Paraventricular nucleus of the hypothalamus and elevated sympathetic activity in heart failure: the altered inhibitory mechanisms.

AIM There is a characteristic neurohumoral activation in heart failure (HF). However, few studies have been performed to examine the role of the central nervous system in the activation of sympathetic outflow during HF. In this paper we review some of our studies, with particular emphasis on examining the role of the paraventricular nucleus (PVN) in the exaggerated sympathetic outflow commonly observed in HF. RESULTS Our studies have revealed that the inhibitory mechanisms regulating sympathetic outflow are mediated by nitric oxide (NO) and gamma-aminobutyric acid (GABA) within the PVN and are attenuated in HF. These alterations are associated with elevated sympathetic activity. Furthermore, these studies have indicated that the interactions among excitatory (angiotensin II and glutamate) and inhibitory (NO and GABA) neurotransmitters/mediators within the PVN significantly influence sympathetic outflow. CONCLUSION Reduced inhibitory actions of NO and/or GABA within the PVN may exaggerate an increase in the actions of excitatory neurotransmitters such as glutamate and angiotensin II within the PVN and this may contribute to the overall sympatho-excitation commonly observed in HF.

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