GABA agonists inhibit the vasopressin-dependent pressor effects of central angiotensin II.

Abstract

Previous studies have demonstrated that intraventricular (IVT) administration of low doses of gamma-aminobutyric acid (GABA) agonists reduced the pressor effects of centrally injected angiotensin II (AII). The following studies were designed to determine if GABA agonists acted to inhibit the pressor response of AII through blockade of the vasopressin-dependent pressor component. Following pretreatment with a vascular vasopressin antagonist, the pressor response of IVT administered AII was reduced approximately 50%. Hypophysectomy produced a similar reduction in this pressor response. These results suggested that vasopressin contributed to one-half 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. Therefore, 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 micrograms of GABA or 50 ng of the GABA agonist muscimol. These doses of GABA and muscimol have previously been shown to reduce the pressor response of IVT administered AII by approximately 60% in untreated rats. Thus, 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.(ABSTRACT TRUNCATED AT 250 WORDS)