Neurophysiological involvement in hypervolemic hyponatremia - evoked by hypersecretion of vasopressin

Arginine vasopressin (AVP) is a neuropeptide mainly synthesized in the supraoptic and paraventricular nuclei in the hypothalamus and released from the posterior pituitary when physiological demands are increased. The major function of circulating AVP is to promote water retention and vasoconstriction, thereby maintaining hydromineral homeostasis and blood volume and pressure. Physiological regulation of AVP secretion includes osmotic and nonosmotic neurohumoral reflexes, actions of bloodborne factors, interactions between glia and AVP neurons, autoregulation, and other cellular events. These modulatory processes, ultimately integrated in AVP neurons, determine their firing rate and pattern and the amount of AVP secretion. In waterretaining diseases such as congestive heart failure and hepatic cirrhosis, efficient arterial volume is relatively low despite water retention in the body; high levels of AVP cannot correct insufficiency of efficient arterial volume and/or high levels of circulating renin-angiotensin-aldosterone. These nonosmotic factors can counterbalance and even override the inhibitory effect of AVP-elicited hyponatremia on AVP secretion. Under this condition, a facilitatory feature of local neural circuits controlling AVP secretion becomes active, leading to further secretion of AVP. This inherent feature in the local circuit mainly includes: 1) adaptive reduction of osmosensory threshold, 2) removal of astrocytic restriction of AVP neuronal activity, and 3) damaging effects of protein tyrosine nitration on enzymes for glutamate conversion and on other functional molecules. These factors will be discussed in this review.