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

• Published in: Acta Physiologica 2011-10, Vol.203 (2), p.289-297
• Main Authors: Shi, Z., Gan, X. -B., Fan, Z. -D., Zhang, F., Zhou, Y. -B., Gao, X.-Y., De, W., Zhu, G. -Q.
• Format: Article
• Language: English
• Subjects: Afferent Pathways - drug effects; Afferent Pathways - physiology; angiotensin; Angiotensin II; Angiotensin II - pharmacology; Animals; Autonomic Pathways - drug effects; Autonomic Pathways - physiology; Biological and medical sciences; Blood Pressure - drug effects; Bradykinin - pharmacology; Cytokines - pharmacology; Fundamental and applied biological sciences. Psychology; Heart - innervation; interleukin; Male; Paraventricular Hypothalamic Nucleus - drug effects; Paraventricular Hypothalamic Nucleus - physiology; paraventricular nucleus; Random Allocation; Rats; Rats, Sprague-Dawley; Reflex - drug effects; Reflex - physiology; sympathetic activity; Sympathetic Nervous System - drug effects; Sympathetic Nervous System - physiology; tumour necrosis factor; Vertebrates: anatomy and physiology, studies on body, several organs or systems
• ISSN: 1748-1708; 1748-1716
• DOI: 10.1111/j.1748-1716.2011.02313.x

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. AT1 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 AT1 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.