthase (NOS), cyclooxygenase (COX), and Ca2+-activated, ATP-sensitive, and voltage-gated K+ channels (KCa, KATP, and KV channels, respectively) modulate the venoarteriolar reflex in human skin. Cutaneous blood flow (laser-Doppler flowmetry) was monitored during a 3-min pre-occlusion baseline and following a 3-min venous occlusion of 45 mmHg, the latter maneuver was used to induce the venoarteriolar reflex. The venoarteriolar reflex was assessed at the following forearm skin sites: Experiment 1 (n = 11): 1) lactated Ringer solution (Control), 2) 10 mM Nω-nitro-L-arginine (NOS inhibitor), 3) 10 mM ketorolac (COX inhibitor), and 4) combined NOS + COX inhibition; Experiment 2 (n = 15): 1) lactated Ringer solution (Control), 2) 50 mM tetraethylammonium (KCa channel blocker), 3) 5 mM glybenclamide (KATP channel blocker), and 4) 10 mM 4-aminopyridine (KV channel blocker). Separate and combined NOS and COX inhibition as well as KATP channel blocker had no effect on venoarteriolar reflex. Conversely, venoarteriolar reflex was attenuated by KCa channel blockade (36–38%) and augmented by KV channel blockade (38–55%). We showed that KCa and KV channels modulate the venoarteriolar reflex with minimum roles of NOS, COX, and KATP channels in human non-glabrous forearm skin in vivo. Thus, cutaneous venoarteriolar reflex 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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U2 - 10.1016/j.ejphar.2019.172828

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JO - European Journal of Pharmacology

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