Abstract
Exposure of adult rat astroglial cultures to lipopolysaccharide (LPS) stimulated the formation of nitric oxide as evidenced by a time-dependent increase in NO2 accumulation after 24 hrs of exposure. Simultaneous addition of angiotensin II (Ang II) with LPS was found to inhibit induction of nitric oxide formation in a dose dependent manner (IC50-1nM). This inhibitory effect was blocked by an Ang II type 1 receptor antagonist losartan but not by the Ang II type 2 receptor antagonist PD123177. Cell pretreatment with Ang II or the simultaneous addition of Ang II with LPS was required for maximal inhibition of NO2 formation. To determine if LPS and Ang II were acting to alter iNOS gene expression and protein, groups of cells were treated with LPS or LPS+Ang II (100nM). Northern and Western blot analyses indicated that Ang II decreases LPS induced iNOS mRNA and protein levels. Down regulation of protein kinase C by 24 hr pretreatment with PMA abolishes the inhibitory effect of Ang II. Cytokine induction of iNOS with interleukin 1β, tumor necrosis factor-α, and interferon-γ (IFN) is not inhibited by Ang II. Also, the inhibitory effect of Ang II on LPS induction of NO is consistently abolished in the presence of IFN. These results suggest that endotoxin and cytokine induction of iNOS act through different messenger pathways. These results indicate that Ang II has a potentially important role in the intracerebral modulation of endotoxin induced inflammation. Grant support by NIH grant NS-19441, NIAAA AA00127 and an Alcohol Beverage Medical Research Foundation grant.
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Kopnisky, K., Sumners, C. & Chandler, J. Angiotensin II Inhibits Inducible Nitric Oxide Formation in Rat Astroglial Cultures. Neuropsychopharmacol 11, 274 (1994). https://doi.org/10.1038/sj.npp.1380169
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DOI: https://doi.org/10.1038/sj.npp.1380169