The hypothalamic paraventricular nucleus and cardiovascular homeostasis: a role in chronic heart failure

A pathophysiological characteristic of chronic heart failure is sympatho-excitation and sympathetic activity is a major factor contributing to the morbidity and mortality of heart failure. Current research suggests a central mechanism to be a major contributor to the abnormal sympathetic activation in heart failure. The paraventricular nucleus of the hypothalamus (PVN) is an important site that integrates sympathetic nerve activity and recent evidence suggests this nucleus plays a role in the exaggerated sympathetic outflow observed in heart failure. Experimental studies using animal models have identified nitric oxide (NO) and γ-aminobutyric acid (GABA) within the PVN as providing inhibitory mechanisms to regulate sympathetic outflow and that these inhibitory mechanisms are attenuated in heart failure. Furthermore, the degree of sympathetic activation is a balance of interactions between excitatory (angiotensin II and glutamate) and inhibitory (NO and GABA) neurotransmitters within the PVN. The attenuated actions of NO and GABA within the PVN may allow for an increase in the actions of angiotensin and glutamate and this may be a source of the sympatho-excitation observed in heart failure.