Conducted vasoconstriction is reduced in a mouse model of sepsis

Darcy Lidington, Yves Ouellette, Fuyan Li, Karel Tyml

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

The ability of an arteriole to conduct vasomotor responses along its length contributes to the control of organ perfusion. Sepsis, a systemic inflammatory response to infection, may compromise this control. We aimed to determine whether sepsis, induced by cecal ligation and perforation (CLP), reduces conducted vasoconstriction 24 h post-CLP. We locally stimulated mouse cremaster arterioles with KCl, measured the resulting local and the conducted constriction (500 μm upstream) and, based on these measurements, determined the communication ratio (CR500) as an index of the conducted response. Sepsis significantly reduced the CR500 from 0.75 to 0.20. Based on a mathematical model, this reduction was predicted to have a significant impact on blood flow control. In septic mice, either a 1-hour wash-out of the cremaster muscle with physiological saline or a treatment of this muscle with the tyrosine kinase inhibitor PP-2 (100 nM) restored the CR500 to the control level. Treatment of septic arterioles with the nitric oxide synthase inhibitor Nω-nitro-L-arginine methyl ester (100 μM) partially restored the CR500 from 0.2 to 0.4. In control mice, lipopolysaccharide (LPS; 10 μg/ml) superfused over the cremaster muscle for 1 h reduced the CR500; the nitric oxide (NO) donor S-nitroso-N-acetyl-penicillamine (50 μM) also reduced the CR500. Thus, LPS and NO could be two factors mediating reduced conduction of vasoconstriction in sepsis. We conclude that sepsis reduces the KCl-induced conducted vasoconstriction in the mouse cremaster muscle by a tyrosine kinase- and nitric oxide- dependent mechanism.

Original languageEnglish (US)
Pages (from-to)149-158
Number of pages10
JournalJournal of Vascular Research
Volume40
Issue number2
DOIs
StatePublished - Jun 30 2003

Keywords

  • Cecal ligation and perforation
  • Conducted arteriolar response
  • Lipopolysaccharide
  • Mouse cremaster muscle
  • Nitric oxide
  • Sepsis
  • Tyrosine kinase

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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