Quick Change Artist

Abstract

See related article, pp 802–808 Vascular endothelial cells importantly contribute to the regulation of vascular smooth muscle tone through the production of a variety of vasoactive substances and by direct electric communication through myoendothelial gap junctions.1,2 Moncada et al3 discovered the first endothelium-derived vasoactive substance, prostacyclin, in the mid 1970s and rapidly identified its structure and chemical composition.4 This was followed by the landmark observations of Furchgott and Zawadzki.5 and the discovery of endothelium-derived relaxing factor in 1980. Seven years later, the endothelium-derived relaxing factor of Furchgott and Zawadzki was positively identified as NO.6 The existence of a nonprostaglandin, non-NO endothelium-derived hyperpolarizing factor (EDHF) was postulated by Komori et al7 in 1988. Twenty-three years later, we know that there is no one EDHF, but rather multiple pathways by which endothelial cells can produce hyperpolarization-induced relaxation of overlying vascular smooth muscle cells, independent from prostacyclin and NO (Figure).1,2 Figure. Pathways for nonprostacyclin-, non-NO–mediated, endothelium-dependent hyperpolarization of vascular smooth muscle in resistance arteries. Schematic diagram of a longitudinal section through a resistance artery showing smooth muscle and endothelial cell cross-sections and depicting several potential pathways by which ACh can produce endothelium-dependent smooth cell hyperpolarization and vasodilatation independent from prostaglandins and NO. On the left, ACh-induced increases in intracellular Ca2+ activate endothelial small conductance (sKCa) and intermediate conductance (IKCa) Ca2+-activated K+ channels. The released K+ ions can then act as an EDHF through activation of smooth muscle inward rectifier K+ channels (KIR) or Na+/K+ ATPase. Smooth muscle hyperpolarization then closes voltage-gated Ca2+ channels (VGCC), leading to …