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

Overview

Journal Neurochem Res

Specialties Chemistry
Neurology

Date 2007 Apr 5

PMID 17406976

Citations 9

Authors

Lusine Danielyan

Ali Lourhmati

Stephan Verleysdonk

Daniela Kabisch

Barbara Proksch

Ulrike Thiess

Sumaira Umbreen

Boris Schmidt

Christoph H Gleiter

Affiliations

Soon will be listed here.

Abstract

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.

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