title: Endothelial calcium-activated potassium channels as therapeutic targets to enhance availability of nitric oxide.
abstract: 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 (K(Ca)) channels, has generally been regarded as a distinct pathway for smooth muscle relaxation. However, recent evidence supports a role for endothelial K(Ca) 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 K(Ca) 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.
authors.affiliation: Department of Pharmacology, 9-62 Medical Sciences Building, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2H7, Canada.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Kerr
authors.forename: Raymond
authors.initials: R
authors.lastname: Tam
authors.forename: Deepak
authors.initials: D
authors.lastname: Narang
authors.forename: Kyle
authors.initials: K
authors.lastname: Potts
authors.forename: Dane
authors.initials: D
authors.lastname: McMillan
authors.forename: Kale
authors.initials: K
authors.lastname: McMillan
authors.forename: Frances
authors.initials: F
authors.lastname: Plane
mesh_terms: D000818:Animals; D001158:Arteries / Q000378:metabolism / Q000502:physiology; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D058990:Molecular Targeted Therapy; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism*
chemical_list: D024681:Potassium Channels, Calcium-Activated; D009569:Nitric Oxide