Stimulation of gastric vagal afferents by systemic administration of cholecystokinin octapeptide (CCK) inhibits gastric motility, reduces food intake, and stimulates pituitary secretion of oxytocin and adrenocorticotropic hormone in rats. To characterize further the central neural circuits responsible for these effects, the present study used triple-labeling immunocytochemical methods to determine whether or not exogenous CCK activates cFos expression in catecholaminergic neurons in the caudal medulla that project to the paraventricular nucleus of the hypothalamus (PVN). To identify these neurons, the retrograde tracer fluorogold (FG) was iontophoresed into the PVN of anesthetized rats under stereotaxic guidance. After 2 weeks, rats were injected with CCK (100 micrograms/kg, i.p.) and then anesthetized and killed 1 hour later by perfusion fixation. Medullary sections were processed for triple immunocytochemical localization of cFos, retrogradely transported FG, and tyrosine hydroxylase (TH). In rats with FG injections centered in the PVN (n = 10), approximately 70% of the FG-labeled neurons in the caudal nucleus of the solitary tract (NST) and ventrolateral medulla (VLM) expressed cFos. Of these activated PVN-projecting neurons, approximately 78% in the NST and 89% in the VLM were catecholaminergic (TH positive). These results indicate that PVN-projecting catecholaminergic neurons within the caudal medulla are activated by peripheral administration of CCK, further implicating these ascending catecholaminergic pathways in the neuroendocrine, physiological, and behavioral effects produced by gastric vagal stimulation.

The cortisol levels in the peripheral blood were measured radioimmunologically at 08.00, 12.00, 16.00, 20.00, 24.00 and 04.00 h in human neonates and infants with ages of 1, 2 and 3 days, 1, 2 and 4 weeks, 2, 3 and 6 months and 1 and 3 years. During the first 2 days of extrauterine life the neonates had high plasma cortisol levels without a circadian rhythm. During the first 2 months there were decreased cortisol levels in the infants, but the diurnal rhythms were still absent, and free-running fluctuations were observed. The typical circadian rhythms of the plasma cortisol levels were present in infants aged 3 months; these rhythms were identical with the diurnal changes of 1- and 3-year-old infants. In the groups of patients studied the data suggest that the circadian rhythm of the adrenocortical function may develop to the adult-type pattern already during early infancy.

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.

Neurohypophysial secretion of vasopressin (AVP) and oxytocin (OT) was studied in rats maintained under hyposmolar conditions for 10-24 days. Graded intravenous infusions of hypertonic saline solutions had no consistent effect on plasma AVP and OT levels until plasma sodium concentration ([Na+]) exceeded 130 mM, after which levels of both hormones increased as an exponential function of plasma [Na+]. Detectable increases in plasma AVP and OT began at significantly lower plasma [Na+] in hyposmolar rats than in normosmolar control rats (10.8 mM lower for AVP and 18.4 mM lower for OT). AVP and OT secretion in hyposmolar rats was also markedly blunted in response to nonosmotic stimuli, including acute and chronic hypovolemia and systemic administration of cholecystokinin. Cessation of 1-desamino-8-D-arginine vasopressin-induced antidiuresis resulted in an appropriately rapid correction of plasma [Na+] to normal levels within 24 h. Consequently, although chronic hyposmolarity caused a moderate downward resetting of the osmotic thresholds for AVP and OT secretion, it did not cause sustained deficits in osmoregulation. These results suggest that osmoreceptor activity is regulated to maintain extracellular fluid and plasma osmolality within narrow absolute ranges rather than responding to relative changes in osmolality.

Axonal injury to hypothalamic magnocellular vasopressin (AVP) and oxytocin (OT) neurons causes degeneration of a substantial subpopulation of these neurons. In this study, we investigated the influence of osmolality on this injury-induced cell death. Normonatremic, chronically hypernatremic, and chronically hyponatremic rats received pituitary stalk compression (SC), which causes degeneration of AVP and OT terminals in the neurohypophysis. Twenty-one days after SC, rats were perfused and hypothalami were serially sectioned and alternately stained for AVP-neurophysin and OT-neurophysin immunoreactivities. Normonatremic and hypernatremic rats exhibited a triphasic pattern of water intake after SC, with peak intakes 3 times higher than those exhibited by sham-operated normonatremic rats. In contrast, hyponatremic SC rats exhibited peak water intakes of 600 ml/24 hr, approximately 9-10 times the water intakes of sham-operated normonatremic rats. In normonatremic rats, SC caused degeneration of 65% of the AVP neuron population in the SON and 73% in the PVN, but only 31% of the OT neuron population in the SON and 35% in the PVN. Similar results were found in hypernatremic rats after SC. However, in hyponatremic rats SC caused degeneration of 97% of the AVP neuron population in the SON and 93% in the PVN, and 90% of the OT neuron population in the SON and 84% in the PVN. Our results, therefore, demonstrate that injury-induced degeneration of magnocellular AVP and OT neurons is markedly exacerbated by chronic hypo-osmolar conditions, but neuronal survival is not enhanced by chronic hyperosmolar conditions.