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, suggesting inhibitory actions of NO. The present study was designed to determine whether a gamma-aminobutyric acid (GABA)ergic pathway is involved in regulation of NO action. AVP and OT secretory patterns during insulin (0.15 IU/kg, i.v.)-tolerance tests (ITT) were examined in seven normal male subjects with (experimental tests) and without (control test) concomitant treatment with L-NAME (40 micrograms/kg injected plus 50 micrograms/kg infused, i.v.), the GABAergic agent sodium valproate (600 mg in three divided doses orally) or the combination of L-NAME and sodium valproate. Insulin-induced hypoglycemia increased by 2-fold (peak vs. baseline) plasma AVP and OT levels. In the presence of L-NAME, plasma AVP and OT levels rose 3-fold in response to hypoglycemia and were significantly higher than those in the control test. Administration of sodium valproate alone changed neither AVP nor OT secretory patterns during ITT. In contrast, sodium valproate abolished the facilitating effect of L-NAME on both AVP and OT responses to hypoglycemia. In the ITT plus L-NAME plus sodium valproate test, plasma AVP and OT levels were not significantly different at any time point from those observed during the control ITT. These data indicate a GABAergic mediation of the inhibitory modulation by NO of the AVP and OT responses to insulin-induced hypoglycemia.
Chiodera
P
P
Department of Internal Medicine, School of Medicine, University of Parma, Italy.
Volpi
R
R
Capretti
L
L
Coiro
V
V
D000328:Adult; D001127:Arginine Vasopressin / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018682:GABA Agents / Q000494:pharmacology; D006801:Humans; D007003:Hypoglycemia / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology*; D010121:Oxytocin / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*; D014635:Valproic Acid / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D001786:Blood Glucose; D004791:Enzyme Inhibitors; D018682:GABA Agents; D007328:Insulin; D001127:Arginine Vasopressin; D009569:Nitric Oxide; D010121:Oxytocin; D005680:gamma-Aminobutyric Acid; D014635:Valproic Acid; D019331:NG-Nitroarginine Methyl Ester