TY - JOUR
T1 - Calcium-activated potassium channels - a therapeutic target for modulating nitric oxide in cardiovascular disease?
AU - Dalsgaard, Thomas
AU - Kroigaard, Christel
AU - Simonsen, Ulf
PY - 2010/8
Y1 - 2010/8
N2 - IMPORTANCE OF THE FIELD: 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.AREAS COVERED IN THIS REVIEW: 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.WHAT THE READER WILL GAIN: 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.TAKE HOME MESSAGE: 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.
AB - IMPORTANCE OF THE FIELD: 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.AREAS COVERED IN THIS REVIEW: 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.WHAT THE READER WILL GAIN: 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.TAKE HOME MESSAGE: 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.
KW - Animals
KW - Cardiovascular Diseases
KW - Humans
KW - Intermediate-Conductance Calcium-Activated Potassium Channels
KW - Mice
KW - Nitric Oxide
KW - Potassium Channels, Calcium-Activated
KW - Rats
KW - Small-Conductance Calcium-Activated Potassium Channels
KW - Vasodilation
U2 - 10.1517/14728222.2010.500616
DO - 10.1517/14728222.2010.500616
M3 - Journal article
C2 - 20560781
SN - 1472-8222
VL - 14
SP - 825
EP - 837
JO - Expert Opinion on Therapeutic Targets
JF - Expert Opinion on Therapeutic Targets
IS - 8
ER -
