INHIBITORY CONTROL OF NITRIC-OXIDE ON THE ARGININE-VASOPRESSIN AND OXYTOCIN RESPONSE TO HYPOGLYCEMIA IN NORMAL MEN

IN order to establish whether nitric oxide (NO) participates in the regulation of arginine-vasopressin (AVP) and/or oxytocin (OT) secretion in humans, six normal men were treated with placebo (normal saline) or the NO synthase inhibitor N,G-nitro-L-arginine methyl ester (L-NAME), given at doses (40 mu kg(-1) injected plus 50 mu g kg(-1) infused i.v.) previously found to be unable to change blood pressure. Experiments were carried out both in basal conditions and during stimulation of posterior pituitary secretion with insulin (0.15 IU kg(-1))-induced hypoglycaemia. The administration of saline or L-NAME alone was unable to change basal AVP or OT levels. Insulin-induced hypoglycaemia, however, enhanced plasma AVP and OT levels by two-fold in the absence of L-NAME and by fourfold in the presence of the NO synthase inhibitor (NOS). Blood glucose levels decreased in a similar manner during the insulin tolerance tests, regardless of L-NAME administration. In all experiments, AVP and OT responses to hypoglycaemia followed a similar pattern, with mean peak levels at 45 min. These data suggest that in normal men NO is not involved in regulation of basal AVP and OT secretions, whereas it exerts an inhibitory role in the control of the posterior pituitary hormone responses to hypoglycaemia.