Na+-K+ pump activation inhibits endothelium-dependent relaxation by activating the forward mode of Na+/Ca2+ exchanger in mouse aorta

Moon Young Kim, Geun Hee Seol, Guo Hua Liang, Ji Aee Kim, Suk Hyo Suh

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15 Citations (Scopus)

Abstract

The effect of Na+-K+ pump activation on endothelium-dependent relaxation (EDR) and on intracellular Ca2+ concentration ([Ca2+]i) was examined in mouse aorta and mouse aortic endothelial cells (MAECs). The Na+-K+ pump was activated by increasing extracellular K+ concentration ([K +]o) from 6 to 12 mM. In aortic rings, the Na+ ionophore monensin evoked EDR, and this EDR was inhibited by the Na +/Ca2+ exchanger (NCX; reverse mode) inhibitor KB-R7943. Monensin-induced Na+ loading or extracellular Na+ depletion (Na+ replaced by Li+) increased [Ca 2+]i in MAECs, and this increase was inhibited by KB-R7943. Na+-K+ pump activation inhibited EDR and [Ca2+]i increase (K+-induced inhibition of EDR and [Ca2+]i increase). The Na+-K+ pump inhibitor ouabain inhibited K+-induced inhibition of EDR. Monensin (>0.1 μM) and the NCX (forward and reverse mode) inhibitors 2′4′-dichlorobenzamil (> 10 μM) or Ni2+ (>100 μM) inhibited K+-induced inhibition of EDR and [Ca 2+]i increase. KB-R7943 did not inhibit K +-induced inhibition at up to 10 μM but did at 30 μM. In current-clamped MAECs, an increase in [K+]o from 6 to 12 mM depolarized the membrane potential, which was inhibited by ouabain, Ni 2+, or KB-R7943. In aortic rings, the concentration of cGMP was significantly increased by acetylcholine and decreased on increasing [K +]o from 6 to 12 mM. This decrease in cGMP was significantly inhibited by pretreating with ouabain (100 μM), Ni2+ (300 μM), or KB-R7943 (30 μM). These results suggest that activation of the forward mode of NCX after Na+-K+ pump activation inhibits Ca2+ mobilization in endothelial cells, thereby modulating vasomotor tone.

Original languageEnglish
Pages (from-to)H2020-H2029
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume289
Issue number5 58-5
DOIs
Publication statusPublished - 2005 Nov
Externally publishedYes

Keywords

  • Endothelial cells
  • Extracellular potassium
  • Forward mode of sodium/calcium exchanger
  • Intracellular calcium
  • Sodium-potassium pump

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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