Neurochemical Research

, Volume 32, Issue 9, pp 1489–1498 | Cite as

Angiotensin Receptor Type 1 Blockade in Astroglia Decreases Hypoxia-Induced Cell Damage and TNF Alpha Release

  • Lusine Danielyan
  • Ali Lourhmati
  • Stephan Verleysdonk
  • Daniela Kabisch
  • Barbara Proksch
  • Ulrike Thiess
  • Sumaira Umbreen
  • Boris Schmidt
  • Christoph H. Gleiter
Original Paper


The present study investigated the role of angiotensin receptors (AT-R) in the survival and inflammatory response of astroglia upon hypoxic injury. Exposure of rat astroglial primary cultures (APC) to hypoxic conditions (HC) led to decreased viability of the cells and to a 3.5-fold increase in TNF-alpha release. AT-R type1 (AT1-R) antagonist losartan and its metabolite EXP3174 decrease the LDH release (by 36 ± 9%; 45 ± 6%) from APC under HC. Losartan diminished TNF-alpha release (by 40 ± 15%) and the number of TUNEL-cells by 204 ± 38% under HC, alone and together with angiotensin II (ATII), while EXP3174 was dependent on ATII for its effect on TNF-alpha. The AT2-R antagonist, PD123.319, did not influence the release of LDH and TNF-alpha under normoxic (NC) and HC. These data suggest that AT1-R may decrease the susceptibility of astrocytes to hypoxic injury and their propensity to release TNF-alpha. AT1-R antagonists may therefore be of therapeutic value during hypoxia-associated neurodegeneration.


Hypoxia Angiotensin Neurodegeneration Astrocytes Losartan EXP3174 PD123.319 



We appreciate the support of Microbionix (Regensburg, Germany) in performing of multiplex analysis. This work was supported by “Dr. Karl-Kuhn Stiftung” (Tuebingen, Germany) and MSD SHARP& DOHME GmbH (Haar, Germany).


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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Lusine Danielyan
    • 1
  • Ali Lourhmati
    • 1
  • Stephan Verleysdonk
    • 2
  • Daniela Kabisch
    • 1
  • Barbara Proksch
    • 1
  • Ulrike Thiess
    • 2
  • Sumaira Umbreen
    • 3
  • Boris Schmidt
    • 3
  • Christoph H. Gleiter
    • 1
  1. 1.Department of Clinical PharmacologyUniversity Hospital of TuebingenTuebingenGermany
  2. 2.Interfaculty Institute of BiochemistryUniversity of TuebingenTuebingenGermany
  3. 3.Clemens Schoepf-Institute for Organic Chemistry and BiochemistryDarmstadtGermany

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