Lipopolysaccharide reduces intercellular coupling in vitro and arteriolar conducted response in vivo

Karel Tyml, Xiaowei Wang, Darcy Lidington, Yves Ouellette

Research output: Contribution to journalArticle

61 Scopus citations

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-α, interleukin (IL)-1β, 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 LIPS. 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.

Original languageEnglish (US)
Pages (from-to)H1397-H1406
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume281
Issue number3 50-3
StatePublished - Oct 1 2001

Keywords

  • Endothelial cell monolayer
  • Mathematical model
  • Mouse cremaster muscle
  • Tyrosine kinase

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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