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Sinoaortic baroreceptor denervation (SAD) results in increased osmotically induced secretion of vasopressin (VP) and oxytocin (OT) and increased cardiovascular responses to many centrally acting pressor agents. Studies were conducted to determine whether SAD increases the cardiovascular and endocrine responses to direct and peripheral osmotic stimulation of the supraoptic nucleus (SON). SON microdialysis was performed in urethane-anesthetized male rats with measurement of dialysate peptides, mean arterial pressure (MAP) and heart rate. Experiment 1 tested the effect of direct stimulation of the SON with hypertonic NaCl in SAD, sham-operated (control) and intake-matched (matched) rats. Osmotically induced VP release into the SON was significantly greater in SAD than in control or matched groups. VP release peaked at 36 +/- 13 and 15 +/- 7 pg in SAD and controls, respectively, with no increase observed in the matched group. Plasma VP was significantly elevated after SON osmotic stimulation with no differences observed among the groups. The pressor response to osmotic stimulation was greater in SAD (29 +/- 4 mm Hg) than in control (20 +/- 3 mm Hg) and matched animals (15 +/- 3 mm Hg). Experiment 2 tested the effect of intraperitoneal injection of hypertonic NaCl on SON VP and OT release. SAD rats showed an increased central VP response to peripheral osmotic stimulation, a 64-fold increase in SAD as compared to a 4-fold one in controls. Central OT release was not significantly altered (peak of 22 +/- 6 vs. 11 +/- 4 pg, SAD vs. control). A direct SON osmotic challenge given 3.5 h after the intraperitoneal test confirmed an increased VP responsiveness in the SAD group. Plasma VP and OT were significantly increased after intraperitoneal hypertonic saline with no difference observed between groups. The MAP response to intraperitoneal hypertonic saline was greater in the SAD group with an elevation of 37 +/- 4 versus 18 +/- 3 mm Hg observed in SAD versus control subjects. These results demonstrate that baroreceptor denervation produces a state of heightened osmotic sensitivity for VP neurons, with evidence for increased central VP release to both direct and peripheral hypertonic NaCl stimulation.

Tetrodotoxin (TTX) was used to (1) distinguish between axonal and dendritic/somatic release of vasopressin (VP) and oxytocin (OT) within the supraoptic nucleus (SON) and (2) to determine whether neuronal inputs trigger intranuclear peptide release in the response to osmotic stimulation. Microdialysis was used to administer TTX (10(-6) M or 10(-4)M) bilaterally into the SON with simultaneous monitoring of central and peripheral peptide release and mean arterial pressure in urethane-anesthetized male rats. Osmotic stimuli were given via the microdialysis probe (1 M NaCl-artificial CSF) or injected intraperitoneally (3.5 M NaCl; 600 mu l/100 g b.w.) SON perfusion with TTX did not alter basal intranuclear VP or OT release or the intranuclear peptide response to direct NaCl stimulation of the SON. However, TTX treatment abolished the effect of peripheral osmotic stimulation on central peptide release. Basal plasma peptide levels were significantly reduced by TTX, e.g. decreases of 94.8 and 75.8% for VP and OT, respectively. TTX also blocked the peripheral endocrine and cardiovascular responses to both modes of osmotic stimulation. The TTX insensitivity of directly stimulated intranuclear release suggests nonsynaptic peptide release from dendrites and/or cell bodies. The ability of TTX to abolish the central peptide response to systemic osmotic stimulation demonstrates that intranuclear release is a part of a cascade produced by osmotic activation of multisynaptic pathways.

Neuroanatomical and physiological evidence indicates that baroreceptors influence hypothalamic vasopressin (VP) and oxytocin (OT) neurons. We evaluated the effects of sinoaortic denervation (SAD) on the molecular and endocrine response to salt loading. Sham-operated or SAD rats were given a 2% NaCl solution to drink for 72 h. A group with limited salt water intake was included as a second control because the denervated rats consumed less salt than the controls. Plasma VP, OT and osmolality and posterior pituitary peptide content were measured. Brains were processed for evaluation of VP and OT mRNA expression using in situ hybridization with computer quantitation. Salt loading produced equivalent increases in plasma VP and OT in the control and SAD groups, however, there was a greater depletion of posterior pituitary peptides in the denervated animals. Salt loading produced significant decreases in pituitary VP and OT in the SAD animals, 69.8 +/- 8.4% and 68.3 +/- 4.0%, respectively. In the control groups, there was no decrease in VP content and a decrease in OT only in the control ad lib group. The peptide mRNA response to salt loading was also altered in the denervated rats. There was a significant increase in the area and intensity of the labeling for OT mRNA in the PVN in the SAD salt group. The control salt rats showed an increase in the SON and the salt-limited group showed no changes. For VP mRNA, the only change noted was in the SON of the salt-loaded SAD animals. These results show that chronic denervation of arterial baroreceptors augments the hypothalamic VP and OT response to salt loading.(ABSTRACT TRUNCATED AT 250 WORDS)

Sinoaortic baroreceptor denervation is reported to produce exaggerated centrally derived cardiovascular and endocrine responses. We examined the effect of sinoaortic denervation (SAD) on the cardiovascular and endocrine responses to two acute stressors, footshock and immobilization, in male Sprague-Dawley rats. Parameters measured were mean arterial pressure (MAP), heart rate (HR) and plasma levels of oxytocin (OT) and vasopressin (VP). Baseline MAP was elevated in the SAD group (approximately 25 mm Hg) and footshock stress increased arterial pressure equivalently in both groups. This stress caused tachycardia and increased plasma OT, with a tendency for the SAD group to show blunted responses. Immobilization increased HR but caused no change in MAP and no significant difference between the groups. This form of stress also increased plasma OT, and again the SAD group showed a diminished response. Plasma VP was not significantly altered by either stressor. The results of these studies indicate that SAD does not uniformly increase the cardiovascular and endocrine responses to all stressors or centrally derived stimuli. These results also suggest that the lack of an increase in plasma VP is not related to baroreceptor-mediated inhibition of secretion under stressful conditions.

Hypothalamic monoamine metabolism was evaluated in male and female mice that were administered monosodium glutamate (MSG, 4 mg/g) on postnatal day 4. Hypothalamic dopamine (DA) content was reduced approximately by 22% across all experiments and pituitary DA content was also significantly decreased. Despite reductions in hypothalamic DA levels, MSG-treated mice did not exhibit significant reductions in the levels of the DA metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). Hypothalamic monoamine and metabolite profiles in MSG-treated and control mice were examined after the administration of pargyline (PAR), alpha-methyl-p-tyrosine (MPT) or reserpine (RES). DA turnover as indexed by PAR and MPT techniques were not as conclusive as the metabolite measures in suggesting an accelerated DA utilization. MSG-treated mice were more resistant to the DA-depleting actions of reserpine than were the controls. No alterations were found in hypothalamic norepinephrine metabolism in MSG-treated mice, however, after drug challenges, alterations were found in serotonin metabolism. These results indicate the extent and nature of the changes that occur in hypothalamic monoamine metabolism after neonatal MSG treatment. The DA neurons that survive MSG treatment appear to exhibit neurochemical characteristics dissimilar to those of tuberoinfundibular DA neurons. Additionally, the neuropharmacological actions of MPT, PAR and RES are discussed as they relate to hypothalamine monoamine metabolism in the mouse.