Response of the magnocellular system in rats to hypovolemia and cholecystokinin during pregnancy and lactation.

To define changes in the magnocellular neuroendocrine system during lactation and pregnancy, we compared plasma levels of oxytocin (OT) and vasopressin (VP) after polyethylene glycol (PEG)-induced hypovolemia and cholecystokinin (CCK) stimulation. Conscious virgin, pregnant (day 20), and lactating (day 6) Sprague-Dawley rats were injected with either PEG (70-600 mg/ml; 35 or 70 ml/kg sc), CCK (100 micrograms/ml; 4 ml/kg ip), or vehicle and decapitated 4 h (PEG) or 5 min (CCK) later. Changes in thresholds for release of hormone and the responsiveness (slopes relating [hormone] to blood volume depletion or to plasma osmolality) of the OT and VP systems were determined using an iterative nonlinear threshold regression model. After PEG, plasma osmolality increased coincident with a decrease in blood volume, with both stimuli contributing to the rise in plasma VP and OT. Compared with virgin rats, neither the threshold nor the responsiveness of the VP system was altered by the combined stimulus, whereas the oxytocinergic system of pregnant rats was more responsive to osmotic component. Lactating rats, however, had a higher threshold for VP release and an apparent elevation of the OT threshold beyond 25% volume depletion. Regardless of the reproductive state, the threshold for VP release was always lower than that for OT. Intraperitoneal CCK elevated plasma [OT] in each reproductive state, although the response in lactating animals was attenuated. In virgin and lactating rats, plasma levels of VP also increased slightly but significantly in response to CCK. During gestation when cardiovascular volume is expanded, both the VP and OT neuroendocrine systems were reset, enabling secretion of both hormones in response to hypovolemia with hypertonicity. During lactation, both neuroendocrine systems are reset such that greater changes in fluid balance are needed to stimulate hormone release. Regardless of the reproductive state, the threshold for VP release was always lower than that for OT, indicative of preferential release of VP with less than a 5% (virgin, pregnant) or a 20% (lactating) loss in blood volume.

Osmoregulation of the magnocellular system during pregnancy and lactation.

We compared the responsiveness of both the vasopressin (VP) and oxytocin (OT) magnocellular systems to osmotic stimulation during pregnancy and lactation to determine if changes in thresholds and sensitivities were similar for both neuropeptides. Virgin, pregnant (day 20), and lactating (day 6) Sprague-Dawley rats were injected with a hypertonic NaCl solution (0.25 M-8.0 M NaCl; 15 ml/kg sc) and decapitated 2 h later. Late in gestation, the apparent osmotic threshold for both VP and OT release was lower by approximately 10 mosmol/kgH2O than that of virgin and lactating animals. The sensitivity (i.e., slope of the linear regression relating plasma osmolality and VP or OT levels) of the magnocellular system to osmoregulation, however, was unchanged in pregnant animals but was significantly attenuated (P < 0.01) for both peptides during lactation (slopes of lactating vs. virgin rats: OT, 1.7 vs. 3.4; VP, 1.1 vs. 1.9). The neural lobe content of VP decreased (P < 0.05) in pregnant rats, whereas OT stores were reduced (P < 0.05) in lactating animals. Thus, during pregnancy, the lower tonicity of plasma is perceived as normal by both VP and OT neuroendocrine systems enabling excretion of an acute sodium or water load.