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

Abstract

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.

Physiological regulation of pro-inflammatory cytokines expression in rat cardiovascular tissues by sympathetic nervous system and angiotensin II

“…Although our data corroborate previous investigations made in other tissue showing an enhanced IL-1β, IL-2, and IL-6 gene expression after central ANG II administration in splenic-intact rats (Ganta et al 2005) and an ANG II modulation of the immune system through activation of efferent sympathetic nerve outflow, a mutual interactions between ANG II and cytokines exist (Wang et al 2012) and cytokines are also able to influence ANG II syntheis in tissues (Suski et al 2013). Inhibition of SNS or ANG II activity may be beneficial to prevent cardiovascular disorders by cytokine overexpression.…”

Importance of Inflammation in Hypertension - Review

“…Entretanto, quando administrada pela via intravenosa a angiotensina II pode estar relacionada com a HAS, lesão glomerular, proteinúria e fibrose intersticial no tecido renal (CAMPBELL, 2013). Ganta et al (2005) e Santisteban et al (2013) reportaram que a administração de angiotensina II, aumenta a atividade do SNS do baço, gânglios linfáticos e da medula óssea, que por sua vez aumenta a atividade e liberação de linfócitos T circulantes e mediadores inflamatórios como IL-1, IL-2, IL-6 e IL-16 na circulação, resultando em disfunção endotelial e inflamação vascular.…”

Hypothermia-enhanced splenic cytokine gene expression is independent of the sympathetic nervous system

“…Results of our recent studies demonstrate that in rats with intact splenic nerves, whole body hyperthermia (19) and central ANG II infusion (20) increase splenic sympathetic nerve discharge (SND) and the expression of selective splenic cytokine genes. Splenic cytokine gene expression responses to whole body hyperthermia and central ANG II infusion are significantly reduced in splenic nerve-denervated compared with splenic nerve-intact rats (19,20), suggesting that activation of splenic SND can enhance splenic cytokine gene expression.Hypothermia, a common side effect of extreme cold environments, anesthesia, and serious traumatic injuries, alters the sympathetic nervous system and immune system regulation (8, 13-15, 21, 27-29, 47-50). Acute cold stress increases plasma concentrations of norepinephrine and epinephrine (18,26,46,52), changes the pattern of synchronized SND bursts (28), influences the frequency-domain relationships between discharge bursts in regionally selective sympathetic nerves (28), and produces nonuniform changes in the level of sympathetic nerve activity to selected target organs (28).…”

“…Results of our recent studies demonstrate that in rats with intact splenic nerves, whole body hyperthermia (19) and central ANG II infusion (20) increase splenic sympathetic nerve discharge (SND) and the expression of selective splenic cytokine genes. Splenic cytokine gene expression responses to whole body hyperthermia and central ANG II infusion are significantly reduced in splenic nerve-denervated compared with splenic nerve-intact rats (19,20), suggesting that activation of splenic SND can enhance splenic cytokine gene expression.…”

“…Splenic cytokine gene expression responses to whole body hyperthermia and central ANG II infusion are significantly reduced in splenic nerve-denervated compared with splenic nerve-intact rats (19,20), suggesting that activation of splenic SND can enhance splenic cytokine gene expression.…”