Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 334, Issue 4, pp 501–507 | Cite as

Thimerosal induces endothelium-dependent vascular smooth muscle relaxations by interacting with thiol groups

Relaxations are likely to be mediated by endothelium-derived relaxing factor (EDRF)
  • Ulrich Förstermann
  • Karin Burgwitz
  • Jürgen C. Frölich
Article
Received:
Accepted:

Summary

  1. 1.

    The sulfhydryl reagent thimerosal, as well as acetylcholine and Ca2+-ionophore A23187, produced concentration-dependent relaxations of intact rabbit aortic strips. The ability of strips to relax in response to these agents was dependent on the presence of vascular endothelium. Purposely removing the endothelium led to a complete loss of the relaxation responses.

     
  2. 2.

    Thimerosal was at least as efficacious as A23187 in inducing endothelium-dependent relaxations, but its relaxations developed much slower than those induced by A23187 or acetylcholine.

     
  3. 3.

    A small concentration of thimerosal that had no appreciable effect by itself, potentiated the relaxing response to acetylcholine in endothelium-intact preparations.

     
  4. 4.

    Endothelium-dependent relaxations induced by larger concentrations of thimerosal, as well as relaxations produced by acetylcholine, were inhibited by the antioxidant and lipoxygenase inhibitor nordihydroguaiaretic acid, by haemoglobin, and by the inhibitor of soluble guanylate cyclase methylene blue. Indomethacin had no effect on these relaxations.

     
  5. 5.

    The thiol compounds glutathion, 2-mercaptoethanol and a low concentration of dithiothreitol prevented (and reversed) relaxations induced by thimerosal, but had little or no effect on ACh relaxations. A high concentration of dithiothreitol also markedly inhibited the ACh relaxation.

     
  6. 6.

    These results are consistent with the hypothesis that thimerosal stimulates endothelial cells to produce a relaxing substance whose properties are similar or the same as those of the endothelium-derived relaxing factor (EDRF) released in response to acetylcholine or A23187. The biochemical mechanism by which thimerosal induces the formation and/or release of this relaxing substance is likely to be different from ACh. Unlike ACh, thimerosal seems to interact with thiol groups (probably of acyltransferase enzymes) when inducing relaxation.

     

Key words

Thimerosal Endothelium-dependent relaxation Nordihydroguaiaretic acid Methylene blue Haemoglobin Thiol compounds 
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Copyright information

© Springer-Verlag 1986

Authors and Affiliations

  • Ulrich Förstermann
    • 1
  • Karin Burgwitz
    • 1
  • Jürgen C. Frölich
    • 1
  1. 1.Department of Clinical PharmacologyHannover Medical SchoolHannover 61Federal Republic of Germany

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