title: Endothelium-derived contracting factors.
abstract: The endothelium not only mediates relaxation but is a source of contracting factors. Endothelium-dependent contractions are elicited by physical and chemical stimuli (i.e., hypoxia, pressure, and stretch) and autacoids, local and circulating hormones. The mechanism of endothelium-dependent contractions to hypoxia involves withdrawal of nitric oxide. The endothelial cyclooxygenase pathway can produce thromboxane A2, prostaglandin H2, and superoxide anions. The peptide endothelin is a potent contracting factor; its production is stimulated by vasopressor hormones, platelet-derived factors, coagulation products, and cytokines, whereas endothelium-derived nitric oxide, prostacyclin, and a smooth muscle cell-derived inhibitory factor reduce endothelin production. In hypertension, the release of cyclooxygenase-dependent endothelium-derived contracting factors to stretch, acetylcholine, and platelet-derived products is augmented. Vascular endothelin production in hypertension remains controversial but appears mostly normal; it is augmented in the presence of vascular disease or renal insufficiency. The endothelium-dependent inhibition of endothelin-induced contractions is reduced in hypertension while the reactivity of vascular smooth muscle may be normal, increased, or reduced. The potentiating effects of low concentrations of endothelin on contractions to norepinephrine are augmented with aging and hypertension. In atherosclerosis, the production of the cyclooxygenase-dependent endothelium-derived contracting factors and endothelin is enhanced. Thus, endothelium-derived contracting factors can profoundly affect vascular tone and counteract relaxing factors produced within the endothelium. In hypertension and atherosclerosis, the role of contracting factors appears to become more dominant, leading to an imbalance of endothelium-dependent vascular regulation.
authors.affiliation: Department of Medicine, University Hospital, Basel, Switzerland.
authors.forename: T F
authors.initials: TF
authors.lastname: Lüscher
authors.forename: C M
authors.initials: CM
authors.lastname: Boulanger
authors.forename: Y
authors.initials: Y
authors.lastname: Dohi
authors.forename: Z H
authors.initials: ZH
authors.lastname: Yang
mesh_terms: D016232:Endothelins / Q000502:physiology*; D006801:Humans; D006973:Hypertension / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology
chemical_list: D016232:Endothelins; D011451:Prostaglandin-Endoperoxide Synthases