Skip to main content

Effects of clonidine on microcirculatory alterations during endotoxemia


Endothelial dysfunction during endotoxemia is responsible for the functional breakdown of microvascular perfusion and microvessel permeability. The cholinergic anti-inflammatory pathway (CAP) is a neurophysiological mechanism that regulates the inflammatory response by inhibiting proinflammatory cytokine synthesis, thereby preventing tissue damage. Endotoxemia-induced microcirculatory dysfunction can be reduced by cholinergic CAP activation. Clonidine improves survival in experimental sepsis [1] by reducing the sympathetic tone, resulting in the parasympathetic-mediated CAP activation. The aim of this study was to determine the effects of clonidine on microcirculatory alterations during endotoxemia.


Using fluorescent intravital microscopy, we determined the venular wall shear rate, macromolecular efflux and leukocyte adhesion in mesenteric postcapillary venules of male Wistar rats. Endotoxemia was induced over 120 minutes by intravenous infusion of lipopolysaccharide (LPS). Control groups received an equivalent volume of saline. Clonidine 10 μg/kg was applied as i.v. bolus in treatment groups. Animals received either (i) saline alone, (ii) clonidine 10 minutes prior to saline administration, (iii) clonidine 45 minutes prior to LPS administration, (iv) clonidine 10 minutes prior to LPS administration, (v) clonidine 30 minutes after LPS administration or (vi) LPS alone.


All LPS groups (iii to vi) showed a significantly reduced venular wall shear rate compared with the saline group after 120 minutes. There were no significant differences between the numbers of adhering leukocytes in the clonidine/LPS groups (iii, iv, v) and the LPS group after 120 minutes. Macromolecular efflux significantly increased in all groups over the time period of 120 minutes. After 120 minutes there was no difference between the LPS group and the clonidine 10 minutes prior to LPS administration group (iv) whereas all other groups (i, ii, iii, v) showed a significantly reduced macromolecular efflux compared with the LPS group.


Clonidine has no positive effect on microhemodynamic alterations and leukocyte-endothelial interaction during endotoxemia. The reduction of capillary leakage in clonidine-treated groups depends on the time interval relative to the initiation of endotoxemia. Endothelial permeability and leukocyte activation are regulated by different pathways when stimulated by clonidine during endotoxemia. We conclude that clonidine might have an important time-dependent anti-inflammatory and protective effect on endothelial activation during inflammation.


  1. 1.

    Hofer S, et al.: Crit Care. 2009, 13: R11. 10.1186/cc7709

    PubMed Central  Article  PubMed  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to K Schmidt.

Rights and permissions

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

About this article

Cite this article

Schmidt, K., Philipsenburg, C., Zivkovic, A. et al. Effects of clonidine on microcirculatory alterations during endotoxemia. Crit Care 17, P388 (2013).

Download citation


  • Clonidine
  • Intravital Microscopy
  • Microvascular Perfusion
  • Postcapillary Venule
  • Experimental Sepsis