Na -K pump activation inhibits endothelium-dependent relaxation by activating the forward mode of Na /Ca exchanger in mouse aorta
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چکیده
Kim, Moon Young, Geun Hee Seol, Guo Hua Liang, Ji Aee Kim, and Suk Hyo Suh. Na -K pump activation inhibits endothelium-dependent relaxation by activating the forward mode of Na /Ca exchanger in mouse aorta. Am J Physiol Heart Circ Physiol 289: H2020–H2029, 2005. First published July 1, 2005; doi:10.1152/ajpheart.00908.2004.—The effect of Na -K pump activation on endothelium-dependent relaxation (EDR) and on intracellular Ca concentration ([Ca ]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 /Ca exchanger (NCX; reverse mode) inhibitor KB-R7943. Monensininduced Na loading or extracellular Na depletion (Na replaced by Li ) increased [Ca ]i in MAECs, and this increase was inhibited by KB-R7943. Na -K pump activation inhibited EDR and [Ca ]i increase (K -induced inhibition of EDR and [Ca ]i increase). The Na -K pump inhibitor ouabain inhibited K -induced inhibition of EDR. Monensin ( 0.1 M) and the NCX (forward and reverse mode) inhibitors 2 4 -dichlorobenzamil ( 10 M) or Ni ( 100 M) inhibited K -induced inhibition of EDR and [Ca ]i increase. KBR7943 did not inhibit K -induced inhibition at up to 10 M but did at 30 M. In current-clamped MAECs, an increase in [K ]o from 6 to 12 mM depolarized the membrane potential, which was inhibited by ouabain, Ni , 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 M), Ni (300 M), or KB-R7943 (30 M). These results suggest that activation of the forward mode of NCX after Na -K pump activation inhibits Ca mobilization in endothelial cells, thereby modulating vasomotor tone.
منابع مشابه
Na+-K+ pump activation inhibits endothelium-dependent relaxation by activating the forward mode of Na+/Ca2+ exchanger in mouse aorta.
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+/Ca...
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