Inhibition of vasopressinergic neurons by central injection of a specific aminopeptidase A inhibitor.

The brain angiotensin (Ang) system plays an important role in the central control of vasopressin release. Using EC33, a selective aminopeptidase A inhibitor which blocks the metabolism of Ang II in Ang III, we previously reported that vasopressin release was under the control of Ang III and not Ang II. To determine accurately the action of EC33, the effects of intracerebroventricular injection of Ang peptides or EC33 on extracellular unit activity of vasopressinergic neurons in the supraoptic nucleus of urethane-anaesthetized rats were examined. Angiotensin II (15-30 ng) or Ang III (15 ng) increased the firing rate of all neurons tested. Conversely, EC33 (10 microg) reduced or completely abolished (30-60 microg) the basal firing rate for 4-6 min in all eight neurons tested. EC33 (30 microg) also inhibited the activity induced by 30 ng Ang II. It was concluded that the observed activity of Ang II required its conversion to Ang III and that endogenous Ang III may exert a tonic control on the basal firing level of vasopressinergic neurons.