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 language | English |
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Pages (from-to) | H2020-H2029 |
Journal | American Journal of Physiology - Heart and Circulatory Physiology |
Volume | 289 |
Issue number | 5 58-5 |
DOIs | |
Publication status | Published - 2005 Nov |
Externally published | Yes |
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)