AJP - Cell Physiology, Vol 257, Issue 5 C875-C881, Copyright © 1989 by American Physiological Society
Role of endothelium in endotoxin blockade of voltage-sensitive Ca2+ channels in smooth muscle cells
M. S. Goligorsky
Department of Medicine, State University of New York, Stony Brook 11794-8152.
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.
