Central angiotensin II-enhanced splenic cytokine gene expression is mediated by the sympathetic nervous system

We tested the hypothesis that central angiotensin II (ANG II) administration would activate splenic sympathetic nerve discharge (SND), which in turn would alter splenic cytokine gene expression. Experiments were completed in sinoaortic nerve-lesioned, urethane-chloralose-anesthetized, splenic nerve-...

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Published in:American journal of physiology. Heart and circulatory physiology 2005-10, Vol.58 (4), p.H1683-H1691
Main Authors: GANTA, Chanran K, NING LU, HELWIG, Bryan G, BLECHA, Frank, GANTA, Roman R, LING ZHENG, ROSS, Christopher R, MUSCH, Timothy I, FELS, Richard J, KENNEY, Michael J
Format: Article
Language:English
Subjects:
Biological and medical sciences
Cytokines
Fundamental and applied biological sciences. Psychology
Gene expression
Nervous system
Rodents
Spleen
Vertebrates: cardiovascular system
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Summary:We tested the hypothesis that central angiotensin II (ANG II) administration would activate splenic sympathetic nerve discharge (SND), which in turn would alter splenic cytokine gene expression. Experiments were completed in sinoaortic nerve-lesioned, urethane-chloralose-anesthetized, splenic nerve-intact (splenic-intact) and splenic nerve-lesioned (splenic-denervated) Sprague-Dawley rats. Splenic cytokine gene expression was determined using gene-array and real-time RT-PCR analyses. Splenic SND was significantly increased after intracerebroventricular administration of ANG II (150 ng/kg, 10 microl), but not artificial cerebrospinal fluid (aCSF). Splenic mRNA expression of IL-1{beta}, IL-6, IL-2, and IL-16 genes was increased in ANG II-treated splenic-intact rats compared with aCSF-treated splenic-intact rats. Splenic IL-1{beta}, IL-2, and IL-6 gene expression responses to ANG II were significantly reduced in splenic-denervated compared with splenic-intact rats. Splenic gene expression responses did not differ significantly in ANG II-treated splenic-denervated and aCSF-treated splenic-intact rats. Splenic blood flow responses to intracerebroventricular ANG II administration did not differ between splenic-intact and splenic-denervated rats. These results provide experimental support for the hypothesis that ANG II modulates the immune system through activation of splenic SND, suggesting a novel relation between ANG II, efferent sympathetic nerve outflow, and splenic cytokine gene expression.[PUBLICATION ABSTRACT]
ISSN:0363-6135
1522-1539