KCa and KV channels modulate the venoarteriolar reflex in non-glabrous human skin with no roles of KATP channels, NOS, and COX
Copyright © 2019 Elsevier B.V. All rights reserved..
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.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2020 |
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Erschienen: |
2020 |
Enthalten in: |
Zur Gesamtaufnahme - volume:866 |
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Enthalten in: |
European journal of pharmacology - 866(2020) vom: 05. Jan., Seite 172828 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Fujii, Naoto [VerfasserIn] |
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Links: |
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Anmerkungen: |
Date Completed 02.06.2020 Date Revised 02.06.2020 published: Print-Electronic Citation Status MEDLINE |
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doi: |
10.1016/j.ejphar.2019.172828 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM303926546 |
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100 | 1 | |a Fujii, Naoto |e verfasserin |4 aut | |
245 | 1 | 0 | |a KCa and KV channels modulate the venoarteriolar reflex in non-glabrous human skin with no roles of KATP channels, NOS, and COX |
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500 | |a published: Print-Electronic | ||
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520 | |a Copyright © 2019 Elsevier B.V. All rights reserved. | ||
520 | |a 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 | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Dermatology | |
650 | 4 | |a Endothelium | |
650 | 4 | |a Heat loss responses | |
650 | 4 | |a Hyperpolarization | |
650 | 4 | |a Ligand-gated ion channels | |
650 | 7 | |a KATP Channels |2 NLM | |
650 | 7 | |a Potassium Channels, Calcium-Activated |2 NLM | |
650 | 7 | |a Potassium Channels, Voltage-Gated |2 NLM | |
650 | 7 | |a Nitric Oxide Synthase |2 NLM | |
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650 | 7 | |a Prostaglandin-Endoperoxide Synthases |2 NLM | |
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700 | 1 | |a McNeely, Brendan D |e verfasserin |4 aut | |
700 | 1 | |a Ichinose, Masashi |e verfasserin |4 aut | |
700 | 1 | |a Nishiyasu, Takeshi |e verfasserin |4 aut | |
700 | 1 | |a Kenny, Glen P |e verfasserin |4 aut | |
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