title: Calcium-activated potassium channels - a therapeutic target for modulating nitric oxide in cardiovascular disease?
abstract: BACKGROUND
  Cardiovascular risk factors are often associated with endothelial dysfunction, which is also prognostic for occurrence of cardiovascular events. Endothelial dysfunction is reflected by blunted vasodilatation and reduced nitric oxide (NO) bioavailability. Endothelium-dependent vasodilatation is mediated by NO, prostacyclin, and an endothelium-derived hyperpolarising factor (EDHF), and involves small (SK) and intermediate (IK) conductance Ca(2+)-activated K(+) channels. Therefore, SK and IK channels may be drug targets for the treatment of endothelial dysfunction in cardiovascular disease.
  
  
  METHODS
  SK and IK channels are involved in EDHF-type vasodilatation, but recent studies suggest that these channels are also involved in the regulation of NO bioavailability. Here we review how SK and IK channels may regulate NO bioavailability.
  
  
  RESULTS
  Opening of SK and IK channels is associated with EDHF-type vasodilatation, but, through increased endothelial cell Ca(2+) influx, L-arginine uptake, and decreased ROS production, it may also lead to increased NO bioavailability and endothelium-dependent vasodilatation.
  
  
  CONCLUSIONS
  Opening of SK and IK channels can increase both EDHF and NO-mediated vasodilatation. Therefore, openers of SK and IK channels may have the potential of improving endothelial cell function in cardiovascular disease.
authors.affiliation: Department of Pharmacology, Aarhus University, DK-8000 Aarhus C, Denmark. thomas.dalsgaard@farm.au.dk
authors.forename: Thomas
authors.initials: T
authors.lastname: Dalsgaard
authors.forename: Christel
authors.initials: C
authors.lastname: Kroigaard
authors.forename: Ulf
authors.initials: U
authors.lastname: Simonsen
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism; D051381:Rats; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism; D014664:Vasodilation / Q000502:physiology
chemical_list: D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D051640:Small-Conductance Calcium-Activated Potassium Channels; D009569:Nitric Oxide