PMID- 15994853
OWN - NLM
STAT- MEDLINE
DCOM- 20051121
LR  - 20200930
IS  - 0363-6135 (Print)
IS  - 0363-6135 (Linking)
VI  - 289
IP  - 5
DP  - 2005 Nov
TI  - Na+-K+ pump activation inhibits endothelium-dependent relaxation by activating 
      the forward mode of Na+/Ca2+ exchanger in mouse aorta.
PG  - H2020-9
AB  - 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 [Ca2+]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 microM) and the NCX (forward and reverse mode) inhibitors 
      2'4'-dichlorobenzamil (>10 microM) or Ni2+ (>100 microM) inhibited K+-induced 
      inhibition of EDR and [Ca2+]i increase. KB-R7943 did not inhibit K+-induced 
      inhibition at up to 10 microM but did at 30 microM. In current-clamped MAECs, an 
      increase in [K+]o from 6 to 12 mM depolarized the membrane potential, which was 
      inhibited by ouabain, Ni2+, 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 microM), Ni2+ (300 microM), or KB-R7943 (30 
      microM). 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.
FAU - Kim, Moon Young
AU  - Kim MY
AD  - Dept. of Physiology, College of Medicine, Ewha Women's Univ., 911-1 Mok-6-dong, 
      Yang Chun-gu, Seoul, Republic of Korea 158-710.
FAU - Seol, Geun Hee
AU  - Seol GH
FAU - Liang, Guo Hua
AU  - Liang GH
FAU - Kim, Ji Aee
AU  - Kim JA
FAU - Suh, Suk Hyo
AU  - Suh SH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050701
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0 (2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate)
RN  - 0 (Ionophores)
RN  - 0 (Sodium-Calcium Exchanger)
RN  - 5ACL011P69 (Ouabain)
RN  - 63231-63-0 (RNA)
RN  - 7OV03QG267 (Nickel)
RN  - 906O0YJ6ZP (Monensin)
RN  - 9NEZ333N27 (Sodium)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 7.2.2.13 (Sodium-Potassium-Exchanging ATPase)
RN  - GYV9AM2QAG (Thiourea)
RN  - RWP5GA015D (Potassium)
SB  - IM
MH  - Animals
MH  - Aorta, Thoracic/metabolism/*physiology
MH  - Cyclic AMP/metabolism
MH  - Endothelium, Vascular/*physiology
MH  - Female
MH  - In Vitro Techniques
MH  - Ionophores/pharmacology
MH  - Male
MH  - Mice
MH  - Monensin/pharmacology
MH  - Muscle Relaxation/physiology
MH  - Muscle, Smooth, Vascular/*physiology
MH  - Nickel/pharmacology
MH  - Ouabain/pharmacology
MH  - Potassium/antagonists & inhibitors/pharmacology
MH  - RNA/biosynthesis
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sodium/physiology
MH  - Sodium-Calcium Exchanger/*metabolism
MH  - Sodium-Potassium-Exchanging ATPase/*metabolism
MH  - Thiourea/analogs & derivatives/pharmacology
EDAT- 2005/07/05 09:00
MHDA- 2005/12/13 09:00
CRDT- 2005/07/05 09:00
PHST- 2005/07/05 09:00 [pubmed]
PHST- 2005/12/13 09:00 [medline]
PHST- 2005/07/05 09:00 [entrez]
AID - 00908.2004 [pii]
AID - 10.1152/ajpheart.00908.2004 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2005 Nov;289(5):H2020-9. doi: 
      10.1152/ajpheart.00908.2004. Epub 2005 Jul 1.