TY - JOUR
T1 - Endothelial calcium-activated potassium channels as therapeutic targets to enhance availability of nitric oxide
AU - Kerr, Paul M.
AU - Tam, Raymond
AU - Narang, Deepak
AU - Potts, Kyle
AU - McMillan, Dane
AU - McMillan, Kale
AU - Plane, Frances
PY - 2012
Y1 - 2012
N2 - The vascular endothelium plays a critical role in vascular health by controlling arterial diameter, regulating local cell growth, and protecting blood vessels from the deleterious consequences of platelet aggregation and activation of inflammatory responses. Circulating chemical mediators and physical forces act directly on the endothelium to release diffusible relaxing factors, such as nitric oxide (NO), and to elicit hyperpolarization of the endothelial cell membrane potential, which can spread to the surrounding smooth muscle cells via gap junctions. Endothelial hyperpolarization, mediated by activation of calcium-activated potassium (KCa) channels, has generally been regarded as a distinct pathway for smooth muscle relaxation. However, recent evidence supports a role for endothelial KCa channels in production of endothelium-derived NO, and indicates that pharmacological activation of these channels can enhance NO-mediated responses. In this review we summarize the current data on the functional role of endothelial KCa channels in regulating NO-mediated changes in arterial diameter and NO production, and explore the tempting possibility that these channels may represent a novel avenue for therapeutic intervention in conditions associated with reduced NO availability such as hypertension, hypercholesterolemia, smoking, and diabetes mellitus.
AB - The vascular endothelium plays a critical role in vascular health by controlling arterial diameter, regulating local cell growth, and protecting blood vessels from the deleterious consequences of platelet aggregation and activation of inflammatory responses. Circulating chemical mediators and physical forces act directly on the endothelium to release diffusible relaxing factors, such as nitric oxide (NO), and to elicit hyperpolarization of the endothelial cell membrane potential, which can spread to the surrounding smooth muscle cells via gap junctions. Endothelial hyperpolarization, mediated by activation of calcium-activated potassium (KCa) channels, has generally been regarded as a distinct pathway for smooth muscle relaxation. However, recent evidence supports a role for endothelial KCa channels in production of endothelium-derived NO, and indicates that pharmacological activation of these channels can enhance NO-mediated responses. In this review we summarize the current data on the functional role of endothelial KCa channels in regulating NO-mediated changes in arterial diameter and NO production, and explore the tempting possibility that these channels may represent a novel avenue for therapeutic intervention in conditions associated with reduced NO availability such as hypertension, hypercholesterolemia, smoking, and diabetes mellitus.
KW - Calcium-activated potassium channels
KW - Endothelial dysfunction
KW - Endothelium
KW - Nitric oxide
KW - Oxidative stress
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U2 - 10.1139/Y2012-075
DO - 10.1139/Y2012-075
M3 - Review article
C2 - 22626011
AN - SCOPUS:84870710884
SN - 0008-4212
VL - 90
SP - 739
EP - 752
JO - Canadian journal of physiology and pharmacology
JF - Canadian journal of physiology and pharmacology
IS - 6
ER -