EFFECT OF CHRONIC HYPONATREMIA ON CENTRAL AND PERIPHERAL OXYTOCIN ANDVASOPRESSIN SECRETION IN RATS

Previous studies have shown that many treatments that stimulate the pe ripheral secretion of oxytocin (OT) and vasopressin (AVP) from the pit uitary simultaneously increase the levels of these peptides in the cer ebrospinal fluid (CSF). Since osmotically and nonosmotically stimulate d pituitary secretion of OT and AVP is markedly blunted in hyponatremi c rats, the present studies evaluated whether central OT and AVP secre tion into the CSF is similarly inhibited during sustained hyponatremia . Adult male rats with indwelling cisterna magna cannulae were rendere d hyponatremic (plasma [Na+] <110 mmol/l) by s.c. infusion of desmopre ssin (dDAVP; 10 ng/h) in combination with ingestion of a liquid diet f or 3 days, then subjected to osmotic (i.v. or i.p. injection of 2 M Na Cl; HS) or nonosmotic (6 mmol/kg of 0.15 M LiCl i.p.) stimulation. In normonatremic rats both i.v. and i.p. HS caused marked increases in pl asma OT and AVP levels 30 min after treatment. Significant elevations of OT, but not AVP, were also present in CSF. Despite similar increase s in plasma Na+ concentrations, plasma OT responses in the hyponatremi c rats were absent after HS i.v, and were significantly blunted after HS i.p., but neither group had increased plasma AW. In parallel with t he plasma results, CSF OT responses were absent in hyponatremic rats g iven HS i.v. and significantly blunted in hyponatremic rats given HS i .p., but neither group had increased CSF AVP. Nonosmotic stimulation w ith isotonic LiCl increased OT levels both in plasma and CSF in normon atremic rats 20 min after treatment. Although plasma OT responses were significantly blunted in the hyponatremic rats, the equivalent decrea ses in the CSF OT responses did not reach statistical significance. Th ese results demonstrate that sustained hyponatremia inhibits both cent ral and neurohypophyseal OT secretion in response to acute osmotic sti muli. The parallel changes in CSF and plasma OT levels under hyperosmo lar and hypoosmolar conditions supports the likelihood that the increa sed CSF OT found during osmotic stimulation is of magnocellular origin , possibly reflecting dendritic release. The incomplete inhibition of plasma and CSF OT responses seen after i.p. injection of HS and LiCl i n hyponatremic rats further indicates that nonosmotic afferent inputs can override osmotic inhibition of magnocellular OT neurons.