Effect of oxidant stress on calcium signaling in vascular endothelial cells.
The endothelial cell is recognized as a critical modulator of blood vessel tone and reactivity. This regulatory function of endothelial cells occurs via synthesis and release of diffusible paracrine substances which induce contraction or relaxation of adjacent vascular smooth muscle. In response to stimulation by blood-borne agonists such as bradykinin or histamine, the endothelial cell utilizes cytosolic ionic Ca2+ as a trigger in the transduction of the stimulatory signal into a paracrine response. Considerable evidence has accumulated to indicate that various forms of biologically important oxidant stress alter vascular function in an endothelium-dependent manner. Further, oxidant stress is known to alter the mechanisms which govern Ca2+ homeostasis in the endothelial cell. Recently, we have described a model in which the oxidant tert-butylhydroperoxide is utilized to examine the effects of oxidant stress on Ca(2+)-dependent signal transduction in vascular endothelial cells. In this model, three temporal phases are evident and consist of (1) inhibition of the agonist-stimulated Ca2+ influx pathway, (2) inhibition of receptor-activated release of Ca2+ from internal stores and elevation of resting cytosolic free Ca2+ concentration, and (3) progressive increase in resting cytosolic Ca2+ concentration and loss of responsiveness to agonist stimulation. In this review, the mechanisms which characterize agonist-stimulated Ca2+ signaling in vascular endothelial cells, and the effects of oxidant stress on signal transduction will be described. The mechanisms potentially responsible for oxidant-induced inhibition of Ca2+ signaling will be considered.
Elliott
S J
SJ
Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030.
Meszaros
J G
JG
Schilling
W P
WP
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism*; D005980:Glutathione Reductase / Q000378:metabolism; D006801:Humans; D016877:Oxidants / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013438:Sulfhydryl Compounds / Q000378:metabolism
D016877:Oxidants; D013438:Sulfhydryl Compounds; D005980:Glutathione Reductase; D002118:Calcium