GAMMA-AMINOBUTYRIC-ACID MEDIATION OF THE INHIBITORY EFFECT OF NITRIC-OXIDE ON THE ARGININE-VASOPRESSIN AND OXYTOCIN RESPONSES TO INSULIN-INDUCED HYPOGLYCEMIA

Previous studies have demonstrated that the nitric oxide (NO) synthase inhibitor L-NAME exerts positive effects on the arginine vasopressin (AVP) and oxytocin (OT) responses to insulin-induced hypoglycemia, sug gesting inhibitory actions of NO. The present study was designed to de termine whether a gamma-aminobutyric acid (GABA)ergic pathway is invol ved in regulation of NO action. AVP and OT secretory patterns during i nsulin (0.15 IU/kg, i.v.)-tolerance tests (ITT) were examined in seven normal male subjects with (experimental tests) and without (control t est) concomitant treatment with L-NAME (40 mu g/kg injected plus 50 mu g/kg infused, i.v.), the GABAergic agent sodium valproate (600 mg in three divided doses orally) or the combination of L-NAME and sodium va lproate. Insulin-induced hypoglycemia increased by 2-fold (peak vs. ba seline) plasma AVP and OT levels. In the presence of L-NAME, plasma AV P and OT levels rose 3-fold in response to hypoglycemia and were signi ficantly higher than those in the control test. Administration of sodi um valproate alone changed neither AVP nor OT secretory patterns durin g ITT. In contrast, sodium valproate abolished the facilitating effect of L-NAME on both AVP and OT responses to hypoglycemia. In the ITT pl us L-NAME plus sodium valproate test, plasma AVP and OT levels were no t significantly different at any time point from those observed during the control ITT. These data indicate a GABAergic mediation of the inh ibitory modulation by NO of the AVP and OT responses to insulin-induce d hypoglycemia.