Intensive Care Medicine

, Volume 37, Issue 5, pp 861–869 | Cite as

Vascular ATP-sensitive potassium channels are over-expressed and partially regulated by nitric oxide in experimental septic shock

  • Solène Collin
  • Nacira Sennoun
  • Anne-Gaëlle Dron
  • Mathilde de la Bourdonnaye
  • Chantal Montemont
  • Pierre Asfar
  • Patrick Lacolley
  • Ferhat Meziani
  • Bruno Levy
Experimental

Abstract

Purpose

To study the activation and expression of vascular (aorta and small mesenteric arteries) potassium channels during septic shock with or without modulation of the NO pathway.

Methods

Septic shock was induced in rats by peritonitis. Selective inhibitors of vascular KATP (PNU-37883A) or BKCa [iberiotoxin (IbTX)] channels were used to demonstrate their involvement in vascular hyporeactivity. Vascular response to phenylephrine was measured on aorta and small mesenteric arteries mounted on a wire myograph. Vascular expression of potassium channels was studied by PCR and Western blot, in the presence or absence of 1400W, an inducible NO synthase (iNOS) inhibitor. Aortic activation of the transcriptional factor nuclear factor-kappaB (NF-κB) was assessed by electrophoretic mobility shift assay.

Results

Arterial pressure as well as in vivo and ex vivo vascular reactivity were reduced by sepsis and improved by PNU-37883A but not by IbTX. Sepsis was associated with an up-regulation of mRNA and protein expression of vascular KATP channels, while expression of vascular BKCa channels remained unchanged. Selective iNOS inhibition blunted the sepsis-induced increase in aortic NO, decreased NF-κB activation, and down-regulated vascular KATP channel expression.

Conclusions

Vascular KATP but not BKCa channels are activated, over-expressed, and partially regulated by NO via NF-κB activation during septic shock. Their selective inhibition restores arterial pressure and vascular reactivity and decreases lactate concentration. The present data suggest that selective vascular KATP channel inhibitors offer potential therapeutic perspectives for septic shock.

Keywords

Septic shock Cardiovascular failure Potassium channels Nitric oxide Inhibitors 

Notes

Acknowledgments

The authors thank W.A. Coetzee and N.Q. Shi for critical reading of the article and for providing antibodies. This work was supported by Inserm and by a grant from the French Society of Intensive Care (SRLF).

Supplementary material

134_2011_2169_MOESM1_ESM.doc (1.6 mb)
Supplementary material 1 (DOC 1657 kb)

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Copyright information

© Copyright jointly held by Springer and ESICM 2011

Authors and Affiliations

  • Solène Collin
    • 1
  • Nacira Sennoun
    • 1
  • Anne-Gaëlle Dron
    • 1
  • Mathilde de la Bourdonnaye
    • 4
  • Chantal Montemont
    • 1
  • Pierre Asfar
    • 3
  • Patrick Lacolley
    • 2
  • Ferhat Meziani
    • 4
  • Bruno Levy
    • 1
  1. 1.Groupe CHOC, Equipe Avenir Inserm, Faculté de MédecineUniversité de NancyVandoeuvre-lès-NancyFrance
  2. 2.Inserm U961, Faculté de MédecineUniversité de NancyVandoeuvre-lès-NancyFrance
  3. 3.Laboratoire HIFIH UPRES EA 3859Université d’AngersAngersFrance
  4. 4.Inserm 771, CNRS UMR 6214, Faculté de MédecineUniversité d’AngersAngersFrance

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