PMID- 17116295
OWN - NLM
STAT- MEDLINE
DCOM- 20070614
LR  - 20171213
IS  - 0008-6363 (Print)
IS  - 0008-6363 (Linking)
VI  - 73
IP  - 3
DP  - 2007 Feb 1
TI  - A new ATP-sensitive potassium channel opener protects endothelial function in 
      cultured aortic endothelial cells.
PG  - 497-503
AB  - OBJECTIVE: Endothelial dysfunction is an early risk factor for cardiovascular 
      disease and hypertension. Mechanisms that participate in endothelial dysfunction 
      include reduced nitric oxide (NO) generation and increased endothelin-1 (ET-1) 
      generation. Endothelial ATP-sensitive potassium (K(ATP)) channels are responsible 
      for maintaining the resting potential of endothelial cells and modulating the 
      release of vasoactive compounds. We hypothesized that activation of endothelial 
      K(ATP) channels might result in the protection against endothelial dysfunction. 
      METHODS: Using cultured bovine or rat aortic endothelial cells, we examined the 
      effects of a new K(ATP) channels opener, iptakalim, on the secretion of 
      vasoactive substances. We also investigated its effects on the expression of 
      adhesion molecules in metabolically disturbed cultured endothelial cells. 
      RESULTS: In cultured aortic endothelial cells, iptakalim caused a 
      concentration-dependent inhibition of ET-1 release and synthesis that correlated 
      with reduced levels of mRNA for ET-1 and endothelin-converting enzyme. These 
      effects of iptakalim were significantly inhibited by pretreatment with 
      glibenclamide (a K(ATP) channel blocker) for 1 h. Similarly, iptakalim enhanced 
      the release of NO in a concentration-dependent manner and increased basal levels 
      of free intracellular calcium. Iptakalim at the concentrations of 100 and 1000 
      microM increased the activities of NO synthase (NOS) significantly. After the 
      activity of NOS was blocked by L-N(omega)-nitro-arginine methyl ester (L-NAME), 
      the inhibition of iptakalim on ET-1 release was abolished. In endothelial cell 
      models of metabolic disturbance induced by low-density lipoprotein, homocysteine, 
      or hyperglycemia, treatment with iptakalim could inhibit the overexpression of 
      monocyte chemoattractant protein-1 (MCP-1), Intercellular adhesive molecule-1 
      (ICAM-1), and vascular cell adhesive molecule-1 (VCAM-1) mRNA. CONCLUSION: 
      Iptakalim is a promising drug that could protect against endothelial dysfunction 
      through activating K(ATP) channels in endothelial cells.
FAU - Wang, Hai
AU  - Wang H
AD  - Department of Cardiovascular Pharmacology, Beijing Institute of Pharmacology and 
      Toxicology, Beijing 100850, China. wh9588@yahoo.com.cn
FAU - Long, Chaoliang
AU  - Long C
FAU - Duan, Zhibian
AU  - Duan Z
FAU - Shi, Cuige
AU  - Shi C
FAU - Jia, Guodong
AU  - Jia G
FAU - Zhang, Yingli
AU  - Zhang Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20061014
PL  - England
TA  - Cardiovasc Res
JT  - Cardiovascular research
JID - 0077427
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Endothelin-1)
RN  - 0 (N-(1-methylethyl)-1,1,2-trimethylpropylamine)
RN  - 0 (Potassium Channel Blockers)
RN  - 0 (Potassium Channels)
RN  - 0 (Propylamines)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - SX6K58TVWC (Glyburide)
RN  - SY7Q814VUP (Calcium)
RN  - V55S2QJN2X (NG-Nitroarginine Methyl Ester)
SB  - IM
CIN - Cardiovasc Res. 2007 Feb 1;73(3):448-9. PMID: 17188255
MH  - ATP-Binding Cassette Transporters/*pharmacology
MH  - Adenosine Triphosphate/*metabolism
MH  - Animals
MH  - Aorta
MH  - Calcium/analysis/metabolism
MH  - Cattle
MH  - Cells, Cultured
MH  - Chemokine CCL2/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Endothelial Cells/drug effects/metabolism
MH  - Endothelin-1/analysis/antagonists & inhibitors/metabolism
MH  - Endothelium, Vascular/*metabolism
MH  - Glyburide/pharmacology
MH  - Humans
MH  - Intercellular Adhesion Molecule-1/metabolism
MH  - Ion Channel Gating/*drug effects
MH  - NG-Nitroarginine Methyl Ester/pharmacology
MH  - Nitric Oxide/analysis/metabolism
MH  - Nitric Oxide Synthase/analysis/antagonists & inhibitors/metabolism
MH  - Potassium Channel Blockers/pharmacology
MH  - Potassium Channels/*drug effects
MH  - Propylamines/*pharmacology
MH  - Vascular Cell Adhesion Molecule-1/metabolism
EDAT- 2006/11/23 09:00
MHDA- 2007/06/15 09:00
CRDT- 2006/11/23 09:00
PHST- 2006/04/11 00:00 [received]
PHST- 2006/10/07 00:00 [revised]
PHST- 2006/10/09 00:00 [accepted]
PHST- 2006/11/23 09:00 [pubmed]
PHST- 2007/06/15 09:00 [medline]
PHST- 2006/11/23 09:00 [entrez]
AID - S0008-6363(06)00461-5 [pii]
AID - 10.1016/j.cardiores.2006.10.007 [doi]
PST - ppublish
SO  - Cardiovasc Res. 2007 Feb 1;73(3):497-503. doi: 10.1016/j.cardiores.2006.10.007. 
      Epub 2006 Oct 14.