Inhibition of endothelium-dependent vasorelaxation by extracellular K +

A novel controlling signal for vascular contractility

Geun Hee Seol, Seung Cheol Ahn, Ji Aee Kim, Bernd Nilius, Suk Hyo Suh

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The effects of extracellular K+ on endothelium-dependent relaxation (EDR) and on intracellular Ca2+ concentration ([Ca 2+]i) were examined in mouse aorta, mouse aorta endothelial cells (MAEC), and human umbilical vein endothelial cells (HUVEC). In mouse aortic rings precontracted with prostaglandin F or norepinephrine, an increase in extracellular K+ concentration ([K+]o) from 6 to 12 mM inhibited EDR concentration dependently. In endothelial cells, an increase in [K+]o inhibited the agonist-induced [Ca2+]i increase concentration dependently. Similar to K+, Cs+ also inhibited EDR and the increase in [Ca2+]i concentration dependently. In current-clamped HUVEC, increasing [K+]o from 6 to 12 mM depolarized membrane potential from -32.8 ± 2.7 to -8.6 ± 4.9 mV (n = 8). In voltage-clamped HUVEC, depolarizing the holding potential from -50 to -25 mV decreased [Ca2+]i significantly from 0.95 ± 0.03 to 0.88 ± 0.03 μM (n = 11, P < 0.01) and further decreased [Ca2+]i, to 0.47 ± 0.04 μM by depolarizing the holding potential from -25 to 0 mV (n = 11, P < 0.001). Tetraethylammonium (1 mM) inhibited EDR and the ATP-induced [Ca2+]i increase in voltage-clamped MAEC. The intermediate-conductance Ca2+-activated K+ channel openers 1-ethyl-2-benzimidazolinone, chlorozoxazone, and zoxazolamine reversed the K+-induced inhibition of EDR and increase in [Ca 2+]i. The K+-induced inhibition of EDR and increase in [Ca2+]i was abolished by the Na +-K+ pump inhibitor ouabain (10 μM). These results indicate that an increase of [K+]o in the physiological range (6-12 mM) inhibits [Ca2+]i increase in endothelial cells and diminishes EDR by depolarizing the membrane potential, decreasing K+ efflux, and activating the Na+-K+ pump, thereby modulating the release of endothelium-derived vasoactive factors from endothelial cells and vasomotor tone.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume286
Issue number1 55-1
Publication statusPublished - 2004 Jan 1
Externally publishedYes

Fingerprint

Vasodilation
Endothelium
Blood Vessels
Endothelial Cells
Human Umbilical Vein Endothelial Cells
Aorta
Membrane Potentials
Zoxazolamine
Calcium-Activated Potassium Channels
Tetraethylammonium
Dinoprost
Ouabain
Norepinephrine
Adenosine Triphosphate

Keywords

  • Endothelial cell
  • Intracellular calcium

ASJC Scopus subject areas

  • Physiology

Cite this

Inhibition of endothelium-dependent vasorelaxation by extracellular K + : A novel controlling signal for vascular contractility. / Seol, Geun Hee; Ahn, Seung Cheol; Kim, Ji Aee; Nilius, Bernd; Suh, Suk Hyo.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 286, No. 1 55-1, 01.01.2004.

Research output: Contribution to journalArticle

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AU - Seol, Geun Hee

AU - Ahn, Seung Cheol

AU - Kim, Ji Aee

AU - Nilius, Bernd

AU - Suh, Suk Hyo

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N2 - The effects of extracellular K+ on endothelium-dependent relaxation (EDR) and on intracellular Ca2+ concentration ([Ca 2+]i) were examined in mouse aorta, mouse aorta endothelial cells (MAEC), and human umbilical vein endothelial cells (HUVEC). In mouse aortic rings precontracted with prostaglandin F2α or norepinephrine, an increase in extracellular K+ concentration ([K+]o) from 6 to 12 mM inhibited EDR concentration dependently. In endothelial cells, an increase in [K+]o inhibited the agonist-induced [Ca2+]i increase concentration dependently. Similar to K+, Cs+ also inhibited EDR and the increase in [Ca2+]i concentration dependently. In current-clamped HUVEC, increasing [K+]o from 6 to 12 mM depolarized membrane potential from -32.8 ± 2.7 to -8.6 ± 4.9 mV (n = 8). In voltage-clamped HUVEC, depolarizing the holding potential from -50 to -25 mV decreased [Ca2+]i significantly from 0.95 ± 0.03 to 0.88 ± 0.03 μM (n = 11, P < 0.01) and further decreased [Ca2+]i, to 0.47 ± 0.04 μM by depolarizing the holding potential from -25 to 0 mV (n = 11, P < 0.001). Tetraethylammonium (1 mM) inhibited EDR and the ATP-induced [Ca2+]i increase in voltage-clamped MAEC. The intermediate-conductance Ca2+-activated K+ channel openers 1-ethyl-2-benzimidazolinone, chlorozoxazone, and zoxazolamine reversed the K+-induced inhibition of EDR and increase in [Ca 2+]i. The K+-induced inhibition of EDR and increase in [Ca2+]i was abolished by the Na +-K+ pump inhibitor ouabain (10 μM). These results indicate that an increase of [K+]o in the physiological range (6-12 mM) inhibits [Ca2+]i increase in endothelial cells and diminishes EDR by depolarizing the membrane potential, decreasing K+ efflux, and activating the Na+-K+ pump, thereby modulating the release of endothelium-derived vasoactive factors from endothelial cells and vasomotor tone.

AB - The effects of extracellular K+ on endothelium-dependent relaxation (EDR) and on intracellular Ca2+ concentration ([Ca 2+]i) were examined in mouse aorta, mouse aorta endothelial cells (MAEC), and human umbilical vein endothelial cells (HUVEC). In mouse aortic rings precontracted with prostaglandin F2α or norepinephrine, an increase in extracellular K+ concentration ([K+]o) from 6 to 12 mM inhibited EDR concentration dependently. In endothelial cells, an increase in [K+]o inhibited the agonist-induced [Ca2+]i increase concentration dependently. Similar to K+, Cs+ also inhibited EDR and the increase in [Ca2+]i concentration dependently. In current-clamped HUVEC, increasing [K+]o from 6 to 12 mM depolarized membrane potential from -32.8 ± 2.7 to -8.6 ± 4.9 mV (n = 8). In voltage-clamped HUVEC, depolarizing the holding potential from -50 to -25 mV decreased [Ca2+]i significantly from 0.95 ± 0.03 to 0.88 ± 0.03 μM (n = 11, P < 0.01) and further decreased [Ca2+]i, to 0.47 ± 0.04 μM by depolarizing the holding potential from -25 to 0 mV (n = 11, P < 0.001). Tetraethylammonium (1 mM) inhibited EDR and the ATP-induced [Ca2+]i increase in voltage-clamped MAEC. The intermediate-conductance Ca2+-activated K+ channel openers 1-ethyl-2-benzimidazolinone, chlorozoxazone, and zoxazolamine reversed the K+-induced inhibition of EDR and increase in [Ca 2+]i. The K+-induced inhibition of EDR and increase in [Ca2+]i was abolished by the Na +-K+ pump inhibitor ouabain (10 μM). These results indicate that an increase of [K+]o in the physiological range (6-12 mM) inhibits [Ca2+]i increase in endothelial cells and diminishes EDR by depolarizing the membrane potential, decreasing K+ efflux, and activating the Na+-K+ pump, thereby modulating the release of endothelium-derived vasoactive factors from endothelial cells and vasomotor tone.

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