Central TNF-α Modulates Norepinephrine In Hypothalamic Paraventricular Nucleus And Contributes To Sympathoexcitation In Hypertension

Objective Angiotensin II (ANG II)-induced inflammatory responses contribute to the pathogenesis of hypertension. In this study, we explored the possible roles of brain tumor necrosis factor-α(TNF-α) and their effects on modulating hypothalamic paraventricular nucleus (PVN) neurotransmitter in the exaggerated sympathetic activity in hypertension.Methods Rats were infused intravenously with ANG II (10ng/kg per min) or saline for 4 weeks. These rats were treated for 4-weeks with a continuous intracerebroventricular (ICV) infusion of the TNF-αblocker pentoxifylline (PTX, 10μg/h) or artificial cerebrospinal fluid (aCSF) via osmotic minipump.Results ANG II infusion resulted in increases (P<0.05) in mean arterial pressure, renal sympathetic nerve activity, plasma pro-inflammatory cytokines (PIC), and plasma norepinephrine. These rats also had higher levels (P<0.05) of PIC and norepinephrine in the PVN than control animals. ICV treatment with PTX attenuated (P<0.05) these ANG II-induced changes.Conclusion This study demonstrates that TNF-αmodulates norepinephrine in the PVN and contribute to sympathoexcitation in hypertension.