Inflammatory cytokines in paraventricular nucleus modulate sympathetic activity and cardiac sympathetic afferent reflex in rats

Acta Physiol (Oxf). 2011 Oct;203(2):289-97. doi: 10.1111/j.1748-1716.2011.02313.x. Epub 2011 May 27.


Aim: This study was to determine the roles of inflammatory cytokines in paraventricular nucleus (PVN) in modulating sympathetic activity, blood pressure and cardiac sympathetic afferent reflex (CSAR).

Methods: Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded in anaesthetized rats with bilateral sinoaortic denervation and vagotomy. The CSAR was evaluated by the RSNA response to epicardial application of bradykinin (BK). The levels of inflammatory cytokines were measured with ELISA.

Results: The PVN microinjection of pro-inflammatory cytokines (PIC), tumour necrosis factor (TNF)-α or interleukin (IL)-1β, increased the baseline MAP and RSNA, and enhanced the CSAR. Anti-inflammatory cytokines (AIC), IL-4 or IL-13, in the PVN only increased the baseline MAP. In the rats pretreated with TNF-α or IL-1β but not in the rats pretreated with IL-4 or IL-13, sub-response dose of angiotensin II caused significant increases in the MAP and RSNA and enhancement in the CSAR. AT(1) receptor antagonist losartan in the PVN attenuated the effects of angiotensin II, TNF-α and IL-1β, but not the effects of IL-4 and IL-13. Stimulation of cardiac sympathetic afferents with epicardial application of BK increased the levels of TNF-α, IL-1β but not IL-4 in the PVN.

Conclusion: TNF-α or IL-1β in the PVN increases blood pressure and sympathetic outflow and enhances the CSAR, which is partially dependent on the AT(1) receptors, while IL-4 or IL-13 in the PVN only increases blood pressure. There is a synergetic effect of Ang II with TNF-α or IL-1β on blood pressure, sympathetic activity and CSAR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Afferent Pathways / drug effects*
  • Afferent Pathways / physiology
  • Angiotensin II / pharmacology
  • Animals
  • Autonomic Pathways / drug effects
  • Autonomic Pathways / physiology
  • Blood Pressure / drug effects
  • Bradykinin / pharmacology
  • Cytokines / pharmacology*
  • Heart / innervation
  • Male
  • Paraventricular Hypothalamic Nucleus / drug effects*
  • Paraventricular Hypothalamic Nucleus / physiology
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Reflex / drug effects*
  • Reflex / physiology*
  • Sympathetic Nervous System / drug effects*
  • Sympathetic Nervous System / physiology*


  • Cytokines
  • Angiotensin II
  • Bradykinin