Abstract
Heart failure (HF) is a serious cardiovascular disease and is characterized by exaggerated sympathetic activity. In this paper, we review these limited studies, with particular emphasis on examining the role of the paraventricular nucleus (PVN) in the neurohumoral excitation in HF. The PVN is an important neuroendocrine and preautonomic output nucleus, and is considered as the important central site for integration of sympathetic nerve activity. Accumulating evidences demonstrate that a number of neurohumoral processes are involved in the pathophysiology of HF, such as renin-angiotensin system (RAS), proinflammatory cytokines (PICs), neurotransmitters, and reactive oxygen species (ROS). Recent studies about neurohumoral regulation indicate that angiotensin II type1 receptor (AT1-R) is the important product mediated by cytoplasmic nuclear factor-kappa B (NF-κB) which is up-regulated along with elevated PICs and angiotensin II (ANG II) in the PVN of HF rats. These findings suggest that the NF-κB mediates the cross-talk between RAS and PICs in the PVN in HF. The further studies indicate that the interaction between AT1-R and NF-κB in the PVN contributes to oxidative stress and sympathoexcitation by modulating neurotransmitters in heart failure, and the superoxide activates NF-κB in the PVN and contributes to neurohumoral excitation. In conclusion, the neurohumoral excitation in HF is based on the interaction of RAS, PICs, ROS, NF-κB and neurotransmitters in the PVN; and the activated NF-κB in the PVN modulates the neurotransmitters and contributes to sympathoexcitation in rats with heart failure.
Highlights
Heart failure (HF) secondary to left ventricular systolic dysfunction is characterized by low cardiac output and neurohumoral excitation (NHE)
Several proinflammatory cytokines (PICs) are up-regulated in HF, we have focused on TNF-α, which appears early in the cytokine cascade [25], since it is generally the first cytokine that is up-regulated in diseases, and it induces the production of several other cytokines
Several possibilities, including indirect effects mediated by PICs, NAD(P)H oxidasedependent generation of superoxide and/or up-regulation of the brain renin-angiotensin system (RAS), and possibly even direct effects mediated by NF-κB signalling pathways
Summary
Heart failure (HF) secondary to left ventricular systolic dysfunction is characterized by low cardiac output and neurohumoral excitation (NHE). After the ICV treatment with low doses of PTX or ETN attenuated, and high doses prevented, increases in levels of glutamate, NE, and TH, and decreases in levels of GABA and GAD67 in the PVN of HF rats These studies from our laboratory clearly indicate that the effects of PICs on the exaggerated sympathetic activity in HF via modulating neurotransmitters in the PVN. PVN infusion of AT1-R blocker losartan or pyrrolidine dithiocarbamate (PDTC, a specific NF-κB inhibitor) attenuated the decreases in GABA, and the increases in gp91phox (a subunit of NAD(P)H oxidase), NF-κB activity, glutamate and NE, in the PVN of HF rats, and attenuated the increases in RSNA and plasma PICs and NE Based on these studies, it is clear that interaction between AT1-R and NF-κB in the PVN contributes to oxidative stress and sympathoexcitation by modulating imbalance between excitatory and inhibitory neurotransmitters in the PVN of HF rats [74].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
