title: Endothelium-derived relaxing factors. A perspective from in vivo data.
abstract: We review below published studies of endothelium-dependent vasodilation in vivo. Endothelium-dependent vasodilation has been demonstrated in conduit arteries in vivo and in the cerebral, coronary, mesenteric, and femoral vascular beds as well as in the microcirculation of the brain and the microcirculation of cremaster muscle. The available evidence, although not complete, strongly suggests that the endothelium-derived relaxing factor generated by acetylcholine in the cerebral microcirculation is a nitrosothiol. The endothelium-derived relaxing factor generated by bradykinin in this vascular bed is an oxygen radical generated in association with enhanced arachidonate metabolism via cyclooxygenase. In the microcirculation of skeletal muscle, on the other hand, the vasodilation from bradykinin is mediated partly by prostacyclin and partly by an endothelium-derived relaxing factor similar to that generated by acetylcholine. Basal secretion of endothelium-derived relaxing factor is controversial in vivo but is usually present in vitro. On the other hand, it appears that endothelium-derived relaxing factor mediates flow-dependent vasodilation in both large vessels and in the microcirculation in vivo. The generation and release of endothelium-derived relaxing factor from endothelium may be abnormal in a variety of conditions including acute and chronic hypertension, atherosclerosis, and ischemia followed by reperfusion. Several mechanisms for these abnormalities have been identified. These include inability to generate endothelium-derived relaxing factor or destruction of endothelium-derived relaxing factor by oxidants after its release in the extracellular space. These abnormalities in endothelium-dependent relaxation may contribute to the vascular abnormalities in these conditions.
authors.affiliation: Department of Medicine, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0281.
authors.forename: J J
authors.initials: JJ
authors.lastname: Marshall
authors.forename: H A
authors.initials: HA
authors.lastname: Kontos
mesh_terms: D000818:Animals; D001161:Arteriosclerosis / Q000503:physiopathology; D006801:Humans; D006878:Hydroxides; D017665:Hydroxyl Radical; D006973:Hypertension / Q000503:physiopathology; D008833:Microcirculation / Q000502:physiology; D009569:Nitric Oxide / Q000032:analysis / Q000502:physiology*; D015427:Reperfusion Injury / Q000503:physiopathology; D014664:Vasodilation
chemical_list: D006878:Hydroxides; D009569:Nitric Oxide; D017665:Hydroxyl Radical