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-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-1beta, 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-1beta, 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.
Ganta
Chanran K
CK
Department of Anatomy and Physiology, Kansas State University, Manhattan, Kansas, USA.
Lu
Ning
N
Helwig
Bryan G
BG
Blecha
Frank
F
Ganta
Roman R
RR
Zheng
Ling
L
Ross
Christopher R
CR
Musch
Timothy I
TI
Fels
Richard J
RJ
Kenney
Michael J
MJ
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure; D002555:Cerebrospinal Fluid; D016207:Cytokines / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D006339:Heart Rate; D007276:Injections, Intraventricular; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000098:blood supply / Q000294:innervation* / Q000502:physiology; D013562:Sympathectomy; D013564:Sympathetic Nervous System / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D016207:Cytokines; D014662:Vasoconstrictor Agents; D000804:Angiotensin II