title: Lipopolysaccharide reduces intercellular coupling in vitro and arteriolar conducted response in vivo.
abstract: 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-alpha, interleukin (IL)-1beta, 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 microg/ml) but not these cytokines reduced intercellular conductance (c(i)) (an index of cell communication) and that 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 prevented by protein tyrosine kinase (PTK) inhibitors (1.5 microM 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.
authors.affiliation: A. C. Burton Laboratory, Lawson Health Research Institute, London, Ontario, Canada N6A 5C1. ktyml@lhsc.on.ca
authors.forename: K
authors.initials: K
authors.lastname: Tyml
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: D
authors.initials: D
authors.lastname: Lidington
authors.forename: Y
authors.initials: Y
authors.lastname: Ouellette
mesh_terms: D000818:Animals; D001160:Arterioles / Q000187:drug effects* / Q000502:physiology*; D002450:Cell Communication / Q000187:drug effects* / Q000502:physiology; D004558:Electric Stimulation; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008955:Models, Cardiovascular; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D051381:Rats; D013779:Tetrodotoxin / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014654:Vascular Patency / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D013779:Tetrodotoxin; D011505:Protein-Tyrosine Kinases