Absence of negative feedback by oxytocin on release from magnocellular neurones in conscious rats

Abstract

Peripheral administration of vasopressin (VP) was previously shown to exert a negative feedback influence on its own release and on the release of oxytocin (OT). In this study we examined the possible influence that OT has on the function of hypothalamic magnocellular neurones. Oxytocin was administered intraperitoneally and its effects on release from VP neurones and from OT neurones were determined as indexed by plasma concentrations of vasopressin-associated neurophysin ([VP-RNP]) and oxytocin-associated neurophysin ([OT-RNP]) under basal conditions and conditions of high plasma osmolality (Posm) induced by acute salt loading. Studies were performed on conscious, chronically instrumented Long-Evans rats. Oxytocin (1 nmol or 10 nmol) dissolved in 1 mL of 0.9% saline was administered intraperitoneally to animals 1 h before they received an intravenous infusion of hypertonic saline over 60 min at a rate designed to raise Posm by approximately 0.75 mosmol∙min−1. Intraperitoneal injection of vehicle or 1 nmol of OT did not significantly alter [VP-RNP], [OT-RNP], or basal Posm. Administration of 10 nmol OT also had no effect on [VP-RNP] or [OT-RNP], but this dose of peptide significantly lowered basal Posm (299 ± 2 to 290 ± 2 mosmol/kg H2O, p < 0.001). Both doses of OT did not significantly alter the responsiveness of VP neurones to hyperosmotic stimulation. The slopes of the relationship between the rise in [VP-RNP] (A[VP-RNP]) and the rise in Posm (ΔPosm) for the groups receiving pretreatment of 1 nmol OT (n = 5), 10 nmol OT (n = 7), and vehicle (n = 7) were similar (6.1 ± 1.4, r = 0.86; 5.1 ± 0.9, r = 0.91; and 6.6 ± 0.9 fmol∙mL−1∙mosmol−1∙kg−1, r = 0.93, respectively). For the 1-nmol dose of OT that generated plasma OT levels in the physiological range, the slopes of the relationship between the rise in [OT-RNP] (Δ[OT-RNP]) and ΔPosm over the period of salt loading for peptide-treated animals and control animals (39.5 ± 8.9, r = 0.89 vs. 23.4 ± 5.9, fmol∙mL−1∙mosmol−1∙kg−1, r = 0.93) indicated an increased responsiveness of OT neurones, but this difference was not significant (p < 0.1426). Higher plasma levels of OT were generated by administering the 10 nmol dose of OT, and the slopes of the relationship between Δ[OT-RNP] and ΔPosm for peptide-treated animals and control animals (13.9 ± 1.6, r = 0.96 vs. 23.4 ± 8.9 fmol∙mL−1∙mosmol−1∙kg−1, r = 0.93) suggested a decreased responsiveness of OT neurones, but again this difference was not significant (p < 0.1637). However, there was a significant difference in the rise in OT-RNP with plasma osmolality for rats receiving high versus low dose of peptide (p < 0.0475). Our data indicate that peripherally administered OT, unlike VP, does not exert a negative feedback influence on osmotically stimulated release from VP neurones and most probably OT neurones. However, it cannot be ruled out that the lack of modulation of magnocellular neurones by the high dose of OT could be due to the summation of a positive OT effect (since the 1-nmol group appeared to exhibit an enhancing effect) and of a negative VP effect as indicated by blood pressure increases and plasma dilution. OT also does not appear to have an influence on basal release from magnocellular neurones.Key words: neurophysins, oxytocin neurones, vasopressin neurones.