DIFFERENT EFFECTS OF THE GABAERGIC AGENT SODIUM VALPROATE ON THE OXYTOCIN RESPONSES TO ANGIOTENSIN-II AND INSULIN-INDUCED HYPOGLYCEMIA IN NORMAL MEN

The present study was performed in order to establish whether angiotensin II (ANG II) and/or insulin-induced hypoglycemia exert their oxytocin (OT)-releasing effects by interacting with a GABAergic pathway. For this purpose, in 14 normal men the OT responses to ANG II (infusion for 60 min of successively increasing doses of 4, 8 and 16 ng/kg.min, each dose for 20 min; n = 7) or to insulin (0.15 IU/kg)-induced hypoglycemia (n = 7) were evaluated with or without previous treatment with the GABAergic agonist sodium valproate (600 mg in 3 divided doses, p.o.). In all subjects insulin produced a similar hypoglycemic response regardless of sodium valproate administration. Both ANG II and insulin-induced hypoglycemia produced significant increases in plasma OT levels (mean peaks were about 60% higher than baseline). The pretreatment with sodium valproate was unable to change the OT response to hypoglycemia, whereas it abolished the ANG-II-induced OT rise. These data suggest that in man a GABAergic mechanism is involved in the regulation of the OT response to ANG II, but not in the mediation of hypoglycemia-induced OT release.