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1 A. C. Burton Laboratory and 2 Child Health Research Institute, Lawson Health Research Institute, and 3 Department of Medical Biophysics, University of Western Ontario, London, Ontario, Canada N6A 5C1
Our recent in vitro study
(Lidington et al. J Cell Physiol 185: 117-125,
2000) suggested that lipopolysaccharide (LPS) reduces communication
along blood vessels. The present investigation extended this study to
determine whether any effect of LPS and/or inflammatory cytokines
[tumor necrosis factor-
, interleukin (IL)-1
, and IL-6] on
endothelial cell coupling in vitro could also be demonstrated for an
arteriolar conducted response in vivo. Using an electrophysiological approach in monolayers of microvascular endothelial cells, we found
that LPS (10 µg/ml) but not these cytokines reduced intercellular conductance (ci) (an index of cell
communication) and that LPS together with these cytokines did not
further reduce ci. Also, ci was restored after LPS washout, and the
LPS-induced reduction was prevented by protein tyrosine kinase (PTK)
inhibitors (1.5 µM Tyr A9 and 10 nM PP-2). In our in vivo experiments
in arterioles of the mouse cremaster muscle, local electrical
stimulation evoked vasoconstriction that conducted along arterioles.
LPS in the muscle superfusate did not alter local vasoconstriction but
reduced the conducted response. Washout of LPS restored the conducted
response, whereas PTK inhibitors prevented the effect of LPS. On the
basis of a newly developed mathematical model, the LPS-induced
reduction in conducted response was predicted to reduce the arteriolar
ability to increase resistance to blood flow. We conclude that LPS can reduce communication in in vitro and in vivo systems comparably in a
reversible and tyrosine kinase-dependent manner. Based on literature
and present results, we suggest that LPS may compromise microvascular
hemodynamics at both the arteriolar responsiveness and the conduction levels.
endothelial cell monolayer; mouse cremaster muscle; tyrosine kinase; mathematical model
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