Calcium signaling and oxidant stress in the vasculature.
Recent evidence suggests that oxidant stress plays a major role in several aspects of vascular biology. Oxygen free radicals are implicated as important factors in signaling mechanisms leading to vascular pathologies such as postischemic reperfusion injury and atherosclerosis. The role of intracellular Ca(2+) in these signaling events is an emerging area of vascular research that is providing insights into the mechanisms mediating these complex physiological processes. This review explores sources of free radicals in the vasculature, as well as effects of free radicals on Ca(2+) signaling in vascular endothelial and smooth muscle cells. In the endothelium, superoxides enhance and peroxides attenuate agonist-stimulated Ca(2+) responses, suggesting differential signaling mechanisms depending on radical species. In smooth muscle cells, both superoxides and peroxides disrupt the sarcoplasmic reticulum Ca(2+)-ATPase, leading to both short- and long-term effects on smooth muscle Ca(2+) handling. Because vascular Ca(2+) signaling is altered by oxidant stress in ischemia-related disease states, understanding these pathways may lead to new strategies for preventing or treating arterial disease.
Department of Pharmacology, University of Vermont School of Medicine, Burlington, VT 05405, USA. klounsbu@zoo.uvm.edu
K M
KM
Lounsbury
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Q
Hu
R C
RC
Ziegelstein
D001808:Blood Vessels / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D002374:Catalase / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology; D005609:Free Radicals; D006801:Humans; D017136:Ion Transport; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology*; D010545:Peroxides / Q000494:pharmacology; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase / Q000502:physiology; D013481:Superoxides / Q000378:metabolism; D014655:Vascular Resistance / Q000502:physiology
D005609:Free Radicals; D009566:Nitrates; D010545:Peroxides; D017382:Reactive Oxygen Species; D013481:Superoxides; C039642:peroxynitric acid; D009569:Nitric Oxide; D002374:Catalase; D013482:Superoxide Dismutase