GABA AGONISTS INHIBIT THE VASOPRESSIN-DEPENDENT PRESSOR EFFECTS OF CENTRAL ANGIOTENSIN-II

Intraventricular (IVT) administration of low doses of GABA agonists have reduced the pressor effects of centrally injected angiotensin II (AII). Whether GABA agonists act to inhibit the pressor response of AII through blockade of the vasopressin-dependent pressor component was investigated in rats. Following pretreatment with a vascular vasopressin antagonist, the pressor response of IVT administered AII was reduced .apprx. 50%. Hypophysectomy produced a similar reduction in this pressor response. Vasopressin apparently contributed to 1/2 of the pressor response of AII. In order to generate a vasopressin-dependent response, the sympathetic nervous system was eliminated with ganglionic blockade by chlorisondamine. The increase in arterial pressure produced by IVT injected AII after ganglionic blockade was augmented compared to untreated rats. This potentiated pressor effect of IVT administered AII after chlorisondamine treatment was markedly reduced by a vascular vasopressin antagonist or by hypophysectomy. The pressor effect of AII after ganglionic blockade was caused principally by the pressor actions of arginine-vasopressin (AVP). This AVP-dependent pressor effect of IVT injected AII was reduced by pretreatment with 100 .mu.g of GABA or 50 ng of the GABA agonist muscimol. These doses of GABA and muscimol have previously reduced the pressor response of IVT administered AII by .apprx. 60% in untreated rats. Pretreatment with low doses of GABA agonists reduced the pressor effect of IVT injected AII in part by inhibiting the vasopressin component of this response. The inhibitory effect of GABA on vasopressin secretion was confirmed by the observation that GABA pretreatment also blocked the increase in plasma AVP levels produced by IVT administered AII.