K. Tyml et al., Lipopolysaccharide reduces intercellular coupling in vitro and arteriolar conducted response in vivo, AM J P-HEAR, 281(3), 2001, pp. H1397-H1406
Citations number
40
Categorie Soggetti
Cardiovascular & Hematology Research
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
Our recent in vitro study (Lidington et al. J Cell Physiol 185: 117-125, 20
00) suggested that lipopolysaccharide (LPS) reduces communication along blo
od vessels. The present investigation extended this study to determine whet
her any effect of LPS and/or inflammatory cytokines [tumor necrosis factor-
alpha, interleukin (IL)-1 beta, and IL-6] on endothelial cell coupling in v
itro could also be demonstrated for an arteriolar conducted response in viv
o. Using an electrophysiological approach in monolayers of microvascular en
dothelial cells, we found that LPS (10 mug/ml) but not these cytokines redu
ced intercellular conductance (c(i)) an index of cell communication and tha
t LPS together with these cytokines did not further reduce c(i). Also, c(i)
was restored after LPS washout, and the LPS-induced reduction was prevente
d by protein tyrosine kinase (PTK) inhibitors (1.5 muM 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 vasoconstrict
ion but reduced the conducted response. Washout of LPS restored the conduct
ed response, whereas PTK inhibitors prevented the effect of LPS. On the bas
is of a newly developed mathematical model, the LPS-induced reduction in co
nducted 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 kinas
e-dependent manner. Based on literature and present results, we suggest tha
t LPS may compromise microvascular hemodynamics at the arteriolar responsiv
eness and the conduction levels.