title: Ca2+ signaling mechanisms of vascular endothelial cells and their role in oxidant-induced endothelial cell dysfunction.
abstract: Endothelial cell function may be compromised in disease states as a result of oxidative injury, which may arise from a variety of sources. Oxidant stress appears to influence vascular reactivity and permeability via alteration in the production, release, or effect of endothelium-derived paracrine substances. An early event associated with endothelial cell dysfunction involves alteration in transmembrane signaling mechanisms. In particular, substantial evidence suggests that oxidant stress alters Ca2+ homeostatic mechanisms of the endothelial cell. Because an increase in the free cytosolic Ca2+ concentration ([Ca2+]i) of the endothelial cell is important for release of paracrine factors responsible for regulation of vascular tone and reactivity, oxidant stress-induced changes in Ca2+ signaling could explain much of the observed pathophysiology associated with oxidative injury. Under normal conditions, agonists such as bradykinin and ATP cause a biphasic increase in [Ca2+]i of the endothelial cell; an initial transient component reflects release of Ca2+ from internal stores, whereas a more long-lasting elevation in [Ca2+]i reflects Ca2+ influx from the extracellular space. After incubation with tert-butyl hydroperoxide, a time-dependent inhibition of the agonist-stimulated changes in [Ca2+]i is observed. The underlying molecular mechanisms associated with normal Ca2+ signaling and how these may be altered in the endothelial cell by oxidative stress is the subject of this review.
authors.affiliation: Department of Molecular Physiology, Baylor College of Medicine, Houston, Texas 77030.
authors.forename: W P
authors.initials: WP
authors.lastname: Schilling
authors.forename: S J
authors.initials: SJ
authors.lastname: Elliott
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D016877:Oxidants / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D016877:Oxidants; D002118:Calcium