Hyponatremia-Induced Inhibition of Magnocellular Neurons Causes Stressor-Selective Impairment of Stimulated Adrenocorticotropin Secretion in Rats*

Abstract

Chronically hyponatremic rats were subjected to various stressors in order to evaluate the possible contribution of magnocellular neurons to the regulation of ACTH secretion, since such rats have markedly inhibited secretion and synthesis of magnocellular arginine vasopressin (AVP) and oxytocin (OT). Stress caused by a novel environment or by insulin-induced hypoglycemia resulted in moderate increases in plasma ACTH, which were of similar magnitude in both hyponatremic and normonatremic rats, and these stressors caused no increase in plasma AVP and OT levels in either group of rats. However, when exposed to ether, hyponatremic rats exhibited a significantly blunted ACTH response compared to normonatremic controls (331 +/- 49 vs. 740 +/- 124 pg/ml; P less than 0.01, respectively), and plasma AVP levels were markedly increased in the normonatremic, but not in the hyponatremic, rats. Intravenous infusion of 2 M NaCl also caused an ACTH release in hyponatremic rats that was significantly smaller than that in their normonatremic counterparts (228 +/- 52 vs. 479 +/- 85 pg/ml; P less than 0.05, respectively), and in this case both plasma AVP and OT levels were markedly increased in the normonatremic, but not in the hyponatremic, rats. However, hyponatremic rats exhibited greatly increased plasma ACTH levels 2 and 96 h after adrenalectomy (ADX), which were statistically equivalent to the increases in ACTH levels in normonatremic rats after ADX. Seven days after ADX parvocellular neurons of the paraventricular nucleus showed strongly increased CRF-41 and AVP-neurophysin, but not OT-neurophysin, immunoreactivities in both normonatremic and hyponatremic rats. These results show that parvocellular CRF-41/AVP-producing neurons in the paraventricular nucleus are not inhibited by chronic hyponatremia, in contrast to magnocellular neurons, and suggest that ACTH secretion induced by ether or hypertonic saline, but not by novel environment or insulin-induced hypoglycemia, is partially mediated by magnocellular AVP and/or OT.

Neuroendocrine Responses to a Cold Pressor Stimulus in Polydipsic Hyponatremic and in Matched Schizophrenic Patients

“…Posm was normalized before the cold pressor ( Table 2), so that concurrent hypoosmolemia/hyponatremia per se can be excluded. Pre-infusion osmolality was negatively correlated with the AVP response, consistent with the recognized blunting effects of chronic hyponatremia on AVP and ACTH responses, (Dohanics et al, 1991;Goldman et al, 1996;Robertson, 2001). Thus the role of long-standing hyponatremia can also be discounted, though inclusion of a non-psychiatric control group with hyponatremia would more definitively address this possibility.…”

Oxytocin actions within the supraoptic and paraventricular nuclei: differential effects on peripheral and intranuclear vasopressin release

“…For example, electrical stimulation of the SON has been demonstrated to increase plasma corticosterone in anesthetized rats (37). Also, an attenuated stress-induced rise in plasma ACTH was found in hyponatremic rats (12) and after peripheral immunoneutralization of OXT (20), indicating the involvement of magnocellular AVP and /or OXT in HPA axis regulation. Similarly, local osmotic stimulation of the SON of conscious rats increased not only local and peripheral AVP and OXT release but also elevated ACTH secretion into blood (62; for a review, see Ref.…”

“…As OXT is locally released within the SON and PVN, for example, during swim stress (57,61), and OXT receptors have been identified within these hypothalamic nuclei (2,5,19,31), we aim to more specifically reveal local OXT actions on basal and stress-induced HPA axis activity. We hypothesize OXT actions on HPA axis functions would occur predominantly within the PVN, but likely also within the SON, as a significant contribution of magnocellular SON neurons to the regulation of HPA axis activity has repeatedly been shown (12,20,37,62, for a review, see Ref. 16).…”

Oxytocin at physiological concentrations evokes adrenocorticotropin (ACTH) release from corticotrophs by increasing intracellular free calcium mobilized mainly from intracellular stores. Oxytocin displays synergistic or additive effects on ACTH-releasing factor or arginine vasopressin-induced ACTH secretion, respectively

“…21). Several studies report 5-to lO-fold increases of OT in blood plasma during stress (4,39,40). Arecent study (41) reported increased OT levels in cerebrospinal fluid, accompanied by increased plasma OT alter different kinds of stress suggesting that cerebrospinal fluid hormone levels reflect to some degree the neurosecretory…”