Role of endothelium in endotoxin blockade of voltage-sensitive Ca2+ channels in smooth muscle cells.
Coculture of endothelial and smooth muscle cells was used to study effects of endotoxin on depolarization-induced Ca2+ transients in fura-2-loaded individual smooth muscle cells. Although endotoxin did not modify the response of cultured smooth muscle cells to depolarization, endotoxin resulted in an attenuation of cytosolic Ca2+ (Cai2+) transients in response to K+ depolarization and failure of KCl-induced contractions in smooth muscle cells when they were cocultured with endothelial cells. The observed endothelial modulation of smooth muscle responses was not accomplished via gap junctions. The possible role of free radical species secreted by endothelial cells in conditioning of smooth muscle responses to depolarization was supported by the results of three sets of experiments: 1) endothelial cells did respond to endotoxin with oxidative burst, 2) pretreatment of cocultured cells with catalase prevented endotoxin-induced downregulation of Ca2+ transients, and 3) in isolated smooth muscle cells, the addition of hydrogen peroxide virtually abolished depolarization-induced Ca2+ transients. Hence vascular endothelium stimulated by endotoxin generates reduced oxygen intermediates, which in turn downregulate depolarization-induced Cai2+ transients in smooth muscle cells. This phenomenon may contribute to the development of hypotension in septicemia.
Goligorsky
M S
MS
Department of Medicine, State University of New York, Stony Brook 11794-8152.
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects* / Q000502:physiology; D003584:Cytological Techniques; D004594:Electrophysiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D004731:Endotoxins / Q000494:pharmacology*; D004926:Escherichia coli; D005609:Free Radicals; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D010084:Oxidation-Reduction
D015220:Calcium Channels; D004731:Endotoxins; D005609:Free Radicals